ID AAPK1_HUMAN Reviewed; 559 AA. AC Q13131; A8MTQ6; B2R7E1; O00286; Q5D0E1; Q86VS1; Q9UNQ4; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 28-JUL-2009, sequence version 4. DT 11-NOV-2015, entry version 172. DE RecName: Full=5'-AMP-activated protein kinase catalytic subunit alpha-1; DE Short=AMPK subunit alpha-1; DE EC=2.7.11.1; DE AltName: Full=Acetyl-CoA carboxylase kinase; DE Short=ACACA kinase; DE EC=2.7.11.27; DE AltName: Full=Hydroxymethylglutaryl-CoA reductase kinase; DE Short=HMGCR kinase; DE EC=2.7.11.31; DE AltName: Full=Tau-protein kinase PRKAA1; DE EC=2.7.11.26; GN Name=PRKAA1; Synonyms=AMPK1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP LEU-10. RC TISSUE=Brain, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-559 (ISOFORM 1). RC TISSUE=Mammary gland; RA Yano K.; RT "Nucleotide sequence of cDNA for human AMP-activated protein kinase RT alpha-1."; RL Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-559 (ISOFORM 1). RC TISSUE=Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-559 (ISOFORM 1). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for RT 300 previously undefined genes expressed in CD34+ hematopoietic RT stem/progenitor cells."; RL Genome Res. 10:1546-1560(2000). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 36-209 (ISOFORM 1). RC TISSUE=Intestine; RA Taboada E.N., Hickey D.A.; RL Submitted (APR-1995) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 303-559 (ISOFORMS 1/2). RC TISSUE=Liver; RX PubMed=8557660; DOI=10.1074/jbc.271.2.611; RA Stapleton D., Mitchelhill K.I., Gao G., Widmer J., Michell B.J., RA Teh T., House C.M., Fernandez C.S., Cox T., Witters L.A., Kemp B.E.; RT "Mammalian AMP-activated protein kinase subfamily."; RL J. Biol. Chem. 271:611-614(1996). RN [8] RP DOMAIN AIS. RX PubMed=9857077; DOI=10.1074/jbc.273.52.35347; RA Crute B.E., Seefeld K., Gamble J., Kemp B.E., Witters L.A.; RT "Functional domains of the alpha1 catalytic subunit of the AMP- RT activated protein kinase."; RL J. Biol. Chem. 273:35347-35354(1998). RN [9] RP FUNCTION. RX PubMed=11554766; DOI=10.1006/bbrc.2001.5627; RA Imamura K., Ogura T., Kishimoto A., Kaminishi M., Esumi H.; RT "Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated RT protein kinase activator, 5-aminoimidazole-4-carboxamide-1-beta-D- RT ribofuranoside, in a human hepatocellular carcinoma cell line."; RL Biochem. Biophys. Res. Commun. 287:562-567(2001). RN [10] RP FUNCTION IN PHOSPHORYLATION OF EP300. RX PubMed=11518699; DOI=10.1074/jbc.C100316200; RA Yang W., Hong Y.H., Shen X.Q., Frankowski C., Camp H.S., Leff T.; RT "Regulation of transcription by AMP-activated protein kinase: RT phosphorylation of p300 blocks its interaction with nuclear RT receptors."; RL J. Biol. Chem. 276:38341-38344(2001). RN [11] RP ENZYME REGULATION. RX PubMed=11602624; DOI=10.1172/JCI13505; RA Zhou G., Myers R., Li Y., Chen Y., Shen X., Fenyk-Melody J., Wu M., RA Ventre J., Doebber T., Fujii N., Musi N., Hirshman M.F., RA Goodyear L.J., Moller D.E.; RT "Role of AMP-activated protein kinase in mechanism of metformin RT action."; RL J. Clin. Invest. 108:1167-1174(2001). RN [12] RP FUNCTION IN PHOSPHORYLATION OF CFTR. RX PubMed=12519745; DOI=10.1152/ajpcell.00227.2002; RA Hallows K.R., Kobinger G.P., Wilson J.M., Witters L.A., Foskett J.K.; RT "Physiological modulation of CFTR activity by AMP-activated protein RT kinase in polarized T84 cells."; RL Am. J. Physiol. 284:C1297-C1308(2003). RN [13] RP FUNCTION IN PHOSPHORYLATION OF TSC2. RX PubMed=14651849; DOI=10.1016/S0092-8674(03)00929-2; RA Inoki K., Zhu T., Guan K.L.; RT "TSC2 mediates cellular energy response to control cell growth and RT survival."; RL Cell 115:577-590(2003). RN [14] RP PHOSPHORYLATION AT THR-183, AND ENZYME REGULATION. RX PubMed=14976552; DOI=10.1038/sj.emboj.7600110; RA Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., RA Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., RA Alessi D.R.; RT "LKB1 is a master kinase that activates 13 kinases of the AMPK RT subfamily, including MARK/PAR-1."; RL EMBO J. 23:833-843(2004). RN [15] RP PHOSPHORYLATION AT THR-183, AND ENZYME REGULATION. RX PubMed=16054095; DOI=10.1016/j.cmet.2005.05.009; RA Hawley S.A., Pan D.A., Mustard K.J., Ross L., Bain J., Edelman A.M., RA Frenguelli B.G., Hardie D.G.; RT "Calmodulin-dependent protein kinase kinase-beta is an alternative RT upstream kinase for AMP-activated protein kinase."; RL Cell Metab. 2:9-19(2005). RN [16] RP PHOSPHORYLATION AT THR-183, AND ENZYME REGULATION. RX PubMed=15980064; DOI=10.1074/jbc.M503824200; RA Hurley R.L., Anderson K.A., Franzone J.M., Kemp B.E., Means A.R., RA Witters L.A.; RT "The Ca2+/calmodulin-dependent protein kinase kinases are AMP- RT activated protein kinase kinases."; RL J. Biol. Chem. 280:29060-29066(2005). RN [17] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=15866171; DOI=10.1016/j.molcel.2005.03.027; RA Jones R.G., Plas D.R., Kubek S., Buzzai M., Mu J., Xu Y., RA Birnbaum M.J., Thompson C.B.; RT "AMP-activated protein kinase induces a p53-dependent metabolic RT checkpoint."; RL Mol. Cell 18:283-293(2005). RN [18] RP INTERACTION WITH FNIP1. RX PubMed=17028174; DOI=10.1073/pnas.0603781103; RA Baba M., Hong S.-B., Sharma N., Warren M.B., Nickerson M.L., RA Iwamatsu A., Esposito D., Gillette W.K., Hopkins R.F. III, RA Hartley J.L., Furihata M., Oishi S., Zhen W., Burke T.R. Jr., RA Linehan W.M., Schmidt L.S., Zbar B.; RT "Folliculin encoded by the BHD gene interacts with a binding protein, RT FNIP1, and AMPK, and is involved in AMPK and mTOR signaling."; RL Proc. Natl. Acad. Sci. U.S.A. 103:15552-15557(2006). RN [19] RP DOMAIN AIS, AND MUTAGENESIS OF VAL-307. RX PubMed=17088252; DOI=10.1074/jbc.M605790200; RA Pang T., Xiong B., Li J.Y., Qiu B.Y., Jin G.Z., Shen J.K., Li J.; RT "Conserved alpha-helix acts as autoinhibitory sequence in AMP- RT activated protein kinase alpha subunits."; RL J. Biol. Chem. 282:495-506(2007). RN [20] RP FUNCTION IN PHOSPHORYLATION OF FOXO3. RX PubMed=17711846; DOI=10.1074/jbc.M705325200; RA Greer E.L., Oskoui P.R., Banko M.R., Maniar J.M., Gygi M.P., RA Gygi S.P., Brunet A.; RT "The energy sensor AMP-activated protein kinase directly regulates the RT mammalian FOXO3 transcription factor."; RL J. Biol. Chem. 282:30107-30119(2007). RN [21] RP FUNCTION IN CELL POLARITY. RX PubMed=17486097; DOI=10.1038/nature05828; RA Lee J.H., Koh H., Kim M., Kim Y., Lee S.Y., Karess R.E., Lee S.H., RA Shong M., Kim J.M., Kim J., Chung J.; RT "Energy-dependent regulation of cell structure by AMP-activated RT protein kinase."; RL Nature 447:1017-1020(2007). RN [22] RP FUNCTION IN PHOSPHORYLATION OF HDAC5. RX PubMed=18184930; DOI=10.2337/db07-0843; RA McGee S.L., van Denderen B.J., Howlett K.F., Mollica J., RA Schertzer J.D., Kemp B.E., Hargreaves M.; RT "AMP-activated protein kinase regulates GLUT4 transcription by RT phosphorylating histone deacetylase 5."; RL Diabetes 57:860-867(2008). RN [23] RP INTERACTION WITH FNIP2. RX PubMed=18403135; DOI=10.1016/j.gene.2008.02.022; RA Hasumi H., Baba M., Hong S.-B., Hasumi Y., Huang Y., Yao M., RA Valera V.A., Linehan W.M., Schmidt L.S.; RT "Identification and characterization of a novel folliculin-interacting RT protein FNIP2."; RL Gene 415:60-67(2008). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-382, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., RA Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for RT efficient phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [25] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [26] RP FUNCTION IN PHOSPHORYLATION OF RPTOR. RX PubMed=18439900; DOI=10.1016/j.molcel.2008.03.003; RA Gwinn D.M., Shackelford D.B., Egan D.F., Mihaylova M.M., Mery A., RA Vasquez D.S., Turk B.E., Shaw R.J.; RT "AMPK phosphorylation of raptor mediates a metabolic checkpoint."; RL Mol. Cell 30:214-226(2008). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [28] RP INTERACTION WITH FNIP2. RX PubMed=18663353; DOI=10.1038/onc.2008.261; RA Takagi Y., Kobayashi T., Shiono M., Wang L., Piao X., Sun G., RA Zhang D., Abe M., Hagiwara Y., Takahashi K., Hino O.; RT "Interaction of folliculin (Birt-Hogg-Dube gene product) with a novel RT Fnip1-like (FnipL/Fnip2) protein."; RL Oncogene 27:5339-5347(2008). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-356; SER-486; THR-490 RP AND SER-496, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-32 AND SER-467, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-382, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [32] RP FUNCTION IN PHOSPHORYLATION OF KLC1. RX PubMed=20074060; DOI=10.1042/BST0380205; RA McDonald A., Fogarty S., Leclerc I., Hill E.V., Hardie D.G., RA Rutter G.A.; RT "Cell-wide analysis of secretory granule dynamics in three dimensions RT in living pancreatic beta-cells: evidence against a role for AMPK- RT dependent phosphorylation of KLC1 at Ser517/Ser520 in glucose- RT stimulated insulin granule movement."; RL Biochem. Soc. Trans. 38:205-208(2010). RN [33] RP FUNCTION. RX PubMed=20160076; DOI=10.1073/pnas.0913860107; RA Alexander A., Cai S.L., Kim J., Nanez A., Sahin M., MacLean K.H., RA Inoki K., Guan K.L., Shen J., Person M.D., Kusewitt D., Mills G.B., RA Kastan M.B., Walker C.L.; RT "ATM signals to TSC2 in the cytoplasm to regulate mTORC1 in response RT to ROS."; RL Proc. Natl. Acad. Sci. U.S.A. 107:4153-4158(2010). RN [34] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [35] RP PHOSPHORYLATION BY ULK1 AND ULK2. RX PubMed=21460634; DOI=10.4161/auto.7.7.15451; RA Loffler A.S., Alers S., Dieterle A.M., Keppeler H., Franz-Wachtel M., RA Kundu M., Campbell D.G., Wesselborg S., Alessi D.R., Stork B.; RT "Ulk1-mediated phosphorylation of AMPK constitutes a negative RT regulatory feedback loop."; RL Autophagy 7:696-706(2011). RN [36] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [37] RP FUNCTION IN PHOSPHORYLATION OF ULK1. RX PubMed=21205641; DOI=10.1126/science.1196371; RA Egan D.F., Shackelford D.B., Mihaylova M.M., Gelino S., Kohnz R.A., RA Mair W., Vasquez D.S., Joshi A., Gwinn D.M., Taylor R., Asara J.M., RA Fitzpatrick J., Dillin A., Viollet B., Kundu M., Hansen M., Shaw R.J.; RT "Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase RT connects energy sensing to mitophagy."; RL Science 331:456-461(2011). RN [38] RP INTERACTION WITH PRKAB1 AND PRKAG1, AND ENZYME REGULATION. RX PubMed=21680840; DOI=10.1126/science.1200094; RA Oakhill J.S., Steel R., Chen Z.P., Scott J.W., Ling N., Tam S., RA Kemp B.E.; RT "AMPK is a direct adenylate charge-regulated protein kinase."; RL Science 332:1433-1435(2011). RN [39] RP REVIEW ON FUNCTION. RX PubMed=17307971; DOI=10.1161/01.RES.0000256090.42690.05; RA Towler M.C., Hardie D.G.; RT "AMP-activated protein kinase in metabolic control and insulin RT signaling."; RL Circ. Res. 100:328-341(2007). RN [40] RP REVIEW ON FUNCTION. RX PubMed=17712357; DOI=10.1038/nrm2249; RA Hardie D.G.; RT "AMP-activated/SNF1 protein kinases: conserved guardians of cellular RT energy."; RL Nat. Rev. Mol. Cell Biol. 8:774-785(2007). RN [41] RP DEPHOSPHORYLATION. RX PubMed=23088624; DOI=10.1042/BJ20121201; RA Chida T., Ando M., Matsuki T., Masu Y., Nagaura Y., RA Takano-Yamamoto T., Tamura S., Kobayashi T.; RT "N-Myristoylation is essential for protein phosphatases PPM1A and RT PPM1B to dephosphorylate their physiological substrates in cells."; RL Biochem. J. 449:741-749(2013). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-355; SER-496; SER-508; RP SER-524 AND SER-527, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [43] RP VARIANT [LARGE SCALE ANALYSIS] ARG-16. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Catalytic subunit of AMP-activated protein kinase CC (AMPK), an energy sensor protein kinase that plays a key role in CC regulating cellular energy metabolism. In response to reduction of CC intracellular ATP levels, AMPK activates energy-producing pathways CC and inhibits energy-consuming processes: inhibits protein, CC carbohydrate and lipid biosynthesis, as well as cell growth and CC proliferation. AMPK acts via direct phosphorylation of metabolic CC enzymes, and by longer-term effects via phosphorylation of CC transcription regulators. Also acts as a regulator of cellular CC polarity by remodeling the actin cytoskeleton; probably by CC indirectly activating myosin. Regulates lipid synthesis by CC phosphorylating and inactivating lipid metabolic enzymes such as CC ACACA, ACACB, GYS1, HMGCR and LIPE; regulates fatty acid and CC cholesterol synthesis by phosphorylating acetyl-CoA carboxylase CC (ACACA and ACACB) and hormone-sensitive lipase (LIPE) enzymes, CC respectively. Regulates insulin-signaling and glycolysis by CC phosphorylating IRS1, PFKFB2 and PFKFB3. AMPK stimulates glucose CC uptake in muscle by increasing the translocation of the glucose CC transporter SLC2A4/GLUT4 to the plasma membrane, possibly by CC mediating phosphorylation of TBC1D4/AS160. Regulates transcription CC and chromatin structure by phosphorylating transcription CC regulators involved in energy metabolism such as CRTC2/TORC2, CC FOXO3, histone H2B, HDAC5, MEF2C, MLXIPL/ChREBP, EP300, HNF4A, CC p53/TP53, SREBF1, SREBF2 and PPARGC1A. Acts as a key regulator of CC glucose homeostasis in liver by phosphorylating CRTC2/TORC2, CC leading to CRTC2/TORC2 sequestration in the cytoplasm. In response CC to stress, phosphorylates 'Ser-36' of histone H2B (H2BS36ph), CC leading to promote transcription. Acts as a key regulator of cell CC growth and proliferation by phosphorylating TSC2, RPTOR and CC ATG1/ULK1: in response to nutrient limitation, negatively CC regulates the mTORC1 complex by phosphorylating RPTOR component of CC the mTORC1 complex and by phosphorylating and activating TSC2. In CC response to nutrient limitation, promotes autophagy by CC phosphorylating and activating ATG1/ULK1. AMPK also acts as a CC regulator of circadian rhythm by mediating phosphorylation of CC CRY1, leading to destabilize it. May regulate the Wnt signaling CC pathway by phosphorylating CTNNB1, leading to stabilize it. Also CC has tau-protein kinase activity: in response to amyloid beta A4 CC protein (APP) exposure, activated by CAMKK2, leading to CC phosphorylation of MAPT/TAU; however the relevance of such data CC remains unclear in vivo. Also phosphorylates CFTR, EEF2K, KLC1, CC NOS3 and SLC12A1. {ECO:0000269|PubMed:11518699, CC ECO:0000269|PubMed:11554766, ECO:0000269|PubMed:12519745, CC ECO:0000269|PubMed:14651849, ECO:0000269|PubMed:15866171, CC ECO:0000269|PubMed:17486097, ECO:0000269|PubMed:17711846, CC ECO:0000269|PubMed:18184930, ECO:0000269|PubMed:18439900, CC ECO:0000269|PubMed:20074060, ECO:0000269|PubMed:20160076, CC ECO:0000269|PubMed:21205641}. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- CATALYTIC ACTIVITY: ATP + [tau protein] = ADP + [tau protein] CC phosphate. CC -!- CATALYTIC ACTIVITY: ATP + [hydroxymethylglutaryl-CoA reductase CC (NADPH)] = ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] CC phosphate. CC -!- CATALYTIC ACTIVITY: ATP + [acetyl-CoA carboxylase] = ADP + CC [acetyl-CoA carboxylase] phosphate. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC -!- ENZYME REGULATION: Activated by phosphorylation on Thr-183. CC Binding of AMP to non-catalytic gamma subunit (PRKAG1, PRKAG2 or CC PRKAG3) results in allosteric activation, inducing phosphorylation CC on Thr-183. AMP-binding to gamma subunit also sustains activity by CC preventing dephosphorylation of Thr-183. ADP also stimulates Thr- CC 183 phosphorylation, without stimulating already phosphorylated CC AMPK. ATP promotes dephosphorylation of Thr-183, rendering the CC enzyme inactive. Under physiological conditions AMPK mainly exists CC in its inactive form in complex with ATP, which is much more CC abundant than AMP. AMPK is activated by antihyperglycemic drug CC metformin, a drug prescribed to patients with type 2 diabetes: in CC vivo, metformin seems to mainly inhibit liver gluconeogenesis. CC However, metformin can be used to activate AMPK in muscle and CC other cells in culture or ex vivo (PubMed:11602624). Selectively CC inhibited by compound C (6-[4-(2-Piperidin-1-yl-ethoxy)-phenyl)]- CC 3-pyridin-4-yl-pyyrazolo[1,5-a] pyrimidine. Activated by CC resveratrol, a natural polyphenol present in red wine, and S17834, CC a synthetic polyphenol. {ECO:0000269|PubMed:11602624, CC ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15980064, CC ECO:0000269|PubMed:16054095, ECO:0000269|PubMed:21680840}. CC -!- SUBUNIT: AMPK is a heterotrimer of an alpha catalytic subunit CC (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non- CC catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with CC FNIP1 and FNIP2. {ECO:0000269|PubMed:17028174, CC ECO:0000269|PubMed:18403135, ECO:0000269|PubMed:18663353, CC ECO:0000269|PubMed:21680840}. CC -!- INTERACTION: CC Q9NYB9:ABI2; NbExp=3; IntAct=EBI-1181405, EBI-743598; CC Q08117:AES; NbExp=3; IntAct=EBI-1181405, EBI-717810; CC O14503:BHLHE40; NbExp=3; IntAct=EBI-1181405, EBI-711810; CC O14627:CDX4; NbExp=3; IntAct=EBI-1181405, EBI-10181162; CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-1181405, EBI-10171858; CC O95073:FSBP; NbExp=3; IntAct=EBI-1181405, EBI-1059030; CC Q08379:GOLGA2; NbExp=3; IntAct=EBI-1181405, EBI-618309; CC Q6NT76:HMBOX1; NbExp=3; IntAct=EBI-1181405, EBI-2549423; CC Q8IX15-3:HOMEZ; NbExp=3; IntAct=EBI-1181405, EBI-10172004; CC P08238:HSP90AB1; NbExp=2; IntAct=EBI-1181405, EBI-352572; CC Q9UKT9:IKZF3; NbExp=3; IntAct=EBI-1181405, EBI-747204; CC Q8NBZ0:INO80E; NbExp=3; IntAct=EBI-1181405, EBI-769401; CC Q6A162:KRT40; NbExp=3; IntAct=EBI-1181405, EBI-10171697; CC Q96JM7:L3MBTL3; NbExp=3; IntAct=EBI-1181405, EBI-2686809; CC Q5JR59:MTUS2; NbExp=3; IntAct=EBI-1181405, EBI-742948; CC Q8IXK0:PHC2; NbExp=3; IntAct=EBI-1181405, EBI-713786; CC Q96PV4:PNMA5; NbExp=3; IntAct=EBI-1181405, EBI-10171633; CC Q9Y478:PRKAB1; NbExp=6; IntAct=EBI-1181405, EBI-719769; CC O43741:PRKAB2; NbExp=12; IntAct=EBI-1181405, EBI-1053424; CC P54619:PRKAG1; NbExp=10; IntAct=EBI-1181405, EBI-1181439; CC Q93062:RBPMS; NbExp=3; IntAct=EBI-1181405, EBI-740322; CC Q8HWS3:RFX6; NbExp=3; IntAct=EBI-1181405, EBI-746118; CC Q9UFD9:RIMBP3; NbExp=3; IntAct=EBI-1181405, EBI-10182375; CC Q9HAT0:ROPN1; NbExp=3; IntAct=EBI-1181405, EBI-1378139; CC Q9Y2D8:SSX2IP; NbExp=3; IntAct=EBI-1181405, EBI-2212028; CC Q9NVV9:THAP1; NbExp=3; IntAct=EBI-1181405, EBI-741515; CC P14373:TRIM27; NbExp=3; IntAct=EBI-1181405, EBI-719493; CC Q15654:TRIP6; NbExp=3; IntAct=EBI-1181405, EBI-742327; CC Q9Y3Q8:TSC22D4; NbExp=3; IntAct=EBI-1181405, EBI-739485; CC Q5T124:UBXN11; NbExp=3; IntAct=EBI-1181405, EBI-746004; CC Q9H9H4:VPS37B; NbExp=3; IntAct=EBI-1181405, EBI-4400866; CC Q8N1B4:VPS52; NbExp=3; IntAct=EBI-1181405, EBI-2799833; CC O96006:ZBED1; NbExp=3; IntAct=EBI-1181405, EBI-740037; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15866171}. CC Nucleus {ECO:0000269|PubMed:15866171}. Note=In response to stress, CC recruited by p53/TP53 to specific promoters. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q13131-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13131-2; Sequence=VSP_035431; CC -!- DOMAIN: The AIS (autoinhibitory sequence) region shows some CC sequence similarity with the ubiquitin-associated domains and CC represses kinase activity. {ECO:0000269|PubMed:17088252, CC ECO:0000269|PubMed:9857077}. CC -!- PTM: Ubiquitinated. {ECO:0000250}. CC -!- PTM: Phosphorylated at Thr-183 by STK11/LKB1 in complex with CC STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Also CC phosphorylated at Thr-183 by CAMKK2; triggered by a rise in CC intracellular calcium ions, without detectable changes in the CC AMP/ATP ratio. CAMKK1 can also phosphorylate Thr-183, but at a CC much lower level. Dephosphorylated by protein phosphatase 2A and CC 2C (PP2A and PP2C). Phosphorylated by ULK1 and ULK2; leading to CC negatively regulate AMPK activity and suggesting the existence of CC a regulatory feedback loop between ULK1, ULK2 and AMPK. CC Dephosphorylated by PPM1A and PPM1B. {ECO:0000269|PubMed:14976552, CC ECO:0000269|PubMed:15980064, ECO:0000269|PubMed:16054095, CC ECO:0000269|PubMed:21460634}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK CC Ser/Thr protein kinase family. SNF1 subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA64850.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAD43027.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAH37303.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=BAA36547.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=BAG35788.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AC008810; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC048980; AAH48980.1; -; mRNA. DR EMBL; AB022017; BAA36547.1; ALT_INIT; mRNA. DR EMBL; AK312947; BAG35788.1; ALT_INIT; mRNA. DR EMBL; BC037303; AAH37303.1; ALT_INIT; mRNA. DR EMBL; AF100763; AAD43027.1; ALT_INIT; mRNA. DR EMBL; U22456; AAA64850.1; ALT_INIT; mRNA. DR EMBL; Y12856; CAA73361.1; -; mRNA. DR CCDS; CCDS3932.2; -. [Q13131-1] DR CCDS; CCDS3933.2; -. [Q13131-2] DR PIR; G01743; G01743. DR RefSeq; NP_006242.5; NM_006251.5. [Q13131-1] DR RefSeq; NP_996790.3; NM_206907.3. [Q13131-2] DR UniGene; Hs.43322; -. DR PDB; 4RED; X-ray; 2.95 A; A/B=22-362. DR PDB; 4RER; X-ray; 4.05 A; A=20-559. DR PDB; 4REW; X-ray; 4.58 A; A=20-559. DR PDBsum; 4RED; -. DR PDBsum; 4RER; -. DR PDBsum; 4REW; -. DR ProteinModelPortal; Q13131; -. DR SMR; Q13131; 20-559. DR BioGrid; 111549; 142. DR DIP; DIP-39973N; -. DR IntAct; Q13131; 93. DR MINT; MINT-6771251; -. DR STRING; 9606.ENSP00000346148; -. DR BindingDB; Q13131; -. DR ChEMBL; CHEMBL3038452; -. DR DrugBank; DB00945; Acetylsalicylic acid. DR DrugBank; DB00131; Adenosine monophosphate. DR DrugBank; DB00171; Adenosine triphosphate. DR DrugBank; DB00914; Phenformin. DR GuidetoPHARMACOLOGY; 1541; -. DR PhosphoSite; Q13131; -. DR BioMuta; PRKAA1; -. DR DMDM; 254763436; -. DR MaxQB; Q13131; -. DR PaxDb; Q13131; -. DR PRIDE; Q13131; -. DR DNASU; 5562; -. DR Ensembl; ENST00000354209; ENSP00000346148; ENSG00000132356. [Q13131-2] DR Ensembl; ENST00000397128; ENSP00000380317; ENSG00000132356. [Q13131-1] DR GeneID; 5562; -. DR KEGG; hsa:5562; -. DR UCSC; uc003jmb.3; human. [Q13131-2] DR UCSC; uc003jmc.3; human. [Q13131-1] DR CTD; 5562; -. DR GeneCards; PRKAA1; -. DR H-InvDB; HIX0004832; -. DR HGNC; HGNC:9376; PRKAA1. DR HPA; CAB005050; -. DR HPA; HPA035409; -. DR MIM; 602739; gene. DR neXtProt; NX_Q13131; -. DR PharmGKB; PA33744; -. DR eggNOG; KOG0586; Eukaryota. DR eggNOG; ENOG410XNQ0; LUCA. DR GeneTree; ENSGT00790000122960; -. DR HOGENOM; HOG000233016; -. DR HOVERGEN; HBG050432; -. DR KO; K07198; -. DR OMA; NYRSCQK; -. DR OrthoDB; EOG7RRF6K; -. DR PhylomeDB; Q13131; -. DR TreeFam; TF314032; -. DR BRENDA; 2.7.11.1; 2681. DR Reactome; R-HSA-1632852; Macroautophagy. DR Reactome; R-HSA-380972; Energy dependent regulation of mTOR by LKB1-AMPK. DR Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes. DR SignaLink; Q13131; -. DR ChiTaRS; PRKAA1; human. DR GeneWiki; Protein_kinase,_AMP-activated,_alpha_1; -. DR GenomeRNAi; 5562; -. DR NextBio; 21546; -. DR PRO; PR:Q13131; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; Q13131; -. DR CleanEx; HS_PRKAA1; -. DR ExpressionAtlas; Q13131; baseline and differential. DR Genevisible; Q13131; HS. DR GO; GO:0031588; C:AMP-activated protein kinase complex; ISS:UniProtKB. DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005622; C:intracellular; IC:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0050405; F:[acetyl-CoA carboxylase] kinase activity; IEA:UniProtKB-EC. DR GO; GO:0047322; F:[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity; IEA:UniProtKB-EC. DR GO; GO:0004679; F:AMP-activated protein kinase activity; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004691; F:cAMP-dependent protein kinase activity; NAS:UniProtKB. DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0035174; F:histone serine kinase activity; ISS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. DR GO; GO:0050321; F:tau-protein kinase activity; IEA:UniProtKB-EC. DR GO; GO:0000187; P:activation of MAPK activity; NAS:UniProtKB. DR GO; GO:0007050; P:cell cycle arrest; TAS:Reactome. DR GO; GO:0071361; P:cellular response to ethanol; IEA:Ensembl. DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl. DR GO; GO:0031669; P:cellular response to nutrient levels; ISS:UniProtKB. DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEA:Ensembl. DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0009631; P:cold acclimation; IEA:Ensembl. DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0055089; P:fatty acid homeostasis; ISS:UniProtKB. DR GO; GO:0019395; P:fatty acid oxidation; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB. DR GO; GO:0006006; P:glucose metabolic process; IEA:Ensembl. DR GO; GO:0035404; P:histone-serine phosphorylation; IBA:GO_Central. DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0008610; P:lipid biosynthetic process; ISS:UniProtKB. DR GO; GO:0016236; P:macroautophagy; TAS:Reactome. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:2001274; P:negative regulation of glucose import in response to insulin stimulus; IEA:Ensembl. DR GO; GO:0046318; P:negative regulation of glucosylceramide biosynthetic process; NAS:UniProtKB. DR GO; GO:0050995; P:negative regulation of lipid catabolic process; ISS:UniProtKB. DR GO; GO:0032007; P:negative regulation of TOR signaling; ISS:UniProtKB. DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0045542; P:positive regulation of cholesterol biosynthetic process; NAS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB. DR GO; GO:0045821; P:positive regulation of glycolytic process; ISS:UniProtKB. DR GO; GO:0048643; P:positive regulation of skeletal muscle tissue development; IEA:Ensembl. DR GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:2000505; P:regulation of energy homeostasis; ISS:UniProtKB. DR GO; GO:0033135; P:regulation of peptidyl-serine phosphorylation; IEA:Ensembl. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0060627; P:regulation of vesicle-mediated transport; IEA:Ensembl. DR GO; GO:0014823; P:response to activity; IEA:Ensembl. DR GO; GO:0031000; P:response to caffeine; IEA:Ensembl. DR GO; GO:1901563; P:response to camptothecin; IEA:Ensembl. DR GO; GO:0010332; P:response to gamma radiation; ISS:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; NAS:UniProtKB. DR GO; GO:0009411; P:response to UV; IEA:Ensembl. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR InterPro; IPR032270; AMPK_C. DR InterPro; IPR028375; KA1/Ssp2_C. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR Pfam; PF16579; AdenylateSensor; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF103243; SSF103243; 1. DR SUPFAM; SSF56112; SSF56112; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Autophagy; KW Biological rhythms; Cholesterol biosynthesis; Cholesterol metabolism; KW Chromatin regulator; Complete proteome; Cytoplasm; KW Fatty acid biosynthesis; Fatty acid metabolism; Kinase; KW Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding; KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Serine/threonine-protein kinase; KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis; KW Sterol metabolism; Transcription; Transcription regulation; KW Transferase; Ubl conjugation; Wnt signaling pathway. FT CHAIN 1 559 5'-AMP-activated protein kinase catalytic FT subunit alpha-1. FT /FTId=PRO_0000085589. FT DOMAIN 27 279 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 33 41 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 302 381 AIS. FT ACT_SITE 150 150 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10027}. FT BINDING 56 56 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 32 32 Phosphothreonine. FT {ECO:0000244|PubMed:19369195}. FT MOD_RES 183 183 Phosphothreonine; by LKB1 and CaMKK2. FT {ECO:0000250}. FT MOD_RES 269 269 Phosphothreonine. FT {ECO:0000250|UniProtKB:P54645}. FT MOD_RES 355 355 Phosphothreonine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 356 356 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 360 360 Phosphoserine; by ULK1. {ECO:0000250}. FT MOD_RES 368 368 Phosphothreonine; by ULK1. {ECO:0000250}. FT MOD_RES 382 382 Phosphothreonine. FT {ECO:0000244|PubMed:18220336, FT ECO:0000244|PubMed:19690332}. FT MOD_RES 397 397 Phosphoserine; by ULK1. FT {ECO:0000305|PubMed:21460634}. FT MOD_RES 467 467 Phosphoserine. FT {ECO:0000244|PubMed:19369195}. FT MOD_RES 486 486 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 488 488 Phosphothreonine; by ULK1. FT {ECO:0000305|PubMed:21460634}. FT MOD_RES 490 490 Phosphothreonine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 496 496 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 508 508 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 524 524 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 527 527 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT VAR_SEQ 121 121 R -> RKSDVPGVVKTGSTKE (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_035431. FT VARIANT 10 10 M -> L (in dbSNP:rs17855679). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_058401. FT VARIANT 16 16 Q -> R (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_035622. FT MUTAGEN 307 307 V->G,Q: Activates the kinase activity. FT {ECO:0000269|PubMed:17088252}. FT CONFLICT 5 5 S -> C (in Ref. 4; BAG35788). FT {ECO:0000305}. FT CONFLICT 9 9 K -> S (in Ref. 5; AAD43027). FT {ECO:0000305}. FT CONFLICT 37 37 T -> A (in Ref. 6; AAA64850). FT {ECO:0000305}. FT CONFLICT 202 202 A -> V (in Ref. 6; AAA64850). FT {ECO:0000305}. FT CONFLICT 208 208 I -> L (in Ref. 6; AAA64850). FT {ECO:0000305}. FT CONFLICT 269 269 T -> S (in Ref. 3; BAA36547). FT {ECO:0000305}. FT STRAND 27 35 {ECO:0000244|PDB:4RED}. FT STRAND 40 49 {ECO:0000244|PDB:4RED}. FT STRAND 52 59 {ECO:0000244|PDB:4RED}. FT HELIX 60 66 {ECO:0000244|PDB:4RED}. FT STRAND 68 70 {ECO:0000244|PDB:4RED}. FT HELIX 71 77 {ECO:0000244|PDB:4RED}. FT STRAND 90 95 {ECO:0000244|PDB:4RED}. FT STRAND 97 105 {ECO:0000244|PDB:4RED}. FT HELIX 112 118 {ECO:0000244|PDB:4RED}. FT HELIX 124 144 {ECO:0000244|PDB:4RED}. FT HELIX 153 155 {ECO:0000244|PDB:4RED}. FT STRAND 156 158 {ECO:0000244|PDB:4RED}. FT STRAND 164 167 {ECO:0000244|PDB:4RED}. FT STRAND 169 171 {ECO:0000244|PDB:4RED}. FT HELIX 193 196 {ECO:0000244|PDB:4RED}. FT HELIX 204 220 {ECO:0000244|PDB:4RED}. FT STRAND 227 229 {ECO:0000244|PDB:4RED}. FT HELIX 231 233 {ECO:0000244|PDB:4RED}. FT HELIX 250 259 {ECO:0000244|PDB:4RED}. FT HELIX 264 266 {ECO:0000244|PDB:4RED}. FT HELIX 270 274 {ECO:0000244|PDB:4RED}. FT HELIX 277 280 {ECO:0000244|PDB:4RED}. FT TURN 296 298 {ECO:0000244|PDB:4RED}. FT HELIX 301 310 {ECO:0000244|PDB:4RED}. FT HELIX 315 323 {ECO:0000244|PDB:4RED}. FT HELIX 330 340 {ECO:0000244|PDB:4RED}. FT TURN 347 351 {ECO:0000244|PDB:4RED}. SQ SEQUENCE 559 AA; 64009 MW; ABAE71FBF912947A CRC64; MRRLSSWRKM ATAEKQKHDG RVKIGHYILG DTLGVGTFGK VKVGKHELTG HKVAVKILNR QKIRSLDVVG KIRREIQNLK LFRHPHIIKL YQVISTPSDI FMVMEYVSGG ELFDYICKNG RLDEKESRRL FQQILSGVDY CHRHMVVHRD LKPENVLLDA HMNAKIADFG LSNMMSDGEF LRTSCGSPNY AAPEVISGRL YAGPEVDIWS SGVILYALLC GTLPFDDDHV PTLFKKICDG IFYTPQYLNP SVISLLKHML QVDPMKRATI KDIREHEWFK QDLPKYLFPE DPSYSSTMID DEALKEVCEK FECSEEEVLS CLYNRNHQDP LAVAYHLIID NRRIMNEAKD FYLATSPPDS FLDDHHLTRP HPERVPFLVA ETPRARHTLD ELNPQKSKHQ GVRKAKWHLG IRSQSRPNDI MAEVCRAIKQ LDYEWKVVNP YYLRVRRKNP VTSTYSKMSL QLYQVDSRTY LLDFRSIDDE ITEAKSGTAT PQRSGSVSNY RSCQRSDSDA EAQGKSSEVS LTSSVTSLDS SPVDLTPRPG SHTIEFFEMC ANLIKILAQ // ID ACTG_HUMAN Reviewed; 375 AA. AC P63261; A8K7C2; P02571; P14104; P99022; Q5U032; Q96E67; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 21-JUL-1986, sequence version 1. DT 11-NOV-2015, entry version 140. DE RecName: Full=Actin, cytoplasmic 2; DE AltName: Full=Gamma-actin; DE Contains: DE RecName: Full=Actin, cytoplasmic 2, N-terminally processed; GN Name=ACTG1; Synonyms=ACTG; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3737401; DOI=10.1093/nar/14.13.5275; RA Erba H.P., Gunning P., Kedes L.; RT "Nucleotide sequence of the human gamma cytoskeletal actin mRNA: RT anomalous evolution of vertebrate non-muscle actin genes."; RL Nucleic Acids Res. 14:5275-5294(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2837653; RA Erba H.P., Eddy R., Shows T., Kedes L., Gunning P.; RT "Structure, chromosome location, and expression of the human gamma- RT actin gene: differential evolution, location, and expression of the RT cytoskeletal beta- and gamma-actin genes."; RL Mol. Cell. Biol. 8:1775-1789(1988). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=B-cell, Eye, Lung, Ovary, Placenta, Skin, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 2-28. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., RA Thomas G.R., Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass RT spectrometric identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [7] RP PROTEIN SEQUENCE OF 2-18; 29-37; 40-50; 85-113; 148-177; 184-191; RP 197-206; 239-254; 292-312 AND 316-326, CLEAVAGE OF INITIATOR RP METHIONINE, ACETYLATION AT GLU-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=B-cell lymphoma; RA Bienvenut W.V.; RL Submitted (JUN-2005) to UniProtKB. RN [8] RP PROTEIN SEQUENCE OF 2-116; 119-210; 216-254 AND 291-372, CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT GLU-2, METHYLATION AT HIS-73, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Ovarian carcinoma; RA Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W., RA Dozynkiewicz M., Norman J.C.; RL Submitted (JUN-2009) to UniProtKB. RN [9] RP PROTEIN SEQUENCE OF 29-39; 85-113; 239-254 AND 292-312, AND RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Brain, and Cajal-Retzius cell; RA Lubec G., Afjehi-Sadat L.; RL Submitted (MAR-2007) to UniProtKB. RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 144-375. RX PubMed=3472224; DOI=10.1073/pnas.84.9.2575; RA Chou C.C., Davis R.C., Fuller M.L., Slovin J.P., Wong A., Wright J., RA Kania S., Shaked R., Gatti R.A., Salser W.A.; RT "Gamma-actin: unusual mRNA 3'-untranslated sequence conservation and RT amino acid substitutions that may be cancer related."; RL Proc. Natl. Acad. Sci. U.S.A. 84:2575-2579(1987). RN [11] RP CROSS-LINK BY V.CHOLERAE TOXIN RTXA (MICROBIAL INFECTION). RX PubMed=19015515; DOI=10.1073/pnas.0808082105; RA Kudryashov D.S., Durer Z.A., Ytterberg A.J., Sawaya M.R., Pashkov I., RA Prochazkova K., Yeates T.O., Loo R.R., Loo J.A., Satchell K.J., RA Reisler E.; RT "Connecting actin monomers by iso-peptide bond is a toxicity mechanism RT of the Vibrio cholerae MARTX toxin."; RL Proc. Natl. Acad. Sci. U.S.A. 105:18537-18542(2008). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLU-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND GLU-2, CLEAVAGE OF RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.M111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., RA Meinnel T., Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1 AND GLU-2, CLEAVAGE OF RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [15] RP METHYLATION AT LYS-84, AND DEMETHYLATION BY ALKBH4. RX PubMed=23673617; DOI=10.1038/ncomms2863; RA Li M.M., Nilsen A., Shi Y., Fusser M., Ding Y.H., Fu Y., Liu B., RA Niu Y., Wu Y.S., Huang C.M., Olofsson M., Jin K.X., Lv Y., Xu X.Z., RA He C., Dong M.Q., Rendtlew Danielsen J.M., Klungland A., Yang Y.G.; RT "ALKBH4-dependent demethylation of actin regulates actomyosin RT dynamics."; RL Nat. Commun. 4:1832-1832(2013). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT GLU-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [17] RP CROSS-LINK BY V.CHOLERAE TOXIN RTXA (MICROBIAL INFECTION). RX PubMed=26228148; DOI=10.1126/science.aab4090; RA Heisler D.B., Kudryashova E., Grinevich D.O., Suarez C., RA Winkelman J.D., Birukov K.G., Kotha S.R., Parinandi N.L., RA Vavylonis D., Kovar D.R., Kudryashov D.S.; RT "ACD toxin-produced actin oligomers poison formin-controlled actin RT polymerization."; RL Science 349:535-539(2015). RN [18] RP VARIANTS DFNA20 ILE-89; MET-118; LEU-264 AND ALA-332. RX PubMed=13680526; DOI=10.1086/379286; RA Zhu M., Yang T., Wei S., DeWan A.T., Morell R.J., Elfenbein J.L., RA Fisher R.A., Leal S.M., Smith R.J.H., Friderici K.H.; RT "Mutations in the gamma-actin gene (ACTG1) are associated with RT dominant progressive deafness (DFNA20/26)."; RL Am. J. Hum. Genet. 73:1082-1091(2003). RN [19] RP VARIANT DFNA20 ILE-278. RX PubMed=14684684; DOI=10.1136/jmg.40.12.879; RA van Wijk E., Krieger E., Kemperman M.H., De Leenheer E.M.R., RA Huygen P.L.M., Cremers C.W.R.J., Cremers F.P.M., Kremer H.; RT "A mutation in the gamma actin 1 (ACTG1) gene causes autosomal RT dominant hearing loss (DFNA20/26)."; RL J. Med. Genet. 40:879-884(2003). RN [20] RP VARIANT DFNA20 ALA-370, AND CHARACTERIZATION OF VARIANT DFNA20 RP ALA-370. RX PubMed=16773128; DOI=10.1038/sj.ejhg.5201670; RA Rendtorff N.D., Zhu M., Fagerheim T., Antal T.L., Jones M., RA Teslovich T.M., Gillanders E.M., Barmada M., Teig E., Trent J.M., RA Friderici K.H., Stephan D.A., Tranebjaerg L.; RT "A novel missense mutation in ACTG1 causes dominant deafness in a RT Norwegian DFNA20/26 family, but ACTG1 mutations are not frequent among RT families with hereditary hearing impairment."; RL Eur. J. Hum. Genet. 14:1097-1105(2006). RN [21] RP VARIANT DFNA20 VAL-122. RX PubMed=18804074; DOI=10.1016/S1673-8527(08)60075-2; RA Liu P., Li H., Ren X., Mao H., Zhu Q., Zhu Z., Yang R., Yuan W., RA Liu J., Wang Q., Liu M.; RT "Novel ACTG1 mutation causing autosomal dominant non-syndromic hearing RT impairment in a Chinese family."; RL J. Genet. Genomics 35:553-558(2008). RN [22] RP VARIANTS DFNA20 ASN-118 AND LYS-241. RX PubMed=19477959; DOI=10.1093/hmg/ddp249; RA Morin M., Bryan K.E., Mayo-Merino F., Goodyear R., Mencia A., RA Modamio-Hoybjor S., del Castillo I., Cabalka J.M., Richardson G., RA Moreno F., Rubenstein P.A., Moreno-Pelayo M.A.; RT "In vivo and in vitro effects of two novel gamma-actin (ACTG1) RT mutations that cause DFNA20/26 hearing impairment."; RL Hum. Mol. Genet. 18:3075-3089(2009). RN [23] RP VARIANTS BRWS2 ILE-120; VAL-135; PHE-155; LYS-203; TRP-254 AND RP TRP-256. RX PubMed=22366783; DOI=10.1038/ng.1091; RA Riviere J.B., van Bon B.W., Hoischen A., Kholmanskikh S.S., RA O'Roak B.J., Gilissen C., Gijsen S., Sullivan C.T., Christian S.L., RA Abdul-Rahman O.A., Atkin J.F., Chassaing N., Drouin-Garraud V., RA Fry A.E., Fryns J.P., Gripp K.W., Kempers M., Kleefstra T., RA Mancini G.M., Nowaczyk M.J., van Ravenswaaij-Arts C.M., Roscioli T., RA Marble M., Rosenfeld J.A., Siu V.M., de Vries B.B., Shendure J., RA Verloes A., Veltman J.A., Brunner H.G., Ross M.E., Pilz D.T., RA Dobyns W.B.; RT "De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser- RT Winter syndrome."; RL Nat. Genet. 44:440-444(2012). CC -!- FUNCTION: Actins are highly conserved proteins that are involved CC in various types of cell motility and are ubiquitously expressed CC in all eukaryotic cells. CC -!- SUBUNIT: Polymerization of globular actin (G-actin) leads to a CC structural filament (F-actin) in the form of a two-stranded helix. CC Each actin can bind to 4 others. CC -!- INTERACTION: CC Self; NbExp=4; IntAct=EBI-351292, EBI-351292; CC P60709:ACTB; NbExp=6; IntAct=EBI-351292, EBI-353944; CC P40123:CAP2; NbExp=5; IntAct=EBI-351292, EBI-1051165; CC O60826:CCDC22; NbExp=3; IntAct=EBI-351292, EBI-3943153; CC P23528:CFL1; NbExp=6; IntAct=EBI-351292, EBI-352733; CC Q549N0:CFL2; NbExp=5; IntAct=EBI-351292, EBI-10201319; CC Q9Y281:CFL2; NbExp=2; IntAct=EBI-351292, EBI-351218; CC P60981:DSTN; NbExp=5; IntAct=EBI-351292, EBI-745191; CC Q08426:EHHADH; NbExp=3; IntAct=EBI-351292, EBI-2339219; CC P40692:MLH1; NbExp=7; IntAct=EBI-351292, EBI-744248; CC Q1KLZ0:PS1TP5BP1; NbExp=3; IntAct=EBI-351292, EBI-9978131; CC Q96HA8:WDYHV1; NbExp=3; IntAct=EBI-351292, EBI-741158; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. CC -!- PTM: The methylhistidine determined by Bienvenut et al is assumed CC to be the tele-methylhistidine isomer by similarity to the mouse CC ortholog. CC -!- PTM: Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or CC MICAL3) to form methionine sulfoxide promotes actin filament CC depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. CC The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote CC actin repolymerization (By similarity). {ECO:0000250}. CC -!- PTM: Monomethylation at Lys-84 (K84me1) regulates actin-myosin CC interaction and actomyosin-dependent processes. Demethylation by CC ALKBH4 is required for maintaining actomyosin dynamics supporting CC normal cleavage furrow ingression during cytokinesis and cell CC migration. {ECO:0000269|PubMed:23673617}. CC -!- PTM: (Microbial infection) Monomeric actin is cross-linked by CC V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial CC toxins mediate the cross-link between Lys-50 of one monomer and CC Glu-270 of another actin monomer, resulting in formation of highly CC toxic actin oligomers that cause cell rounding (PubMed:19015515). CC The toxin can be highly efficient at very low concentrations by CC acting on formin homology family proteins: toxic actin oligomers CC bind with high affinity to formins and adversely affect both CC nucleation and elongation abilities of formins, causing their CC potent inhibition in both profilin-dependent and independent CC manners (PubMed:26228148). {ECO:0000305|PubMed:19015515, CC ECO:0000305|PubMed:26228148}. CC -!- DISEASE: Deafness, autosomal dominant, 20 (DFNA20) [MIM:604717]: A CC form of non-syndromic sensorineural hearing loss. Sensorineural CC deafness results from damage to the neural receptors of the inner CC ear, the nerve pathways to the brain, or the area of the brain CC that receives sound information. {ECO:0000269|PubMed:13680526, CC ECO:0000269|PubMed:14684684, ECO:0000269|PubMed:16773128, CC ECO:0000269|PubMed:18804074, ECO:0000269|PubMed:19477959}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Baraitser-Winter syndrome 2 (BRWS2) [MIM:614583]: A rare CC developmental disorder characterized by the combination of CC congenital ptosis, high-arched eyebrows, hypertelorism, ocular CC colobomata, and a brain malformation consisting of anterior- CC predominant lissencephaly. Other typical features include CC postnatal short stature and microcephaly, intellectual disability, CC seizures, and hearing loss. {ECO:0000269|PubMed:22366783}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- MISCELLANEOUS: In vertebrates 3 main groups of actin isoforms, CC alpha, beta and gamma have been identified. The alpha actins are CC found in muscle tissues and are a major constituent of the CC contractile apparatus. The beta and gamma actins coexist in most CC cell types as components of the cytoskeleton and as mediators of CC internal cell motility. CC -!- SIMILARITY: Belongs to the actin family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Mendelian genes actin, gamma 1 (ACTG1); CC Note=Leiden Open Variation Database (LOVD); CC URL="http://www.lovd.nl/ACTG1"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X04098; CAA27723.1; -; mRNA. DR EMBL; M19283; AAA51579.1; -; Genomic_DNA. DR EMBL; AK291937; BAF84626.1; -; mRNA. DR EMBL; BT019856; AAV38659.1; -; mRNA. DR EMBL; BC000292; AAH00292.1; -; mRNA. DR EMBL; BC001920; AAH01920.1; -; mRNA. DR EMBL; BC007442; AAH07442.1; -; mRNA. DR EMBL; BC009848; AAH09848.1; -; mRNA. DR EMBL; BC010999; AAH10999.1; -; mRNA. DR EMBL; BC012050; AAH12050.1; -; mRNA. DR EMBL; BC015005; AAH15005.1; -; mRNA. DR EMBL; BC015695; AAH15695.1; -; mRNA. DR EMBL; BC015779; AAH15779.1; -; mRNA. DR EMBL; BC018774; AAH18774.1; -; mRNA. DR EMBL; BC053572; AAH53572.1; -; mRNA. DR EMBL; M16247; AAA51580.1; -; mRNA. DR CCDS; CCDS11782.1; -. DR PIR; A28098; ATHUG. DR PIR; JC5818; JC5818. DR RefSeq; NP_001186883.1; NM_001199954.1. DR RefSeq; NP_001605.1; NM_001614.3. DR UniGene; Hs.514581; -. DR UniGene; Hs.713764; -. DR ProteinModelPortal; P63261; -. DR SMR; P63261; 6-375. DR BioGrid; 106586; 93. DR IntAct; P63261; 46. DR MINT; MINT-4998686; -. DR STRING; 9606.ENSP00000331514; -. DR PhosphoSite; P63261; -. DR BioMuta; ACTG1; -. DR DMDM; 54036678; -. DR DOSAC-COBS-2DPAGE; P60709_OR_P63261; -. DR DOSAC-COBS-2DPAGE; P63261; -. DR OGP; P63261; -. DR REPRODUCTION-2DPAGE; P63261; -. DR SWISS-2DPAGE; P63261; -. DR MaxQB; P63261; -. DR PaxDb; P63261; -. DR PRIDE; P63261; -. DR DNASU; 71; -. DR Ensembl; ENST00000331925; ENSP00000331514; ENSG00000184009. DR Ensembl; ENST00000573283; ENSP00000458435; ENSG00000184009. DR Ensembl; ENST00000575087; ENSP00000459124; ENSG00000184009. DR Ensembl; ENST00000575842; ENSP00000458162; ENSG00000184009. DR Ensembl; ENST00000576544; ENSP00000461672; ENSG00000184009. DR Ensembl; ENST00000615544; ENSP00000477968; ENSG00000184009. DR GeneID; 71; -. DR KEGG; hsa:71; -. DR UCSC; uc002kak.2; human. DR CTD; 71; -. DR GeneCards; ACTG1; -. DR GeneReviews; ACTG1; -. DR H-InvDB; HIX0001479; -. DR H-InvDB; HIX0199868; -. DR HGNC; HGNC:144; ACTG1. DR HPA; HPA041264; -. DR HPA; HPA041271; -. DR MIM; 102560; gene. DR MIM; 604717; phenotype. DR MIM; 614583; phenotype. DR neXtProt; NX_P63261; -. DR Orphanet; 90635; Autosomal dominant non-syndromic sensorineural deafness type DFNA. DR Orphanet; 2995; Baraitser-Winter syndrome. DR PharmGKB; PA24468; -. DR eggNOG; KOG0676; Eukaryota. DR eggNOG; COG5277; LUCA. DR GeneTree; ENSGT00760000118957; -. DR HOVERGEN; HBG003771; -. DR InParanoid; P63261; -. DR KO; K05692; -. DR OMA; TFQQART; -. DR PhylomeDB; P63261; -. DR TreeFam; TF354237; -. DR Reactome; R-HSA-1445148; Translocation of GLUT4 to the plasma membrane. DR Reactome; R-HSA-190873; Gap junction degradation. DR Reactome; R-HSA-196025; Formation of annular gap junctions. DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation. DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling. DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells. DR Reactome; R-HSA-418990; Adherens junctions interactions. DR Reactome; R-HSA-437239; Recycling pathway of L1. DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway. DR Reactome; R-HSA-445095; Interaction between L1 and Ankyrins. DR Reactome; R-HSA-446353; Cell-extracellular matrix interactions. DR Reactome; R-HSA-5626467; RHO GTPases activate IQGAPs. DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs. DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins. DR Reactome; R-HSA-5674135; MAP2K and MAPK activation. DR SignaLink; P63261; -. DR ChiTaRS; ACTG1; human. DR GeneWiki; ACTG1; -. DR GenomeRNAi; 71; -. DR NextBio; 279; -. DR PMAP-CutDB; P63261; -. DR PRO; PR:P63261; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; P63261; -. DR CleanEx; HS_ACTB; -. DR CleanEx; HS_ACTG1; -. DR ExpressionAtlas; P63261; baseline and differential. DR Genevisible; P63261; HS. DR GO; GO:0072562; C:blood microparticle; IDA:UniProtKB. DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0097433; C:dense body; ISS:AgBase. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB. DR GO; GO:0031941; C:filamentous actin; IEA:Ensembl. DR GO; GO:0005925; C:focal adhesion; ISS:AgBase. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0043209; C:myelin sheath; IEA:Ensembl. DR GO; GO:0030016; C:myofibril; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:AgBase. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005200; F:structural constituent of cytoskeleton; IC:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0034332; P:adherens junction organization; TAS:Reactome. DR GO; GO:0007411; P:axon guidance; TAS:Reactome. DR GO; GO:0034329; P:cell junction assembly; TAS:Reactome. DR GO; GO:0045216; P:cell-cell junction organization; TAS:Reactome. DR GO; GO:0048013; P:ephrin receptor signaling pathway; TAS:Reactome. DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0061024; P:membrane organization; TAS:Reactome. DR GO; GO:0006928; P:movement of cell or subcellular component; TAS:UniProtKB. DR GO; GO:0070527; P:platelet aggregation; IMP:UniProtKB. DR GO; GO:0051592; P:response to calcium ion; IEA:Ensembl. DR GO; GO:0001895; P:retina homeostasis; IEP:UniProtKB. DR GO; GO:0045214; P:sarcomere organization; IEA:Ensembl. DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; TAS:Reactome. DR InterPro; IPR004000; Actin. DR InterPro; IPR020902; Actin/actin-like_CS. DR InterPro; IPR004001; Actin_CS. DR PANTHER; PTHR11937; PTHR11937; 1. DR Pfam; PF00022; Actin; 1. DR PRINTS; PR00190; ACTIN. DR SMART; SM00268; ACTIN; 1. DR PROSITE; PS00406; ACTINS_1; 1. DR PROSITE; PS00432; ACTINS_2; 1. DR PROSITE; PS01132; ACTINS_ACT_LIKE; 1. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Complete proteome; Cytoplasm; Cytoskeleton; KW Deafness; Direct protein sequencing; Disease mutation; KW Isopeptide bond; Mental retardation; Methylation; KW Non-syndromic deafness; Nucleotide-binding; Oxidation; Polymorphism; KW Reference proteome. FT CHAIN 1 375 Actin, cytoplasmic 2. FT /FTId=PRO_0000367100. FT INIT_MET 1 1 Removed; alternate. FT {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22223895, FT ECO:0000244|PubMed:22814378, FT ECO:0000244|PubMed:25944712, FT ECO:0000269|PubMed:12665801, FT ECO:0000269|Ref.7, ECO:0000269|Ref.8}. FT CHAIN 2 375 Actin, cytoplasmic 2, N-terminally FT processed. FT /FTId=PRO_0000000831. FT MOD_RES 1 1 N-acetylmethionine. FT {ECO:0000244|PubMed:22223895, FT ECO:0000244|PubMed:22814378}. FT MOD_RES 2 2 N-acetylglutamate; in Actin, cytoplasmic FT 2, N-terminally processed; partial. FT {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22223895, FT ECO:0000244|PubMed:22814378, FT ECO:0000244|PubMed:25944712, FT ECO:0000269|Ref.7, ECO:0000269|Ref.8}. FT MOD_RES 44 44 Methionine (R)-sulfoxide. {ECO:0000250}. FT MOD_RES 47 47 Methionine (R)-sulfoxide. {ECO:0000250}. FT MOD_RES 73 73 Tele-methylhistidine. FT {ECO:0000269|Ref.8}. FT MOD_RES 84 84 N6-methyllysine. FT {ECO:0000269|PubMed:23673617}. FT CROSSLNK 50 50 Isoglutamyl lysine isopeptide (Lys-Glu) FT (interchain with E-270); by Vibrio toxins FT RtxA and VgrG1. FT {ECO:0000250|UniProtKB:P60709}. FT CROSSLNK 270 270 Isoglutamyl lysine isopeptide (Glu-Lys) FT (interchain with K-50); by Vibrio toxins FT RtxA and VgrG1. FT {ECO:0000250|UniProtKB:P60709}. FT VARIANT 89 89 T -> I (in DFNA20; dbSNP:rs28999111). FT {ECO:0000269|PubMed:13680526}. FT /FTId=VAR_032434. FT VARIANT 118 118 K -> M (in DFNA20). FT {ECO:0000269|PubMed:13680526}. FT /FTId=VAR_032435. FT VARIANT 118 118 K -> N (in DFNA20; dbSNP:rs267606630). FT {ECO:0000269|PubMed:19477959}. FT /FTId=VAR_067824. FT VARIANT 120 120 T -> I (in BRWS2; dbSNP:rs281875325). FT {ECO:0000269|PubMed:22366783}. FT /FTId=VAR_067814. FT VARIANT 122 122 I -> V (in DFNA20; dbSNP:rs281875330). FT {ECO:0000269|PubMed:18804074}. FT /FTId=VAR_067825. FT VARIANT 135 135 A -> V (in BRWS2; dbSNP:rs11549190). FT {ECO:0000269|PubMed:22366783}. FT /FTId=VAR_067815. FT VARIANT 155 155 S -> F (in BRWS2; dbSNP:rs281875326). FT {ECO:0000269|PubMed:22366783}. FT /FTId=VAR_067816. FT VARIANT 160 160 T -> I (in dbSNP:rs11549206). FT /FTId=VAR_048186. FT VARIANT 203 203 T -> K (in BRWS2; dbSNP:rs281875327). FT {ECO:0000269|PubMed:22366783}. FT /FTId=VAR_067817. FT VARIANT 241 241 E -> K (in DFNA20; dbSNP:rs267606631). FT {ECO:0000269|PubMed:19477959}. FT /FTId=VAR_067826. FT VARIANT 243 243 P -> L (in dbSNP:rs11546899). FT /FTId=VAR_055482. FT VARIANT 254 254 R -> W (in BRWS2; dbSNP:rs281875328). FT {ECO:0000269|PubMed:22366783}. FT /FTId=VAR_067818. FT VARIANT 256 256 R -> W (in BRWS2; dbSNP:rs281875329). FT {ECO:0000269|PubMed:22366783}. FT /FTId=VAR_067819. FT VARIANT 264 264 P -> L (in DFNA20). FT {ECO:0000269|PubMed:13680526}. FT /FTId=VAR_032436. FT VARIANT 278 278 T -> I (in DFNA20; dbSNP:rs28999112). FT {ECO:0000269|PubMed:14684684}. FT /FTId=VAR_032437. FT VARIANT 332 332 P -> A (in DFNA20). FT {ECO:0000269|PubMed:13680526}. FT /FTId=VAR_032438. FT VARIANT 370 370 V -> A (in DFNA20; restricts cell growth FT at elevated temperature or under FT hyperosmolar stress as measured in growth FT assays with yeast expressing the FT mutation). {ECO:0000269|PubMed:16773128}. FT /FTId=VAR_032439. FT CONFLICT 316 316 E -> K (in Ref. 10; AAA51580). FT {ECO:0000305}. FT CONFLICT 344 344 S -> F (in Ref. 10; AAA51580). FT {ECO:0000305}. SQ SEQUENCE 375 AA; 41793 MW; 54D08F986964EFD5 CRC64; MEEEIAALVI DNGSGMCKAG FAGDDAPRAV FPSIVGRPRH QGVMVGMGQK DSYVGDEAQS KRGILTLKYP IEHGIVTNWD DMEKIWHHTF YNELRVAPEE HPVLLTEAPL NPKANREKMT QIMFETFNTP AMYVAIQAVL SLYASGRTTG IVMDSGDGVT HTVPIYEGYA LPHAILRLDL AGRDLTDYLM KILTERGYSF TTTAEREIVR DIKEKLCYVA LDFEQEMATA ASSSSLEKSY ELPDGQVITI GNERFRCPEA LFQPSFLGME SCGIHETTFN SIMKCDVDIR KDLYANTVLS GGTTMYPGIA DRMQKEITAL APSTMKIKII APPERKYSVW IGGSILASLS TFQQMWISKQ EYDESGPSIV HRKCF // ID AKTIP_HUMAN Reviewed; 292 AA. AC Q9H8T0; Q503B1; Q53H38; DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 11-NOV-2015, entry version 119. DE RecName: Full=AKT-interacting protein; DE AltName: Full=Ft1; DE AltName: Full=Fused toes protein homolog; GN Name=AKTIP; Synonyms=FTS; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Ovary; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Dermoid cancer; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, INTERACTION WITH AKT1, AND SUBCELLULAR LOCATION. RX PubMed=14749367; DOI=10.1128/MCB.24.4.1493-1504.2004; RA Remy I., Michnick S.W.; RT "Regulation of apoptosis by the Ft1 protein, a new modulator of RT protein kinase B/Akt."; RL Mol. Cell. Biol. 24:1493-1504(2004). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE FHF RP COMPLEX, FUNCTION, ASSOCIATION WITH THE HOPS COMPLEX, AND MUTAGENESIS RP OF 106-TRP-PHE-107. RX PubMed=18799622; DOI=10.1091/mbc.E08-05-0473; RA Xu L., Sowa M.E., Chen J., Li X., Gygi S.P., Harper J.W.; RT "An FTS/Hook/p107(FHIP) complex interacts with and promotes endosomal RT clustering by the homotypic vacuolar protein sorting complex."; RL Mol. Biol. Cell 19:5059-5071(2008). CC -!- FUNCTION: Component of the FTS/Hook/FHIP complex (FHF complex). CC The FHF complex may function to promote vesicle trafficking and/or CC fusion via the homotypic vesicular protein sorting complex (the CC HOPS complex). Regulates apoptosis by enhancing phosphorylation CC and activation of AKT1. Increases release of TNFSF6 via the CC AKT1/GSK3B/NFATC1 signaling cascade. {ECO:0000269|PubMed:14749367, CC ECO:0000269|PubMed:18799622}. CC -!- SUBUNIT: Component of the FTS/Hook/FHIP complex (FHF complex), CC composed of AKTIP/FTS, FAM160A2, and one or more members of the CC Hook family of proteins HOOK1, HOOK2, and HOOK3. May interact CC directly with HOOK1, HOOK2 and HOOK3. The FHF complex associates CC with the homotypic vesicular sorting complex (the HOPS complex). CC Also interacts with AKT1. {ECO:0000269|PubMed:14749367, CC ECO:0000269|PubMed:18799622}. CC -!- INTERACTION: CC Q9UJC3:HOOK1; NbExp=3; IntAct=EBI-711399, EBI-746704; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14749367}. CC Cell membrane {ECO:0000269|PubMed:14749367}; Peripheral membrane CC protein {ECO:0000269|PubMed:14749367}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9H8T0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9H8T0-2; Sequence=VSP_037631; CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. CC FTS subfamily. {ECO:0000255|PROSITE-ProRule:PRU00388}. CC -!- CAUTION: Lacks the conserved Cys residue necessary for ubiquitin- CC conjugating enzyme E2 activity. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AK023320; BAB14524.1; -; mRNA. DR EMBL; CR457308; CAG33589.1; -; mRNA. DR EMBL; AK222743; BAD96463.1; -; mRNA. DR EMBL; CH471092; EAW82805.1; -; Genomic_DNA. DR EMBL; BC001134; AAH01134.1; -; mRNA. DR EMBL; BC095401; AAH95401.1; -; mRNA. DR CCDS; CCDS10749.1; -. [Q9H8T0-1] DR CCDS; CCDS76866.1; -. [Q9H8T0-2] DR RefSeq; NP_001012398.1; NM_001012398.2. [Q9H8T0-1] DR RefSeq; NP_001295254.1; NM_001308325.1. [Q9H8T0-2] DR RefSeq; NP_071921.1; NM_022476.3. [Q9H8T0-1] DR RefSeq; XP_005256152.1; XM_005256095.3. [Q9H8T0-2] DR RefSeq; XP_005256153.1; XM_005256096.3. [Q9H8T0-2] DR RefSeq; XP_005256154.1; XM_005256097.3. [Q9H8T0-2] DR RefSeq; XP_005256155.1; XM_005256098.3. [Q9H8T0-2] DR UniGene; Hs.380897; -. DR ProteinModelPortal; Q9H8T0; -. DR BioGrid; 122157; 34. DR IntAct; Q9H8T0; 29. DR STRING; 9606.ENSP00000378152; -. DR PhosphoSite; Q9H8T0; -. DR BioMuta; AKTIP; -. DR DMDM; 54035954; -. DR MaxQB; Q9H8T0; -. DR PaxDb; Q9H8T0; -. DR PRIDE; Q9H8T0; -. DR DNASU; 64400; -. DR Ensembl; ENST00000300245; ENSP00000300245; ENSG00000166971. [Q9H8T0-2] DR Ensembl; ENST00000394657; ENSP00000378152; ENSG00000166971. [Q9H8T0-1] DR Ensembl; ENST00000570004; ENSP00000455874; ENSG00000166971. [Q9H8T0-1] DR GeneID; 64400; -. DR KEGG; hsa:64400; -. DR UCSC; uc002ehk.3; human. [Q9H8T0-1] DR UCSC; uc002ehm.3; human. [Q9H8T0-2] DR CTD; 64400; -. DR GeneCards; AKTIP; -. DR HGNC; HGNC:16710; AKTIP. DR HPA; HPA041794; -. DR HPA; HPA046300; -. DR MIM; 608483; gene. DR neXtProt; NX_Q9H8T0; -. DR PharmGKB; PA162376210; -. DR eggNOG; KOG0429; Eukaryota. DR eggNOG; ENOG410ZQ9Z; LUCA. DR GeneTree; ENSGT00390000010125; -. DR HOGENOM; HOG000033885; -. DR HOVERGEN; HBG095637; -. DR InParanoid; Q9H8T0; -. DR OMA; KSIRECK; -. DR OrthoDB; EOG7QG45C; -. DR PhylomeDB; Q9H8T0; -. DR TreeFam; TF314386; -. DR SignaLink; Q9H8T0; -. DR GeneWiki; AKTIP; -. DR GenomeRNAi; 64400; -. DR NextBio; 66346; -. DR PRO; PR:Q9H8T0; -. DR Proteomes; UP000005640; Chromosome 16. DR Bgee; Q9H8T0; -. DR CleanEx; HS_AKTIP; -. DR ExpressionAtlas; Q9H8T0; baseline and differential. DR Genevisible; Q9H8T0; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0070695; C:FHF complex; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IBA:GO_Central. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IBA:GO_Central. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0045022; P:early endosome to late endosome transport; IMP:UniProtKB. DR GO; GO:0007032; P:endosome organization; IMP:UniProtKB. DR GO; GO:0008333; P:endosome to lysosome transport; IMP:UniProtKB. DR GO; GO:0007040; P:lysosome organization; IMP:UniProtKB. DR GO; GO:0032092; P:positive regulation of protein binding; IDA:MGI. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:MGI. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central. DR Gene3D; 3.10.110.10; -; 1. DR InterPro; IPR000608; UBQ-conjugat_E2. DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD. DR Pfam; PF00179; UQ_con; 1. DR SUPFAM; SSF54495; SSF54495; 1. DR PROSITE; PS50127; UBIQUITIN_CONJUGAT_2; 1. PE 1: Evidence at protein level; KW Alternative splicing; Apoptosis; Cell membrane; Complete proteome; KW Cytoplasm; Membrane; Phosphoprotein; Protein transport; KW Reference proteome; Transport. FT CHAIN 1 292 AKT-interacting protein. FT /FTId=PRO_0000082609. FT MOD_RES 30 30 Phosphoserine. FT {ECO:0000250|UniProtKB:Q64362}. FT VAR_SEQ 256 256 Q -> QK (in isoform 2). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.3}. FT /FTId=VSP_037631. FT MUTAGEN 106 107 WF->AA: Impairs interaction with HOOK1, FT HOOK2 and HOOK3. FT {ECO:0000269|PubMed:18799622}. FT CONFLICT 212 212 K -> N (in Ref. 5; AAH95401). FT {ECO:0000305}. SQ SEQUENCE 292 AA; 33128 MW; 3DD4E32980463324 CRC64; MNPFWSMSTS SVRKRSEGEE KTLTGDVKTS PPRTAPKKQL PSIPKNALPI TKPTSPAPAA QSTNGTHASY GPFYLEYSLL AEFTLVVKQK LPGVYVQPSY RSALMWFGVI FIRHGLYQDG VFKFTVYIPD NYPDGDCPRL VFDIPVFHPL VDPTSGELDV KRAFAKWRRN HNHIWQVLMY ARRVFYKIDT ASPLNPEAAV LYEKDIQLFK SKVVDSVKVC TARLFDQPKI EDPYAISFSP WNPSVHDEAR EKMLTQKKPE EQHNKSVHVA GLSWVKPGSV QPFSKEEKTV AT // ID AP2A_HUMAN Reviewed; 437 AA. AC P05549; Q13777; Q5TAV5; Q8N1C6; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1989, sequence version 1. DT 11-NOV-2015, entry version 163. DE RecName: Full=Transcription factor AP-2-alpha; DE Short=AP2-alpha; DE AltName: Full=AP-2 transcription factor; DE AltName: Full=Activating enhancer-binding protein 2-alpha; DE AltName: Full=Activator protein 2; DE Short=AP-2; GN Name=TFAP2A; Synonyms=AP2TF, TFAP2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PARTIAL PROTEIN SEQUENCE. RX PubMed=3063603; DOI=10.1101/gad.2.12a.1557; RA Williams T., Admon A., Luescher B., Tjian R.; RT "Cloning and expression of AP-2, a cell-type-specific transcription RT factor that activates inducible enhancer elements."; RL Genes Dev. 2:1557-1569(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 4). RC TISSUE=Teratocarcinoma; RX PubMed=8321221; RA Buettner R., Kannan P., Imhof A., Bauer R., Yim S.O., Glockshuber R., RA Van Dyke M.W., Tainsky M.A.; RT "An alternatively spliced mRNA from the AP-2 gene encodes a negative RT regulator of transcriptional activation by AP-2."; RL Mol. Cell. Biol. 13:4174-4185(1993). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8190633; DOI=10.1093/nar/22.8.1413; RA Bauer R., Imhof A., Pscherer A., Kopp H., Moser M., Seegers S., RA Kerscher M., Tainsky M.A., Hofstaedter F., Buettner R.; RT "The genomic structure of the human AP-2 transcription factor."; RL Nucleic Acids Res. 22:1413-1420(1994). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Prostate; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP SUBUNIT. RX PubMed=1998122; DOI=10.1126/science.1998122; RA Williams T., Tjian R.; RT "Characterization of a dimerization motif in AP-2 and its function in RT heterologous DNA-binding proteins."; RL Science 251:1067-1071(1991). RN [8] RP DNA-BINDING. RX PubMed=2010091; DOI=10.1101/gad.5.4.670; RA Williams T., Tjian R.; RT "Analysis of the DNA-binding and activation properties of the human RT transcription factor AP-2."; RL Genes Dev. 5:670-682(1991). RN [9] RP PHOSPHORYLATION AT SER-239, AND MUTAGENESIS OF SER-239. RX PubMed=10037142; DOI=10.1016/S0014-5793(99)00021-6; RA Garcia M.A., Campillos M., Marina A., Valdivieso F., Vazquez J.; RT "Transcription factor AP-2 activity is modulated by protein kinase A- RT mediated phosphorylation."; RL FEBS Lett. 444:27-31(1999). RN [10] RP FUNCTION, AND INTERACTION WITH CITED2. RX PubMed=11694877; DOI=10.1038/ng768; RA Bamforth S.D., Braganca J., Eloranta J.J., Murdoch J.N., Marques F.I., RA Kranc K.R., Farza H., Henderson D.J., Hurst H.C., Bhattacharya S.; RT "Cardiac malformations, adrenal agenesis, neural crest defects and RT exencephaly in mice lacking Cited2, a new Tfap2 co-activator."; RL Nat. Genet. 29:469-474(2001). RN [11] RP INTERACTION WITH CITED4. RX PubMed=11744733; DOI=10.1074/jbc.M110850200; RA Braganca J., Swingler T., Marques F.I.R., Jones T., Eloranta J.J., RA Hurst H.C., Shioda T., Bhattacharya S.; RT "Human CREB-binding protein/p300-interacting transactivator with ED- RT rich tail (CITED) 4, a new member of the CITED family, functions as a RT co-activator for transcription factor AP-2."; RL J. Biol. Chem. 277:8559-8565(2002). RN [12] RP INTERACTION WITH UBE2I, AND SUMOYLATION AT LYS-10. RX PubMed=12072434; DOI=10.1074/jbc.M202780200; RA Eloranta J.J., Hurst H.C.; RT "Transcription factor AP-2 interacts with the SUMO-conjugating enzyme RT UBC9 and is sumolated in vivo."; RL J. Biol. Chem. 277:30798-30804(2002). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, DNA-BINDING, AND INTERACTION WITH RP CITED2 AND EP300. RX PubMed=12586840; DOI=10.1074/jbc.M208144200; RA Braganca J., Eloranta J.J., Bamforth S.D., Ibbitt J.C., Hurst H.C., RA Bhattacharya S.; RT "Physical and functional interactions among AP-2 transcription RT factors, p300/CREB-binding protein, and CITED2."; RL J. Biol. Chem. 278:16021-16029(2003). RN [14] RP INTERACTION WITH RALBP1. RX PubMed=12775724; DOI=10.1074/jbc.M302191200; RA Rosse C., L'Hoste S., Offner N., Picard A., Camonis J.; RT "RLIP, an effector of the Ral GTPases, is a platform for Cdk1 to RT phosphorylate epsin during the switch off of endocytosis in mitosis."; RL J. Biol. Chem. 278:30597-30604(2003). RN [15] RP INTERACTION WITH WWOX, AND DOMAIN. RX PubMed=15548692; DOI=10.1158/0008-5472.CAN-04-2055; RA Aqeilan R.I., Palamarchuk A., Weigel R.J., Herrero J.J., Pekarsky Y., RA Croce C.M.; RT "Physical and functional interactions between the Wwox tumor RT suppressor protein and the AP-2gamma transcription factor."; RL Cancer Res. 64:8256-8261(2004). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [17] RP INTERACTION WITH KCTD1. RX PubMed=19115315; DOI=10.1002/jcb.22002; RA Ding X., Luo C., Zhou J., Zhong Y., Hu X., Zhou F., Ren K., Gan L., RA He A., Zhu J., Gao X., Zhang J.; RT "The interaction of KCTD1 with transcription factor AP-2alpha inhibits RT its transactivation."; RL J. Cell. Biochem. 106:285-295(2009). RN [18] RP INTERACTION WITH KCTD15. RX PubMed=23382213; DOI=10.1073/pnas.1300203110; RA Zarelli V.E., Dawid I.B.; RT "Inhibition of neural crest formation by Kctd15 involves regulation of RT transcription factor AP-2."; RL Proc. Natl. Acad. Sci. U.S.A. 110:2870-2875(2013). RN [19] RP VARIANTS BOFS PRO-249; GLY-254; GLY-255 AND GLU-262. RX PubMed=18423521; DOI=10.1016/j.ajhg.2008.03.005; RA Milunsky J.M., Maher T.A., Zhao G., Roberts A.E., Stalker H.J., RA Zori R.T., Burch M.N., Clemens M., Mulliken J.B., Smith R., Lin A.E.; RT "TFAP2A mutations result in branchio-oculo-facial syndrome."; RL Am. J. Hum. Genet. 82:1171-1177(2008). CC -!- FUNCTION: Sequence-specific DNA-binding protein that interacts CC with inducible viral and cellular enhancer elements to regulate CC transcription of selected genes. AP-2 factors bind to the CC consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in CC a large spectrum of important biological functions including CC proper eye, face, body wall, limb and neural tube development. CC They also suppress a number of genes including MCAM/MUC18, C/EBP CC alpha and MYC. AP-2-alpha is the only AP-2 protein required for CC early morphogenesis of the lens vesicle. Together with the CITED2 CC coactivator, stimulates the PITX2 P1 promoter transcription CC activation. Associates with chromatin to the PITX2 P1 promoter CC region. {ECO:0000269|PubMed:11694877, CC ECO:0000269|PubMed:12586840}. CC -!- SUBUNIT: Binds DNA as a dimer. Can form homodimers or heterodimers CC with other AP-2 family members. Interacts with WWOX. Interacts CC with CITED4. Interacts with UBE2I. Interacts with RALBP1 in a CC complex also containing EPN1 and NUMB during interphase and CC mitosis. Interacts with KCTD1; this interaction represses CC transcription activation. Interacts (via C-terminus) with CITED2 CC (via C-terminus); the interaction stimulates TFAP2A- CC transcriptional activation. Interacts (via N-terminus) with EP300 CC (via N-terminus); the interaction requires CITED2. Interacts with CC KCTD15; this interaction inhibits TFAP2A transcriptional CC activation. {ECO:0000269|PubMed:11694877, CC ECO:0000269|PubMed:11744733, ECO:0000269|PubMed:12072434, CC ECO:0000269|PubMed:12586840, ECO:0000269|PubMed:12775724, CC ECO:0000269|PubMed:15548692, ECO:0000269|PubMed:19115315, CC ECO:0000269|PubMed:1998122, ECO:0000269|PubMed:23382213}. CC -!- INTERACTION: CC Q09472:EP300; NbExp=7; IntAct=EBI-347351, EBI-447295; CC Q9H4Y5:GSTO2; NbExp=3; IntAct=EBI-347351, EBI-10194609; CC Q13064:MKRN3; NbExp=3; IntAct=EBI-347351, EBI-2340269; CC P06748:NPM1; NbExp=6; IntAct=EBI-347351, EBI-78579; CC P63279:UBE2I; NbExp=4; IntAct=EBI-347351, EBI-80168; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12586840}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Comment=Experimental confirmation may be lacking for some CC isoforms.; CC Name=1; Synonyms=AP-2A; CC IsoId=P05549-1; Sequence=Displayed; CC Name=2; CC IsoId=P05549-5; Sequence=VSP_043268; CC Note=No experimental confirmation available.; CC Name=4; Synonyms=AP-2B; CC IsoId=P05549-2; Sequence=VSP_006401; CC Note=May be an aberrantly processed form with no significant CC distribution in vivo.; CC Name=5; CC IsoId=P05549-6; Sequence=VSP_047050; CC Note=Gene prediction based on EST data.; CC -!- DOMAIN: The WW-binding motif mediates interaction with WWOX. CC {ECO:0000250}. CC -!- PTM: Sumoylated on Lys-10; which inhibits transcriptional CC activity. {ECO:0000305|PubMed:12072434}. CC -!- DISEASE: Branchiooculofacial syndrome (BOFS) [MIM:113620]: A CC syndrome characterized by growth retardation, bilateral branchial CC sinus defects with hemangiomatous, scarred skin, cleft lip with or CC without cleft palate, pseudocleft of the upper lip, nasolacrimal CC duct obstruction, low set ears with posterior rotation, a CC malformed, asymmetrical nose with a broad bridge and flattened CC tip, conductive or sensorineural deafness, ocular and renal CC anomalies. {ECO:0000269|PubMed:18423521}. Note=The disease is CC caused by mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the AP-2 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Activatin protein 2 entry; CC URL="https://en.wikipedia.org/wiki/Activating_protein_2"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/TFAP2AID42526ch6p24.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M36711; AAA35539.1; -; mRNA. DR EMBL; M61156; AAA02487.1; -; mRNA. DR EMBL; X52611; CAA36842.1; -; mRNA. DR EMBL; X77343; CAB59735.1; -; Genomic_DNA. DR EMBL; AL138885; CAI20064.1; -; Genomic_DNA. DR EMBL; CH471087; EAW55249.1; -; Genomic_DNA. DR EMBL; BC017754; AAH17754.1; -; mRNA. DR CCDS; CCDS34337.1; -. [P05549-5] DR CCDS; CCDS43422.1; -. [P05549-6] DR CCDS; CCDS4510.1; -. [P05549-1] DR PIR; A31752; A31752. DR RefSeq; NP_001027451.1; NM_001032280.2. [P05549-5] DR RefSeq; NP_001035890.1; NM_001042425.1. [P05549-6] DR RefSeq; NP_003211.1; NM_003220.2. [P05549-1] DR UniGene; Hs.519880; -. DR ProteinModelPortal; P05549; -. DR BioGrid; 112878; 34. DR IntAct; P05549; 80. DR MINT; MINT-1524309; -. DR STRING; 9606.ENSP00000368924; -. DR PhosphoSite; P05549; -. DR BioMuta; TFAP2A; -. DR DMDM; 135302; -. DR MaxQB; P05549; -. DR PaxDb; P05549; -. DR PRIDE; P05549; -. DR DNASU; 7020; -. DR Ensembl; ENST00000319516; ENSP00000316516; ENSG00000137203. [P05549-6] DR Ensembl; ENST00000379608; ENSP00000368928; ENSG00000137203. [P05549-5] DR Ensembl; ENST00000482890; ENSP00000418541; ENSG00000137203. [P05549-1] DR GeneID; 7020; -. DR KEGG; hsa:7020; -. DR UCSC; uc003myq.3; human. [P05549-5] DR UCSC; uc003myr.3; human. [P05549-1] DR UCSC; uc003myt.3; human. DR UCSC; uc003myu.1; human. [P05549-2] DR CTD; 7020; -. DR GeneCards; TFAP2A; -. DR GeneReviews; TFAP2A; -. DR HGNC; HGNC:11742; TFAP2A. DR HPA; CAB000326; -. DR HPA; HPA028850; -. DR HPA; HPA056871; -. DR MIM; 107580; gene. DR MIM; 113620; phenotype. DR neXtProt; NX_P05549; -. DR Orphanet; 1297; Branchio-oculo-facial syndrome. DR PharmGKB; PA36459; -. DR eggNOG; KOG3811; Eukaryota. DR eggNOG; ENOG410XR9E; LUCA. DR GeneTree; ENSGT00550000074577; -. DR HOGENOM; HOG000231737; -. DR HOVERGEN; HBG002455; -. DR InParanoid; P05549; -. DR KO; K09176; -. DR PhylomeDB; P05549; -. DR TreeFam; TF313718; -. DR ChiTaRS; TFAP2A; human. DR GeneWiki; TFAP2A; -. DR GenomeRNAi; 7020; -. DR NextBio; 27423; -. DR PMAP-CutDB; P05549; -. DR PRO; PR:P05549; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; P05549; -. DR CleanEx; HS_TFAP2A; -. DR ExpressionAtlas; P05549; baseline and differential. DR Genevisible; P05549; HS. DR GO; GO:0005813; C:centrosome; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0000987; F:core promoter proximal region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; TAS:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0000982; F:transcription factor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:UniProtKB. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:UniProtKB. DR GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:UniProtKB. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:UniProtKB. DR GO; GO:0060349; P:bone morphogenesis; ISS:UniProtKB. DR GO; GO:0071281; P:cellular response to iron ion; IDA:UniProtKB. DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; ISS:UniProtKB. DR GO; GO:0035115; P:embryonic forelimb morphogenesis; ISS:UniProtKB. DR GO; GO:0061029; P:eyelid development in camera-type eye; ISS:UniProtKB. DR GO; GO:0042472; P:inner ear morphogenesis; IMP:UniProtKB. DR GO; GO:0001822; P:kidney development; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell proliferation; IDA:UniProtKB. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IDA:UniProtKB. DR GO; GO:0010944; P:negative regulation of transcription by competitive promoter binding; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0021623; P:oculomotor nerve formation; ISS:UniProtKB. DR GO; GO:0003409; P:optic cup structural organization; ISS:UniProtKB. DR GO; GO:0003404; P:optic vesicle morphogenesis; ISS:UniProtKB. DR GO; GO:0060021; P:palate development; IMP:UniProtKB. DR GO; GO:0030501; P:positive regulation of bone mineralization; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IDA:UniProtKB. DR GO; GO:0070172; P:positive regulation of tooth mineralization; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0045595; P:regulation of cell differentiation; IDA:UniProtKB. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0009414; P:response to water deprivation; IEA:Ensembl. DR GO; GO:0010842; P:retina layer formation; IEP:UniProtKB. DR GO; GO:0014044; P:Schwann cell development; IEA:Ensembl. DR GO; GO:0007605; P:sensory perception of sound; IMP:UniProtKB. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IDA:GOC. DR GO; GO:0021559; P:trigeminal nerve development; ISS:UniProtKB. DR InterPro; IPR004979; TF_AP2. DR InterPro; IPR008121; TF_AP2_alpha_N. DR InterPro; IPR013854; TF_AP2_C. DR PANTHER; PTHR10812; PTHR10812; 1. DR Pfam; PF03299; TF_AP-2; 1. DR PRINTS; PR01749; AP2ATNSCPFCT. DR PRINTS; PR01748; AP2TNSCPFCT. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Complete proteome; KW Direct protein sequencing; Disease mutation; DNA-binding; KW Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; KW Transcription; Transcription regulation; Ubl conjugation. FT CHAIN 1 437 Transcription factor AP-2-alpha. FT /FTId=PRO_0000184796. FT REGION 280 410 H-S-H (helix-span-helix), dimerization. FT MOTIF 57 62 WW-binding. FT COMPBIAS 29 117 Gln/Pro-rich (transactivation domain). FT MOD_RES 239 239 Phosphoserine; by PKA. FT {ECO:0000269|PubMed:10037142}. FT CROSSLNK 10 10 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT {ECO:0000305}. FT VAR_SEQ 1 15 MLWKLTDNIKYEDCE -> MLVHSFSAM (in isoform FT 2). {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_043268. FT VAR_SEQ 1 15 MLWKLTDNIKYEDCE -> MSILAKMGDWQ (in FT isoform 5). {ECO:0000305}. FT /FTId=VSP_047050. FT VAR_SEQ 296 437 EAVHLARDFGYVCETEFPAKAVAEFLNRQHSDPNEQVTRKN FT MLLATKQICKEFTDLLAQDRSPLGNSRPNPILEPGIQSCLT FT HFNLISHGFGSPAVCAAVTALQNYLTEALKAMDKMYLSNNP FT NSHTDNNAKSSDKEEKHRK -> KRIHLLTRRNFLLGKWII FT FSGQMFGRILCQLGSFIFAENIARCEWNYFMAKRNICMYSY FT TSILLPSFPLP (in isoform 4). FT {ECO:0000303|PubMed:8321221}. FT /FTId=VSP_006401. FT VARIANT 249 249 L -> P (in BOFS). FT {ECO:0000269|PubMed:18423521}. FT /FTId=VAR_045838. FT VARIANT 254 254 R -> G (in BOFS). FT {ECO:0000269|PubMed:18423521}. FT /FTId=VAR_045839. FT VARIANT 255 255 R -> G (in BOFS). FT {ECO:0000269|PubMed:18423521}. FT /FTId=VAR_045840. FT VARIANT 262 262 G -> E (in BOFS). FT {ECO:0000269|PubMed:18423521}. FT /FTId=VAR_045841. FT MUTAGEN 239 239 S->A: No phosphorylation. FT {ECO:0000269|PubMed:10037142}. SQ SEQUENCE 437 AA; 48062 MW; FB8FA33C3AEED71F CRC64; MLWKLTDNIK YEDCEDRHDG TSNGTARLPQ LGTVGQSPYT SAPPLSHTPN ADFQPPYFPP PYQPIYPQSQ DPYSHVNDPY SLNPLHAQPQ PQHPGWPGQR QSQESGLLHT HRGLPHQLSG LDPRRDYRRH EDLLHGPHAL SSGLGDLSIH SLPHAIEEVP HVEDPGINIP DQTVIKKGPV SLSKSNSNAV SAIPINKDNL FGGVVNPNEV FCSVPGRLSL LSSTSKYKVT VAEVQRRLSP PECLNASLLG GVLRRAKSKN GGRSLREKLD KIGLNLPAGR RKAANVTLLT SLVEGEAVHL ARDFGYVCET EFPAKAVAEF LNRQHSDPNE QVTRKNMLLA TKQICKEFTD LLAQDRSPLG NSRPNPILEP GIQSCLTHFN LISHGFGSPA VCAAVTALQN YLTEALKAMD KMYLSNNPNS HTDNNAKSSD KEEKHRK // ID BAZ2B_HUMAN Reviewed; 2168 AA. AC Q9UIF8; D3DPA8; Q96EA1; Q96SQ8; Q9P252; Q9Y4N8; DT 30-AUG-2002, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 3. DT 11-NOV-2015, entry version 152. DE RecName: Full=Bromodomain adjacent to zinc finger domain protein 2B; DE AltName: Full=hWALp4; GN Name=BAZ2B; Synonyms=KIAA1476; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4). RC TISSUE=Testis; RX PubMed=10662543; DOI=10.1006/geno.1999.6071; RA Jones M.H., Hamana N., Nezu J., Shimane M.; RT "A novel family of bromodomain genes."; RL Genomics 63:40-45(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). RC TISSUE=Brain; RX PubMed=10819331; DOI=10.1093/dnares/7.2.143; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVII. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 7:143-150(2000). RN [3] RP SEQUENCE REVISION. RA Ohara O., Nagase T., Kikuno R.; RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-967 (ISOFORM 1), RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1720-2168 (ISOFORMS RP 1/2/3/4/5), AND VARIANTS THR-71 AND SER-422. RC TISSUE=Melanoma, and Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 95-986 (ISOFORM 2), AND RP VARIANT SER-422. RC TISSUE=Skeletal muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 670-1411 (ISOFORM 3). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [9] RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-1538. RC TISSUE=Mammary cancer; RX PubMed=17370265; DOI=10.1002/pmic.200600410; RA Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.; RT "Tryptic digestion of ubiquitin standards reveals an improved strategy RT for identifying ubiquitinated proteins by mass spectrometry."; RL Proteomics 7:868-874(2007). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1462, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1680; THR-2014 AND RP SER-2019, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [12] RP STRUCTURE BY NMR OF 2062-2166. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the bromodomain from human bromodomain adjacent RT to zinc finger domain 2B."; RL Submitted (JUL-2007) to the PDB data bank. RN [13] RP X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 2054-2168, AND SUBUNIT. RX PubMed=22464331; DOI=10.1016/j.cell.2012.02.013; RA Filippakopoulos P., Picaud S., Mangos M., Keates T., Lambert J.P., RA Barsyte-Lovejoy D., Felletar I., Volkmer R., Muller S., Pawson T., RA Gingras A.C., Arrowsmith C.H., Knapp S.; RT "Histone recognition and large-scale structural analysis of the human RT bromodomain family."; RL Cell 149:214-231(2012). CC -!- FUNCTION: May play a role in transcriptional regulation CC interacting with ISWI. CC -!- SUBUNIT: Interacts with acetylated lysine residues on histone CC H1.4, H2A, H2B, H3 and H4 (in vitro). CC {ECO:0000269|PubMed:22464331}. CC -!- INTERACTION: CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-10321972, EBI-10171902; CC P51116:FXR2; NbExp=3; IntAct=EBI-10321972, EBI-740459; CC Q96MF2:STAC3; NbExp=3; IntAct=EBI-10321972, EBI-745680; CC O43829:ZBTB14; NbExp=3; IntAct=EBI-10321972, EBI-10176632; CC Q96BR9:ZBTB8A; NbExp=3; IntAct=EBI-10321972, EBI-742740; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE- CC ProRule:PRU00063}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Comment=Experimental confirmation may be lacking for some CC isoforms.; CC Name=1; CC IsoId=Q9UIF8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UIF8-2; Sequence=VSP_037115, VSP_000553; CC Name=3; CC IsoId=Q9UIF8-3; Sequence=VSP_000554; CC Name=4; CC IsoId=Q9UIF8-4; Sequence=VSP_037114; CC Name=5; CC IsoId=Q9UIF8-5; Sequence=VSP_037115, VSP_000554; CC -!- TISSUE SPECIFICITY: Expressed at varying levels in several CC tissues, whereas a smaller transcript was expressed specifically CC in testis. CC -!- SIMILARITY: Belongs to the WAL family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 bromo domain. {ECO:0000255|PROSITE- CC ProRule:PRU00035}. CC -!- SIMILARITY: Contains 1 DDT domain. {ECO:0000255|PROSITE- CC ProRule:PRU00063}. CC -!- SIMILARITY: Contains 1 MBD (methyl-CpG-binding) domain. CC {ECO:0000255|PROSITE-ProRule:PRU00338}. CC -!- SIMILARITY: Contains 1 PHD-type zinc finger. {ECO:0000255|PROSITE- CC ProRule:PRU00146}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH12576.1; Type=Frameshift; Positions=927; Evidence={ECO:0000305}; CC Sequence=AAH12576.1; Type=Miscellaneous discrepancy; Note=contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=BAA96000.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAB55231.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AB032255; BAA89212.1; -; mRNA. DR EMBL; AB040909; BAA96000.2; ALT_INIT; mRNA. DR EMBL; AL080173; CAB45759.1; -; mRNA. DR EMBL; AL834381; CAD39044.2; -; mRNA. DR EMBL; CH471058; EAX11404.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11405.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11407.1; -; Genomic_DNA. DR EMBL; BC012576; AAH12576.1; ALT_SEQ; mRNA. DR EMBL; AK027612; BAB55231.1; ALT_INIT; mRNA. DR CCDS; CCDS2209.2; -. [Q9UIF8-1] DR CCDS; CCDS74594.1; -. [Q9UIF8-5] DR PIR; T12495; T12495. DR RefSeq; NP_001276904.1; NM_001289975.1. [Q9UIF8-5] DR RefSeq; NP_038478.2; NM_013450.3. [Q9UIF8-1] DR UniGene; Hs.470369; -. DR UniGene; Hs.731786; -. DR PDB; 2E7O; NMR; -; A=2062-2166. DR PDB; 3G0L; X-ray; 2.03 A; A=2054-2168. DR PDB; 3Q2F; X-ray; 2.06 A; A=2054-2168. DR PDB; 4CUP; X-ray; 1.88 A; A=2054-2168. DR PDB; 4CUQ; X-ray; 2.11 A; A=2054-2168. DR PDB; 4CUR; X-ray; 1.84 A; A=2054-2168. DR PDB; 4CUS; X-ray; 1.78 A; A=2054-2168. DR PDB; 4CUT; X-ray; 1.84 A; A=2054-2168. DR PDB; 4CUU; X-ray; 1.80 A; A=2054-2168. DR PDB; 4IR3; X-ray; 2.00 A; A=2054-2168. DR PDB; 4IR4; X-ray; 2.05 A; A=2054-2168. DR PDB; 4IR5; X-ray; 1.70 A; A=2054-2168. DR PDB; 4IR6; X-ray; 1.80 A; A=2054-2168. DR PDB; 4NR9; X-ray; 1.98 A; A=2054-2168. DR PDB; 4NRA; X-ray; 1.85 A; A=2054-2168. DR PDB; 4NRB; X-ray; 2.08 A; A=2054-2168. DR PDB; 4NRC; X-ray; 1.86 A; A=2054-2168. DR PDB; 4QC1; X-ray; 1.99 A; A/B=2062-2166. DR PDB; 4QC3; X-ray; 1.60 A; A/B=2062-2166. DR PDB; 4QF3; X-ray; 1.60 A; A/B=1928-1983. DR PDB; 4RVR; X-ray; 1.98 A; A=2054-2168. DR PDB; 4XUA; X-ray; 1.75 A; A=2054-2168. DR PDB; 4XUB; X-ray; 1.98 A; A=2054-2168. DR PDB; 5CQ3; X-ray; 1.93 A; A=2054-2168. DR PDB; 5CQ4; X-ray; 1.78 A; A=2054-2168. DR PDB; 5CQ5; X-ray; 1.96 A; A=2054-2168. DR PDB; 5CQ6; X-ray; 1.97 A; A=2054-2168. DR PDB; 5CQ7; X-ray; 1.86 A; A=2054-2166. DR PDB; 5CQ8; X-ray; 1.65 A; A=2054-2168. DR PDB; 5CQA; X-ray; 2.13 A; A=2054-2166. DR PDB; 5CU8; X-ray; 2.05 A; A=2054-2166. DR PDB; 5CUA; X-ray; 1.89 A; A=2054-2168. DR PDB; 5CUB; X-ray; 2.10 A; A=2054-2166. DR PDB; 5CUC; X-ray; 1.85 A; A=2054-2166. DR PDB; 5CUD; X-ray; 1.75 A; A=2054-2168. DR PDB; 5CUE; X-ray; 2.08 A; A=2054-2166. DR PDB; 5CUG; X-ray; 1.78 A; A=2054-2168. DR PDBsum; 2E7O; -. DR PDBsum; 3G0L; -. DR PDBsum; 3Q2F; -. DR PDBsum; 4CUP; -. DR PDBsum; 4CUQ; -. DR PDBsum; 4CUR; -. DR PDBsum; 4CUS; -. DR PDBsum; 4CUT; -. DR PDBsum; 4CUU; -. DR PDBsum; 4IR3; -. DR PDBsum; 4IR4; -. DR PDBsum; 4IR5; -. DR PDBsum; 4IR6; -. DR PDBsum; 4NR9; -. DR PDBsum; 4NRA; -. DR PDBsum; 4NRB; -. DR PDBsum; 4NRC; -. DR PDBsum; 4QC1; -. DR PDBsum; 4QC3; -. DR PDBsum; 4QF3; -. DR PDBsum; 4RVR; -. DR PDBsum; 4XUA; -. DR PDBsum; 4XUB; -. DR PDBsum; 5CQ3; -. DR PDBsum; 5CQ4; -. DR PDBsum; 5CQ5; -. DR PDBsum; 5CQ6; -. DR PDBsum; 5CQ7; -. DR PDBsum; 5CQ8; -. DR PDBsum; 5CQA; -. DR PDBsum; 5CU8; -. DR PDBsum; 5CUA; -. DR PDBsum; 5CUB; -. DR PDBsum; 5CUC; -. DR PDBsum; 5CUD; -. DR PDBsum; 5CUE; -. DR PDBsum; 5CUG; -. DR ProteinModelPortal; Q9UIF8; -. DR SMR; Q9UIF8; 1928-1983, 2062-2166. DR BioGrid; 119019; 10. DR IntAct; Q9UIF8; 9. DR MINT; MINT-1483920; -. DR STRING; 9606.ENSP00000376534; -. DR BindingDB; Q9UIF8; -. DR ChEMBL; CHEMBL1741220; -. DR GuidetoPHARMACOLOGY; 2722; -. DR PhosphoSite; Q9UIF8; -. DR BioMuta; BAZ2B; -. DR DMDM; 229462995; -. DR MaxQB; Q9UIF8; -. DR PaxDb; Q9UIF8; -. DR PRIDE; Q9UIF8; -. DR Ensembl; ENST00000392782; ENSP00000376533; ENSG00000123636. [Q9UIF8-5] DR Ensembl; ENST00000392783; ENSP00000376534; ENSG00000123636. [Q9UIF8-1] DR GeneID; 29994; -. DR KEGG; hsa:29994; -. DR UCSC; uc002uao.3; human. [Q9UIF8-1] DR UCSC; uc002uap.3; human. [Q9UIF8-5] DR CTD; 29994; -. DR GeneCards; BAZ2B; -. DR H-InvDB; HIX0002531; -. DR HGNC; HGNC:963; BAZ2B. DR HPA; HPA019819; -. DR MIM; 605683; gene. DR neXtProt; NX_Q9UIF8; -. DR PharmGKB; PA25273; -. DR eggNOG; KOG1245; Eukaryota. DR eggNOG; COG5076; LUCA. DR GeneTree; ENSGT00760000119099; -. DR HOGENOM; HOG000231981; -. DR HOVERGEN; HBG050670; -. DR InParanoid; Q9UIF8; -. DR OMA; QMKSGVS; -. DR OrthoDB; EOG783MTG; -. DR PhylomeDB; Q9UIF8; -. DR TreeFam; TF329083; -. DR ChiTaRS; BAZ2B; human. DR EvolutionaryTrace; Q9UIF8; -. DR GenomeRNAi; 29994; -. DR NextBio; 52792; -. DR PRO; PR:Q9UIF8; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; Q9UIF8; -. DR CleanEx; HS_BAZ2B; -. DR ExpressionAtlas; Q9UIF8; baseline and differential. DR Genevisible; Q9UIF8; HS. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:BHF-UCL. DR GO; GO:0006351; P:transcription, DNA-templated; NAS:BHF-UCL. DR Gene3D; 1.20.920.10; -; 1. DR Gene3D; 3.30.40.10; -; 1. DR Gene3D; 3.30.890.10; -; 1. DR InterPro; IPR001487; Bromodomain. DR InterPro; IPR018359; Bromodomain_CS. DR InterPro; IPR004022; DDT_dom. DR InterPro; IPR018500; DDT_dom_subgr. DR InterPro; IPR018501; DDT_dom_superfamily. DR InterPro; IPR016177; DNA-bd_dom. DR InterPro; IPR001739; Methyl_CpG_DNA-bd. DR InterPro; IPR028935; WHIM3_domain. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR001965; Znf_PHD. DR InterPro; IPR019787; Znf_PHD-finger. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR Pfam; PF00439; Bromodomain; 1. DR Pfam; PF02791; DDT; 1. DR Pfam; PF01429; MBD; 1. DR Pfam; PF00628; PHD; 1. DR Pfam; PF15614; WHIM3; 1. DR PRINTS; PR00503; BROMODOMAIN. DR SMART; SM00297; BROMO; 1. DR SMART; SM00571; DDT; 1. DR SMART; SM00391; MBD; 1. DR SMART; SM00249; PHD; 1. DR SUPFAM; SSF47370; SSF47370; 1. DR SUPFAM; SSF54171; SSF54171; 1. DR SUPFAM; SSF57903; SSF57903; 1. DR PROSITE; PS00633; BROMODOMAIN_1; 1. DR PROSITE; PS50014; BROMODOMAIN_2; 1. DR PROSITE; PS50827; DDT; 1. DR PROSITE; PS50982; MBD; 1. DR PROSITE; PS50016; ZF_PHD_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Bromodomain; KW Coiled coil; Complete proteome; DNA-binding; Isopeptide bond; KW Metal-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Transcription; Transcription regulation; KW Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1 2168 Bromodomain adjacent to zinc finger FT domain protein 2B. FT /FTId=PRO_0000211174. FT DOMAIN 739 810 MBD. {ECO:0000255|PROSITE- FT ProRule:PRU00338}. FT DOMAIN 1087 1152 DDT. {ECO:0000255|PROSITE- FT ProRule:PRU00063}. FT DOMAIN 2077 2147 Bromo. {ECO:0000255|PROSITE- FT ProRule:PRU00035}. FT ZN_FING 1931 1981 PHD-type. {ECO:0000255|PROSITE- FT ProRule:PRU00146}. FT COILED 883 1061 {ECO:0000255}. FT COILED 1334 1375 {ECO:0000255}. FT COMPBIAS 149 265 Ser-rich. FT COMPBIAS 269 275 Poly-Glu. FT COMPBIAS 595 666 Asp/Glu-rich (acidic). FT COMPBIAS 837 868 Arg-rich. FT COMPBIAS 902 1061 Lys-rich. FT COMPBIAS 1296 1339 Asp-rich. FT MOD_RES 1462 1462 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 1680 1680 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT MOD_RES 2014 2014 Phosphothreonine. FT {ECO:0000244|PubMed:21406692}. FT MOD_RES 2019 2019 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT CROSSLNK 1538 1538 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000269|PubMed:17370265}. FT VAR_SEQ 1 196 Missing (in isoform 4). FT {ECO:0000303|PubMed:10662543}. FT /FTId=VSP_037114. FT VAR_SEQ 112 113 Missing (in isoform 2 and isoform 5). FT {ECO:0000303|PubMed:10819331, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_037115. FT VAR_SEQ 633 730 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_000553. FT VAR_SEQ 789 822 Missing (in isoform 3 and isoform 5). FT {ECO:0000303|PubMed:10819331, FT ECO:0000303|PubMed:14702039}. FT /FTId=VSP_000554. FT VARIANT 71 71 M -> T (in dbSNP:rs10202670). FT {ECO:0000269|PubMed:17974005}. FT /FTId=VAR_055549. FT VARIANT 422 422 L -> S (in dbSNP:rs3213790). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:17974005}. FT /FTId=VAR_055550. FT VARIANT 530 530 P -> L (in dbSNP:rs3732287). FT /FTId=VAR_055551. FT VARIANT 702 702 G -> V (in dbSNP:rs2302924). FT /FTId=VAR_055552. FT VARIANT 2024 2024 S -> N (in dbSNP:rs415793). FT /FTId=VAR_055553. FT CONFLICT 95 95 L -> G (in Ref. 6; AAH12576). FT {ECO:0000305}. FT CONFLICT 333 333 S -> F (in Ref. 1; BAA89212). FT {ECO:0000305}. FT CONFLICT 823 823 G -> E (in Ref. 1; BAA89212). FT {ECO:0000305}. FT CONFLICT 918 918 E -> K (in Ref. 6; AAH12576). FT {ECO:0000305}. FT CONFLICT 986 986 R -> Q (in Ref. 6; AAH12576). FT {ECO:0000305}. FT CONFLICT 1324 1324 K -> Q (in Ref. 1; BAA89212). FT {ECO:0000305}. FT CONFLICT 1379 1379 Q -> P (in Ref. 1; BAA89212). FT {ECO:0000305}. FT CONFLICT 1391 1391 Q -> R (in Ref. 1; BAA89212). FT {ECO:0000305}. FT CONFLICT 1649 1649 S -> L (in Ref. 1; BAA89212). FT {ECO:0000305}. FT CONFLICT 2034 2034 K -> Q (in Ref. 1; BAA89212). FT {ECO:0000305}. FT TURN 1935 1937 {ECO:0000244|PDB:4QF3}. FT HELIX 1943 1945 {ECO:0000244|PDB:4QF3}. FT STRAND 1946 1949 {ECO:0000244|PDB:4QF3}. FT TURN 1950 1952 {ECO:0000244|PDB:4QF3}. FT STRAND 1955 1957 {ECO:0000244|PDB:4QF3}. FT TURN 1958 1960 {ECO:0000244|PDB:4QF3}. FT STRAND 1961 1963 {ECO:0000244|PDB:4QF3}. FT HELIX 1976 1982 {ECO:0000244|PDB:4QF3}. FT HELIX 2063 2077 {ECO:0000244|PDB:4QC3}. FT HELIX 2080 2082 {ECO:0000244|PDB:3Q2F}. FT HELIX 2083 2085 {ECO:0000244|PDB:4QC3}. FT TURN 2091 2093 {ECO:0000244|PDB:4QC3}. FT STRAND 2094 2096 {ECO:0000244|PDB:2E7O}. FT HELIX 2097 2100 {ECO:0000244|PDB:4QC3}. FT HELIX 2107 2115 {ECO:0000244|PDB:4QC3}. FT HELIX 2122 2139 {ECO:0000244|PDB:4QC3}. FT STRAND 2142 2144 {ECO:0000244|PDB:4IR5}. FT HELIX 2145 2165 {ECO:0000244|PDB:4QC3}. SQ SEQUENCE 2168 AA; 240459 MW; C64EEEE6243CF779 CRC64; MESGERLPSS AASSTTPTSS STPSVASVVS KGGLSTGVAS LSSTINPCGH LFRTAGDQPF NLSTVSSAFP MVSHPVFGLH SASSGHSEFG GLGTLGTPTA LAAHPQLASF PGAEWWRTTD AHTRTGATFF PPLLGIPPLF APPAQNHDSS SFHSRTSGKS NRNGPEKGVN GSINGSNTSS VIGINTSVLS TTASSSMGQT KSTSSGGGNR KCNQEQSKNQ PLDARVDKIK DKKPRKKAME SSSNSDSDSG TSSDTSSEGI SSSDSDDLEE DEEEEDQSIE ESEDDDSDSE SEAQHKSNNQ VLLHGISDPK ADGQKATEKA QEKRIHQPLP LASESQTHSF QSQQKQPQVL SQQLPFIFQS SQAKEESVNK HTSVIQSTGL VSNVKPLSLV NQAKKETYMK LIVPSPDVLK AGNKNTSEES SLLTSELRSK REQYKQAFPS QLKKQESSKS LKKVIAALSN PKATSSSPAH PKQTLENNHP NPFLTNALLG NHQPNGVIQS VIQEAPLALT TKTKMQSKIN ENIAAASSTP FSSPVNLSTS GRRTPGNQTP VMPSASPILH SQGKEKAVSN NVNPVKTQHH SHPAKSLVEQ FRGTDSDIPS SKDSEDSNED EEEDDEEEDE EDDEDDESDD SQSESDSNSE SDTEGSEEED DDDKDQDESD SDTEGEKTSM KLNKTTSSVK SPSMSLTGHS TPRNLHIAKA PGSAPAALCS ESQSPAFLGT SSSTLTSSPH SGTSKRRRVT DERELRIPLE YGWQRETRIR NFGGRLQGEV AYYAPCGKKL RQYPEVIKYL SRNGIMDISR DNFSFSAKIR VGDFYEARDG PQGMQWCLLK EEDVIPRIRA MEGRRGRPPN PDRQRAREES RMRRRKGRPP NVGNAEFLDN ADAKLLRKLQ AQEIARQAAQ IKLLRKLQKQ EQARVAKEAK KQQAIMAAEE KRKQKEQIKI MKQQEKIKRI QQIRMEKELR AQQILEAKKK KKEEAANAKL LEAEKRIKEK EMRRQQAVLL KHQERERRRQ HMMLMKAMEA RKKAEEKERL KQEKRDEKRL NKERKLEQRR LELEMAKELK KPNEDMCLAD QKPLPELPRI PGLVLSGSTF SDCLMVVQFL RNFGKVLGFD VNIDVPNLSV LQEGLLNIGD SMGEVQDLLV RLLSAAVCDP GLITGYKAKT ALGEHLLNVG VNRDNVSEIL QIFMEAHCGQ TELTESLKTK AFQAHTPAQK ASVLAFLINE LACSKSVVSE IDKNIDYMSN LRRDKWVVEG KLRKLRIIHA KKTGKRDTSG GIDLGEEQHP LGTPTPGRKR RRKGGDSDYD DDDDDDSDDQ GDEDDEDEED KEDKKGKKTD ICEDEDEGDQ AASVEELEKQ IEKLSKQQSQ YRRKLFDASH SLRSVMFGQD RYRRRYWILP QCGGIFVEGM ESGEGLEEIA KEREKLKKAE SVQIKEEMFE TSGDSLNCSN TDHCEQKEDL KEKDNTNLFL QKPGSFSKLS KLLEVAKMPP ESEVMTPKPN AGANGCTLSY QNSGKHSLGS VQSTATQSNV EKADSNNLFN TGSSGPGKFY SPLPNDQLLK TLTEKNRQWF SLLPRTPCDD TSLTHADMST ASLVTPQSQP PSKSPSPTPA PLGSSAQNPV GLNPFALSPL QVKGGVSMMG LQFCGWPTGV VTSNIPFTSS VPSLGSGLGL SEGNGNSFLT SNVASSKSES PVPQNEKATS AQPAAVEVAK PVDFPSPKPI PEEMQFGWWR IIDPEDLKAL LKVLHLRGIR EKALQKQIQK HLDYITQACL KNKDVAIIEL NENEENQVTR DIVENWSVEE QAMEMDLSVL QQVEDLERRV ASASLQVKGW MCPEPASERE DLVYFEHKSF TKLCKEHDGE FTGEDESSAH ALERKSDNPL DIAVTRLADL ERNIERRIEE DIAPGLRVWR RALSEARSAA QVALCIQQLQ KSIAWEKSIM KVYCQICRKG DNEELLLLCD GCDKGCHTYC HRPKITTIPD GDWFCPACIA KASGQTLKIK KLHVKGKKTN ESKKGKKVTL TGDTEDEDSA STSSSLKRGN KDLKKRKMEE NTSINLSKQE SFTSVKKPKR DDSKDLALCS MILTEMETHE DAWPFLLPVN LKLVPGYKKV IKKPMDFSTI REKLSSGQYP NLETFALDVR LVFDNCETFN EDDSDIGRAG HNMRKYFEKK WTDTFKVS // ID BCAS3_HUMAN Reviewed; 928 AA. AC Q9H6U6; Q17RM0; Q6KF21; Q8IXI6; Q8NDR8; Q8TDL9; Q8TDM1; Q8WY55; AC Q9BVF0; Q9H957; Q9H9Y9; Q9NXP4; DT 25-JUL-2003, integrated into UniProtKB/Swiss-Prot. DT 30-NOV-2010, sequence version 3. DT 11-NOV-2015, entry version 130. DE RecName: Full=Breast carcinoma-amplified sequence 3 {ECO:0000312|HGNC:HGNC:14347, ECO:0000312|MIM:607470}; DE AltName: Full=GAOB1; GN Name=BCAS3 {ECO:0000312|HGNC:HGNC:14347, ECO:0000312|MIM:607470}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, RP CHROMOSOMAL TRANSLOCATION WITH BCAS4, AND VARIANT SER-87. RC TISSUE=Liver; RX PubMed=12378525; DOI=10.1002/gcc.10121; RA Baerlund M., Monni O., Weaver J.D., Kauraniemi P., Sauter G., RA Heiskanen M., Kallioniemi O.-P., Kallioniemi A.; RT "Cloning of BCAS3 (17q23) and BCAS4 (20q13) genes that undergo RT amplification, overexpression, and fusion in breast cancer."; RL Genes Chromosomes Cancer 35:311-317(2002). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 5 AND 6), RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 478-928 (ISOFORM 3), AND RP VARIANT SER-87. RC TISSUE=Colon; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in RT the human lineage."; RL Nature 440:1045-1049(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-87. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP SER-87. RC TISSUE=Brain, and Cervix; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-433 (ISOFORM 6), AND PARTIAL RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RA Bauer M.; RT "Cloning and sequencing of a new isoform similar to FLJ20128 and RT BCAS3."; RL Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 475-928 (ISOFORM 4). RC TISSUE=Brain; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 510-928 (ISOFORMS 1/6). RA Wu G., Couch F.J.; RT "Five novel genes from 17q23 amplicon have different amplification and RT overexpression frequency in breast cancer."; RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases. RN [9] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION. RX PubMed=16617102; DOI=10.1073/pnas.0601989103; RA Gururaj A.E., Singh R.R., Rayala S.K., Holm C., den Hollander P., RA Zhang H., Balasenthil S., Talukder A.H., Landberg G., Kumar R.; RT "MTA1, a transcriptional activator of breast cancer amplified sequence RT 3."; RL Proc. Natl. Acad. Sci. U.S.A. 103:6670-6675(2006). RN [10] RP ERRATUM. RA Gururaj A.E., Singh R.R., Rayala S.K., Holm C., den Hollander P., RA Zhang H., Balasenthil S., Talukder A.H., Landberg G., Kumar R.; RL Proc. Natl. Acad. Sci. U.S.A. 110:4147-4148(2013). RN [11] RP FUNCTION, INTERACTION WITH HISTONE H3; ESR1; KAT2B AND PELP1, RP SUBCELLULAR LOCATION, AND CHROMATIN-BINDING. RX PubMed=17505058; DOI=10.1210/me.2006-0514; RA Gururaj A.E., Peng S., Vadlamudi R.K., Kumar R.; RT "Estrogen induces expression of BCAS3, a novel estrogen receptor-alpha RT coactivator, through proline-, glutamic acid-, and leucine-rich RT protein-1 (PELP1)."; RL Mol. Endocrinol. 21:1847-1860(2007). RN [12] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=18030336; DOI=10.1371/journal.pone.0001202; RA Siva K., Venu P., Mahadevan A., Shankar S.K., Inamdar M.S.; RT "Human BCAS3 expression in embryonic stem cells and vascular RT precursors suggests a role in human embryogenesis and tumor RT angiogenesis."; RL PLoS ONE 2:E1202-E1202(2007). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-480, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-886, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP INTERACTION WITH BETA-TUBULIN AND VIM. RX PubMed=22300583; DOI=10.1016/j.yexcr.2012.01.016; RA Jain M., Bhat G.P., Vijayra havan K., Inamdar M.S.; RT "Rudhira/BCAS3 is a cytoskeletal protein that controls Cdc42 RT activation and directional cell migration during angiogenesis."; RL Exp. Cell Res. 318:753-767(2012). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Plays a role in angiogenesis. Participates in the CC regulation of cell polarity and directional endothelial cell CC migration by mediating both the activation and recruitment of CC CDC42 and the reorganization of the actin cytoskeleton at the cell CC leading edge. Promotes filipodia formation (By similarity). CC Functions synergistically with PELP1 as a transcriptional CC coactivator of estrogen receptor-responsive genes. Stimulates CC histone acetyltransferase activity. Binds to chromatin. CC {ECO:0000250|UniProtKB:Q8CCN5, ECO:0000269|PubMed:17505058}. CC -!- SUBUNIT: Interacts with histone H3, ESR1, KAT2B and PELP1; the CC interactions occur in a estrogen-dependent manner. Interacts with CC beta-tubulin and VIM. {ECO:0000269|PubMed:17505058, CC ECO:0000269|PubMed:22300583}. CC -!- INTERACTION: CC Q9BSU1:C16orf70; NbExp=3; IntAct=EBI-10307911, EBI-946080; CC Q9UJX2:CDC23; NbExp=3; IntAct=EBI-6083685, EBI-396137; CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-6083685, EBI-10171858; CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-6083685, EBI-10171902; CC P08670:VIM; NbExp=3; IntAct=EBI-6083685, EBI-353844; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16617102, CC ECO:0000269|PubMed:17505058}. Cytoplasm CC {ECO:0000269|PubMed:16617102, ECO:0000269|PubMed:17505058, CC ECO:0000269|PubMed:18030336}. Cytoplasm, cytoskeleton CC {ECO:0000250|UniProtKB:Q8CCN5}. Note=Localizes in the cytoplasm in CC stationary cells. Translocates from the cytoplasm to the leading CC edge in motile cells. Colocalizes with microtubules and CC intermediate filaments in both stationary and motile cells (By CC similarity). Associates with chromatin. Recruited to estrogen CC receptor-induced promoters in a PELP1-dependent manner. CC {ECO:0000250|UniProtKB:Q8CCN5, ECO:0000269|PubMed:17505058}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=6; CC Name=2; CC IsoId=Q9H6U6-1; Sequence=Displayed; CC Name=1; CC IsoId=Q9H6U6-2; Sequence=VSP_007858; CC Name=3; CC IsoId=Q9H6U6-3; Sequence=VSP_007858, VSP_007860; CC Name=4; CC IsoId=Q9H6U6-8; Sequence=VSP_007860; CC Name=5; Synonyms=Maaab1; CC IsoId=Q9H6U6-7; Sequence=VSP_007858, VSP_040113; CC Note=No experimental confirmation available. Ref.2 (AK225757) CC sequence differs from that shown due to a frameshift in position CC 895. Ref.4 (CAD54076) sequence differs from that shown due to a CC frameshift in position 894. Ref.4 (CAD54076) sequence is in CC conflict in position: 891:G->R. {ECO:0000305}; CC Name=6; Synonyms=Maaab2; CC IsoId=Q9H6U6-6; Sequence=VSP_040112, VSP_007858; CC -!- TISSUE SPECIFICITY: Expressed in stomach, liver, lung, kidney, CC prostate, testis, thyroid gland, adrenal gland, brain, heart, CC skeletal muscle, colon, spleen, small intestine, placenta, blood CC leukocyte and mammary epithelial cells. Expressed in CC undifferentiated ES cells. Expressed in blood islands and nascent CC blood vessels derived from differentiated ES cells into embryoid CC bodies (BD). Expressed in endothelial cells. Not detected in CC brain. Expressed in brain tumors (at protein level). Expressed in CC brain. Highly expressed in breast cancers and in glioma cell CC lines. {ECO:0000269|PubMed:12378525, ECO:0000269|PubMed:16617102, CC ECO:0000269|PubMed:18030336}. CC -!- DEVELOPMENTAL STAGE: Fetal. CC -!- INDUCTION: By estrogen. {ECO:0000269|PubMed:16617102}. CC -!- DISEASE: Note=A chromosomal aberration involving BCAS3 has been CC found in some breast carcinoma cell lines. Translocation CC t(17;20)(q23;q13) with BCAS4. CC -!- SIMILARITY: Belongs to the WD repeat BCAS3 family. {ECO:0000305}. CC -!- SIMILARITY: Contains 7 WD repeats. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF70324.1; Type=Frameshift; Positions=693; Evidence={ECO:0000305}; CC Sequence=AAL99634.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAA90966.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=BAB14078.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/BCAS3ID766.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF361219; AAL99632.1; -; mRNA. DR EMBL; AF361221; AAL99634.1; ALT_INIT; mRNA. DR EMBL; AK000135; BAA90966.1; ALT_INIT; mRNA. DR EMBL; AK022526; BAB14078.1; ALT_INIT; mRNA. DR EMBL; AK023054; BAB14380.1; -; mRNA. DR EMBL; AK025510; BAB15156.1; -; mRNA. DR EMBL; AK225757; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC005746; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005856; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC005884; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC015876; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC079005; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC110602; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471179; EAW51414.1; -; Genomic_DNA. DR EMBL; BC001250; AAH01250.2; -; mRNA. DR EMBL; BC117275; AAI17276.1; -; mRNA. DR EMBL; BC143386; AAI43387.1; -; mRNA. DR EMBL; AJ511332; CAD54076.1; ALT_FRAME; mRNA. DR EMBL; AJ518105; CAD57723.1; -; mRNA. DR EMBL; AL831895; CAD38568.1; -; mRNA. DR EMBL; AF260268; AAF70324.1; ALT_FRAME; mRNA. DR CCDS; CCDS11626.1; -. [Q9H6U6-2] DR CCDS; CCDS45749.1; -. [Q9H6U6-1] DR RefSeq; NP_001092902.1; NM_001099432.1. [Q9H6U6-1] DR RefSeq; NP_060149.3; NM_017679.3. [Q9H6U6-2] DR RefSeq; XP_005257529.1; XM_005257472.1. [Q9H6U6-8] DR RefSeq; XP_005257532.1; XM_005257475.1. [Q9H6U6-7] DR RefSeq; XP_011523254.1; XM_011524952.1. [Q9H6U6-6] DR UniGene; Hs.655028; -. DR ProteinModelPortal; Q9H6U6; -. DR SMR; Q9H6U6; 348-381. DR BioGrid; 120182; 15. DR IntAct; Q9H6U6; 19. DR STRING; 9606.ENSP00000375067; -. DR PhosphoSite; Q9H6U6; -. DR BioMuta; BCAS3; -. DR DMDM; 313104248; -. DR MaxQB; Q9H6U6; -. DR PaxDb; Q9H6U6; -. DR PRIDE; Q9H6U6; -. DR Ensembl; ENST00000390652; ENSP00000375067; ENSG00000141376. [Q9H6U6-1] DR Ensembl; ENST00000407086; ENSP00000385323; ENSG00000141376. [Q9H6U6-2] DR Ensembl; ENST00000408905; ENSP00000386173; ENSG00000141376. [Q9H6U6-3] DR Ensembl; ENST00000588462; ENSP00000468592; ENSG00000141376. [Q9H6U6-8] DR Ensembl; ENST00000588874; ENSP00000464825; ENSG00000141376. [Q9H6U6-6] DR Ensembl; ENST00000589222; ENSP00000466078; ENSG00000141376. [Q9H6U6-7] DR GeneID; 54828; -. DR KEGG; hsa:54828; -. DR UCSC; uc002iyu.4; human. [Q9H6U6-2] DR UCSC; uc002iyv.4; human. [Q9H6U6-1] DR UCSC; uc002iyw.4; human. [Q9H6U6-7] DR UCSC; uc002iyy.4; human. [Q9H6U6-6] DR UCSC; uc002iyz.4; human. [Q9H6U6-8] DR UCSC; uc002iza.4; human. [Q9H6U6-3] DR CTD; 54828; -. DR GeneCards; BCAS3; -. DR H-InvDB; HIX0021877; -. DR HGNC; HGNC:14347; BCAS3. DR HPA; HPA052409; -. DR MIM; 607470; gene. DR neXtProt; NX_Q9H6U6; -. DR PharmGKB; PA25286; -. DR eggNOG; KOG2109; Eukaryota. DR eggNOG; KOG4415; Eukaryota. DR eggNOG; ENOG410XSW7; LUCA. DR GeneTree; ENSGT00390000006454; -. DR HOVERGEN; HBG050676; -. DR InParanoid; Q9H6U6; -. DR OMA; TSRNMEF; -. DR OrthoDB; EOG75MVVN; -. DR PhylomeDB; Q9H6U6; -. DR TreeFam; TF105856; -. DR SignaLink; Q9H6U6; -. DR ChiTaRS; BCAS3; human. DR GeneWiki; BCAS3; -. DR GenomeRNAi; 54828; -. DR NextBio; 57598; -. DR PRO; PR:Q9H6U6; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; Q9H6U6; -. DR ExpressionAtlas; Q9H6U6; baseline and differential. DR Genevisible; Q9H6U6; HS. DR GO; GO:0031252; C:cell leading edge; ISS:UniProtKB. DR GO; GO:0071944; C:cell periphery; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005881; C:cytoplasmic microtubule; ISS:UniProtKB. DR GO; GO:0045111; C:intermediate filament cytoskeleton; ISS:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0035327; C:transcriptionally active chromatin; IDA:UniProtKB. DR GO; GO:0010698; F:acetyltransferase activator activity; IDA:UniProtKB. DR GO; GO:0048487; F:beta-tubulin binding; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0035035; F:histone acetyltransferase binding; IPI:UniProtKB. DR GO; GO:0042393; F:histone binding; IDA:UniProtKB. DR GO; GO:0035257; F:nuclear hormone receptor binding; IPI:UniProtKB. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0090630; P:activation of GTPase activity; ISS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0071391; P:cellular response to estrogen stimulus; IDA:UniProtKB. DR GO; GO:0007030; P:Golgi organization; ISS:UniProtKB. DR GO; GO:0031023; P:microtubule organizing center organization; ISS:UniProtKB. DR GO; GO:0051895; P:negative regulation of focal adhesion assembly; ISS:UniProtKB. DR GO; GO:0034260; P:negative regulation of GTPase activity; ISS:UniProtKB. DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; ISS:UniProtKB. DR GO; GO:0043085; P:positive regulation of catalytic activity; IDA:UniProtKB. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB. DR GO; GO:0051491; P:positive regulation of filopodium assembly; ISS:UniProtKB. DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB. DR GO; GO:0090316; P:positive regulation of intracellular protein transport; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:2000114; P:regulation of establishment of cell polarity; ISS:UniProtKB. DR GO; GO:0042594; P:response to starvation; IBA:GO_Central. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0035148; P:tube formation; ISS:UniProtKB. DR Gene3D; 2.130.10.10; -; 2. DR InterPro; IPR022175; BCAS3. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom. DR InterPro; IPR001680; WD40_repeat. DR InterPro; IPR017986; WD40_repeat_dom. DR Pfam; PF12490; BCAS3; 1. DR SMART; SM00320; WD40; 2. DR SUPFAM; SSF50978; SSF50978; 2. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Angiogenesis; KW Chromosomal rearrangement; Complete proteome; Cytoplasm; Cytoskeleton; KW Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW WD repeat. FT CHAIN 1 928 Breast carcinoma-amplified sequence 3. FT /FTId=PRO_0000050883. FT REPEAT 69 110 WD 1. FT REPEAT 111 175 WD 2. FT REPEAT 176 234 WD 3. FT REPEAT 235 288 WD 4. FT REPEAT 289 341 WD 5. FT REPEAT 342 394 WD 6. FT REPEAT 395 433 WD 7. FT SITE 824 825 Breakpoint for translocation to form FT BCAS4-BCAS3. FT MOD_RES 1 1 N-acetylmethionine. FT {ECO:0000244|PubMed:22814378}. FT MOD_RES 461 461 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8CCN5}. FT MOD_RES 480 480 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 488 488 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8CCN5}. FT MOD_RES 838 838 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8CCN5}. FT MOD_RES 886 886 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 898 898 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8CCN5}. FT VAR_SEQ 1 229 Missing (in isoform 6). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|Ref.6}. FT /FTId=VSP_040112. FT VAR_SEQ 547 561 Missing (in isoform 1, isoform 3, isoform FT 5 and isoform 6). FT {ECO:0000303|PubMed:12378525, FT ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.6}. FT /FTId=VSP_007858. FT VAR_SEQ 879 879 T -> TDTALDVAVKTFPPERHVAVKCF (in isoform FT 3 and isoform 4). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:17974005}. FT /FTId=VSP_007860. FT VAR_SEQ 880 928 ELQREGSIETLSNSSGSTSGSIPRNFDGYRSPLPTNESQPL FT SLFPTGFP -> DTALDVAVKTFPPERHVAVKCFGKKKGKK FT KQCQQPSVREQPNSNKACVRDGGRTSARGKHRDSE (in FT isoform 5). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_040113. FT VARIANT 87 87 N -> S (in dbSNP:rs2643103). FT {ECO:0000269|PubMed:12378525, FT ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.4}. FT /FTId=VAR_065093. FT VARIANT 106 106 I -> V (in dbSNP:rs34712615). FT /FTId=VAR_057583. FT CONFLICT 29 29 E -> K (in Ref. 1; AAL99632). FT {ECO:0000305}. FT CONFLICT 127 127 R -> K (in Ref. 1; AAL99632). FT {ECO:0000305}. FT CONFLICT 199 200 VV -> II (in Ref. 2; BAB15156). FT {ECO:0000305}. FT CONFLICT 533 533 K -> E (in Ref. 2; BAB14078/BAB14380). FT {ECO:0000305}. FT CONFLICT 640 640 D -> G (in Ref. 2; BAB15156). FT {ECO:0000305}. FT CONFLICT 666 666 Q -> R (in Ref. 2; BAB14078). FT {ECO:0000305}. FT CONFLICT 806 806 S -> P (in Ref. 2; BAB15156). FT {ECO:0000305}. SQ SEQUENCE 928 AA; 101237 MW; 00D82E2EDCD1E8D7 CRC64; MNEAMATDSP RRPSRCTGGV VVRPQAVTEQ SYMESVVTFL QDVVPQAYSG TPLTEEKEKI VWVRFENADL NDTSRNLEFH EIHSTGNEPP LLIMIGYSDG MQVWSIPISG EAQELFSVRH GPIRAARILP APQFGAQKCD NFAEKRPLLG VCKSIGSSGT SPPYCCVDLY SLRTGEMVKS IQFKTPIYDL HCNKRILVVV LQEKIAAFDS CTFTKKFFVT SCYPCPGPNM NPIALGSRWL AYAENKLIRC HQSRGGACGD NIQSYTATVI SAAKTLKSGL TMVGKVVTQL TGTLPSGVTE DDVAIHSNSR RSPLVPGIIT VIDTETVGEG QVLVSEDSDS DGIVAHFPAH EKPVCCMAFN TSGMLLVTTD TLGHDFHVFQ ILTHPWSSSQ CAVHHLYTLH RGETEAKVQD ICFSHDCRWV VVSTLRGTSH VFPINPYGGQ PCVRTHMSPR VVNRMSRFQK SAGLEEIEQE LTSKQGGRCS PVPGLSSSPS GSPLHGKLNS QDSYNNFTNN NPGNPRLSPL PSLMVVMPLA QIKQPMTLGT ITKRTGPYLF GAGCFSIKAP CKVKPPPQIS PSKSMGGEFC VAAIFGTSRS WFANNAGLKR EKDQSKQVVV ESLYIISCYG TLVEHMMEPR PLSTAPKISD DTPLEMMTSP RASWTLVRTP QWNELQPPFN ANHPLLLAAD AVQYYQFLLA GLVPPGSPGP ITRHGSYDSL ASDHSGQEDE EWLSQVEIVT HTGPHRRLWM GPQFQFKTIH PSGQTTVISS SSSVLQSHGP SDTPQPLLDF DTDDLDLNSL RIQPVRSDPV SMPGSSRPVS DRRGVSTVID AASGTFDRSV TLLEVCGSWP EGFGLRHMSS MEHTEEGLRE RLADAMAESP SRDVVGSGTE LQREGSIETL SNSSGSTSGS IPRNFDGYRS PLPTNESQPL SLFPTGFP // ID BCL3_HUMAN Reviewed; 454 AA. AC P20749; DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot. DT 20-APR-2010, sequence version 2. DT 11-NOV-2015, entry version 159. DE RecName: Full=B-cell lymphoma 3 protein; DE Short=BCL-3; DE AltName: Full=Proto-oncogene BCL3; GN Name=BCL3; Synonyms=BCL4, D19S37; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=2180580; DOI=10.1016/0092-8674(90)90347-H; RA Ohno H., Takimoto G., McKeithan T.W.; RT "The candidate proto-oncogene bcl-3 is related to genes implicated in RT cell lineage determination and cell cycle control."; RL Cell 60:991-997(1990). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 87-454. RC TISSUE=Leukemia; RX PubMed=7896265; DOI=10.1006/geno.1994.1588; RA McKeithan T.W., Ohno H., Dickstein J., Hume E.; RT "Genomic structure of the candidate proto-oncogene BCL3."; RL Genomics 24:120-126(1994). RN [4] RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH NFKB2/P52. RX PubMed=8453667; DOI=10.1016/0092-8674(93)90401-B; RA Bours V., Franzoso G., Azarenko V., Park S., Kanno T., Brown K., RA Siebenlist U.; RT "The oncoprotein Bcl-3 directly transactivates through kappa B motifs RT via association with DNA-binding p50B homodimers."; RL Cell 72:729-739(1993). RN [5] RP IDENTIFICATION IN A COMPLEX WITH NFKB1/P50. RX PubMed=10469655; DOI=10.1093/emboj/18.17.4766; RA Heissmeyer V., Krappmann D., Wulczyn F.G., Scheidereit C.; RT "NF-kappaB p105 is a target of IkappaB kinases and controls signal RT induction of Bcl-3-p50 complexes."; RL EMBO J. 18:4766-4778(1999). RN [6] RP INTERACTION WITH COPS5 AND PIR. RX PubMed=10362352; DOI=10.1038/sj.onc.1202717; RA Dechend R., Hirano F., Lehmann K., Heissmeyer V., Ansieau S., RA Wulczyn F.G., Scheidereit C., Leutz A.; RT "The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel RT and nuclear co-regulators."; RL Oncogene 18:3316-3323(1999). RN [7] RP INTERACTION WITH N4BP2. RX PubMed=12730195; DOI=10.1074/jbc.M303518200; RA Watanabe N., Wachi S., Fujita T.; RT "Identification and characterization of BCL-3-binding protein: RT implications for transcription and DNA repair or recombination."; RL J. Biol. Chem. 278:26102-26110(2003). RN [8] RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 127-367. RX PubMed=11707390; DOI=10.1093/emboj/20.22.6180; RA Michel F., Soler-Lopez M., Petosa C., Cramer P., Siebenlist U., RA Muller C.W.; RT "Crystal structure of the ankyrin repeat domain of Bcl-3: a unique RT member of the IkappaB protein family."; RL EMBO J. 20:6180-6190(2001). RN [9] RP PHOSPHORYLATION AT SER-402 AND SER-406. RX PubMed=15469820; DOI=10.1016/j.molcel.2004.09.004; RA Viatour P., Dejardin E., Warnier M., Lair F., Claudio E., Bureau F., RA Marine J.C., Merville M.P., Maurer U., Green D., Piette J., RA Siebenlist U., Bours V., Chariot A.; RT "GSK3-mediated BCL-3 phosphorylation modulates its degradation and its RT oncogenicity."; RL Mol. Cell 16:35-45(2004). CC -!- FUNCTION: Contributes to the regulation of transcriptional CC activation of NF-kappa-B target genes. In the cytoplasm, inhibits CC the nuclear translocation of the NF-kappa-B p50 subunit. In the CC nucleus, acts as transcriptional activator that promotes CC transcription of NF-kappa-B target genes. Contributes to the CC regulation of cell proliferation (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Component of a complex consisting of the NF-kappa-B p52- CC p52 homodimer and BCL3. Component of a complex consisting of the CC NF-kappa-B p50-p50 homodimer and BCL3. Interacts with N4BP2, COPS5 CC and PIR. Interacts with CYLD (By similarity). {ECO:0000250}. CC -!- INTERACTION: CC O95999:BCL10; NbExp=3; IntAct=EBI-958997, EBI-958922; CC P56545:CTBP2; NbExp=2; IntAct=EBI-958997, EBI-741533; CC P06239:LCK; NbExp=3; IntAct=EBI-958997, EBI-1348; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm {ECO:0000250}. Cytoplasm, CC perinuclear region {ECO:0000250}. Note=Ubiquitination via 'Lys- CC 63'-linked ubiquitin chains is required for nuclear accumulation. CC {ECO:0000250}. CC -!- PTM: Polyubiquitinated. Ubiquitination via 'Lys-63'-linked CC ubiquitin chains is required for nuclear accumulation. CC Deubiquitinated by CYLD, which acts on 'Lys-63'-linked ubiquitin CC chains. Deubiquitination by CYLD prevents nuclear accumulation (By CC similarity). {ECO:0000250}. CC -!- PTM: Activated by phosphorylation. {ECO:0000269|PubMed:15469820}. CC -!- DISEASE: Note=A chromosomal aberration involving BCL3 may be a CC cause of B-cell chronic lymphocytic leukemia (B-CLL). CC Translocation t(14;19)(q32;q13.1) with immunoglobulin gene CC regions. CC -!- SIMILARITY: Contains 7 ANK repeats. {ECO:0000255|PROSITE- CC ProRule:PRU00023}. CC -!- CAUTION: It is uncertain whether Met-1 or Met-9 is the initiator. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA51815.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAA51816.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAH64993.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M31731; AAA51816.1; ALT_INIT; Genomic_DNA. DR EMBL; M31732; AAA51815.1; ALT_INIT; mRNA. DR EMBL; AC092066; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC064993; AAH64993.1; ALT_INIT; mRNA. DR EMBL; AH006679; AAC51348.1; -; Genomic_DNA. DR CCDS; CCDS12642.2; -. DR PIR; A34794; A34794. DR RefSeq; NP_005169.2; NM_005178.4. DR RefSeq; XP_011525499.1; XM_011527197.1. DR UniGene; Hs.31210; -. DR PDB; 1K1A; X-ray; 1.86 A; A=127-367. DR PDB; 1K1B; X-ray; 1.90 A; A=127-367. DR PDBsum; 1K1A; -. DR PDBsum; 1K1B; -. DR ProteinModelPortal; P20749; -. DR SMR; P20749; 133-432. DR BioGrid; 107074; 42. DR IntAct; P20749; 11. DR MINT; MINT-105740; -. DR STRING; 9606.ENSP00000164227; -. DR PhosphoSite; P20749; -. DR BioMuta; BCL3; -. DR DMDM; 294862410; -. DR MaxQB; P20749; -. DR PaxDb; P20749; -. DR PRIDE; P20749; -. DR Ensembl; ENST00000164227; ENSP00000164227; ENSG00000069399. DR GeneID; 602; -. DR KEGG; hsa:602; -. DR UCSC; uc010xxe.2; human. DR CTD; 602; -. DR GeneCards; BCL3; -. DR HGNC; HGNC:998; BCL3. DR HPA; CAB002051; -. DR HPA; HPA047514; -. DR MIM; 109560; gene. DR neXtProt; NX_P20749; -. DR PharmGKB; PA25310; -. DR eggNOG; KOG0504; Eukaryota. DR eggNOG; COG0666; LUCA. DR GeneTree; ENSGT00550000074527; -. DR HOGENOM; HOG000095189; -. DR HOVERGEN; HBG108320; -. DR InParanoid; P20749; -. DR KO; K09258; -. DR OMA; PLYPMMC; -. DR OrthoDB; EOG7W154S; -. DR PhylomeDB; P20749; -. DR TreeFam; TF320166; -. DR EvolutionaryTrace; P20749; -. DR GeneWiki; BCL3; -. DR GenomeRNAi; 602; -. DR NextBio; 2447; -. DR PRO; PR:P20749; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; P20749; -. DR CleanEx; HS_BCL3; -. DR ExpressionAtlas; P20749; baseline and differential. DR Genevisible; P20749; HS. DR GO; GO:0032996; C:Bcl3-Bcl10 complex; IDA:UniProtKB. DR GO; GO:0033257; C:Bcl3/NF-kappaB2 complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0045171; C:intercellular bridge; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0043234; C:protein complex; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:Ensembl. DR GO; GO:0030674; F:protein binding, bridging; TAS:UniProtKB. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0019730; P:antimicrobial humoral response; IEA:Ensembl. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB. DR GO; GO:0042742; P:defense response to bacterium; IEA:Ensembl. DR GO; GO:0042832; P:defense response to protozoan; IEA:Ensembl. DR GO; GO:0030330; P:DNA damage response, signal transduction by p53 class mediator; IMP:UniProtKB. DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl. DR GO; GO:0002268; P:follicular dendritic cell differentiation; IEA:Ensembl. DR GO; GO:0002467; P:germinal center formation; IEA:Ensembl. DR GO; GO:0002455; P:humoral immune response mediated by circulating immunoglobulin; IEA:Ensembl. DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB. DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:MGI. DR GO; GO:0051457; P:maintenance of protein location in nucleus; NAS:UniProtKB. DR GO; GO:0002315; P:marginal zone B cell differentiation; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0045415; P:negative regulation of interleukin-8 biosynthetic process; IMP:UniProtKB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0042536; P:negative regulation of tumor necrosis factor biosynthetic process; IEA:Ensembl. DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IEA:Ensembl. DR GO; GO:0045082; P:positive regulation of interleukin-10 biosynthetic process; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB. DR GO; GO:0000060; P:protein import into nucleus, translocation; IMP:UniProtKB. DR GO; GO:0042981; P:regulation of apoptotic process; IDA:UniProtKB. DR GO; GO:0051101; P:regulation of DNA binding; IEP:UniProtKB. DR GO; GO:0042345; P:regulation of NF-kappaB import into nucleus; IEP:UniProtKB. DR GO; GO:0010225; P:response to UV-C; IDA:UniProtKB. DR GO; GO:0009615; P:response to virus; IDA:UniProtKB. DR GO; GO:0048536; P:spleen development; IEA:Ensembl. DR GO; GO:0042088; P:T-helper 1 type immune response; IEA:Ensembl. DR GO; GO:0045064; P:T-helper 2 cell differentiation; IEA:Ensembl. DR GO; GO:0006351; P:transcription, DNA-templated; IDA:UniProtKB. DR Gene3D; 1.25.40.20; -; 1. DR InterPro; IPR002110; Ankyrin_rpt. DR InterPro; IPR020683; Ankyrin_rpt-contain_dom. DR Pfam; PF12796; Ank_2; 1. DR PRINTS; PR01415; ANKYRIN. DR SMART; SM00248; ANK; 6. DR SUPFAM; SSF48403; SSF48403; 1. DR PROSITE; PS50297; ANK_REP_REGION; 1. DR PROSITE; PS50088; ANK_REPEAT; 5. PE 1: Evidence at protein level; KW 3D-structure; Activator; ANK repeat; Chromosomal rearrangement; KW Complete proteome; Cytoplasm; Nucleus; Phosphoprotein; Proto-oncogene; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1 454 B-cell lymphoma 3 protein. FT /FTId=PRO_0000066976. FT REPEAT 134 163 ANK 1. FT REPEAT 171 200 ANK 2. FT REPEAT 204 235 ANK 3. FT REPEAT 241 270 ANK 4. FT REPEAT 275 304 ANK 5. FT REPEAT 308 337 ANK 6. FT REPEAT 338 367 ANK 7. FT COMPBIAS 9 120 Pro-rich. FT COMPBIAS 365 454 Pro/Ser-rich. FT MOD_RES 402 402 Phosphoserine; by GSK3. FT {ECO:0000269|PubMed:15469820}. FT MOD_RES 406 406 Phosphoserine; by GSK3. FT {ECO:0000269|PubMed:15469820}. FT HELIX 138 144 {ECO:0000244|PDB:1K1A}. FT HELIX 148 160 {ECO:0000244|PDB:1K1A}. FT HELIX 175 181 {ECO:0000244|PDB:1K1A}. FT HELIX 185 193 {ECO:0000244|PDB:1K1A}. FT HELIX 208 214 {ECO:0000244|PDB:1K1A}. FT HELIX 218 227 {ECO:0000244|PDB:1K1A}. FT HELIX 245 252 {ECO:0000244|PDB:1K1A}. FT HELIX 255 263 {ECO:0000244|PDB:1K1A}. FT TURN 273 275 {ECO:0000244|PDB:1K1A}. FT HELIX 279 285 {ECO:0000244|PDB:1K1A}. FT HELIX 289 297 {ECO:0000244|PDB:1K1A}. FT HELIX 312 319 {ECO:0000244|PDB:1K1A}. FT HELIX 322 330 {ECO:0000244|PDB:1K1A}. FT TURN 345 348 {ECO:0000244|PDB:1K1A}. FT HELIX 352 358 {ECO:0000244|PDB:1K1A}. SQ SEQUENCE 454 AA; 47584 MW; 385F5320DB72C0E0 CRC64; MPRCPAGAMD EGPVDLRTRP KAAGLPGAAL PLRKRPLRAP SPEPAAPRGA AGLVVPLDPL RGGCDLPAVP GPPHGLARPE ALYYPGALLP LYPTRAMGSP FPLVNLPTPL YPMMCPMEHP LSADIAMATR ADEDGDTPLH IAVVQGNLPA VHRLVNLFQQ GGRELDIYNN LRQTPLHLAV ITTLPSVVRL LVTAGASPMA LDRHGQTAAH LACEHRSPTC LRALLDSAAP GTLDLEARNY DGLTALHVAV NTECQETVQL LLERGADIDA VDIKSGRSPL IHAVENNSLS MVQLLLQHGA NVNAQMYSGS SALHSASGRG LLPLVRTLVR SGADSSLKNC HNDTPLMVAR SRRVIDILRG KATRPASTSQ PDPSPDRSAN TSPESSSRLS SNGLLSASPS SSPSQSPPRD PPGFPMAPPN FFLPSPSPPA FLPFAGVLRG PGRPVPPSPA PGGS // ID C8AP2_HUMAN Reviewed; 1982 AA. AC Q9UKL3; A2RUB7; E1P553; Q6PH76; Q7LCQ7; Q86YD9; Q9NUQ4; Q9NZV9; AC Q9P2N1; Q9Y563; DT 20-DEC-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 11-NOV-2015, entry version 108. DE RecName: Full=CASP8-associated protein 2; DE AltName: Full=FLICE-associated huge protein; GN Name=CASP8AP2 {ECO:0000312|HGNC:HGNC:1510}; GN Synonyms=FLASH, KIAA1315 {ECO:0000312|EMBL:BAA92553.2}, GN RIP25 {ECO:0000312|EMBL:AAD45537.2}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=T-cell; RA Kimura T., Imai Y., Yonehara S.; RT "Reply: searching for FLASH domains."; RL Nature 401:662-663(1999). RN [2] {ECO:0000312|EMBL:AAD45537.2} RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Peripheral blood leukocyte {ECO:0000312|EMBL:AAD45537.2}; RA Yan M.D., Sun L.Y., Liu X.Y., Zheng Z.C.; RT "RIP25, a human homolog of Mus musculus FLASH, is involved in IL-2 RT signaling."; RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases. RN [3] {ECO:0000312|EMBL:BAA92553.2} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain {ECO:0000312|EMBL:BAA92553.2}; RX PubMed=10718198; DOI=10.1093/dnares/7.1.65; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVI. RT The complete sequences of 150 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 7:65-73(2000). RN [4] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [6] {ECO:0000312|EMBL:AAD45537.2} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] {ECO:0000305, ECO:0000312|EMBL:AAH56685.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin {ECO:0000312|EMBL:AAH42577.1}, and RC Testis {ECO:0000312|EMBL:AAH56685.1}; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] {ECO:0000305, ECO:0000312|EMBL:BAA92067.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1478-1982. RC TISSUE=Placenta {ECO:0000312|EMBL:BAA92067.1}; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] {ECO:0000312|EMBL:AAF03367.1} RP NUCLEOTIDE SEQUENCE [MRNA] OF 714-1982. RX PubMed=10537104; DOI=10.1038/44317; RA Koonin E.V., Aravind L., Hofmann K., Tschopp J., Dixit V.M.; RT "Apoptosis. Searching for FLASH domains."; RL Nature 401:662-662(1999). RN [10] {ECO:0000305} RP FUNCTION, INTERACTION WITH NCOA2, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=12477726; DOI=10.1074/jbc.M209234200; RA Kino T., Chrousos G.P.; RT "Tumor necrosis factor alpha receptor- and Fas-associated FLASH RT inhibit transcriptional activity of the glucocorticoid receptor by RT binding to and interfering with its interaction with p160 type nuclear RT receptor coactivators."; RL J. Biol. Chem. 278:3023-3029(2003). RN [11] {ECO:0000305} RP FUNCTION, AND INTERACTION WITH NCOA3. RX PubMed=15698540; DOI=10.1016/j.jsbmb.2004.09.003; RA Kino T., Ichijo T., Chrousos G.P.; RT "FLASH interacts with p160 coactivator subtypes and differentially RT suppresses transcriptional activity of steroid hormone receptors."; RL J. Steroid Biochem. Mol. Biol. 92:357-363(2004). RN [12] RP FUNCTION, INTERACTION WITH NPAT, AND SUBCELLULAR LOCATION. RX PubMed=17003125; DOI=10.1073/pnas.0604227103; RA Barcaroli D., Bongiorno-Borbone L., Terrinoni A., Hofmann T.G., RA Rossi M., Knight R.A., Matera A.G., Melino G., De Laurenzi V.; RT "FLASH is required for histone transcription and S-phase RT progression."; RL Proc. Natl. Acad. Sci. U.S.A. 103:14808-14812(2006). RN [13] RP FUNCTION IN FAS-MEDIATED APOPTOSIS, INTERACTION WITH CASP8 AND SP100, RP AND SUBCELLULAR LOCATION. RX PubMed=17245429; DOI=10.1038/sj.emboj.7601504; RA Milovic-Holm K., Krieghoff E., Jensen K., Will H., Hofmann T.G.; RT "FLASH links the CD95 signaling pathway to the cell nucleus and RT nuclear bodies."; RL EMBO J. 26:391-401(2007). RN [14] RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-92 AND LYS-93. RC TISSUE=Mammary cancer; RX PubMed=17370265; DOI=10.1002/pmic.200600410; RA Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D.; RT "Tryptic digestion of ubiquitin standards reveals an improved strategy RT for identifying ubiquitinated proteins by mass spectrometry."; RL Proteomics 7:868-874(2007). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [16] RP INTERACTION WITH SRRT. RX PubMed=19546234; DOI=10.1128/MCB.00289-09; RA Kiriyama M., Kobayashi Y., Saito M., Ishikawa F., Yonehara S.; RT "Interaction of FLASH with arsenite resistance protein 2 is involved RT in cell cycle progression at S phase."; RL Mol. Cell. Biol. 29:4729-4741(2009). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT SER-20, CLEAVAGE OF INITIATOR METHIONINE [LARGE RP SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [19] RP IDENTIFICATION OF REPEAT SUMO-INTERACTING MOTIF, AND INTERACTION WITH RP SUMO1 AND SUMO2. RX PubMed=23086935; DOI=10.1074/jbc.M112.410985; RA Sun H., Hunter T.; RT "PolySUMO-binding proteins identified through a string search."; RL J. Biol. Chem. 287:42071-42083(2012). RN [20] {ECO:0000312|EMBL:AAD45537.2} RP STRUCTURE BY NMR OF 1916-1982. RG Northeast structural genomics consortium (NESG); RT "Solution NMR structure of CASP8-associated protein 2 from Homo RT sapiens, Northeast structural genomics consortium (NESG) target RT HR8150A."; RL Submitted (JUN-2012) to the PDB data bank. CC -!- FUNCTION: Participates in TNF-alpha-induced blockade of CC glucocorticoid receptor (GR) transactivation at the nuclear CC receptor coactivator level, upstream and independently of NF- CC kappa-B. Suppresses both NCOA2- and NCOA3-induced enhancement of CC GR transactivation. Involved in TNF-alpha-induced activation of CC NF-kappa-B via a TRAF2-dependent pathway. Acts as a downstream CC mediator for CASP8-induced activation of NF-kappa-B. Required for CC the activation of CASP8 in FAS-mediated apoptosis. Required for CC histone gene transcription and progression through S phase. CC {ECO:0000269|PubMed:12477726, ECO:0000269|PubMed:15698540, CC ECO:0000269|PubMed:17003125, ECO:0000269|PubMed:17245429}. CC -!- SUBUNIT: Self-associates. Component of the death-inducing CC signaling complex (DISC) with CASP8, FADD and FAS. Interacts with CC NCOA2 and NCOA3. Interacts with SRRT. Interacts with TRAF2. CC Interacts with NPAT. Interacts (via SIM domains) with SUMO1 and CC SUMO2. Interacts with SP100; may negatively regulate CASP8AP2 CC export from the nucleus to the cytoplasm. CC {ECO:0000269|PubMed:12477726, ECO:0000269|PubMed:15698540, CC ECO:0000269|PubMed:17003125, ECO:0000269|PubMed:17245429, CC ECO:0000269|PubMed:19546234, ECO:0000269|PubMed:23086935}. CC -!- INTERACTION: CC Q14790:CASP8; NbExp=3; IntAct=EBI-2339650, EBI-78060; CC O75925:PIAS1; NbExp=4; IntAct=EBI-2339650, EBI-629434; CC P23497:SP100; NbExp=5; IntAct=EBI-2339650, EBI-751145; CC O15350-1:TP73; NbExp=2; IntAct=EBI-2339650, EBI-389619; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus, PML body. CC Mitochondrion. Note=Exported from the nucleus to the mitochondria CC upon FAS activation. CC -!- INDUCTION: By TNF which induces strong nuclear localization. CC {ECO:0000269|PubMed:12477726}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH56685.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence starting in position 364.; Evidence={ECO:0000305}; CC Sequence=BAA92067.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF154415; AAF03367.1; -; mRNA. DR EMBL; AF164678; AAD45537.2; -; mRNA. DR EMBL; AB037736; BAA92553.2; -; mRNA. DR EMBL; AL353692; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW48540.1; -; Genomic_DNA. DR EMBL; CH471051; EAW48542.1; -; Genomic_DNA. DR EMBL; CH471051; EAW48544.1; -; Genomic_DNA. DR EMBL; BC042577; AAH42577.1; -; mRNA. DR EMBL; BC056685; AAH56685.1; ALT_SEQ; mRNA. DR EMBL; BC132828; AAI32829.1; -; mRNA. DR EMBL; BC132830; AAI32831.1; -; mRNA. DR EMBL; AK002070; BAA92067.1; ALT_INIT; mRNA. DR EMBL; AF165161; AAD45157.1; -; mRNA. DR RefSeq; NP_001131139.1; NM_001137667.1. DR RefSeq; NP_001131140.1; NM_001137668.1. DR RefSeq; NP_036247.1; NM_012115.3. DR UniGene; Hs.558218; -. DR PDB; 2LR8; NMR; -; A=1916-1982. DR PDBsum; 2LR8; -. DR ProteinModelPortal; Q9UKL3; -. DR SMR; Q9UKL3; 1916-1982. DR BioGrid; 115315; 21. DR DIP; DIP-40986N; -. DR IntAct; Q9UKL3; 13. DR MINT; MINT-91616; -. DR PhosphoSite; Q9UKL3; -. DR BioMuta; CASP8AP2; -. DR DMDM; 74721007; -. DR MaxQB; Q9UKL3; -. DR PRIDE; Q9UKL3; -. DR GeneID; 9994; -. DR KEGG; hsa:9994; -. DR UCSC; uc003pnr.3; human. DR CTD; 9994; -. DR GeneCards; CASP8AP2; -. DR HGNC; HGNC:1510; CASP8AP2. DR MIM; 606880; gene. DR neXtProt; NX_Q9UKL3; -. DR PharmGKB; PA26093; -. DR HOVERGEN; HBG080371; -. DR InParanoid; Q9UKL3; -. DR PhylomeDB; Q9UKL3; -. DR ChiTaRS; CASP8AP2; human. DR GeneWiki; CASP8AP2; -. DR GenomeRNAi; 9994; -. DR NextBio; 37755; -. DR PRO; PR:Q9UKL3; -. DR Proteomes; UP000005640; Unplaced. DR CleanEx; HS_CASP8AP2; -. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; ISS:UniProtKB. DR GO; GO:0005123; F:death receptor binding; TAS:ProtInc. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. DR GO; GO:0016505; F:peptidase activator activity involved in apoptotic process; ISS:UniProtKB. DR GO; GO:0032184; F:SUMO polymer binding; IDA:UniProtKB. DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB. DR GO; GO:0006919; P:activation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB. DR GO; GO:0097190; P:apoptotic signaling pathway; TAS:ProtInc. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IMP:UniProtKB. DR GO; GO:0036337; P:Fas signaling pathway; IMP:UniProtKB. DR GO; GO:1903507; P:negative regulation of nucleic acid-templated transcription; IDA:GOC. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 1.10.10.60; -; 1. DR InterPro; IPR009057; Homeodomain-like. DR SUPFAM; SSF46689; SSF46689; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Apoptosis; Cell cycle; KW Complete proteome; Cytoplasm; Isopeptide bond; Mitochondrion; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Repressor; KW Transcription; Transcription regulation; Ubl conjugation. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:20068231}. FT CHAIN 2 1982 CASP8-associated protein 2. FT /FTId=PRO_0000076188. FT REGION 1709 1982 NCOA2-binding. FT {ECO:0000269|PubMed:12477726}. FT MOTIF 1683 1687 SUMO interaction motif 1 (SIM); mediates FT the binding to polysumoylated substrates. FT {ECO:0000250}. FT MOTIF 1737 1741 SUMO interaction motif 2 (SIM); mediates FT the binding to polysumoylated substrates. FT {ECO:0000250}. FT MOTIF 1794 1798 SUMO interaction motif 3 (SIM); mediates FT the binding to polysumoylated substrates. FT {ECO:0000250}. FT MOD_RES 2 2 N-acetylalanine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 20 20 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 1343 1343 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q9WUF3}. FT CROSSLNK 92 92 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000269|PubMed:17370265}. FT CROSSLNK 93 93 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000269|PubMed:17370265}. FT VARIANT 1659 1659 P -> S (in dbSNP:rs3799896). FT /FTId=VAR_050700. FT CONFLICT 278 278 L -> S (in Ref. 2; AAD45537). FT {ECO:0000305}. FT CONFLICT 362 362 D -> E (in Ref. 7; AAH56685). FT {ECO:0000305}. FT CONFLICT 638 638 L -> P (in Ref. 2; AAD45537). FT {ECO:0000305}. FT CONFLICT 668 668 M -> T (in Ref. 2; AAD45537). FT {ECO:0000305}. FT CONFLICT 861 861 N -> S (in Ref. 2; AAD45537). FT {ECO:0000305}. FT CONFLICT 1713 1713 C -> Y (in Ref. 2; AAD45537). FT {ECO:0000305}. FT CONFLICT 1754 1754 Missing (in Ref. 3; BAA92553). FT {ECO:0000305}. FT CONFLICT 1832 1832 S -> P (in Ref. 8; BAA92067). FT {ECO:0000305}. FT STRAND 1925 1927 {ECO:0000244|PDB:2LR8}. FT HELIX 1931 1943 {ECO:0000244|PDB:2LR8}. FT HELIX 1948 1958 {ECO:0000244|PDB:2LR8}. FT HELIX 1962 1977 {ECO:0000244|PDB:2LR8}. SQ SEQUENCE 1982 AA; 222658 MW; AF2B1A7798C19E39 CRC64; MAADDDNGDG TSLFDVFSAS PLKNNDEGSL DIYAGLDSAV SDSASKSCVP SRNCLDLYEE ILTEEGTAKE ATYNDLQVEY GKCQLQMKEL MKKFKEIQTQ NFSLINENQS LKKNISALIK TARVEINRKD EEISNLHQRL SEFPHFRNNH KTARTFDTVK TKDLKSRSPH LDDCSKTDHR AKSDVSKDVH HSTSLPNLEK EGKPHSDKRS TSHLPTSVEK HCTNGVWSRS HYQVGEGSSN EDSRRGRKDI RHSQFNRGTE RVRKDLSTGC GDGEPRILEA SQRLQGHPEK YGKGEPKTES KSSKFKSNSD SDYKGERINS SWEKETPGER SHSRVDSQSD KKLERQSERS QNINRKEVKS QDKEERKVDQ KPKSVVKDQD HWRRSERASL PHSKNEITFS HNSSKYHLEE RRGWEDCKRD KSVNSHSFQD GRCPSSLSNS RTHKNIDSKE VDAMHQWENT PLKAERHRTE DKRKREQESK EENRHIRNEK RVPTEHLQKT NKETKKTTTD LKKQNEPKTD KGEVLDNGVS EGADNKELAM KAESGPNETK NKDLKLSFMK KLNLTLSPAK KQPVSQDNQH KITDIPKSSG VCDSESSMQV KTVAYVPSIS EHILGEAAVS EHTMGETKST LLEPKVALLA VTEPRIGISE TNKEDENSLL VRSVDNTMHC EEPICGTETS FPSPMEIQQT ESLFPSTGMK QTINNGRAAA PVVMDVLQTD VSQNFGLELD TKRNDNSDYC GISEGMEMKV ALSTTVSETT ESILQPSIEE ADILPIMLSE DNNPKFEPSV IVTPLVESKS CHLEPCLPKE TLDSSLQQTE LMDHRMATGE TNSVYHDDDN SVLSIDLNHL RPIPEAISPL NSPVRPVAKV LRNESPPQVP VYNNSHKDVF LPNSAHSTSK SQSDLNKENQ KPIYKSDKCT EADTCKNSPL DELEEGEIRS DSETSKPQES FEKNSKRRVS ADVRKSKTIP RRGKSTVCLD KDSRKTHVRI HQTNNKWNKR PDKSSRSSKT EKKDKVMSTS SLEKIVPIIA VPSSEQEIMH MLRMIRKHVR KNYMKFKAKF SLIQFHRIIE SAILSFTSLI KHLNLHKISK SVTTLQKNLC DIIESKLKQV KKNGIVDRLF EQQLPDMKKK LWKFVDDQLD YLFAKLKKIL VCDSKSFGRD SDEGKLEKTS KQNAQYSNSQ KRSVDNSNRE LLKEKLSKSE DPVHYKSLVG CKKSEENYQD QNNSSINTVK HDIKKNFNIC FDNIKNSQSE ERSLEVHCPS TPKSEKNEGS SIEDAQTSQH ATLKPERSFE ILTEQQASSL TFNLVSDAQM GEIFKSLLQG SDLLDSSVNC TEKSEWELKT PEKQLLETLK CESIPACTTE ELVSGVASPC PKMISDDNWS LLSSEKGPSL SSGLSLPVHP DVLDESCMFE VSTNLPLSKD NVCSVEKSKP CVSSILLEDL AVSLTVPSPL KSDGHLSFLK PDMSSSSTPE EVISAHFSED ALLEEEDASE QDIHLALESD NSSSKSSCSS SWTSRSVAPG FQYHPNLPMH AVIMEKSNDH FIVKIRRATP STSSGLKQSM MPDELLTSLP RHGKEADEGP EKEYISCQNT VFKSVEELEN SNKNVDGSKS THEEQSSMIQ TQVPDIYEFL KDASDKMGHS DEVADECFKL HQVWETKVPE SIEELPSMEE ISHSVGEHLP NTYVDLTKDP VTETKNLGEF IEVTVLHIDQ LGCSGGNLNQ SAQILDNSLQ ADTVGAFIDL TQDASSEAKS EGNHPALAVE DLGCGVIQVD EDNCKEEKAQ VANRPLKCIV EETYIDLTTE SPSSCEVKKD ELKSEPGSNC DNSELPGTLH NSHKKRRNIS DLNHPHKKQR KETDLTNKEK TKKPTQDSCE NTEAHQKKAS KKKAPPVTKD PSSLKATPGI KDSSAALATS TSLSAKNVIK KKGEIIILWT RNDDREILLE CQKRGPSFKT FAYLAAKLDK NPNQVSERFQ QLMKLFEKSK CR // ID CCNH_HUMAN Reviewed; 323 AA. AC P51946; Q53X72; Q8TBL9; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 11-NOV-2015, entry version 170. DE RecName: Full=Cyclin-H; DE AltName: Full=MO15-associated protein; DE AltName: Full=p34; DE AltName: Full=p37; GN Name=CCNH; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 2-20; 106-133 AND RP 256-279. RC TISSUE=Liver; RX PubMed=8078587; DOI=10.1038/371254a0; RA Maekelae T.P., Tassan J.-P., Nigg E.A., Frutiger S., Hughes G.J., RA Weinberg R.A.; RT "A cyclin associated with the CDK-activating kinase MO15."; RL Nature 371:254-257(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 10-21; 90-102 AND RP 190-197. RX PubMed=8069918; DOI=10.1016/0092-8674(94)90535-5; RA Fisher R.P., Morgan D.O.; RT "A novel cyclin associates with MO15/CDK7 to form the CDK-activating RT kinase."; RL Cell 78:713-724(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-270. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-28; VAL-54; RP ARG-138 AND ALA-270. RG NIEHS SNPs program; RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-270. RC TISSUE=Bone marrow, Brain, Embryonic brain, and Urinary bladder; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION. RX PubMed=7533895; DOI=10.1038/374283a0; RA Shiekhattar R., Mermelstein F., Fisher R.P., Drapkin R., Dynlacht B., RA Wessling H.C., Morgan D.O., Reinberg D.; RT "Cdk-activating kinase complex is a component of human transcription RT factor TFIIH."; RL Nature 374:283-287(1995). RN [7] RP IDENTIFICATION IN THE TFIIH BASAL TRANSCRIPTION FACTOR. RX PubMed=9852112; DOI=10.1074/jbc.273.51.34444; RA Kershnar E., Wu S.-Y., Chiang C.-M.; RT "Immunoaffinity purification and functional characterization of human RT transcription factor IIH and RNA polymerase II from clonal cell lines RT that conditionally express epitope-tagged subunits of the multiprotein RT complexes."; RL J. Biol. Chem. 273:34444-34453(1998). RN [8] RP FUNCTION. RX PubMed=10024882; DOI=10.1016/S1097-2765(00)80177-X; RA Tirode F., Busso D., Coin F., Egly J.-M.; RT "Reconstitution of the transcription factor TFIIH: assignment of RT functions for the three enzymatic subunits, XPB, XPD, and cdk7."; RL Mol. Cell 3:87-95(1999). RN [9] RP PHOSPHORYLATION AT SER-5 AND SER-304, AND MUTAGENESIS OF SER-5 AND RP SER-304. RX PubMed=10993082; DOI=10.1038/35024111; RA Akoulitchev S., Chuikov S., Reinberg D.; RT "TFIIH is negatively regulated by cdk8-containing mediator RT complexes."; RL Nature 407:102-106(2000). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-315, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-132; THR-315 AND RP SER-322, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-315, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-315, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-315 AND SER-322, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-315, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [18] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS). RX PubMed=8836101; DOI=10.1038/nsb1096-849; RA Kim K.K., Chamberlin H.M., Morgan D.O., Kim S.-H.; RT "Three-dimensional structure of human cyclin H, a positive regulator RT of the CDK-activating kinase."; RL Nat. Struct. Biol. 3:849-855(1996). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 11-287. RX PubMed=9118957; DOI=10.1093/emboj/16.5.958; RA Andersen G., Busso D., Poterszman A., Hwang J.R., Wurtz J.-M., RA Ripp R., Thierry J.-C., Egly J.-M., Moras D.; RT "The structure of cyclin H: common mode of kinase activation and RT specific features."; RL EMBO J. 16:958-967(1997). CC -!- FUNCTION: Regulates CDK7, the catalytic subunit of the CDK- CC activating kinase (CAK) enzymatic complex. CAK activates the CC cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine CC phosphorylation. CAK complexed to the core-TFIIH basal CC transcription factor activates RNA polymerase II by serine CC phosphorylation of the repetitive C-terminal domain (CTD) of its CC large subunit (POLR2A), allowing its escape from the promoter and CC elongation of the transcripts. Involved in cell cycle control and CC in RNA transcription by RNA polymerase II. Its expression and CC activity are constant throughout the cell cycle. CC {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:7533895}. CC -!- SUBUNIT: Associates primarily with CDK7 and MAT1 to form the CAK CC complex. CAK can further associate with the core-TFIIH to form the CC TFIIH basal transcription factor. {ECO:0000269|PubMed:9852112}. CC -!- INTERACTION: CC Q13137:CALCOCO2; NbExp=3; IntAct=EBI-741406, EBI-739580; CC Q8IYT3:CCDC170; NbExp=3; IntAct=EBI-741406, EBI-2808089; CC P24941:CDK2; NbExp=2; IntAct=EBI-741406, EBI-375096; CC P56545:CTBP2; NbExp=5; IntAct=EBI-741406, EBI-741533; CC Q9UNI6:DUSP12; NbExp=3; IntAct=EBI-741406, EBI-715161; CC Q08379:GOLGA2; NbExp=5; IntAct=EBI-741406, EBI-618309; CC Q6P597:KLC3; NbExp=3; IntAct=EBI-741406, EBI-1643885; CC O14777:NDC80; NbExp=3; IntAct=EBI-741406, EBI-715849; CC Q13136:PPFIA1; NbExp=3; IntAct=EBI-741406, EBI-745426; CC P25786:PSMA1; NbExp=4; IntAct=EBI-741406, EBI-359352; CC P31947:SFN; NbExp=3; IntAct=EBI-741406, EBI-476295; CC O60232:SSSCA1; NbExp=4; IntAct=EBI-741406, EBI-741415; CC Q9Y2D8:SSX2IP; NbExp=4; IntAct=EBI-741406, EBI-2212028; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- SIMILARITY: Belongs to the cyclin family. Cyclin C subfamily. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/ccnh/"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U11791; AAA21361.1; -; mRNA. DR EMBL; U12685; AAA57006.1; -; mRNA. DR EMBL; CR407658; CAG28586.1; -; mRNA. DR EMBL; AF477979; AAL74271.1; -; Genomic_DNA. DR EMBL; BC005280; AAH05280.1; -; mRNA. DR EMBL; BC016705; AAH16705.1; -; mRNA. DR EMBL; BC016823; AAH16823.1; -; mRNA. DR EMBL; BC022351; AAH22351.1; -; mRNA. DR CCDS; CCDS4064.1; -. DR PIR; I38731; I38731. DR RefSeq; NP_001230.1; NM_001239.3. DR UniGene; Hs.292524; -. DR PDB; 1JKW; X-ray; 2.60 A; A=1-323. DR PDB; 1KXU; X-ray; 2.60 A; A=1-323. DR PDBsum; 1JKW; -. DR PDBsum; 1KXU; -. DR DisProt; DP00307; -. DR ProteinModelPortal; P51946; -. DR SMR; P51946; 11-286. DR BioGrid; 107342; 52. DR DIP; DIP-5996N; -. DR IntAct; P51946; 23. DR MINT; MINT-1434271; -. DR STRING; 9606.ENSP00000256897; -. DR BindingDB; P51946; -. DR ChEMBL; CHEMBL2111288; -. DR PhosphoSite; P51946; -. DR BioMuta; CCNH; -. DR DMDM; 1706232; -. DR MaxQB; P51946; -. DR PaxDb; P51946; -. DR PeptideAtlas; P51946; -. DR PRIDE; P51946; -. DR DNASU; 902; -. DR Ensembl; ENST00000256897; ENSP00000256897; ENSG00000134480. DR GeneID; 902; -. DR UCSC; uc003kja.3; human. DR CTD; 902; -. DR GeneCards; CCNH; -. DR HGNC; HGNC:1594; CCNH. DR HPA; CAB019416; -. DR HPA; HPA044138; -. DR MIM; 601953; gene. DR neXtProt; NX_P51946; -. DR PharmGKB; PA26159; -. DR eggNOG; KOG2496; Eukaryota. DR eggNOG; COG5333; LUCA. DR GeneTree; ENSGT00390000008634; -. DR HOGENOM; HOG000232149; -. DR HOVERGEN; HBG050840; -. DR InParanoid; P51946; -. DR OMA; RKFKCKV; -. DR PhylomeDB; P51946; -. DR TreeFam; TF101008; -. DR Reactome; R-HSA-110302; Formation of transcription-coupled NER (TC-NER) repair complex. DR Reactome; R-HSA-110304; Dual incision reaction in TC-NER. DR Reactome; R-HSA-112382; Formation of RNA Pol II elongation complex. DR Reactome; R-HSA-113418; Formation of the Early Elongation Complex. DR Reactome; R-HSA-167152; Formation of HIV elongation complex in the absence of HIV Tat. DR Reactome; R-HSA-167158; Formation of the HIV-1 Early Elongation Complex. DR Reactome; R-HSA-167160; RNA Pol II CTD phosphorylation and interaction with CE. DR Reactome; R-HSA-167161; HIV Transcription Initiation. DR Reactome; R-HSA-167162; RNA Polymerase II HIV Promoter Escape. DR Reactome; R-HSA-167172; Transcription of the HIV genome. DR Reactome; R-HSA-167200; Formation of HIV-1 elongation complex containing HIV-1 Tat. DR Reactome; R-HSA-167246; Tat-mediated elongation of the HIV-1 transcript. DR Reactome; R-HSA-427413; NoRC negatively regulates rRNA expression. DR Reactome; R-HSA-674695; RNA Polymerase II Pre-transcription Events. DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition. DR Reactome; R-HSA-69231; Cyclin D associated events in G1. DR Reactome; R-HSA-69273; Cyclin A/B1 associated events during G2/M transition. DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry. DR Reactome; R-HSA-72086; mRNA Capping. DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation. DR Reactome; R-HSA-73772; RNA Polymerase I Promoter Escape. DR Reactome; R-HSA-73776; RNA Polymerase II Promoter Escape. DR Reactome; R-HSA-73777; RNA Polymerase I Chain Elongation. DR Reactome; R-HSA-73779; RNA Polymerase II Transcription Pre-Initiation And Promoter Opening. DR Reactome; R-HSA-73863; RNA Polymerase I Transcription Termination. DR Reactome; R-HSA-73935; Formation of incision complex in GG-NER. DR Reactome; R-HSA-73941; Dual incision reaction in GG-NER. DR Reactome; R-HSA-75953; RNA Polymerase II Transcription Initiation. DR Reactome; R-HSA-75955; RNA Polymerase II Transcription Elongation. DR Reactome; R-HSA-76042; RNA Polymerase II Transcription Initiation And Promoter Clearance. DR Reactome; R-HSA-77075; RNA Pol II CTD phosphorylation and interaction with CE. DR SignaLink; P51946; -. DR ChiTaRS; CCNH; human. DR EvolutionaryTrace; P51946; -. DR GeneWiki; Cyclin_H; -. DR GenomeRNAi; 902; -. DR NextBio; 3728; -. DR PRO; PR:P51946; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; P51946; -. DR CleanEx; HS_CCNH; -. DR ExpressionAtlas; P51946; baseline and differential. DR Genevisible; P51946; HS. DR GO; GO:0019907; C:cyclin-dependent protein kinase activating kinase holoenzyme complex; IDA:UniProtKB. DR GO; GO:0005675; C:holo TFIIH complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0070985; C:TFIIK complex; IEA:InterPro. DR GO; GO:0016538; F:cyclin-dependent protein serine/threonine kinase regulator activity; IBA:GO_Central. DR GO; GO:0016301; F:kinase activity; IEA:Ensembl. DR GO; GO:0006370; P:7-methylguanosine mRNA capping; TAS:Reactome. DR GO; GO:0006281; P:DNA repair; TAS:Reactome. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome. DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; TAS:Reactome. DR GO; GO:0006289; P:nucleotide-excision repair; TAS:Reactome. DR GO; GO:0000718; P:nucleotide-excision repair, DNA damage removal; TAS:Reactome. DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central. DR GO; GO:1901409; P:positive regulation of phosphorylation of RNA polymerase II C-terminal domain; IBA:GO_Central. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0050434; P:positive regulation of viral transcription; TAS:Reactome. DR GO; GO:0006468; P:protein phosphorylation; IDA:GOC. DR GO; GO:0040029; P:regulation of gene expression, epigenetic; TAS:Reactome. DR GO; GO:0006363; P:termination of RNA polymerase I transcription; TAS:Reactome. DR GO; GO:0006362; P:transcription elongation from RNA polymerase I promoter; TAS:Reactome. DR GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0006360; P:transcription from RNA polymerase I promoter; TAS:Reactome. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0006361; P:transcription initiation from RNA polymerase I promoter; TAS:Reactome. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; TAS:Reactome. DR GO; GO:0016032; P:viral process; TAS:Reactome. DR Gene3D; 1.10.472.10; -; 2. DR InterPro; IPR013763; Cyclin-like. DR InterPro; IPR031658; Cyclin_C_2. DR InterPro; IPR006671; Cyclin_N. DR InterPro; IPR027081; CyclinH/Ccl1. DR Pfam; PF16899; Cyclin_C_2; 1. DR Pfam; PF00134; Cyclin_N; 1. DR SMART; SM00385; CYCLIN; 1. DR SUPFAM; SSF47954; SSF47954; 2. DR TIGRFAMs; TIGR00569; ccl1; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell cycle; Complete proteome; Cyclin; KW Direct protein sequencing; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Transcription; Transcription regulation. FT CHAIN 1 323 Cyclin-H. FT /FTId=PRO_0000080471. FT COMPBIAS 310 313 Poly-Glu. FT MOD_RES 5 5 Phosphoserine; by CDK8. FT {ECO:0000269|PubMed:10993082}. FT MOD_RES 132 132 Phosphoserine. FT {ECO:0000244|PubMed:18691976}. FT MOD_RES 304 304 Phosphoserine; by CDK8. FT {ECO:0000269|PubMed:10993082}. FT MOD_RES 315 315 Phosphothreonine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 322 322 Phosphoserine. FT {ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:20068231}. FT VARIANT 28 28 R -> L (in dbSNP:rs2234942). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_013067. FT VARIANT 54 54 M -> V (in dbSNP:rs3093785). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_013068. FT VARIANT 138 138 K -> R (in dbSNP:rs2266691). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_013069. FT VARIANT 270 270 V -> A (in dbSNP:rs2230641). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.3, ECO:0000269|Ref.4}. FT /FTId=VAR_013070. FT MUTAGEN 5 5 S->A: No effect on the transcriptional FT activity of the reconstituted TFIIH FT complex. {ECO:0000269|PubMed:10993082}. FT MUTAGEN 304 304 S->A: No effect on the transcriptional FT activity of the reconstituted TFIIH FT complex. {ECO:0000269|PubMed:10993082}. FT HELIX 16 36 {ECO:0000244|PDB:1JKW}. FT STRAND 38 40 {ECO:0000244|PDB:1JKW}. FT HELIX 50 70 {ECO:0000244|PDB:1JKW}. FT TURN 72 74 {ECO:0000244|PDB:1JKW}. FT HELIX 77 90 {ECO:0000244|PDB:1JKW}. FT HELIX 91 93 {ECO:0000244|PDB:1JKW}. FT TURN 96 98 {ECO:0000244|PDB:1JKW}. FT HELIX 101 115 {ECO:0000244|PDB:1JKW}. FT HELIX 122 125 {ECO:0000244|PDB:1JKW}. FT HELIX 126 128 {ECO:0000244|PDB:1JKW}. FT STRAND 129 131 {ECO:0000244|PDB:1JKW}. FT HELIX 133 153 {ECO:0000244|PDB:1JKW}. FT TURN 154 156 {ECO:0000244|PDB:1JKW}. FT HELIX 164 177 {ECO:0000244|PDB:1JKW}. FT HELIX 179 182 {ECO:0000244|PDB:1KXU}. FT HELIX 184 198 {ECO:0000244|PDB:1JKW}. FT TURN 200 202 {ECO:0000244|PDB:1KXU}. FT HELIX 203 206 {ECO:0000244|PDB:1JKW}. FT HELIX 209 224 {ECO:0000244|PDB:1JKW}. FT HELIX 231 235 {ECO:0000244|PDB:1JKW}. FT STRAND 240 242 {ECO:0000244|PDB:1JKW}. FT HELIX 246 260 {ECO:0000244|PDB:1JKW}. FT HELIX 267 282 {ECO:0000244|PDB:1JKW}. SQ SEQUENCE 323 AA; 37643 MW; BB48D55DA397A0E4 CRC64; MYHNSSQKRH WTFSSEEQLA RLRADANRKF RCKAVANGKV LPNDPVFLEP HEEMTLCKYY EKRLLEFCSV FKPAMPRSVV GTACMYFKRF YLNNSVMEYH PRIIMLTCAF LACKVDEFNV SSPQFVGNLR ESPLGQEKAL EQILEYELLL IQQLNFHLIV HNPYRPFEGF LIDLKTRYPI LENPEILRKT ADDFLNRIAL TDAYLLYTPS QIALTAILSS ASRAGITMES YLSESLMLKE NRTCLSQLLD IMKSMRNLVK KYEPPRSEEV AVLKQKLERC HSAELALNVI TKKRKGYEDD DYVSKKSKHE EEEWTDDDLV ESL // ID CCR5_HUMAN Reviewed; 352 AA. AC P51681; O14692; O14693; O14695; O14696; O14697; O14698; O14699; AC O14700; O14701; O14702; O14703; O14704; O14705; O14706; O14707; AC O14708; O15538; Q9UPA4; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 11-NOV-2015, entry version 160. DE RecName: Full=C-C chemokine receptor type 5; DE Short=C-C CKR-5; DE Short=CC-CKR-5; DE Short=CCR-5; DE Short=CCR5; DE AltName: Full=CHEMR13; DE AltName: Full=HIV-1 fusion coreceptor; DE AltName: CD_antigen=CD195; GN Name=CCR5; Synonyms=CMKBR5; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=8639485; DOI=10.1021/bi952950g; RA Samson M., Labbe O., Mollereau C., Vassart G., Parmentier M.; RT "Molecular cloning and functional expression of a new human CC- RT chemokine receptor gene."; RL Biochemistry 35:3362-3367(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CCL4 AND CCL5, RP AND TISSUE SPECIFICITY. RC TISSUE=Macrophage; RX PubMed=8663314; DOI=10.1074/jbc.271.29.17161; RA Raport C.J., Gosling J., Schweichart V.L., Gray P.W., Charo I.F.; RT "Molecular cloning and functional characterization of a novel human CC RT chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha."; RL J. Biol. Chem. 271:17161-17166(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND INTERACTION WITH CCL3; CCL4 RP AND CCL5. RX PubMed=8699119; RA Combadiere C., Ahuja S.K., Tiffany H.L., Murphy P.M.; RT "Cloning and functional expression of CC CKR5, a human monocyte CC RT chemokine receptor selective for MIP-1(alpha), MIP-1(beta), and RT RANTES."; RL J. Leukoc. Biol. 60:147-152(1996). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9343222; RA Kuhmann S.E., Platt E.J., Kozak S.L., Kabat D.; RT "Polymorphisms in the CCR5 genes of African green monkeys and mice RT implicate specific amino acids in infections by simian and human RT immunodeficiency viruses."; RL J. Virol. 71:8642-8656(1997). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], AND POLYMORPHISM. RX PubMed=9359654; DOI=10.1089/aid.1997.13.1357; RA Zhang L., Carruthers C.D., He T., Huang Y., Cao Y., Wang G., Hahn B., RA Ho D.D.; RT "HIV type 1 subtypes, coreceptor usage, and CCR5 polymorphism."; RL AIDS Res. Hum. Retroviruses 13:1357-1366(1997). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9388201; DOI=10.1074/jbc.272.49.30662; RA Mummidi S., Ahuja S.S., McDaniel B.L., Ahuja S.K.; RT "The human CC chemokine receptor 5 (CCR5) gene. Multiple transcripts RT with 5'-end heterogeneity, dual promoter usage, and evidence for RT polymorphisms within the regulatory regions and noncoding exons."; RL J. Biol. Chem. 272:30662-30671(1997). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-178. RA Magierowska M., Barre-Sinoussi F., Issafras H., Theodorou I., RA Debre P.; RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kopatz S.A., Aronstam R.S., Sharma S.V.; RT "cDNA clones of human proteins involved in signal transduction RT sequenced by the Guthrie cDNA resource center (www.cdna.org)."; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., RA Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [11] RP FUNCTION AS A HIV-1 CORECEPTOR. RX PubMed=8649511; DOI=10.1038/381661a0; RA Deng H., Liu R., Ellmeier W., Choe S., Unutmaz D., Burkhart M., RA di Marzio P., Marmon S., Sutton R.E., Hill C.M., Davis C.B., RA Peiper S.C., Schall T.J., Littman D.R., Landau N.R.; RT "Identification of a major co-receptor for primary isolates of HIV- RT 1."; RL Nature 381:661-666(1996). RN [12] RP FUNCTION AS A HIV-1 CORECEPTOR. RX PubMed=8649512; DOI=10.1038/381667a0; RA Dragic T., Litwin V., Allaway G.P., Martin S.R., Huang Y., RA Nagashima K.A., Cayanan C., Maddon P.J., Koup R.A., Moore J.P., RA Paxton W.A.; RT "HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC- RT CKR-5."; RL Nature 381:667-673(1996). RN [13] RP INTERACTION WITH HIV-1 SURFACE PROTEIN GP120, AND FUNCTION (MICROBIAL RP INFECTION). RX PubMed=9632396; DOI=10.1126/science.280.5371.1949; RA Rizzuto C.D., Wyatt R., Hernandez-Ramos N., Sun Y., Kwong P.D., RA Hendrickson W.A., Sodroski J.; RT "A conserved HIV gp120 glycoprotein structure involved in chemokine RT receptor binding."; RL Science 280:1949-1953(1998). RN [14] RP SULFATION AT TYR-3, GLYCOSYLATION, AND MUTAGENESIS OF TYR-3; TYR-10; RP TYR-14 AND TYR-15. RX PubMed=10089882; DOI=10.1016/S0092-8674(00)80577-2; RA Farzan M., Mirzabekov T., Kolchinsky P., Wyatt R., Cayabyab M., RA Gerard N.P., Gerard C., Sodroski J., Choe H.; RT "Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 RT entry."; RL Cell 96:667-676(1999). RN [15] RP PHOSPHORYLATION AT SER-336; SER-337; SER-342 AND SER-349, MUTAGENESIS RP OF SER-336; SER-337; SER-342 AND SER-349, AND INTERACTION WITH ADRBK1. RX PubMed=10085131; DOI=10.1074/jbc.274.13.8875; RA Oppermann M., Mack M., Proudfoot A.E., Olbrich H.; RT "Differential effects of CC chemokines on CC chemokine receptor 5 RT (CCR5) phosphorylation and identification of phosphorylation sites on RT the CCR5 carboxyl terminus."; RL J. Biol. Chem. 274:8875-8885(1999). RN [16] RP PALMITOYLATION AT CYS-321; CYS-323 AND CYS-324, SUBCELLULAR LOCATION, RP FUNCTION, AND MUTAGENESIS OF CYS-321; CYS-323 AND CYS-324. RX PubMed=11323418; DOI=10.1074/jbc.M100583200; RA Blanpain C., Wittamer V., Vanderwinden J.-M., Boom A., Renneboog B., RA Lee B., Le Poul E., El Asmar L., Govaerts C., Vassart G., Doms R.W., RA Parmentier M.; RT "Palmitoylation of CCR5 is critical for receptor trafficking and RT efficient activation of intracellular signaling pathways."; RL J. Biol. Chem. 276:23795-23804(2001). RN [17] RP INTERACTION WITH ARRB2, AND MUTAGENESIS OF SER-336; SER-337; SER-342 RP AND SER-349. RX PubMed=11448957; DOI=10.1074/jbc.M102782200; RA Kraft K., Olbrich H., Majoul I., Mack M., Proudfoot A., Oppermann M.; RT "Characterization of sequence determinants within the carboxyl- RT terminal domain of chemokine receptor CCR5 that regulate signaling and RT receptor internalization."; RL J. Biol. Chem. 276:34408-34418(2001). RN [18] RP SULFATION, GLYCOSYLATION AT SER-6, INTERACTION WITH CCL3; CCL4 AND RP CCL5, MUTAGENESIS OF TYR-3; SER-6; SER-7; TYR-10; TYR-14; TYR-15; RP THR-16 AND SER-17, AND CHARACTERIZATION OF VARIANT ASP-10. RX PubMed=11733580; DOI=10.1084/jem.194.11.1661; RA Bannert N., Craig S., Farzan M., Sogah D., Santo N.V., Choe H., RA Sodroski J.; RT "Sialylated O-glycans and sulfated tyrosines in the NH2-terminal RT domain of CC chemokine receptor 5 contribute to high affinity binding RT of chemokines."; RL J. Exp. Med. 194:1661-1673(2001). RN [19] RP INTERACTION WITH PRAF2. RX PubMed=15757671; DOI=10.1016/j.febslet.2005.02.037; RA Schweneker M., Bachmann A.S., Moelling K.; RT "JM4 is a four-transmembrane protein binding to the CCR5 receptor."; RL FEBS Lett. 579:1751-1758(2005). RN [20] RP INTERACTION WITH ARRB1 AND ARRB2. RX PubMed=16144840; DOI=10.1074/jbc.M500535200; RA Huettenrauch F., Pollok-Kopp B., Oppermann M.; RT "G protein-coupled receptor kinases promote phosphorylation and beta- RT arrestin-mediated internalization of CCR5 homo- and hetero- RT oligomers."; RL J. Biol. Chem. 280:37503-37515(2005). RN [21] RP INVOLVEMENT IN WEST NILE VIRUS INFECTION SUSCEPTIBILITY. RX PubMed=16418398; DOI=10.1084/jem.20051970; RA Glass W.G., McDermott D.H., Lim J.K., Lekhong S., Yu S.F., Frank W.A., RA Pape J., Cheshier R.C., Murphy P.M.; RT "CCR5 deficiency increases risk of symptomatic West Nile virus RT infection."; RL J. Exp. Med. 203:35-40(2006). RN [22] RP INDUCTION (MICROBIAL INFECTION), AND INTERACTION WITH HHV-5 PROTEIN RP UL78. RX PubMed=22496149; DOI=10.1182/blood-2011-08-372516; RA Tadagaki K., Tudor D., Gbahou F., Tschische P., Waldhoer M., RA Bomsel M., Jockers R., Kamal M.; RT "Human cytomegalovirus-encoded UL33 and UL78 heteromerize with host RT CCR5 and CXCR4 impairing their HIV coreceptor activity."; RL Blood 119:4908-4918(2012). RN [23] RP 3D-STRUCTURE MODELING. RX PubMed=12496074; DOI=10.1016/S0006-3495(02)75307-1; RA Paterlini M.G.; RT "Structure modeling of the chemokine receptor CCR5: implications for RT ligand binding and selectivity."; RL Biophys. J. 83:3012-3031(2002). RN [24] RP 3D-STRUCTURE MODELING. RX PubMed=14517611; DOI=10.1007/s00894-003-0154-9; RA Liu S., Fan S., Sun Z.; RT "Structural and functional characterization of the human CCR5 receptor RT in complex with HIV gp120 envelope glycoprotein and CD4 receptor by RT molecular modeling studies."; RL J. Mol. Model. 9:329-336(2003). RN [25] RP STRUCTURE BY NMR OF 1-27 IN COMPLEX WITH HIV-1 GP120 AND CD4 MIMIC RP PEPTIDE, FUNCTION (MICROBIAL INFECTION), AND SULFATION AT TYR-10 AND RP TYR-14. RX PubMed=21763489; DOI=10.1016/j.jmb.2011.04.023; RA Schnur E., Noah E., Ayzenshtat I., Sargsyan H., Inui T., Ding F.X., RA Arshava B., Sagi Y., Kessler N., Levy R., Scherf T., Naider F., RA Anglister J.; RT "The conformation and orientation of a 27-residue CCR5 peptide in a RT ternary complex with HIV-1 gp120 and a CD4-mimic peptide."; RL J. Mol. Biol. 410:778-797(2011). RN [26] RP VARIANTS GLN-55; LEU-215; GLN-223; VAL-335 AND PHE-339. RX PubMed=9207783; DOI=10.1038/ng0797-221; RA Ansari-Lari M.A., Liu X.-M., Metzker M.L., Rut A.R., Gibbs R.A.; RT "The extent of genetic variation in the CCR5 gene."; RL Nat. Genet. 16:221-222(1997). RN [27] RP VARIANTS LEU-12; SER-20; SER-29; PHE-42; GLN-55; SER-60; VAL-73; RP GLN-223; LYS-228 DEL; VAL-301; VAL-335 AND PHE-339, AND ASSOCIATION RP WITH SUSCEPTIBILITY TO HIV-1. RX PubMed=9399903; DOI=10.1086/301645; RA Carrington M., Kissner T., Gerrard B., Ivanov S., O'Brien S.J., RA Dean M.; RT "Novel alleles of the chemokine-receptor gene CCR5."; RL Am. J. Hum. Genet. 61:1261-1267(1997). RN [28] RP CHARACTERIZATION OF VARIANT SER-60. RX PubMed=11369664; DOI=10.1182/blood.V97.11.3651; RA Tamasauskas D., Powell V., Saksela K., Yazdanbakhsh K.; RT "A homologous naturally occurring mutation in Duffy and CCR5 leading RT to reduced receptor expression."; RL Blood 97:3651-3654(2001). RN [29] RP INVOLVEMENT IN IDDM22. RX PubMed=19073967; DOI=10.1056/NEJMoa0807917; RA Smyth D.J., Plagnol V., Walker N.M., Cooper J.D., Downes K., RA Yang J.H.M., Howson J.M.M., Stevens H., McManus R., Wijmenga C., RA Heap G.A., Dubois P.C., Clayton D.G., Hunt K.A., van Heel D.A., RA Todd J.A.; RT "Shared and distinct genetic variants in type 1 diabetes and celiac RT disease."; RL N. Engl. J. Med. 359:2767-2777(2008). RN [30] RP INTERACTION WITH CNIH4. RX PubMed=24405750; DOI=10.1111/tra.12148; RA Sauvageau E., Rochdi M.D., Oueslati M., Hamdan F.F., Percherancier Y., RA Simpson J.C., Pepperkok R., Bouvier M.; RT "CNIH4 interacts with newly synthesized GPCR and controls their export RT from the endoplasmic reticulum."; RL Traffic 15:383-400(2014). CC -!- FUNCTION: Receptor for a number of inflammatory CC-chemokines CC including MIP-1-alpha, MIP-1-beta and RANTES and subsequently CC transduces a signal by increasing the intracellular calcium ion CC level. May play a role in the control of granulocytic lineage CC proliferation or differentiation. Acts as a coreceptor (CD4 being CC the primary receptor) for HIV-1 R5 isolates. CC {ECO:0000269|PubMed:11323418, ECO:0000269|PubMed:8639485, CC ECO:0000269|PubMed:8649511, ECO:0000269|PubMed:8649512, CC ECO:0000269|PubMed:8663314, ECO:0000269|PubMed:8699119}. CC -!- FUNCTION: (Microbial infection) Acts as a receptor for human CC immunodeficiency virus-1/HIV-1. {ECO:0000269|PubMed:21763489, CC ECO:0000269|PubMed:9632396}. CC -!- SUBUNIT: Interacts with PRAF2. Efficient ligand binding to CC CCL3/MIP-1alpha and CCL4/MIP-1beta requires sulfation, O- CC glycosylation and sialic acid modifications. Glycosylation on Ser- CC 6 is required for efficient binding of CCL4. Interacts with CC ADRBK1. Interacts with ARRB1 and ARRB2. Interacts with CNIH4 CC (PubMed:24405750). ARRB2. (Microbial infection) Interacts with CC HIV-1 surface protein gp120 (PubMed:9632396, PubMed:21763489). CC (Microbial infection) May interact with human cytomegalovirus/HHV- CC 5 protein UL78 (PubMed:22496149). {ECO:0000269|PubMed:10085131, CC ECO:0000269|PubMed:11448957, ECO:0000269|PubMed:11733580, CC ECO:0000269|PubMed:15757671, ECO:0000269|PubMed:16144840, CC ECO:0000269|PubMed:21763489, ECO:0000269|PubMed:22496149, CC ECO:0000269|PubMed:24405750, ECO:0000269|PubMed:8663314, CC ECO:0000269|PubMed:8699119, ECO:0000269|PubMed:9632396}. CC -!- INTERACTION: CC P13236:CCL4; NbExp=2; IntAct=EBI-489374, EBI-6625160; CC P13501:CCL5; NbExp=4; IntAct=EBI-489374, EBI-2848366; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11323418}; CC Multi-pass membrane protein {ECO:0000269|PubMed:11323418}. CC -!- TISSUE SPECIFICITY: Highly expressed in spleen, thymus, in the CC myeloid cell line THP-1, in the promyeloblastic cell line KG-1a CC and on CD4+ and CD8+ T-cells. Medium levels in peripheral blood CC leukocytes and in small intestine. Low levels in ovary and lung. CC {ECO:0000269|PubMed:8639485, ECO:0000269|PubMed:8663314}. CC -!- INDUCTION: (Microbial infection) May be down-regulated by human CC cytomegalovirus/HHV-5 protein UL78. {ECO:0000269|PubMed:22496149}. CC -!- PTM: Sulfated on at least 2 of the N-terminal tyrosines. Sulfation CC contributes to the efficiency of HIV-1 entry and is required for CC efficient binding of the chemokines, CCL3 and CCL4. CC {ECO:0000269|PubMed:10089882, ECO:0000269|PubMed:11733580, CC ECO:0000269|PubMed:21763489}. CC -!- PTM: O-glycosylated, but not N-glycosylated. Ser-6 appears to be CC the major site. Also sialylated glycans present which contribute CC to chemokine binding. Thr-16 and Ser-17 may also be glycosylated CC and, if so, with small moieties such as a T-antigen. CC {ECO:0000269|PubMed:10089882, ECO:0000269|PubMed:11733580}. CC -!- PTM: Palmitoylation in the C-terminal is important for cell CC surface expression, and to a lesser extent, for HIV entry. CC {ECO:0000269|PubMed:11323418}. CC -!- PTM: Phosphorylation on serine residues in the C-terminal is CC stimulated by binding CC chemokines especially by APO-RANTES. CC {ECO:0000269|PubMed:10085131}. CC -!- POLYMORPHISM: Variations in CCR5 are associated with resistance or CC susceptibility to immunodeficiency virus type 1 (resistance or CC susceptibility to HIV-1) [MIM:609423]. Variations in CCR5 gene CC also influence the rate of progression to AIDS after infection. CC -!- POLYMORPHISM: Ser-60 variant, a naturally occurring mutation in a CC conserved residue in the first intracellular domain of CCR5, CC results in reduced amounts of the protein in the membrane and CC consequently may be associated with reduced susceptibility to CC infection by microbes that depend on these molecules as their CC receptors. CC -!- POLYMORPHISM: Variations in CCR5 are associated with CC susceptibility to West Nile virus (WNV) infection [MIM:610379]. CC -!- DISEASE: Diabetes mellitus, insulin-dependent, 22 (IDDM22) CC [MIM:612522]: A multifactorial disorder of glucose homeostasis CC that is characterized by susceptibility to ketoacidosis in the CC absence of insulin therapy. Clinical features are polydipsia, CC polyphagia and polyuria which result from hyperglycemia-induced CC osmotic diuresis and secondary thirst. These derangements result CC in long-term complications that affect the eyes, kidneys, nerves, CC and blood vessels. {ECO:0000269|PubMed:19073967}. Note=Disease CC susceptibility is associated with variations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00521}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=CC chemokine receptors entry; CC URL="https://en.wikipedia.org/wiki/CC_chemokine_receptors"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=CCR5 receptor entry; CC URL="http://en.wikipedia.org/wiki/CCR5"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X91492; CAA62796.1; -; Genomic_DNA. DR EMBL; U54994; AAC50598.1; -; mRNA. DR EMBL; U57840; AAB17071.1; -; mRNA. DR EMBL; U83326; AAC51797.1; -; Genomic_DNA. DR EMBL; AF011500; AAB65700.1; -; mRNA. DR EMBL; AF011501; AAB65701.1; -; mRNA. DR EMBL; AF011502; AAB65702.1; -; mRNA. DR EMBL; AF011503; AAB65703.1; -; mRNA. DR EMBL; AF011505; AAB65705.1; -; mRNA. DR EMBL; AF011506; AAB65706.1; -; mRNA. DR EMBL; AF011507; AAB65707.1; -; mRNA. DR EMBL; AF011508; AAB65708.1; -; mRNA. DR EMBL; AF011509; AAB65709.1; -; mRNA. DR EMBL; AF011510; AAB65710.1; -; mRNA. DR EMBL; AF011511; AAB65711.1; -; mRNA. DR EMBL; AF011512; AAB65712.1; -; mRNA. DR EMBL; AF011513; AAB65713.1; -; mRNA. DR EMBL; AF011514; AAB65714.1; -; mRNA. DR EMBL; AF011515; AAB65715.1; -; mRNA. DR EMBL; AF011516; AAB65716.1; -; mRNA. DR EMBL; AF011517; AAB65717.1; -; mRNA. DR EMBL; AF011518; AAB65718.1; -; mRNA. DR EMBL; AF011519; AAB65719.1; -; mRNA. DR EMBL; AF011520; AAB65720.1; -; mRNA. DR EMBL; AF011521; AAB65721.1; -; mRNA. DR EMBL; AF011522; AAB65722.1; -; mRNA. DR EMBL; AF011523; AAB65723.1; -; mRNA. DR EMBL; AF011524; AAB65724.1; -; mRNA. DR EMBL; AF011525; AAB65725.1; -; mRNA. DR EMBL; AF011526; AAB65726.1; -; mRNA. DR EMBL; AF011527; AAB65727.1; -; mRNA. DR EMBL; AF011528; AAB65728.1; -; mRNA. DR EMBL; AF011529; AAB65729.1; -; mRNA. DR EMBL; AF011530; AAB65730.1; -; mRNA. DR EMBL; AF011531; AAB65731.1; -; mRNA. DR EMBL; AF011532; AAB65732.1; -; mRNA. DR EMBL; AF011533; AAB65733.1; -; mRNA. DR EMBL; AF011534; AAB65734.1; -; mRNA. DR EMBL; AF011535; AAB65735.1; -; mRNA. DR EMBL; AF011536; AAB65736.1; -; mRNA. DR EMBL; AF011537; AAB65737.1; -; mRNA. DR EMBL; AF031237; AAB94735.1; -; Genomic_DNA. DR EMBL; AF052539; AAD18131.1; -; Genomic_DNA. DR EMBL; AY221093; AAO65971.1; -; Genomic_DNA. DR EMBL; U95626; AAB57793.1; -; Genomic_DNA. DR EMBL; BC038398; AAH38398.1; -; mRNA. DR CCDS; CCDS2739.1; -. DR PIR; A43113; A43113. DR RefSeq; NP_000570.1; NM_000579.3. DR RefSeq; NP_001093638.1; NM_001100168.1. DR UniGene; Hs.450802; -. DR PDB; 1ND8; Model; -; A=1-352. DR PDB; 1NE0; Model; -; A=1-352. DR PDB; 1OPN; Model; -; A=1-352. DR PDB; 1OPT; Model; -; A=1-352. DR PDB; 1OPW; Model; -; A=1-352. DR PDB; 2L87; NMR; -; A=1-27. DR PDB; 2MZX; NMR; -; A=186-195. DR PDB; 2RLL; NMR; -; A=7-15. DR PDB; 2RRS; NMR; -; A=157-174. DR PDB; 4MBS; X-ray; 2.71 A; A/B=3-223. DR PDBsum; 1ND8; -. DR PDBsum; 1NE0; -. DR PDBsum; 1OPN; -. DR PDBsum; 1OPT; -. DR PDBsum; 1OPW; -. DR PDBsum; 2L87; -. DR PDBsum; 2MZX; -. DR PDBsum; 2RLL; -. DR PDBsum; 2RRS; -. DR PDBsum; 4MBS; -. DR ProteinModelPortal; P51681; -. DR SMR; P51681; 19-313. DR BioGrid; 107639; 17. DR DIP; DIP-5866N; -. DR IntAct; P51681; 11. DR MINT; MINT-103024; -. DR STRING; 9606.ENSP00000292303; -. DR BindingDB; P51681; -. DR ChEMBL; CHEMBL274; -. DR DrugBank; DB04835; Maraviroc. DR GuidetoPHARMACOLOGY; 62; -. DR PhosphoSite; P51681; -. DR BioMuta; CCR5; -. DR DMDM; 1705896; -. DR PaxDb; P51681; -. DR PRIDE; P51681; -. DR Ensembl; ENST00000292303; ENSP00000292303; ENSG00000160791. DR Ensembl; ENST00000445772; ENSP00000404881; ENSG00000160791. DR GeneID; 1234; -. DR KEGG; hsa:1234; -. DR UCSC; uc003cpo.4; human. DR CTD; 1234; -. DR GeneCards; CCR5; -. DR HGNC; HGNC:1606; CCR5. DR MIM; 601373; gene. DR MIM; 609423; phenotype. DR MIM; 610379; phenotype. DR MIM; 612522; phenotype. DR neXtProt; NX_P51681; -. DR Orphanet; 319269; Susceptibility/resistance to HIV infection. DR PharmGKB; PA26170; -. DR eggNOG; KOG3656; Eukaryota. DR eggNOG; ENOG410XRW9; LUCA. DR HOVERGEN; HBG106917; -. DR InParanoid; P51681; -. DR KO; K04180; -. DR OMA; GNTMCQL; -. DR OrthoDB; EOG738051; -. DR PhylomeDB; P51681; -. DR TreeFam; TF330966; -. DR Reactome; R-HSA-173107; Binding and entry of HIV virion. DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines. DR Reactome; R-HSA-418594; G alpha (i) signalling events. DR SignaLink; P51681; -. DR EvolutionaryTrace; P51681; -. DR GeneWiki; CCR5; -. DR GenomeRNAi; 1234; -. DR NextBio; 5035; -. DR PRO; PR:P51681; -. DR Proteomes; UP000005640; Chromosome 3. DR Bgee; P51681; -. DR ExpressionAtlas; P51681; baseline and differential. DR Genevisible; P51681; HS. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc. DR GO; GO:0005829; C:cytosol; TAS:GOC. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; IDA:UniProtKB. DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0003779; F:actin binding; IDA:UniProtKB. DR GO; GO:0019957; F:C-C chemokine binding; IPI:UniProtKB. DR GO; GO:0016493; F:C-C chemokine receptor activity; NAS:UniProtKB. DR GO; GO:0071791; F:chemokine (C-C motif) ligand 5 binding; IPI:UniProtKB. DR GO; GO:0004950; F:chemokine receptor activity; TAS:ProtInc. DR GO; GO:0015026; F:coreceptor activity; TAS:ProtInc. DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; TAS:ProtInc. DR GO; GO:0006816; P:calcium ion transport; IDA:UniProtKB. DR GO; GO:0019722; P:calcium-mediated signaling; IDA:UniProtKB. DR GO; GO:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc. DR GO; GO:0007267; P:cell-cell signaling; IDA:UniProtKB. DR GO; GO:0006968; P:cellular defense response; TAS:ProtInc. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEP:UniProtKB. DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IDA:GOC. DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc. DR GO; GO:0002407; P:dendritic cell chemotaxis; TAS:BHF-UCL. DR GO; GO:0030260; P:entry into host cell; TAS:Reactome. DR GO; GO:0007186; P:G-protein coupled receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc. DR GO; GO:0000165; P:MAPK cascade; IEP:UniProtKB. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; TAS:ProtInc. DR GO; GO:0014808; P:release of sequestered calcium ion into cytosol by sarcoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0070723; P:response to cholesterol; IMP:UniProtKB. DR GO; GO:0023052; P:signaling; IEP:UniProtKB. DR GO; GO:0016032; P:viral process; TAS:Reactome. DR InterPro; IPR002240; Chemokine_CCR5. DR InterPro; IPR000355; Chemokine_rcpt. DR InterPro; IPR000276; GPCR_Rhodpsn. DR InterPro; IPR017452; GPCR_Rhodpsn_7TM. DR Pfam; PF00001; 7tm_1; 1. DR PRINTS; PR00657; CCCHEMOKINER. DR PRINTS; PR01110; CHEMOKINER5. DR PRINTS; PR00237; GPCRRHODOPSN. DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1. DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Complete proteome; Diabetes mellitus; KW Disulfide bond; G-protein coupled receptor; Glycoprotein; KW Host cell receptor for virus entry; Host-virus interaction; KW Lipoprotein; Membrane; Palmitate; Phosphoprotein; Polymorphism; KW Receptor; Reference proteome; Sulfation; Transducer; Transmembrane; KW Transmembrane helix. FT CHAIN 1 352 C-C chemokine receptor type 5. FT /FTId=PRO_0000069257. FT TOPO_DOM 1 30 Extracellular. {ECO:0000255}. FT TRANSMEM 31 58 Helical; Name=1. {ECO:0000255}. FT TOPO_DOM 59 68 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 69 89 Helical; Name=2. {ECO:0000255}. FT TOPO_DOM 90 102 Extracellular. {ECO:0000255}. FT TRANSMEM 103 124 Helical; Name=3. {ECO:0000255}. FT TOPO_DOM 125 141 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 142 166 Helical; Name=4. {ECO:0000255}. FT TOPO_DOM 167 198 Extracellular. {ECO:0000255}. FT TRANSMEM 199 218 Helical; Name=5. {ECO:0000255}. FT TOPO_DOM 219 235 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 236 260 Helical; Name=6. {ECO:0000255}. FT TOPO_DOM 261 277 Extracellular. {ECO:0000255}. FT TRANSMEM 278 301 Helical; Name=7. {ECO:0000255}. FT TOPO_DOM 302 352 Cytoplasmic. {ECO:0000255}. FT MOD_RES 3 3 Sulfotyrosine. FT {ECO:0000269|PubMed:10089882}. FT MOD_RES 10 10 Sulfotyrosine. FT {ECO:0000269|PubMed:21763489}. FT MOD_RES 14 14 Sulfotyrosine. FT {ECO:0000269|PubMed:21763489}. FT MOD_RES 15 15 Sulfotyrosine. {ECO:0000255}. FT MOD_RES 336 336 Phosphoserine; by BARK1. FT {ECO:0000269|PubMed:10085131}. FT MOD_RES 337 337 Phosphoserine; by BARK1. FT {ECO:0000269|PubMed:10085131}. FT MOD_RES 342 342 Phosphoserine; by BARK1. FT {ECO:0000269|PubMed:10085131}. FT MOD_RES 349 349 Phosphoserine; by BARK1. FT {ECO:0000269|PubMed:10085131}. FT LIPID 321 321 S-palmitoyl cysteine. FT {ECO:0000269|PubMed:11323418}. FT LIPID 323 323 S-palmitoyl cysteine. FT {ECO:0000269|PubMed:11323418}. FT LIPID 324 324 S-palmitoyl cysteine. FT {ECO:0000269|PubMed:11323418}. FT CARBOHYD 6 6 O-linked (GalNAc...). FT {ECO:0000269|PubMed:11733580}. FT CARBOHYD 7 7 O-linked (GalNAc...). FT {ECO:0000305|PubMed:10089882}. FT CARBOHYD 16 16 O-linked (GalNAc...). {ECO:0000255}. FT CARBOHYD 17 17 O-linked (GalNAc...). {ECO:0000255}. FT DISULFID 101 178 {ECO:0000255|PROSITE-ProRule:PRU00521}. FT VARIANT 10 10 Y -> D (in INCCR5-71A; results in absent FT sulfation and greatly decreased binding FT CCL4 and CCL5 when associated with D-3, FT D-10 and D-15; restored most CCL4 binding FT when associated with D-3 and D-15). FT {ECO:0000269|PubMed:11733580}. FT /FTId=VAR_003481. FT VARIANT 12 12 I -> L. {ECO:0000269|PubMed:9399903}. FT /FTId=VAR_024066. FT VARIANT 20 20 C -> S. {ECO:0000269|PubMed:9399903}. FT /FTId=VAR_024067. FT VARIANT 29 29 A -> S (in dbSNP:rs1800939). FT {ECO:0000269|PubMed:9399903}. FT /FTId=VAR_011839. FT VARIANT 31 31 R -> H (in INCCR5-72A; dbSNP:rs56340326). FT /FTId=VAR_003482. FT VARIANT 34 34 P -> L (in TZCCR5-179). FT /FTId=VAR_003483. FT VARIANT 42 42 I -> F. {ECO:0000269|PubMed:9399903}. FT /FTId=VAR_024068. FT VARIANT 55 55 L -> Q (in dbSNP:rs1799863). FT {ECO:0000269|PubMed:9207783, FT ECO:0000269|PubMed:9399903}. FT /FTId=VAR_011840. FT VARIANT 60 60 R -> S (associated with susceptibility to FT HIV-1; reduced surface expression and FT function of CCR5 protein; FT dbSNP:rs1800940). FT {ECO:0000269|PubMed:11369664, FT ECO:0000269|PubMed:9399903}. FT /FTId=VAR_011841. FT VARIANT 62 62 K -> R (in UGCCR5-145B). FT /FTId=VAR_003484. FT VARIANT 68 68 Y -> H (in ZWCCR5-7). FT /FTId=VAR_003485. FT VARIANT 73 73 A -> V (in dbSNP:rs56198941). FT {ECO:0000269|PubMed:9399903}. FT /FTId=VAR_024069. FT VARIANT 95 95 D -> N (in MWCCR5-107). FT /FTId=VAR_003486. FT VARIANT 97 97 G -> E (in INCCR5-467). FT /FTId=VAR_003487. FT VARIANT 122 122 L -> P (in ZWCCR5-7). FT /FTId=VAR_003488. FT VARIANT 158 158 F -> S (in UGCCR5-145A). FT /FTId=VAR_003489. FT VARIANT 176 176 Y -> C (in KECCR5-116). FT /FTId=VAR_003490. FT VARIANT 177 177 T -> A (in INCCR5-45C). FT /FTId=VAR_003491. FT VARIANT 178 178 C -> R (found in a HIV-resistant FT individiual; dbSNP:rs199824195). FT {ECO:0000269|Ref.7}. FT /FTId=VAR_012481. FT VARIANT 185 185 S -> N (in UGCCR5-145A). FT /FTId=VAR_003492. FT VARIANT 210 210 M -> V (in ZWCCR5-7). FT /FTId=VAR_003493. FT VARIANT 214 214 Y -> C (in KECCR5-3B). FT /FTId=VAR_003494. FT VARIANT 215 215 S -> L. {ECO:0000269|PubMed:9207783}. FT /FTId=VAR_024070. FT VARIANT 223 223 R -> Q (in dbSNP:rs1800452). FT {ECO:0000269|PubMed:9207783, FT ECO:0000269|PubMed:9399903}. FT /FTId=VAR_011842. FT VARIANT 228 228 Missing. {ECO:0000269|PubMed:9399903}. FT /FTId=VAR_024071. FT VARIANT 239 239 T -> S (in INCCR5-71A). FT /FTId=VAR_003495. FT VARIANT 246 246 L -> P (in UGCCR5-145A). FT /FTId=VAR_003496. FT VARIANT 288 288 T -> M (in INCCR5-72A). FT /FTId=VAR_003497. FT VARIANT 301 301 G -> V (in dbSNP:rs1800943). FT {ECO:0000269|PubMed:9399903}. FT /FTId=VAR_011843. FT VARIANT 302 302 E -> G (in TZCCR5-179). FT /FTId=VAR_003498. FT VARIANT 303 303 K -> E (in THCCR5-5). FT /FTId=VAR_003499. FT VARIANT 306 306 N -> S (in MWCCR5-1567). FT /FTId=VAR_003500. FT VARIANT 322 322 K -> R (in THCCR5-5). FT /FTId=VAR_003501. FT VARIANT 333 333 E -> G (in THCCR5-2). FT /FTId=VAR_003502. FT VARIANT 335 335 A -> V (in MWCCR5-1567, MWCCR5-1568, FT ZWCCR5-14 and ZWCCR5-112; FT dbSNP:rs1800944). FT {ECO:0000269|PubMed:9207783, FT ECO:0000269|PubMed:9399903}. FT /FTId=VAR_003503. FT VARIANT 339 339 Y -> F (in TZCCR5-181A and MWCCR5-107; FT dbSNP:rs1800945). FT {ECO:0000269|PubMed:9207783, FT ECO:0000269|PubMed:9399903}. FT /FTId=VAR_003504. FT VARIANT 345 345 E -> G (in UGCCR5-145C). FT /FTId=VAR_003505. FT MUTAGEN 3 3 Y->D: No sulfation and greatly decreased FT binding CCL4 and CCL5; when associated FT with D-10; D-14 and D-15. Restored most FT CCL4 binding; when associated with D-10 FT and D-15. {ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580}. FT MUTAGEN 3 3 Y->F: No sulfation and greatly decreases FT binding of CCL4 and CCL5; when associated FT with F-10; F-14 and F-15. FT {ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580}. FT MUTAGEN 6 6 S->A: No change in glycosylation status FT and greatly decreased CCL4 binding. Loss FT of molecular mass of about 2 kDa as FT compared to wild type. Dramatically FT reduced binding of CCL4; when associated FT with A-7; A-16; A-17. Similar molecular FT mass loss. Dramatically reduced binding FT of CCL4; when associated with A-7 only. FT {ECO:0000269|PubMed:11733580}. FT MUTAGEN 7 7 S->A: No change in glycosylation status FT and binds CCL4 as efficiently as wild FT type. Loss of molecular mass of about 2 FT kDa as compared to wild type. FT Dramatically reduced binding of CCL4; FT when associated with A-6; A-16; A-17. FT Similar molecular mass loss. Dramatically FT reduced binding of CCL4; when associated FT with A-6 only. FT {ECO:0000269|PubMed:11733580}. FT MUTAGEN 10 10 Y->F: No sulfation and greatly decreases FT binding of CCL4 and CCL5; when associated FT with F-3; F-14 and F-15. Small loss of FT sulfation; when associated with F-14 and FT F-15. {ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580}. FT MUTAGEN 14 14 Y->D: No sulfation and greatly decreased FT binding CCL4 and CCL5; when associated FT with D-3; D-10 and D-14. No restoration FT of CCL4 binding; when associated with D- FT 10 and D-15. FT {ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580}. FT MUTAGEN 14 14 Y->F: No sulfation and greatly decreases FT binding of CCL4 and CCL5; when associated FT with F-3; F-10; and F-15. Small loss of FT sulfation; when associated with F-10 and FT F-15. {ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580}. FT MUTAGEN 15 15 Y->D: No sulfation and greatly decreased FT binding CCL4 and CCL5; when associated FT with D-3; D-10 and D-14. Restored most FT CCL4 binding; when associated with D-3 FT and D-10. {ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580}. FT MUTAGEN 15 15 Y->F: No sulfation and greatly decreases FT binding of CCL4 and CCL5; when associated FT with F-3; F-10 and F-14. Small loss of FT sulfation; when associated with F-10 and FT F-14. {ECO:0000269|PubMed:10089882, FT ECO:0000269|PubMed:11733580}. FT MUTAGEN 16 16 T->A: Similar decrease in molecular mass FT when treated with O-glycosidase as for FT wild type; when associated with A-17. FT {ECO:0000269|PubMed:11733580}. FT MUTAGEN 17 17 S->A: Similar decrease in molecular mass FT when treated with O-glycosidase as for FT wild type; when associated with A-16. FT {ECO:0000269|PubMed:11733580}. FT MUTAGEN 321 321 C->A: Small reduction in palmitoylation. FT Cell surface expression reduced by 50%. FT Greatly reduced palmitoylation. Cell FT surface expression greatly reduced; when FT associated with A-323 or A-324. No FT palmitoylation. Cell surface expression FT greatly reduced. HIV entry reduced by FT 50%; when associated with A-323 and A- FT 324. {ECO:0000269|PubMed:11323418}. FT MUTAGEN 323 323 C->A: Small reduction in palmitoylation. FT Cell surface expression reduced by 50%. FT Greatly reduced palmitoylation. Cell FT surface expression greatly reduced; when FT associated with A-321 or A-324. No FT palmitoylation. Cell surface expression FT greatly reduced. HIV entry reduced by FT 50%; when associated with A-321 and A- FT 324. {ECO:0000269|PubMed:11323418}. FT MUTAGEN 324 324 C->A: Small reduction in palmitoylation. FT Cell surface expression reduced by 50%. FT Greatly reduced palmitoylation. Cell FT surface expression greatly reduced; when FT associated with A-321 or A-323. No FT palmitoylation. Cell surface expression FT greatly reduced. HIV entry reduced by FT 50%; when associated with A-321 and A- FT 323. {ECO:0000269|PubMed:11323418}. FT MUTAGEN 336 336 S->A: APO-RANTES-stimulated FT phosphorylation reduced by 15%; APO- FT RANTES-stimulated phosphorylation reduced FT by 30-50%; when associated with A-337 or FT A-342 or A-349; APO-RANTES-stimulated FT phosphorylation reduced by 80%; when FT associated with A-337 and A-342 or A-349; FT No APO-RANTES-stimulated phosphorylation; FT when associated with A-337; A-342 and FT A349; abolishes interaction with ARRB2; FT when associated with S-337; S-342 and S- FT 349. {ECO:0000269|PubMed:10085131, FT ECO:0000269|PubMed:11448957}. FT MUTAGEN 337 337 S->A: APO-RANTES-stimulated FT phosphorylation reduced by 18%; APO- FT RANTES-stimulated phosphorylation reduced FT by 30-50% on APO-RANTES stimulation; when FT associated with A-336 or A-342 or A-349; FT APO-RANTES-stimulated phosphorylation FT reduced by 80%; when associated with A- FT 336 and A-342 or A-349; No APO-RANTES- FT stimulated phosphorylation; when FT associated with A-336; A-342 and A349; FT abolishes interaction with ARRB2; when FT associated with S-336; S-342 and S-349. FT {ECO:0000269|PubMed:10085131, FT ECO:0000269|PubMed:11448957}. FT MUTAGEN 342 342 S->A: APO-RANTES-stimulated FT phosphorylation reduced by 42%. FT Phosphorylation reduced by 50% on APO- FT RANTES stimulation; when associated with FT A-336 or A-337 or A-349; APO-RANTES- FT stimulated phosphorylation reduced by 80% FT when associated with A-336 and A-337 or FT A-349; No APO-RANTES-stimulated FT phosphorylation; when associated with A- FT 336; A-337 and A349; abolishes FT interaction with ARRB2; when associated FT with S-336; S-337 and S-349. FT {ECO:0000269|PubMed:10085131, FT ECO:0000269|PubMed:11448957}. FT MUTAGEN 349 349 S->A: APO-RANTES-stimulated FT phosphorylation reduced by 43%; APO- FT RANTES-stimulated phosphorylation reduced FT by 30-50%; when associated with A-336 or FT A-337 or A-342; APO-RANTES-stimulated FT phosphorylation reduced by 80%; when FT associated with A-336 and A-337 or A-342; FT No APO-RANTES-stimulated phosphorylation FT stimulation; when associated with A-336; FT A-337 and A347; abolishes interaction FT with ARRB2; when associated with S-336; FT S-337 and S-342. FT {ECO:0000269|PubMed:10085131, FT ECO:0000269|PubMed:11448957}. FT HELIX 10 13 {ECO:0000244|PDB:2L87}. FT HELIX 14 17 {ECO:0000244|PDB:2L87}. FT TURN 20 22 {ECO:0000244|PDB:2L87}. FT HELIX 26 57 {ECO:0000244|PDB:4MBS}. FT HELIX 64 91 {ECO:0000244|PDB:4MBS}. FT HELIX 98 131 {ECO:0000244|PDB:4MBS}. FT HELIX 133 139 {ECO:0000244|PDB:4MBS}. FT HELIX 142 165 {ECO:0000244|PDB:4MBS}. FT STRAND 167 172 {ECO:0000244|PDB:4MBS}. FT STRAND 175 180 {ECO:0000244|PDB:4MBS}. FT HELIX 187 202 {ECO:0000244|PDB:4MBS}. FT HELIX 204 223 {ECO:0000244|PDB:4MBS}. FT HELIX 229 232 {ECO:0000244|PDB:4MBS}. FT HELIX 234 259 {ECO:0000244|PDB:4MBS}. FT HELIX 261 264 {ECO:0000244|PDB:4MBS}. FT HELIX 269 288 {ECO:0000244|PDB:4MBS}. FT HELIX 289 291 {ECO:0000244|PDB:4MBS}. FT HELIX 293 300 {ECO:0000244|PDB:4MBS}. FT HELIX 302 312 {ECO:0000244|PDB:4MBS}. SQ SEQUENCE 352 AA; 40524 MW; 88ECE1F38E6D45A7 CRC64; MDYQVSSPIY DINYYTSEPC QKINVKQIAA RLLPPLYSLV FIFGFVGNML VILILINCKR LKSMTDIYLL NLAISDLFFL LTVPFWAHYA AAQWDFGNTM CQLLTGLYFI GFFSGIFFII LLTIDRYLAV VHAVFALKAR TVTFGVVTSV ITWVVAVFAS LPGIIFTRSQ KEGLHYTCSS HFPYSQYQFW KNFQTLKIVI LGLVLPLLVM VICYSGILKT LLRCRNEKKR HRAVRLIFTI MIVYFLFWAP YNIVLLLNTF QEFFGLNNCS SSNRLDQAMQ VTETLGMTHC CINPIIYAFV GEKFRNYLLV FFQKHIAKRF CKCCSIFQQE APERASSVYT RSTGEQEISV GL // ID CEP68_HUMAN Reviewed; 757 AA. AC Q76N32; B4DRQ1; D6W5F1; D6W5F2; O60326; Q9BQ18; Q9UDM9; DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 26-APR-2005, sequence version 2. DT 11-NOV-2015, entry version 108. DE RecName: Full=Centrosomal protein of 68 kDa; DE Short=Cep68; GN Name=CEP68; Synonyms=KIAA0582; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9628581; DOI=10.1093/dnares/5.1.31; RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., RA Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. IX. RT The complete sequences of 100 new cDNA clones from brain which can RT code for large proteins in vitro."; RL DNA Res. 5:31-39(1998). RN [2] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT RP SER-74. RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., RA Mann M.; RT "Proteomic characterization of the human centrosome by protein RT correlation profiling."; RL Nature 426:570-574(2003). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-478, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). CC -!- INTERACTION: CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-9051024, EBI-10171858; CC Q8N6Y0:USHBP1; NbExp=3; IntAct=EBI-9051024, EBI-739895; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, microtubule CC organizing center, centrosome {ECO:0000269|PubMed:14654843}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q76N32-1; Sequence=Displayed; CC Name=2; CC IsoId=Q76N32-2; Sequence=VSP_013476; CC Note=No experimental confirmation available.; CC -!- SEQUENCE CAUTION: CC Sequence=BAA25508.2; Type=Erroneous initiation; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AB011154; BAA25508.2; ALT_INIT; mRNA. DR EMBL; AC007386; AAF03518.2; -; Genomic_DNA. DR EMBL; AK299373; BAG61363.1; -; mRNA. DR EMBL; CH471053; EAW99926.1; -; Genomic_DNA. DR EMBL; CH471053; EAW99927.1; -; Genomic_DNA. DR EMBL; CH471053; EAW99928.1; -; Genomic_DNA. DR EMBL; CH471053; EAW99929.1; -; Genomic_DNA. DR EMBL; BC002982; AAH02982.1; -; mRNA. DR EMBL; BC004873; AAH04873.1; -; mRNA. DR CCDS; CCDS1880.2; -. [Q76N32-1] DR RefSeq; NP_055962.2; NM_015147.2. [Q76N32-1] DR RefSeq; XP_005264275.1; XM_005264218.3. [Q76N32-1] DR UniGene; Hs.709257; -. DR ProteinModelPortal; Q76N32; -. DR BioGrid; 116789; 7. DR IntAct; Q76N32; 3. DR MINT; MINT-7034577; -. DR STRING; 9606.ENSP00000367229; -. DR PhosphoSite; Q76N32; -. DR BioMuta; CEP68; -. DR DMDM; 62899863; -. DR MaxQB; Q76N32; -. DR PaxDb; Q76N32; -. DR PRIDE; Q76N32; -. DR Ensembl; ENST00000260569; ENSP00000260569; ENSG00000011523. [Q76N32-2] DR Ensembl; ENST00000377990; ENSP00000367229; ENSG00000011523. [Q76N32-1] DR GeneID; 23177; -. DR KEGG; hsa:23177; -. DR UCSC; uc002sdk.4; human. [Q76N32-2] DR UCSC; uc002sdl.4; human. [Q76N32-1] DR CTD; 23177; -. DR GeneCards; CEP68; -. DR HGNC; HGNC:29076; CEP68. DR HPA; HPA040493; -. DR HPA; HPA040620; -. DR neXtProt; NX_Q76N32; -. DR PharmGKB; PA134991391; -. DR eggNOG; ENOG410IIDK; Eukaryota. DR eggNOG; ENOG41129RE; LUCA. DR GeneTree; ENSGT00810000125473; -. DR HOVERGEN; HBG050898; -. DR InParanoid; Q76N32; -. DR KO; K16764; -. DR OMA; QAEYWAC; -. DR OrthoDB; EOG7NW68J; -. DR PhylomeDB; Q76N32; -. DR TreeFam; TF333570; -. DR ChiTaRS; CEP68; human. DR GeneWiki; CEP68; -. DR GenomeRNAi; 23177; -. DR NextBio; 44621; -. DR PRO; PR:Q76N32; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; Q76N32; -. DR CleanEx; HS_CEP68; -. DR ExpressionAtlas; Q76N32; baseline and differential. DR Genevisible; Q76N32; HS. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005815; C:microtubule organizing center; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0010457; P:centriole-centriole cohesion; IMP:UniProtKB. DR GO; GO:0051297; P:centrosome organization; IMP:UniProtKB. DR GO; GO:0033365; P:protein localization to organelle; IMP:UniProtKB. DR InterPro; IPR026696; AKAP6/CEP68. DR PANTHER; PTHR14514; PTHR14514; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Cytoplasm; Cytoskeleton; KW Phosphoprotein; Polymorphism; Reference proteome. FT CHAIN 1 757 Centrosomal protein of 68 kDa. FT /FTId=PRO_0000089494. FT COMPBIAS 532 537 Poly-Ser. FT MOD_RES 472 472 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8C0D9}. FT MOD_RES 478 478 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT VAR_SEQ 492 628 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_013476. FT VARIANT 27 27 R -> G (in dbSNP:rs12611491). FT /FTId=VAR_050794. FT VARIANT 74 74 G -> S (in dbSNP:rs7572857). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_022363. FT VARIANT 397 397 L -> P (in dbSNP:rs35501092). FT /FTId=VAR_050795. FT VARIANT 462 462 R -> C (in dbSNP:rs35694840). FT /FTId=VAR_050796. FT VARIANT 473 473 E -> Q (in dbSNP:rs35089924). FT /FTId=VAR_050797. SQ SEQUENCE 757 AA; 81102 MW; 3FC969065CD5D2D7 CRC64; MALGEEKAEA EASEDTKAQS YGRGSCRERE LDIPGPMSGE QPPRLEAEGG LISPVWGAEG IPAPTCWIGT DPGGPSRAHQ PQASDANREP VAERSEPALS GLPPATMGSG DLLLSGESQV EKTKLSSSEE FPQTLSLPRT TTICSGHDAD TEDDPSLADL PQALDLSQQP HSSGLSCLSQ WKSVLSPGSA AQPSSCSISA SSTGSSLQGH QERAEPRGGS LAKVSSSLEP VVPQEPSSVV GLGPRPQWSP QPVFSGGDAS GLGRRRLSFQ AEYWACVLPD SLPPSPDRHS PLWNPNKEYE DLLDYTYPLR PGPQLPKHLD SRVPADPVLQ DSGVDLDSFS VSPASTLKSP TNVSPNCPPA EATALPFSGP REPSLKQWPS RVPQKQGGMG LASWSQLAST PRAPGSRDAR WERREPALRG AKDRLTIGKH LDMGSPQLRT RDRGWPSPRP EREKRTSQSA RRPTCTESRW KSEEEVESDD EYLALPARLT QVSSLVSYLG SISTLVTLPT GDIKGQSPLE VSDSDGPASF PSSSSQSQLP PGAALQGSGD PEGQNPCFLR SFVRAHDSAG EGSLGSSQAL GVSSGLLKTR PSLPARLDRW PFSDPDVEGQ LPRKGGEQGK ESLVQCVKTF CCQLEELICW LYNVADVTDH GTAARSNLTS LKSSLQLYRQ FKKDIDEHQS LTESVLQKGE ILLQCLLENT PVLEDVLGRI AKQSGELESH ADRLYDSILA SLDMLAGCTL IPDKKPMAAM EHPCEGV // ID CHD3_HUMAN Reviewed; 2000 AA. AC Q12873; D3DTQ9; E9PG89; Q9Y4I0; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 07-FEB-2006, sequence version 3. DT 11-NOV-2015, entry version 169. DE RecName: Full=Chromodomain-helicase-DNA-binding protein 3; DE Short=CHD-3; DE EC=3.6.4.12; DE AltName: Full=ATP-dependent helicase CHD3; DE AltName: Full=Mi-2 autoantigen 240 kDa protein; DE AltName: Full=Mi2-alpha; DE AltName: Full=Zinc finger helicase; DE Short=hZFH; GN Name=CHD3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND TISSUE SPECIFICITY. RX PubMed=9688266; DOI=10.1046/j.1432-1327.1998.2540558.x; RA Aubry F., Mattei M.-G., Galibert F.; RT "Identification of a human 17p-located cDNA encoding a protein of the RT Snf2-like helicase family."; RL Eur. J. Biochem. 254:558-564(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in RT the human lineage."; RL Nature 440:1045-1049(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-1966 (ISOFORM 2). RC TISSUE=Fetus; RX PubMed=9326634; DOI=10.1073/pnas.94.21.11472; RA Woodage T., Basrai M.A., Baxevanis A.D., Hieter P., Collins F.S.; RT "Characterization of the CHD family of proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 94:11472-11477(1997). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 121-654. RC TISSUE=Thymus; RX PubMed=7560064; DOI=10.1172/JCI118218; RA Ge Q., Nilasena D.S., O'Brien C.A., Frank M.B., Targoff I.N.; RT "Molecular analysis of a major antigenic region of the 240 kD protein RT of Mi-2 autoantigen."; RL J. Clin. Invest. 96:1730-1737(1995). RN [6] RP IDENTIFICATION AS A COMPONENT OF THE NURD COMPLEX, AND FUNCTION. RX PubMed=9804427; DOI=10.1038/27699; RA Tong J.K., Hassig C.A., Schnitzler G.R., Kingston R.E., RA Schreiber S.L.; RT "Chromatin deacetylation by an ATP-dependent nucleosome remodelling RT complex."; RL Nature 395:917-921(1998). RN [7] RP INTERACTION WITH TRIM28. RX PubMed=11230151; DOI=10.1101/gad.869501; RA Schultz D.C., Friedman J.R., Rauscher F.J. III; RT "Targeting histone deacetylase complexes via KRAB-zinc finger RT proteins: the PHD and bromodomains of KAP-1 form a cooperative unit RT that recruits a novel isoform of the Mi-2alpha subunit of NuRD."; RL Genes Dev. 15:428-443(2001). RN [8] RP INTERACTION WITH HABP4 AND SERBP1. RX PubMed=12505151; DOI=10.1016/S0014-5793(02)03737-7; RA Lemos T.A., Passos D.O., Nery F.C., Kobarg J.; RT "Characterization of a new family of proteins that interact with the RT C-terminal region of the chromatin-remodeling factor CHD-3."; RL FEBS Lett. 533:14-20(2003). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-324; SER-1601 AND RP SER-1605, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [10] RP INTERACTION WITH PCNT, SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=17626165; DOI=10.1091/mbc.E06-07-0604; RA Sillibourne J.E., Delaval B., Redick S., Sinha M., Doxsey S.J.; RT "Chromatin remodeling proteins interact with pericentrin to regulate RT centrosome integrity."; RL Mol. Biol. Cell 18:3667-3680(2007). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1601, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-713; SER-1367; SER-1601 RP AND SER-1605, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-713; SER-1601 AND RP SER-1605, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1601 AND SER-1605, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1601, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1308, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). CC -!- FUNCTION: Component of the histone deacetylase NuRD complex which CC participates in the remodeling of chromatin by deacetylating CC histones. Required for anchoring centrosomal pericentrin in both CC interphase and mitosis, for spindle organization and centrosome CC integrity. {ECO:0000269|PubMed:17626165, CC ECO:0000269|PubMed:9804427}. CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. CC -!- SUBUNIT: Central component of the nucleosome remodeling and CC histone deacetylase (NuRD) repressive complex. Interacts with CC TRIM28 and SERBP1. Interacts (via its C-terminal) with HABP4. CC Interacts with PCNT; the interaction regulates centrosome CC integrity. {ECO:0000269|PubMed:11230151, CC ECO:0000269|PubMed:12505151, ECO:0000269|PubMed:17626165}. CC -!- INTERACTION: CC Q99728:BARD1; NbExp=2; IntAct=EBI-523590, EBI-473181; CC P17844:DDX5; NbExp=4; IntAct=EBI-523590, EBI-351962; CC Q9Y2X7:GIT1; NbExp=2; IntAct=EBI-523590, EBI-466061; CC P42858:HTT; NbExp=3; IntAct=EBI-523590, EBI-466029; CC O60341:KDM1A; NbExp=4; IntAct=EBI-523590, EBI-710124; CC O75400:PRPF40A; NbExp=2; IntAct=EBI-523590, EBI-473291; CC Q8NC51:SERBP1; NbExp=5; IntAct=EBI-523590, EBI-523558; CC P61956:SUMO2; NbExp=3; IntAct=EBI-523590, EBI-473220; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17626165}. CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome CC {ECO:0000269|PubMed:17626165}. Note=Associates with centrosomes in CC interphase and mitosis. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q12873-1; Sequence=Displayed; CC Name=2; CC IsoId=Q12873-2; Sequence=VSP_017231; CC Name=3; CC IsoId=Q12873-3; Sequence=VSP_047097; CC Note=No experimental confirmation available. Gene prediction CC based on EST data.; CC -!- TISSUE SPECIFICITY: Widely expressed. CC {ECO:0000269|PubMed:9688266}. CC -!- MISCELLANEOUS: One of the main antigens reacting with anti-MI-2 CC positive sera of dermatomyositis. CC -!- SIMILARITY: Belongs to the SNF2/RAD54 helicase family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 2 chromo domains. {ECO:0000255|PROSITE- CC ProRule:PRU00053}. CC -!- SIMILARITY: Contains 1 helicase ATP-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00541}. CC -!- SIMILARITY: Contains 1 helicase C-terminal domain. CC {ECO:0000255|PROSITE-ProRule:PRU00542}. CC -!- SIMILARITY: Contains 2 PHD-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00146}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB87383.1; Type=Miscellaneous discrepancy; Note=Differs from position 1967 onward for unknown reasons.; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U91543; AAC39923.1; -; mRNA. DR EMBL; AC104581; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471108; EAW90114.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90116.1; -; Genomic_DNA. DR EMBL; AF006515; AAB87383.1; ALT_TERM; mRNA. DR EMBL; U08379; AAC50228.1; -; mRNA. DR CCDS; CCDS32553.2; -. [Q12873-3] DR CCDS; CCDS32554.1; -. [Q12873-1] DR CCDS; CCDS32555.1; -. [Q12873-2] DR RefSeq; NP_001005271.2; NM_001005271.2. [Q12873-3] DR RefSeq; NP_001005273.1; NM_001005273.2. [Q12873-1] DR RefSeq; NP_005843.2; NM_005852.3. [Q12873-2] DR UniGene; Hs.25601; -. DR ProteinModelPortal; Q12873; -. DR SMR; Q12873; 374-429, 453-686. DR BioGrid; 107532; 135. DR DIP; DIP-32496N; -. DR IntAct; Q12873; 97. DR MINT; MINT-1185641; -. DR STRING; 9606.ENSP00000369716; -. DR PhosphoSite; Q12873; -. DR BioMuta; CHD3; -. DR DMDM; 88911273; -. DR MaxQB; Q12873; -. DR PaxDb; Q12873; -. DR PRIDE; Q12873; -. DR Ensembl; ENST00000330494; ENSP00000332628; ENSG00000170004. [Q12873-1] DR Ensembl; ENST00000358181; ENSP00000350907; ENSG00000170004. [Q12873-2] DR Ensembl; ENST00000380358; ENSP00000369716; ENSG00000170004. [Q12873-3] DR GeneID; 1107; -. DR KEGG; hsa:1107; -. DR UCSC; uc002gje.2; human. [Q12873-1] DR UCSC; uc002gjf.2; human. [Q12873-2] DR CTD; 1107; -. DR GeneCards; CHD3; -. DR H-InvDB; HIX0013516; -. DR HGNC; HGNC:1918; CHD3. DR HPA; HPA043368; -. DR MIM; 602120; gene. DR neXtProt; NX_Q12873; -. DR PharmGKB; PA26454; -. DR eggNOG; KOG0383; Eukaryota. DR eggNOG; COG0553; LUCA. DR GeneTree; ENSGT00760000119067; -. DR HOGENOM; HOG000231124; -. DR HOVERGEN; HBG005326; -. DR InParanoid; Q12873; -. DR KO; K11642; -. DR OMA; GKGPGYK; -. DR OrthoDB; EOG7C8GG7; -. DR PhylomeDB; Q12873; -. DR TreeFam; TF106448; -. DR Reactome; R-HSA-3214815; HDACs deacetylate histones. DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation. DR ChiTaRS; CHD3; human. DR GeneWiki; CHD3; -. DR GenomeRNAi; 1107; -. DR NextBio; 4590; -. DR PRO; PR:Q12873; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; Q12873; -. DR CleanEx; HS_CHD3; -. DR ExpressionAtlas; Q12873; baseline and differential. DR Genevisible; Q12873; HS. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016581; C:NuRD complex; IDA:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004003; F:ATP-dependent DNA helicase activity; TAS:ProtInc. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0004386; F:helicase activity; NAS:UniProtKB. DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB. DR GO; GO:0051297; P:centrosome organization; IDA:UniProtKB. DR GO; GO:0006333; P:chromatin assembly or disassembly; IEA:Ensembl. DR GO; GO:0016568; P:chromatin modification; IEA:UniProtKB-KW. DR GO; GO:0006325; P:chromatin organization; TAS:Reactome. DR GO; GO:0032508; P:DNA duplex unwinding; TAS:GOC. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB. DR GO; GO:0007051; P:spindle organization; IDA:UniProtKB. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 1.10.30.10; -; 1. DR Gene3D; 3.30.40.10; -; 2. DR Gene3D; 3.40.50.300; -; 2. DR InterPro; IPR028722; CHD3. DR InterPro; IPR012957; CHD_C2. DR InterPro; IPR012958; CHD_N. DR InterPro; IPR000953; Chromo/shadow_dom. DR InterPro; IPR023780; Chromo_domain. DR InterPro; IPR016197; Chromodomain-like. DR InterPro; IPR023779; Chromodomain_CS. DR InterPro; IPR002464; DNA/RNA_helicase_DEAH_CS. DR InterPro; IPR009462; DUF1086. DR InterPro; IPR009463; DUF1087. DR InterPro; IPR014001; Helicase_ATP-bd. DR InterPro; IPR001650; Helicase_C. DR InterPro; IPR009071; HMG_box_dom. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR000330; SNF2_N. DR InterPro; IPR019786; Zinc_finger_PHD-type_CS. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR001965; Znf_PHD. DR InterPro; IPR019787; Znf_PHD-finger. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR10799:SF544; PTHR10799:SF544; 4. DR Pfam; PF08074; CHDCT2; 1. DR Pfam; PF08073; CHDNT; 1. DR Pfam; PF00385; Chromo; 1. DR Pfam; PF06461; DUF1086; 1. DR Pfam; PF06465; DUF1087; 1. DR Pfam; PF00271; Helicase_C; 1. DR Pfam; PF00628; PHD; 2. DR Pfam; PF00176; SNF2_N; 1. DR SMART; SM00298; CHROMO; 2. DR SMART; SM00487; DEXDc; 1. DR SMART; SM00490; HELICc; 1. DR SMART; SM00249; PHD; 2. DR SMART; SM00184; RING; 2. DR SUPFAM; SSF47095; SSF47095; 1. DR SUPFAM; SSF52540; SSF52540; 2. DR SUPFAM; SSF54160; SSF54160; 3. DR SUPFAM; SSF57903; SSF57903; 1. DR PROSITE; PS00598; CHROMO_1; 1. DR PROSITE; PS50013; CHROMO_2; 2. DR PROSITE; PS00690; DEAH_ATP_HELICASE; 1. DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1. DR PROSITE; PS51194; HELICASE_CTER; 1. DR PROSITE; PS01359; ZF_PHD_1; 2. DR PROSITE; PS50016; ZF_PHD_2; 2. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Chromatin regulator; KW Complete proteome; Cytoplasm; Cytoskeleton; DNA-binding; Helicase; KW Hydrolase; Isopeptide bond; Metal-binding; Nucleotide-binding; KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; KW Transcription; Transcription regulation; Ubl conjugation; Zinc; KW Zinc-finger. FT CHAIN 1 2000 Chromodomain-helicase-DNA-binding protein FT 3. FT /FTId=PRO_0000080227. FT DOMAIN 494 594 Chromo 1. {ECO:0000255|PROSITE- FT ProRule:PRU00053}. FT DOMAIN 631 673 Chromo 2. {ECO:0000255|PROSITE- FT ProRule:PRU00053}. FT DOMAIN 748 932 Helicase ATP-binding. FT {ECO:0000255|PROSITE-ProRule:PRU00541}. FT DOMAIN 1064 1229 Helicase C-terminal. FT {ECO:0000255|PROSITE-ProRule:PRU00542}. FT ZN_FING 379 426 PHD-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00146}. FT ZN_FING 456 503 PHD-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00146}. FT NP_BIND 761 768 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00541}. FT REGION 1566 1966 Required for interaction with PCNT. FT MOTIF 883 886 DEAH box. FT COMPBIAS 206 221 Poly-Ala. FT COMPBIAS 243 246 Poly-Pro. FT COMPBIAS 355 358 Poly-Lys. FT COMPBIAS 434 446 Poly-Glu. FT COMPBIAS 697 703 Poly-Lys. FT MOD_RES 308 308 Phosphoserine. FT {ECO:0000250|UniProtKB:Q14839}. FT MOD_RES 324 324 Phosphoserine. FT {ECO:0000244|PubMed:17081983}. FT MOD_RES 376 376 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q14839}. FT MOD_RES 713 713 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332}. FT MOD_RES 1219 1219 Phosphoserine. FT {ECO:0000250|UniProtKB:Q6PDQ2}. FT MOD_RES 1367 1367 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 1532 1532 Phosphoserine. FT {ECO:0000250|UniProtKB:Q14839}. FT MOD_RES 1538 1538 Phosphoserine. FT {ECO:0000250|UniProtKB:Q14839}. FT MOD_RES 1601 1601 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 1605 1605 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231}. FT CROSSLNK 1308 1308 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 1573 1573 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000250|UniProtKB:Q14839}. FT VAR_SEQ 1 32 MKAADTVILWARSKNDQLRISFPPGLCWGDRM -> MASPL FT RDEEEEEEEMVVSEEEEEEEEEGDEEEEEEVEAADEDDEED FT DDEGVLGRGPGHDRGRDRHSPPGCHLFPPPPPPPPPLPPPP FT PPPP (in isoform 3). {ECO:0000305}. FT /FTId=VSP_047097. FT VAR_SEQ 1642 1675 Missing (in isoform 2). FT {ECO:0000303|PubMed:9326634, FT ECO:0000303|PubMed:9688266}. FT /FTId=VSP_017231. FT VARIANT 3 3 A -> V (in dbSNP:rs931543). FT /FTId=VAR_048728. FT CONFLICT 121 126 GEGDGG -> PHFQQK (in Ref. 5; AAC50228). FT {ECO:0000305}. FT CONFLICT 309 312 Missing (in Ref. 5; AAC50228). FT {ECO:0000305}. FT CONFLICT 653 653 W -> G (in Ref. 5; AAC50228). FT {ECO:0000305}. FT CONFLICT 1704 1704 K -> N (in Ref. 1; AAC39923). FT {ECO:0000305}. SQ SEQUENCE 2000 AA; 226592 MW; 4494F56E5D0E7083 CRC64; MKAADTVILW ARSKNDQLRI SFPPGLCWGD RMPDKDDIRL LPSALGVKKR KRGPKKQKEN KPGKPRKRKK RDSEEEFGSE RDEYREKSES GGSEYGTGPG RKRRRKHREK KEKKTKRRKK GEGDGGQKQV EQKSSATLLL TWGLEDVEHV FSEEDYHTLT NYKAFSQFMR PLIAKKNPKI PMSKMMTILG AKWREFSANN PFKGSAAAVA AAAAAAAAAV AEQVSAAVSS ATPIAPSGPP ALPPPPAADI QPPPIRRAKT KEGKGPGHKR RSKSPRVPDG RKKLRGKKMA PLKIKLGLLG GKRKKGGSYV FQSDEGPEPE AEESDLDSGS VHSASGRPDG PVRTKKLKRG RPGRKKKKVL GCPAVAGEEE VDGYETDHQD YCEVCQQGGE IILCDTCPRA YHLVCLDPEL DRAPEGKWSC PHCEKEGVQW EAKEEEEEYE EEGEEEGEKE EEDDHMEYCR VCKDGGELLC CDACISSYHI HCLNPPLPDI PNGEWLCPRC TCPVLKGRVQ KILHWRWGEP PVAVPAPQQA DGNPDVPPPR PLQGRSEREF FVKWVGLSYW HCSWAKELQL EIFHLVMYRN YQRKNDMDEP PPLDYGSGED DGKSDKRKVK DPHYAEMEEK YYRFGIKPEW MTVHRIINHS VDKKGNYHYL VKWRDLPYDQ STWEEDEMNI PEYEEHKQSY WRHRELIMGE DPAQPRKYKK KKKELQGDGP PSSPTNDPTV KYETQPRFIT ATGGTLHMYQ LEGLNWLRFS WAQGTDTILA DEMGLGKTIQ TIVFLYSLYK EGHTKGPFLV SAPLSTIINW EREFQMWAPK FYVVTYTGDK DSRAIIRENE FSFEDNAIKG GKKAFKMKRE AQVKFHVLLT SYELITIDQA ALGSIRWACL VVDEAHRLKN NQSKFFRVLN GYKIDHKLLL TGTPLQNNLE ELFHLLNFLT PERFNNLEGF LEEFADISKE DQIKKLHDLL GPHMLRRLKA DVFKNMPAKT ELIVRVELSP MQKKYYKYIL TRNFEALNSR GGGNQVSLLN IMMDLKKCCN HPYLFPVAAM ESPKLPSGAY EGGALIKSSG KLMLLQKMLR KLKEQGHRVL IFSQMTKMLD LLEDFLDYEG YKYERIDGGI TGALRQEAID RFNAPGAQQF CFLLSTRAGG LGINLATADT VIIFDSDWNP HNDIQAFSRA HRIGQANKVM IYRFVTRASV EERITQVAKR KMMLTHLVVR PGLGSKAGSM SKQELDDILK FGTEELFKDE NEGENKEEDS SVIHYDNEAI ARLLDRNQDA TEDTDVQNMN EYLSSFKVAQ YVVREEDKIE EIEREIIKQE ENVDPDYWEK LLRHHYEQQQ EDLARNLGKG KRVRKQVNYN DAAQEDQDNQ SEYSVGSEEE DEDFDERPEG RRQSKRQLRN EKDKPLPPLL ARVGGNIEVL GFNTRQRKAF LNAVMRWGMP PQDAFTTQWL VRDLRGKTEK EFKAYVSLFM RHLCEPGADG SETFADGVPR EGLSRQQVLT RIGVMSLVKK KVQEFEHING RWSMPELMPD PSADSKRSSR ASSPTKTSPT TPEASATNSP CTSKPATPAP SEKGEGIRTP LEKEEAENQE EKPEKNSRIG EKMETEADAP SPAPSLGERL EPRKIPLEDE VPGVPGEMEP EPGYRGDREK SATESTPGER GEEKPLDGQE HRERPEGETG DLGKREDVKG DRELRPGPRD EPRSNGRREE KTEKPRFMFN IADGGFTELH TLWQNEERAA ISSGKLNEIW HRRHDYWLLA GIVLHGYARW QDIQNDAQFA IINEPFKTEA NKGNFLEMKN KFLARRFKLL EQALVIEEQL RRAAYLNLSQ EPAHPAMALH ARFAEAECLA ESHQHLSKES LAGNKPANAV LHKVLNQLEE LLSDMKADVT RLPATLSRIP PIAARLQMSE RSILSRLASK GTEPHPTPAY PPGPYATPPG YGAAFSAAPV GALAAAGANY SQMPAGSFIT AATNGPPVLV KKEKEMVGAL VSDGLDRKEP RAGEVICIDD // ID CO039_HUMAN Reviewed; 1047 AA. AC Q6ZRI6; B3KWI3; C9J888; Q71JB1; Q7L3S0; Q8N3F2; Q96FB6; Q9NTU5; DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 3. DT 11-NOV-2015, entry version 85. DE RecName: Full=Uncharacterized protein C15orf39; GN Name=C15orf39; ORFNames=FP6578; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT RP ASP-945. RC TISSUE=Testis; RX PubMed=11230166; DOI=10.1101/gr.GR1547R; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D., RA Wambutt R., Korn B., Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and RT analysis of 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS RP PRO-119; ASP-491 AND ASP-945. RC TISSUE=Spleen, Testis, and Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS RP ASP-491; ALA-536 AND ASP-945. RX PubMed=15498874; DOI=10.1073/pnas.0404089101; RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., RA Gu J.; RT "Large-scale cDNA transfection screening for genes related to cancer RT development and progression."; RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT RP ASP-945. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., RA Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human RT chromosome 15."; RL Nature 440:671-675(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND RP VARIANTS ASP-491 AND ASP-945. RC TISSUE=Eye, Lymph, and Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 561-1047 (ISOFORM 2). RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-208; SER-391 AND RP THR-397, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-17, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q6ZRI6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6ZRI6-2; Sequence=VSP_019540, VSP_019541; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=Q6ZRI6-3; Sequence=VSP_019538, VSP_019539; CC -!- SEQUENCE CAUTION: CC Sequence=AAQ06680.1; Type=Frameshift; Positions=267; Evidence={ECO:0000305}; CC Sequence=CAB55985.3; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=CAD39045.1; Type=Frameshift; Positions=900; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AL117540; CAB55985.3; ALT_INIT; mRNA. DR EMBL; AK125111; BAG54145.1; -; mRNA. DR EMBL; AK125604; BAC86215.1; -; mRNA. DR EMBL; AK128205; BAC87324.1; -; mRNA. DR EMBL; AF495726; AAQ06680.1; ALT_FRAME; mRNA. DR EMBL; CR533482; CAG38513.1; -; mRNA. DR EMBL; AC113208; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC001762; AAH01762.1; -; mRNA. DR EMBL; BC011379; AAH11379.2; -; mRNA. DR EMBL; BC011905; AAH11905.1; -; mRNA. DR EMBL; BC051235; AAH51235.1; -; mRNA. DR EMBL; BC110367; AAI10368.1; -; mRNA. DR EMBL; AL834382; CAD39045.1; ALT_FRAME; mRNA. DR CCDS; CCDS10276.1; -. [Q6ZRI6-1] DR PIR; T17295; T17295. DR RefSeq; NP_056307.2; NM_015492.4. DR RefSeq; XP_005254608.1; XM_005254551.2. [Q6ZRI6-1] DR RefSeq; XP_011520094.1; XM_011521792.1. [Q6ZRI6-2] DR UniGene; Hs.17936; -. DR ProteinModelPortal; Q6ZRI6; -. DR BioGrid; 121235; 16. DR IntAct; Q6ZRI6; 3. DR MINT; MINT-1421651; -. DR STRING; 9606.ENSP00000353854; -. DR PhosphoSite; Q6ZRI6; -. DR BioMuta; C15orf39; -. DR DMDM; 296439396; -. DR MaxQB; Q6ZRI6; -. DR PaxDb; Q6ZRI6; -. DR PRIDE; Q6ZRI6; -. DR Ensembl; ENST00000360639; ENSP00000353854; ENSG00000167173. [Q6ZRI6-1] DR Ensembl; ENST00000394987; ENSP00000378438; ENSG00000167173. [Q6ZRI6-1] DR Ensembl; ENST00000567617; ENSP00000458025; ENSG00000167173. [Q6ZRI6-2] DR GeneID; 56905; -. DR KEGG; hsa:56905; -. DR UCSC; uc002azp.4; human. [Q6ZRI6-1] DR CTD; 56905; -. DR GeneCards; C15orf39; -. DR H-InvDB; HIX0012438; -. DR H-InvDB; HIX0172847; -. DR HGNC; HGNC:24497; C15orf39. DR HPA; HPA039961; -. DR HPA; HPA041907; -. DR neXtProt; NX_Q6ZRI6; -. DR PharmGKB; PA142672275; -. DR eggNOG; ENOG410IGI4; Eukaryota. DR eggNOG; ENOG410YQ9P; LUCA. DR GeneTree; ENSGT00390000002672; -. DR HOVERGEN; HBG081296; -. DR InParanoid; Q6ZRI6; -. DR OMA; AIFVPIH; -. DR OrthoDB; EOG7NKKK1; -. DR PhylomeDB; Q6ZRI6; -. DR TreeFam; TF338672; -. DR ChiTaRS; C15orf39; human. DR GenomeRNAi; 56905; -. DR NextBio; 62371; -. DR PRO; PR:Q6ZRI6; -. DR Proteomes; UP000005640; Chromosome 15. DR Bgee; Q6ZRI6; -. DR CleanEx; HS_C15orf39; -. DR ExpressionAtlas; Q6ZRI6; baseline and differential. DR Genevisible; Q6ZRI6; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Complete proteome; Phosphoprotein; KW Polymorphism; Reference proteome. FT CHAIN 1 1047 Uncharacterized protein C15orf39. FT /FTId=PRO_0000244343. FT MOD_RES 17 17 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 208 208 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 391 391 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 397 397 Phosphothreonine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 496 496 Phosphoserine. FT {ECO:0000250|UniProtKB:Q3TEI4}. FT MOD_RES 497 497 Phosphoserine. FT {ECO:0000250|UniProtKB:Q3TEI4}. FT MOD_RES 936 936 Phosphoserine. FT {ECO:0000250|UniProtKB:Q3TEI4}. FT MOD_RES 988 988 Phosphoserine. FT {ECO:0000250|UniProtKB:Q3TEI4}. FT MOD_RES 996 996 Phosphoserine. FT {ECO:0000250|UniProtKB:Q3TEI4}. FT VAR_SEQ 1 910 Missing (in isoform 3). FT {ECO:0000303|PubMed:11230166, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.4}. FT /FTId=VSP_019538. FT VAR_SEQ 911 925 DLLGLQWRDCVRRQL -> MGQPQWPPELCEQVT (in FT isoform 3). {ECO:0000303|PubMed:11230166, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.4}. FT /FTId=VSP_019539. FT VAR_SEQ 927 938 DFDTEAGAVSSS -> EHGAAPVATGAV (in isoform FT 2). {ECO:0000303|PubMed:17974005}. FT /FTId=VSP_019540. FT VAR_SEQ 939 1047 Missing (in isoform 2). FT {ECO:0000303|PubMed:17974005}. FT /FTId=VSP_019541. FT VARIANT 119 119 A -> P (in dbSNP:rs1873379). FT {ECO:0000269|PubMed:14702039}. FT /FTId=VAR_026891. FT VARIANT 491 491 G -> D (in dbSNP:rs11072532). FT {ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15498874}. FT /FTId=VAR_026892. FT VARIANT 536 536 S -> A (in dbSNP:rs28509789). FT {ECO:0000269|PubMed:15498874}. FT /FTId=VAR_026893. FT VARIANT 945 945 G -> D (in dbSNP:rs3743211). FT {ECO:0000269|PubMed:11230166, FT ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:15498874, FT ECO:0000269|Ref.4}. FT /FTId=VAR_026894. FT CONFLICT 592 592 R -> H (in Ref. 7; CAD39045). FT {ECO:0000305}. FT CONFLICT 913 913 L -> P (in Ref. 3; BAC87324). FT {ECO:0000305}. SQ SEQUENCE 1047 AA; 110673 MW; 4D31AB94689FED5F CRC64; MAEKRPLRTL GPVMYGKLPR LETDSGLEHS LPHSVGNQDP CTYKGSYFSC PMAGTPKAES EQLASWTPYP PLYSTGMAGP PLQADNLLTN CLFYRSPAEG PEKMQDSSPV ELLPFSPQAH SYPGPPLAAP KPVYRNPLCY GLSTCLGEGA VKRPLDVDWT LATGPLLPSA DPPCSLAPAP SKGQTLDGTF LRGVPAEGSS KDSSGSFSPC QPFLEKYQTI HSTGFLASRY TGPYPRNSKQ AMSEGPSSPW TQLAQPLGPP CQDTGPTHYP PPHHPPPHPP QALPCPPACR HPEKQGSYSP ALPLQPLGGH KGTGYQAGGL GSPYLRQQAA QAPYIPPLGL DAYPYPSAPL PAPSPGLKLE PPLTPRCPLD FAPQTLSFPY ARDDLSLYGA SPGLGGTPPS QNNVRAVPQP GAFQRACQPL PASQPCSEPV RPAQEAEEKT WLPSCRKEKL QPRLSEHSGP PIVIRDSPVP CTPPALPPCA RECQSLPQKE GARPPSSPPM PVIDNVFSLA PYRDYLDVPA PEATTEPDSA TAEPDSAPAT SEGQDKGCRG TLPAQEGPSG SKPLRGSLKE EVALDLSVRK PTAEASPVKA SRSVEHAKPT AAMDVPDVGN MVSDLPGLKK IDTEAPGLPG VPVTTDAMPR TNFHSSVAFM FRKFKILRPA PLPAAVVPST PTSAPAPTQP APTPTSGPIG LRILAQQPLS VTCFSLALPS PPAVAVASPA PAPAPSPAPA RAQAPASARD PAPAPAPVAG PAPASTSAPG DSLEQHFTGL HASLCDAISG SVAHSPPEKL REWLETAGPW GQAAWQDCQG VQGLLAKLLS QLQRFDRTHR CPFPHVVRAG AIFVPIHLVK ERLFPRLPPA SVDHVLQEHR VELRPTTLSE ERALRELALP GCTSRMLKLL ALRQLPDIYP DLLGLQWRDC VRRQLGDFDT EAGAVSSSEP TVARGEPESL ALAQKSPAPK VRKPGRKPPT PGPEKAEAAA GEESCGASPT PATSASPPGP TLKARFRSLL ETAWLNGLAL PTWGHKSSRP DQPSPCPQLL DSQSHHL // ID COM1_HUMAN Reviewed; 897 AA. AC Q99708; A6NKN2; A8K8W6; E7ETY1; O75371; Q8NHQ3; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 11-NOV-2015, entry version 147. DE RecName: Full=DNA endonuclease RBBP8; DE EC=3.1.-.-; DE AltName: Full=CtBP-interacting protein; DE Short=CtIP; DE AltName: Full=Retinoblastoma-binding protein 8; DE Short=RBBP-8; DE AltName: Full=Retinoblastoma-interacting protein and myosin-like; DE Short=RIM; DE AltName: Full=Sporulation in the absence of SPO11 protein 2 homolog; DE Short=SAE2; GN Name=RBBP8; Synonyms=CTIP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH RB1. RX PubMed=9721205; DOI=10.1006/geno.1998.5368; RA Fusco C., Reymond A., Zervos A.S.; RT "Molecular cloning and characterization of a novel retinoblastoma- RT binding protein."; RL Genomics 51:351-358(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH CTBP1. RX PubMed=9535825; DOI=10.1074/jbc.273.15.8549; RA Schaeper U., Subramanian T., Lim L., Boyd J.M., Chinnadurai G.; RT "Interaction between a cellular protein that binds to the C-terminal RT region of adenovirus E1A (CtBP) and a novel cellular protein is RT disrupted by E1A through a conserved PLDLS motif."; RL J. Biol. Chem. 273:8549-8552(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Endometrial cancer; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16177791; DOI=10.1038/nature03983; RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R., RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., RA O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.; RT "DNA sequence and analysis of human chromosome 18."; RL Nature 437:551-555(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH BRCA1. RX PubMed=10764811; DOI=10.1074/jbc.M909494199; RA Yu X., Baer R.; RT "Nuclear localization and cell cycle-specific expression of CtIP, a RT protein that associates with the BRCA1 tumor suppressor."; RL J. Biol. Chem. 275:18541-18549(2000). RN [9] RP FUNCTION, PHOSPHORYLATION AT SER-664 AND SER-745, AND MUTAGENESIS OF RP SER-664 AND SER-745. RX PubMed=10910365; DOI=10.1038/35018134; RA Li S., Ting N.S.Y., Zheng L., Chen P.-L., Ziv Y., Shiloh Y., RA Lee E.Y.-H.P., Lee W.-H.; RT "Functional link of BRCA1 and ataxia telangiectasia gene product in RT DNA damage response."; RL Nature 406:210-215(2000). RN [10] RP INTERACTION WITH LMO4. RX PubMed=11751867; DOI=10.1074/jbc.M110603200; RA Sum E.Y., Peng B., Yu X., Chen J., Byrne J., Lindeman G.J., RA Visvader J.E.; RT "The LIM domain protein LMO4 interacts with the cofactor CtIP and the RT tumor suppressor BRCA1 and inhibits BRCA1 activity."; RL J. Biol. Chem. 277:7849-7856(2002). RN [11] RP INTERACTION WITH SIAH1, AND UBIQUITINATION. RX PubMed=14654780; DOI=10.1038/sj.onc.1206994; RA Germani A., Prabel A., Mourah S., Podgorniak M.-P., Di Carlo A., RA Ehrlich R., Gisselbrecht S., Varin-Blank N., Calvo F., RA Bruzzoni-Giovanelli H.; RT "SIAH-1 interacts with CtIP and promotes its degradation by the RT proteasome pathway."; RL Oncogene 22:8845-8851(2003). RN [12] RP SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=15084581; DOI=10.1074/jbc.M313974200; RA Dubin M.J., Stokes P.H., Sum E.Y., Williams R.S., Valova V.A., RA Robinson P.J., Lindeman G.J., Glover J.N., Visvader J.E., RA Matthews J.M.; RT "Dimerization of CtIP, a BRCA1- and CtBP-interacting protein, is RT mediated by an N-terminal coiled-coil motif."; RL J. Biol. Chem. 279:26932-26938(2004). RN [13] RP FUNCTION, PHOSPHORYLATION AT SER-327, INTERACTION WITH BRCA1, AND RP MUTAGENESIS OF SER-327. RX PubMed=15485915; DOI=10.1128/MCB.24.21.9478-9486.2004; RA Yu X., Chen J.; RT "DNA damage-induced cell cycle checkpoint control requires CtIP, a RT phosphorylation-dependent binding partner of BRCA1 C-terminal RT domains."; RL Mol. Cell. Biol. 24:9478-9486(2004). RN [14] RP INTERACTION WITH BRCA1, FUNCTION, UBIQUITINATION, AND MUTAGENESIS OF RP SER-327. RX PubMed=16818604; DOI=10.1101/gad.1431006; RA Yu X., Fu S., Lai M., Baer R., Chen J.; RT "BRCA1 ubiquitinates its phosphorylation-dependent binding partner RT CtIP."; RL Genes Dev. 20:1721-1726(2006). RN [15] RP FUNCTION. RX PubMed=16581787; DOI=10.1128/MCB.26.8.3124-3134.2006; RA Liu F., Lee W.H.; RT "CtIP activates its own and cyclin D1 promoters via the E2F/RB pathway RT during G1/S progression."; RL Mol. Cell. Biol. 26:3124-3134(2006). RN [16] RP FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND INTERACTION WITH RP BRCA1; MRE11A AND RAD50. RX PubMed=17965729; DOI=10.1038/nature06337; RA Sartori A.A., Lukas C., Coates J., Mistrik M., Fu S., Bartek J., RA Baer R., Lukas J., Jackson S.P.; RT "Human CtIP promotes DNA end resection."; RL Nature 450:509-514(2007). RN [17] RP ASSOCIATION WITH OVARIAN CANCER SURVIVAL. RX PubMed=19270026; DOI=10.1093/hmg/ddp107; RA Quaye L., Dafou D., Ramus S.J., Song H., Gentry-Maharaj A., RA Notaridou M., Hogdall E., Kjaer S.K., Christensen L., Hogdall C., RA Easton D.F., Jacobs I., Menon U., Pharoah P.D., Gayther S.A.; RT "Functional complementation studies identify candidate genes and RT common genetic variants associated with ovarian cancer survival."; RL Hum. Mol. Genet. 18:1869-1878(2009). RN [18] RP FUNCTION, DNA-BINDING, PHOSPHORYLATION AT THR-847, AND MUTAGENESIS OF RP THR-847. RX PubMed=19202191; DOI=10.1074/jbc.M808906200; RA Huertas P., Jackson S.P.; RT "Human CtIP mediates cell cycle control of DNA end resection and RT double strand break repair."; RL J. Biol. Chem. 284:9558-9565(2009). RN [19] RP FUNCTION, INTERACTION WITH MRE11A; RAD50 AND NBN, AND MUTAGENESIS OF RP HIS-31; VAL-35; LYS-41 AND LEU-45. RX PubMed=19759395; DOI=10.1074/jbc.M109.023424; RA Yuan J., Chen J.; RT "N terminus of CtIP is critical for homologous recombination-mediated RT double-strand break repair."; RL J. Biol. Chem. 284:31746-31752(2009). RN [20] RP FUNCTION, AND MUTAGENESIS OF LYS-513 AND LYS-515. RX PubMed=20064462; DOI=10.1016/j.molcel.2009.12.002; RA You Z., Shi L.Z., Zhu Q., Wu P., Zhang Y.W., Basilio A., Tonnu N., RA Verma I.M., Berns M.W., Hunter T.; RT "CtIP links DNA double-strand break sensing to resection."; RL Mol. Cell 36:954-969(2009). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-723, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [23] RP FUNCTION, ACETYLATION AT LYS-432; LYS-526 AND LYS-604, INTERACTION RP WITH SIRT6, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF RP LYS-432; LYS-526 AND LYS-604. RX PubMed=20829486; DOI=10.1126/science.1192049; RA Kaidi A., Weinert B.T., Choudhary C., Jackson S.P.; RT "Human SIRT6 promotes DNA end resection through CtIP deacetylation."; RL Science 329:1348-1353(2010). RN [24] RP ASSOCIATION WITH BREAST CANCER. RX PubMed=21799032; DOI=10.1158/0008-5472.CAN-11-0773; RA Rebbeck T.R., Mitra N., Domchek S.M., Wan F., Friebel T.M., Tran T.V., RA Singer C.F., Tea M.K., Blum J.L., Tung N., Olopade O.I., Weitzel J.N., RA Lynch H.T., Snyder C.L., Garber J.E., Antoniou A.C., Peock S., RA Evans D.G., Paterson J., Kennedy M.J., Donaldson A., Dorkins H., RA Easton D.F., Rubinstein W.S., Daly M.B., Isaacs C., Nevanlinna H., RA Couch F.J., Andrulis I.L., Freidman E., Laitman Y., Ganz P.A., RA Tomlinson G.E., Neuhausen S.L., Narod S.A., Phelan C.M., Greenberg R., RA Nathanson K.L.; RT "Modification of BRCA1-associated breast and ovarian cancer risk by RT BRCA1-interacting genes."; RL Cancer Res. 71:5792-5805(2011). RN [25] RP INVOLVEMENT IN JWDS, AND INVOLVEMENT IN SCKL2. RX PubMed=21998596; DOI=10.1371/journal.pgen.1002310; RA Jackson S.P., Borglum A.D.; RT "CtIP mutations cause Seckel and Jawad syndromes."; RL PLoS Genet. 7:E1002310-E1002310(2011). RN [26] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-869, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). CC -!- FUNCTION: Endonuclease that cooperates with the MRE11-RAD50-NBN CC (MRN) complex in processing meiotic and mitotic double-strand CC breaks (DSBs) by ensuring both resection and intrachromosomal CC association of the broken ends. Functions downstream of the MRN CC complex and ATM, promotes ATR activation and its recruitment to CC DSBs in the S/G2 phase facilitating the generation of ssDNA. CC Component of the BRCA1-RBBP8 complex that regulates CHEK1 CC activation and controls cell cycle G2/M checkpoints on DNA damage. CC Promotes microhomology-mediated alternative end joining (A-NHEJ) CC during class-switch recombination and plays an essential role in CC chromosomal translocations. {ECO:0000269|PubMed:10764811, CC ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:15485915, CC ECO:0000269|PubMed:16581787, ECO:0000269|PubMed:16818604, CC ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19202191, CC ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:20064462, CC ECO:0000269|PubMed:20829486}. CC -!- SUBUNIT: Homodimer; dimerizes via the coiled coil domain. CC Interacts (via the PXDLS motif) with CTBP1; the interaction is CC disrupted via binding of the adenovirus E1A to CTBP1. Component of CC the BRCA1-RBBBP8 complex. Interacts (the Ser-327 phosphorylated CC form) with BRCA1 (via the C-terminal BRCA1 domains): the CC interaction occurs in the G2 phase, ubiquitinates RBBP8 and CC involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA CC damage. Interacts with RB1. Interacts with the MRN complex. CC Interacts directly with MRE11A; the interaction is required for CC efficient homologous recombination (HR) and regulation of the MRN CC complex. Interacts directly with RAD50. Interacts directly with CC NBN. Interacts with SIRT6; the interaction deacetylates RBBP8 upon CC DNA damage. Interacts with LM04 (via the LIM zinc-binding 1 CC domain). {ECO:0000269|PubMed:10764811, CC ECO:0000269|PubMed:11751867, ECO:0000269|PubMed:14654780, CC ECO:0000269|PubMed:15084581, ECO:0000269|PubMed:15485915, CC ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17965729, CC ECO:0000269|PubMed:19759395, ECO:0000269|PubMed:20829486, CC ECO:0000269|PubMed:9535825, ECO:0000269|PubMed:9721205}. CC -!- INTERACTION: CC P38398:BRCA1; NbExp=9; IntAct=EBI-745715, EBI-349905; CC Q9UQ84:EXO1; NbExp=3; IntAct=EBI-745715, EBI-944667; CC P25800:LMO1; NbExp=3; IntAct=EBI-10203615, EBI-8639312; CC P61968:LMO4; NbExp=3; IntAct=EBI-10203615, EBI-2798728; CC Q13526:PIN1; NbExp=3; IntAct=EBI-10203615, EBI-714158; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10764811, CC ECO:0000269|PubMed:17965729}. Note=Associates with sites of DNA CC damage in S/G2 phase. Ubiquitinated RBBP8 binds to chromatin CC following DNA damage. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q99708-1; Sequence=Displayed; CC Name=2; CC IsoId=Q99708-2; Sequence=VSP_043220; CC Name=3; CC IsoId=Q99708-3; Sequence=VSP_045247, VSP_045248; CC Note=No experimental confirmation available. Ref.4 (BX648221) CC sequence is in conflict in position: 862:S->G. {ECO:0000305}; CC -!- INDUCTION: Levels increase dramatically as dividing cells traverse CC the G1/S boubdary. Down-regulated in tamoxifen-resistant breast CC cancer cells. CC -!- DOMAIN: The PXDLS motif binds to a cleft in CtBP proteins. CC -!- DOMAIN: The damage-recruitment motif is required for DNA binding CC and translocation to sites of DNA damage. CC -!- PTM: Acetylated. Deacetylation by SIRT6 upon DNA damage promotes CC DNA end resection. {ECO:0000269|PubMed:20829486}. CC -!- PTM: Hyperphosphorylation upon ionizing radiation results in CC dissociation from BRCA1. Phosphorylation at Thr-847 by CDK1 is CC essential for the recruitment to DNA and the DNA repair function. CC Phosphorylated on Ser-327 as cells enter G2 phase. This CC phosphorylation is required for binding BRCA1 and for the G2/M DNA CC damage transition checkpoint control. CC {ECO:0000269|PubMed:10910365, ECO:0000269|PubMed:15485915, CC ECO:0000269|PubMed:17965729, ECO:0000269|PubMed:19202191}. CC -!- PTM: Ubiquitinated. Ubiquitination at multiple sites by BRCA1 (via CC its N-terminal RING domain) does not lead to its proteosomal CC degradation but instead the ubiquitinated RBBP8 binds to chromatin CC following DNA damage and may play a role in G2/M checkpoint CC control. {ECO:0000269|PubMed:14654780, CC ECO:0000269|PubMed:16818604}. CC -!- DISEASE: Seckel syndrome 2 (SCKL2) [MIM:606744]: A rare autosomal CC recessive disorder characterized by proportionate dwarfism of CC prenatal onset associated with low birth weight, growth CC retardation, severe microcephaly with a bird-headed like CC appearance, and mental retardation. {ECO:0000269|PubMed:21998596}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- DISEASE: Jawad syndrome (JWDS) [MIM:251255]: A syndrome CC characterized by congenital microcephaly, moderately severe mental CC retardation, and symmetrical digital anomalies. Digital CC malformations of variable degree include hallux valgus, syndactyly CC of toes 4 and 5, short fifth fingers, single flexion crease of CC fifth fingers, polydactyly and synpolydactyly. CC {ECO:0000269|PubMed:21998596}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Note=Genetic variability in RBBP8 is noted as a factor in CC BRCA1-associated breast cancer risk. Exhibits sensitivity to CC tamoxifen in certain breast cancer cell lines. CC -!- SIMILARITY: Belongs to the COM1/SAE2/CtIP family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/RBBP8ID42066ch18q11.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF043431; AAC34368.1; -; mRNA. DR EMBL; U72066; AAC14371.1; -; mRNA. DR EMBL; AK292481; BAF85170.1; -; mRNA. DR EMBL; BX648221; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AC091147; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC106033; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471088; EAX01144.1; -; Genomic_DNA. DR EMBL; BC030590; AAH30590.1; -; mRNA. DR CCDS; CCDS11874.1; -. [Q99708-3] DR CCDS; CCDS11875.1; -. [Q99708-1] DR RefSeq; NP_002885.1; NM_002894.2. [Q99708-1] DR RefSeq; NP_976036.1; NM_203291.1. [Q99708-1] DR RefSeq; NP_976037.1; NM_203292.1. [Q99708-3] DR RefSeq; XP_006722582.1; XM_006722519.1. [Q99708-1] DR RefSeq; XP_006722583.1; XM_006722520.1. [Q99708-1] DR RefSeq; XP_006722584.1; XM_006722521.1. [Q99708-1] DR RefSeq; XP_011524434.1; XM_011526132.1. [Q99708-1] DR UniGene; Hs.546282; -. DR PDB; 2L4Z; NMR; -; A=641-685. DR PDB; 4D2H; X-ray; 1.90 A; A/B/C/D/E/F/G/H=18-52. DR PDBsum; 2L4Z; -. DR PDBsum; 4D2H; -. DR ProteinModelPortal; Q99708; -. DR SMR; Q99708; 18-52, 641-677. DR BioGrid; 111867; 43. DR DIP; DIP-24244N; -. DR IntAct; Q99708; 27. DR MINT; MINT-102295; -. DR STRING; 9606.ENSP00000323050; -. DR PhosphoSite; Q99708; -. DR BioMuta; RBBP8; -. DR DMDM; 116242745; -. DR MaxQB; Q99708; -. DR PaxDb; Q99708; -. DR PRIDE; Q99708; -. DR DNASU; 5932; -. DR Ensembl; ENST00000327155; ENSP00000323050; ENSG00000101773. [Q99708-1] DR Ensembl; ENST00000399722; ENSP00000382628; ENSG00000101773. [Q99708-1] DR Ensembl; ENST00000399725; ENSP00000382630; ENSG00000101773. [Q99708-3] DR GeneID; 5932; -. DR KEGG; hsa:5932; -. DR UCSC; uc002ktw.3; human. [Q99708-1] DR UCSC; uc002ktz.3; human. DR CTD; 5932; -. DR GeneCards; RBBP8; -. DR GeneReviews; RBBP8; -. DR HGNC; HGNC:9891; RBBP8. DR HPA; HPA039890; -. DR HPA; HPA052946; -. DR MIM; 251255; phenotype. DR MIM; 604124; gene. DR MIM; 606744; phenotype. DR neXtProt; NX_Q99708; -. DR Orphanet; 313795; Jawad syndrome. DR Orphanet; 808; Seckel syndrome. DR PharmGKB; PA34255; -. DR eggNOG; ENOG410IJ39; Eukaryota. DR eggNOG; ENOG410ZSBE; LUCA. DR GeneTree; ENSGT00530000063835; -. DR HOGENOM; HOG000293331; -. DR HOVERGEN; HBG057046; -. DR InParanoid; Q99708; -. DR OrthoDB; EOG771274; -. DR PhylomeDB; Q99708; -. DR TreeFam; TF106469; -. DR Reactome; R-HSA-912446; Meiotic recombination. DR ChiTaRS; RBBP8; human. DR EvolutionaryTrace; Q99708; -. DR GeneWiki; RBBP8; -. DR GenomeRNAi; 5932; -. DR NextBio; 23118; -. DR PRO; PR:Q99708; -. DR Proteomes; UP000005640; Chromosome 18. DR Bgee; Q99708; -. DR CleanEx; HS_RBBP8; -. DR ExpressionAtlas; Q99708; baseline and differential. DR Genevisible; Q99708; HS. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0017053; C:transcriptional repressor complex; IDA:BHF-UCL. DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB. DR GO; GO:0001103; F:RNA polymerase II repressing transcription factor binding; IPI:BHF-UCL. DR GO; GO:0001106; F:RNA polymerase II transcription corepressor activity; IDA:BHF-UCL. DR GO; GO:0000014; F:single-stranded DNA endodeoxyribonuclease activity; IMP:UniProtKB. DR GO; GO:0001835; P:blastocyst hatching; IEA:Ensembl. DR GO; GO:0000075; P:cell cycle checkpoint; TAS:ProtInc. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0010792; P:DNA double-strand break processing involved in repair via single-strand annealing; IMP:UniProtKB. DR GO; GO:0006281; P:DNA repair; TAS:ProtInc. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:UniProtKB. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0031572; P:G2 DNA damage checkpoint; IDA:UniProtKB. DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW. DR GO; GO:0007067; P:mitotic nuclear division; IEA:UniProtKB-KW. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:GOC. DR GO; GO:0006289; P:nucleotide-excision repair; IMP:CACAO. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR InterPro; IPR013882; Com1/Ctip_fam. DR InterPro; IPR019518; CtIP_N. DR Pfam; PF10482; CtIP_N; 1. DR Pfam; PF08573; SAE2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell cycle; KW Cell division; Coiled coil; Complete proteome; DNA damage; DNA repair; KW DNA-binding; Dwarfism; Endonuclease; Hydrolase; Isopeptide bond; KW Meiosis; Mental retardation; Mitosis; Nuclease; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation. FT CHAIN 1 897 DNA endonuclease RBBP8. FT /FTId=PRO_0000097179. FT REGION 22 45 Essential for binding to the MRN complex FT and for RPA focus formation on DNA FT damage. FT REGION 509 557 Damage-recruitment motif. FT COILED 28 157 {ECO:0000255}. FT MOTIF 490 494 PXDLS motif. FT COMPBIAS 750 753 Poly-Glu. FT MOD_RES 233 233 Phosphoserine. FT {ECO:0000250|UniProtKB:Q80YR6}. FT MOD_RES 326 326 Phosphoserine. FT {ECO:0000269|PubMed:17965729}. FT MOD_RES 327 327 Phosphoserine. FT {ECO:0000269|PubMed:15485915}. FT MOD_RES 349 349 Phosphoserine. FT {ECO:0000269|PubMed:17965729}. FT MOD_RES 432 432 N6-acetyllysine. FT {ECO:0000269|PubMed:20829486}. FT MOD_RES 526 526 N6-acetyllysine. FT {ECO:0000269|PubMed:20829486}. FT MOD_RES 604 604 N6-acetyllysine. FT {ECO:0000269|PubMed:20829486}. FT MOD_RES 664 664 Phosphoserine; by ATM. FT {ECO:0000269|PubMed:10910365}. FT MOD_RES 679 679 Phosphoserine. FT {ECO:0000269|PubMed:17965729}. FT MOD_RES 723 723 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 745 745 Phosphoserine; by ATM. FT {ECO:0000269|PubMed:10910365}. FT MOD_RES 847 847 Phosphothreonine; by CDK1. FT {ECO:0000269|PubMed:19202191}. FT CROSSLNK 869 869 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT VAR_SEQ 714 714 S -> SMLFYI (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_043220. FT VAR_SEQ 786 867 RETSLQNFPHIEVVRKKEERRKLLGHTCKECEIYYADMPAE FT EREKKLASCSRHRFRYIPPNTPENFWEVGFPSTQTCMERGY FT -> SIMQICQQKKEKRNWLPAQDTDSATFHPTHQRIFGKLV FT FLPLRLVWKEVILRKILILVLVQKDVSLTTQYFLQKARSRR FT HRR (in isoform 3). FT {ECO:0000303|PubMed:17974005}. FT /FTId=VSP_045247. FT VAR_SEQ 868 897 Missing (in isoform 3). FT {ECO:0000303|PubMed:17974005}. FT /FTId=VSP_045248. FT VARIANT 357 357 K -> N (in dbSNP:rs34678569). FT /FTId=VAR_051308. FT VARIANT 387 387 H -> Y (in dbSNP:rs1804732). FT /FTId=VAR_028308. FT MUTAGEN 31 31 H->A: No effect on RPA focus formation on FT DNA damage. FT {ECO:0000269|PubMed:19759395}. FT MUTAGEN 35 35 V->A: No effect on RPA focus formation on FT DNA damage. FT {ECO:0000269|PubMed:19759395}. FT MUTAGEN 41 41 K->A: No effect on RPA focus formation on FT DNA damage. FT {ECO:0000269|PubMed:19759395}. FT MUTAGEN 45 45 L->A: No effect on RPA focus formation on FT DNA damage. FT {ECO:0000269|PubMed:19759395}. FT MUTAGEN 327 327 S->A: Abolishes BRCA1 interaction and FT ubiquitination. No activation of CHEK1 FT after DNA damage. FT {ECO:0000269|PubMed:15485915, FT ECO:0000269|PubMed:16818604}. FT MUTAGEN 432 432 K->R: Greatly reduced acetylation. FT Alleviates resection defects caused by FT depletion of SIRT6; when associated with FT R-526 and R-604. FT {ECO:0000269|PubMed:20829486}. FT MUTAGEN 513 513 K->A: Abolishes damage recruitment FT capability. FT {ECO:0000269|PubMed:20064462}. FT MUTAGEN 515 515 K->A: Abolishes damage recruitment FT capability. FT {ECO:0000269|PubMed:20064462}. FT MUTAGEN 526 526 K->R: Greatly reduced acetylation. FT Alleviates resection defects caused by FT depletion of SIRT6; when associated with FT R-432 and R-604. FT {ECO:0000269|PubMed:20829486}. FT MUTAGEN 604 604 K->R: Greatly reduced acetylation. FT Alleviates resection defects caused by FT depletion of SIRT6; when associated with FT R-432 and R-526. FT {ECO:0000269|PubMed:20829486}. FT MUTAGEN 664 664 S->A: Abrogates dissociation of BRCA1. FT {ECO:0000269|PubMed:10910365}. FT MUTAGEN 745 745 S->A: Abrogates dissociation of BRCA1. FT {ECO:0000269|PubMed:10910365}. FT MUTAGEN 847 847 T->A: Impairs DNA resection. FT {ECO:0000269|PubMed:19202191}. FT MUTAGEN 847 847 T->E: Mimics constitutive FT phosphorylation. FT {ECO:0000269|PubMed:19202191}. FT CONFLICT 4 4 S -> L (in Ref. 1; AAC14371). FT {ECO:0000305}. FT CONFLICT 74 74 H -> Q (in Ref. 4; BX648221). FT {ECO:0000305}. FT CONFLICT 92 92 C -> Y (in Ref. 3; BAF85170). FT {ECO:0000305}. FT CONFLICT 123 123 E -> G (in Ref. 3; BAF85170). FT {ECO:0000305}. FT CONFLICT 341 341 D -> G (in Ref. 4; BX648221). FT {ECO:0000305}. FT CONFLICT 515 515 K -> R (in Ref. 4; BX648221). FT {ECO:0000305}. FT CONFLICT 521 521 L -> P (in Ref. 3; BAF85170). FT {ECO:0000305}. FT CONFLICT 642 642 L -> P (in Ref. 4; BX648221). FT {ECO:0000305}. FT HELIX 18 50 {ECO:0000244|PDB:4D2H}. FT STRAND 648 650 {ECO:0000244|PDB:2L4Z}. FT HELIX 651 653 {ECO:0000244|PDB:2L4Z}. FT TURN 662 666 {ECO:0000244|PDB:2L4Z}. FT STRAND 677 679 {ECO:0000244|PDB:2L4Z}. SQ SEQUENCE 897 AA; 101942 MW; E028DE56DE55C0F2 CRC64; MNISGSSCGS PNSADTSSDF KDLWTKLKEC HDREVQGLQV KVTKLKQERI LDAQRLEEFF TKNQQLREQQ KVLHETIKVL EDRLRAGLCD RCAVTEEHMR KKQQEFENIR QQNLKLITEL MNERNTLQEE NKKLSEQLQQ KIENDQQHQA AELECEEDVI PDSPITAFSF SGVNRLRRKE NPHVRYIEQT HTKLEHSVCA NEMRKVSKSS THPQHNPNEN EILVADTYDQ SQSPMAKAHG TSSYTPDKSS FNLATVVAET LGLGVQEESE TQGPMSPLGD ELYHCLEGNH KKQPFEESTR NTEDSLRFSD STSKTPPQEE LPTRVSSPVF GATSSIKSGL DLNTSLSPSL LQPGKKKHLK TLPFSNTCIS RLEKTRSKSE DSALFTHHSL GSEVNKIIIQ SSNKQILINK NISESLGEQN RTEYGKDSNT DKHLEPLKSL GGRTSKRKKT EEESEHEVSC PQASFDKENA FPFPMDNQFS MNGDCVMDKP LDLSDRFSAI QRQEKSQGSE TSKNKFRQVT LYEALKTIPK GFSSSRKASD GNCTLPKDSP GEPCSQECII LQPLNKCSPD NKPSLQIKEE NAVFKIPLRP RESLETENVL DDIKSAGSHE PIKIQTRSDH GGCELASVLQ LNPCRTGKIK SLQNNQDVSF ENIQWSIDPG ADLSQYKMDV TVIDTKDGSQ SKLGGETVDM DCTLVSETVL LKMKKQEQKG EKSSNEERKM NDSLEDMFDR TTHEEYESCL ADSFSQAADE EEELSTATKK LHTHGDKQDK VKQKAFVEPY FKGDERETSL QNFPHIEVVR KKEERRKLLG HTCKECEIYY ADMPAEEREK KLASCSRHRF RYIPPNTPEN FWEVGFPSTQ TCMERGYIKE DLDPCPRPKR RQPYNAIFSP KGKEQKT // ID CRY2_HUMAN Reviewed; 593 AA. AC Q49AN0; B4DH32; B4DZD6; O75148; Q8IV71; DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot. DT 28-NOV-2006, sequence version 2. DT 11-NOV-2015, entry version 102. DE RecName: Full=Cryptochrome-2; GN Name=CRY2; Synonyms=KIAA0658; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Fetal brain; RX PubMed=8909283; DOI=10.1021/bi962209o; RA Hsu D.S., Zhao X., Zhao S., Kazantsev A., Wang R.-P., Todo T., RA Wei Y.-F., Sancar A.; RT "Putative human blue-light photoreceptors hCRY1 and hCRY2 are RT flavoproteins."; RL Biochemistry 35:13871-13877(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain, and Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-593 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9734811; DOI=10.1093/dnares/5.3.169; RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., RA Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. X. RT The complete sequences of 100 new cDNA clones from brain which can RT code for large proteins in vitro."; RL DNA Res. 5:169-176(1998). RN [6] RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION. RX PubMed=9801304; DOI=10.1093/nar/26.22.5086; RA Kobayashi K., Kanno S., Smit B., van der Horst G.T.J., Takao M., RA Yasui A.; RT "Characterization of photolyase/blue-light receptor homologs in mouse RT and human cells."; RL Nucleic Acids Res. 26:5086-5092(1998). RN [7] RP FUNCTION. RX PubMed=10531061; DOI=10.1126/science.286.5440.768; RA Griffin E.A. Jr., Staknis D., Weitz C.J.; RT "Light-independent role of CRY1 and CRY2 in the mammalian circadian RT clock."; RL Science 286:768-771(1999). RN [8] RP UBIQUITINATION. RX PubMed=11889036; DOI=10.1093/emboj/21.6.1301; RA Yagita K., Tamanini F., Yasuda M., Hoeijmakers J.H., RA van der Horst G.T., Okamura H.; RT "Nucleocytoplasmic shuttling and mCRY-dependent inhibition of RT ubiquitylation of the mPER2 clock protein."; RL EMBO J. 21:1301-1314(2002). RN [9] RP FUNCTION. RX PubMed=14672706; DOI=10.1016/j.bbrc.2003.11.099; RA Kawamoto T., Noshiro M., Sato F., Maemura K., Takeda N., Nagai R., RA Iwata T., Fujimoto K., Furukawa M., Miyazaki K., Honma S., Honma K.I., RA Kato Y.; RT "A novel autofeedback loop of Dec1 transcription involved in circadian RT rhythm regulation."; RL Biochem. Biophys. Res. Commun. 313:117-124(2004). RN [10] RP FUNCTION, AND INTERACTION WITH PPP5C. RX PubMed=16790549; DOI=10.1073/pnas.0604138103; RA Partch C.L., Shields K.F., Thompson C.L., Selby C.P., Sancar A.; RT "Posttranslational regulation of the mammalian circadian clock by RT cryptochrome and protein phosphatase 5."; RL Proc. Natl. Acad. Sci. U.S.A. 103:10467-10472(2006). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY, UBIQUITINATION BY FBXL3, AND RP INTERACTION WITH FBXL3. RX PubMed=17463251; DOI=10.1126/science.1141194; RA Busino L., Bassermann F., Maiolica A., Lee C., Nolan P.M., RA Godinho S.I., Draetta G.F., Pagano M.; RT "SCFFbxl3 controls the oscillation of the circadian clock by directing RT the degradation of cryptochrome proteins."; RL Science 316:900-904(2007). RN [12] RP REVIEW. RX PubMed=23303907; DOI=10.1152/physrev.00016.2012; RA Eckel-Mahan K., Sassone-Corsi P.; RT "Metabolism and the circadian clock converge."; RL Physiol. Rev. 93:107-135(2013). RN [13] RP REVIEW. RX PubMed=23916625; DOI=10.1016/j.tcb.2013.07.002; RA Partch C.L., Green C.B., Takahashi J.S.; RT "Molecular architecture of the mammalian circadian clock."; RL Trends Cell Biol. 24:90-99(2014). CC -!- FUNCTION: Transcriptional repressor which forms a core component CC of the circadian clock. The circadian clock, an internal time- CC keeping system, regulates various physiological processes through CC the generation of approximately 24 hour circadian rhythms in gene CC expression, which are translated into rhythms in metabolism and CC behavior. It is derived from the Latin roots 'circa' (about) and CC 'diem' (day) and acts as an important regulator of a wide array of CC physiological functions including metabolism, sleep, body CC temperature, blood pressure, endocrine, immune, cardiovascular, CC and renal function. Consists of two major components: the central CC clock, residing in the suprachiasmatic nucleus (SCN) of the brain, CC and the peripheral clocks that are present in nearly every tissue CC and organ system. Both the central and peripheral clocks can be CC reset by environmental cues, also known as Zeitgebers (German for CC 'timegivers'). The predominant Zeitgeber for the central clock is CC light, which is sensed by retina and signals directly to the SCN. CC The central clock entrains the peripheral clocks through neuronal CC and hormonal signals, body temperature and feeding-related cues, CC aligning all clocks with the external light/dark cycle. Circadian CC rhythms allow an organism to achieve temporal homeostasis with its CC environment at the molecular level by regulating gene expression CC to create a peak of protein expression once every 24 hours to CC control when a particular physiological process is most active CC with respect to the solar day. Transcription and translation of CC core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, CC PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm CC generation, whereas delays imposed by post-translational CC modifications (PTMs) are important for determining the period CC (tau) of the rhythms (tau refers to the period of a rhythm and is CC the length, in time, of one complete cycle). A diurnal rhythm is CC synchronized with the day/night cycle, while the ultradian and CC infradian rhythms have a period shorter and longer than 24 hours, CC respectively. Disruptions in the circadian rhythms contribute to CC the pathology of cardiovascular diseases, cancer, metabolic CC syndromes and aging. A transcription/translation feedback loop CC (TTFL) forms the core of the molecular circadian clock mechanism. CC Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or CC ARNTL2/BMAL2, form the positive limb of the feedback loop, act in CC the form of a heterodimer and activate the transcription of core CC clock genes and clock-controlled genes (involved in key metabolic CC processes), harboring E-box elements (5'-CACGTG-3') within their CC promoters. The core clock genes: PER1/2/3 and CRY1/2 which are CC transcriptional repressors form the negative limb of the feedback CC loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 CC heterodimer inhibiting its activity and thereby negatively CC regulating their own expression. This heterodimer also activates CC nuclear receptors NR1D1/2 and RORA/B/G, which form a second CC feedback loop and which activate and repress ARNTL/BMAL1 CC transcription, respectively. CRY1 and CRY2 have redundant CC functions but also differential and selective contributions at CC least in defining the pace of the SCN circadian clock and its CC circadian transcriptional outputs. Less potent transcriptional CC repressor in cerebellum and liver than CRY1, though less effective CC in lengthening the period of the SCN oscillator. Seems to play a CC critical role in tuning SCN circadian period by opposing the CC action of CRY1. With CRY1, dispensable for circadian rhythm CC generation but necessary for the development of intercellular CC networks for rhythm synchrony. May mediate circadian regulation of CC cAMP signaling and gluconeogenesis by blocking glucagon-mediated CC increases in intracellular cAMP concentrations and in CREB1 CC phosphorylation. Besides its role in the maintenance of the CC circadian clock, is also involved in the regulation of other CC processes. Plays a key role in glucose and lipid metabolism CC modulation, in part, through the transcriptional regulation of CC genes involved in these pathways, such as LEP or ACSL4. Represses CC glucocorticoid receptor NR3C1/GR-induced transcriptional activity CC by binding to glucocorticoid response elements (GREs). Represses CC the CLOCK-ARNTL/BMAL1 induced transcription of BHLHE40/DEC1. CC Represses the CLOCK-ARNTL/BMAL1 induced transcription of NAMPT (By CC similarity). {ECO:0000250|UniProtKB:Q9R194, CC ECO:0000269|PubMed:10531061, ECO:0000269|PubMed:14672706, CC ECO:0000269|PubMed:16790549}. CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250}; CC Note=Binds 1 FAD per subunit. Only a minority of the protein CC molecules contain bound FAD. Contrary to the situation in CC photolyases, the FAD is bound in a shallow, surface-exposed CC pocket. {ECO:0000250}; CC -!- COFACTOR: CC Name=5,10-methylenetetrahydrofolate; Xref=ChEBI:CHEBI:12071; CC Evidence={ECO:0000250}; CC Note=Binds 1 5,10-methenyltetrahydrofolate non-covalently per CC subunit. {ECO:0000250}; CC -!- SUBUNIT: Component of the circadian core oscillator, which CC includes the CRY proteins, CLOCK or NPAS2, ARNTL/BMAL1 or CC ARNTL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS, and the PER CC proteins. Interacts directly with PER1 and PER2 C-terminal CC domains. Interaction with PER2 inhibits its ubiquitination and CC vice versa. Interacts with NFIL3. Interacts with FBXL3 and FBXL21. CC FBXL3, PER2 and the cofactor FAD compete for overlapping binding CC sites. FBXL3 cannot bind CRY2 that interacts already with PER2 or CC that contains bound FAD. Interacts with PPP5C (via TPR repeats); CC the interaction downregulates the PPP5C phosphatase activity on CC CSNK1E. AR, NR1D1, NR3C1/GR, RORA and RORC; the interaction, at CC least, with NR3C1/GR is ligand dependent. Interacts with PRKDC and CC CIART. {ECO:0000269|PubMed:16790549, ECO:0000269|PubMed:17463251}. CC -!- INTERACTION: CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-2212355, EBI-10171858; CC Q5JR59:MTUS2; NbExp=3; IntAct=EBI-2212355, EBI-742948; CC O76083:PDE9A; NbExp=3; IntAct=EBI-2212355, EBI-742764; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9801304}. CC Nucleus {ECO:0000269|PubMed:9801304}. Note=Translocated to the CC nucleus through interaction with other Clock proteins such as PER2 CC or ARNTL. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q49AN0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q49AN0-2; Sequence=VSP_038970; CC Note=No experimental confirmation available. Ref.2 (BAG57993) CC sequence is in conflict in position: 9:H->L. {ECO:0000305}; CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined including CC fetal brain, fibroblasts, heart, brain, placenta, lung, liver, CC skeletal muscle, kidney, pancreas, spleen, thymus, prostate, CC testis, ovary, small intestine, colon and leukocytes. Highest CC levels in heart and skeletal muscle. {ECO:0000269|PubMed:8909283, CC ECO:0000269|PubMed:9801304}. CC -!- PTM: Phosphorylation on Ser-266 by MAPK is important for the CC inhibition of CLOCK-ARNTL-mediated transcriptional activity. CC Phosphorylation by CSKNE requires interaction with PER1 or PER2. CC Phosphorylated in a circadian manner at Ser-554 and Ser-558 in the CC suprachiasmatic nucleus (SCN) and liver. Phosphorylation at Ser- CC 558 by DYRK1A promotes subsequent phosphorylation at Ser-554 by CC GSK3-beta: the two-step phosphorylation at the neighboring Ser CC residues leads to its proteasomal degradation. CC {ECO:0000250|UniProtKB:Q9R194}. CC -!- PTM: Ubiquitinated by the SCF(FBXL3) and SCF(FBXL21) complexes, CC regulating the balance between degradation and stabilization. The CC SCF(FBXL3) complex is mainly nuclear and mediates ubiquitination CC and subsequent degradation of CRY2. In contrast, cytoplasmic CC SCF(FBXL21) complex-mediated ubiquitination leads to stabilize CC CRY2 and counteract the activity of the SCF(FBXL3) complex. The CC SCF(FBXL3) and SCF(FBXL21) complexes probably mediate CC ubiquitination at different Lys residues. The SCF(FBXL3) complex CC recognizes and binds CRY2 phosphorylated at Ser-554 and Ser-558. CC Ubiquitination may be inhibited by PER2. CC {ECO:0000269|PubMed:11889036, ECO:0000269|PubMed:17463251}. CC -!- SIMILARITY: Belongs to the DNA photolyase class-1 family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 photolyase/cryptochrome alpha/beta domain. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH35161.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact. Aberrant splice sites.; Evidence={ECO:0000305}; CC Sequence=BAG57993.1; Type=Erroneous termination; Positions=110; Note=Translated as Trp.; Evidence={ECO:0000305}; CC Sequence=BAG57993.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305}; CC Sequence=BAG64048.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Cryptochrome entry; CC URL="https://en.wikipedia.org/wiki/Cryptochrome"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AK294904; BAG57993.1; ALT_SEQ; mRNA. DR EMBL; AK302865; BAG64048.1; ALT_INIT; mRNA. DR EMBL; AC068385; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; KF455380; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC035161; AAH35161.1; ALT_SEQ; mRNA. DR EMBL; BC041814; AAH41814.1; -; mRNA. DR EMBL; AB014558; BAA31633.1; -; mRNA. DR CCDS; CCDS44576.1; -. [Q49AN0-2] DR RefSeq; NP_001120929.1; NM_001127457.2. [Q49AN0-2] DR RefSeq; NP_066940.2; NM_021117.3. DR UniGene; Hs.532491; -. DR DisProt; DP00473; -. DR ProteinModelPortal; Q49AN0; -. DR SMR; Q49AN0; 22-513. DR BioGrid; 107798; 35. DR DIP; DIP-47396N; -. DR IntAct; Q49AN0; 7. DR STRING; 9606.ENSP00000406751; -. DR BioMuta; CRY2; -. DR DMDM; 118572252; -. DR MaxQB; Q49AN0; -. DR PaxDb; Q49AN0; -. DR PRIDE; Q49AN0; -. DR DNASU; 1408; -. DR Ensembl; ENST00000417225; ENSP00000397419; ENSG00000121671. [Q49AN0-2] DR Ensembl; ENST00000616080; ENSP00000484684; ENSG00000121671. [Q49AN0-1] DR GeneID; 1408; -. DR KEGG; hsa:1408; -. DR UCSC; uc009ykw.3; human. [Q49AN0-2] DR UCSC; uc010rgn.2; human. DR UCSC; uc010rgo.2; human. [Q49AN0-1] DR CTD; 1408; -. DR GeneCards; CRY2; -. DR H-InvDB; HIX0201587; -. DR HGNC; HGNC:2385; CRY2. DR HPA; HPA037577; -. DR MIM; 603732; gene. DR neXtProt; NX_Q49AN0; -. DR PharmGKB; PA26905; -. DR eggNOG; KOG0133; Eukaryota. DR eggNOG; COG0415; LUCA. DR GeneTree; ENSGT00500000044813; -. DR HOGENOM; HOG000245622; -. DR HOVERGEN; HBG053470; -. DR InParanoid; Q49AN0; -. DR KO; K02295; -. DR OrthoDB; EOG7QG43M; -. DR PhylomeDB; Q49AN0; -. DR Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression. DR Reactome; R-HSA-400253; Circadian Clock. DR ChiTaRS; CRY2; human. DR GenomeRNAi; 1408; -. DR NextBio; 5757; -. DR PRO; PR:Q49AN0; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; Q49AN0; -. DR CleanEx; HS_CRY2; -. DR ExpressionAtlas; Q49AN0; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005576; C:extracellular region; IDA:MGI. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0009882; F:blue light photoreceptor activity; NAS:UniProtKB. DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0071949; F:FAD binding; ISS:UniProtKB. DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0000989; F:transcription factor activity, transcription factor binding; IDA:BHF-UCL. DR GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; ISS:UniProtKB. DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB. DR GO; GO:0009785; P:blue light signaling pathway; NAS:UniProtKB. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB. DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB. DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB. DR GO; GO:0042593; P:glucose homeostasis; ISS:UniProtKB. DR GO; GO:0042754; P:negative regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:2000323; P:negative regulation of glucocorticoid receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0018298; P:protein-chromophore linkage; IEA:UniProtKB-KW. DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:2000118; P:regulation of sodium-dependent phosphate transport; IDA:MGI. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.40.50.620; -; 1. DR InterPro; IPR005101; Cryptochr/Photolyase_FAD-bd. DR InterPro; IPR006050; DNA_photolyase_N. DR InterPro; IPR014729; Rossmann-like_a/b/a_fold. DR Pfam; PF00875; DNA_photolyase; 1. DR Pfam; PF03441; FAD_binding_7; 1. DR SUPFAM; SSF48173; SSF48173; 1. DR SUPFAM; SSF52425; SSF52425; 1. DR PROSITE; PS51645; PHR_CRY_ALPHA_BETA; 1. PE 1: Evidence at protein level; KW Alternative splicing; Biological rhythms; Chromophore; KW Complete proteome; Cytoplasm; FAD; Flavoprotein; Isopeptide bond; KW Nucleotide-binding; Nucleus; Phosphoprotein; Photoreceptor protein; KW Receptor; Reference proteome; Repressor; Sensory transduction; KW Transcription; Transcription regulation; Ubl conjugation. FT CHAIN 1 593 Cryptochrome-2. FT /FTId=PRO_0000261148. FT DOMAIN 22 151 Photolyase/cryptochrome alpha/beta. FT NP_BIND 406 408 FAD. {ECO:0000250}. FT REGION 390 489 Required for inhibition of CLOCK-ARNTL- FT mediated transcription. {ECO:0000250}. FT BINDING 271 271 FAD; via amide nitrogen. {ECO:0000250}. FT BINDING 308 308 FAD. {ECO:0000250}. FT BINDING 374 374 FAD. {ECO:0000250}. FT MOD_RES 90 90 Phosphoserine. FT {ECO:0000250|UniProtKB:P97784}. FT MOD_RES 266 266 Phosphoserine; by MAPK. FT {ECO:0000250|UniProtKB:Q9R194}. FT MOD_RES 299 299 Phosphoserine. FT {ECO:0000250|UniProtKB:P97784}. FT MOD_RES 554 554 Phosphoserine; by GSK3-beta. FT {ECO:0000250|UniProtKB:Q9R194}. FT MOD_RES 558 558 Phosphoserine; by DYRK1A and MAPK. FT {ECO:0000250|UniProtKB:Q9R194}. FT CROSSLNK 126 126 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000250|UniProtKB:Q9R194}. FT CROSSLNK 242 242 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000250|UniProtKB:Q9R194}. FT CROSSLNK 348 348 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000250|UniProtKB:Q9R194}. FT CROSSLNK 475 475 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000250|UniProtKB:Q9R194}. FT CROSSLNK 504 504 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000250|UniProtKB:Q9R194}. FT VAR_SEQ 1 72 MAATVATAAAVAPAPAPGTDSASSVHWFRKGLRLHDNPALL FT AAVRGARCVRCVYILDPWFAASSSVGINRWR -> MPAPPG FT RTHTW (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_038970. FT CONFLICT 422 422 S -> G (in Ref. 4; AAH35161). FT {ECO:0000305}. SQ SEQUENCE 593 AA; 66947 MW; BF380424092BEBFB CRC64; MAATVATAAA VAPAPAPGTD SASSVHWFRK GLRLHDNPAL LAAVRGARCV RCVYILDPWF AASSSVGINR WRFLLQSLED LDTSLRKLNS RLFVVRGQPA DVFPRLFKEW GVTRLTFEYD SEPFGKERDA AIMKMAKEAG VEVVTENSHT LYDLDRIIEL NGQKPPLTYK RFQAIISRME LPKKPVGLVT SQQMESCRAE IQENHDETYG VPSLEELGFP TEGLGPAVWQ GGETEALARL DKHLERKAWV ANYERPRMNA NSLLASPTGL SPYLRFGCLS CRLFYYRLWD LYKKVKRNST PPLSLFGQLL WREFFYTAAT NNPRFDRMEG NPICIQIPWD RNPEALAKWA EGKTGFPWID AIMTQLRQEG WIHHLARHAV ACFLTRGDLW VSWESGVRVF DELLLDADFS VNAGSWMWLS CSAFFQQFFH CYCPVGFGRR TDPSGDYIRR YLPKLKAFPS RYIYEPWNAP ESIQKAAKCI IGVDYPRPIV NHAETSRLNI ERMKQIYQQL SRYRGLCLLA SVPSCVEDLS HPVAEPSSSQ AGSMSSAGPR PLPSGPASPK RKLEAAEEPP GEELSKRARV AELPTPELPS KDA // ID CTBP1_HUMAN Reviewed; 440 AA. AC Q13363; Q4W5N3; Q7Z2Q5; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1999, sequence version 2. DT 11-NOV-2015, entry version 173. DE RecName: Full=C-terminal-binding protein 1; DE Short=CtBP1; DE EC=1.1.1.-; GN Name=CTBP1; Synonyms=CTBP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 98-108, RP AND INTERACTION WITH RBBP8 AND ADENOVIRUS E1A. RC TISSUE=B-cell, and Cervix carcinoma; RX PubMed=7479821; DOI=10.1073/pnas.92.23.10467; RA Schaeper U., Boyd J.M., Verma S., Uhlmann E., Subramanian T., RA Chinnadurai G.; RT "Molecular cloning and characterization of a cellular phosphoprotein RT that interacts with a conserved C-terminal domain of adenovirus E1A RT involved in negative modulation of oncogenic transformation."; RL Proc. Natl. Acad. Sci. U.S.A. 92:10467-10471(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SEQUENCE REVISION, AND RP FUNCTION. RX PubMed=9858600; RA Sewalt R.G.A.B., Gunster M.J., van der Vlag J., Satijn D.P.E., RA Otte A.P.; RT "C-terminal binding protein is a transcriptional repressor that RT interacts with a specific class of vertebrate polycomb proteins."; RL Mol. Cell. Biol. 19:777-787(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP INTERACTION WITH ADENOVIRUS E1A, AND PHOSPHORYLATION. RX PubMed=8440238; RA Boyd J.M., Subramanian T., Schaeper U., la Regina M., Bayley S., RA Chinnadurai G.; RT "A region in the C-terminus of adenovirus 2/5 E1a protein is required RT for association with a cellular phosphoprotein and important for the RT negative modulation of T24-ras mediated transformation, tumorigenesis RT and metastasis."; RL EMBO J. 12:469-478(1993). RN [7] RP INTERACTION WITH MECOM. RX PubMed=11568182; DOI=10.1074/jbc.M106733200; RA Chakraborty S., Senyuk V., Sitailo S., Chi Y., Nucifora G.; RT "Interaction of EVI1 with cAMP-responsive element-binding protein- RT binding protein (CBP) and p300/CBP-associated factor (P/CAF) results RT in reversible acetylation of EVI1 and in co-localization in nuclear RT speckles."; RL J. Biol. Chem. 276:44936-44943(2001). RN [8] RP INTERACTION WITH EBV EBNA6. RX PubMed=11462050; DOI=10.1128/JVI.75.16.7749-7755.2001; RA Touitou R., Hickabottom M., Parker G., Crook T., Allday M.J.; RT "Physical and functional interactions between the corepressor CtBP and RT the Epstein-Barr virus nuclear antigen EBNA3C."; RL J. Virol. 75:7749-7755(2001). RN [9] RP INTERACTION WITH NRIP1. RX PubMed=11509661; DOI=10.1128/MCB.21.18.6181-6188.2001; RA Vo N., Fjeld C., Goodman R.H.; RT "Acetylation of nuclear hormone receptor-interacting protein RIP140 RT regulates binding of the transcriptional corepressor CtBP."; RL Mol. Cell. Biol. 21:6181-6188(2001). RN [10] RP INTERACTION WITH EBV EBNA3. RX PubMed=12372828; DOI=10.1074/jbc.M208116200; RA Hickabottom M., Parker G.A., Freemont P., Crook T., Allday M.J.; RT "Two nonconsensus sites in the Epstein-Barr virus oncoprotein EBNA3A RT cooperate to bind the co-repressor carboxyl-terminal-binding protein RT (CtBP)."; RL J. Biol. Chem. 277:47197-47204(2002). RN [11] RP SUMOYLATION AT LYS-428, AND SUBCELLULAR LOCATION. RX PubMed=12679040; DOI=10.1016/S0092-8674(03)00159-4; RA Kagey M.H., Melhuish T.A., Wotton D.; RT "The polycomb protein Pc2 is a SUMO E3."; RL Cell 113:127-137(2003). RN [12] RP INTERACTION WITH HIPK2, PHOSPHORYLATION AT SER-422, AND MUTAGENESIS OF RP SER-422. RX PubMed=14567915; DOI=10.1016/S0092-8674(03)00802-X; RA Zhang Q., Yoshimatsu Y., Hildebrand J., Frisch S.M., Goodman R.H.; RT "Homeodomain interacting protein kinase 2 promotes apoptosis by RT downregulating the transcriptional corepressor CtBP."; RL Cell 115:177-186(2003). RN [13] RP FUNCTION IN TRANSCRIPTIONAL REPRESSION, AND INTERACTION WITH PNN. RX PubMed=15542832; DOI=10.1128/MCB.24.23.10223-10235.2004; RA Alpatov R., Munguba G.C., Caton P., Joo J.H., Shi Y., Shi Y., RA Hunt M.E., Sugrue S.P.; RT "Nuclear speckle-associated protein Pnn/DRS binds to the RT transcriptional corepressor CtBP and relieves CtBP-mediated repression RT of the E-cadherin gene."; RL Mol. Cell. Biol. 24:10223-10235(2004). RN [14] RP INTERACTION WITH NRIP1. RX PubMed=15060175; DOI=10.1093/nar/gkh524; RA Castet A., Boulahtouf A., Versini G., Bonnet S., Augereau P., RA Vignon F., Khochbin S., Jalaguier S., Cavailles V.; RT "Multiple domains of the receptor-interacting protein 140 contribute RT to transcription inhibition."; RL Nucleic Acids Res. 32:1957-1966(2004). RN [15] RP INTERACTION WITH ZFHX1B. RX PubMed=16061479; DOI=10.1074/jbc.M504477200; RA Long J., Zuo D., Park M.; RT "Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates RT transcriptional repression of E-cadherin."; RL J. Biol. Chem. 280:35477-35489(2005). RN [16] RP INTERACTION WITH MECOM. RX PubMed=15897867; DOI=10.1038/sj.onc.1208754; RA Nitta E., Izutsu K., Yamaguchi Y., Imai Y., Ogawa S., Chiba S., RA Kurokawa M., Hirai H.; RT "Oligomerization of Evi-1 regulated by the PR domain contributes to RT recruitment of corepressor CtBP."; RL Oncogene 24:6165-6173(2005). RN [17] RP INTERACTION WITH FOXP1. RX PubMed=16609867; DOI=10.1007/s00427-006-0073-8; RA Schoen C., Wochnik A., Roessner A., Donow C., Knoechel W.; RT "The FoxP subclass in Xenopus laevis development."; RL Dev. Genes Evol. 216:641-646(2006). RN [18] RP INTERACTION WITH WIZ. RX PubMed=16702210; DOI=10.1074/jbc.M603087200; RA Ueda J., Tachibana M., Ikura T., Shinkai Y.; RT "Zinc finger protein Wiz links G9a/GLP histone methyltransferases to RT the co-repressor molecule CtBP."; RL J. Biol. Chem. 281:20120-20128(2006). RN [19] RP INTERACTION WITH ZNF366. RX PubMed=17085477; DOI=10.1093/nar/gkl875; RA Lopez-Garcia J., Periyasamy M., Thomas R.S., Christian M., Leao M., RA Jat P., Kindle K.B., Heery D.M., Parker M.G., Buluwela L., RA Kamalati T., Ali S.; RT "ZNF366 is an estrogen receptor corepressor that acts through CtBP and RT histone deacetylases."; RL Nucleic Acids Res. 34:6126-6136(2006). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-300, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [21] RP FUNCTION AS COREPRESSOR, INTERACTION WITH BCL6, AND TISSUE RP SPECIFICITY. RX PubMed=18212045; DOI=10.1128/MCB.01400-07; RA Mendez L.M., Polo J.M., Yu J.J., Krupski M., Ding B.B., Melnick A., RA Ye B.H.; RT "CtBP is an essential corepressor for BCL6 autoregulation."; RL Mol. Cell. Biol. 28:2175-2186(2008). RN [22] RP FUNCTION, AND INTERACTION WITH SATB1. RX PubMed=19103759; DOI=10.1128/MCB.00822-08; RA Purbey P.K., Singh S., Notani D., Kumar P.P., Limaye A.S., Galande S.; RT "Acetylation-dependent interaction of SATB1 and CtBP1 mediates RT transcriptional repression by SATB1."; RL Mol. Cell. Biol. 29:1321-1337(2009). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [24] RP INTERACTION WITH HADV5 E1A. RX PubMed=23747199; DOI=10.1016/j.virol.2013.05.018; RA Subramanian T., Zhao L.J., Chinnadurai G.; RT "Interaction of CtBP with adenovirus E1A suppresses immortalization of RT primary epithelial cells and enhances virus replication during RT productive infection."; RL Virology 443:313-320(2013). RN [25] RP INTERACTION WITH FAM195B. RX PubMed=25728771; DOI=10.1016/j.molcel.2015.01.023; RA Ichikawa K., Kubota Y., Nakamura T., Weng J.S., Tomida T., Saito H., RA Takekawa M.; RT "MCRIP1, an ERK substrate, mediates ERK-induced gene silencing during RT epithelial-mesenchymal transition by regulating the co-repressor RT CtBP."; RL Mol. Cell 58:35-46(2015). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [27] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 28-353 IN COMPLEX WITH NAD, RP FUNCTION, COFACTOR, MUTAGENESIS OF CYS-134; ASN-138; ARG-141; RP 141-ARG-ARG-142; LEU-150; ARG-163; ARG-171; GLY-181; GLY-183; ASP-204; RP ARG-266; ASP-290; GLU-295 AND HIS-315, AND DIMERIZATION. RX PubMed=12419229; DOI=10.1016/S1097-2765(02)00650-0; RA Kumar V., Carlson J.E., Ohgi K.A., Edwards T.A., Rose D.W., RA Escalante C.R., Rosenfeld M.G., Aggarwal A.K.; RT "Transcription corepressor CtBP is an NAD(+)-regulated RT dehydrogenase."; RL Mol. Cell 10:857-869(2002). CC -!- FUNCTION: Corepressor targeting diverse transcription regulators CC such as GLIS2 or BCL6. Has dehydrogenase activity. Involved in CC controlling the equilibrium between tubular and stacked structures CC in the Golgi complex. Functions in brown adipose tissue (BAT) CC differentiation. {ECO:0000269|PubMed:12419229, CC ECO:0000269|PubMed:15542832, ECO:0000269|PubMed:18212045, CC ECO:0000269|PubMed:19103759, ECO:0000269|PubMed:9858600}. CC -!- COFACTOR: CC Name=NAD(+); Xref=ChEBI:CHEBI:57540; CC Evidence={ECO:0000269|PubMed:12419229}; CC Note=NAD is required for efficient interaction with E1A. Cofactor CC binding induces a conformation change. CC {ECO:0000269|PubMed:12419229}; CC -!- SUBUNIT: Homo- or heterodimer. Heterodimer with CTBP2. Interacts CC with PRDM16; the interaction represses white adipose tissue (WAT)- CC specific genes expression. Interacts with GLIS2, FOXP2, HDAC4, CC HDAC5, HDAC9 and ZNF217. Interacts with adenovirus E1A protein CC (via its C-terminus); the interaction disrupts the interaction of CC CTBP1 with RBBP8. Interacts with Epstein-Barr virus EBNA3 and CC EBNA6. Interacts with ELK3 (via its PXDLS motif). Interacts with CC RBBP8 (via its PXDLS motif); the interaction is disrupted by CC binding to adenovirus E1A. Interacts with FOXP1, HIPK2, PNN, CC NRIP1, MECOM, ZNF366, ZFHX1B and WIZ. Interaction with SATB1 (non- CC acetylated form); the interaction stabilizes its attachment to DNA CC and promotes transcription repression. Interacts with BCL6; the CC interaction is required for BCL6 transcriptional autoinhibition CC and inhibition of some BCL6 target genes. Interacts with IKZF4 (By CC similarity). Interacts with human adenovirus 5 E1A protein; this CC interaction seems to potentiate viral replication CC (PubMed:23747199). Interacts with FAM195B (unphosphorylated form, CC via the PXDLS motif); competitively inhibiting CTBP-ZEB1 CC interaction (PubMed:25728771). {ECO:0000250|UniProtKB:O88712, CC ECO:0000269|PubMed:11462050, ECO:0000269|PubMed:11509661, CC ECO:0000269|PubMed:11568182, ECO:0000269|PubMed:12372828, CC ECO:0000269|PubMed:12419229, ECO:0000269|PubMed:14567915, CC ECO:0000269|PubMed:15060175, ECO:0000269|PubMed:15542832, CC ECO:0000269|PubMed:15897867, ECO:0000269|PubMed:16061479, CC ECO:0000269|PubMed:16609867, ECO:0000269|PubMed:16702210, CC ECO:0000269|PubMed:17085477, ECO:0000269|PubMed:18212045, CC ECO:0000269|PubMed:19103759, ECO:0000269|PubMed:23747199, CC ECO:0000269|PubMed:25728771, ECO:0000269|PubMed:7479821, CC ECO:0000269|PubMed:8440238}. CC -!- INTERACTION: CC Q9H6U6:BCAS3; NbExp=3; IntAct=EBI-10171858, EBI-6083685; CC Q76N32:CEP68; NbExp=3; IntAct=EBI-10171858, EBI-9051024; CC Q49AN0:CRY2; NbExp=3; IntAct=EBI-10171858, EBI-2212355; CC P56545:CTBP2; NbExp=3; IntAct=EBI-10171858, EBI-741533; CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-10171858, EBI-10171902; CC I6L9A0:DMRTB1; NbExp=3; IntAct=EBI-10171858, EBI-10178554; CC O15409:FOXP2; NbExp=3; IntAct=EBI-10171858, EBI-983612; CC Q9BXL5:HEMGN; NbExp=2; IntAct=EBI-908846, EBI-3916399; CC Q14526:HIC1; NbExp=4; IntAct=EBI-908846, EBI-2507362; CC P09067:HOXB5; NbExp=3; IntAct=EBI-10171858, EBI-3893317; CC Q13422:IKZF1; NbExp=3; IntAct=EBI-10171858, EBI-745305; CC Q9Y4X4:KLF12; NbExp=3; IntAct=EBI-10171858, EBI-750750; CC O43474:KLF4; NbExp=4; IntAct=EBI-908846, EBI-7232405; CC P45984:MAPK9; NbExp=3; IntAct=EBI-10171858, EBI-713568; CC O94818-2:NOL4; NbExp=3; IntAct=EBI-10171858, EBI-10190763; CC Q96MY1:NOL4L; NbExp=3; IntAct=EBI-10171858, EBI-6660790; CC Q9NQ66:PLCB1; NbExp=3; IntAct=EBI-10171858, EBI-3396023; CC Q13131:PRKAA1; NbExp=3; IntAct=EBI-10171858, EBI-1181405; CC Q15583:TGIF1; NbExp=3; IntAct=EBI-10171858, EBI-714215; CC Q96EK4:THAP11; NbExp=2; IntAct=EBI-908846, EBI-1790529; CC A1L0U7:TSHZ3; NbExp=3; IntAct=EBI-10171858, EBI-10171826; CC A2APF7:Zbp1 (xeno); NbExp=2; IntAct=EBI-908846, EBI-6115394; CC Q8N895:ZNF366; NbExp=5; IntAct=EBI-908846, EBI-2813661; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12679040}. CC Nucleus {ECO:0000269|PubMed:12679040}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q13363-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13363-2; Sequence=VSP_043305; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed in germinal center B-cells. CC {ECO:0000269|PubMed:18212045}. CC -!- PTM: The level of phosphorylation appears to be regulated during CC the cell cycle. Phosphorylation by HIPK2 on Ser-422 induces CC proteasomal degradation. {ECO:0000269|PubMed:14567915, CC ECO:0000269|PubMed:8440238}. CC -!- PTM: ADP-ribosylated; when cells are exposed to brefeldin A. CC {ECO:0000250}. CC -!- PTM: Sumoylation on Lys-428 is promoted by the E3 SUMO-protein CC ligase CBX4. {ECO:0000269|PubMed:12679040}. CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid CC dehydrogenase family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U37408; AAC62822.1; -; mRNA. DR EMBL; AF091555; AAD14597.1; -; mRNA. DR EMBL; AC092535; AAY40989.1; -; Genomic_DNA. DR EMBL; CH471131; EAW82599.1; -; Genomic_DNA. DR EMBL; CH471131; EAW82600.1; -; Genomic_DNA. DR EMBL; CH471131; EAW82601.1; -; Genomic_DNA. DR EMBL; BC011655; AAH11655.1; -; mRNA. DR EMBL; BC053320; AAH53320.1; -; mRNA. DR CCDS; CCDS3348.1; -. [Q13363-1] DR CCDS; CCDS43203.1; -. [Q13363-2] DR RefSeq; NP_001012632.1; NM_001012614.1. [Q13363-2] DR RefSeq; NP_001319.1; NM_001328.2. [Q13363-1] DR UniGene; Hs.208597; -. DR PDB; 1MX3; X-ray; 1.95 A; A=28-353. DR PDB; 4LCE; X-ray; 2.38 A; A=28-353. DR PDB; 4U6Q; X-ray; 2.30 A; A=28-353. DR PDB; 4U6S; X-ray; 2.10 A; A=28-353. DR PDBsum; 1MX3; -. DR PDBsum; 4LCE; -. DR PDBsum; 4U6Q; -. DR PDBsum; 4U6S; -. DR ProteinModelPortal; Q13363; -. DR SMR; Q13363; 28-352. DR BioGrid; 107869; 137. DR DIP; DIP-24245N; -. DR IntAct; Q13363; 40. DR MINT; MINT-94454; -. DR STRING; 9606.ENSP00000290921; -. DR PhosphoSite; Q13363; -. DR BioMuta; CTBP1; -. DR DMDM; 6014741; -. DR MaxQB; Q13363; -. DR PaxDb; Q13363; -. DR PRIDE; Q13363; -. DR DNASU; 1487; -. DR Ensembl; ENST00000290921; ENSP00000290921; ENSG00000159692. [Q13363-1] DR Ensembl; ENST00000382952; ENSP00000372411; ENSG00000159692. [Q13363-2] DR GeneID; 1487; -. DR KEGG; hsa:1487; -. DR UCSC; uc003gcu.1; human. [Q13363-2] DR UCSC; uc003gcv.1; human. [Q13363-1] DR CTD; 1487; -. DR GeneCards; CTBP1; -. DR HGNC; HGNC:2494; CTBP1. DR HPA; CAB004217; -. DR HPA; HPA018987; -. DR HPA; HPA044971; -. DR MIM; 602618; gene. DR neXtProt; NX_Q13363; -. DR PharmGKB; PA26995; -. DR eggNOG; KOG0067; Eukaryota. DR eggNOG; COG0111; LUCA. DR GeneTree; ENSGT00530000063021; -. DR HOGENOM; HOG000136701; -. DR HOVERGEN; HBG001898; -. DR InParanoid; Q13363; -. DR KO; K04496; -. DR OMA; DRDHPSD; -. DR OrthoDB; EOG761BT9; -. DR PhylomeDB; Q13363; -. DR TreeFam; TF313593; -. DR Reactome; R-HSA-3769402; deactivation of the beta-catenin transactivating complex. DR Reactome; R-HSA-4641265; repression of WNT target genes. DR Reactome; R-HSA-5339700; TCF7L2 mutants don't bind CTBP. DR SignaLink; Q13363; -. DR ChiTaRS; CTBP1; human. DR EvolutionaryTrace; Q13363; -. DR GeneWiki; CTBP1; -. DR GenomeRNAi; 1487; -. DR NextBio; 6105; -. DR PRO; PR:Q13363; -. DR Proteomes; UP000005640; Chromosome 4. DR Bgee; Q13363; -. DR CleanEx; HS_CTBP1; -. DR ExpressionAtlas; Q13363; baseline and differential. DR Genevisible; Q13363; HS. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005667; C:transcription factor complex; IEA:Ensembl. DR GO; GO:0017053; C:transcriptional repressor complex; ISS:UniProtKB. DR GO; GO:0051287; F:NAD binding; ISS:UniProtKB. DR GO; GO:0070404; F:NADH binding; IBA:GO_Central. DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central. DR GO; GO:0008022; F:protein C-terminus binding; TAS:ProtInc. DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central. DR GO; GO:0070491; F:repressing transcription factor binding; IPI:BHF-UCL. DR GO; GO:0001106; F:RNA polymerase II transcription corepressor activity; IDA:BHF-UCL. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc. DR GO; GO:0035067; P:negative regulation of histone acetylation; IMP:BHF-UCL. DR GO; GO:0090241; P:negative regulation of histone H4 acetylation; IMP:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL. DR GO; GO:1903758; P:negative regulation of transcription from RNA polymerase II promoter by histone modification; IMP:BHF-UCL. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB. DR GO; GO:0031065; P:positive regulation of histone deacetylation; IMP:BHF-UCL. DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc. DR GO; GO:0051726; P:regulation of cell cycle; IMP:BHF-UCL. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0019079; P:viral genome replication; TAS:ProtInc. DR GO; GO:0050872; P:white fat cell differentiation; ISS:UniProtKB. DR InterPro; IPR006139; D-isomer_2_OHA_DH_cat_dom. DR InterPro; IPR029753; D-isomer_DH_CS. DR InterPro; IPR029752; D-isomer_DH_CS1. DR InterPro; IPR006140; D-isomer_DH_NAD-bd. DR InterPro; IPR016040; NAD(P)-bd_dom. DR Pfam; PF00389; 2-Hacid_dh; 1. DR Pfam; PF02826; 2-Hacid_dh_C; 1. DR SUPFAM; SSF51735; SSF51735; 1. DR PROSITE; PS00065; D_2_HYDROXYACID_DH_1; 1. DR PROSITE; PS00671; D_2_HYDROXYACID_DH_3; 1. PE 1: Evidence at protein level; KW 3D-structure; ADP-ribosylation; Alternative splicing; KW Complete proteome; Cytoplasm; Differentiation; KW Direct protein sequencing; Host-virus interaction; Isopeptide bond; KW NAD; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome; KW Repressor; Transcription; Transcription regulation; Ubl conjugation. FT CHAIN 1 440 C-terminal-binding protein 1. FT /FTId=PRO_0000076041. FT NP_BIND 180 185 NAD. {ECO:0000250}. FT NP_BIND 237 243 NAD. {ECO:0000250}. FT NP_BIND 264 266 NAD. {ECO:0000250}. FT NP_BIND 315 318 NAD. {ECO:0000250}. FT REGION 1 70 Interaction with GLIS2 1. {ECO:0000250}. FT REGION 288 360 Interaction with GLIS2 2. {ECO:0000250}. FT ACT_SITE 266 266 {ECO:0000250}. FT ACT_SITE 295 295 {ECO:0000250}. FT ACT_SITE 315 315 Proton donor. {ECO:0000250}. FT BINDING 100 100 NAD. {ECO:0000250}. FT BINDING 204 204 NAD. {ECO:0000250}. FT BINDING 290 290 NAD. {ECO:0000250}. FT MOD_RES 300 300 Phosphoserine. FT {ECO:0000244|PubMed:17525332}. FT MOD_RES 422 422 Phosphoserine; by HIPK2. FT {ECO:0000269|PubMed:14567915}. FT CROSSLNK 428 428 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT VAR_SEQ 1 13 MGSSHLLNKGLPL -> MS (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_043305. FT MUTAGEN 134 134 C->A: Strongly reduces E1A binding; when FT associated with A-138; A-141 and A-150. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 138 138 N->A: Strongly reduces E1A binding; when FT associated with A-134; A-141 and A-150. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 141 142 RR->AA: Strongly reduces E1A binding; FT when associated with A-163 and A-171. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 141 141 R->A: Strongly reduces E1A binding; when FT associated with A-134; A-138 and A-150. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 150 150 L->A: Strongly reduces E1A binding; when FT associated with A-134; A-138 and A-141. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 163 163 R->A: Strongly reduces E1A binding; when FT associated with A-141; A-142 and A-171. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 171 171 R->A: Strongly reduces E1A binding; when FT associated with A-141; A-142 and A-163. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 181 181 G->V: Strongly reduces E1A binding; when FT associated with V-183 and A-204. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 183 183 G->V: Strongly reduces E1A binding; when FT associated with V-181 and A-204. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 204 204 D->A: Strongly reduces E1A binding; when FT associated with V-181 and V-183. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 266 266 R->A: Strongly reduces E1A binding; when FT associated with A-290; A-295 and A-315. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 290 290 D->A: Strongly reduces E1A binding; when FT associated with A-266; A-295 and A-315. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 295 295 E->A: Strongly reduces E1A binding; when FT associated with A-266; A-290 and A-315. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 315 315 H->A: Strongly reduces E1A binding; when FT associated with A-266; A-290 and A-295. FT {ECO:0000269|PubMed:12419229}. FT MUTAGEN 422 422 S->A: Abolishes phosphorylation by HIPK2 FT and prevents UV-induced clearance. FT {ECO:0000269|PubMed:14567915}. FT STRAND 29 34 {ECO:0000244|PDB:1MX3}. FT TURN 39 41 {ECO:0000244|PDB:1MX3}. FT HELIX 42 45 {ECO:0000244|PDB:1MX3}. FT TURN 46 48 {ECO:0000244|PDB:1MX3}. FT STRAND 50 53 {ECO:0000244|PDB:1MX3}. FT HELIX 59 61 {ECO:0000244|PDB:1MX3}. FT HELIX 64 69 {ECO:0000244|PDB:1MX3}. FT STRAND 70 75 {ECO:0000244|PDB:1MX3}. FT STRAND 77 79 {ECO:0000244|PDB:1MX3}. FT HELIX 83 86 {ECO:0000244|PDB:1MX3}. FT STRAND 94 100 {ECO:0000244|PDB:1MX3}. FT HELIX 107 112 {ECO:0000244|PDB:1MX3}. FT STRAND 116 118 {ECO:0000244|PDB:1MX3}. FT TURN 121 124 {ECO:0000244|PDB:4U6S}. FT HELIX 125 141 {ECO:0000244|PDB:1MX3}. FT HELIX 143 151 {ECO:0000244|PDB:1MX3}. FT HELIX 159 165 {ECO:0000244|PDB:1MX3}. FT TURN 166 168 {ECO:0000244|PDB:1MX3}. FT STRAND 176 180 {ECO:0000244|PDB:1MX3}. FT HELIX 184 194 {ECO:0000244|PDB:1MX3}. FT TURN 195 197 {ECO:0000244|PDB:1MX3}. FT STRAND 199 203 {ECO:0000244|PDB:1MX3}. FT HELIX 211 215 {ECO:0000244|PDB:1MX3}. FT HELIX 223 229 {ECO:0000244|PDB:1MX3}. FT STRAND 231 235 {ECO:0000244|PDB:1MX3}. FT STRAND 246 248 {ECO:0000244|PDB:1MX3}. FT HELIX 249 252 {ECO:0000244|PDB:1MX3}. FT STRAND 259 263 {ECO:0000244|PDB:1MX3}. FT HELIX 267 269 {ECO:0000244|PDB:4U6S}. FT HELIX 272 280 {ECO:0000244|PDB:1MX3}. FT STRAND 283 290 {ECO:0000244|PDB:1MX3}. FT STRAND 293 296 {ECO:0000244|PDB:1MX3}. FT TURN 303 306 {ECO:0000244|PDB:1MX3}. FT STRAND 308 312 {ECO:0000244|PDB:1MX3}. FT HELIX 321 340 {ECO:0000244|PDB:1MX3}. FT TURN 343 346 {ECO:0000244|PDB:1MX3}. FT STRAND 348 350 {ECO:0000244|PDB:1MX3}. SQ SEQUENCE 440 AA; 47535 MW; F071DD30B385603F CRC64; MGSSHLLNKG LPLGVRPPIM NGPLHPRPLV ALLDGRDCTV EMPILKDVAT VAFCDAQSTQ EIHEKVLNEA VGALMYHTIT LTREDLEKFK ALRIIVRIGS GFDNIDIKSA GDLGIAVCNV PAASVEETAD STLCHILNLY RRATWLHQAL REGTRVQSVE QIREVASGAA RIRGETLGII GLGRVGQAVA LRAKAFGFNV LFYDPYLSDG VERALGLQRV STLQDLLFHS DCVTLHCGLN EHNHHLINDF TVKQMRQGAF LVNTARGGLV DEKALAQALK EGRIRGAALD VHESEPFSFS QGPLKDAPNL ICTPHAAWYS EQASIEMREE AAREIRRAIT GRIPDSLKNC VNKDHLTAAT HWASMDPAVV HPELNGAAYR YPPGVVGVAP TGIPAAVEGI VPSAMSLSHG LPPVAHPPHA PSPGQTVKPE ADRDHASDQL // ID CTBP2_HUMAN Reviewed; 445 AA. AC P56545; A8K2X5; D3DRF5; O43449; Q5SQP7; Q69YI3; Q86SV0; Q9H2T8; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1998, sequence version 1. DT 11-NOV-2015, entry version 156. DE RecName: Full=C-terminal-binding protein 2; DE Short=CtBP2; GN Name=CTBP2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9479502; DOI=10.1006/geno.1997.5115; RA Katsanis N., Fisher E.M.C.; RT "A novel C-terminal binding protein (CTBP2) is closely related to RT CTBP1, an adenovirus E1A-binding protein, and maps to human chromosome RT 21q21.3."; RL Genomics 47:294-299(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=11163272; DOI=10.1016/S0896-6273(00)00159-8; RA Schmitz F., Koenigstorfer A., Suedhof T.C.; RT "RIBEYE, a component of synaptic ribbons: a protein's journey through RT evolution provides insight into synaptic ribbon function."; RL Neuron 28:857-872(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Umbilical cord blood; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Melanoma; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon, Kidney, Pancreas, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP PROTEIN SEQUENCE OF 263-272, AND PHOSPHORYLATION. RC TISSUE=B-cell, and Cervix carcinoma; RX PubMed=7479821; DOI=10.1073/pnas.92.23.10467; RA Schaeper U., Boyd J.M., Verma S., Uhlmann E., Subramanian T., RA Chinnadurai G.; RT "Molecular cloning and characterization of a cellular phosphoprotein RT that interacts with a conserved C-terminal domain of adenovirus E1A RT involved in negative modulation of oncogenic transformation."; RL Proc. Natl. Acad. Sci. U.S.A. 92:10467-10471(1995). RN [11] RP INTERACTION WITH PNN. RX PubMed=15542832; DOI=10.1128/MCB.24.23.10223-10235.2004; RA Alpatov R., Munguba G.C., Caton P., Joo J.H., Shi Y., Shi Y., RA Hunt M.E., Sugrue S.P.; RT "Nuclear speckle-associated protein Pnn/DRS binds to the RT transcriptional corepressor CtBP and relieves CtBP-mediated repression RT of the E-cadherin gene."; RL Mol. Cell. Biol. 24:10223-10235(2004). RN [12] RP INTERACTION WITH NRIP1. RX PubMed=15060175; DOI=10.1093/nar/gkh524; RA Castet A., Boulahtouf A., Versini G., Bonnet S., Augereau P., RA Vignon F., Khochbin S., Jalaguier S., Cavailles V.; RT "Multiple domains of the receptor-interacting protein 140 contribute RT to transcription inhibition."; RL Nucleic Acids Res. 32:1957-1966(2004). RN [13] RP INTERACTION WITH WIZ. RX PubMed=16702210; DOI=10.1074/jbc.M603087200; RA Ueda J., Tachibana M., Ikura T., Shinkai Y.; RT "Zinc finger protein Wiz links G9a/GLP histone methyltransferases to RT the co-repressor molecule CtBP."; RL J. Biol. Chem. 281:20120-20128(2006). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [16] RP INTERACTION WITH HADV5 E1A. RX PubMed=23747199; DOI=10.1016/j.virol.2013.05.018; RA Subramanian T., Zhao L.J., Chinnadurai G.; RT "Interaction of CtBP with adenovirus E1A suppresses immortalization of RT primary epithelial cells and enhances virus replication during RT productive infection."; RL Virology 443:313-320(2013). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-428, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [18] RP INTERACTION WITH FAM195B. RX PubMed=25728771; DOI=10.1016/j.molcel.2015.01.023; RA Ichikawa K., Kubota Y., Nakamura T., Weng J.S., Tomida T., Saito H., RA Takekawa M.; RT "MCRIP1, an ERK substrate, mediates ERK-induced gene silencing during RT epithelial-mesenchymal transition by regulating the co-repressor RT CtBP."; RL Mol. Cell 58:35-46(2015). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 31-364 IN COMPLEX WITH NAD. RG Structural genomics consortium (SGC); RT "Crystal structure of human CTBP2 dehydrogenase complexed with RT NAD(H)."; RL Submitted (FEB-2009) to the PDB data bank. CC -!- FUNCTION: Corepressor targeting diverse transcription regulators. CC Functions in brown adipose tissue (BAT) differentiation (By CC similarity). {ECO:0000250}. CC -!- FUNCTION: Isoform 2 probably acts as a scaffold for specialized CC synapses. CC -!- SUBUNIT: Interacts with the C-terminus of adenovirus E1A protein. CC Can form homodimers or heterodimers of CTBP1 and CTBP2. Interacts CC with HIPK2 and ZNF217. Interacts with PRDM16; represses white CC adipose tissue (WAT)-specific genes expression (By similarity). CC Interacts with PNN, NRIP1 and WIZ. Interacts with human adenovirus CC 5 E1A protein; this interaction seems to potentiate viral CC replication (PubMed:23747199). Interacts with FAM195B CC (PubMed:25728771). {ECO:0000250, ECO:0000269|PubMed:15060175, CC ECO:0000269|PubMed:15542832, ECO:0000269|PubMed:16702210, CC ECO:0000269|PubMed:23747199, ECO:0000269|PubMed:25728771, CC ECO:0000269|Ref.19}. CC -!- INTERACTION: CC P20749:BCL3; NbExp=2; IntAct=EBI-741533, EBI-958997; CC P51946:CCNH; NbExp=5; IntAct=EBI-741533, EBI-741406; CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-741533, EBI-10171858; CC O15409:FOXP2; NbExp=3; IntAct=EBI-741533, EBI-983612; CC Q8IVP5:FUNDC1; NbExp=3; IntAct=EBI-741533, EBI-3059266; CC Q14526:HIC1; NbExp=2; IntAct=EBI-741533, EBI-2507362; CC Q13422:IKZF1; NbExp=5; IntAct=EBI-741533, EBI-745305; CC Q9UKS7:IKZF2; NbExp=3; IntAct=EBI-741533, EBI-3893057; CC Q96JN0:LCOR; NbExp=3; IntAct=EBI-741533, EBI-8833163; CC O94818-2:NOL4; NbExp=3; IntAct=EBI-741533, EBI-10190763; CC Q96MY1:NOL4L; NbExp=3; IntAct=EBI-741533, EBI-6660790; CC Q9NQ66:PLCB1; NbExp=3; IntAct=EBI-741533, EBI-3396023; CC O75807:PPP1R15A; NbExp=2; IntAct=EBI-741533, EBI-714746; CC Q92786:PROX1; NbExp=2; IntAct=EBI-741533, EBI-3912635; CC Q9Y5P3:RAI2; NbExp=4; IntAct=EBI-741533, EBI-746228; CC Q9UN79:SOX13; NbExp=2; IntAct=EBI-741533, EBI-3928516; CC Q15583:TGIF1; NbExp=5; IntAct=EBI-741533, EBI-714215; CC A2APF7:Zbp1 (xeno); NbExp=2; IntAct=EBI-741533, EBI-6115394; CC Q32MQ0:ZNF750; NbExp=3; IntAct=EBI-741533, EBI-10240029; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Cell junction, CC synapse {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P56545-1; Sequence=Displayed; CC Name=2; Synonyms=Ribeye; CC IsoId=P56545-2; Sequence=VSP_027615; CC Note=Ref.2 (AAG45951) sequence is in conflict in positions: CC 455:Y->H, 539:Q->E. {ECO:0000305}; CC -!- TISSUE SPECIFICITY: Ubiquitous. Highest levels in heart, skeletal CC muscle, and pancreas. CC -!- SIMILARITY: Belongs to the D-isomer specific 2-hydroxyacid CC dehydrogenase family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF016507; AAC39603.1; -; mRNA. DR EMBL; AF222711; AAG45951.1; -; mRNA. DR EMBL; BT007012; AAP35658.1; -; mRNA. DR EMBL; AK290390; BAF83079.1; -; mRNA. DR EMBL; AL833398; CAH10590.1; -; mRNA. DR EMBL; AL596261; CAH72472.1; -; Genomic_DNA. DR EMBL; AL731571; CAH72472.1; JOINED; Genomic_DNA. DR EMBL; AL731571; CAI16100.1; -; Genomic_DNA. DR EMBL; AL596261; CAI16100.1; JOINED; Genomic_DNA. DR EMBL; AL731571; CAI16102.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49247.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49250.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49249.1; -; Genomic_DNA. DR EMBL; BC002486; AAH02486.1; -; mRNA. DR EMBL; BC047018; AAH47018.1; -; mRNA. DR EMBL; BC052276; AAH52276.1; -; mRNA. DR EMBL; BC072020; AAH72020.1; -; mRNA. DR CCDS; CCDS7643.1; -. [P56545-1] DR CCDS; CCDS7644.1; -. [P56545-2] DR RefSeq; NP_001077383.1; NM_001083914.1. [P56545-1] DR RefSeq; NP_001277143.1; NM_001290214.1. [P56545-1] DR RefSeq; NP_001277144.1; NM_001290215.1. [P56545-1] DR RefSeq; NP_001320.1; NM_001329.2. [P56545-1] DR RefSeq; NP_073713.2; NM_022802.2. [P56545-2] DR RefSeq; XP_005269618.1; XM_005269561.2. [P56545-1] DR RefSeq; XP_005269621.1; XM_005269564.2. [P56545-1] DR RefSeq; XP_005269622.1; XM_005269565.2. [P56545-1] DR RefSeq; XP_005269624.1; XM_005269567.2. [P56545-1] DR RefSeq; XP_005269625.1; XM_005269568.3. [P56545-1] DR RefSeq; XP_005269626.1; XM_005269569.2. [P56545-1] DR RefSeq; XP_005269627.1; XM_005269570.2. [P56545-1] DR RefSeq; XP_005269628.1; XM_005269571.2. [P56545-1] DR RefSeq; XP_005269629.1; XM_005269572.3. [P56545-1] DR RefSeq; XP_006717704.1; XM_006717641.2. [P56545-1] DR RefSeq; XP_006717705.1; XM_006717642.2. [P56545-1] DR RefSeq; XP_006717706.1; XM_006717643.2. [P56545-1] DR RefSeq; XP_011537652.1; XM_011539350.1. [P56545-1] DR RefSeq; XP_011537653.1; XM_011539351.1. [P56545-1] DR RefSeq; XP_011537654.1; XM_011539352.1. [P56545-1] DR RefSeq; XP_011537655.1; XM_011539353.1. [P56545-1] DR RefSeq; XP_011537656.1; XM_011539354.1. [P56545-1] DR RefSeq; XP_011537657.1; XM_011539355.1. [P56545-1] DR RefSeq; XP_011537658.1; XM_011539356.1. [P56545-1] DR UniGene; Hs.501345; -. DR PDB; 2OME; X-ray; 2.80 A; A/B/C/D/E/F/G/H=31-364. DR PDB; 4LCJ; X-ray; 2.86 A; A/B/C/D/E/F/G/H=31-362. DR PDBsum; 2OME; -. DR PDBsum; 4LCJ; -. DR ProteinModelPortal; P56545; -. DR SMR; P56545; 33-362. DR BioGrid; 107870; 89. DR IntAct; P56545; 44. DR MINT; MINT-1188878; -. DR STRING; 9606.ENSP00000311825; -. DR BioMuta; CTBP2; -. DR DMDM; 3182976; -. DR MaxQB; P56545; -. DR PaxDb; P56545; -. DR PRIDE; P56545; -. DR DNASU; 1488; -. DR Ensembl; ENST00000309035; ENSP00000311825; ENSG00000175029. [P56545-2] DR Ensembl; ENST00000337195; ENSP00000338615; ENSG00000175029. [P56545-1] DR Ensembl; ENST00000411419; ENSP00000410474; ENSG00000175029. [P56545-1] DR Ensembl; ENST00000494626; ENSP00000436285; ENSG00000175029. [P56545-1] DR Ensembl; ENST00000531469; ENSP00000434630; ENSG00000175029. [P56545-1] DR GeneID; 1488; -. DR KEGG; hsa:1488; -. DR UCSC; uc001lie.4; human. [P56545-2] DR UCSC; uc001lif.4; human. [P56545-1] DR CTD; 1488; -. DR GeneCards; CTBP2; -. DR HGNC; HGNC:2495; CTBP2. DR HPA; CAB031916; -. DR HPA; HPA023559; -. DR HPA; HPA023564; -. DR HPA; HPA044971; -. DR MIM; 602619; gene. DR neXtProt; NX_P56545; -. DR PharmGKB; PA26996; -. DR eggNOG; KOG0067; Eukaryota. DR eggNOG; COG0111; LUCA. DR GeneTree; ENSGT00530000063021; -. DR HOVERGEN; HBG001898; -. DR InParanoid; P56545; -. DR KO; K04496; -. DR OrthoDB; EOG761BT9; -. DR PhylomeDB; P56545; -. DR TreeFam; TF313593; -. DR Reactome; R-HSA-4641265; repression of WNT target genes. DR Reactome; R-HSA-5339700; TCF7L2 mutants don't bind CTBP. DR SignaLink; P56545; -. DR ChiTaRS; CTBP2; human. DR EvolutionaryTrace; P56545; -. DR GeneWiki; CTBP2; -. DR GenomeRNAi; 1488; -. DR NextBio; 6111; -. DR PRO; PR:P56545; -. DR Proteomes; UP000005640; Chromosome 10. DR Bgee; P56545; -. DR CleanEx; HS_CTBP2; -. DR ExpressionAtlas; P56545; baseline and differential. DR Genevisible; P56545; HS. DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0097470; C:ribbon synapse; IEA:Ensembl. DR GO; GO:0017053; C:transcriptional repressor complex; ISS:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0070404; F:NADH binding; IBA:GO_Central. DR GO; GO:0016616; F:oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor; IBA:GO_Central. DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central. DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl. DR GO; GO:0003714; F:transcription corepressor activity; IBA:GO_Central. DR GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IBA:GO_Central. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB. DR GO; GO:0035563; P:positive regulation of chromatin binding; IEA:Ensembl. DR GO; GO:0048386; P:positive regulation of retinoic acid receptor signaling pathway; IMP:MGI. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:MGI. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0019079; P:viral genome replication; TAS:ProtInc. DR GO; GO:0050872; P:white fat cell differentiation; ISS:UniProtKB. DR InterPro; IPR006139; D-isomer_2_OHA_DH_cat_dom. DR InterPro; IPR029753; D-isomer_DH_CS. DR InterPro; IPR006140; D-isomer_DH_NAD-bd. DR InterPro; IPR016040; NAD(P)-bd_dom. DR Pfam; PF00389; 2-Hacid_dh; 1. DR Pfam; PF02826; 2-Hacid_dh_C; 1. DR SUPFAM; SSF51735; SSF51735; 1. DR PROSITE; PS00671; D_2_HYDROXYACID_DH_3; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell junction; Complete proteome; KW Differentiation; Direct protein sequencing; Host-virus interaction; KW NAD; Nucleus; Oxidoreductase; Phosphoprotein; Polymorphism; KW Reference proteome; Repressor; Synapse; Transcription; KW Transcription regulation. FT CHAIN 1 445 C-terminal-binding protein 2. FT /FTId=PRO_0000076044. FT NP_BIND 186 191 NAD. {ECO:0000269|Ref.19}. FT NP_BIND 243 249 NAD. {ECO:0000269|Ref.19}. FT NP_BIND 270 272 NAD. {ECO:0000269|Ref.19}. FT NP_BIND 321 324 NAD. {ECO:0000269|Ref.19}. FT ACT_SITE 272 272 {ECO:0000250}. FT ACT_SITE 301 301 {ECO:0000250}. FT ACT_SITE 321 321 Proton donor. {ECO:0000250}. FT BINDING 106 106 NAD. {ECO:0000250}. FT BINDING 210 210 NAD. {ECO:0000269|Ref.19}. FT BINDING 296 296 NAD. {ECO:0000269|Ref.19}. FT MOD_RES 428 428 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT VAR_SEQ 1 20 MALVDKHKVKRQRLDRICEG -> MPVPSRHINIGRSQSWD FT AAGWYEGPWENAESLRPLGRRSSLTYGTAEGTWFEPNHRPQ FT DAALPVAAEPYLYREAVYNSVAARKGSTPDFTFYDSRQAVM FT SGRSPLLPREYYSDPSGAARVPKEPPLYRDPGVSRPVPSYG FT VLGSRTSWDPMQGRSPALQDAGHLYRDPGGKMIPQGRQTQS FT RAASPGRYGREQPDTRYGAEVPAYPLSQVFSDISERPIDPA FT PARQVAPTCLVVDPSSAAAPEGSTGVAPGALNRGYGPARES FT IPSKMAYETYEADLSTFQGPGGKRTVLPEFLAFLRAEGLAE FT ATLGALLQQGFDSPAVLATLEDADIKSVAPNLGQARVLSRL FT ANSCRTEMQLRRQDRGGPLPRARSSSFSHRSELLHGDLASL FT GAAAPLQTASPRAGDPARRPSSAPSQHLLETAATYSAPGVG FT THAPHFPSNSGYSSPTPCALTARLSPTYPLQAGVALTNPGP FT SNPLHPGPRTAYSTAYTVPMELLKRERNVAASPLPSPHGSP FT QVLRKPGAPLGPSTLPPASQSLHTPHSPYQKVARRTGAPII FT VSTMLAPEPS (in isoform 2). FT {ECO:0000303|PubMed:11163272}. FT /FTId=VSP_027615. FT VARIANT 47 47 E -> D (in dbSNP:rs3198926). FT /FTId=VAR_033844. FT CONFLICT 87 87 L -> F (in Ref. 2; AAG45951). FT {ECO:0000305}. FT CONFLICT 88 88 T -> N (in Ref. 2; AAG45951). FT {ECO:0000305}. FT CONFLICT 112 112 D -> N (in Ref. 2; AAG45951). FT {ECO:0000305}. FT CONFLICT 411 411 I -> T (in Ref. 9; AAH47018). FT {ECO:0000305}. FT STRAND 35 38 {ECO:0000244|PDB:2OME}. FT HELIX 47 51 {ECO:0000244|PDB:2OME}. FT TURN 52 54 {ECO:0000244|PDB:2OME}. FT STRAND 56 59 {ECO:0000244|PDB:2OME}. FT HELIX 65 67 {ECO:0000244|PDB:2OME}. FT HELIX 70 75 {ECO:0000244|PDB:2OME}. FT STRAND 76 81 {ECO:0000244|PDB:2OME}. FT STRAND 83 85 {ECO:0000244|PDB:2OME}. FT HELIX 89 93 {ECO:0000244|PDB:2OME}. FT STRAND 100 106 {ECO:0000244|PDB:2OME}. FT HELIX 113 118 {ECO:0000244|PDB:2OME}. FT STRAND 122 124 {ECO:0000244|PDB:2OME}. FT STRAND 128 130 {ECO:0000244|PDB:2OME}. FT HELIX 131 147 {ECO:0000244|PDB:2OME}. FT HELIX 149 157 {ECO:0000244|PDB:2OME}. FT HELIX 165 171 {ECO:0000244|PDB:2OME}. FT TURN 172 174 {ECO:0000244|PDB:2OME}. FT STRAND 182 186 {ECO:0000244|PDB:2OME}. FT HELIX 190 199 {ECO:0000244|PDB:2OME}. FT HELIX 200 202 {ECO:0000244|PDB:2OME}. FT STRAND 205 209 {ECO:0000244|PDB:2OME}. FT HELIX 217 220 {ECO:0000244|PDB:2OME}. FT HELIX 229 235 {ECO:0000244|PDB:2OME}. FT STRAND 237 241 {ECO:0000244|PDB:2OME}. FT HELIX 255 258 {ECO:0000244|PDB:2OME}. FT STRAND 265 269 {ECO:0000244|PDB:2OME}. FT HELIX 273 275 {ECO:0000244|PDB:2OME}. FT HELIX 278 286 {ECO:0000244|PDB:2OME}. FT STRAND 289 296 {ECO:0000244|PDB:2OME}. FT STRAND 299 302 {ECO:0000244|PDB:2OME}. FT TURN 309 312 {ECO:0000244|PDB:2OME}. FT STRAND 314 318 {ECO:0000244|PDB:2OME}. FT HELIX 327 346 {ECO:0000244|PDB:2OME}. FT TURN 349 352 {ECO:0000244|PDB:2OME}. FT STRAND 354 356 {ECO:0000244|PDB:2OME}. SQ SEQUENCE 445 AA; 48945 MW; 0A8C21CEB36807FA CRC64; MALVDKHKVK RQRLDRICEG IRPQIMNGPL HPRPLVALLD GRDCTVEMPI LKDLATVAFC DAQSTQEIHE KVLNEAVGAM MYHTITLTRE DLEKFKALRV IVRIGSGYDN VDIKAAGELG IAVCNIPSAA VEETADSTIC HILNLYRRNT WLYQALREGT RVQSVEQIRE VASGAARIRG ETLGLIGFGR TGQAVAVRAK AFGFSVIFYD PYLQDGIERS LGVQRVYTLQ DLLYQSDCVS LHCNLNEHNH HLINDFTIKQ MRQGAFLVNA ARGGLVDEKA LAQALKEGRI RGAALDVHES EPFSFAQGPL KDAPNLICTP HTAWYSEQAS LEMREAAATE IRRAITGRIP ESLRNCVNKE FFVTSAPWSV IDQQAIHPEL NGATYRYPPG IVGVAPGGLP AAMEGIIPGG IPVTHNLPTV AHPSQAPSPN QPTKHGDNRE HPNEQ // ID CTNA1_HUMAN Reviewed; 906 AA. AC P35221; Q12795; Q8N1C0; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 1. DT 11-NOV-2015, entry version 166. DE RecName: Full=Catenin alpha-1; DE AltName: Full=Alpha E-catenin; DE AltName: Full=Cadherin-associated protein; DE AltName: Full=Renal carcinoma antigen NY-REN-13; GN Name=CTNNA1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=8404069; RA Furukawa Y., Nakatsuru S., Nagafuchi A., Tsukita S., Muto T., RA Nakamura Y., Horii A.; RT "Structure, expression and chromosome assignment of the human catenin RT (cadherin-associated protein) alpha 1 gene (CTNNA1)."; RL Cytogenet. Cell Genet. 65:74-78(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Colon, and Lung; RX PubMed=8323564; DOI=10.1006/bbrc.1993.1710; RA Oda T., Kanai Y., Shimoyama Y., Nagafuchi A., Tsukita S., RA Hirohashi S.; RT "Cloning of the human alpha-catenin cDNA and its aberrant mRNA in a RT human cancer cell line."; RL Biochem. Biophys. Res. Commun. 193:897-904(1993). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Colon; RX PubMed=7945318; DOI=10.1006/bbrc.1994.2381; RA Rimm D.L., Kebriaei P., Morrow J.S.; RT "Molecular cloning reveals alternative splice forms of human alpha(E)- RT catenin."; RL Biochem. Biophys. Res. Commun. 203:1691-1699(1994). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING, AND RP SUBCELLULAR LOCATION (ISOFORM 3). RC TISSUE=Hippocampus; RX PubMed=21708131; DOI=10.1016/j.bbrc.2011.06.085; RA Kask M., Pruunsild P., Timmusk T.; RT "Bidirectional transcription from human LRRTM2/CTNNA1 and RT LRRTM1/CTNNA2 gene loci leads to expression of N-terminally truncated RT CTNNA1 and CTNNA2 isoforms."; RL Biochem. Biophys. Res. Commun. 411:56-61(2011). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Nollet F.H., Vanpoucke G.G., van Roy F.M.; RT "Genomic organization of the human alphaE-catenin gene (CTNNA1)."; RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-179 AND SER-219. RG NIEHS SNPs program; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Brain, and Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP PROTEIN SEQUENCE OF 2-12; 166-178 AND 617-623, CLEAVAGE OF INITIATOR RP METHIONINE, ACETYLATION AT THR-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Colon carcinoma; RA Bienvenut W.V., Zebisch A., Kolch W.; RL Submitted (DEC-2008) to UniProtKB. RN [11] RP NUCLEOTIDE SEQUENCE [MRNA] OF 159-250. RC TISSUE=Prostate; RX PubMed=8188230; DOI=10.1006/geno.1994.1042; RA McPherson J.D., Morton R.A., Ewing C.M., Wasmuth J.J., Overhauser J., RA Nagafuchi A., Tsukita S., Isaacs W.B.; RT "Assignment of the human alpha-catenin gene (CTNNA1) to chromosome RT 5q21-q22."; RL Genomics 19:188-190(1994). RN [12] RP IDENTIFICATION IN AN E-CADHERIN/CATENIN ADHESION COMPLEX. RX PubMed=7982500; DOI=10.1016/0014-5793(94)01205-9; RA Butz S., Kemler R.; RT "Distinct cadherin-catenin complexes in Ca(2+)-dependent cell-cell RT adhesion."; RL FEBS Lett. 355:195-200(1994). RN [13] RP SUBUNIT, AND INTERACTION WITH CTNNB1. RX PubMed=9341178; DOI=10.1074/jbc.272.43.27301; RA Koslov E.R., Maupin P., Pradhan D., Morrow J.S., Rimm D.L.; RT "Alpha-catenin can form asymmetric homodimeric complexes and/or RT heterodimeric complexes with beta-catenin."; RL J. Biol. Chem. 272:27301-27306(1997). RN [14] RP INTERACTION WITH JUP; CTNNB1 AND ALPHA-ACTININ. RX PubMed=9152027; RA Nieset J.E., Redfield A.R., Jin F., Knudsen K.A., Johnson K.R., RA Wheelock M.J.; RT "Characterization of the interactions of alpha-catenin with alpha- RT actinin and beta-catenin/plakoglobin."; RL J. Cell Sci. 110:1013-1022(1997). RN [15] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX PubMed=10508479; RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal- RT cell carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [16] RP INTERACTION WITH AJUBA. RX PubMed=12417594; DOI=10.1074/jbc.M205391200; RA Marie H., Pratt S.J., Betson M., Epple H., Kittler J.T., Meek L., RA Moss S.J., Troyanovsky S., Attwell D., Longmore G.D., Braga V.M.; RT "The LIM protein Ajuba is recruited to cadherin-dependent cell RT junctions through an association with alpha-catenin."; RL J. Biol. Chem. 278:1220-1228(2003). RN [17] RP SUMOYLATION. RX PubMed=15561718; DOI=10.1074/jbc.M411718200; RA Gocke C.B., Yu H., Kang J.; RT "Systematic identification and analysis of mammalian small ubiquitin- RT like modifier substrates."; RL J. Biol. Chem. 280:5004-5012(2005). RN [18] RP INTERACTION WITH ARHGAP21. RX PubMed=16184169; DOI=10.1038/ncb1308; RA Sousa S., Cabanes D., Archambaud C., Colland F., Lemichez E., RA Popoff M., Boisson-Dupuis S., Gouin E., Lecuit M., Legrain P., RA Cossart P.; RT "ARHGAP10 is necessary for alpha-catenin recruitment at adherens RT junctions and for Listeria invasion."; RL Nat. Cell Biol. 7:954-960(2005). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein RT phosphorylation analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Pituitary; RX PubMed=16807684; DOI=10.1007/s11102-006-8916-x; RA Beranova-Giorgianni S., Zhao Y., Desiderio D.M., Giorgianni F.; RT "Phosphoproteomic analysis of the human pituitary."; RL Pituitary 9:109-120(2006). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-652, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Prostate cancer; RX PubMed=17487921; DOI=10.1002/elps.200600782; RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.; RT "Toward a global characterization of the phosphoproteome in prostate RT cancer cells: identification of phosphoproteins in the LNCaP cell RT line."; RL Electrophoresis 28:2027-2034(2007). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., RA Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for RT efficient phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641 AND SER-652, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [25] RP INTERACTION WITH LIMA1. RX PubMed=18093941; DOI=10.1073/pnas.0710504105; RA Abe K., Takeichi M.; RT "EPLIN mediates linkage of the cadherin catenin complex to F-actin and RT stabilizes the circumferential actin belt."; RL Proc. Natl. Acad. Sci. U.S.A. 105:13-19(2008). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641 AND THR-645, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by RT enrichment and fractionation of phosphopeptides with strong anion RT exchange chromatography."; RL Proteomics 8:1346-1361(2008). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-641, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-634; SER-641 AND RP SER-652, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-264; SER-268; SER-295; RP SER-297; THR-634; SER-641 AND SER-851, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [34] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 377-632, PARTIAL PROTEIN RP SEQUENCE, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=11447106; DOI=10.1093/emboj/20.14.3645; RA Yang J., Dokurno P., Tonks N.K., Barford D.; RT "Crystal structure of the M-fragment of alpha-catenin: implications RT for modulation of cell adhesion."; RL EMBO J. 20:3645-3656(2001). RN [35] RP POSSIBLE INVOLVEMENT IN HDGC. RX PubMed=23208944; DOI=10.1002/path.4152; RA Majewski I.J., Kluijt I., Cats A., Scerri T.S., de Jong D., RA Kluin R.J., Hansford S., Hogervorst F.B., Bosma A.J., Hofland I., RA Winter M., Huntsman D., Jonkers J., Bahlo M., Bernards R.; RT "An alpha-E-catenin (CTNNA1) mutation in hereditary diffuse gastric RT cancer."; RL J. Pathol. 229:621-629(2013). CC -!- FUNCTION: Associates with the cytoplasmic domain of a variety of CC cadherins. The association of catenins to cadherins produces a CC complex which is linked to the actin filament network, and which CC seems to be of primary importance for cadherins cell-adhesion CC properties. Can associate with both E- and N-cadherins. Originally CC believed to be a stable component of E-cadherin/catenin adhesion CC complexes and to mediate the linkage of cadherins to the actin CC cytoskeleton at adherens junctions. In contrast, cortical actin CC was found to be much more dynamic than E-cadherin/catenin CC complexes and CTNNA1 was shown not to bind to F-actin when CC assembled in the complex suggesting a different linkage between CC actin and adherens junctions components. The homodimeric form may CC regulate actin filament assembly and inhibit actin branching by CC competing with the Arp2/3 complex for binding to actin filaments. CC May play a crucial role in cell differentiation. CC -!- SUBUNIT: Monomer and homodimer; the monomer preferentially binds CC to CTNNB1 and the homodimer to actin. Binds MLLT4 and F-actin. CC Possible component of an E-cadherin/ catenin adhesion complex CC together with E-cadherin/CDH1 and beta-catenin/CTNNB1 or gamma- CC catenin/JUP; the complex is located to adherens junctions. The CC stable association of CTNNA1 is controversial as CTNNA1 was shown CC not to bind to F-actin when assembled in the complex. CC Alternatively, the CTNNA1-containing complex may be linked to F- CC actin by other proteins such as LIMA1. Interacts with ARHGAP21 and CC with AJUBA. Interacts with LIMA1 (By similarity). {ECO:0000250}. CC -!- INTERACTION: CC P25054:APC; NbExp=2; IntAct=EBI-701918, EBI-727707; CC P32121:ARRB2; NbExp=3; IntAct=EBI-701918, EBI-714559; CC P00533:EGFR; NbExp=4; IntAct=EBI-701918, EBI-297353; CC P14923:JUP; NbExp=2; IntAct=EBI-701918, EBI-702484; CC -!- SUBCELLULAR LOCATION: Isoform 1: Cytoplasm, cytoskeleton. Cell CC junction, adherens junction. Cell membrane; Peripheral membrane CC protein; Cytoplasmic side. Cell junction. Note=Found at cell-cell CC boundaries and probably at cell-matrix boundaries. CC -!- SUBCELLULAR LOCATION: Isoform 3: Cell membrane CC {ECO:0000269|PubMed:21708131}; Peripheral membrane protein CC {ECO:0000269|PubMed:21708131}; Cytoplasmic side CC {ECO:0000269|PubMed:21708131}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=CTNNA1a; CC IsoId=P35221-1; Sequence=Displayed; CC Name=2; CC IsoId=P35221-2; Sequence=VSP_017494; CC Name=3; Synonyms=CTNNA1b; CC IsoId=P35221-3; Sequence=VSP_047810; CC Note=Expressed at high levels in the nervous system. Lacks the CC beta-catenin interaction domain.; CC -!- TISSUE SPECIFICITY: Expressed ubiquitously in normal tissues. CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:15561718}. CC -!- DISEASE: Hereditary diffuse gastric cancer (HDGC) [MIM:137215]: A CC cancer predisposition syndrome with increased susceptibility to CC diffuse gastric cancer. Diffuse gastric cancer is a malignant CC disease characterized by poorly differentiated infiltrating CC lesions resulting in thickening of the stomach. Malignant tumors CC start in the stomach, can spread to the esophagus or the small CC intestine, and can extend through the stomach wall to nearby lymph CC nodes and organs. It also can metastasize to other parts of the CC body. {ECO:0000269|PubMed:23208944}. Note=The gene represented in CC this entry may be involved in disease pathogenesis. CC -!- SIMILARITY: Belongs to the vinculin/alpha-catenin family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/ctnna1/"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; D14705; BAA03530.1; -; mRNA. DR EMBL; D13866; BAA02979.1; -; mRNA. DR EMBL; L23805; AAA86430.1; -; mRNA. DR EMBL; U03100; AAA18949.1; -; mRNA. DR EMBL; HQ589335; AEF32483.1; -; mRNA. DR EMBL; AF102803; AAC99459.1; -; Genomic_DNA. DR EMBL; AF102787; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102788; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102789; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102790; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102791; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102792; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102793; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102794; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102795; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102796; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102797; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102798; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102799; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102800; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102801; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AF102802; AAC99459.1; JOINED; Genomic_DNA. DR EMBL; AY884207; AAW56940.1; -; Genomic_DNA. DR EMBL; AC010453; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC011405; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC034243; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC113340; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471062; EAW62124.1; -; Genomic_DNA. DR EMBL; BC000385; AAH00385.1; -; mRNA. DR EMBL; BC031262; AAH31262.1; -; mRNA. DR EMBL; L22080; AAA35502.1; -; mRNA. DR CCDS; CCDS34243.1; -. [P35221-1] DR CCDS; CCDS75315.1; -. [P35221-3] DR PIR; JC2542; JC2542. DR PIR; JN0607; JN0607. DR RefSeq; NP_001277236.1; NM_001290307.1. DR RefSeq; NP_001277238.1; NM_001290309.1. DR RefSeq; NP_001277239.1; NM_001290310.1. DR RefSeq; NP_001277241.1; NM_001290312.1. [P35221-3] DR RefSeq; NP_001894.2; NM_001903.3. [P35221-1] DR RefSeq; XP_005271956.1; XM_005271899.2. [P35221-3] DR RefSeq; XP_006714599.1; XM_006714536.2. [P35221-1] DR RefSeq; XP_011541474.1; XM_011543172.1. [P35221-1] DR UniGene; Hs.445981; -. DR PDB; 1H6G; X-ray; 2.20 A; A/B=377-632. DR PDB; 4EHP; X-ray; 2.66 A; B=277-382. DR PDB; 4IGG; X-ray; 3.66 A; A/B=82-906. DR PDBsum; 1H6G; -. DR PDBsum; 4EHP; -. DR PDBsum; 4IGG; -. DR ProteinModelPortal; P35221; -. DR SMR; P35221; 19-878. DR BioGrid; 107876; 57. DR DIP; DIP-515N; -. DR IntAct; P35221; 40. DR MINT; MINT-4998962; -. DR STRING; 9606.ENSP00000304669; -. DR PhosphoSite; P35221; -. DR BioMuta; CTNNA1; -. DR DMDM; 461853; -. DR MaxQB; P35221; -. DR PaxDb; P35221; -. DR PeptideAtlas; P35221; -. DR PRIDE; P35221; -. DR DNASU; 1495; -. DR Ensembl; ENST00000302763; ENSP00000304669; ENSG00000044115. [P35221-1] DR Ensembl; ENST00000540387; ENSP00000438476; ENSG00000044115. [P35221-3] DR GeneID; 1495; -. DR KEGG; hsa:1495; -. DR UCSC; uc003ldh.3; human. [P35221-1] DR CTD; 1495; -. DR GeneCards; CTNNA1; -. DR HGNC; HGNC:2509; CTNNA1. DR HPA; CAB021089; -. DR HPA; HPA046119; -. DR MIM; 116805; gene. DR MIM; 137215; phenotype. DR neXtProt; NX_P35221; -. DR PharmGKB; PA27008; -. DR eggNOG; KOG3681; Eukaryota. DR eggNOG; ENOG410XSRU; LUCA. DR GeneTree; ENSGT00550000074411; -. DR HOGENOM; HOG000280724; -. DR HOVERGEN; HBG000069; -. DR InParanoid; P35221; -. DR KO; K05691; -. DR OMA; WERQVRV; -. DR OrthoDB; EOG7HQN7B; -. DR PhylomeDB; P35221; -. DR TreeFam; TF313686; -. DR Reactome; R-HSA-375170; CDO in myogenesis. DR Reactome; R-HSA-418990; Adherens junctions interactions. DR Reactome; R-HSA-5218920; VEGFR2 mediated vascular permeability. DR Reactome; R-HSA-5626467; RHO GTPases activate IQGAPs. DR ChiTaRS; CTNNA1; human. DR EvolutionaryTrace; P35221; -. DR GeneWiki; Catenin_(cadherin-associated_protein),_alpha_1; -. DR GenomeRNAi; 1495; -. DR NextBio; 6145; -. DR PRO; PR:P35221; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; P35221; -. DR CleanEx; HS_CTNNA1; -. DR ExpressionAtlas; P35221; baseline and differential. DR Genevisible; P35221; HS. DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl. DR GO; GO:0015629; C:actin cytoskeleton; IEA:InterPro. DR GO; GO:0016342; C:catenin complex; IDA:BHF-UCL. DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016600; C:flotillin complex; IEA:Ensembl. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0014704; C:intercalated disc; IEA:Ensembl. DR GO; GO:0030027; C:lamellipodium; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0005915; C:zonula adherens; IEA:Ensembl. DR GO; GO:0008013; F:beta-catenin binding; IPI:BHF-UCL. DR GO; GO:0045296; F:cadherin binding; IPI:UniProtKB. DR GO; GO:0045295; F:gamma-catenin binding; IPI:BHF-UCL. DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0005198; F:structural molecule activity; IEA:InterPro. DR GO; GO:0017166; F:vinculin binding; IPI:UniProtKB. DR GO; GO:0007015; P:actin filament organization; IEA:InterPro. DR GO; GO:0034332; P:adherens junction organization; TAS:Reactome. DR GO; GO:0007568; P:aging; IEA:Ensembl. DR GO; GO:0043297; P:apical junction assembly; NAS:UniProtKB. DR GO; GO:0031103; P:axon regeneration; IEA:Ensembl. DR GO; GO:0007155; P:cell adhesion; NAS:ProtInc. DR GO; GO:0034329; P:cell junction assembly; TAS:Reactome. DR GO; GO:0045216; P:cell-cell junction organization; TAS:Reactome. DR GO; GO:0034613; P:cellular protein localization; IEA:Ensembl. DR GO; GO:0071681; P:cellular response to indole-3-methanol; IDA:UniProtKB. DR GO; GO:0090136; P:epithelial cell-cell adhesion; IEA:Ensembl. DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IEA:Ensembl. DR GO; GO:0016264; P:gap junction assembly; IEA:Ensembl. DR GO; GO:0008584; P:male gonad development; IEA:Ensembl. DR GO; GO:0042692; P:muscle cell differentiation; TAS:Reactome. DR GO; GO:2000146; P:negative regulation of cell motility; IEA:Ensembl. DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl. DR GO; GO:2001045; P:negative regulation of integrin-mediated signaling pathway; IEA:Ensembl. DR GO; GO:0007406; P:negative regulation of neuroblast proliferation; IEA:Ensembl. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl. DR GO; GO:0001541; P:ovarian follicle development; IEA:Ensembl. DR GO; GO:2001241; P:positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; IEA:Ensembl. DR GO; GO:0051149; P:positive regulation of muscle cell differentiation; TAS:Reactome. DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IEA:Ensembl. DR GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl. DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl. DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; TAS:Reactome. DR InterPro; IPR001033; Alpha_catenin. DR InterPro; IPR030047; CTNNA1. DR InterPro; IPR006077; Vinculin/catenin. DR InterPro; IPR000633; Vinculin_CS. DR PANTHER; PTHR18914; PTHR18914; 1. DR PANTHER; PTHR18914:SF24; PTHR18914:SF24; 1. DR Pfam; PF01044; Vinculin; 2. DR PRINTS; PR00805; ALPHACATENIN. DR SUPFAM; SSF47220; SSF47220; 4. DR PROSITE; PS00663; VINCULIN_1; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cell adhesion; KW Cell junction; Cell membrane; Complete proteome; Cytoplasm; KW Cytoskeleton; Direct protein sequencing; Membrane; Phosphoprotein; KW Polymorphism; Reference proteome; Ubl conjugation. FT INIT_MET 1 1 Removed. {ECO:0000269|Ref.10}. FT CHAIN 2 906 Catenin alpha-1. FT /FTId=PRO_0000064261. FT REGION 2 228 Involved in homodimerization. FT REGION 97 148 Interaction with JUP and CTNNB1. FT REGION 325 394 Interaction with alpha-actinin. FT MOD_RES 2 2 N-acetylthreonine. {ECO:0000269|Ref.10}. FT MOD_RES 264 264 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 268 268 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 295 295 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 297 297 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 634 634 Phosphothreonine. FT {ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 641 641 Phosphoserine. FT {ECO:0000244|PubMed:16807684, FT ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18220336, FT ECO:0000244|PubMed:18318008, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 645 645 Phosphothreonine. FT {ECO:0000244|PubMed:18318008}. FT MOD_RES 652 652 Phosphoserine. FT {ECO:0000244|PubMed:17487921, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 655 655 Phosphoserine. FT {ECO:0000250|UniProtKB:P26231}. FT MOD_RES 658 658 Phosphothreonine. FT {ECO:0000250|UniProtKB:P26231}. FT MOD_RES 851 851 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT VAR_SEQ 1 370 Missing (in isoform 3). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:21708131}. FT /FTId=VSP_047810. FT VAR_SEQ 811 811 G -> GNCDTCGALQGLKGWPPPLCLATHW (in FT isoform 2). {ECO:0000303|PubMed:7945318}. FT /FTId=VSP_017494. FT VARIANT 179 179 A -> V (in dbSNP:rs28363394). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_022303. FT VARIANT 219 219 P -> S (in dbSNP:rs28363406). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_022304. FT CONFLICT 92 92 A -> V (in Ref. 3; AAA86430/AAA18949). FT {ECO:0000305}. FT CONFLICT 129 129 R -> P (in Ref. 3; AAA18949). FT {ECO:0000305}. FT CONFLICT 175 175 I -> N (in Ref. 3; AAA86430/AAA18949). FT {ECO:0000305}. FT CONFLICT 216 216 K -> S (in Ref. 3; AAA86430/AAA18949). FT {ECO:0000305}. FT CONFLICT 342 342 Q -> K (in Ref. 1; BAA03530). FT {ECO:0000305}. FT CONFLICT 344 348 LQDLL -> CRTCV (in Ref. 3; AAA86430). FT {ECO:0000305}. FT CONFLICT 460 460 L -> G (in Ref. 3; AAA86430/AAA18949). FT {ECO:0000305}. FT CONFLICT 469 469 L -> TW (in Ref. 3; AAA86430/AAA18949). FT {ECO:0000305}. FT CONFLICT 473 473 A -> P (in Ref. 3; AAA86430/AAA18949). FT {ECO:0000305}. FT CONFLICT 653 653 R -> E (in Ref. 3; AAA86430/AAA18949). FT {ECO:0000305}. FT CONFLICT 685 685 A -> R (in Ref. 3; AAA86430/AAA18949). FT {ECO:0000305}. FT CONFLICT 764 764 A -> R (in Ref. 3; AAA86430/AAA18949). FT {ECO:0000305}. FT CONFLICT 789 789 Q -> H (in Ref. 1; BAA03530). FT {ECO:0000305}. FT CONFLICT 859 859 W -> M (in Ref. 3; AAA86430/AAA18949). FT {ECO:0000305}. FT HELIX 293 299 {ECO:0000244|PDB:4EHP}. FT STRAND 300 302 {ECO:0000244|PDB:4EHP}. FT HELIX 305 316 {ECO:0000244|PDB:4EHP}. FT HELIX 325 327 {ECO:0000244|PDB:4EHP}. FT HELIX 328 352 {ECO:0000244|PDB:4EHP}. FT HELIX 353 355 {ECO:0000244|PDB:4EHP}. FT HELIX 378 386 {ECO:0000244|PDB:1H6G}. FT HELIX 387 389 {ECO:0000244|PDB:1H6G}. FT TURN 393 395 {ECO:0000244|PDB:1H6G}. FT HELIX 398 409 {ECO:0000244|PDB:1H6G}. FT HELIX 413 438 {ECO:0000244|PDB:1H6G}. FT HELIX 444 473 {ECO:0000244|PDB:1H6G}. FT HELIX 478 506 {ECO:0000244|PDB:1H6G}. FT HELIX 509 531 {ECO:0000244|PDB:1H6G}. FT HELIX 535 559 {ECO:0000244|PDB:1H6G}. FT TURN 560 562 {ECO:0000244|PDB:1H6G}. FT HELIX 567 581 {ECO:0000244|PDB:1H6G}. FT HELIX 583 598 {ECO:0000244|PDB:1H6G}. FT STRAND 600 602 {ECO:0000244|PDB:1H6G}. FT HELIX 608 630 {ECO:0000244|PDB:1H6G}. SQ SEQUENCE 906 AA; 100071 MW; 7AAE6F5DDBAF5099 CRC64; MTAVHAGNIN FKWDPKSLEI RTLAVERLLE PLVTQVTTLV NTNSKGPSNK KRGRSKKAHV LAASVEQATE NFLEKGDKIA KESQFLKEEL VAAVEDVRKQ GDLMKAAAGE FADDPCSSVK RGNMVRAARA LLSAVTRLLI LADMADVYKL LVQLKVVEDG ILKLRNAGNE QDLGIQYKAL KPEVDKLNIM AAKRQQELKD VGHRDQMAAA RGILQKNVPI LYTASQACLQ HPDVAAYKAN RDLIYKQLQQ AVTGISNAAQ ATASDDASQH QGGGGGELAY ALNNFDKQII VDPLSFSEER FRPSLEERLE SIISGAALMA DSSCTRDDRR ERIVAECNAV RQALQDLLSE YMGNAGRKER SDALNSAIDK MTKKTRDLRR QLRKAVMDHV SDSFLETNVP LLVLIEAAKN GNEKEVKEYA QVFREHANKL IEVANLACSI SNNEEGVKLV RMSASQLEAL CPQVINAALA LAAKPQSKLA QENMDLFKEQ WEKQVRVLTD AVDDITSIDD FLAVSENHIL EDVNKCVIAL QEKDVDGLDR TAGAIRGRAA RVIHVVTSEM DNYEPGVYTE KVLEATKLLS NTVMPRFTEQ VEAAVEALSS DPAQPMDENE FIDASRLVYD GIRDIRKAVL MIRTPEELDD SDFETEDFDV RSRTSVQTED DQLIAGQSAR AIMAQLPQEQ KAKIAEQVAS FQEEKSKLDA EVSKWDDSGN DIIVLAKQMC MIMMEMTDFT RGKGPLKNTS DVISAAKKIA EAGSRMDKLG RTIADHCPDS ACKQDLLAYL QRIALYCHQL NICSKVKAEV QNLGGELVVS GVDSAMSLIQ AAKNLMNAVV QTVKASYVAS TKYQKSQGMA SLNLPAVSWK MKAPEKKPLV KREKQDETQT KIKRASQKKH VNPVQALSEF KAMDSI // ID DMRTB_HUMAN Reviewed; 342 AA. AC Q96MA1; Q96SD2; DT 15-JAN-2008, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 11-NOV-2015, entry version 111. DE RecName: Full=Doublesex- and mab-3-related transcription factor B1; GN Name=DMRTB1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-342, AND TISSUE SPECIFICITY. RC TISSUE=Testis; RX PubMed=11863363; DOI=10.1006/geno.2002.6711; RA Ottolenghi C., Fellous M., Barbieri M., McElreavey K.; RT "Novel paralogy relations among human chromosomes support a link RT between the phylogeny of doublesex-related genes and the evolution of RT sex determination."; RL Genomics 79:333-343(2002). CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE- CC ProRule:PRU00070}. CC -!- TISSUE SPECIFICITY: Testis. {ECO:0000269|PubMed:11863363}. CC -!- SIMILARITY: Belongs to the DMRT family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 DM DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00070}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AK057273; BAB71407.1; -; mRNA. DR EMBL; AL365445; CAI22836.1; -; Genomic_DNA. DR EMBL; CH471059; EAX06736.1; -; Genomic_DNA. DR EMBL; AJ291671; CAC40654.1; -; mRNA. DR CCDS; CCDS581.1; -. DR RefSeq; NP_149056.1; NM_033067.2. DR UniGene; Hs.131654; -. DR ProteinModelPortal; Q96MA1; -. DR SMR; Q96MA1; 7-65. DR BioGrid; 122012; 15. DR IntAct; Q96MA1; 8. DR MINT; MINT-1437877; -. DR STRING; 9606.ENSP00000360500; -. DR PhosphoSite; Q96MA1; -. DR BioMuta; DMRTB1; -. DR DMDM; 74752030; -. DR PaxDb; Q96MA1; -. DR PRIDE; Q96MA1; -. DR Ensembl; ENST00000371445; ENSP00000360500; ENSG00000143006. DR GeneID; 63948; -. DR KEGG; hsa:63948; -. DR UCSC; uc001cvq.1; human. DR CTD; 63948; -. DR GeneCards; DMRTB1; -. DR HGNC; HGNC:13913; DMRTB1. DR HPA; HPA036490; -. DR HPA; HPA058553; -. DR MIM; 614805; gene. DR neXtProt; NX_Q96MA1; -. DR PharmGKB; PA27386; -. DR eggNOG; KOG3815; Eukaryota. DR eggNOG; ENOG410XSK9; LUCA. DR GeneTree; ENSGT00550000074486; -. DR HOGENOM; HOG000112231; -. DR HOVERGEN; HBG095592; -. DR InParanoid; Q96MA1; -. DR KO; K19492; -. DR OMA; CYLISER; -. DR OrthoDB; EOG741Z32; -. DR PhylomeDB; Q96MA1; -. DR TreeFam; TF317837; -. DR GenomeRNAi; 63948; -. DR NextBio; 65732; -. DR PRO; PR:Q96MA1; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; Q96MA1; -. DR CleanEx; HS_DMRTB1; -. DR Genevisible; Q96MA1; HS. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 4.10.1040.10; -; 1. DR InterPro; IPR001275; DM_DNA-bd. DR InterPro; IPR026607; DMRT/dsx/mab-3. DR PANTHER; PTHR12322; PTHR12322; 1. DR Pfam; PF00751; DM; 1. DR SMART; SM00301; DM; 1. DR SUPFAM; SSF82927; SSF82927; 1. DR PROSITE; PS40000; DM_1; 1. DR PROSITE; PS50809; DM_2; 1. PE 2: Evidence at transcript level; KW Complete proteome; DNA-binding; Metal-binding; Nucleus; KW Reference proteome; Transcription; Transcription regulation; Zinc. FT CHAIN 1 342 Doublesex- and mab-3-related FT transcription factor B1. FT /FTId=PRO_0000316012. FT DNA_BIND 11 58 DM. {ECO:0000255|PROSITE- FT ProRule:PRU00070}. FT COMPBIAS 80 84 Poly-Ala. FT COMPBIAS 85 304 Pro-rich. SQ SEQUENCE 342 AA; 36205 MW; 18B0D5B0A6DB03EB CRC64; MADKMVRTPK CSRCRNHGFL VPVKGHAGKC RWKQCLCEKC YLISERQKIM AAQKVLKTQA AEEEQEAALC AQGPKQASGA AAAAPAPVPV PAASLRPLSP GTPSGDADPG PEGRAAACFF EQPPRGRNPG PRALQPVLGG RSHVEPSERA AVAMPSLAGP PFGAEAAGSG YPGPLDLRRP MRTVPGPLFT DFVRPLNINP DRALGPEYPG GSSMHPYCPF PLGYLDAPPG VPLQQGFRHV SRSQYQGGGL VSEPGGDFQP SYYLPPPPPP LPPLPPLPPQ PQFLPPGYLS ALHFLPPPPP PPPPSSFSLT VLFDTDKENT DDQDAEVLSG EPSQPSSQEQ SD // ID DVL2_HUMAN Reviewed; 736 AA. AC O14641; D3DTN3; Q53XM0; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 11-NOV-2015, entry version 160. DE RecName: Full=Segment polarity protein dishevelled homolog DVL-2; DE Short=Dishevelled-2; DE AltName: Full=DSH homolog 2; GN Name=DVL2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND PHOSPHORYLATION. RX PubMed=9192851; DOI=10.1006/geno.1997.4713; RA Semenov M.V., Snyder M.; RT "Human dishevelled genes constitute a DHR-containing multigene RT family."; RL Genomics 42:302-310(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP INTERACTION WITH ARRB1. RX PubMed=11742073; DOI=10.1073/pnas.211572798; RA Chen W., Hu L.A., Semenov M.V., Yanagawa S., Kikuchi A., RA Lefkowitz R.J., Miller W.E.; RT "beta-Arrestin1 modulates lymphoid enhancer factor transcriptional RT activity through interaction with phosphorylated dishevelled RT proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 98:14889-14894(2001). RN [6] RP INTERACTION WITH DIXDC1 AND RAC. RX PubMed=15262978; DOI=10.1074/jbc.M404598200; RA Wong C.K., Luo W., Deng Y., Zou H., Ye Z., Lin S.-C.; RT "The DIX domain protein coiled-coil-DIX1 inhibits c-Jun N-terminal RT kinase activation by Axin and dishevelled through distinct RT mechanisms."; RL J. Biol. Chem. 279:39366-39373(2004). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [9] RP PHOSPHORYLATION BY CSNK1D/CK1. RX PubMed=21422228; DOI=10.1083/jcb.201011111; RA Greer Y.E., Rubin J.S.; RT "Casein kinase 1 delta functions at the centrosome to mediate Wnt-3a- RT dependent neurite outgrowth."; RL J. Cell Biol. 192:993-1004(2011). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [11] RP INTERACTION WITH DACT1. RX PubMed=22610794; DOI=10.1002/humu.22121; RA Shi Y., Ding Y., Lei Y.P., Yang X.Y., Xie G.M., Wen J., Cai C.Q., RA Li H., Chen Y., Zhang T., Wu B.L., Jin L., Chen Y.G., Wang H.Y.; RT "Identification of novel rare mutations of DACT1 in human neural tube RT defects."; RL Hum. Mutat. 33:1450-1455(2012). RN [12] RP INTERACTION WITH FAM105B. RX PubMed=23708998; DOI=10.1038/nature12296; RA Rivkin E., Almeida S.M., Ceccarelli D.F., Juang Y.C., Maclean T.A., RA Srikumar T., Huang H., Dunham W.H., Fukumura R., Xie G., Gondo Y., RA Raught B., Gingras A.C., Sicheri F., Cordes S.P.; RT "The linear ubiquitin-specific deubiquitinase gumby regulates RT angiogenesis."; RL Nature 498:318-324(2013). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP INTERACTION WITH DCDC2. RX PubMed=25557784; DOI=10.1016/j.ajhg.2014.12.002; RA Schueler M., Braun D.A., Chandrasekar G., Gee H.Y., Klasson T.D., RA Halbritter J., Bieder A., Porath J.D., Airik R., Zhou W., RA LoTurco J.J., Che A., Otto E.A., Boeckenhauer D., Sebire N.J., RA Honzik T., Harris P.C., Koon S.J., Gunay-Aygun M., Saunier S., RA Zerres K., Bruechle N.O., Drenth J.P., Pelletier L., Tapia-Paez I., RA Lifton R.P., Giles R.H., Kere J., Hildebrandt F.; RT "DCDC2 mutations cause a renal-hepatic ciliopathy by disrupting Wnt RT signaling."; RL Am. J. Hum. Genet. 96:81-92(2015). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.38 ANGSTROMS) OF 264-353, AND FUNCTION. RX PubMed=19252499; DOI=10.1038/nchembio.152; RA Zhang Y., Appleton B.A., Wiesmann C., Lau T., Costa M., Hannoush R.N., RA Sidhu S.S.; RT "Inhibition of Wnt signaling by Dishevelled PDZ peptides."; RL Nat. Chem. Biol. 5:217-219(2009). RN [16] RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 261-354. RG Structural genomics consortium (SGC); RT "Crystal structure of the PDZ domains of human dishevelled 2 RT (homologous to Drosophila dsh)."; RL Submitted (FEB-2009) to the PDB data bank. RN [17] RP VARIANT THR-282. RX PubMed=21248752; DOI=10.1038/nature09639; RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., RA Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., RA Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., RA Jia M., Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., RA Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., RA Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., RA Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., RA Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., RA Futreal P.A.; RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex RT gene PBRM1 in renal carcinoma."; RL Nature 469:539-542(2011). CC -!- FUNCTION: Participates in Wnt signaling by binding to the CC cytoplasmic C-terminus of frizzled family members and transducing CC the Wnt signal to down-stream effectors. Promotes internalization CC and degradation of frizzled proteins upon Wnt signaling. Plays a CC role both in canonical and non-canonical Wnt signaling. Plays a CC role in the signal transduction pathways mediated by multiple Wnt CC genes (By similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts through its PDZ domain with the C-terminal CC regions of VANGL1 and VANGL2. Interacts with Rac. Interacts with CC ARRB1; the interaction is enhanced by phosphorylation of DVL1 (By CC similarity). Can form large oligomers (via DIX domain). Interacts CC (via DIX domain) with DIXDC1 (via DIX domain). Interacts (via DEP CC domain) with AP2M1 and the AP-2 complex (By similarity). Interacts CC with DACT1 and FAM105B/otulin. Interacts with DCDC2. CC {ECO:0000250|UniProtKB:Q60838, ECO:0000269|PubMed:11742073, CC ECO:0000269|PubMed:15262978, ECO:0000269|PubMed:22610794, CC ECO:0000269|PubMed:23708998, ECO:0000269|PubMed:25557784}. CC -!- INTERACTION: CC Self; NbExp=2; IntAct=EBI-740850, EBI-740850; CC Q5R2U3:CK1E; NbExp=2; IntAct=EBI-740850, EBI-9106301; CC Q9NYF0:DACT1; NbExp=6; IntAct=EBI-740850, EBI-3951744; CC Q155Q3:DIXDC1; NbExp=2; IntAct=EBI-740850, EBI-1104700; CC Q5S007:LRRK2; NbExp=3; IntAct=EBI-740850, EBI-5323863; CC Q9Z101:Pard6a (xeno); NbExp=6; IntAct=EBI-740850, EBI-81732; CC A2A5Z6:Smurf2 (xeno); NbExp=8; IntAct=EBI-740850, EBI-2348309; CC Q14134:TRIM29; NbExp=5; IntAct=EBI-740850, EBI-702370; CC Q9GZV5:WWTR1; NbExp=4; IntAct=EBI-740850, EBI-747743; CC P49910:ZNF165; NbExp=2; IntAct=EBI-740850, EBI-741694; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Peripheral CC membrane protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. CC Cytoplasm, cytosol {ECO:0000250}. Cytoplasmic vesicle CC {ECO:0000250}. Note=Localizes at the cell membrane upon CC interaction with frizzled family members and promotes their CC internalization. Localizes to cytoplasmic puncta (By similarity). CC {ECO:0000250}. CC -!- DOMAIN: The DIX domain mediates homooligomerization. CC {ECO:0000250}. CC -!- PTM: Phosphorylated by CSNK1D. {ECO:0000269|PubMed:21422228, CC ECO:0000269|PubMed:9192851}. CC -!- SIMILARITY: Belongs to the DSH family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 DEP domain. {ECO:0000255|PROSITE- CC ProRule:PRU00066}. CC -!- SIMILARITY: Contains 1 DIX domain. {ECO:0000255|PROSITE- CC ProRule:PRU00069}. CC -!- SIMILARITY: Contains 1 PDZ (DHR) domain. {ECO:0000255|PROSITE- CC ProRule:PRU00143}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF006012; AAB65243.1; -; mRNA. DR EMBL; BT009822; AAP88824.1; -; mRNA. DR EMBL; CH471108; EAW90244.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90245.1; -; Genomic_DNA. DR EMBL; BC014844; AAH14844.1; -; mRNA. DR CCDS; CCDS11091.1; -. DR RefSeq; NP_004413.1; NM_004422.2. DR UniGene; Hs.118640; -. DR PDB; 2REY; X-ray; 1.55 A; A=261-355. DR PDB; 3CBX; X-ray; 1.70 A; A/B=264-354. DR PDB; 3CBY; X-ray; 1.50 A; A/B=264-354. DR PDB; 3CBZ; X-ray; 1.38 A; A=264-354. DR PDB; 3CC0; X-ray; 1.75 A; A/B/C=264-354. DR PDB; 4WIP; X-ray; 2.69 A; A/B/C=12-106. DR PDBsum; 2REY; -. DR PDBsum; 3CBX; -. DR PDBsum; 3CBY; -. DR PDBsum; 3CBZ; -. DR PDBsum; 3CC0; -. DR PDBsum; 4WIP; -. DR ProteinModelPortal; O14641; -. DR SMR; O14641; 12-92, 263-353, 422-582. DR BioGrid; 108189; 77. DR DIP; DIP-34433N; -. DR IntAct; O14641; 83. DR MINT; MINT-1435227; -. DR STRING; 9606.ENSP00000005340; -. DR BindingDB; O14641; -. DR ChEMBL; CHEMBL1255125; -. DR PhosphoSite; O14641; -. DR BioMuta; DVL2; -. DR MaxQB; O14641; -. DR PaxDb; O14641; -. DR PRIDE; O14641; -. DR DNASU; 1856; -. DR Ensembl; ENST00000005340; ENSP00000005340; ENSG00000004975. DR GeneID; 1856; -. DR KEGG; hsa:1856; -. DR UCSC; uc002gez.1; human. DR CTD; 1856; -. DR GeneCards; DVL2; -. DR HGNC; HGNC:3086; DVL2. DR HPA; CAB009312; -. DR HPA; HPA022914; -. DR MIM; 602151; gene. DR neXtProt; NX_O14641; -. DR PharmGKB; PA27542; -. DR eggNOG; KOG3571; Eukaryota. DR eggNOG; ENOG410Y5G4; LUCA. DR GeneTree; ENSGT00390000013552; -. DR HOGENOM; HOG000017084; -. DR HOVERGEN; HBG005542; -. DR InParanoid; O14641; -. DR KO; K02353; -. DR OMA; SFHLAMG; -. DR OrthoDB; EOG7BP82N; -. DR PhylomeDB; O14641; -. DR TreeFam; TF318198; -. DR Reactome; R-HSA-201681; TCF dependent signaling in response to WNT. DR Reactome; R-HSA-201688; WNT mediated activation of DVL. DR Reactome; R-HSA-2028269; Signaling by Hippo. DR Reactome; R-HSA-4086400; PCP/CE pathway. DR Reactome; R-HSA-4608870; Asymmetric localization of PCP proteins. DR Reactome; R-HSA-4641258; degradation of DVL. DR Reactome; R-HSA-4641262; disassembly of the destruction complex and recruitment of AXIN to the membrane. DR Reactome; R-HSA-5099900; WNT5A-dependent internalization of FZD4. DR Reactome; R-HSA-5368598; negative regulation of TCF-dependent signaling by DVL-interacting proteins. DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins. DR SignaLink; O14641; -. DR ChiTaRS; DVL2; human. DR EvolutionaryTrace; O14641; -. DR GeneWiki; DVL2; -. DR GenomeRNAi; 1856; -. DR NextBio; 7605; -. DR PRO; PR:O14641; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; O14641; -. DR CleanEx; HS_DVL2; -. DR ExpressionAtlas; O14641; baseline and differential. DR Genevisible; O14641; HS. DR GO; GO:0045177; C:apical part of cell; IEA:Ensembl. DR GO; GO:0045334; C:clathrin-coated endocytic vesicle; TAS:Reactome. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:MGI. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005109; F:frizzled binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:BHF-UCL. DR GO; GO:0044340; P:canonical Wnt signaling pathway involved in regulation of cell proliferation; IDA:BHF-UCL. DR GO; GO:0034613; P:cellular protein localization; IEA:Ensembl. DR GO; GO:0090103; P:cochlea morphogenesis; IEA:Ensembl. DR GO; GO:0022007; P:convergent extension involved in neural plate elongation; IEA:Ensembl. DR GO; GO:0007507; P:heart development; ISS:BHF-UCL. DR GO; GO:0035329; P:hippo signaling; TAS:Reactome. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; TAS:Reactome. DR GO; GO:0001843; P:neural tube closure; ISS:BHF-UCL. DR GO; GO:0035567; P:non-canonical Wnt signaling pathway; IMP:BHF-UCL. DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL. DR GO; GO:0090179; P:planar cell polarity pathway involved in neural tube closure; IBA:GO_Central. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; TAS:Reactome. DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:BHF-UCL. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:BHF-UCL. DR GO; GO:0061098; P:positive regulation of protein tyrosine kinase activity; IEA:Ensembl. DR GO; GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL. DR GO; GO:0007379; P:segment specification; ISS:BHF-UCL. DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0016055; P:Wnt signaling pathway; IGI:MGI. DR GO; GO:0060071; P:Wnt signaling pathway, planar cell polarity pathway; IDA:BHF-UCL. DR Gene3D; 1.10.10.10; -; 1. DR Gene3D; 2.30.42.10; -; 1. DR InterPro; IPR000591; DEP_dom. DR InterPro; IPR024580; Dishevelled_C-dom. DR InterPro; IPR008339; Dishevelled_fam. DR InterPro; IPR003351; Dishevelled_protein_dom. DR InterPro; IPR001158; DIX. DR InterPro; IPR015506; Dsh/Dvl-rel. DR InterPro; IPR008341; DVL2. DR InterPro; IPR001478; PDZ. DR InterPro; IPR029071; Ubiquitin-rel_dom. DR InterPro; IPR011991; WHTH_DNA-bd_dom. DR PANTHER; PTHR10878; PTHR10878; 1. DR PANTHER; PTHR10878:SF8; PTHR10878:SF8; 1. DR Pfam; PF00610; DEP; 1. DR Pfam; PF02377; Dishevelled; 1. DR Pfam; PF00778; DIX; 1. DR Pfam; PF12316; Dsh_C; 1. DR Pfam; PF00595; PDZ; 1. DR PRINTS; PR01760; DISHEVELLED. DR PRINTS; PR01762; DISHEVELLED2. DR SMART; SM00021; DAX; 1. DR SMART; SM00049; DEP; 1. DR SMART; SM00228; PDZ; 1. DR SUPFAM; SSF50156; SSF50156; 1. DR SUPFAM; SSF54236; SSF54236; 1. DR PROSITE; PS50186; DEP; 1. DR PROSITE; PS50841; DIX; 1. DR PROSITE; PS50106; PDZ; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Complete proteome; Cytoplasm; KW Cytoplasmic vesicle; Developmental protein; Membrane; Methylation; KW Phosphoprotein; Polymorphism; Reference proteome; KW Wnt signaling pathway. FT CHAIN 1 736 Segment polarity protein dishevelled FT homolog DVL-2. FT /FTId=PRO_0000145746. FT DOMAIN 11 93 DIX. {ECO:0000255|PROSITE- FT ProRule:PRU00069}. FT DOMAIN 267 339 PDZ. {ECO:0000255|PROSITE- FT ProRule:PRU00143}. FT DOMAIN 433 507 DEP. {ECO:0000255|PROSITE- FT ProRule:PRU00066}. FT COMPBIAS 7 12 Poly-Gly. FT COMPBIAS 235 240 Poly-Arg. FT COMPBIAS 686 694 Poly-Pro. FT MOD_RES 37 37 Omega-N-methylarginine. FT {ECO:0000250|UniProtKB:Q92997}. FT MOD_RES 59 59 Phosphoserine. FT {ECO:0000250|UniProtKB:Q92997}. FT MOD_RES 143 143 Phosphoserine. FT {ECO:0000250|UniProtKB:Q92997}. FT MOD_RES 211 211 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231}. FT MOD_RES 231 231 Omega-N-methylarginine. FT {ECO:0000250|UniProtKB:Q92997}. FT MOD_RES 289 289 Asymmetric dimethylarginine; alternate. FT {ECO:0000250|UniProtKB:Q92997}. FT MOD_RES 289 289 Symmetric dimethylarginine; alternate. FT {ECO:0000250|UniProtKB:Q92997}. FT MOD_RES 364 364 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q92997}. FT MOD_RES 632 632 Symmetric dimethylarginine. FT {ECO:0000250|UniProtKB:Q92997}. FT MOD_RES 718 718 Dimethylated arginine; alternate. FT {ECO:0000250|UniProtKB:Q92997}. FT MOD_RES 718 718 Omega-N-methylarginine; alternate. FT {ECO:0000250|UniProtKB:Q92997}. FT MOD_RES 720 720 Phosphoserine. FT {ECO:0000250|UniProtKB:Q92997}. FT VARIANT 282 282 I -> T (found in a renal cell carcinoma FT case; somatic mutation). FT {ECO:0000269|PubMed:21248752}. FT /FTId=VAR_064708. FT STRAND 14 20 {ECO:0000244|PDB:4WIP}. FT STRAND 27 33 {ECO:0000244|PDB:4WIP}. FT TURN 35 37 {ECO:0000244|PDB:4WIP}. FT HELIX 40 47 {ECO:0000244|PDB:4WIP}. FT STRAND 54 61 {ECO:0000244|PDB:4WIP}. FT TURN 62 64 {ECO:0000244|PDB:4WIP}. FT STRAND 65 71 {ECO:0000244|PDB:4WIP}. FT STRAND 84 90 {ECO:0000244|PDB:4WIP}. FT STRAND 265 270 {ECO:0000244|PDB:3CBZ}. FT HELIX 272 275 {ECO:0000244|PDB:3CBZ}. FT STRAND 280 285 {ECO:0000244|PDB:3CBZ}. FT STRAND 293 299 {ECO:0000244|PDB:3CBZ}. FT HELIX 304 308 {ECO:0000244|PDB:3CBZ}. FT STRAND 316 320 {ECO:0000244|PDB:3CBZ}. FT HELIX 330 341 {ECO:0000244|PDB:3CBZ}. FT STRAND 343 345 {ECO:0000244|PDB:3CBZ}. FT STRAND 347 352 {ECO:0000244|PDB:3CBZ}. SQ SEQUENCE 736 AA; 78948 MW; 4BAD95B6C3FE531B CRC64; MAGSSTGGGG VGETKVIYHL DEEETPYLVK IPVPAERITL GDFKSVLQRP AGAKYFFKSM DQDFGVVKEE ISDDNARLPC FNGRVVSWLV SSDNPQPEMA PPVHEPRAEL APPAPPLPPL PPERTSGIGD SRPPSFHPNV SSSHENLEPE TETESVVSLR RERPRRRDSS EHGAGGHRTG GPSRLERHLA GYESSSTLMT SELESTSLGD SDEEDTMSRF SSSTEQSSAS RLLKRHRRRR KQRPPRLERT SSFSSVTDST MSLNIITVTL NMEKYNFLGI SIVGQSNERG DGGIYIGSIM KGGAVAADGR IEPGDMLLQV NDMNFENMSN DDAVRVLRDI VHKPGPIVLT VAKCWDPSPQ AYFTLPRNEP IQPIDPAAWV SHSAALTGTF PAYPGSSSMS TITSGSSLPD GCEGRGLSVH TDMASVTKAM AAPESGLEVR DRMWLKITIP NAFLGSDVVD WLYHHVEGFP ERREARKYAS GLLKAGLIRH TVNKITFSEQ CYYVFGDLSG GCESYLVNLS LNDNDGSSGA SDQDTLAPLP GATPWPLLPT FSYQYPAPHP YSPQPPPYHE LSSYTYGGGS ASSQHSEGSR SSGSTRSDGG AGRTGRPEER APESKSGSGS ESEPSSRGGS LRRGGEASGT SDGGPPPSRG STGGAPNLRA HPGLHPYGPP PGMALPYNPM MVVMMPPPPP PVPPAVQPPG APPVRDLGSV PPELTASRQS FHMAMGNPSE FFVDVM // ID DYR1B_HUMAN Reviewed; 629 AA. AC Q9Y463; O75258; O75788; O75789; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 11-NOV-2015, entry version 158. DE RecName: Full=Dual specificity tyrosine-phosphorylation-regulated kinase 1B; DE EC=2.7.12.1; DE AltName: Full=Minibrain-related kinase; DE AltName: Full=Mirk protein kinase; GN Name=DYRK1B; Synonyms=MIRK; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Testis; RX PubMed=9918863; DOI=10.1006/bbrc.1998.9967; RA Leder S., Weber Y., Altafaj X., Estivill X., Joost H.-G., Becker W.; RT "Cloning and characterization of DYRK1B, a novel member of the DYRK RT family of protein kinases."; RL Biochem. Biophys. Res. Commun. 254:474-479(1999). RN [2] RP NUCLEOTIDE SEQUENCE (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, RP PHOSPHORYLATION AT TYR-271 AND TYR-273, AND MUTAGENESIS OF LYS-140; RP TYR-271 AND TYR-273. RC TISSUE=Colon carcinoma; RX PubMed=10910078; RA Lee K., Deng X., Friedman E.; RT "Mirk protein kinase is a mitogen-activated protein kinase substrate RT that mediates survival of colon cancer cells."; RL Cancer Res. 60:3631-3637(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M., RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Pancreas; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, AND INTERACTION WITH DCOHM; MAP2K3 AND TCF1. RC TISSUE=Muscle; RX PubMed=11980910; DOI=10.1074/jbc.M203257200; RA Lim S., Jin K., Friedman E.; RT "Mirk protein kinase is activated by MKK3 and functions as a RT transcriptional activator of HNF1alpha."; RL J. Biol. Chem. 277:25040-25046(2002). RN [6] RP FUNCTION, DIMERIZATION, INTERACTION WITH RANBP9, AND IDENTIFICATION IN RP A COMPLEX WITH RAN; RANBP9 AND COPS5. RX PubMed=14500717; DOI=10.1074/jbc.M307556200; RA Zou Y., Lim S., Lee K., Deng X., Friedman E.; RT "Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epithelial RT cell migration and is negatively regulated by the Met adaptor Ran- RT binding protein M."; RL J. Biol. Chem. 278:49573-49581(2003). RN [7] RP INTERACTION WITH DCAF7. RX PubMed=14593110; DOI=10.1074/jbc.M301769200; RA Skurat A.V., Dietrich A.D.; RT "Phosphorylation of Ser640 in muscle glycogen synthase by DYRK family RT protein kinases."; RL J. Biol. Chem. 279:2490-2498(2004). RN [8] RP CATALYTIC ACTIVITY. RX PubMed=22998443; DOI=10.1021/jm301034u; RA Tahtouh T., Elkins J.M., Filippakopoulos P., Soundararajan M., RA Burgy G., Durieu E., Cochet C., Schmid R.S., Lo D.C., Delhommel F., RA Oberholzer A.E., Pearl L.H., Carreaux F., Bazureau J.P., Knapp S., RA Meijer L.; RT "Selectivity, cocrystal structures, and neuroprotective properties of RT leucettines, a family of protein kinase inhibitors derived from the RT marine sponge alkaloid leucettamine B."; RL J. Med. Chem. 55:9312-9330(2012). RN [9] RP FUNCTION, VARIANTS AOMS3 PRO-90 AND CYS-102, AND CHARACTERIZATION OF RP VARIANTS AOMS3 PRO-90 AND CYS-102. RX PubMed=24827035; DOI=10.1056/NEJMoa1301824; RA Keramati A.R., Fathzadeh M., Go G.W., Singh R., Choi M., Faramarzi S., RA Mane S., Kasaei M., Sarajzadeh-Fard K., Hwa J., Kidd K.K., RA Babaee Bigi M.A., Malekzadeh R., Hosseinian A., Babaei M., RA Lifton R.P., Mani A.; RT "A form of the metabolic syndrome associated with mutations in RT DYRK1B."; RL N. Engl. J. Med. 370:1909-1919(2014). RN [10] RP VARIANTS [LARGE SCALE ANALYSIS] PRO-28; HIS-102; GLY-234 AND ARG-275. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Dual-specificity kinase which possesses both CC serine/threonine and tyrosine kinase activities. Enhances the CC transcriptional activity of TCF1/HNF1A and FOXO1. Inhibits CC epithelial cell migration. Mediates colon carcinoma cell survival CC in mitogen-poor environments. Inhibits the SHH and WNT1 pathways, CC thereby enhancing adipogenesis. In addition, promotes expression CC of the gluconeogenic enzyme glucose-6-phosphatase (G6PC). CC {ECO:0000269|PubMed:10910078, ECO:0000269|PubMed:11980910, CC ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:24827035}. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC {ECO:0000269|PubMed:22998443}. CC -!- ENZYME REGULATION: Inhibited by RANBP9. CC -!- SUBUNIT: Dimer. Interacts with DCOHM, MAP2K3/MKK3, RANBP9 and CC TCF1/HNF1A. Part of a complex consisting of RANBP9, RAN, DYRK1B CC and COPS5. Interacts with DCAF7. {ECO:0000269|PubMed:11980910, CC ECO:0000269|PubMed:14500717, ECO:0000269|PubMed:14593110}. CC -!- INTERACTION: CC P61962:DCAF7; NbExp=2; IntAct=EBI-634187, EBI-359808; CC P20823:HNF1A; NbExp=4; IntAct=EBI-634187, EBI-636034; CC Q9BRK4:LZTS2; NbExp=3; IntAct=EBI-634187, EBI-741037; CC P46734:MAP2K3; NbExp=2; IntAct=EBI-634187, EBI-602462; CC Q9H0N5:PCBD2; NbExp=2; IntAct=EBI-634187, EBI-634289; CC Q96S59:RANBP9; NbExp=4; IntAct=EBI-634187, EBI-636085; CC P06400:RB1; NbExp=3; IntAct=EBI-634187, EBI-491274; CC P28749:RBL1; NbExp=3; IntAct=EBI-634187, EBI-971402; CC Q12815:TROAP; NbExp=3; IntAct=EBI-634187, EBI-2349743; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9Y463-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y463-2; Sequence=VSP_004925; CC Name=3; CC IsoId=Q9Y463-3; Sequence=VSP_004926; CC -!- TISSUE SPECIFICITY: Highest expression in skeletal muscle, testis, CC heart and brain with little expression in colon or lung. Expressed CC in a variety of tumor cell lines. {ECO:0000269|PubMed:10910078}. CC -!- PTM: Autophosphorylated on tyrosine residues. Phosphorylated by CC MAP kinase. Tyrosine phosphorylation may be required for CC dimerization. {ECO:0000269|PubMed:10910078}. CC -!- DISEASE: Abdominal obesity-metabolic syndrome 3 (AOMS3) CC [MIM:615812]: A form of abdominal obesity-metabolic syndrome, a CC disorder characterized by abdominal obesity, high triglycerides, CC low levels of high density lipoprotein cholesterol, high blood CC pressure, and elevated fasting glucose levels. AOMS3 is CC characterized by early-onset coronary artery disease, central CC obesity, hypertension, and diabetes. CC {ECO:0000269|PubMed:24827035}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC CC Ser/Thr protein kinase family. MNB/DYRK subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC28914.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/DYRK1BID43235ch19q13.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; Y17999; CAA76991.1; -; mRNA. DR EMBL; Y17999; CAA76990.1; -; mRNA. DR EMBL; Y17999; CAA76989.1; -; mRNA. DR EMBL; AF205861; AAF15893.1; -; mRNA. DR EMBL; AC005393; AAC28914.1; ALT_SEQ; Genomic_DNA. DR EMBL; BC018751; AAH18751.1; -; mRNA. DR EMBL; BC025291; AAH25291.1; -; mRNA. DR CCDS; CCDS12543.1; -. [Q9Y463-1] DR CCDS; CCDS12544.1; -. [Q9Y463-3] DR CCDS; CCDS46075.1; -. [Q9Y463-2] DR PIR; JG0195; JG0195. DR RefSeq; NP_004705.1; NM_004714.2. [Q9Y463-1] DR RefSeq; NP_006474.1; NM_006483.2. [Q9Y463-2] DR RefSeq; NP_006475.1; NM_006484.2. [Q9Y463-3] DR RefSeq; XP_005259455.1; XM_005259398.3. [Q9Y463-1] DR RefSeq; XP_011547118.1; XM_011548816.1. [Q9Y463-1] DR UniGene; Hs.130988; -. DR ProteinModelPortal; Q9Y463; -. DR SMR; Q9Y463; 95-443. DR BioGrid; 114596; 58. DR IntAct; Q9Y463; 54. DR MINT; MINT-2790122; -. DR STRING; 9606.ENSP00000312789; -. DR BindingDB; Q9Y463; -. DR ChEMBL; CHEMBL5543; -. DR GuidetoPHARMACOLOGY; 2010; -. DR PhosphoSite; Q9Y463; -. DR BioMuta; DYRK1B; -. DR DMDM; 9296963; -. DR MaxQB; Q9Y463; -. DR PaxDb; Q9Y463; -. DR PRIDE; Q9Y463; -. DR DNASU; 9149; -. DR Ensembl; ENST00000323039; ENSP00000312789; ENSG00000105204. [Q9Y463-1] DR Ensembl; ENST00000348817; ENSP00000221803; ENSG00000105204. [Q9Y463-3] DR Ensembl; ENST00000430012; ENSP00000403182; ENSG00000105204. [Q9Y463-2] DR Ensembl; ENST00000593685; ENSP00000469863; ENSG00000105204. [Q9Y463-1] DR Ensembl; ENST00000597639; ENSP00000472941; ENSG00000105204. [Q9Y463-3] DR Ensembl; ENST00000625388; ENSP00000486839; ENSG00000281320. [Q9Y463-3] DR Ensembl; ENST00000625438; ENSP00000487313; ENSG00000281320. [Q9Y463-3] DR Ensembl; ENST00000625757; ENSP00000485915; ENSG00000281320. [Q9Y463-1] DR Ensembl; ENST00000627034; ENSP00000487539; ENSG00000281320. [Q9Y463-2] DR Ensembl; ENST00000631090; ENSP00000486377; ENSG00000281320. [Q9Y463-1] DR GeneID; 9149; -. DR KEGG; hsa:9149; -. DR UCSC; uc002omi.3; human. [Q9Y463-3] DR UCSC; uc002omj.3; human. [Q9Y463-1] DR UCSC; uc002omk.3; human. [Q9Y463-2] DR CTD; 9149; -. DR GeneCards; DYRK1B; -. DR HGNC; HGNC:3092; DYRK1B. DR HPA; HPA028786; -. DR MIM; 604556; gene. DR MIM; 615812; phenotype. DR neXtProt; NX_Q9Y463; -. DR PharmGKB; PA27549; -. DR eggNOG; KOG0667; Eukaryota. DR eggNOG; ENOG410XPET; LUCA. DR GeneTree; ENSGT00760000119032; -. DR HOGENOM; HOG000220863; -. DR HOVERGEN; HBG051425; -. DR InParanoid; Q9Y463; -. DR KO; K08825; -. DR OMA; HKPAATQ; -. DR OrthoDB; EOG77127N; -. DR PhylomeDB; Q9Y463; -. DR TreeFam; TF314624; -. DR BioCyc; MetaCyc:HS02690-MONOMER; -. DR BRENDA; 2.7.12.1; 2681. DR SignaLink; Q9Y463; -. DR ChiTaRS; DYRK1B; human. DR GeneWiki; DYRK1B; -. DR GenomeRNAi; 9149; -. DR NextBio; 34319; -. DR PRO; PR:Q9Y463; -. DR Proteomes; UP000005640; Chromosome 1. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; Q9Y463; -. DR CleanEx; HS_DYRK1B; -. DR ExpressionAtlas; Q9Y463; baseline and differential. DR Genevisible; Q9Y463; HS. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0060612; P:adipose tissue development; IMP:UniProtKB. DR GO; GO:0007520; P:myoblast fusion; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; SSF56112; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Complete proteome; KW Diabetes mellitus; Kinase; Nucleotide-binding; Nucleus; Obesity; KW Phosphoprotein; Polymorphism; Reference proteome; KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase. FT CHAIN 1 629 Dual specificity tyrosine- FT phosphorylation-regulated kinase 1B. FT /FTId=PRO_0000085934. FT DOMAIN 111 431 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 117 125 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 190 193 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT REGION 480 520 Interaction with RANBP9. FT MOTIF 69 86 Bipartite nuclear localization signal. FT {ECO:0000255}. FT COMPBIAS 558 561 Poly-Pro. FT ACT_SITE 239 239 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10027}. FT BINDING 140 140 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 63 63 Phosphotyrosine. FT {ECO:0000250|UniProtKB:Q13627}. FT MOD_RES 92 92 Phosphotyrosine. FT {ECO:0000250|UniProtKB:Q13627}. FT MOD_RES 111 111 Phosphotyrosine. FT {ECO:0000250|UniProtKB:Q13627}. FT MOD_RES 129 129 Phosphotyrosine. FT {ECO:0000250|UniProtKB:Q13627}. FT MOD_RES 171 171 Phosphotyrosine. FT {ECO:0000250|UniProtKB:Q63470}. FT MOD_RES 262 262 Phosphoserine. FT {ECO:0000250|UniProtKB:Q13627}. FT MOD_RES 271 271 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:10910078}. FT MOD_RES 273 273 Phosphotyrosine; by autocatalysis. FT {ECO:0000269|PubMed:10910078}. FT MOD_RES 401 401 Phosphotyrosine. FT {ECO:0000250|UniProtKB:Q13627}. FT MOD_RES 624 624 Phosphoserine. FT {ECO:0000250|UniProtKB:Q13627}. FT VAR_SEQ 366 405 Missing (in isoform 2). FT {ECO:0000303|PubMed:9918863}. FT /FTId=VSP_004925. FT VAR_SEQ 378 405 Missing (in isoform 3). FT {ECO:0000303|PubMed:9918863}. FT /FTId=VSP_004926. FT VARIANT 28 28 L -> P (in dbSNP:rs34587974). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_040454. FT VARIANT 90 90 H -> P (in AOMS3; expression of glucose- FT 6-phosphatase is significantly higher FT than wild-type). FT {ECO:0000269|PubMed:24827035}. FT /FTId=VAR_071773. FT VARIANT 102 102 R -> C (in AOMS3; accumulation of FT intracellular lipid is significantly FT greater than with wild-type protein; FT cells expressing the variant are able to FT transform into mature adipocytes without FT requiring adipogenic medium; expression FT levels of CEBPA, PPARG forms 1 and 2 and FT PPARGC1A are higher and those of GLI1 and FT CDKN1B are lower in cells transfected FT with the mutant protein compared to wild- FT type; WNT1 signaling activity is lower in FT mutant cells compared to wild-type). FT {ECO:0000269|PubMed:24827035}. FT /FTId=VAR_071774. FT VARIANT 102 102 R -> H (in dbSNP:rs55687541). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_040455. FT VARIANT 234 234 S -> G (in dbSNP:rs35858874). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_040456. FT VARIANT 275 275 Q -> R (in a metastatic melanoma sample; FT somatic mutation). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_040457. FT MUTAGEN 140 140 K->R: Abolishes kinase activity. FT {ECO:0000269|PubMed:10910078}. FT MUTAGEN 271 271 Y->F: Abolishes kinase activity; when FT associated with F-273. FT {ECO:0000269|PubMed:10910078}. FT MUTAGEN 273 273 Y->F: Abolishes kinase activity; when FT associated with F-271. FT {ECO:0000269|PubMed:10910078}. SQ SEQUENCE 629 AA; 69198 MW; D7C354AC55943A8B CRC64; MAVPPGHGPF SGFPGPQEHT QVLPDVRLLP RRLPLAFRDA TSAPLRKLSV DLIKTYKHIN EVYYAKKKRR AQQAPPQDSS NKKEKKVLNH GYDDDNHDYI VRSGERWLER YEIDSLIGKG SFGQVVKAYD HQTQELVAIK IIKNKKAFLN QAQIELRLLE LMNQHDTEMK YYIVHLKRHF MFRNHLCLVF ELLSYNLYDL LRNTHFRGVS LNLTRKLAQQ LCTALLFLAT PELSIIHCDL KPENILLCNP KRSAIKIVDF GSSCQLGQRI YQYIQSRFYR SPEVLLGTPY DLAIDMWSLG CILVEMHTGE PLFSGSNEVD QMNRIVEVLG IPPAAMLDQA PKARKYFERL PGGGWTLRRT KELRKDYQGP GTRRLQEVLG VQTGGPGGRR AGEPGHSPAD YLRFQDLVLR MLEYEPAARI SPLGALQHGF FRRTADEATN TGPAGSSAST SPAPLDTCPS SSTASSISSS GGSSGSSSDN RTYRYSNRYC GGPGPPITDC EMNSPQVPPS QPLRPWAGGD VPHKTHQAPA SASSLPGTGA QLPPQPRYLG RPPSPTSPPP PELMDVSLVG GPADCSPPHP APAPQHPAAS ALRTRMTGGR PPLPPPDDPA TLGPHLGLRG VPQSTAASS // ID FLI1_HUMAN Reviewed; 452 AA. AC Q01543; B2R8H2; B4DFV4; B4DTC6; G3V183; Q14319; Q92480; Q9UE07; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 1. DT 11-NOV-2015, entry version 177. DE RecName: Full=Friend leukemia integration 1 transcription factor; DE AltName: Full=Proto-oncogene Fli-1; DE AltName: Full=Transcription factor ERGB; GN Name=FLI1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Bone marrow; RX PubMed=1522903; DOI=10.1038/359162a0; RA Delattre O., Zucman J., Plougastel B., Desmaze C., Melot T., Peter M., RA Kovar H., Joubert I., de Jong P., Rouleau G., Aurias A., Thomas G.; RT "Gene fusion with an ETS DNA-binding domain caused by chromosome RT translocation in human tumours."; RL Nature 359:162-165(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1445800; RA Watson D.K., Smyth F.E., Thompson D.M., Cheng J.Q., Testa J.R., RA Papas T.S., Seth A.; RT "The ERGB/Fli-1 gene: isolation and characterization of a new member RT of the family of human ETS transcription factors."; RL Cell Growth Differ. 3:705-713(1992). RN [3] RP SEQUENCE REVISION. RA Watson D.; RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1394211; RA Prasad D.D., Rao V.N., Reddy E.S.; RT "Structure and expression of human Fli-1 gene."; RL Cancer Res. 52:5833-5837(1992). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Blood; RX PubMed=8439553; DOI=10.1016/0167-4781(93)90283-J; RA Hromas R., May W., Denny C., Raskind W., Moore J., Maki R.A., Beck E., RA Klemsz M.J.; RT "Human FLI-1 localizes to chromosome 11q24 and has an aberrant RT transcript in neuroepithelioma."; RL Biochim. Biophys. Acta 1172:155-158(1993). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND CHROMOSOMAL RP TRANSLOCATION. RX PubMed=1765382; DOI=10.1016/0888-7543(91)90124-W; RA Baud V., Lipinski M., Rassart E., Poliquin L., Bergeron D.; RT "The human homolog of the mouse common viral integration region, FLI1, RT maps to 11q23-q24."; RL Genomics 11:223-224(1991). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Ubhi B.T.S., Rainey D.R., Meredith D.M.; RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4). RC TISSUE=Amygdala, Placenta, and Thymus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 58-452. RX PubMed=9751743; DOI=10.1073/pnas.95.20.11786; RA Zucman-Rossi J., Legoix P., Victor J.M., Lopez B., Thomas G.; RT "Chromosome translocation based on illegitimate recombination in human RT tumors."; RL Proc. Natl. Acad. Sci. U.S.A. 95:11786-11791(1998). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 278-301. RC TISSUE=Placenta; RX PubMed=7542907; DOI=10.1002/gcc.2870130209; RA Bhagirath T., Abe S., Nojima T., Yoshida M.C.; RT "Molecular analysis of a t(11;22) translocation junction in a case of RT Ewing's sarcoma."; RL Genes Chromosomes Cancer 13:126-132(1995). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP STRUCTURE BY NMR OF 276-373. RX PubMed=7773776; DOI=10.1038/nsb1294-871; RA Liang H., Mao X., Olejniczak E.T., Nettesheim D.G., Yu L., RA Meadows R.P., Thompson C.B., Fesik S.W.; RT "Solution structure of the ets domain of Fli-1 when bound to DNA."; RL Nat. Struct. Biol. 1:871-875(1994). RN [16] RP STRUCTURE BY NMR OF 114-198. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the SAM_pnt-domain of the human Friend leukemia RT integration 1 transcription factor."; RL Submitted (NOV-2005) to the PDB data bank. CC -!- FUNCTION: Sequence-specific transcriptional activator. Recognizes CC the DNA sequence 5'-C[CA]GGAAGT-3'. CC -!- SUBUNIT: Can form homodimers or heterodimers with ETV6/TEL1. CC -!- INTERACTION: CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-2271018, EBI-10171902; CC Q8IUQ4:SIAH1; NbExp=3; IntAct=EBI-2271018, EBI-747107; CC O94993:SOX30; NbExp=3; IntAct=EBI-2271018, EBI-742973; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q01543-1; Sequence=Displayed; CC Name=2; CC IsoId=Q01543-2; Sequence=VSP_001478; CC Name=3; CC IsoId=Q01543-3; Sequence=VSP_045276; CC Note=No experimental confirmation available.; CC Name=4; CC IsoId=Q01543-4; Sequence=VSP_046943; CC -!- DISEASE: Ewing sarcoma (ES) [MIM:612219]: A highly malignant, CC metastatic, primitive small round cell tumor of bone and soft CC tissue that affects children and adolescents. It belongs to the CC Ewing sarcoma family of tumors, a group of morphologically CC heterogeneous neoplasms that share the same cytogenetic features. CC They are considered neural tumors derived from cells of the neural CC crest. Ewing sarcoma represents the less differentiated form of CC the tumors. Note=The gene represented in this entry is involved in CC disease pathogenesis. A chromosomal aberration involving FLI1 is CC found in patients with Erwing sarcoma. Translocation CC t(11;22)(q24;q12) with EWSR1. CC -!- MISCELLANEOUS: Located on a fragment of chromosome 11 flanked on CC the centromeric side by the acute lymphoblastic leukemia- CC associated t(4;11)(q21;q23) translocation breakpoint and on the CC telomeric side by the Ewing- and neuroepithelioma-associated CC t(11;22) (q24;q12) breakpoint. CC -!- SIMILARITY: Belongs to the ETS family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 ETS DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00237}. CC -!- SIMILARITY: Contains 1 PNT (pointed) domain. {ECO:0000255|PROSITE- CC ProRule:PRU00762}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/FLI1ID79ch11q24.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X67001; CAA47399.1; -; mRNA. DR EMBL; M98833; AAA35812.2; -; mRNA. DR EMBL; S45205; AAB23637.1; -; mRNA. DR EMBL; M93255; AAA58479.1; -; mRNA. DR EMBL; M93255; AAA58480.1; -; mRNA. DR EMBL; AY029368; AAK50443.1; -; mRNA. DR EMBL; AK294279; BAG57565.1; -; mRNA. DR EMBL; AK300153; BAG61938.1; -; mRNA. DR EMBL; AK313370; BAG36169.1; -; mRNA. DR EMBL; AP001122; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471065; EAW67715.1; -; Genomic_DNA. DR EMBL; CH471065; EAW67718.1; -; Genomic_DNA. DR EMBL; BC001670; AAH01670.1; -; mRNA. DR EMBL; BC010115; AAH10115.1; -; mRNA. DR EMBL; Y17293; CAA76731.1; -; Genomic_DNA. DR EMBL; D38408; BAA07463.1; ALT_TERM; Genomic_DNA. DR CCDS; CCDS44768.1; -. [Q01543-1] DR CCDS; CCDS53725.1; -. [Q01543-3] DR CCDS; CCDS59230.1; -. [Q01543-4] DR CCDS; CCDS59231.1; -. [Q01543-2] DR PIR; I37565; I37565. DR PIR; S29844; S29844. DR RefSeq; NP_001161153.1; NM_001167681.2. [Q01543-3] DR RefSeq; NP_001257939.1; NM_001271010.1. [Q01543-2] DR RefSeq; NP_001257941.1; NM_001271012.1. [Q01543-4] DR RefSeq; NP_002008.2; NM_002017.4. [Q01543-1] DR RefSeq; XP_011541003.1; XM_011542701.1. [Q01543-3] DR UniGene; Hs.504281; -. DR PDB; 1FLI; NMR; -; A=276-373. DR PDB; 1X66; NMR; -; A=114-198. DR PDB; 2YTU; NMR; -; A=100-220. DR PDBsum; 1FLI; -. DR PDBsum; 1X66; -. DR PDBsum; 2YTU; -. DR ProteinModelPortal; Q01543; -. DR SMR; Q01543; 114-254, 276-373. DR BioGrid; 108602; 17. DR IntAct; Q01543; 7. DR MINT; MINT-1189961; -. DR STRING; 9606.ENSP00000399985; -. DR PhosphoSite; Q01543; -. DR BioMuta; FLI1; -. DR DMDM; 399496; -. DR MaxQB; Q01543; -. DR PaxDb; Q01543; -. DR PRIDE; Q01543; -. DR DNASU; 2313; -. DR Ensembl; ENST00000281428; ENSP00000281428; ENSG00000151702. [Q01543-2] DR Ensembl; ENST00000344954; ENSP00000339627; ENSG00000151702. [Q01543-4] DR Ensembl; ENST00000527786; ENSP00000433488; ENSG00000151702. [Q01543-1] DR Ensembl; ENST00000534087; ENSP00000432950; ENSG00000151702. [Q01543-3] DR GeneID; 2313; -. DR KEGG; hsa:2313; -. DR UCSC; uc009zci.3; human. [Q01543-2] DR UCSC; uc010sbt.2; human. DR UCSC; uc010sbu.2; human. [Q01543-1] DR CTD; 2313; -. DR GeneCards; FLI1; -. DR HGNC; HGNC:3749; FLI1. DR MIM; 193067; gene. DR MIM; 612219; phenotype. DR neXtProt; NX_Q01543; -. DR Orphanet; 319; Ewing sarcoma. DR Orphanet; 370334; Extraskeletal Ewing sarcoma. DR Orphanet; 248340; Isolated delta-storage pool disease. DR Orphanet; 851; Paris-Trousseau thrombocytopenia. DR Orphanet; 370348; Peripheral primitive neuroectodermal tumor. DR PharmGKB; PA28170; -. DR eggNOG; KOG3806; Eukaryota. DR eggNOG; ENOG410Z0ZF; LUCA. DR GeneTree; ENSGT00760000118907; -. DR HOGENOM; HOG000290658; -. DR HOVERGEN; HBG001553; -. DR InParanoid; Q01543; -. DR KO; K09436; -. DR OMA; KNGPPPN; -. DR OrthoDB; EOG73V6K8; -. DR PhylomeDB; Q01543; -. DR TreeFam; TF350537; -. DR ChiTaRS; FLI1; human. DR EvolutionaryTrace; Q01543; -. DR GeneWiki; FLI1; -. DR GenomeRNAi; 2313; -. DR NextBio; 35471593; -. DR PMAP-CutDB; Q01543; -. DR PRO; PR:Q01543; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; Q01543; -. DR CleanEx; HS_FLI1; -. DR ExpressionAtlas; Q01543; baseline and differential. DR Genevisible; Q01543; HS. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IEA:Ensembl. DR GO; GO:0008015; P:blood circulation; IEA:Ensembl. DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central. DR GO; GO:0007599; P:hemostasis; TAS:ProtInc. DR GO; GO:0035855; P:megakaryocyte development; IEA:Ensembl. DR GO; GO:0009887; P:organ morphogenesis; TAS:ProtInc. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IBA:GO_Central. DR Gene3D; 1.10.10.10; -; 1. DR Gene3D; 1.10.150.50; -; 1. DR InterPro; IPR000418; Ets_dom. DR InterPro; IPR003118; Pointed_dom. DR InterPro; IPR013761; SAM/pointed. DR InterPro; IPR011991; WHTH_DNA-bd_dom. DR Pfam; PF00178; Ets; 1. DR Pfam; PF02198; SAM_PNT; 1. DR PRINTS; PR00454; ETSDOMAIN. DR SMART; SM00413; ETS; 1. DR SMART; SM00251; SAM_PNT; 1. DR SUPFAM; SSF47769; SSF47769; 1. DR PROSITE; PS00345; ETS_DOMAIN_1; 1. DR PROSITE; PS00346; ETS_DOMAIN_2; 1. DR PROSITE; PS50061; ETS_DOMAIN_3; 1. DR PROSITE; PS51433; PNT; 1. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; KW Chromosomal rearrangement; Complete proteome; DNA-binding; Nucleus; KW Phosphoprotein; Proto-oncogene; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1 452 Friend leukemia integration 1 FT transcription factor. FT /FTId=PRO_0000204124. FT DOMAIN 112 198 PNT. {ECO:0000255|PROSITE- FT ProRule:PRU00762}. FT DNA_BIND 281 361 ETS. {ECO:0000255|PROSITE- FT ProRule:PRU00237}. FT MOD_RES 39 39 Phosphoserine. FT {ECO:0000250|UniProtKB:P26323}. FT VAR_SEQ 1 197 MDGTIKEALSVVSDDQSLFDSAYGAAAHLPKADMTASGSPD FT YGQPHKINPLPPQQEWINQPVRVNVKREYDHMNGSRESPVD FT CSVSKCSKLVGGGESNPMNYNSYMDEKNGPPPPNMTTNERR FT VIVPADPTLWTQEHVRQWLEWAIKEYSLMEIDTSFFQNMDG FT KELCKMNKEDFLRATTLYNTEVLLSHLSYLRES -> MDPG FT (in isoform 4). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_046943. FT VAR_SEQ 1 76 MDGTIKEALSVVSDDQSLFDSAYGAAAHLPKADMTASGSPD FT YGQPHKINPLPPQQEWINQPVRVNVKREYDHMNGS -> ME FT GGLAGERA (in isoform 2). FT {ECO:0000303|PubMed:1765382, FT ECO:0000303|PubMed:8439553}. FT /FTId=VSP_001478. FT VAR_SEQ 1 33 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_045276. FT CONFLICT 69 69 E -> V (in Ref. 5; AAA58479). FT {ECO:0000305}. FT CONFLICT 77 77 Missing (in Ref. 5; AAA58479). FT {ECO:0000305}. FT CONFLICT 130 130 P -> A (in Ref. 5; AAA58479/AAA58480). FT {ECO:0000305}. FT CONFLICT 133 133 W -> V (in Ref. 5; AAA58479/AAA58480). FT {ECO:0000305}. FT CONFLICT 294 294 S -> N (in Ref. 8; BAG61938). FT {ECO:0000305}. FT CONFLICT 323 323 E -> Q (in Ref. 4; AAB23637 and 5; FT AAA58479/AAA58480). {ECO:0000305}. FT CONFLICT 426 426 Missing (in Ref. 5; AAA58479/AAA58480). FT {ECO:0000305}. FT STRAND 112 114 {ECO:0000244|PDB:2YTU}. FT STRAND 120 122 {ECO:0000244|PDB:1X66}. FT HELIX 130 132 {ECO:0000244|PDB:1X66}. FT HELIX 137 148 {ECO:0000244|PDB:1X66}. FT HELIX 156 159 {ECO:0000244|PDB:1X66}. FT HELIX 164 169 {ECO:0000244|PDB:1X66}. FT HELIX 172 176 {ECO:0000244|PDB:1X66}. FT HELIX 181 195 {ECO:0000244|PDB:1X66}. FT HELIX 284 292 {ECO:0000244|PDB:1FLI}. FT STRAND 298 301 {ECO:0000244|PDB:1FLI}. FT STRAND 305 308 {ECO:0000244|PDB:1FLI}. FT HELIX 314 324 {ECO:0000244|PDB:1FLI}. FT HELIX 333 344 {ECO:0000244|PDB:1FLI}. FT HELIX 352 354 {ECO:0000244|PDB:1FLI}. FT STRAND 355 357 {ECO:0000244|PDB:1FLI}. FT STRAND 366 368 {ECO:0000244|PDB:1FLI}. SQ SEQUENCE 452 AA; 50982 MW; 9C2AAEEAF683F3FA CRC64; MDGTIKEALS VVSDDQSLFD SAYGAAAHLP KADMTASGSP DYGQPHKINP LPPQQEWINQ PVRVNVKREY DHMNGSRESP VDCSVSKCSK LVGGGESNPM NYNSYMDEKN GPPPPNMTTN ERRVIVPADP TLWTQEHVRQ WLEWAIKEYS LMEIDTSFFQ NMDGKELCKM NKEDFLRATT LYNTEVLLSH LSYLRESSLL AYNTTSHTDQ SSRLSVKEDP SYDSVRRGAW GNNMNSGLNK SPPLGGAQTI SKNTEQRPQP DPYQILGPTS SRLANPGSGQ IQLWQFLLEL LSDSANASCI TWEGTNGEFK MTDPDEVARR WGERKSKPNM NYDKLSRALR YYYDKNIMTK VHGKRYAYKF DFHGIAQALQ PHPTESSMYK YPSDISYMPS YHAHQQKVNF VPPHPSSMPV TSSSFFGAAS QYWTSPTGGI YPNPNVPRHP NTHVPSHLGS YY // ID FOG1_HUMAN Reviewed; 1006 AA. AC Q8IX07; DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 11-NOV-2015, entry version 120. DE RecName: Full=Zinc finger protein ZFPM1; DE AltName: Full=Friend of GATA protein 1; DE Short=FOG-1; DE Short=Friend of GATA 1; DE AltName: Full=Zinc finger protein 89A; DE AltName: Full=Zinc finger protein multitype 1; GN Name=ZFPM1; Synonyms=FOG1, ZFN89A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INTERACTION WITH RP GATA1 AND GATA2. RC TISSUE=Megakaryocyte; RX PubMed=12483298; DOI=10.1007/s00439-002-0832-1; RA Freson K., Thys C., Wittewrongel C., Vermylen J., Hoylaerts M.F., RA Van Geet C.; RT "Molecular cloning and characterization of the GATA1 cofactor human RT FOG1 and assessment of its binding to GATA1 proteins carrying D218 RT substitutions."; RL Hum. Genet. 112:42-49(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., RA Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Prostate cancer; RX PubMed=17487921; DOI=10.1002/elps.200600782; RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.; RT "Toward a global characterization of the phosphoproteome in prostate RT cancer cells: identification of phosphoproteins in the LNCaP cell RT line."; RL Electrophoresis 28:2027-2034(2007). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-786, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-901 AND SER-909, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-671; SER-786; SER-901 RP AND SER-914, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Transcription regulator that plays an essential role in CC erythroid and megakaryocytic cell differentiation. Essential CC cofactor that acts via the formation of a heterodimer with CC transcription factors of the GATA family GATA1, GATA2 and GATA3. CC Such heterodimer can both activate or repress transcriptional CC activity, depending on the cell and promoter context. The CC heterodimer formed with GATA proteins is essential to activate CC expression of genes such as NFE2, ITGA2B, alpha- and beta-globin, CC while it represses expression of KLF1. May be involved in CC regulation of some genes in gonads. May also be involved in CC cardiac development, in a non-redundant way with ZFPM2/FOG2 (By CC similarity). {ECO:0000250}. CC -!- SUBUNIT: Interacts with corepressor CTBP2; this interaction is CC however not essential for corepressor activity (By similarity). CC Interacts with the N-terminal zinc-finger of GATA1, GATA2 and CC probably GATA3. {ECO:0000250, ECO:0000269|PubMed:12483298}. CC -!- INTERACTION: CC P49841:GSK3B; NbExp=2; IntAct=EBI-3942619, EBI-373586; CC Q09028:RBBP4; NbExp=4; IntAct=EBI-3942619, EBI-620823; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Mainly expressed in hematopoietic tissues. CC Also expressed in adult cerebellum, stomach, lymph node, liver and CC pancreas. Expressed in fetal heart, liver and spleen. CC {ECO:0000269|PubMed:12483298}. CC -!- DOMAIN: The CCHC-type zinc fingers 1, 5, 6 and 9 directly bind to CC GATA-type zinc fingers. The Tyr residue adjacent to the last Cys CC of the CCHC-type zinc finger is essential for the interaction with CC GATA-type zinc fingers (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the FOG (Friend of GATA) family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 4 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- SIMILARITY: Contains 5 C2HC-type zinc fingers. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF488691; AAN45858.1; -; mRNA. DR EMBL; AC116552; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC135049; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471184; EAW66806.1; -; Genomic_DNA. DR CCDS; CCDS32502.1; -. DR RefSeq; NP_722520.2; NM_153813.2. DR UniGene; Hs.632218; -. DR PDB; 2XU7; X-ray; 1.90 A; C/D=1-15. DR PDBsum; 2XU7; -. DR ProteinModelPortal; Q8IX07; -. DR SMR; Q8IX07; 85-209, 315-347. DR BioGrid; 127806; 10. DR DIP; DIP-48415N; -. DR IntAct; Q8IX07; 3. DR STRING; 9606.ENSP00000326630; -. DR PhosphoSite; Q8IX07; -. DR BioMuta; ZFPM1; -. DR DMDM; 296434508; -. DR MaxQB; Q8IX07; -. DR PaxDb; Q8IX07; -. DR PRIDE; Q8IX07; -. DR Ensembl; ENST00000319555; ENSP00000326630; ENSG00000179588. DR GeneID; 161882; -. DR KEGG; hsa:161882; -. DR UCSC; uc002fkv.3; human. DR CTD; 161882; -. DR GeneCards; ZFPM1; -. DR HGNC; HGNC:19762; ZFPM1. DR HPA; HPA046603; -. DR MIM; 601950; gene. DR neXtProt; NX_Q8IX07; -. DR PharmGKB; PA134920282; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00530000063823; -. DR HOGENOM; HOG000112626; -. DR HOVERGEN; HBG101018; -. DR InParanoid; Q8IX07; -. DR KO; K17441; -. DR OMA; YSCPAAP; -. DR OrthoDB; EOG74TWXR; -. DR PhylomeDB; Q8IX07; -. DR TreeFam; TF331342; -. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR ChiTaRS; ZFPM1; human. DR GeneWiki; ZFPM1; -. DR GenomeRNAi; 161882; -. DR NextBio; 88126; -. DR PRO; PR:Q8IX07; -. DR Proteomes; UP000005640; Chromosome 16. DR Bgee; Q8IX07; -. DR CleanEx; HS_ZFPM1; -. DR ExpressionAtlas; Q8IX07; baseline and differential. DR Genevisible; Q8IX07; HS. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005667; C:transcription factor complex; IDA:BHF-UCL. DR GO; GO:0017053; C:transcriptional repressor complex; IDA:BHF-UCL. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0001085; F:RNA polymerase II transcription factor binding; IPI:BHF-UCL. DR GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:BHF-UCL. DR GO; GO:0060413; P:atrial septum morphogenesis; ISS:BHF-UCL. DR GO; GO:0003181; P:atrioventricular valve morphogenesis; ISS:BHF-UCL. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; ISS:BHF-UCL. DR GO; GO:0060318; P:definitive erythrocyte differentiation; IEA:Ensembl. DR GO; GO:0035162; P:embryonic hemopoiesis; ISS:BHF-UCL. DR GO; GO:0030218; P:erythrocyte differentiation; ISS:BHF-UCL. DR GO; GO:0030851; P:granulocyte differentiation; IEA:Ensembl. DR GO; GO:0007507; P:heart development; IBA:GO_Central. DR GO; GO:0035855; P:megakaryocyte development; IEA:Ensembl. DR GO; GO:0030219; P:megakaryocyte differentiation; ISS:BHF-UCL. DR GO; GO:0003192; P:mitral valve formation; ISS:BHF-UCL. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:BHF-UCL. DR GO; GO:0045403; P:negative regulation of interleukin-4 biosynthetic process; IDA:BHF-UCL. DR GO; GO:0060377; P:negative regulation of mast cell differentiation; ISS:BHF-UCL. DR GO; GO:0032091; P:negative regulation of protein binding; ISS:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:GOC. DR GO; GO:0003151; P:outflow tract morphogenesis; ISS:BHF-UCL. DR GO; GO:0030220; P:platelet formation; IGI:BHF-UCL. DR GO; GO:0045078; P:positive regulation of interferon-gamma biosynthetic process; IDA:BHF-UCL. DR GO; GO:0060319; P:primitive erythrocyte differentiation; IEA:Ensembl. DR GO; GO:0032642; P:regulation of chemokine production; IEA:Ensembl. DR GO; GO:0010724; P:regulation of definitive erythrocyte differentiation; IDA:BHF-UCL. DR GO; GO:0002295; P:T-helper cell lineage commitment; IC:BHF-UCL. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0071733; P:transcriptional activation by promoter-enhancer looping; ISS:BHF-UCL. DR GO; GO:0003195; P:tricuspid valve formation; ISS:BHF-UCL. DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL. DR Gene3D; 3.30.160.60; -; 2. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR SMART; SM00355; ZnF_C2H2; 9. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 2. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 2. PE 1: Evidence at protein level; KW 3D-structure; Activator; Complete proteome; DNA-binding; KW Metal-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 1006 Zinc finger protein ZFPM1. FT /FTId=PRO_0000221041. FT ZN_FING 241 264 C2HC-type 1. FT ZN_FING 290 314 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 320 342 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 348 371 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 577 699 C2HC-type 2. FT ZN_FING 683 705 C2HC-type 3. FT ZN_FING 817 839 C2HC-type 4. FT ZN_FING 854 877 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 974 1000 C2HC-type 5. FT REGION 330 341 Interaction with TACC3. {ECO:0000250}. FT REGION 794 800 Interaction with CTBP2. {ECO:0000250}. FT MOD_RES 128 128 Phosphoserine. FT {ECO:0000250|UniProtKB:O35615}. FT MOD_RES 272 272 Phosphoserine. FT {ECO:0000250|UniProtKB:O35615}. FT MOD_RES 491 491 Phosphoserine. FT {ECO:0000250|UniProtKB:O35615}. FT MOD_RES 494 494 Phosphoserine. FT {ECO:0000250|UniProtKB:O35615}. FT MOD_RES 671 671 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 786 786 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 901 901 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 909 909 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 914 914 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 935 935 Phosphoserine. FT {ECO:0000250|UniProtKB:O35615}. FT VARIANT 70 70 G -> A (in dbSNP:rs34916016). FT /FTId=VAR_057491. FT CONFLICT 22 22 R -> G (in Ref. 1; AAN45858). FT {ECO:0000305}. FT CONFLICT 444 447 EPLA -> AP (in Ref. 1; AAN45858). FT {ECO:0000305}. SQ SEQUENCE 1006 AA; 104888 MW; E9C2363503A64898 CRC64; MSRRKQSNPR QIKRSLGDME AREEVQLVGA SHMEQKATAP EAPSPPSADV NSPPPLPPPT SPGGPKELEG QEPEPRPTEE EPGSPWSGPD ELEPVVQDGQ RRIRARLSLA TGLSWGPFHG SVQTRASSPR QAEPSPALTL LLVDEACWLR TLPQALTEAE ANTEIHRKDD ALWCRVTKPV PAGGLLSVLL TAEPHSTPGH PVKKEPAEPT CPAPAHDLQL LPQQAGMASI LATAVINKDV FPCKDCGIWY RSERNLQAHL LYYCASRQGT GSPAAAATDE KPKETYPNER VCPFPQCRKS CPSASSLEIH MRSHSGERPF VCLICLSAFT TKANCERHLK VHTDTLSGVC HSCGFISTTR DILYSHLVTN HMVCQPGSKG EIYSPGAGHP ATKLPPDSLG SFQQQHTALQ GPLASADLGL APTPSPGLDR KALAEATNGE ARAEPLAQNG GSSEPPAAPR SIKVEAVEEP EAAPILGPGE PGPQAPSRTP SPRSPAPARV KAELSSPTPG SSPVPGELGL AGALFLPQYV FGPDAAPPAS EILAKMSELV HSRLQQGAGA GAGGAQTGLF PGAPKGATCF ECEITFSNVN NYYVHKRLYC SGRRAPEDAP AARRPKAPPG PARAPPGQPA EPDAPRSSPG PGAREEGAGG AATPEDGAGG RGSEGSQSPG SSVDDAEDDP SRTLCEACNI RFSRHETYTV HKRYYCASRH DPPPRRPAAP PGPPGPAAPP APSPAAPVRT RRRRKLYELH AAGAPPPPPP GHAPAPESPR PGSGSGSGPG LAPARSPGPA ADGPIDLSKK PRRPLPGAPA PALADYHECT ACRVSFHSLE AYLAHKKYSC PAAPPPGALG LPAAACPYCP PNGPVRGDLL EHFRLAHGLL LGAPLAGPGV EARTPADRGP SPAPAPAASP QPGSRGPRDG LGPEPQEPPP GPPPSPAAAP EAVPPPPAPP SYSDKGVQTP SKGTPAPLPN GNHRYCRLCN IKFSSLSTFI AHKKYYCSSH AAEHVK // ID FOXP2_HUMAN Reviewed; 715 AA. AC O15409; A0AUV6; A4D0U8; A6NNW4; B4DLD9; Q6ZND1; Q75MJ3; Q8IZE0; AC Q8N0W2; Q8N6B7; Q8N6B8; Q8NFQ1; Q8NFQ2; Q8NFQ3; Q8NFQ4; Q8TD74; DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot. DT 05-DEC-2001, sequence version 2. DT 11-NOV-2015, entry version 157. DE RecName: Full=Forkhead box protein P2; DE AltName: Full=CAG repeat protein 44; DE AltName: Full=Trinucleotide repeat-containing gene 10 protein; GN Name=FOXP2; Synonyms=CAGH44, TNRC10; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, AND RP VARIANT SPCH1 HIS-553. RX PubMed=11586359; DOI=10.1038/35097076; RA Lai C.S.L., Fisher S.E., Hurst J.A., Vargha-Khadem F., Monaco A.P.; RT "A forkhead-domain gene is mutated in a severe speech and language RT disorder."; RL Nature 413:519-523(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 7), NUCLEOTIDE SEQUENCE [MRNA] OF RP 1-415 (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 259-715 (ISOFORM 6), RP AND TISSUE SPECIFICITY. RC TISSUE=Brain, Corpus striatum, Fetal brain, and Frontal cortex; RX PubMed=12189486; DOI=10.1007/s00439-002-0768-5; RA Bruce H.A., Margolis R.L.; RT "FOXP2: novel exons, splice variants, and CAG repeat length RT stability."; RL Hum. Genet. 111:136-144(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RA Vincent J.B., Scherer S.W.; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4). RC TISSUE=Brain; RA Guo J.H., Chen L., Yu L.; RL Submitted (AUG-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 8 AND 9). RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., RA Mural R.J., Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-304 (ISOFORM 1). RC TISSUE=Brain cortex; RX PubMed=9225980; DOI=10.1007/s004390050476; RA Margolis R.L., Abraham M.R., Gatchell S.B., Li S.-H., Kidwai A.S., RA Breschel T.S., Stine O.C., Callahan C., McInnis M.G., Ross C.A.; RT "cDNAs with long CAG trinucleotide repeats from human brain."; RL Hum. Genet. 100:114-122(1997). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 113-329. RX PubMed=12192408; DOI=10.1038/nature01025; RA Enard W., Przeworski M., Fisher S.E., Lai C.S.L., Wiebe V., Kitano T., RA Monaco A.P., Paeaebo S.; RT "Molecular evolution of FOXP2, a gene involved in speech and RT language."; RL Nature 418:869-872(2002). RN [12] RP DEVELOPMENTAL STAGE. RX PubMed=15056695; DOI=10.1523/JNEUROSCI.5589-03.2004; RA Teramitsu I., Kudo L.C., London S.E., Geschwind D.H., White S.A.; RT "Parallel FoxP1 and FoxP2 expression in songbird and human brain RT predicts functional interaction."; RL J. Neurosci. 24:3152-3163(2004). CC -!- FUNCTION: Transcriptional repressor that may play a role in the CC specification and differentiation of lung epithelium. May also CC play a role in developing neural, gastrointestinal and CC cardiovascular tissues. Can act with CTBP1 to synergistically CC repress transcription but CTPBP1 is not essential. Plays a role in CC synapse formation by regulating SRPX2 levels. Involved in neural CC mechanisms mediating the development of speech and language. CC -!- SUBUNIT: Forms homodimers and heterodimers with FOXP1 and FOXP4. CC Dimerization is required for DNA-binding. Interacts with CTBP1 (By CC similarity). {ECO:0000250}. CC -!- INTERACTION: CC Q08117:AES; NbExp=3; IntAct=EBI-983612, EBI-717810; CC P24863:CCNC; NbExp=3; IntAct=EBI-983612, EBI-395261; CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-983612, EBI-10171858; CC P56545:CTBP2; NbExp=3; IntAct=EBI-983612, EBI-741533; CC Q86V42:FAM124A; NbExp=3; IntAct=EBI-983612, EBI-744506; CC Q13526:PIN1; NbExp=3; IntAct=EBI-983612, EBI-714158; CC O00560:SDCBP; NbExp=3; IntAct=EBI-983612, EBI-727004; CC Q96A04:TSACC; NbExp=3; IntAct=EBI-983612, EBI-740411; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=9; CC Name=1; Synonyms=I; CC IsoId=O15409-1; Sequence=Displayed; CC Name=2; Synonyms=II; CC IsoId=O15409-3; Sequence=Not described; CC Name=3; Synonyms=III, IV; CC IsoId=O15409-2; Sequence=VSP_001558; CC Name=4; CC IsoId=O15409-4; Sequence=VSP_011532; CC Name=5; CC IsoId=O15409-5; Sequence=VSP_011532, VSP_011535, VSP_011536; CC Name=6; Synonyms=FOXP2-S; CC IsoId=O15409-6; Sequence=VSP_011538, VSP_011539; CC Name=7; CC IsoId=O15409-7; Sequence=VSP_011537; CC Name=8; CC IsoId=O15409-8; Sequence=VSP_011533, VSP_011534; CC Note=No experimental confirmation available.; CC Name=9; CC IsoId=O15409-9; Sequence=VSP_043464; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 6 are expressed in adult CC and fetal brain, caudate nucleus and lung. CC {ECO:0000269|PubMed:12189486}. CC -!- DEVELOPMENTAL STAGE: Expressed in the brain at 15 and 22 weeks of CC gestation, with a pattern of strong cortical, basal ganglia, CC thalamic and cerebellar expression. Highly expressed in the head CC and tail of nucleus caudatus and putamen. Restricted expression CC within the globus pallidus, with high levels in the pars interna, CC which provides the principal source of output from the basal CC ganglia to the nucleus centrum medianum thalami (CM) and the major CC motor relay nuclei of the thalamus. In the thalamus, present in CC the CM and nucleus medialis dorsalis thalami. Lower levels are CC observed in the nuclei anterior thalami, dorsal and ventral, and CC the nucleus parafascicularis thalami. Expressed in the ventrobasal CC complex comprising the nucleus ventralis posterior CC lateralis/medialis. The ventral tier of the thalamus exhibits CC strong expression, including nuclei ventralis anterior, lateralis CC and posterior lateralis pars oralis. Also expressed in the nucleus CC subthalamicus bilaterally and in the nucleus ruber. CC {ECO:0000269|PubMed:15056695}. CC -!- DOMAIN: The leucine-zipper is required for dimerization and CC transcriptional repression. {ECO:0000250}. CC -!- DISEASE: Speech-language disorder 1 (SPCH1) [MIM:602081]: A CC disorder characterized by severe orofacial dyspraxia resulting in CC largely incomprehensible speech. Affected individuals have severe CC impairment in the selection and sequencing of fine orofacial CC movements which are necessary for articulation, and deficits in CC several facets of grammatical skills and language processing, such CC as the ability to break up words into their constituent phonemes. CC {ECO:0000269|PubMed:11586359}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Note=A chromosomal aberration involving FOXP2 is a cause CC of severe speech and language impairment. Translocation CC t(5;7)(q22;q31.2). CC -!- SIMILARITY: Contains 1 C2H2-type zinc finger. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 fork-head DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00089}. CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Talking heads - Issue CC 51 of October 2004; CC URL="http://web.expasy.org/spotlight/back_issues/051"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=FOXP2 entry; CC URL="https://en.wikipedia.org/wiki/FOXP2"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF337817; AAL10762.1; -; mRNA. DR EMBL; AF467252; AAM60762.1; -; mRNA. DR EMBL; AF467253; AAM60763.1; -; mRNA. DR EMBL; AF467254; AAM60764.1; -; mRNA. DR EMBL; AF467255; AAM60765.1; -; mRNA. DR EMBL; AF467256; AAM60766.1; -; mRNA. DR EMBL; AF467257; AAM60767.1; -; mRNA. DR EMBL; AF493430; AAM13672.1; -; mRNA. DR EMBL; AY144615; AAN60016.1; -; mRNA. DR EMBL; AK131266; BAD18444.1; ALT_SEQ; mRNA. DR EMBL; AK296957; BAG59501.1; -; mRNA. DR EMBL; AC003992; AAS07399.1; -; Genomic_DNA. DR EMBL; AC020606; AAS07502.1; -; Genomic_DNA. DR EMBL; AC073626; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC074000; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC092148; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC092606; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH236947; EAL24367.1; -; Genomic_DNA. DR EMBL; CH236947; EAL24369.1; -; Genomic_DNA. DR EMBL; CH471070; EAW83484.1; -; Genomic_DNA. DR EMBL; CH471070; EAW83486.1; -; Genomic_DNA. DR EMBL; BC126104; AAI26105.1; -; mRNA. DR EMBL; BC143866; AAI43867.1; -; mRNA. DR EMBL; U80741; AAB91439.1; -; mRNA. DR EMBL; AF515031; AAN03389.1; -; Genomic_DNA. DR EMBL; AF515032; AAN03390.1; -; Genomic_DNA. DR EMBL; AF515033; AAN03391.1; -; Genomic_DNA. DR EMBL; AF515034; AAN03392.1; -; Genomic_DNA. DR EMBL; AF515035; AAN03393.1; -; Genomic_DNA. DR EMBL; AF515036; AAN03394.1; -; Genomic_DNA. DR EMBL; AF515037; AAN03395.1; -; Genomic_DNA. DR EMBL; AF515038; AAN03396.1; -; Genomic_DNA. DR EMBL; AF515039; AAN03397.1; -; Genomic_DNA. DR EMBL; AF515040; AAN03398.1; -; Genomic_DNA. DR EMBL; AF515041; AAN03399.1; -; Genomic_DNA. DR EMBL; AF515042; AAN03400.1; -; Genomic_DNA. DR EMBL; AF515043; AAN03401.1; -; Genomic_DNA. DR EMBL; AF515044; AAN03402.1; -; Genomic_DNA. DR EMBL; AF515045; AAN03403.1; -; Genomic_DNA. DR EMBL; AF515046; AAN03404.1; -; Genomic_DNA. DR EMBL; AF515047; AAN03405.1; -; Genomic_DNA. DR EMBL; AF515048; AAN03406.1; -; Genomic_DNA. DR EMBL; AF515049; AAN03407.1; -; Genomic_DNA. DR EMBL; AF515050; AAN03408.1; -; Genomic_DNA. DR CCDS; CCDS43635.1; -. [O15409-4] DR CCDS; CCDS55154.1; -. [O15409-9] DR CCDS; CCDS5760.1; -. [O15409-1] DR CCDS; CCDS5761.2; -. [O15409-6] DR RefSeq; NP_001166237.1; NM_001172766.2. DR RefSeq; NP_001166238.1; NM_001172767.2. DR RefSeq; NP_055306.1; NM_014491.3. [O15409-1] DR RefSeq; NP_683696.2; NM_148898.3. [O15409-4] DR RefSeq; NP_683697.2; NM_148899.3. [O15409-6] DR RefSeq; NP_683698.2; NM_148900.3. [O15409-9] DR UniGene; Hs.282787; -. DR PDB; 2A07; X-ray; 1.90 A; F/G/H/I/J/K=502-594. DR PDB; 2AS5; X-ray; 2.70 A; F/G=502-594. DR PDBsum; 2A07; -. DR PDBsum; 2AS5; -. DR ProteinModelPortal; O15409; -. DR SMR; O15409; 351-409, 503-584. DR BioGrid; 125073; 28. DR DIP; DIP-29004N; -. DR IntAct; O15409; 9. DR STRING; 9606.ENSP00000386200; -. DR PhosphoSite; O15409; -. DR BioMuta; FOXP2; -. DR MaxQB; O15409; -. DR PaxDb; O15409; -. DR PRIDE; O15409; -. DR Ensembl; ENST00000350908; ENSP00000265436; ENSG00000128573. [O15409-1] DR Ensembl; ENST00000360232; ENSP00000353367; ENSG00000128573. [O15409-6] DR Ensembl; ENST00000378237; ENSP00000367482; ENSG00000128573. [O15409-7] DR Ensembl; ENST00000393489; ENSP00000377129; ENSG00000128573. [O15409-2] DR Ensembl; ENST00000393494; ENSP00000377132; ENSG00000128573. [O15409-1] DR Ensembl; ENST00000403559; ENSP00000385069; ENSG00000128573. [O15409-9] DR Ensembl; ENST00000408937; ENSP00000386200; ENSG00000128573. [O15409-4] DR Ensembl; ENST00000412402; ENSP00000405470; ENSG00000128573. [O15409-8] DR Ensembl; ENST00000441290; ENSP00000416825; ENSG00000128573. [O15409-8] DR GeneID; 93986; -. DR KEGG; hsa:93986; -. DR UCSC; uc003vgv.1; human. [O15409-7] DR UCSC; uc003vgw.3; human. [O15409-5] DR UCSC; uc003vgx.2; human. [O15409-1] DR UCSC; uc003vgz.3; human. [O15409-4] DR UCSC; uc003vhd.3; human. [O15409-6] DR UCSC; uc011kmu.2; human. [O15409-9] DR CTD; 93986; -. DR GeneCards; FOXP2; -. DR HGNC; HGNC:13875; FOXP2. DR HPA; CAB011488; -. DR HPA; HPA000382; -. DR HPA; HPA000383; -. DR MIM; 602081; phenotype. DR MIM; 605317; gene. DR neXtProt; NX_O15409; -. DR Orphanet; 251061; 7q31 microdeletion syndrome. DR Orphanet; 209908; Childhood apraxia of speech. DR PharmGKB; PA28242; -. DR eggNOG; KOG4385; Eukaryota. DR eggNOG; COG5025; LUCA. DR GeneTree; ENSGT00800000124075; -. DR HOGENOM; HOG000092089; -. DR HOVERGEN; HBG051657; -. DR InParanoid; O15409; -. DR KO; K09409; -. DR OMA; PETKLCV; -. DR OrthoDB; EOG7M6D7G; -. DR PhylomeDB; O15409; -. DR TreeFam; TF326978; -. DR ChiTaRS; FOXP2; human. DR EvolutionaryTrace; O15409; -. DR GeneWiki; FOXP2; -. DR GenomeRNAi; 93986; -. DR NextBio; 78260; -. DR PRO; PR:O15409; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; O15409; -. DR ExpressionAtlas; O15409; baseline and differential. DR Genevisible; O15409; HS. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IEA:Ensembl. DR GO; GO:0043010; P:camera-type eye development; IEA:Ensembl. DR GO; GO:0021757; P:caudate nucleus development; IMP:UniProtKB. DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl. DR GO; GO:0021987; P:cerebral cortex development; IEP:BHF-UCL. DR GO; GO:0040007; P:growth; IEA:Ensembl. DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:BHF-UCL. DR GO; GO:0060501; P:positive regulation of epithelial cell proliferation involved in lung morphogenesis; IEA:Ensembl. DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl. DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl. DR GO; GO:0021758; P:putamen development; IMP:UniProtKB. DR GO; GO:0060013; P:righting reflex; IEA:Ensembl. DR GO; GO:0007519; P:skeletal muscle tissue development; IEA:Ensembl. DR GO; GO:0048745; P:smooth muscle tissue development; IEA:Ensembl. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0042297; P:vocal learning; IEA:Ensembl. DR Gene3D; 1.10.10.10; -; 1. DR InterPro; IPR001766; Fork_head_dom. DR InterPro; IPR032354; FOXP-CC. DR InterPro; IPR011991; WHTH_DNA-bd_dom. DR InterPro; IPR015880; Znf_C2H2-like. DR Pfam; PF00250; Forkhead; 1. DR Pfam; PF16159; FOXP-CC; 1. DR PRINTS; PR00053; FORKHEAD. DR SMART; SM00339; FH; 1. DR SMART; SM00355; ZnF_C2H2; 1. DR PROSITE; PS00658; FORK_HEAD_2; 1. DR PROSITE; PS50039; FORK_HEAD_3; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromosomal rearrangement; KW Complete proteome; Disease mutation; DNA-binding; Metal-binding; KW Nucleus; Reference proteome; Repressor; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 715 Forkhead box protein P2. FT /FTId=PRO_0000091879. FT ZN_FING 346 371 C2H2-type. FT DNA_BIND 504 594 Fork-head. {ECO:0000255|PROSITE- FT ProRule:PRU00089}. FT REGION 388 409 Leucine-zipper. FT REGION 422 426 CTBP1-binding. {ECO:0000250}. FT COMPBIAS 53 268 Gln-rich. FT VAR_SEQ 1 92 Missing (in isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_001558. FT VAR_SEQ 86 86 Q -> QELLPETKLCICGHSSGDGHPHNTFA (in FT isoform 4 and isoform 5). FT {ECO:0000303|Ref.3, ECO:0000303|Ref.4}. FT /FTId=VSP_011532. FT VAR_SEQ 87 87 V -> P (in isoform 8). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_011533. FT VAR_SEQ 88 715 Missing (in isoform 8). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_011534. FT VAR_SEQ 132 132 Q -> QDFLDSGLENFRAALEKN (in isoform 9). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_043464. FT VAR_SEQ 133 143 QQLQEFYKKQQ -> VMWVTCFGVLA (in isoform FT 5). {ECO:0000303|Ref.3}. FT /FTId=VSP_011535. FT VAR_SEQ 144 715 Missing (in isoform 5). FT {ECO:0000303|Ref.3}. FT /FTId=VSP_011536. FT VAR_SEQ 366 715 Missing (in isoform 7). FT {ECO:0000303|PubMed:12189486}. FT /FTId=VSP_011537. FT VAR_SEQ 423 432 LNLVSSVTMS -> VSAYCFINSK (in isoform 6). FT {ECO:0000303|PubMed:12189486}. FT /FTId=VSP_011538. FT VAR_SEQ 433 715 Missing (in isoform 6). FT {ECO:0000303|PubMed:12189486}. FT /FTId=VSP_011539. FT VARIANT 553 553 R -> H (in SPCH1). FT {ECO:0000269|PubMed:11586359}. FT /FTId=VAR_012278. FT CONFLICT 29 29 A -> V (in Ref. 2; AAM60762). FT {ECO:0000305}. FT CONFLICT 134 134 Q -> H (in Ref. 10; AAB91439). FT {ECO:0000305}. FT CONFLICT 290 304 DLTTNNSSSTTSSNT -> EEFPVQGPAAVCAGL (in FT Ref. 10; AAB91439). {ECO:0000305}. FT CONFLICT 414 414 S -> L (in Ref. 2; AAM60766). FT {ECO:0000305}. FT HELIX 509 519 {ECO:0000244|PDB:2A07}. FT HELIX 527 541 {ECO:0000244|PDB:2A07}. FT HELIX 545 558 {ECO:0000244|PDB:2A07}. FT STRAND 562 567 {ECO:0000244|PDB:2AS5}. FT STRAND 568 572 {ECO:0000244|PDB:2A07}. FT HELIX 577 583 {ECO:0000244|PDB:2A07}. SQ SEQUENCE 715 AA; 79919 MW; 4F9FBDB6D90516E0 CRC64; MMQESATETI SNSSMNQNGM STLSSQLDAG SRDGRSSGDT SSEVSTVELL HLQQQQALQA ARQLLLQQQT SGLKSPKSSD KQRPLQVPVS VAMMTPQVIT PQQMQQILQQ QVLSPQQLQA LLQQQQAVML QQQQLQEFYK KQQEQLHLQL LQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QHPGKQAKEQ QQQQQQQQQL AAQQLVFQQQ LLQMQQLQQQ QHLLSLQRQG LISIPPGQAA LPVQSLPQAG LSPAEIQQLW KEVTGVHSME DNGIKHGGLD LTTNNSSSTT SSNTSKASPP ITHHSIVNGQ SSVLSARRDS SSHEETGASH TLYGHGVCKW PGCESICEDF GQFLKHLNNE HALDDRSTAQ CRVQMQVVQQ LEIQLSKERE RLQAMMTHLH MRPSEPKPSP KPLNLVSSVT MSKNMLETSP QSLPQTPTTP TAPVTPITQG PSVITPASVP NVGAIRRRHS DKYNIPMSSE IAPNYEFYKN ADVRPPFTYA TLIRQAIMES SDRQLTLNEI YSWFTRTFAY FRRNAATWKN AVRHNLSLHK CFVRVENVKG AVWTVDEVEY QKRRSQKITG SPTLVKNIPT SLGYGAALNA SLQAALAESS LPLLSNPGLI NNASSGLLQA VHEDLNGSLD HIDSNGNSSP GCSPQPHIHS IHVKEEPVIA EDEDCPMSLV TTANHSPELE DDREIEEEPL SEDLE // ID FUND1_HUMAN Reviewed; 155 AA. AC Q8IVP5; DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 11-NOV-2015, entry version 97. DE RecName: Full=FUN14 domain-containing protein 1; GN Name=FUNDC1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, TISSUE SPECIFICITY, RP PHOSPHORYLATION AT TYR-18, INTERACTION WITH MAP1LC3A; MAP1LC3B AND RP GABARAP, AND MUTAGENESIS OF TYR-18; LEU-21 AND 31-TRP-TRP-32. RX PubMed=22267086; DOI=10.1038/ncb2422; RA Liu L., Feng D., Chen G., Chen M., Zheng Q., Song P., Ma Q., Zhu C., RA Wang R., Qi W., Huang L., Xue P., Li B., Wang X., Jin H., Wang J., RA Yang F., Liu P., Zhu Y., Sui S., Chen Q.; RT "Mitochondrial outer-membrane protein FUNDC1 mediates hypoxia-induced RT mitophagy in mammalian cells."; RL Nat. Cell Biol. 14:177-185(2012). CC -!- FUNCTION: Acts as an activator of hypoxia-induced mitophagy, an CC important mechanism for mitochondrial quality control. CC {ECO:0000269|PubMed:22267086}. CC -!- SUBUNIT: Interacts (via YXXL motif) with MAP1 LC3 family proteins CC MAP1LC3A, MAP1LC3B and GABARAP. {ECO:0000269|PubMed:22267086}. CC -!- INTERACTION: CC P56545:CTBP2; NbExp=3; IntAct=EBI-3059266, EBI-741533; CC Q08426:EHHADH; NbExp=3; IntAct=EBI-3059266, EBI-2339219; CC P60520:GABARAPL2; NbExp=3; IntAct=EBI-3059266, EBI-720116; CC Q9H492:MAP1LC3A; NbExp=4; IntAct=EBI-3059266, EBI-720768; CC Q9GZQ8:MAP1LC3B; NbExp=8; IntAct=EBI-3059266, EBI-373144; CC Q96E29:MTERF3; NbExp=3; IntAct=EBI-3059266, EBI-7825321; CC Q9HC62:SENP2; NbExp=3; IntAct=EBI-3059266, EBI-714881; CC Q9Y371:SH3GLB1; NbExp=3; IntAct=EBI-3059266, EBI-2623095; CC Q96AG3:SLC25A46; NbExp=3; IntAct=EBI-3059266, EBI-10281975; CC Q13596:SNX1; NbExp=3; IntAct=EBI-3059266, EBI-2822329; CC P49411:TUFM; NbExp=3; IntAct=EBI-3059266, EBI-359097; CC O70405:Ulk1 (xeno); NbExp=3; IntAct=EBI-3059266, EBI-8390771; CC P07947:YES1; NbExp=3; IntAct=EBI-3059266, EBI-515331; CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane CC {ECO:0000269|PubMed:22267086}; Multi-pass membrane protein CC {ECO:0000269|PubMed:22267086}. CC -!- TISSUE SPECIFICITY: Widely expressed. CC {ECO:0000269|PubMed:22267086}. CC -!- DOMAIN: The YXXL motif mediates the interaction with MAP1 LC3 CC family proteins MAP1LC3A, MAP1LC3B and GABARAP. CC {ECO:0000269|PubMed:22267086}. CC -!- PTM: Phosphorylation at Tyr-18 by SRC inhibits activation of CC mitophagy. Following hypoxia, dephosphorylated at Tyr-18, leading CC to interaction with MAP1 LC3 family proteins and triggering CC mitophagy. {ECO:0000269|PubMed:22267086}. CC -!- SIMILARITY: Belongs to the FUN14 family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AL136137; CAI40461.1; -; Genomic_DNA. DR EMBL; AL022163; CAI40461.1; JOINED; Genomic_DNA. DR EMBL; AL022163; CAI42944.1; -; Genomic_DNA. DR EMBL; AL136137; CAI42944.1; JOINED; Genomic_DNA. DR EMBL; BC035015; AAH35015.1; -; mRNA. DR EMBL; BC042813; AAH42813.1; -; mRNA. DR CCDS; CCDS14263.1; -. DR RefSeq; NP_776155.1; NM_173794.3. DR UniGene; Hs.7549; -. DR ProteinModelPortal; Q8IVP5; -. DR BioGrid; 126561; 15. DR IntAct; Q8IVP5; 15. DR STRING; 9606.ENSP00000367284; -. DR PhosphoSite; Q8IVP5; -. DR BioMuta; FUNDC1; -. DR DMDM; 74750673; -. DR MaxQB; Q8IVP5; -. DR PaxDb; Q8IVP5; -. DR PRIDE; Q8IVP5; -. DR Ensembl; ENST00000378045; ENSP00000367284; ENSG00000069509. DR GeneID; 139341; -. DR KEGG; hsa:139341; -. DR UCSC; uc004dgc.3; human. DR CTD; 139341; -. DR GeneCards; FUNDC1; -. DR HGNC; HGNC:28746; FUNDC1. DR HPA; HPA038773; -. DR MIM; 300871; gene. DR neXtProt; NX_Q8IVP5; -. DR PharmGKB; PA134875965; -. DR eggNOG; KOG4099; Eukaryota. DR eggNOG; ENOG41122V1; LUCA. DR GeneTree; ENSGT00390000003926; -. DR HOGENOM; HOG000232100; -. DR HOVERGEN; HBG054805; -. DR InParanoid; Q8IVP5; -. DR KO; K17986; -. DR OMA; NHSGYVQ; -. DR OrthoDB; EOG7PCJJT; -. DR PhylomeDB; Q8IVP5; -. DR TreeFam; TF300280; -. DR GeneWiki; FUNDC1; -. DR GenomeRNAi; 139341; -. DR NextBio; 83947; -. DR PRO; PR:Q8IVP5; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; Q8IVP5; -. DR CleanEx; HS_FUNDC1; -. DR Genevisible; Q8IVP5; HS. DR GO; GO:0031307; C:integral component of mitochondrial outer membrane; IDA:UniProtKB. DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:MGI. DR GO; GO:0000422; P:mitophagy; IDA:UniProtKB. DR GO; GO:0001666; P:response to hypoxia; IDA:UniProtKB. DR InterPro; IPR007014; FUN14. DR Pfam; PF04930; FUN14; 1. PE 1: Evidence at protein level; KW Autophagy; Complete proteome; Membrane; Mitochondrion; KW Mitochondrion outer membrane; Phosphoprotein; Reference proteome; KW Transmembrane; Transmembrane helix. FT CHAIN 1 155 FUN14 domain-containing protein 1. FT /FTId=PRO_0000271345. FT TOPO_DOM 1 47 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 48 68 Helical. {ECO:0000255}. FT TOPO_DOM 69 74 Mitochondrial intermembrane. FT {ECO:0000255}. FT TRANSMEM 75 95 Helical. {ECO:0000255}. FT TOPO_DOM 96 133 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 134 154 Helical. {ECO:0000255}. FT TOPO_DOM 155 155 Mitochondrial intermembrane. FT {ECO:0000255}. FT MOTIF 18 21 YXXL. FT MOD_RES 13 13 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332}. FT MOD_RES 18 18 Phosphotyrosine; by SRC. FT {ECO:0000269|PubMed:22267086}. FT MUTAGEN 18 18 Y->A: Impairs interaction with MAP1 LC3 FT family proteins. FT {ECO:0000269|PubMed:22267086}. FT MUTAGEN 18 18 Y->W: Abolishes phosphorylation by SRC. FT {ECO:0000269|PubMed:22267086}. FT MUTAGEN 21 21 L->A: Impairs interaction with MAP1 LC3 FT family proteins. FT {ECO:0000269|PubMed:22267086}. FT MUTAGEN 32 33 WW->AA: Does not affect interaction with FT MAP1 LC3 family proteins. SQ SEQUENCE 155 AA; 17178 MW; 4E9ABF640795F0A9 CRC64; MATRNPPPQD YESDDDSYEV LDLTEYARRH QWWNRVFGHS SGPMVEKYSV ATQIVMGGVT GWCAGFLFQK VGKLAATAVG GGFLLLQIAS HSGYVQIDWK RVEKDVNKAK RQIKKRANKA APEINNLIEE ATEFIKQNIV ISSGFVGGFL LGLAS // ID HDAC1_HUMAN Reviewed; 482 AA. AC Q13547; Q92534; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 1. DT 11-NOV-2015, entry version 189. DE RecName: Full=Histone deacetylase 1; DE Short=HD1; DE EC=3.5.1.98; GN Name=HDAC1; Synonyms=RPD3L1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=T-cell; RX PubMed=8602529; DOI=10.1126/science.272.5260.408; RA Taunton J., Hassig C.A., Schreiber S.L.; RT "A mammalian histone deacetylase related to the yeast transcriptional RT regulator Rpd3p."; RL Science 272:408-411(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Fetal lung; RX PubMed=8646880; RA Furukawa Y., Kawakami T., Sudo K., Inazawa J., Matsumine A., RA Akiyama T., Nakamura Y.; RT "Isolation and mapping of a human gene (RPD3L1) that is homologous to RT RPD3, a transcription factor in Saccharomyces cerevisiae."; RL Cytogenet. Cell Genet. 73:130-133(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH HDAC9. RX PubMed=10487760; DOI=10.1093/emboj/18.18.5085; RA Sparrow D.B., Miska E.A., Langley E., Reynaud-Deonauth S., Kotecha S., RA Towers N., Spohr G., Kouzarides T., Mohun T.J.; RT "MEF-2 function is modified by a novel co-repressor, MITR."; RL EMBO J. 18:5085-5098(1999). RN [5] RP INTERACTION WITH BCOR. RX PubMed=10898795; RA Huynh K.D., Fischle W., Verdin E., Bardwell V.J.; RT "BCoR, a novel corepressor involved in BCL-6 repression."; RL Genes Dev. 14:1810-1823(2000). RN [6] RP INTERACTION WITH THE 9-1-1 COMPLEX AND HUS1, AND SUBCELLULAR LOCATION. RX PubMed=10846170; DOI=10.1074/jbc.M000168200; RA Cai R.L., Yan-Neale Y., Cueto M.A., Xu H., Cohen D.; RT "HDAC1, a histone deacetylase, forms a complex with Hus1 and Rad9, two RT G2/M checkpoint Rad proteins."; RL J. Biol. Chem. 275:27909-27916(2000). RN [7] RP INTERACTION WITH NRIP1. RX PubMed=11006275; DOI=10.1074/jbc.M004821200; RA Wei L.-N., Hu X., Chandra D., Seto E., Farooqui M.; RT "Receptor-interacting protein 140 directly recruits histone RT deacetylases for gene silencing."; RL J. Biol. Chem. 275:40782-40787(2000). RN [8] RP INTERACTION WITH DAXX. RX PubMed=10669754; DOI=10.1128/MCB.20.5.1784-1796.2000; RA Li H., Leo C., Zhu J., Wu X., O'Neil J., Park E.-J., Chen J.D.; RT "Sequestration and inhibition of Daxx-mediated transcriptional RT repression by PML."; RL Mol. Cell. Biol. 20:1784-1796(2000). RN [9] RP INTERACTION WITH HDAC9. RX PubMed=10655483; DOI=10.1073/pnas.97.3.1056; RA Zhou X., Richon V.M., Rifkind R.A., Marks P.A.; RT "Identification of a transcriptional repressor related to the RT noncatalytic domain of histone deacetylases 4 and 5."; RL Proc. Natl. Acad. Sci. U.S.A. 97:1056-1061(2000). RN [10] RP PHOSPHORYLATION AT SER-421 AND SER-423, MUTAGENESIS OF SER-421 AND RP SER-423, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=11602581; DOI=10.1074/jbc.M105590200; RA Pflum M.K.H., Tong J.K., Lane W.S., Schreiber S.L.; RT "Histone deacetylase 1 phosphorylation promotes enzymatic activity and RT complex formation."; RL J. Biol. Chem. 276:47733-47741(2001). RN [11] RP INTERACTION WITH MINT. RX PubMed=11331609; DOI=10.1101/gad.871201; RA Shi Y., Downes M., Xie W., Kao H.-Y., Ordentlich P., Tsai C.-C., RA Hon M., Evans R.M.; RT "Sharp, an inducible cofactor that integrates nuclear receptor RT repression and activation."; RL Genes Dev. 15:1140-1151(2001). RN [12] RP INTERACTION WITH MBD2 AND MBD3. RX PubMed=11102443; DOI=10.1074/jbc.M007372200; RA Humphrey G.W., Wang Y., Russanova V.R., Hirai T., Qin J., Nakatani Y., RA Howard B.H.; RT "Stable histone deacetylase complexes distinguished by the presence of RT SANT domain proteins CoREST/kiaa0071 and Mta-L1."; RL J. Biol. Chem. 276:6817-6824(2001). RN [13] RP INTERACTION WITH TGIF2. RX PubMed=11427533; DOI=10.1074/jbc.M103377200; RA Melhuish T.A., Gallo C.M., Wotton D.; RT "TGIF2 interacts with histone deacetylase 1 and represses RT transcription."; RL J. Biol. Chem. 276:32109-32114(2001). RN [14] RP INTERACTION WITH CBFA2T3. RX PubMed=11533236; DOI=10.1128/MCB.21.19.6470-6483.2001; RA Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N., RA Downing J.R., Meyers S., Hiebert S.W.; RT "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts RT with multiple histone deacetylases and binds mSin3A through its RT oligomerization domain."; RL Mol. Cell. Biol. 21:6470-6483(2001). RN [15] RP SUMOYLATION. RX PubMed=12032081; DOI=10.1093/emboj/21.11.2682; RA Kirsh O., Seeler J.-S., Pichler A., Gast A., Mueller S., Miska E., RA Mathieu M., Harel-Bellan A., Kouzarides T., Melchior F., Dejean A.; RT "The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 RT deacetylase."; RL EMBO J. 21:2682-2691(2002). RN [16] RP SUMOYLATION AT LYS-444 AND LYS-476. RX PubMed=11960997; DOI=10.1074/jbc.M203690200; RA David G., Neptune M.A., DePinho R.A.; RT "SUMO-1 modification of histone deacetylase 1 (HDAC1) modulates its RT biological activities."; RL J. Biol. Chem. 277:23658-23663(2002). RN [17] RP INTERACTION WITH APEX1. RX PubMed=14633989; DOI=10.1093/emboj/cdg595; RA Bhakat K.K., Izumi T., Yang S.H., Hazra T.K., Mitra S.; RT "Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation RT of the parathyroid hormone gene."; RL EMBO J. 22:6299-6309(2003). RN [18] RP INTERACTION WITH HCFC1. RX PubMed=12670868; DOI=10.1101/gad.252103; RA Wysocka J., Myers M.P., Laherty C.D., Eisenman R.N., Herr W.; RT "Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 RT methyltransferase are tethered together selectively by the cell- RT proliferation factor HCF-1."; RL Genes Dev. 17:896-911(2003). RN [19] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE BHC RP COMPLEX WITH PHF21A; HDAC2; HMG20B; KDM1A; RCOR1; ZMYM2; ZNF217; RP ZMYM3; KIAA0182 AND GTF2I. RX PubMed=12493763; DOI=10.1074/jbc.M208992200; RA Hakimi M.-A., Dong Y., Lane W.S., Speicher D.W., Shiekhattar R.; RT "A candidate X-linked mental retardation gene is a component of a new RT family of histone deacetylase-containing complexes."; RL J. Biol. Chem. 278:7234-7239(2003). RN [20] RP INTERACTION WITH SP3, AND FUNCTION. RX PubMed=12837748; DOI=10.1074/jbc.M305961200; RA Ammanamanchi S., Freeman J.W., Brattain M.G.; RT "Acetylated SP3 is a transcriptional activator."; RL J. Biol. Chem. 278:35775-35780(2003). RN [21] RP INTERACTION WITH MIER1. RX PubMed=12482978; DOI=10.1128/MCB.23.1.250-258.2003; RA Ding Z., Gillespie L.L., Paterno G.D.; RT "Human MI-ER1 alpha and beta function as transcriptional repressors by RT recruitment of histone deacetylase 1 to their conserved ELM2 domain."; RL Mol. Cell. Biol. 23:250-258(2003). RN [22] RP IDENTIFICATION IN A MSIN3A COREPRESSOR COMPLEX WITH SIN3A; SAP130; RP SUDS3; ARID4B; HDAC1 AND HDAC2. RX PubMed=12724404; DOI=10.1128/MCB.23.10.3456-3467.2003; RA Fleischer T.C., Yun U.J., Ayer D.E.; RT "Identification and characterization of three new components of the RT mSin3A corepressor complex."; RL Mol. Cell. Biol. 23:3456-3467(2003). RN [23] RP INTERACTION WITH E4F1. RX PubMed=12730668; DOI=10.1038/sj.onc.1206379; RA Colombo R., Draetta G.F., Chiocca S.; RT "Modulation of p120E4F transcriptional activity by the Gam1 adenoviral RT early protein."; RL Oncogene 22:2541-2547(2003). RN [24] RP INTERACTION WITH BRMS1L. RX PubMed=15451426; DOI=10.1016/j.bbrc.2004.08.227; RA Nikolaev A.Y., Papanikolaou N.A., Li M., Qin J., Gu W.; RT "Identification of a novel BRMS1-homologue protein p40 as a component RT of the mSin3A/p33(ING1b)/HDAC1 deacetylase complex."; RL Biochem. Biophys. Res. Commun. 323:1216-1222(2004). RN [25] RP INTERACTION WITH BCL6, AND IDENTIFICATION IN THE NURD COMPLEX. RX PubMed=15454082; DOI=10.1016/j.cell.2004.09.014; RA Fujita N., Jaye D.L., Geigerman C., Akyildiz A., Mooney M.R., RA Boss J.M., Wade P.A.; RT "MTA3 and the Mi-2/NuRD complex regulate cell fate during B lymphocyte RT differentiation."; RL Cell 119:75-86(2004). RN [26] RP INTERACTION WITH NFE4. RX PubMed=15273251; DOI=10.1074/jbc.M405129200; RA Zhao Q., Cumming H., Cerruti L., Cunningham J.M., Jane S.M.; RT "Site-specific acetylation of the fetal globin activator NF-E4 RT prevents its ubiquitination and regulates its interaction with the RT histone deacetylase, HDAC1."; RL J. Biol. Chem. 279:41477-41486(2004). RN [27] RP DESUMOYLATION BY SENP1. RX PubMed=15199155; DOI=10.1128/MCB.24.13.6021-6028.2004; RA Cheng J., Wang D., Wang Z., Yeh E.T.H.; RT "SENP1 enhances androgen receptor-dependent transcription through RT desumoylation of histone deacetylase 1."; RL Mol. Cell. Biol. 24:6021-6028(2004). RN [28] RP INTERACTION WITH UHRF1 AND UHRF2. RX PubMed=15361834; DOI=10.1038/sj.onc.1208053; RA Unoki M., Nishidate T., Nakamura Y.; RT "ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG RT through its SRA domain."; RL Oncogene 23:7601-7610(2004). RN [29] RP REVIEW ON DEACETYLASE COMPLEXES. RX PubMed=10904264; DOI=10.1016/S0168-9525(00)02066-7; RA Ahringer J.; RT "NuRD and SIN3 histone deacetylase complexes in development."; RL Trends Genet. 16:351-356(2000). RN [30] RP INTERACTION WITH KDM4A. RX PubMed=15927959; DOI=10.1074/jbc.M413687200; RA Gray S.G., Iglesias A.H., Lizcano F., Villanueva R., Camelo S., RA Jingu H., Teh B.T., Koibuchi N., Chin W.W., Kokkotou E., Dangond F.; RT "Functional characterization of JMJD2A, a histone deacetylase- and RT retinoblastoma-binding protein."; RL J. Biol. Chem. 280:28507-28518(2005). RN [31] RP INTERACTION WITH BANP. RX PubMed=16166625; DOI=10.1128/MCB.25.19.8415-8429.2005; RA Rampalli S., Pavithra L., Bhatt A., Kundu T.K., Chattopadhyay S.; RT "Tumor suppressor SMAR1 mediates cyclin D1 repression by recruitment RT of the SIN3/histone deacetylase 1 complex."; RL Mol. Cell. Biol. 25:8415-8429(2005). RN [32] RP INTERACTION WITH INSM1. RX PubMed=16569215; DOI=10.1042/BJ20051669; RA Liu W.D., Wang H.W., Muguira M., Breslin M.B., Lan M.S.; RT "INSM1 functions as a transcriptional repressor of the neuroD/beta2 RT gene through the recruitment of cyclin D1 and histone deacetylases."; RL Biochem. J. 397:169-177(2006). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-393; SER-421 AND RP SER-423, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [34] RP INTERACTION WITH SP1, AND FUNCTION. RX PubMed=16478997; DOI=10.1128/MCB.26.5.1770-1785.2006; RA Hung J.J., Wang Y.T., Chang W.C.; RT "Sp1 deacetylation induced by phorbol ester recruits p300 to activate RT 12(S)-lipoxygenase gene transcription."; RL Mol. Cell. Biol. 26:1770-1785(2006). RN [35] RP FUNCTION, AND INTERACTION WITH BRMS1. RX PubMed=17000776; DOI=10.1128/MCB.00940-06; RA Liu Y., Smith P.W., Jones D.R.; RT "Breast cancer metastasis suppressor 1 functions as a corepressor by RT enhancing histone deacetylase 1-mediated deacetylation of RelA/p65 and RT promoting apoptosis."; RL Mol. Cell. Biol. 26:8683-8696(2006). RN [36] RP INTERACTION WITH SAP30L. RX PubMed=16820529; DOI=10.1093/nar/gkl401; RA Viiri K.M., Korkeamaeki H., Kukkonen M.K., Nieminen L.K., Lindfors K., RA Peterson P., Maeki M., Kainulainen H., Lohi O.; RT "SAP30L interacts with members of the Sin3A corepressor complex and RT targets Sin3A to the nucleolus."; RL Nucleic Acids Res. 34:3288-3298(2006). RN [37] RP INTERACTION WITH PPHLN1. RX PubMed=17963697; DOI=10.1016/j.bbrc.2007.10.090; RA Kurita M., Suzuki H., Kawano Y., Aiso S., Matsuoka M.; RT "CR/periphilin is a transcriptional co-repressor involved in cell RT cycle progression."; RL Biochem. Biophys. Res. Commun. 364:930-936(2007). RN [38] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-393, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Prostate cancer; RX PubMed=17487921; DOI=10.1002/elps.200600782; RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.; RT "Toward a global characterization of the phosphoproteome in prostate RT cancer cells: identification of phosphoproteins in the LNCaP cell RT line."; RL Electrophoresis 28:2027-2034(2007). RN [39] RP INTERACTION WITH SP3. RX PubMed=17548428; DOI=10.1096/fj.07-8621com; RA Wooten-Blanks L.G., Song P., Senkal C.E., Ogretmen B.; RT "Mechanisms of ceramide-mediated repression of the human telomerase RT reverse transcriptase promoter via deacetylation of Sp3 by histone RT deacetylase 1."; RL FASEB J. 21:3386-3397(2007). RN [40] RP INTERACTION WITH KDM5B. RX PubMed=17373667; DOI=10.1002/ijc.22673; RA Barrett A., Santangelo S., Tan K., Catchpole S., Roberts K., RA Spencer-Dene B., Hall D., Scibetta A., Burchell J., Verdin E., RA Freemont P., Taylor-Papadimitriou J.; RT "Breast cancer associated transcriptional repressor PLU-1/JARID1B RT interacts directly with histone deacetylases."; RL Int. J. Cancer 121:265-275(2007). RN [41] RP INTERACTION WITH TRIM28, AND FUNCTION. RX PubMed=17704056; DOI=10.1074/jbc.M704757200; RA Wang C., Rauscher F.J. III, Cress W.D., Chen J.; RT "Regulation of E2F1 function by the nuclear corepressor KAP1."; RL J. Biol. Chem. 282:29902-29909(2007). RN [42] RP INTERACTION WITH DDIT3. RX PubMed=17872950; DOI=10.1074/jbc.M703735200; RA Ohoka N., Hattori T., Kitagawa M., Onozaki K., Hayashi H.; RT "Critical and functional regulation of CHOP (C/EBP homologous protein) RT through the N-terminal portion."; RL J. Biol. Chem. 282:35687-35694(2007). RN [43] RP INTERACTION WITH SV40 LARGE T ANTIGEN. RX PubMed=17341466; DOI=10.1093/nar/gkl1113; RA Valls E., Blanco-Garcia N., Aquizu N., Piedra D., Estaras C., RA de la Cruz X., Martinez-Balbas M.A.; RT "Involvement of chromatin and histone deacetylation in SV40 T antigen RT transcription regulation."; RL Nucleic Acids Res. 35:1958-1968(2007). RN [44] RP INTERACTION WITH DDX5. RX PubMed=17369852; DOI=10.1038/sj.onc.1210387; RA Jacobs A.M., Nicol S.M., Hislop R.G., Jaffray E.G., Hay R.T., RA Fuller-Pace F.V.; RT "SUMO modification of the DEAD box protein p68 modulates its RT transcriptional activity and promotes its interaction with HDAC1."; RL Oncogene 26:5866-5876(2007). RN [45] RP FUNCTION, AND INTERACTION WITH NR1D2. RX PubMed=17996965; DOI=10.1016/j.bbamcr.2007.09.004; RA Wang J., Liu N., Liu Z., Li Y., Song C., Yuan H., Li Y.Y., Zhao X., RA Lu H.; RT "The orphan nuclear receptor Rev-erbbeta recruits Tip60 and HDAC1 to RT regulate apolipoprotein CIII promoter."; RL Biochim. Biophys. Acta 1783:224-236(2008). RN [46] RP INTERACTION WITH TRAF6. RX PubMed=18093978; DOI=10.1074/jbc.M706307200; RA Pham L.V., Zhou H.J., Lin-Lee Y.C., Tamayo A.T., Yoshimura L.C., RA Fu L., Darnay B.G., Ford R.J.; RT "Nuclear tumor necrosis factor receptor-associated factor 6 in RT lymphoid cells negatively regulates c-Myb-mediated transactivation RT through small ubiquitin-related modifier-1 modification."; RL J. Biol. Chem. 283:5081-5089(2008). RN [47] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-393, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [48] RP IDENTIFICATION IN A COMPLEX WITH CDYL; MIER1; MIER2 AND HDAC2. RX PubMed=19061646; DOI=10.1016/j.molcel.2008.10.025; RA Mulligan P., Westbrook T.F., Ottinger M., Pavlova N., Chang B., RA Macia E., Shi Y.J., Barretina J., Liu J., Howley P.M., Elledge S.J., RA Shi Y.; RT "CDYL bridges REST and histone methyltransferases for gene repression RT and suppression of cellular transformation."; RL Mol. Cell 32:718-726(2008). RN [49] RP METHYLATION AT LYS-432. RX PubMed=18438403; DOI=10.1038/nchembio.88; RA Rathert P., Dhayalan A., Murakami M., Zhang X., Tamas R., RA Jurkowska R., Komatsu Y., Shinkai Y., Cheng X., Jeltsch A.; RT "Protein lysine methyltransferase G9a acts on non-histone targets."; RL Nat. Chem. Biol. 4:344-346(2008). RN [50] RP FUNCTION, AND INTERACTION WITH RB1 AND SMARCA4/BRG1. RX PubMed=19081374; DOI=10.1016/j.neuron.2008.09.040; RA Qiu Z., Ghosh A.; RT "A calcium-dependent switch in a CREST-BRG1 complex regulates RT activity-dependent gene expression."; RL Neuron 60:775-787(2008). RN [51] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [52] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421 AND SER-423, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by RT enrichment and fractionation of phosphopeptides with strong anion RT exchange chromatography."; RL Proteomics 8:1346-1361(2008). RN [53] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [54] RP INTERACTION WITH PRDM16 AND SMAD3. RX PubMed=19049980; DOI=10.1074/jbc.M808989200; RA Takahata M., Inoue Y., Tsuda H., Imoto I., Koinuma D., Hayashi M., RA Ichikura T., Yamori T., Nagasaki K., Yoshida M., Matsuoka M., RA Morishita K., Yuki K., Hanyu A., Miyazawa K., Inazawa J., Miyazono K., RA Imamura T.; RT "SKI and MEL1 cooperate to inhibit transforming growth factor-beta RT signal in gastric cancer cells."; RL J. Biol. Chem. 284:3334-3344(2009). RN [55] RP FUNCTION, INTERACTION WITH TSHZ3, AND IDENTIFICATION IN A TRIMERIC RP COMPLEX WITH APBB1 AND TSHZ3. RX PubMed=19343227; DOI=10.1371/journal.pone.0005071; RA Kajiwara Y., Akram A., Katsel P., Haroutunian V., Schmeidler J., RA Beecham G., Haines J.L., Pericak-Vance M.A., Buxbaum J.D.; RT "FE65 binds Teashirt, inhibiting expression of the primate-specific RT caspase-4."; RL PLoS ONE 4:E5071-E5071(2009). RN [56] RP UBIQUITINATION, INTERACTION WITH CHFR, AND MUTAGENESIS OF HIS-141; RP PHE-287 AND MET-297. RX PubMed=19182791; DOI=10.1038/ncb1837; RA Oh Y.M., Kwon Y.E., Kim J.M., Bae S.J., Lee B.K., Yoo S.J., RA Chung C.H., Deshaies R.J., Seol J.H.; RT "Chfr is linked to tumour metastasis through the downregulation of RT HDAC1."; RL Nat. Cell Biol. 11:295-302(2009). RN [57] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-393 AND SER-421, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [58] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-74 AND LYS-220, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [59] RP INTERACTION WITH CCAR2. RX PubMed=21030595; DOI=10.1074/jbc.M110.153270; RA Chini C.C., Escande C., Nin V., Chini E.N.; RT "HDAC3 is negatively regulated by the nuclear protein DBC1."; RL J. Biol. Chem. 285:40830-40837(2010). RN [60] RP UBIQUITINATION BY KCTD11. RX PubMed=20081843; DOI=10.1038/ncb2013; RA Canettieri G., Di Marcotullio L., Greco A., Coni S., Antonucci L., RA Infante P., Pietrosanti L., De Smaele E., Ferretti E., Miele E., RA Pelloni M., De Simone G., Pedone E.M., Gallinari P., Giorgi A., RA Steinkuhler C., Vitagliano L., Pedone C., Schinin M.E., Screpanti I., RA Gulino A.; RT "Histone deacetylase and Cullin3-REN(KCTD11) ubiquitin ligase RT interplay regulates Hedgehog signalling through Gli acetylation."; RL Nat. Cell Biol. 12:132-142(2010). RN [61] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-393; SER-421 AND RP SER-423, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [62] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [63] RP INTERACTION WITH SMARCAD1. RX PubMed=21549307; DOI=10.1016/j.molcel.2011.02.036; RA Rowbotham S.P., Barki L., Neves-Costa A., Santos F., Dean W., RA Hawkes N., Choudhary P., Will W.R., Webster J., Oxley D., Green C.M., RA Varga-Weisz P., Mermoud J.E.; RT "Maintenance of silent chromatin through replication requires SWI/SNF- RT like chromatin remodeler SMARCAD1."; RL Mol. Cell 42:285-296(2011). RN [64] RP INTERACTION WITH BHLHE40. RX PubMed=21829689; DOI=10.1371/journal.pone.0023046; RA Hong Y., Xing X., Li S., Bi H., Yang C., Zhao F., Liu Y., Ao X., RA Chang A.K., Wu H.; RT "SUMOylation of DEC1 protein regulates its transcriptional activity RT and enhances its stability."; RL PLoS ONE 6:E23046-E23046(2011). RN [65] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-393; SER-421 AND RP SER-423, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [66] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-393, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [67] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-444; LYS-457 AND LYS-476, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [68] RP INTERACTION WITH DNTTIP1, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=25653165; DOI=10.1093/nar/gkv068; RA Itoh T., Fairall L., Muskett F.W., Milano C.P., Watson P.J., RA Arnaudo N., Saleh A., Millard C.J., El-Mezgueldi M., Martino F., RA Schwabe J.W.; RT "Structural and functional characterization of a cell cycle associated RT HDAC1/2 complex reveals the structural basis for complex assembly and RT nucleosome targeting."; RL Nucleic Acids Res. 43:2033-2044(2015). CC -!- FUNCTION: Responsible for the deacetylation of lysine residues on CC the N-terminal part of the core histones (H2A, H2B, H3 and H4). CC Histone deacetylation gives a tag for epigenetic repression and CC plays an important role in transcriptional regulation, cell cycle CC progression and developmental events. Histone deacetylases act via CC the formation of large multiprotein complexes. Deacetylates SP CC proteins, SP1 and SP3, and regulates their function. Component of CC the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST- CC mediated transcription in resting neurons. Upon calcium CC stimulation, HDAC1 is released from the complex and CREBBP is CC recruited, which facilitates transcriptional activation. CC Deacetylates TSHZ3 and regulates its transcriptional repressor CC activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the CC transcriptional activity of NF-kappa-B. Deacetylates NR1D2 and CC abrogates the effect of KAT5-mediated relieving of NR1D2 CC transcription repression activity. Component of a CC RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone CC deacetylase (HDAC) recruitment, a number of genes implicated in CC multilineage blood cell development. Involved in CIART-mediated CC transcriptional repression of the circadian transcriptional CC activator: CLOCK-ARNTL/BMAL1 heterodimer. Required for the CC transcriptional repression of circadian target genes, such as CC PER1, mediated by the large PER complex or CRY1 through histone CC deacetylation. {ECO:0000269|PubMed:12837748, CC ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:17000776, CC ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17996965, CC ECO:0000269|PubMed:19081374, ECO:0000269|PubMed:19343227}. CC -!- CATALYTIC ACTIVITY: Hydrolysis of an N(6)-acetyl-lysine residue of CC a histone to yield a deacetylated histone. CC -!- SUBUNIT: Part of the core histone deacetylase (HDAC) complex CC composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core complex CC associates with MTA2, MBD2, MBD3, MTA1L1, CHD3 and CHD4 to form CC the nucleosome remodeling and histone deacetylation (NuRD) CC complex, or with SIN3, SAP18 and SAP30 to form the SIN3 HDAC CC complex. Component of a BHC histone deacetylase complex that CC contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST and CC PHF21A/BHC80. The BHC complex may also contain ZMYM2, ZNF217, CC ZMYM3, GSE1 and GTF2I. Component of a mSin3A corepressor complex CC that contains SIN3A, SAP130, SUDS3/SAP45, ARID4B/SAP180, HDAC1 and CC HDAC2. Found in a trimeric complex with APBB1 and TSHZ3; the CC interaction between HDAC1 and APBB1 is mediated by TSHZ3. CC Component of a RCOR/GFI/KDM1A/HDAC complex. Part of a complex CC composed of TRIM28, HDAC1, HDAC2 and EHMT2. Part of a complex CC containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2. The large CC PER complex involved in the histone deacetylation is composed of CC at least HDAC1, PER2, SFPQ and SIN3A. Associates with the 9-1-1 CC complex; interacts with HUS1. Found in a complex with DNMT3A and CC HDAC7. Interacts with the non-histone region of H2AFY. Interacts CC with TRIM28; the interaction recruits HDAC1 to E2F1 and inhibits CC its acetylation. Interacts with SP1; the interaction deacetylates CC SP1 and regulates its transcriptional activity. Interacts with CC SP3; the interaction deacetylates SP3 and regulates its CC transcriptional activity. In vitro, C(18) ceramides increase this CC interaction and the subsequent SP3 deacetylation and SP3-mediated CC repression of the TERT promoter. Interacts with TSHZ3 (via N- CC terminus); the interaction is direct. Interacts with APEX1; the CC interaction is not dependent on the acetylated status of APEX1. CC Interacts with C10orf90/FATS (via its N-terminal); the interaction CC prevents binding of HDAC1 to CDKN1A/p21 and facilitates the CC acetylation and stabilization of CDKN1A/p21. Interacts with CC CDKN1A/p21. Interacts with CDK5 complexed to CDK5R1 (p25). CC Interacts directly with GFI1 and GFI1B. Interacts with NR1D2 (via CC C-terminus). Interacts with TSC22D3 isoform 1; this interaction CC affects HDAC1 activity on MYOG promoter and thus inhibits MYOD1 CC transcriptional activity. Interacts with BAZ2A/TIP5, BANP, BCL6, CC BCOR, BHLHE40/DEC1, BRMS1, BRMS1L, CBFA2T3, CHFR, CIART, CRY1, CC DAXX, DDIT3/CHOP, DDX5, DNMT1, E4F1, EP300, HCFC1, HDAC9, INSM1, CC NFE4, NR4A2/NURR1, MIER1, KDM4A, KDM5B, KLF1, MINT, NRIP1, PCAF, CC PHB2, PRDM6, PRDM16, RB1, RERE, SAMSN1, SAP30L, SETDB1, SMAD3, CC SMARCA4/BRG1, SMYD2, SUV39H1, TGIF, TGIF2, TRAF6, UHRF1, UHRF2, CC ZMYND15, ZNF431 and ZNF541. Interacts with KDM5A (By similarity). CC Interacts with DNTTIP1 (PubMed:25653165). Identified in a histone CC deacetylase complex that contains DNTTIP1, HDAC1 and ELMSAN1; this CC complex assembles into a tetramer that contains four copies of CC each protein chain (PubMed:25653165). Interacts with CCAR2 CC (PubMed:21030595). Interacts with PPHLN1 (PubMed:17963697). CC {ECO:0000250|UniProtKB:O09106, ECO:0000269|PubMed:10487760, CC ECO:0000269|PubMed:10655483, ECO:0000269|PubMed:10669754, CC ECO:0000269|PubMed:10846170, ECO:0000269|PubMed:10898795, CC ECO:0000269|PubMed:11006275, ECO:0000269|PubMed:11102443, CC ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:11427533, CC ECO:0000269|PubMed:11533236, ECO:0000269|PubMed:12482978, CC ECO:0000269|PubMed:12493763, ECO:0000269|PubMed:12670868, CC ECO:0000269|PubMed:12724404, ECO:0000269|PubMed:12730668, CC ECO:0000269|PubMed:12837748, ECO:0000269|PubMed:14633989, CC ECO:0000269|PubMed:15273251, ECO:0000269|PubMed:15361834, CC ECO:0000269|PubMed:15451426, ECO:0000269|PubMed:15454082, CC ECO:0000269|PubMed:15927959, ECO:0000269|PubMed:16166625, CC ECO:0000269|PubMed:16478997, ECO:0000269|PubMed:16569215, CC ECO:0000269|PubMed:16820529, ECO:0000269|PubMed:17000776, CC ECO:0000269|PubMed:17341466, ECO:0000269|PubMed:17369852, CC ECO:0000269|PubMed:17373667, ECO:0000269|PubMed:17548428, CC ECO:0000269|PubMed:17704056, ECO:0000269|PubMed:17872950, CC ECO:0000269|PubMed:17963697, ECO:0000269|PubMed:17996965, CC ECO:0000269|PubMed:18093978, ECO:0000269|PubMed:19049980, CC ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:19081374, CC ECO:0000269|PubMed:19182791, ECO:0000269|PubMed:19343227, CC ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:21549307, CC ECO:0000269|PubMed:21829689, ECO:0000269|PubMed:25653165}. CC -!- INTERACTION: CC Q9UKG1:APPL1; NbExp=2; IntAct=EBI-301834, EBI-741243; CC Q14865:ARID5B; NbExp=4; IntAct=EBI-301834, EBI-1210388; CC Q9C0K0:BCL11B; NbExp=3; IntAct=EBI-301834, EBI-6597578; CC Q9HCU9:BRMS1; NbExp=4; IntAct=EBI-301834, EBI-714781; CC Q6PH81:C16orf87; NbExp=3; IntAct=EBI-301834, EBI-6598617; CC Q14839:CHD4; NbExp=6; IntAct=EBI-301834, EBI-372916; CC P68400:CSNK2A1; NbExp=2; IntAct=EBI-301834, EBI-347804; CC Q9UER7:DAXX; NbExp=2; IntAct=EBI-301834, EBI-77321; CC Q92841-4:DDX17; NbExp=3; IntAct=EBI-301834, EBI-5280703; CC P17844:DDX5; NbExp=4; IntAct=EBI-301834, EBI-351962; CC Q7L2E3:DHX30; NbExp=3; IntAct=EBI-301834, EBI-1211456; CC Q9UJW3:DNMT3L; NbExp=3; IntAct=EBI-301834, EBI-740967; CC Q66K89:E4F1; NbExp=3; IntAct=EBI-301834, EBI-1227043; CC Q96KQ7:EHMT2; NbExp=3; IntAct=EBI-301834, EBI-744366; CC Q8N140:EID3; NbExp=2; IntAct=EBI-301834, EBI-744483; CC Q9NP50:FAM60A; NbExp=4; IntAct=EBI-301834, EBI-741906; CC Q99684:GFI1; NbExp=4; IntAct=EBI-301834, EBI-949368; CC P51610:HCFC1; NbExp=2; IntAct=EBI-301834, EBI-396176; CC Q92769:HDAC2; NbExp=10; IntAct=EBI-301834, EBI-301821; CC P62805:HIST2H4B; NbExp=2; IntAct=EBI-301834, EBI-302023; CC P43355:MAGEA1; NbExp=2; IntAct=EBI-301834, EBI-740978; CC Q9UIS9:MBD1; NbExp=2; IntAct=EBI-301834, EBI-867196; CC Q8N108:MIER1; NbExp=7; IntAct=EBI-301834, EBI-3504940; CC Q13330:MTA1; NbExp=4; IntAct=EBI-301834, EBI-714236; CC Q9Y618:NCOR2; NbExp=2; IntAct=EBI-301834, EBI-80830; CC P19838:NFKB1; NbExp=5; IntAct=EBI-301834, EBI-300010; CC P06748:NPM1; NbExp=2; IntAct=EBI-301834, EBI-78579; CC Q9Y5X4:NR2E3; NbExp=2; IntAct=EBI-301834, EBI-7216962; CC Q9NQX1:PRDM5; NbExp=3; IntAct=EBI-301834, EBI-4292031; CC Q96N64:PWWP2A; NbExp=4; IntAct=EBI-301834, EBI-6597774; CC P06400:RB1; NbExp=4; IntAct=EBI-301834, EBI-491274; CC Q09028:RBBP4; NbExp=6; IntAct=EBI-301834, EBI-620823; CC Q16576:RBBP7; NbExp=5; IntAct=EBI-301834, EBI-352227; CC Q04206:RELA; NbExp=6; IntAct=EBI-301834, EBI-73886; CC O00422:SAP18; NbExp=2; IntAct=EBI-301834, EBI-1044156; CC O95863:SNAI1; NbExp=3; IntAct=EBI-301834, EBI-1045459; CC O43463:SUV39H1; NbExp=3; IntAct=EBI-301834, EBI-349968; CC P04637:TP53; NbExp=7; IntAct=EBI-301834, EBI-366083; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10846170}. CC -!- TISSUE SPECIFICITY: Ubiquitous, with higher levels in heart, CC pancreas and testis, and lower levels in kidney and brain. CC -!- PTM: Sumoylated on Lys-444 and Lys-476; which promotes enzymatic CC activity. Desumoylated by SENP1. {ECO:0000269|PubMed:11960997, CC ECO:0000269|PubMed:12032081, ECO:0000269|PubMed:15199155}. CC -!- PTM: Phosphorylation on Ser-421 and Ser-423 promotes enzymatic CC activity and interactions with NuRD and SIN3 complexes. CC Phosphorylated by CDK5. {ECO:0000269|PubMed:11602581}. CC -!- PTM: Ubiquitinated by CHFR, leading to its degradation by the CC proteasome. Ubiquitinated by KCTD11, leading to proteasomal CC degradation. {ECO:0000269|PubMed:19182791, CC ECO:0000269|PubMed:20081843}. CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 1 CC subfamily. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U50079; AAC50475.1; -; mRNA. DR EMBL; D50405; BAA08909.1; -; mRNA. DR EMBL; BC000301; AAH00301.1; -; mRNA. DR CCDS; CCDS360.1; -. DR RefSeq; NP_004955.2; NM_004964.2. DR UniGene; Hs.88556; -. DR PDB; 1TYI; Model; -; A=1-482. DR PDB; 4BKX; X-ray; 3.00 A; B=1-482. DR PDBsum; 1TYI; -. DR PDBsum; 4BKX; -. DR ProteinModelPortal; Q13547; -. DR SMR; Q13547; 8-376. DR BioGrid; 109315; 494. DR DIP; DIP-24184N; -. DR IntAct; Q13547; 174. DR MINT; MINT-90475; -. DR STRING; 9606.ENSP00000362649; -. DR BindingDB; Q13547; -. DR ChEMBL; CHEMBL2093865; -. DR DrugBank; DB02546; Vorinostat. DR GuidetoPHARMACOLOGY; 2658; -. DR PhosphoSite; Q13547; -. DR BioMuta; HDAC1; -. DR DMDM; 2498443; -. DR MaxQB; Q13547; -. DR PaxDb; Q13547; -. DR PeptideAtlas; Q13547; -. DR PRIDE; Q13547; -. DR DNASU; 3065; -. DR Ensembl; ENST00000373548; ENSP00000362649; ENSG00000116478. DR GeneID; 3065; -. DR KEGG; hsa:3065; -. DR UCSC; uc001bvb.1; human. DR CTD; 3065; -. DR GeneCards; HDAC1; -. DR HGNC; HGNC:4852; HDAC1. DR HPA; CAB005017; -. DR HPA; CAB068191; -. DR HPA; HPA029693; -. DR MIM; 601241; gene. DR neXtProt; NX_Q13547; -. DR PharmGKB; PA29226; -. DR eggNOG; KOG1342; Eukaryota. DR eggNOG; COG0123; LUCA. DR HOGENOM; HOG000225180; -. DR HOVERGEN; HBG057112; -. DR InParanoid; Q13547; -. DR KO; K06067; -. DR OMA; HASCVKF; -. DR OrthoDB; EOG7DNNTW; -. DR PhylomeDB; Q13547; -. DR TreeFam; TF106171; -. DR BRENDA; 3.5.1.98; 2681. DR Reactome; R-HSA-1538133; G0 and Early G1. DR Reactome; R-HSA-193670; p75NTR negatively regulates cell cycle via SC1. DR Reactome; R-HSA-201722; formation of the beta-catenin:TCF transactivating complex. DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription. DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity. DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription. DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants. DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants. DR Reactome; R-HSA-3214815; HDACs deacetylate histones. DR Reactome; R-HSA-3769402; deactivation of the beta-catenin transactivating complex. DR Reactome; R-HSA-427413; NoRC negatively regulates rRNA expression. DR Reactome; R-HSA-4641265; repression of WNT target genes. DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation. DR Reactome; R-HSA-983231; Factors involved in megakaryocyte development and platelet production. DR SABIO-RK; Q13547; -. DR ChiTaRS; HDAC1; human. DR GeneWiki; HDAC1; -. DR GenomeRNAi; 3065; -. DR NextBio; 12125; -. DR PRO; PR:Q13547; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; Q13547; -. DR CleanEx; HS_HDAC1; -. DR ExpressionAtlas; Q13547; baseline and differential. DR Genevisible; Q13547; HS. DR GO; GO:0000785; C:chromatin; IDA:ParkinsonsUK-UCL. DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0000118; C:histone deacetylase complex; TAS:UniProtKB. DR GO; GO:0000790; C:nuclear chromatin; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016581; C:NuRD complex; IDA:UniProtKB. DR GO; GO:0043234; C:protein complex; IDA:UniProtKB. DR GO; GO:0016580; C:Sin3 complex; IDA:BHF-UCL. DR GO; GO:0033613; F:activating transcription factor binding; IPI:UniProtKB. DR GO; GO:0001047; F:core promoter binding; IDA:UniProtKB. DR GO; GO:0019213; F:deacetylase activity; ISS:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0004407; F:histone deacetylase activity; IMP:UniProtKB. DR GO; GO:0042826; F:histone deacetylase binding; IPI:BHF-UCL. DR GO; GO:0032041; F:NAD-dependent histone deacetylase activity (H3-K14 specific); IEA:UniProtKB-EC. DR GO; GO:0051059; F:NF-kappaB binding; IPI:UniProtKB. DR GO; GO:0033558; F:protein deacetylase activity; IDA:UniProtKB. DR GO; GO:0047485; F:protein N-terminus binding; IDA:MGI. DR GO; GO:0070491; F:repressing transcription factor binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0001103; F:RNA polymerase II repressing transcription factor binding; IPI:BHF-UCL. DR GO; GO:0001106; F:RNA polymerase II transcription corepressor activity; IDA:BHF-UCL. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0000976; F:transcription regulatory region sequence-specific DNA binding; ISS:UniProtKB. DR GO; GO:0043044; P:ATP-dependent chromatin remodeling; IDA:UniProtKB. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0016568; P:chromatin modification; TAS:UniProtKB. DR GO; GO:0006325; P:chromatin organization; TAS:Reactome. DR GO; GO:0006338; P:chromatin remodeling; IC:BHF-UCL. DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB. DR GO; GO:0042733; P:embryonic digit morphogenesis; ISS:BHF-UCL. DR GO; GO:0009913; P:epidermal cell differentiation; ISS:BHF-UCL. DR GO; GO:0061029; P:eyelid development in camera-type eye; ISS:BHF-UCL. DR GO; GO:0061198; P:fungiform papilla formation; ISS:BHF-UCL. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0060789; P:hair follicle placode formation; ISS:BHF-UCL. DR GO; GO:0016575; P:histone deacetylation; IMP:UniProtKB. DR GO; GO:0070932; P:histone H3 deacetylation; IDA:BHF-UCL. DR GO; GO:0070933; P:histone H4 deacetylation; IDA:BHF-UCL. DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome. DR GO; GO:0043922; P:negative regulation by host of viral transcription; IMP:UniProtKB. DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:BHF-UCL. DR GO; GO:0045786; P:negative regulation of cell cycle; TAS:Reactome. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:CACAO. DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; TAS:Reactome. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome. DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISS:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell proliferation; IMP:BHF-UCL. DR GO; GO:0010870; P:positive regulation of receptor biosynthetic process; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL. DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB. DR GO; GO:0040029; P:regulation of gene expression, epigenetic; TAS:Reactome. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0006351; P:transcription, DNA-templated; TAS:Reactome. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. DR Gene3D; 3.40.800.20; -; 1. DR InterPro; IPR000286; His_deacetylse. DR InterPro; IPR003084; His_deacetylse_1. DR InterPro; IPR023801; His_deacetylse_dom. DR PANTHER; PTHR10625; PTHR10625; 1. DR Pfam; PF00850; Hist_deacetyl; 1. DR PIRSF; PIRSF037913; His_deacetylse_1; 1. DR PRINTS; PR01270; HDASUPER. DR PRINTS; PR01271; HISDACETLASE. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Biological rhythms; Chromatin regulator; KW Complete proteome; Host-virus interaction; Hydrolase; Isopeptide bond; KW Methylation; Nucleus; Phosphoprotein; Reference proteome; Repressor; KW Transcription; Transcription regulation; Ubl conjugation. FT CHAIN 1 482 Histone deacetylase 1. FT /FTId=PRO_0000114687. FT REGION 9 321 Histone deacetylase. FT ACT_SITE 141 141 FT MOD_RES 74 74 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 220 220 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 393 393 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:17487921, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 421 421 Phosphoserine; by CK2. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18318008, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000269|PubMed:11602581}. FT MOD_RES 423 423 Phosphoserine; by CK2. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18318008, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000269|PubMed:11602581}. FT MOD_RES 432 432 N6-methylated lysine; by EHMT2. FT {ECO:0000269|PubMed:18438403}. FT CROSSLNK 444 444 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO); FT alternate. {ECO:0000269|PubMed:11960997}. FT CROSSLNK 444 444 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2); FT alternate. {ECO:0000244|PubMed:25218447}. FT CROSSLNK 457 457 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 476 476 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO); FT alternate. {ECO:0000269|PubMed:11960997}. FT CROSSLNK 476 476 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2); FT alternate. {ECO:0000244|PubMed:25218447}. FT MUTAGEN 141 141 H->A: Abolishes histone deacetylase FT activity. {ECO:0000269|PubMed:19182791}. FT MUTAGEN 287 287 F->Y: Abolishes interaction with CHFR; FT when associated with I-297. FT {ECO:0000269|PubMed:19182791}. FT MUTAGEN 297 297 M->I: Abolishes interaction with CHFR; FT when associated with Y-287. FT {ECO:0000269|PubMed:19182791}. FT MUTAGEN 391 482 Missing: Strongly decreases deacetylase FT activity, and disrupts interaction with FT NuRD and SIN3 complexes. FT MUTAGEN 421 421 S->A: Strongly decreases deacetylase FT activity, and disrupts interaction with FT NuRD and SIN3 complexes. FT {ECO:0000269|PubMed:11602581}. FT MUTAGEN 421 421 S->D,E: Slightly decreases deacetylase FT activity. {ECO:0000269|PubMed:11602581}. FT MUTAGEN 423 423 S->A: Strongly decreases deacetylase FT activity, and disrupts interaction with FT NuRD and SIN3 complexes. FT {ECO:0000269|PubMed:11602581}. FT MUTAGEN 423 423 S->D,E: Decreases deacetylase activity. FT {ECO:0000269|PubMed:11602581}. FT MUTAGEN 424 424 E->A: Slightly decreases deacetylase FT activity, no effect on interaction with FT NuRD and SIN3 complexes. FT MUTAGEN 425 425 E->A: No effect on deacetylase activity, FT no effect on interaction with NuRD and FT SIN3 complexes. FT MUTAGEN 426 426 E->A: Decreases deacetylase activity, and FT disrupts interaction with NuRD and SIN3 FT complexes. FT CONFLICT 312 312 W -> R (in Ref. 2; BAA08909). FT {ECO:0000305}. FT STRAND 11 14 {ECO:0000244|PDB:4BKX}. FT HELIX 19 21 {ECO:0000244|PDB:4BKX}. FT HELIX 33 44 {ECO:0000244|PDB:4BKX}. FT HELIX 48 50 {ECO:0000244|PDB:4BKX}. FT STRAND 51 56 {ECO:0000244|PDB:4BKX}. FT HELIX 61 64 {ECO:0000244|PDB:4BKX}. FT TURN 65 67 {ECO:0000244|PDB:4BKX}. FT HELIX 70 78 {ECO:0000244|PDB:4BKX}. FT TURN 83 86 {ECO:0000244|PDB:4BKX}. FT HELIX 88 94 {ECO:0000244|PDB:4BKX}. FT TURN 97 99 {ECO:0000244|PDB:4BKX}. FT HELIX 106 125 {ECO:0000244|PDB:4BKX}. FT STRAND 130 136 {ECO:0000244|PDB:4BKX}. FT STRAND 151 153 {ECO:0000244|PDB:4BKX}. FT HELIX 155 163 {ECO:0000244|PDB:4BKX}. FT TURN 164 166 {ECO:0000244|PDB:4BKX}. FT STRAND 170 174 {ECO:0000244|PDB:4BKX}. FT STRAND 176 178 {ECO:0000244|PDB:4BKX}. FT HELIX 181 186 {ECO:0000244|PDB:4BKX}. FT TURN 187 189 {ECO:0000244|PDB:4BKX}. FT STRAND 191 200 {ECO:0000244|PDB:4BKX}. FT STRAND 205 207 {ECO:0000244|PDB:4BKX}. FT HELIX 217 219 {ECO:0000244|PDB:4BKX}. FT STRAND 223 228 {ECO:0000244|PDB:4BKX}. FT HELIX 234 252 {ECO:0000244|PDB:4BKX}. FT STRAND 255 260 {ECO:0000244|PDB:4BKX}. FT HELIX 263 265 {ECO:0000244|PDB:4BKX}. FT HELIX 278 289 {ECO:0000244|PDB:4BKX}. FT STRAND 295 298 {ECO:0000244|PDB:4BKX}. FT HELIX 305 319 {ECO:0000244|PDB:4BKX}. FT HELIX 334 336 {ECO:0000244|PDB:4BKX}. FT TURN 338 340 {ECO:0000244|PDB:4BKX}. FT HELIX 356 371 {ECO:0000244|PDB:4BKX}. SQ SEQUENCE 482 AA; 55103 MW; 4D35B7C1ED7838D6 CRC64; MAQTQGTRRK VCYYYDGDVG NYYYGQGHPM KPHRIRMTHN LLLNYGLYRK MEIYRPHKAN AEEMTKYHSD DYIKFLRSIR PDNMSEYSKQ MQRFNVGEDC PVFDGLFEFC QLSTGGSVAS AVKLNKQQTD IAVNWAGGLH HAKKSEASGF CYVNDIVLAI LELLKYHQRV LYIDIDIHHG DGVEEAFYTT DRVMTVSFHK YGEYFPGTGD LRDIGAGKGK YYAVNYPLRD GIDDESYEAI FKPVMSKVME MFQPSAVVLQ CGSDSLSGDR LGCFNLTIKG HAKCVEFVKS FNLPMLMLGG GGYTIRNVAR CWTYETAVAL DTEIPNELPY NDYFEYFGPD FKLHISPSNM TNQNTNEYLE KIKQRLFENL RMLPHAPGVQ MQAIPEDAIP EESGDEDEDD PDKRISICSS DKRIACEEEF SDSEEEGEGG RKNSSNFKKA KRVKTEDEKE KDPEEKKEVT EEEKTKEEKP EAKGVKEEVK LA // ID HEMGN_HUMAN Reviewed; 484 AA. AC Q9BXL5; Q6XAR3; Q86XY5; Q9NPC0; DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 11-NOV-2015, entry version 99. DE RecName: Full=Hemogen; DE AltName: Full=Erythroid differentiation-associated gene protein; DE Short=EDAG-1; DE AltName: Full=Hemopoietic gene protein; DE AltName: Full=Negative differentiation regulator protein; GN Name=HEMGN; Synonyms=EDAG, NDR; ORFNames=PRO1037, PRO1620; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL RP STAGE. RC TISSUE=Bone marrow; RX PubMed=11404085; DOI=10.1016/S0925-4773(01)00376-8; RA Yang L.V., Nicholson R.H., Kaplan J., Galy A., Li L.; RT "Hemogen is a novel nuclear factor specifically expressed in mouse RT hematopoietic development and its human homologue EDAG maps to RT chromosome 9q22, a region containing breakpoints of hematological RT neoplasms."; RL Mech. Dev. 104:105-111(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX PubMed=14648837; DOI=10.1002/dvdy.10399; RA Yang L.V., Heng H.H., Wan J., Southwood C.M., Gow A., Li L.; RT "Alternative promoters and polyadenylation regulate tissue-specific RT expression of Hemogen isoforms during hematopoiesis and RT spermatogenesis."; RL Dev. Dyn. 228:606-616(2003). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION, AND TISSUE RP SPECIFICITY. RX PubMed=15332117; DOI=10.1038/sj.cdd.4401490; RA Li C.Y., Zhan Y.Q., Xu C.W., Xu W.X., Wang S.Y., Lv J., Zhou Y., RA Yue P.B., Chen B., Yang X.M.; RT "EDAG regulates the proliferation and differentiation of hematopoietic RT cells and resists cell apoptosis through the activation of nuclear RT factor-kappa B."; RL Cell Death Differ. 11:1299-1308(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, RP DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, AND INDUCTION. RX PubMed=14730214; DOI=10.1007/BF02256553; RA Liu C.C., Chou Y.L., Ch'ang L.Y.; RT "Down-regulation of human NDR gene in megakaryocytic differentiation RT of erythroleukemia K562 cells."; RL J. Biomed. Sci. 11:104-116(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., RA Rogers J., Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-484. RC TISSUE=Fetal liver; RA Zhang C., Yu Y., Zhang S., Wei H., Bi J., Zhou G., Dong C., Zai Y., RA Xu W., Gao F., Liu M., He F.; RT "Functional prediction of the coding sequences of 75 new genes deduced RT by analysis of cDNA clones from human fetal liver."; RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 115-484. RC TISSUE=Fetal liver; RA Zhang C., Yu Y., Zhang S., Wei H., Zhou G., Ouyang S., Luo L., Bi J., RA Liu M., He F.; RT "Functional prediction of the coding sequences of 121 new genes RT deduced by analysis of cDNA clones from human fetal liver."; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [9] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=15920494; DOI=10.1038/sj.leu.2403808; RA An L.-L., Li G., Wu K.-F., Ma X.-T., Zheng G.-G., Qiu L.-G., RA Song Y.-H.; RT "High expression of EDAG and its significance in AML."; RL Leukemia 19:1499-1502(2005). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP TISSUE SPECIFICITY. RX PubMed=23436708; DOI=10.1002/pmic.201200489; RA Liu M., Hu Z., Qi L., Wang J., Zhou T., Guo Y., Zeng Y., Zheng B., RA Wu Y., Zhang P., Chen X., Tu W., Zhang T., Zhou Q., Jiang M., Guo X., RA Zhou Z., Sha J.; RT "Scanning of novel cancer/testis proteins by human testis proteomic RT analysis."; RL Proteomics 13:1200-1210(2013). CC -!- FUNCTION: Regulates the proliferation and differentiation of CC hematopoietic cells. Overexpression block the TPA-induced CC megakaryocytic differentiation in the K562 cell model. May also CC prevent cell apoptosis through the activation of the nuclear CC factor-kappa B (NF-kB). {ECO:0000269|PubMed:14730214, CC ECO:0000269|PubMed:15332117, ECO:0000269|PubMed:15920494}. CC -!- INTERACTION: CC Q13363:CTBP1; NbExp=2; IntAct=EBI-3916399, EBI-908846; CC P06748:NPM1; NbExp=7; IntAct=EBI-3916399, EBI-78579; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14730214}. CC -!- TISSUE SPECIFICITY: Expressed in hematopoietic precursor cells, CC thyroid and spermatids (at protein level). Expressed in bone CC marrow, testis, thymus. Expressed in prostate cancer and ovarian CC cancer. Also expressed in thymus and thyroid tumors, non-Hodgkin CC lymphoma, various leukemia cell lines, peripheral blood CC mononuclear cells (PBMCs) and bone marrow mononuclear cells CC (BMMCs) of patients with leukemia. {ECO:0000269|PubMed:11404085, CC ECO:0000269|PubMed:14648837, ECO:0000269|PubMed:14730214, CC ECO:0000269|PubMed:15332117, ECO:0000269|PubMed:15920494, CC ECO:0000269|PubMed:23436708}. CC -!- DEVELOPMENTAL STAGE: Expressed in fetal liver, kidney and brain. CC {ECO:0000269|PubMed:11404085, ECO:0000269|PubMed:14730214}. CC -!- INDUCTION: Down-regulated during megakaryocytic differentiation of CC K562 cells by 12-O-tetradecanoylphorbol-13-acetate (TPA) (at CC protein level). Up-regulated in normal PBMCs by mitogens. CC {ECO:0000269|PubMed:14730214, ECO:0000269|PubMed:15332117}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF67133.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAF71041.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAG35488.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF322875; AAK26295.1; -; mRNA. DR EMBL; AY244805; AAP75762.1; -; mRNA. DR EMBL; AY255672; AAP81221.1; -; mRNA. DR EMBL; AF228713; AAF67133.1; ALT_INIT; mRNA. DR EMBL; AL499604; CAI12808.1; -; Genomic_DNA. DR EMBL; BC048324; AAH48324.1; -; mRNA. DR EMBL; AF130060; AAG35488.1; ALT_INIT; mRNA. DR EMBL; AF116617; AAF71041.1; ALT_INIT; mRNA. DR CCDS; CCDS6731.1; -. DR RefSeq; NP_060907.2; NM_018437.4. DR RefSeq; NP_932095.1; NM_197978.2. DR RefSeq; XP_005252143.1; XM_005252086.1. DR RefSeq; XP_011517147.1; XM_011518845.1. DR RefSeq; XP_011517148.1; XM_011518846.1. DR UniGene; Hs.176626; -. DR ProteinModelPortal; Q9BXL5; -. DR BioGrid; 120641; 1. DR IntAct; Q9BXL5; 32. DR MINT; MINT-7220237; -. DR STRING; 9606.ENSP00000259456; -. DR PhosphoSite; Q9BXL5; -. DR DMDM; 74752432; -. DR MaxQB; Q9BXL5; -. DR PaxDb; Q9BXL5; -. DR PeptideAtlas; Q9BXL5; -. DR PRIDE; Q9BXL5; -. DR Ensembl; ENST00000259456; ENSP00000259456; ENSG00000136929. DR Ensembl; ENST00000616898; ENSP00000480020; ENSG00000136929. DR GeneID; 55363; -. DR KEGG; hsa:55363; -. DR UCSC; uc004axy.4; human. DR CTD; 55363; -. DR GeneCards; HEMGN; -. DR HGNC; HGNC:17509; HEMGN. DR HPA; HPA019572; -. DR HPA; HPA019604; -. DR HPA; HPA019606; -. DR MIM; 610715; gene. DR neXtProt; NX_Q9BXL5; -. DR PharmGKB; PA38458; -. DR eggNOG; ENOG410IXJU; Eukaryota. DR eggNOG; ENOG411096P; LUCA. DR GeneTree; ENSGT00390000004522; -. DR HOGENOM; HOG000061736; -. DR HOVERGEN; HBG080273; -. DR InParanoid; Q9BXL5; -. DR OMA; PEIYQET; -. DR OrthoDB; EOG7K3TN9; -. DR PhylomeDB; Q9BXL5; -. DR TreeFam; TF338654; -. DR ChiTaRS; HEMGN; human. DR GeneWiki; HEMGN; -. DR GenomeRNAi; 55363; -. DR NextBio; 59739; -. DR PRO; PR:Q9BXL5; -. DR Proteomes; UP000005640; Chromosome 9. DR Bgee; Q9BXL5; -. DR CleanEx; HS_HEMGN; -. DR ExpressionAtlas; Q9BXL5; baseline and differential. DR Genevisible; Q9BXL5; HS. DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW. DR GO; GO:0045667; P:regulation of osteoblast differentiation; IBA:GO_Central. PE 1: Evidence at protein level; KW Complete proteome; Developmental protein; Differentiation; Nucleus; KW Phosphoprotein; Reference proteome. FT CHAIN 1 484 Hemogen. FT /FTId=PRO_0000245361. FT REGION 7 87 Necessary for nuclear localization. FT MOD_RES 159 159 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9ERZ0}. FT MOD_RES 201 201 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9ERZ0}. FT MOD_RES 246 246 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q9ERZ0}. FT MOD_RES 367 367 Phosphoserine. FT {ECO:0000250|UniProtKB:Q6AZ54}. FT CONFLICT 78 78 R -> K (in Ref. 2; AAP75762 and 3; FT AAF67133). {ECO:0000305}. FT CONFLICT 96 97 IV -> M (in Ref. 6; AAH48324). FT {ECO:0000305}. SQ SEQUENCE 484 AA; 55341 MW; E1464D1C7BEA1F07 CRC64; MDLGKDQSHL KHHQTPDPHQ EENHSPEVIG TWSLRNRELL RKRKAEVHEK ETSQWLFGEQ KKRKQQRTGK GNRRGRKRQQ NTELKVEPQP QIEKEIVEKA LAPIEKKTEP PGSITKVFPS VASPQKVVPE EHFSEICQES NIYQENFSEY QEIAVQNHSS ETCQHVSEPE DLSPKMYQEI SVLQDNSSKI CQDMKEPEDN SPNTCQVISV IQDHPFKMYQ DMAKREDLAP KMCQEAAVPK ILPCPTSEDT ADLAGCSLQA YPKPDVPKGY ILDTDQNPAE PEEYNETDQG IAETEGLFPK IQEIAEPKDL STKTHQESAE PKYLPHKTCN EIIVPKAPSH KTIQETPHSE DYSIEINQET PGSEKYSPET YQEIPGLEEY SPEIYQETSQ LEEYSPEIYQ ETPGPEDLST ETYKNKDVPK ECFPEPHQET GGPQGQDPKA HQEDAKDAYT FPQEMKEKPK EEPGIPAILN ESHPENDVYS YVLF // ID HIC1_HUMAN Reviewed; 733 AA. AC Q14526; D3DTI4; DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 5. DT 11-NOV-2015, entry version 147. DE RecName: Full=Hypermethylated in cancer 1 protein; DE Short=Hic-1; DE AltName: Full=Zinc finger and BTB domain-containing protein 29; GN Name=HIC1; Synonyms=ZBTB29; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2), AND VARIANT GLY-725. RX PubMed=7585125; DOI=10.1038/nm0695-570; RA Wales M.M., Biel M.A., el Deiry W., Nelkin B.D., Issa J.-P., RA Cavenee W.K., Kuerbitz S.J., Baylin S.B.; RT "p53 activates expression of HIC-1, a new candidate tumour suppressor RT gene on 17p13.3."; RL Nat. Med. 1:570-577(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in RT the human lineage."; RL Nature 440:1045-1049(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP SELF-ASSOCIATION. RX PubMed=10611298; DOI=10.1073/pnas.96.26.14831; RA Deltour S., Guerardel C., Leprince D.; RT "Recruitment of SMRT/N-CoR-mSin3A-HDAC-repressing complexes is not a RT general mechanism for BTB/POZ transcriptional repressors: the case of RT HIC-1 and gammaFBP-B."; RL Proc. Natl. Acad. Sci. U.S.A. 96:14831-14836(1999). RN [5] RP ALTERNATIVE SPLICING, INTERACTION WITH HIC2, AND SUBCELLULAR LOCATION. RX PubMed=11554746; DOI=10.1006/bbrc.2001.5624; RA Deltour S., Pinte S., Guerardel C., Leprince D.; RT "Characterization of HRG22, a human homologue of the putative tumor RT suppressor gene HIC1."; RL Biochem. Biophys. Res. Commun. 287:427-434(2001). RN [6] RP FUNCTION, SELF-ASSOCIATION, AND INTERACTION WITH CTBP1. RX PubMed=12052894; DOI=10.1128/MCB.22.13.4890-4901.2002; RA Deltour S., Pinte S., Guerardel C., Wasylyk B., Leprince D.; RT "The human candidate tumor suppressor gene HIC1 recruits CtBP through RT a degenerate GLDLSKK motif."; RL Mol. Cell. Biol. 22:4890-4901(2002). RN [7] RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF CYS-540. RX PubMed=15231840; DOI=10.1074/jbc.M401610200; RA Pinte S., Stankovic-Valentin N., Deltour S., Rood B.R., Guerardel C., RA Leprince D.; RT "The tumor suppressor gene HIC1 (hypermethylated in cancer 1) is a RT sequence-specific transcriptional repressor: definition of its RT consensus binding sequence and analysis of its DNA binding and RT repressive properties."; RL J. Biol. Chem. 279:38313-38324(2004). RN [8] RP FUNCTION. RX PubMed=16269335; DOI=10.1016/j.cell.2005.08.011; RA Chen W.Y., Wang D.H., Yen R.C., Luo J., Gu W., Baylin S.B.; RT "Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53- RT dependent DNA-damage responses."; RL Cell 123:437-448(2005). RN [9] RP FUNCTION. RX PubMed=16690027; DOI=10.1016/j.bbrc.2006.04.052; RA Briones V.R., Chen S., Riegel A.T., Lechleider R.J.; RT "Mechanism of fibroblast growth factor-binding protein 1 repression by RT TGF-beta."; RL Biochem. Biophys. Res. Commun. 345:595-601(2006). RN [10] RP FUNCTION IN WNT SIGNALING, AND INTERACTION WITH TCF7L2. RX PubMed=16724116; DOI=10.1038/sj.emboj.7601147; RA Valenta T., Lukas J., Doubravska L., Fafilek B., Korinek V.; RT "HIC1 attenuates Wnt signaling by recruitment of TCF-4 and beta- RT catenin to the nuclear bodies."; RL EMBO J. 25:2326-2337(2006). RN [11] RP INTERACTION WITH CTBP1 AND CTBP2, AND MUTAGENESIS OF LEU-244. RX PubMed=16762039; DOI=10.1111/j.1742-4658.2006.05301.x; RA Stankovic-Valentin N., Verger A., Deltour-Balerdi S., Quinlan K.G., RA Crossley M., Leprince D.; RT "A L225A substitution in the human tumour suppressor HIC1 abolishes RT its interaction with the corepressor CtBP."; RL FEBS J. 273:2879-2890(2006). RN [12] RP SUMOYLATION AT LYS-333, ACETYLATION AT LYS-333, AND MUTAGENESIS OF RP LYS-333; GLU-335 AND PRO-336. RX PubMed=17283066; DOI=10.1128/MCB.01098-06; RA Stankovic-Valentin N., Deltour S., Seeler J., Pinte S., Vergoten G., RA Guerardel C., Dejean A., Leprince D.; RT "An acetylation/deacetylation-SUMOylation switch through a RT phylogenetically conserved psiKXEP motif in the tumor suppressor HIC1 RT regulates transcriptional repression activity."; RL Mol. Cell. Biol. 27:2661-2675(2007). RN [13] RP FUNCTION, AND INTERACTION WITH CTBP1. RX PubMed=17213307; DOI=10.1073/pnas.0610590104; RA Zhang Q., Wang S.Y., Fleuriel C., Leprince D., Rocheleau J.V., RA Piston D.W., Goodman R.H.; RT "Metabolic regulation of SIRT1 transcription via a HIC1:CtBP RT corepressor complex."; RL Proc. Natl. Acad. Sci. U.S.A. 104:829-833(2007). RN [14] RP FUNCTION. RX PubMed=18347096; DOI=10.1101/gad.1640908; RA Briggs K.J., Corcoran-Schwartz I.M., Zhang W., Harcke T., RA Devereux W.L., Baylin S.B., Eberhart C.G., Watkins D.N.; RT "Cooperation between the Hic1 and Ptch1 tumor suppressors in RT medulloblastoma."; RL Genes Dev. 22:770-785(2008). RN [15] RP ERRATUM. RA Briggs K.J., Corcoran-Schwartz I.M., Zhang W., Harcke T., RA Devereux W.L., Baylin S.B., Eberhart C.G., Watkins D.N.; RL Genes Dev. 22:1410-1410(2008). RN [16] RP FUNCTION, AND INTERACTION WITH ARID1A. RX PubMed=19486893; DOI=10.1016/j.bbrc.2009.05.115; RA Van Rechem C., Boulay G., Leprince D.; RT "HIC1 interacts with a specific subunit of SWI/SNF complexes, RT ARID1A/BAF250A."; RL Biochem. Biophys. Res. Commun. 385:586-590(2009). RN [17] RP FUNCTION. RX PubMed=19525223; DOI=10.1074/jbc.M109.022350; RA Van Rechem C., Rood B.R., Touka M., Pinte S., Jenal M., Guerardel C., RA Ramsey K., Monte D., Begue A., Tschan M.P., Stephan D.A., Leprince D.; RT "Scavenger chemokine (CXC motif) receptor 7 (CXCR7) is a direct target RT gene of HIC1 (hypermethylated in cancer 1)."; RL J. Biol. Chem. 284:20927-20935(2009). RN [18] RP FUNCTION, INTERACTION WITH MTA1 AND MBD3, AND MUTAGENESIS OF LYS-333; RP GLU-335 AND PRO-336. RX PubMed=20547755; DOI=10.1128/MCB.00582-09; RA Van Rechem C., Boulay G., Pinte S., Stankovic-Valentin N., RA Guerardel C., Leprince D.; RT "Differential regulation of HIC1 target genes by CtBP and NuRD, via an RT acetylation/SUMOylation switch, in quiescent versus proliferating RT cells."; RL Mol. Cell. Biol. 30:4045-4059(2010). RN [19] RP FUNCTION. RX PubMed=20154726; DOI=10.1038/onc.2010.12; RA Zhang W., Zeng X., Briggs K.J., Beaty R., Simons B., Chiu Yen R.W., RA Tyler M.A., Tsai H.C., Ye Y., Gesell G.S., Herman J.G., Baylin S.B., RA Watkins D.N.; RT "A potential tumor suppressor role for Hic1 in breast cancer through RT transcriptional repression of ephrin-A1."; RL Oncogene 29:2467-2476(2010). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-237; SER-248 AND RP SER-366, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Transcriptional repressor. Recognizes and binds to the CC consensus sequence '5-[CG]NG[CG]GGGCA[CA]CC-3'. May act as a tumor CC suppressor. May be involved in development of head, face, limbs CC and ventral body wall. Involved in down-regulation of SIRT1 and CC thereby is involved in regulation of p53/TP53-dependent apoptotic CC DNA-damage responses. The specific target gene promoter CC association seems to be depend on corepressors, such as CTBP1 or CC CTBP2 and MTA1. The regulation of SIRT1 transcription in response CC to nutrient deprivation seems to involve CTBP1. In cooperation CC with MTA1 (indicative for an association with the NuRD complex) CC represses transcription from CCND1/cyclin-D1 and CDKN1C/p57Kip2 CC specifically in quiescent cells. Involved in regulation of the Wnt CC signaling pathway probably by association with TCF7L2 and CC preventing TCF7L2 and CTNNB1 association with promoters of TCF- CC responsive genes. Seems to repress transcription from E2F1 and CC ATOH1 which involves ARID1A, indicative for the participation of a CC distinct SWI/SNF-type chromatin-remodeling complex. Probably CC represses transcription from ACKR3, FGFBP1 and EFNA1. CC {ECO:0000269|PubMed:12052894, ECO:0000269|PubMed:15231840, CC ECO:0000269|PubMed:16269335, ECO:0000269|PubMed:16690027, CC ECO:0000269|PubMed:16724116, ECO:0000269|PubMed:17213307, CC ECO:0000269|PubMed:18347096, ECO:0000269|PubMed:19486893, CC ECO:0000269|PubMed:19525223, ECO:0000269|PubMed:20154726, CC ECO:0000269|PubMed:20547755}. CC -!- SUBUNIT: Self-associates. Interacts with HIC2. Interacts with CC CTBP1 and CTBP2. Interacts with TCF7L2 and ARID1A. Interacts with CC MTA1 and MBD3; indicative for an association with the NuRD CC complex. {ECO:0000269|PubMed:11554746, CC ECO:0000269|PubMed:12052894, ECO:0000269|PubMed:16724116, CC ECO:0000269|PubMed:16762039, ECO:0000269|PubMed:17213307, CC ECO:0000269|PubMed:19486893, ECO:0000269|PubMed:20547755}. CC -!- INTERACTION: CC O14497:ARID1A; NbExp=2; IntAct=EBI-2507362, EBI-637887; CC Q13363:CTBP1; NbExp=4; IntAct=EBI-2507362, EBI-908846; CC O88712:Ctbp1 (xeno); NbExp=10; IntAct=EBI-2507362, EBI-604547; CC P56545:CTBP2; NbExp=2; IntAct=EBI-2507362, EBI-741533; CC P56546:Ctbp2 (xeno); NbExp=2; IntAct=EBI-2507362, EBI-1384883; CC Q9NQB0:TCF7L2; NbExp=6; IntAct=EBI-2507362, EBI-924724; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11554746}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Comment=Additional isoforms seem to exist.; CC Name=1; CC IsoId=Q14526-1; Sequence=Displayed; CC Name=2; CC IsoId=Q14526-2; Sequence=VSP_006826; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels CC found in lung, colon, prostate, thymus, testis and ovary. CC Expression is absent or decreased in many tumor cells. CC -!- DOMAIN: The BTB domain inhibits the binding to a single consensus CC binding site, but mediates cooperative binding to multiple binding CC sites. CC -!- PTM: Acetylated on several residues, including Lys-333. Lys-333 is CC deacetylated by SIRT1. {ECO:0000269|PubMed:17283066}. CC -!- PTM: Sumoylated on Lys-333 by a PIAS family member, which enhances CC interaction with MTA1, positively regulates transcriptional CC repression activity and is enhanced by HDAC4. CC {ECO:0000269|PubMed:17283066}. CC -!- MISCELLANEOUS: The HIC1 gene is frequently found epigenetically CC silenced or deleted in different types of solid tumors. CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein CC family. Hic subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 BTB (POZ) domain. {ECO:0000255|PROSITE- CC ProRule:PRU00037}. CC -!- SIMILARITY: Contains 5 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/HIC1ID40819ch17p13.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; L41919; AAD09201.1; -; Genomic_DNA. DR EMBL; AC090617; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471108; EAW90562.1; -; Genomic_DNA. DR EMBL; CH471108; EAW90563.1; -; Genomic_DNA. DR CCDS; CCDS42229.1; -. [Q14526-1] DR CCDS; CCDS42230.1; -. [Q14526-2] DR RefSeq; NP_001091672.1; NM_001098202.1. [Q14526-1] DR RefSeq; NP_006488.2; NM_006497.3. [Q14526-2] DR UniGene; Hs.695682; -. DR UniGene; Hs.72956; -. DR ProteinModelPortal; Q14526; -. DR SMR; Q14526; 25-145, 429-613. DR BioGrid; 109337; 26. DR IntAct; Q14526; 11. DR MINT; MINT-2730619; -. DR STRING; 9606.ENSP00000314080; -. DR PhosphoSite; Q14526; -. DR BioMuta; HIC1; -. DR DMDM; 296439502; -. DR PaxDb; Q14526; -. DR PRIDE; Q14526; -. DR DNASU; 3090; -. DR Ensembl; ENST00000322941; ENSP00000314080; ENSG00000177374. [Q14526-1] DR Ensembl; ENST00000399849; ENSP00000382742; ENSG00000177374. [Q14526-2] DR Ensembl; ENST00000619757; ENSP00000477858; ENSG00000177374. [Q14526-2] DR GeneID; 3090; -. DR KEGG; hsa:3090; -. DR UCSC; uc002fty.4; human. [Q14526-1] DR CTD; 3090; -. DR GeneCards; HIC1; -. DR H-InvDB; HIX0039113; -. DR HGNC; HGNC:4909; HIC1. DR HPA; HPA043372; -. DR MIM; 603825; gene. DR neXtProt; NX_Q14526; -. DR Orphanet; 531; Miller-Dieker syndrome. DR PharmGKB; PA29282; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00800000124025; -. DR HOGENOM; HOG000026793; -. DR HOVERGEN; HBG031606; -. DR InParanoid; Q14526; -. DR OMA; PPDPFRG; -. DR OrthoDB; EOG74J97F; -. DR PhylomeDB; Q14526; -. DR TreeFam; TF333488; -. DR SignaLink; Q14526; -. DR GeneWiki; HIC1; -. DR GenomeRNAi; 3090; -. DR NextBio; 12259; -. DR PRO; PR:Q14526; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; Q14526; -. DR CleanEx; HS_HIC1; -. DR ExpressionAtlas; Q14526; baseline and differential. DR Genevisible; Q14526; HS. DR GO; GO:0000785; C:chromatin; ISS:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0042826; F:histone deacetylase binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB. DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB. DR GO; GO:0043517; P:positive regulation of DNA damage response, signal transduction by p53 class mediator; ISS:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:UniProtKB. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR Gene3D; 3.30.160.60; -; 4. DR InterPro; IPR000210; BTB/POZ_dom. DR InterPro; IPR028424; HIC1. DR InterPro; IPR011333; POZ_dom. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR PANTHER; PTHR24409:SF69; PTHR24409:SF69; 1. DR Pfam; PF00651; BTB; 1. DR Pfam; PF00096; zf-C2H2; 1. DR SMART; SM00225; BTB; 1. DR SMART; SM00355; ZnF_C2H2; 5. DR SUPFAM; SSF54695; SSF54695; 1. DR PROSITE; PS50097; BTB; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 5. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Complete proteome; KW Developmental protein; DNA-binding; Isopeptide bond; Metal-binding; KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; KW Repressor; Transcription; Transcription regulation; Tumor suppressor; KW Ubl conjugation; Wnt signaling pathway; Zinc; Zinc-finger. FT CHAIN 1 733 Hypermethylated in cancer 1 protein. FT /FTId=PRO_0000046942. FT DOMAIN 47 110 BTB. {ECO:0000255|PROSITE- FT ProRule:PRU00037}. FT ZN_FING 439 459 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 509 529 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 537 557 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 565 585 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 593 613 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT REGION 154 315 Mediates HDAC-dependent transcriptional FT repression. FT REGION 241 247 Interaction with CTBP1. FT COMPBIAS 110 119 Poly-Ala. FT COMPBIAS 160 167 Poly-Gly. FT COMPBIAS 195 199 Poly-Pro. FT MOD_RES 237 237 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 248 248 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 333 333 N6-acetyllysine; alternate. FT {ECO:0000269|PubMed:17283066}. FT MOD_RES 366 366 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 704 704 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9R1Y5}. FT CROSSLNK 333 333 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO); FT alternate. FT VAR_SEQ 1 19 Missing (in isoform 2). {ECO:0000305}. FT /FTId=VSP_006826. FT VARIANT 725 725 R -> G (in dbSNP:rs1063317). FT {ECO:0000269|PubMed:7585125}. FT /FTId=VAR_063109. FT MUTAGEN 244 244 L->A: Abolishes interaction with CTBP1 FT and CTBP2. Impairs transcriptional FT repression. FT {ECO:0000269|PubMed:16762039}. FT MUTAGEN 333 333 K->Q: Mimicks acetylation. Impairs FT interaction with RBBP4 and MTA1 and no FT effect on interaction with CTBP2. Reduces FT transcriptional repression. FT {ECO:0000269|PubMed:17283066, FT ECO:0000269|PubMed:20547755}. FT MUTAGEN 333 333 K->R: Abolishes sumoylation; impairs FT transcriptional repression activity. FT {ECO:0000269|PubMed:17283066, FT ECO:0000269|PubMed:20547755}. FT MUTAGEN 335 335 E->A: Impairs transcriptional repression FT activity. Decreases interaction with FT MTA1. {ECO:0000269|PubMed:17283066, FT ECO:0000269|PubMed:20547755}. FT MUTAGEN 336 336 P->A: Impairs K-333 acetylation; no FT effect on sumoylation. Decreases FT interaction with MTA1. FT {ECO:0000269|PubMed:17283066, FT ECO:0000269|PubMed:20547755}. FT MUTAGEN 540 540 C->S: Abolishes repression activity. FT {ECO:0000269|PubMed:15231840}. FT CONFLICT 190 190 P -> R (in Ref. 1; AAD09201). FT {ECO:0000305}. SQ SEQUENCE 733 AA; 76508 MW; 6DDD0F49C4E490D3 CRC64; MTFPEADILL KSGECAGQTM LDTMEAPGHS RQLLLQLNNQ RTKGFLCDVI IVVQNALFRA HKNVLAASSA YLKSLVVHDN LLNLDHDMVS PAVFRLVLDF IYTGRLADGA EAAAAAAVAP GAEPSLGAVL AAASYLQIPD LVALCKKRLK RHGKYCHLRG GGGGGGGYAP YGRPGRGLRA ATPVIQACYP SPVGPPPPPA AEPPSGPEAA VNTHCAELYA SGPGPAAALC ASERRCSPLC GLDLSKKSPP GSAAPERPLA ERELPPRPDS PPSAGPAAYK EPPLALPSLP PLPFQKLEEA APPSDPFRGG SGSPGPEPPG RPDGPSLLYR WMKHEPGLGS YGDELGRERG SPSERCEERG GDAAVSPGGP PLGLAPPPRY PGSLDGPGAG GDGDDYKSSS EETGSSEDPS PPGGHLEGYP CPHLAYGEPE SFGDNLYVCI PCGKGFPSSE QLNAHVEAHV EEEEALYGRA EAAEVAAGAA GLGPPFGGGG DKVAGAPGGL GELLRPYRCA SCDKSYKDPA TLRQHEKTHW LTRPYPCTIC GKKFTQRGTM TRHMRSHLGL KPFACDACGM RFTRQYRLTE HMRIHSGEKP YECQVCGGKF AQQRNLISHM KMHAVGGAAG AAGALAGLGG LPGVPGPDGK GKLDFPEGVF AVARLTAEQL SLKQQDKAAA AELLAQTTHF LHDPKVALES LYPLAKFTAE LGLSPDKAAE VLSQGAHLAA GPDGRTIDRF SPT // ID HXB5_HUMAN Reviewed; 269 AA. AC P09067; B2RC69; P09069; Q17RP4; DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 3. DT 11-NOV-2015, entry version 156. DE RecName: Full=Homeobox protein Hox-B5; DE AltName: Full=Homeobox protein HHO.C10; DE AltName: Full=Homeobox protein Hox-2A; DE AltName: Full=Homeobox protein Hu-1; GN Name=HOXB5; Synonyms=HOX2A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1355360; RA Galang C.K., Hauser C.A.; RT "Cooperative DNA binding of the highly conserved human Hox 2.1 RT homeodomain gene product."; RL New Biol. 4:558-568(1992). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Kidd K.K., Busygina V., DeMille M.M.C., Speed W.C., Ruggeri V., RA Kidd J.R., Pakstis A.J.; RT "Overall linkage disequilibrium in 33 populations for highly RT informative multisite haplotypes spanning the HOXB gene cluster."; RL Am. J. Hum. Genet. 67:235-235(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 188-269. RX PubMed=4075393; DOI=10.1016/0092-8674(85)90008-X; RA Hauser C.A., Joyner A.L., Klein R.D., Learned T.K., Martin G.R., RA Tjian R.; RT "Expression of homologous homeo-box-containing genes in differentiated RT human teratocarcinoma cells and mouse embryos."; RL Cell 43:19-28(1985). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 191-269. RX PubMed=6091895; DOI=10.1016/0092-8674(84)90261-7; RA Levine M., Rubin G.M., Tjian R.; RT "Human DNA sequences homologous to a protein coding region conserved RT between homeotic genes of Drosophila."; RL Cell 38:667-673(1984). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 200-269. RX PubMed=3453105; DOI=10.1038/320763a0; RA Simeone A., Mavilio F., Bottero L., Giampaolo A., Russo G., RA Faiella A., Boncinelli E., Peschle C.; RT "A human homoeo box gene specifically expressed in spinal cord during RT embryonic development."; RL Nature 320:763-765(1986). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 199-269. RX PubMed=2576652; RA Boncinelli E., Acampora D., Pannese M., D'Esposito M., Somma R., RA Gaudino G., Stornaiuolo A., Cafiero M., Faiella A., Simeone A.; RT "Organization of human class I homeobox genes."; RL Genome 31:745-756(1989). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 217-269. RC TISSUE=Osteosarcoma; RA Waye M.M.Y.; RT "Cloning of a homeobox-containing cDNA (HHO.c10 or Hu-1) from a gt11 RT cDNA library of human osteosarcoma cell MG-63."; RL Submitted (FEB-1993) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Sequence-specific transcription factor which is part of CC a developmental regulatory system that provides cells with CC specific positional identities on the anterior-posterior axis. CC -!- INTERACTION: CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-3893317, EBI-10171858; CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-3893317, EBI-10171902; CC P43364-2:MAGEA11; NbExp=3; IntAct=EBI-3893317, EBI-10178634; CC P36406:TRIM23; NbExp=3; IntAct=EBI-3893317, EBI-740098; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- TISSUE SPECIFICITY: Spinal cord. CC -!- DEVELOPMENTAL STAGE: Embryo. CC -!- SIMILARITY: Belongs to the Antp homeobox family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00108}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA52681.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M92299; AAA52682.1; -; mRNA. DR EMBL; AF287967; AAG31553.1; -; Genomic_DNA. DR EMBL; AK314964; BAG37466.1; -; mRNA. DR EMBL; BC117247; AAI17248.1; -; mRNA. DR EMBL; X03794; CAA27420.1; -; mRNA. DR EMBL; K02572; AAA52681.1; ALT_INIT; Genomic_DNA. DR EMBL; M86726; AAB59430.1; -; mRNA. DR CCDS; CCDS11530.1; -. DR PIR; A24777; A24777. DR PIR; A45578; A45578. DR RefSeq; NP_002138.1; NM_002147.3. DR UniGene; Hs.654456; -. DR ProteinModelPortal; P09067; -. DR SMR; P09067; 201-256. DR BioGrid; 109455; 50. DR IntAct; P09067; 5. DR STRING; 9606.ENSP00000239151; -. DR PhosphoSite; P09067; -. DR BioMuta; HOXB5; -. DR DMDM; 400000; -. DR PaxDb; P09067; -. DR PRIDE; P09067; -. DR Ensembl; ENST00000239151; ENSP00000239151; ENSG00000120075. DR GeneID; 3215; -. DR KEGG; hsa:3215; -. DR UCSC; uc002inr.3; human. DR CTD; 3215; -. DR GeneCards; HOXB5; -. DR HGNC; HGNC:5116; HOXB5. DR MIM; 142960; gene. DR neXtProt; NX_P09067; -. DR PharmGKB; PA29392; -. DR eggNOG; KOG0489; Eukaryota. DR eggNOG; ENOG410ZTBY; LUCA. DR GeneTree; ENSGT00760000118945; -. DR HOGENOM; HOG000231178; -. DR HOVERGEN; HBG016849; -. DR InParanoid; P09067; -. DR KO; K09305; -. DR OMA; TNGESHG; -. DR OrthoDB; EOG780RP4; -. DR PhylomeDB; P09067; -. DR TreeFam; TF316310; -. DR GeneWiki; HOXB5; -. DR GenomeRNAi; 3215; -. DR NextBio; 12792; -. DR PRO; PR:P09067; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; P09067; -. DR CleanEx; HS_HOXB5; -. DR Genevisible; P09067; HS. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0000980; F:RNA polymerase II distal enhancer sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0001205; F:transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding; IEA:Ensembl. DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc. DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl. DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IEA:Ensembl. DR GO; GO:0045446; P:endothelial cell differentiation; IEA:Ensembl. DR Gene3D; 1.10.10.60; -; 1. DR InterPro; IPR017995; Homeobox_antennapedia. DR InterPro; IPR001827; Homeobox_Antennapedia_CS. DR InterPro; IPR017970; Homeobox_CS. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR020479; Homeobox_metazoa. DR InterPro; IPR009057; Homeodomain-like. DR Pfam; PF00046; Homeobox; 1. DR PRINTS; PR00025; ANTENNAPEDIA. DR PRINTS; PR00024; HOMEOBOX. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; SSF46689; 1. DR PROSITE; PS00032; ANTENNAPEDIA; 1. DR PROSITE; PS00027; HOMEOBOX_1; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. PE 1: Evidence at protein level; KW Complete proteome; Developmental protein; DNA-binding; Homeobox; KW Nucleus; Reference proteome; Transcription; Transcription regulation. FT CHAIN 1 269 Homeobox protein Hox-B5. FT /FTId=PRO_0000200128. FT DNA_BIND 194 253 Homeobox. {ECO:0000255|PROSITE- FT ProRule:PRU00108}. FT MOTIF 176 181 Antp-type hexapeptide. SQ SEQUENCE 269 AA; 29434 MW; 58197F105DB0F8C4 CRC64; MSSYFVNSFS GRYPNGPDYQ LLNYGSGSSL SGSYRDPAAM HTGSYGYNYN GMDLSVNRSS ASSSHFGAVG ESSRAFPAPA QEPRFRQAAS SCSLSSPESL PCTNGDSHGA KPSASSPSDQ ATSASSSANF TEIDEASASS EPEEAASQLS SPSLARAQPE PMATSTAAPE GQTPQIFPWM RKLHISHDMT GPDGKRARTA YTRYQTLELE KEFHFNRYLT RRRRIEIAHA LCLSERQIKI WFQNRRMKWK KDNKLKSMSL ATAGSAFQP // ID IKZF2_HUMAN Reviewed; 526 AA. AC Q9UKS7; Q53YJ5; Q6PQC5; Q6PQC6; Q6PQC7; Q6PQC8; Q6PQD0; Q6PQD1; AC Q8N6S1; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 2. DT 11-NOV-2015, entry version 144. DE RecName: Full=Zinc finger protein Helios; DE AltName: Full=Ikaros family zinc finger protein 2; GN Name=IKZF2; Synonyms=HELIOS, ZNFN1A2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=10541817; DOI=10.1007/s002510050696; RA Hosokawa Y., Maeda Y., Seto M.; RT "Human Helios, an Ikaros-related zinc finger DNA binding protein: cDNA RT cloning and tissue expression pattern."; RL Immunogenetics 50:106-108(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4; 5; 6; 7 AND 8), AND RP ALTERNATIVE SPLICING. RA Lopez-Segura V., Gonzalez-Sarmiento R.; RT "Molecular characterization of new Helios isoforms."; RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH IKZF4 AND IKZF5. RX PubMed=10978333; DOI=10.1074/jbc.M005457200; RA Perdomo J., Holmes M., Chong B., Crossley M.; RT "Eos and pegasus, two members of the Ikaros family of proteins with RT distinct DNA binding activities."; RL J. Biol. Chem. 275:38347-38354(2000). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-56; SER-78 AND SER-79, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [6] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-288, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). CC -!- FUNCTION: Associates with Ikaros at centromeric heterochromatin. CC -!- SUBUNIT: Interacts with IKZF4 AND IKZF5. CC {ECO:0000269|PubMed:10978333}. CC -!- INTERACTION: CC P29972:AQP1; NbExp=3; IntAct=EBI-3893057, EBI-745213; CC P56545:CTBP2; NbExp=3; IntAct=EBI-3893057, EBI-741533; CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-3893057, EBI-10171902; CC P09022:Hoxa1 (xeno); NbExp=3; IntAct=EBI-3893057, EBI-3957603; CC Q17RB8:LONRF1; NbExp=3; IntAct=EBI-3893057, EBI-2341787; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Name=1; CC IsoId=Q9UKS7-1; Sequence=Displayed; CC Name=2; Synonyms=Helios 1v; CC IsoId=Q9UKS7-2; Sequence=VSP_006845; CC Name=3; Synonyms=Helios del(Ex3,4); CC IsoId=Q9UKS7-3; Sequence=VSP_055347, VSP_055348; CC Name=4; Synonyms=Helios del(Ex6)v; CC IsoId=Q9UKS7-4; Sequence=VSP_006845, VSP_055350; CC Name=5; Synonyms=Helios 1+2a,2b, Helios 1v+2a, Helios del(Ex3)+2a; CC IsoId=Q9UKS7-5; Sequence=VSP_055345, VSP_055346; CC Name=6; Synonyms=Helios 1+5a, Helios 1+5a,5b; CC IsoId=Q9UKS7-6; Sequence=VSP_055351, VSP_055352; CC Name=7; Synonyms=Helios del(Ex5)v; CC IsoId=Q9UKS7-7; Sequence=VSP_006845, VSP_055349; CC Name=8; Synonyms=Helios S; CC IsoId=Q9UKS7-8; Sequence=VSP_055344; CC -!- SIMILARITY: Belongs to the Ikaros C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 6 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/IKZF2ID42885ch2q34.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF130863; AAF09441.1; -; mRNA. DR EMBL; AY587062; AAS99855.1; -; mRNA. DR EMBL; AY587064; AAS99857.1; -; mRNA. DR EMBL; AY587065; AAS99858.1; -; mRNA. DR EMBL; AY587066; AAS99859.1; -; mRNA. DR EMBL; AY587067; AAS99860.1; -; mRNA. DR EMBL; AY587068; AAS99861.1; -; mRNA. DR EMBL; AY587069; AAS99862.1; -; mRNA. DR EMBL; AY587070; AAS99863.1; -; mRNA. DR EMBL; AY587071; AAS99864.1; -; mRNA. DR EMBL; AY587072; AAS99865.1; -; mRNA. DR EMBL; BC028936; AAH28936.1; -; mRNA. DR CCDS; CCDS2395.1; -. [Q9UKS7-1] DR CCDS; CCDS46507.1; -. [Q9UKS7-2] DR RefSeq; NP_001072994.1; NM_001079526.1. [Q9UKS7-2] DR RefSeq; NP_057344.2; NM_016260.2. [Q9UKS7-1] DR RefSeq; XP_005246441.1; XM_005246384.3. [Q9UKS7-1] DR RefSeq; XP_005246442.1; XM_005246385.2. [Q9UKS7-1] DR RefSeq; XP_011509116.1; XM_011510814.1. [Q9UKS7-1] DR UniGene; Hs.604950; -. DR ProteinModelPortal; Q9UKS7; -. DR SMR; Q9UKS7; 63-215, 462-523. DR BioGrid; 116485; 18. DR IntAct; Q9UKS7; 7. DR STRING; 9606.ENSP00000410447; -. DR PhosphoSite; Q9UKS7; -. DR BioMuta; IKZF2; -. DR DMDM; 116242509; -. DR MaxQB; Q9UKS7; -. DR PaxDb; Q9UKS7; -. DR PRIDE; Q9UKS7; -. DR DNASU; 22807; -. DR Ensembl; ENST00000374319; ENSP00000363439; ENSG00000030419. [Q9UKS7-2] DR Ensembl; ENST00000374326; ENSP00000363446; ENSG00000030419. [Q9UKS7-5] DR Ensembl; ENST00000412444; ENSP00000413680; ENSG00000030419. [Q9UKS7-5] DR Ensembl; ENST00000431520; ENSP00000396253; ENSG00000030419. [Q9UKS7-6] DR Ensembl; ENST00000434687; ENSP00000412869; ENSG00000030419. [Q9UKS7-1] DR Ensembl; ENST00000439848; ENSP00000389548; ENSG00000030419. [Q9UKS7-3] DR Ensembl; ENST00000453575; ENSP00000411444; ENSG00000030419. [Q9UKS7-5] DR GeneID; 22807; -. DR KEGG; hsa:22807; -. DR UCSC; uc002vei.3; human. [Q9UKS7-1] DR UCSC; uc002vel.3; human. [Q9UKS7-2] DR CTD; 22807; -. DR GeneCards; IKZF2; -. DR HGNC; HGNC:13177; IKZF2. DR HPA; HPA059142; -. DR MIM; 606234; gene. DR neXtProt; NX_Q9UKS7; -. DR PharmGKB; PA162391927; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00550000074392; -. DR HOGENOM; HOG000049114; -. DR HOVERGEN; HBG004752; -. DR InParanoid; Q9UKS7; -. DR KO; K09220; -. DR PhylomeDB; Q9UKS7; -. DR TreeFam; TF331189; -. DR ChiTaRS; IKZF2; human. DR GeneWiki; IKZF2; -. DR GenomeRNAi; 22807; -. DR NextBio; 43178; -. DR PMAP-CutDB; Q9UKS7; -. DR PRO; PR:Q9UKS7; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; Q9UKS7; -. DR CleanEx; HS_IKZF2; -. DR ExpressionAtlas; Q9UKS7; baseline and differential. DR Genevisible; Q9UKS7; HS. DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IBA:GO_Central. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IBA:GO_Central. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.30.160.60; -; 4. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR SMART; SM00355; ZnF_C2H2; 6. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4. PE 1: Evidence at protein level; KW Acetylation; Activator; Alternative splicing; Complete proteome; KW DNA-binding; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Zinc; Zinc-finger. FT CHAIN 1 526 Zinc finger protein Helios. FT /FTId=PRO_0000047092. FT ZN_FING 112 134 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 140 162 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 168 190 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 196 219 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 471 493 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 499 523 C2H2-type 6. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT MOD_RES 56 56 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 78 78 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 79 79 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 288 288 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT VAR_SEQ 46 341 Missing (in isoform 8). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_055344. FT VAR_SEQ 47 52 TNSVKL -> RSFSKI (in isoform 5). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_055345. FT VAR_SEQ 53 526 Missing (in isoform 5). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_055346. FT VAR_SEQ 111 136 Missing (in isoform 2, isoform 4 and FT isoform 7). {ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.2}. FT /FTId=VSP_006845. FT VAR_SEQ 137 148 ERPFHCNQCGAS -> VAVVKTTFSEFC (in isoform FT 3). {ECO:0000303|Ref.2}. FT /FTId=VSP_055347. FT VAR_SEQ 149 526 Missing (in isoform 3). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_055348. FT VAR_SEQ 192 237 Missing (in isoform 7). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_055349. FT VAR_SEQ 238 285 Missing (in isoform 4). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_055350. FT VAR_SEQ 238 239 VP -> DS (in isoform 6). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_055351. FT VAR_SEQ 240 526 Missing (in isoform 6). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_055352. FT VARIANT 93 93 N -> S (in dbSNP:rs16849611). FT /FTId=VAR_028227. FT CONFLICT 4 4 E -> D (in Ref. 1; AAF09441 and 2; FT AAS99855/AAS99857/AAS99858/AAS99859/ FT AAS99860/AAS99861/AAS99862/AAS99863/ FT AAS99864/AAS99865). {ECO:0000305}. FT CONFLICT 69 69 D -> N (in Ref. 1; AAF09441 and 2; FT AAS99857/AAS99859/AAS99861/AAS99862/ FT AAS99863/AAS99864). {ECO:0000305}. SQ SEQUENCE 526 AA; 59574 MW; 949BE60E242BA8E8 CRC64; METEAIDGYI TCDNELSPER EHSNMAIDLT SSTPNGQHAS PSHMTSTNSV KLEMQSDEEC DRKPLSREDE IRGHDEGSSL EEPLIESSEV ADNRKVQELQ GEGGIRLPNG KLKCDVCGMV CIGPNVLMVH KRSHTGERPF HCNQCGASFT QKGNLLRHIK LHSGEKPFKC PFCSYACRRR DALTGHLRTH SVGKPHKCNY CGRSYKQRSS LEEHKERCHN YLQNVSMEAA GQVMSHHVPP MEDCKEQEPI MDNNISLVPF ERPAVIEKLT GNMGKRKSST PQKFVGEKLM RFSYPDIHFD MNLTYEKEAE LMQSHMMDQA INNAITYLGA EALHPLMQHP PSTIAEVAPV ISSAYSQVYH PNRIERPISR ETADSHENNM DGPISLIRPK SRPQEREASP SNSCLDSTDS ESSHDDHQSY QGHPALNPKR KQSPAYMKED VKALDTTKAP KGSLKDIYKV FNGEGEQIRA FKCEHCRVLF LDHVMYTIHM GCHGYRDPLE CNICGYRSQD RYEFSSHIVR GEHTFH // ID IKZF1_HUMAN Reviewed; 519 AA. AC Q13422; A4D260; B4E0Z1; D3DVM5; O00598; Q53XL2; Q69BM4; Q8WVA3; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 11-NOV-2015, entry version 150. DE RecName: Full=DNA-binding protein Ikaros; DE AltName: Full=Ikaros family zinc finger protein 1; DE AltName: Full=Lymphoid transcription factor LyF-1; GN Name=IKZF1; Synonyms=IK1, IKAROS, LYF1, ZNFN1A1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND TISSUE RP SPECIFICITY. RC TISSUE=Bone marrow; RX PubMed=8964602; DOI=10.1016/0165-2478(95)02479-4; RA Nietfeld W., Meyerhans A.; RT "Cloning and sequencing of hIk-1, a cDNA encoding a human homologue of RT mouse Ikaros/LyF-1."; RL Immunol. Lett. 49:139-141(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND TISSUE RP SPECIFICITY. RX PubMed=8543809; RA Molnar A., Wu P., Largespada D.A., Vortkamp A., Scherer S., RA Copeland N.G., Jenkins N.A., Bruns G., Georgopoulos K.; RT "The Ikaros gene encodes a family of lymphocyte-restricted zinc finger RT DNA binding proteins, highly conserved in human and mouse."; RL J. Immunol. 156:585-592(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM IKX). RA Sanchez-Tapia E.M., Rodriguez R.E., Gonzalez-Sarmiento R.; RT "Molecular misreading is involved in generation of Ikaros diversity."; RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IK2). RC TISSUE=Thymus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IK7). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12690205; DOI=10.1126/science.1083423; RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., RA Mural R.J., Adams M.D., Tsui L.-C.; RT "Human chromosome 7: DNA sequence and biology."; RL Science 300:767-772(2003). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM IK7). RC TISSUE=Lymph; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP IDENTIFICATION IN THE NURD COMPLEX, IDENTIFICATION IN THE BAF COMPLEX, RP INTERACTION WITH SMARCA4 AND CHD4, AND FUNCTION. RX PubMed=10204490; DOI=10.1016/S1074-7613(00)80034-5; RA Kim J., Sif S., Jones B., Jackson A., Koipally J., Heller E., RA Winandy S., Viel A., Sawyer A., Ikeda T., Kingston R., RA Georgopoulos K.; RT "Ikaros DNA-binding proteins direct formation of chromatin remodeling RT complexes in lymphocytes."; RL Immunity 10:345-355(1999). RN [11] RP INVOLVEMENT IN B-CELL NON-HODGKIN LYMPHOMA, AND CHROMOSOMAL RP TRANSLOCATION WITH BCL6. RX PubMed=10753856; RA Hosokawa Y., Maeda Y., Ichinohasama R., Miura I., Taniwaki M., RA Seto M.; RT "The Ikaros gene, a central regulator of lymphoid differentiation, RT fuses to the BCL6 gene as a result of t(3;7)(q27;p12) translocation in RT a patient with diffuse large B-cell lymphoma."; RL Blood 95:2719-2721(2000). RN [12] RP INTERACTION WITH IKZF4 AND IKZF5. RX PubMed=10978333; DOI=10.1074/jbc.M005457200; RA Perdomo J., Holmes M., Chong B., Crossley M.; RT "Eos and pegasus, two members of the Ikaros family of proteins with RT distinct DNA binding activities."; RL J. Biol. Chem. 275:38347-38354(2000). RN [13] RP FUNCTION, ALTERNATIVE SPLICING, SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=17135265; DOI=10.1074/jbc.M605627200; RA Ronni T., Payne K.J., Ho S., Bradley M.N., Dorsam G., Dovat S.; RT "Human Ikaros function in activated T cells is regulated by RT coordinated expression of its largest isoforms."; RL J. Biol. Chem. 282:2538-2547(2007). RN [14] RP FUNCTION, AND ALTERNATIVE SPLICING. RX PubMed=17934067; DOI=10.1182/blood-2007-07-098202; RA Dijon M., Bardin F., Murati A., Batoz M., Chabannon C., Tonnelle C.; RT "The role of Ikaros in human erythroid differentiation."; RL Blood 111:1138-1146(2008). RN [15] RP FUNCTION IN GAMMA SATELLITE DNA BINDING. RX PubMed=19141594; DOI=10.1101/gr.086496.108; RA Kim J.-H., Ebersole T., Kouprina N., Noskov V.N., Ohzeki J.-I., RA Masumoto H., Mravinac B., Sullivan B.A., Pavlicek A., Dovat S., RA Pack S.D., Kwon Y.-W., Flanagan P.T., Loukinov D., Lobanenkov V., RA Larionov V.; RT "Human gamma-satellite DNA maintains open chromatin structure and RT protects a transgene from epigenetic silencing."; RL Genome Res. 19:533-544(2009). RN [16] RP INVOLVEMENT IN ACUTE LYMPHOBLASIC LEUKEMIA. RX PubMed=19129520; DOI=10.1056/NEJMoa0808253; RA Mullighan C.G., Su X., Zhang J., Radtke I., Phillips L.A., RA Miller C.B., Ma J., Liu W., Cheng C., Schulman B.A., Harvey R.C., RA Chen I.-M., Clifford R.J., Carroll W.L., Reaman G., Bowman W.P., RA Devidas M., Gerhard D.S., Yang W., Relling M.V., Shurtleff S.A., RA Campana D., Borowitz M.J., Pui C.H., Smith M., Hunger S.P., RA Willman C.L., Downing J.R.; RT "Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia."; RL N. Engl. J. Med. 360:470-480(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-63; SER-258; SER-361 AND RP SER-364, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP FUNCTION IN DNA BINDING, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND RP ALTERNATIVE SPLICING. RX PubMed=22106042; DOI=10.1002/pbc.23406; RA Li Z., Song C., Ouyang H., Lai L., Payne K.J., Dovat S.; RT "Cell cycle-specific function of Ikaros in human leukemia."; RL Pediatr. Blood Cancer 59:69-76(2012). RN [20] RP PHOSPHORYLATION AT SER-361 AND SER-364 BY SYK, AND SUBCELLULAR RP LOCATION. RX PubMed=23071339; DOI=10.1073/pnas.1209828109; RA Uckun F.M., Ma H., Zhang J., Ozer Z., Dovat S., Mao C., Ishkhanian R., RA Goodman P., Qazi S.; RT "Serine phosphorylation by SYK is critical for nuclear localization RT and transcription factor function of Ikaros."; RL Proc. Natl. Acad. Sci. U.S.A. 109:18072-18077(2012). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-445, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Transcription regulator of hematopoietic cell CC differentiation (PubMed:17934067). Binds gamma-satellite DNA CC (PubMed:17135265, PubMed:19141594). Plays a role in the CC development of lymphocytes, B- and T-cells. Binds and activates CC the enhancer (delta-A element) of the CD3-delta gene. Repressor of CC the TDT (fikzfterminal deoxynucleotidyltransferase) gene during CC thymocyte differentiation. Regulates transcription through CC association with both HDAC-dependent and HDAC-independent CC complexes. Targets the 2 chromatin-remodeling complexes, NuRD and CC BAF (SWI/SNF), in a single complex (PYR complex), to the beta- CC globin locus in adult erythrocytes. Increases normal apoptosis in CC adult erythroid cells. Confers early temporal competence to CC retinal progenitor cells (RPCs) (By similarity). Function is CC isoform-specific and is modulated by dominant-negative inactive CC isoforms (PubMed:17135265, PubMed:17934067). CC {ECO:0000250|UniProtKB:Q03267, ECO:0000269|PubMed:10204490, CC ECO:0000269|PubMed:17135265, ECO:0000269|PubMed:17934067, CC ECO:0000269|PubMed:19141594}. CC -!- SUBUNIT: Heterodimer formed by the various isoforms; this CC modulates transcription regulator activity (PubMed:17135265, CC PubMed:17934067). Heterodimer with other IKAROS family members. CC Interacts with IKZF4 AND IKZF5 (PubMed:10978333). Component of the CC chromatin-remodeling NuRD repressor complex which includes at CC least HDAC1, HDAC2, RBBP4, RBBP7, IKZF1, MTA2, MBD2, MBD3, MTA1L1, CC CHD3 and CHD4. Interacts directly with the CHD4 component of the CC NuRD complex. Component of the BAF (SWI/SNF) gene activator CC complex which includes ACTB, ARID1A, ARID1B, IKZF1, ARID1A, CC ARID1B, SMARCA2, SMARCA4 and at least one BAF subunit. Interacts CC directly with the SMARCA4 component of the BAF complex (By CC similarity). Interacts with SUMO1; the interaction sumoylates CC IKAROS, promoted by PIAS2 and PIAS3. Interacts with PIAS2 (isoform CC alpha); the interaction promotes sumoylation and reduces CC transcription repression. Interacts, to a lesser extent, with CC PIAS3. Interacts with PPP1CC; the interaction targets PPP1CC to CC pericentromeric heterochromatin, dephosphorylates IKAROS, CC stabilizes it and prevents it from degradation. Interacts with CC IKZF3 (By similarity). {ECO:0000250, ECO:0000269|PubMed:10204490, CC ECO:0000269|PubMed:10978333, ECO:0000305|PubMed:17135265, CC ECO:0000305|PubMed:17934067}. CC -!- INTERACTION: CC A8K932:-; NbExp=3; IntAct=EBI-745305, EBI-10174671; CC Q8WTP8:AEN; NbExp=3; IntAct=EBI-745305, EBI-8637627; CC Q96Q83:ALKBH3; NbExp=3; IntAct=EBI-745305, EBI-6658697; CC Q9BXS5:AP1M1; NbExp=3; IntAct=EBI-745305, EBI-541426; CC Q9H6L4:ARMC7; NbExp=3; IntAct=EBI-745305, EBI-742909; CC Q13895:BYSL; NbExp=5; IntAct=EBI-745305, EBI-358049; CC Q9NUL5:C19orf66; NbExp=3; IntAct=EBI-745305, EBI-10313866; CC Q9NX04:C1orf109; NbExp=3; IntAct=EBI-745305, EBI-8643161; CC Q8IYL3:C1orf174; NbExp=3; IntAct=EBI-745305, EBI-715898; CC Q9H7E9:C8orf33; NbExp=3; IntAct=EBI-745305, EBI-715389; CC Q9HC52:CBX8; NbExp=3; IntAct=EBI-745305, EBI-712912; CC Q8IYX8-2:CEP57L1; NbExp=3; IntAct=EBI-745305, EBI-10181988; CC P61024:CKS1B; NbExp=3; IntAct=EBI-745305, EBI-456371; CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-745305, EBI-10171858; CC P56545:CTBP2; NbExp=5; IntAct=EBI-745305, EBI-741533; CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-745305, EBI-10171902; CC O43602:DCX; NbExp=4; IntAct=EBI-745305, EBI-8646694; CC P26196:DDX6; NbExp=3; IntAct=EBI-745305, EBI-351257; CC Q92630:DYRK2; NbExp=3; IntAct=EBI-745305, EBI-749432; CC Q3B820:FAM161A; NbExp=3; IntAct=EBI-745305, EBI-719941; CC Q7L5A3:FAM214B; NbExp=4; IntAct=EBI-745305, EBI-745689; CC Q9Y247:FAM50B; NbExp=4; IntAct=EBI-745305, EBI-742802; CC Q5TZK3:FAM74A6; NbExp=3; IntAct=EBI-745305, EBI-10247271; CC P61328:FGF12; NbExp=3; IntAct=EBI-745305, EBI-6657662; CC Q96NE9:FRMD6; NbExp=3; IntAct=EBI-745305, EBI-741729; CC O76003:GLRX3; NbExp=3; IntAct=EBI-745305, EBI-374781; CC Q8NEA9:GMCL1P1; NbExp=3; IntAct=EBI-745305, EBI-745707; CC Q9H1K1:ISCU; NbExp=3; IntAct=EBI-745305, EBI-1047335; CC Q8TAP4:LMO3; NbExp=3; IntAct=EBI-745305, EBI-742259; CC Q9Y4Z0:LSM4; NbExp=3; IntAct=EBI-745305, EBI-372521; CC Q9UI95:MAD2L2; NbExp=3; IntAct=EBI-745305, EBI-77889; CC Q96EZ8:MCRS1; NbExp=3; IntAct=EBI-745305, EBI-348259; CC Q9UBU8:MORF4L1; NbExp=3; IntAct=EBI-745305, EBI-399246; CC Q15014:MORF4L2; NbExp=3; IntAct=EBI-745305, EBI-399257; CC Q13330:MTA1; NbExp=3; IntAct=EBI-745305, EBI-714236; CC Q9HC98:NEK6; NbExp=3; IntAct=EBI-745305, EBI-740364; CC Q9BVI4:NOC4L; NbExp=3; IntAct=EBI-745305, EBI-395927; CC Q13526:PIN1; NbExp=3; IntAct=EBI-745305, EBI-714158; CC Q96T60:PNKP; NbExp=3; IntAct=EBI-745305, EBI-1045072; CC O43741:PRKAB2; NbExp=3; IntAct=EBI-745305, EBI-1053424; CC P25786:PSMA1; NbExp=3; IntAct=EBI-745305, EBI-359352; CC P25789:PSMA4; NbExp=3; IntAct=EBI-745305, EBI-359310; CC Q7Z474:PSMA4; NbExp=3; IntAct=EBI-745305, EBI-10257551; CC O75771:RAD51D; NbExp=4; IntAct=EBI-745305, EBI-1055693; CC P57060:RWDD2B; NbExp=4; IntAct=EBI-745305, EBI-724442; CC Q9BWG6:SCNM1; NbExp=3; IntAct=EBI-745305, EBI-748391; CC O00560:SDCBP; NbExp=3; IntAct=EBI-745305, EBI-727004; CC Q9H788:SH2D4A; NbExp=3; IntAct=EBI-745305, EBI-747035; CC P62306:SNRPF; NbExp=3; IntAct=EBI-745305, EBI-356900; CC Q13573:SNW1; NbExp=3; IntAct=EBI-745305, EBI-632715; CC Q9H0A9:SPATC1L; NbExp=3; IntAct=EBI-745305, EBI-372911; CC Q9BSW7:SYT17; NbExp=3; IntAct=EBI-745305, EBI-745392; CC Q7KZS0:UBE2I; NbExp=3; IntAct=EBI-745305, EBI-10180829; CC Q15007:WTAP; NbExp=3; IntAct=EBI-745305, EBI-751647; CC Q96NC0:ZMAT2; NbExp=3; IntAct=EBI-745305, EBI-2682299; CC Q8TAU3:ZNF417; NbExp=3; IntAct=EBI-745305, EBI-740727; CC Q9P0T4:ZNF581; NbExp=3; IntAct=EBI-745305, EBI-745520; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17135265, CC ECO:0000269|PubMed:22106042, ECO:0000269|PubMed:23071339}. Note=In CC resting lymphocytes, distributed diffusely throughout the nucleus. CC Localizes to pericentromeric heterochromatin in proliferating CC cells. This localization requires DNA binding which is regulated CC by phosphorylation / dephosphorylation events. CC {ECO:0000269|PubMed:17135265, ECO:0000269|PubMed:22106042}. CC -!- SUBCELLULAR LOCATION: Isoform Ik2: Nucleus. Note=In resting CC lymphocytes, distributed diffusely throughout the nucleus. CC Localizes to pericentromeric heterochromatin in proliferating CC cells. This localization requires DNA binding which is regulated CC by phosphorylation / dephosphorylation events (By similarity). CC {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Isoform Ik6: Cytoplasm {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=8; CC Name=Ik1; CC IsoId=Q13422-1; Sequence=Displayed; CC Name=Ik2; CC IsoId=Q13422-2; Sequence=VSP_006848; CC Name=Ik3; CC IsoId=Q13422-3; Sequence=VSP_006850; CC Name=Ik4; CC IsoId=Q13422-4; Sequence=VSP_006847, VSP_006850; CC Name=Ik5; CC IsoId=Q13422-5; Sequence=VSP_006852; CC Name=Ik6; CC IsoId=Q13422-6; Sequence=VSP_006849; CC Name=Ik7; CC IsoId=Q13422-7; Sequence=VSP_006851; CC Name=Ikx; CC IsoId=Q13422-8; Sequence=VSP_006851, VSP_053404, VSP_053405; CC -!- TISSUE SPECIFICITY: Abundantly expressed in thymus, spleen and CC peripheral blood Leukocytes and lymph nodes. Lower expression in CC bone marrow and small intestine. {ECO:0000269|PubMed:8543809, CC ECO:0000269|PubMed:8964602}. CC -!- DOMAIN: The N-terminal zinc-fingers 2 and 3 are required for DNA CC binding as well as for targeting IKFZ1 to pericentromeric CC heterochromatin. {ECO:0000250}. CC -!- DOMAIN: The C-terminal zinc-finger domain is required for CC dimerization. {ECO:0000250}. CC -!- PTM: Phosphorylation controls cell-cycle progression from late CC G(1) stage to S stage. Hyperphosphorylated during G2/M phase. CC Dephosphorylated state during late G(1) phase. Phosphorylation on CC Thr-140 is required for DNA and pericentromeric location during CC mitosis. CK2 is the main kinase, in vitro. GSK3 and CDK may also CC contribute to phosphorylation of the C-terminal serine and CC threonine residues. Phosphorylation on these C-terminal residues CC reduces the DNA-binding ability. Phosphorylation/dephosphorylation CC events on Ser-13 and Ser-295 regulate TDT expression during CC thymocyte differentiation. Dephosphorylation by protein CC phosphatase 1 regulates stability and pericentromeric CC heterochromatin location. Phosphorylated in both lymphoid and non- CC lymphoid tissues (By similarity). Phosphorylation at Ser-361 and CC Ser-364 downstream of SYK induces nuclear translocation. CC {ECO:0000250, ECO:0000269|PubMed:22106042, CC ECO:0000269|PubMed:23071339}. CC -!- PTM: Sumoylated. Simulataneous sumoylation on the 2 sites results CC in a loss of both HDAC-dependent and HDAC-independent repression. CC Has no effect on pericentromeric heterochromatin location. CC Desumoylated by SENP1 (By similarity). {ECO:0000250}. CC -!- PTM: Polyubiquitinated. {ECO:0000250}. CC -!- DISEASE: Note=Defects in IKZF1 are frequent occurrences (28.6%) in CC acute lymphoblasic leukemia (ALL). Such alterations or deletions CC lead to poor prognosis for ALL. CC -!- DISEASE: Note=Chromosomal aberrations involving IKZF1 are a cause CC of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation CC t(3;7)(q27;p12), with BCL6. CC -!- SIMILARITY: Belongs to the Ikaros C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 6 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/IkarosID258.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U40462; AAC50459.1; -; mRNA. DR EMBL; S80876; AAB50683.1; -; mRNA. DR EMBL; AY377974; AAR84585.1; -; mRNA. DR EMBL; AK303586; BAG64603.1; -; mRNA. DR EMBL; BT009836; AAP88838.1; -; mRNA. DR EMBL; AC124014; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC233268; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471128; EAW60977.1; -; Genomic_DNA. DR EMBL; CH471128; EAW60978.1; -; Genomic_DNA. DR EMBL; CH471128; EAW60981.1; -; Genomic_DNA. DR EMBL; CH236955; EAL23900.1; -; Genomic_DNA. DR EMBL; CH471128; EAW60979.1; -; Genomic_DNA. DR EMBL; BC018349; AAH18349.1; -; mRNA. DR CCDS; CCDS59055.1; -. [Q13422-7] DR CCDS; CCDS69299.1; -. [Q13422-5] DR CCDS; CCDS75596.1; -. [Q13422-1] DR CCDS; CCDS75597.1; -. [Q13422-3] DR CCDS; CCDS78233.1; -. [Q13422-2] DR RefSeq; NP_001207694.1; NM_001220765.2. [Q13422-7] DR RefSeq; NP_001207696.1; NM_001220767.2. DR RefSeq; NP_001207697.1; NM_001220768.2. [Q13422-3] DR RefSeq; NP_001207699.1; NM_001220770.2. DR RefSeq; NP_001207700.1; NM_001220771.2. [Q13422-5] DR RefSeq; NP_001278766.1; NM_001291837.1. [Q13422-7] DR RefSeq; NP_001278767.1; NM_001291838.1. [Q13422-2] DR RefSeq; NP_001278768.1; NM_001291839.1. DR RefSeq; NP_001278769.1; NM_001291840.1. [Q13422-6] DR RefSeq; NP_001278770.1; NM_001291841.1. DR RefSeq; NP_001278771.1; NM_001291842.1. DR RefSeq; NP_001278772.1; NM_001291843.1. DR RefSeq; NP_001278773.1; NM_001291844.1. DR RefSeq; NP_006051.1; NM_006060.5. [Q13422-1] DR RefSeq; XP_011513370.1; XM_011515068.1. [Q13422-1] DR RefSeq; XP_011513371.1; XM_011515069.1. [Q13422-1] DR RefSeq; XP_011513377.1; XM_011515075.1. [Q13422-2] DR RefSeq; XP_011513378.1; XM_011515076.1. [Q13422-2] DR UniGene; Hs.435949; -. DR UniGene; Hs.488251; -. DR UniGene; Hs.646004; -. DR UniGene; Hs.731495; -. DR ProteinModelPortal; Q13422; -. DR SMR; Q13422; 112-220, 460-509. DR BioGrid; 115604; 118. DR DIP; DIP-41110N; -. DR IntAct; Q13422; 68. DR MINT; MINT-129252; -. DR STRING; 9606.ENSP00000331614; -. DR PhosphoSite; Q13422; -. DR BioMuta; IKZF1; -. DR DMDM; 3913926; -. DR MaxQB; Q13422; -. DR PaxDb; Q13422; -. DR PRIDE; Q13422; -. DR DNASU; 10320; -. DR Ensembl; ENST00000331340; ENSP00000331614; ENSG00000185811. [Q13422-1] DR Ensembl; ENST00000343574; ENSP00000342750; ENSG00000185811. [Q13422-2] DR Ensembl; ENST00000349824; ENSP00000342485; ENSG00000185811. [Q13422-5] DR Ensembl; ENST00000357364; ENSP00000349928; ENSG00000185811. [Q13422-3] DR Ensembl; ENST00000359197; ENSP00000352123; ENSG00000185811. [Q13422-7] DR Ensembl; ENST00000438033; ENSP00000396554; ENSG00000185811. [Q13422-2] DR Ensembl; ENST00000439701; ENSP00000413025; ENSG00000185811. [Q13422-7] DR GeneID; 10320; -. DR KEGG; hsa:10320; -. DR UCSC; uc003tow.4; human. [Q13422-1] DR UCSC; uc003tox.4; human. [Q13422-7] DR UCSC; uc003tpa.4; human. [Q13422-6] DR UCSC; uc011kck.2; human. [Q13422-2] DR UCSC; uc022acq.1; human. [Q13422-5] DR UCSC; uc022acs.1; human. [Q13422-4] DR UCSC; uc022acx.1; human. [Q13422-3] DR CTD; 10320; -. DR GeneCards; IKZF1; -. DR HGNC; HGNC:13176; IKZF1. DR HPA; CAB009247; -. DR HPA; HPA035221; -. DR HPA; HPA035222; -. DR MIM; 603023; gene. DR neXtProt; NX_Q13422; -. DR Orphanet; 317473; Pancytopenia due to IKZF1 mutations. DR Orphanet; 99860; Precursor B-cell acute lymphoblastic leukemia. DR PharmGKB; PA37748; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00550000074392; -. DR HOVERGEN; HBG004752; -. DR InParanoid; Q13422; -. DR KO; K09220; -. DR OMA; GDKCLSD; -. DR PhylomeDB; Q13422; -. DR TreeFam; TF331189; -. DR SignaLink; Q13422; -. DR ChiTaRS; IKZF1; human. DR GeneWiki; IKZF1; -. DR GenomeRNAi; 10320; -. DR NextBio; 39123; -. DR PRO; PR:Q13422; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; Q13422; -. DR CleanEx; HS_IKZF1; -. DR ExpressionAtlas; Q13422; baseline and differential. DR Genevisible; Q13422; HS. DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005721; C:pericentric heterochromatin; IEA:Ensembl. DR GO; GO:0043234; C:protein complex; IDA:MGI. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IBA:GO_Central. DR GO; GO:0035881; P:amacrine cell differentiation; IEA:Ensembl. DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0016568; P:chromatin modification; IEA:UniProtKB-KW. DR GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB. DR GO; GO:0030900; P:forebrain development; IEA:Ensembl. DR GO; GO:0048535; P:lymph node development; IEA:Ensembl. DR GO; GO:0030098; P:lymphocyte differentiation; IMP:UniProtKB. DR GO; GO:0007498; P:mesoderm development; TAS:ProtInc. DR GO; GO:0001779; P:natural killer cell differentiation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IBA:GO_Central. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB. DR GO; GO:0048541; P:Peyer's patch development; IEA:Ensembl. DR GO; GO:0045579; P:positive regulation of B cell differentiation; IEA:Ensembl. DR GO; GO:0040018; P:positive regulation of multicellular organism growth; IEA:Ensembl. DR GO; GO:0045660; P:positive regulation of neutrophil differentiation; IEA:Ensembl. DR GO; GO:0051138; P:positive regulation of NK T cell differentiation; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IBA:GO_Central. DR GO; GO:0060040; P:retinal bipolar neuron differentiation; IEA:Ensembl. DR GO; GO:0030217; P:T cell differentiation; IEA:Ensembl. DR GO; GO:0048538; P:thymus development; IEA:Ensembl. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.30.160.60; -; 4. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Pfam; PF00096; zf-C2H2; 1. DR SMART; SM00355; ZnF_C2H2; 6. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Cell cycle; Chromatin regulator; KW Chromosomal rearrangement; Complete proteome; Cytoplasm; KW Developmental protein; DNA-binding; Isopeptide bond; Metal-binding; KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor; KW Transcription; Transcription regulation; Ubl conjugation; Zinc; KW Zinc-finger. FT CHAIN 1 519 DNA-binding protein Ikaros. FT /FTId=PRO_0000047094. FT ZN_FING 117 139 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 145 167 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 173 195 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 201 224 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 462 484 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 490 514 C2H2-type 6. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT REGION 154 163 Required for both high-affinity DNA FT binding and pericentromeric FT heterochromatin localization. FT {ECO:0000250}. FT REGION 180 195 Required for both high-affinity DNA FT binding and pericentromeric FT heterochromatin localization. FT {ECO:0000250}. FT REGION 468 471 Required for binding PP1CC. FT {ECO:0000250}. FT COMPBIAS 373 376 Poly-Leu. FT SITE 159 159 Required for both pericentromeric FT heterochromatin localization and complete FT DNA binding. {ECO:0000250}. FT SITE 162 162 Required for both pericentromeric FT heterochromatin localization and complete FT DNA binding. {ECO:0000250}. FT SITE 188 188 Required for both pericentromeric FT heterochromatin localization and DNA FT binding. {ECO:0000250}. FT MOD_RES 13 13 Phosphoserine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 23 23 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 63 63 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 101 101 Phosphoserine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 140 140 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 168 168 Phosphoserine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 196 196 Phosphoserine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 258 258 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 295 295 Phosphoserine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 361 361 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000269|PubMed:23071339}. FT MOD_RES 364 364 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000269|PubMed:23071339}. FT MOD_RES 389 389 Phosphoserine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 391 391 Phosphoserine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 393 393 Phosphoserine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 397 397 Phosphoserine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 398 398 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 402 402 Phosphoserine. FT {ECO:0000250|UniProtKB:Q03267}. FT MOD_RES 445 445 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT CROSSLNK 58 58 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT {ECO:0000250}. FT CROSSLNK 241 241 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT {ECO:0000250}. FT VAR_SEQ 10 53 Missing (in isoform Ik4). {ECO:0000305}. FT /FTId=VSP_006847. FT VAR_SEQ 54 283 Missing (in isoform Ik6). {ECO:0000305}. FT /FTId=VSP_006849. FT VAR_SEQ 54 140 Missing (in isoform Ik2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_006848. FT VAR_SEQ 141 283 Missing (in isoform Ik5). {ECO:0000305}. FT /FTId=VSP_006852. FT VAR_SEQ 197 283 Missing (in isoform Ik3 and isoform Ik4). FT {ECO:0000305}. FT /FTId=VSP_006850. FT VAR_SEQ 197 238 Missing (in isoform Ik7 and isoform Ikx). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.3, ECO:0000303|Ref.5}. FT /FTId=VSP_006851. FT VAR_SEQ 260 268 RSLVLDRLA -> ISRAGQTSK (in isoform Ikx). FT {ECO:0000303|Ref.3}. FT /FTId=VSP_053404. FT VAR_SEQ 269 519 Missing (in isoform Ikx). FT {ECO:0000303|Ref.3}. FT /FTId=VSP_053405. FT CONFLICT 11 12 QV -> FS (in Ref. 2; AAB50683). FT {ECO:0000305}. FT CONFLICT 214 214 S -> T (in Ref. 2; AAB50683). FT {ECO:0000305}. FT CONFLICT 245 245 N -> K (in Ref. 2; AAB50683). FT {ECO:0000305}. FT CONFLICT 296 296 Missing (in Ref. 2; AAB50683). FT {ECO:0000305}. FT CONFLICT 298 298 S -> T (in Ref. 2; AAB50683). FT {ECO:0000305}. FT CONFLICT 352 355 KPLA -> RRS (in Ref. 2; AAB50683). FT {ECO:0000305}. FT CONFLICT 372 372 N -> Y (in Ref. 2; AAB50683). FT {ECO:0000305}. FT CONFLICT 420 426 PHARNGL -> RRAQRV (in Ref. 2; AAB50683). FT {ECO:0000305}. SQ SEQUENCE 519 AA; 57528 MW; 7B0129C4E3FE41A8 CRC64; MDADEGQDMS QVSGKESPPV SDTPDEGDEP MPIPEDLSTT SGGQQSSKSD RVVASNVKVE TQSDEENGRA CEMNGEECAE DLRMLDASGE KMNGSHRDQG SSALSGVGGI RLPNGKLKCD ICGIICIGPN VLMVHKRSHT GERPFQCNQC GASFTQKGNL LRHIKLHSGE KPFKCHLCNY ACRRRDALTG HLRTHSVGKP HKCGYCGRSY KQRSSLEEHK ERCHNYLESM GLPGTLYPVI KEETNHSEMA EDLCKIGSER SLVLDRLASN VAKRKSSMPQ KFLGDKGLSD TPYDSSASYE KENEMMKSHV MDQAINNAIN YLGAESLRPL VQTPPGGSEV VPVISPMYQL HKPLAEGTPR SNHSAQDSAV ENLLLLSKAK LVPSEREASP SNSCQDSTDT ESNNEEQRSG LIYLTNHIAP HARNGLSLKE EHRAYDLLRA ASENSQDALR VVSTSGEQMK VYKCEHCRVL FLDHVMYTIH MGCHGFRDPF ECNMCGYHSQ DRYEFSSHIT RGEHRFHMS // ID KLF12_HUMAN Reviewed; 402 AA. AC Q9Y4X4; A8K5T2; L0R3J4; Q5VZM7; Q9UHZ0; DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 07-MAR-2006, sequence version 2. DT 11-NOV-2015, entry version 138. DE RecName: Full=Krueppel-like factor 12; DE AltName: Full=Transcriptional repressor AP-2rep; GN Name=KLF12; Synonyms=AP2REP; ORFNames=HSPC122; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=10704285; DOI=10.1006/geno.1999.6084; RA Roth C., Schuierer M., Gunther K., Buettner R.; RT "Genomic structure and DNA binding properties of the human zinc finger RT transcriptional repressor AP-2rep (KLF12)."; RL Genomics 63:384-390(2000). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11433524; DOI=10.1002/gcc.1152; RA Chen C., Brabham W.W., Stultz B.G., Frierson H.F. Jr., Barrett J.C., RA Sawyers C.L., Isaacs J.T., Dong J.T.; RT "Defining a common region of deletion at 13q21 in human cancers."; RL Genes Chromosomes Cancer 31:333-344(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND ALTERNATIVE SPLICING. RX PubMed=23134681; DOI=10.1096/fj.12-220319; RA Camacho-Vanegas O., Till J., Miranda-Lorenzo I., Ozturk B., RA Camacho S.C., Martignetti J.A.; RT "Shaking the family tree: Identification of novel and biologically RT active alternatively spliced isoforms across the KLF family of RT transcription factors."; RL FASEB J. 27:432-436(2013). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Hypothalamus; RA Jiang C., Peng Y., Gu J., Gu Y., Fu S., Wu T., Dong H., Jin W., Fu G., RA Han Z., Chen Z., Wang Y.; RT "A novel gene expressed in the human hypothalamus."; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for RT 300 previously undefined genes expressed in CD34+ hematopoietic RT stem/progenitor cells."; RL Genome Res. 10:1546-1560(2000). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T., RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., RA Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., RA Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP METHYLATION AT LYS-313. RX PubMed=18438403; DOI=10.1038/nchembio.88; RA Rathert P., Dhayalan A., Murakami M., Zhang X., Tamas R., RA Jurkowska R., Komatsu Y., Shinkai Y., Cheng X., Jeltsch A.; RT "Protein lysine methyltransferase G9a acts on non-histone targets."; RL Nat. Chem. Biol. 4:344-346(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-202, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). CC -!- FUNCTION: Confers strong transcriptional repression to the AP-2- CC alpha gene. Binds to a regulatory element (A32) in the AP-2-alpha CC gene promoter. CC -!- INTERACTION: CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-750750, EBI-10171858; CC Q9NVV9:THAP1; NbExp=3; IntAct=EBI-750750, EBI-741515; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9Y4X4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y4X4-2; Sequence=VSP_006876; CC Name=3; CC IsoId=Q9Y4X4-3; Sequence=VSP_047486, VSP_047487; CC -!- SIMILARITY: Belongs to the Sp1 C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 3 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AJ243274; CAB46982.1; -; mRNA. DR EMBL; AF312872; AAK12082.1; -; Genomic_DNA. DR EMBL; AF312866; AAK12082.1; JOINED; Genomic_DNA. DR EMBL; AF312867; AAK12082.1; JOINED; Genomic_DNA. DR EMBL; AF312868; AAK12082.1; JOINED; Genomic_DNA. DR EMBL; AF312869; AAK12082.1; JOINED; Genomic_DNA. DR EMBL; AF312870; AAK12082.1; JOINED; Genomic_DNA. DR EMBL; AF312871; AAK12082.1; JOINED; Genomic_DNA. DR EMBL; HF546212; CCO02798.1; -; mRNA. DR EMBL; AF113122; AAF14863.1; -; mRNA. DR EMBL; AF161471; AAF29086.1; -; mRNA. DR EMBL; AK291397; BAF84086.1; -; mRNA. DR EMBL; AL159972; CAH70670.1; -; Genomic_DNA. DR EMBL; AL138713; CAH70670.1; JOINED; Genomic_DNA. DR EMBL; AL139036; CAH70670.1; JOINED; Genomic_DNA. DR EMBL; AL160032; CAH70670.1; JOINED; Genomic_DNA. DR EMBL; AL139036; CAH71998.1; -; Genomic_DNA. DR EMBL; AL138713; CAH71998.1; JOINED; Genomic_DNA. DR EMBL; AL159972; CAH71998.1; JOINED; Genomic_DNA. DR EMBL; AL160032; CAH71998.1; JOINED; Genomic_DNA. DR EMBL; AL160032; CAH74171.1; -; Genomic_DNA. DR EMBL; AL138713; CAH74171.1; JOINED; Genomic_DNA. DR EMBL; AL139036; CAH74171.1; JOINED; Genomic_DNA. DR EMBL; AL159972; CAH74171.1; JOINED; Genomic_DNA. DR EMBL; AL138713; CAI15634.1; -; Genomic_DNA. DR EMBL; AL139036; CAI15634.1; JOINED; Genomic_DNA. DR EMBL; AL159972; CAI15634.1; JOINED; Genomic_DNA. DR EMBL; AL160032; CAI15634.1; JOINED; Genomic_DNA. DR EMBL; CH471093; EAW80529.1; -; Genomic_DNA. DR EMBL; BC019680; AAH19680.1; -; mRNA. DR CCDS; CCDS9449.1; -. [Q9Y4X4-1] DR RefSeq; NP_009180.3; NM_007249.4. [Q9Y4X4-1] DR RefSeq; XP_005266308.1; XM_005266251.2. [Q9Y4X4-1] DR RefSeq; XP_005266309.1; XM_005266252.3. [Q9Y4X4-1] DR RefSeq; XP_011533211.1; XM_011534909.1. [Q9Y4X4-1] DR UniGene; Hs.373857; -. DR UniGene; Hs.729350; -. DR ProteinModelPortal; Q9Y4X4; -. DR SMR; Q9Y4X4; 306-402. DR BioGrid; 116434; 5. DR IntAct; Q9Y4X4; 3. DR MINT; MINT-199288; -. DR STRING; 9606.ENSP00000366894; -. DR PhosphoSite; Q9Y4X4; -. DR BioMuta; KLF12; -. DR DMDM; 91771555; -. DR MaxQB; Q9Y4X4; -. DR PaxDb; Q9Y4X4; -. DR PRIDE; Q9Y4X4; -. DR DNASU; 11278; -. DR Ensembl; ENST00000377669; ENSP00000366897; ENSG00000118922. [Q9Y4X4-1] DR GeneID; 11278; -. DR KEGG; hsa:11278; -. DR UCSC; uc001vjf.3; human. [Q9Y4X4-1] DR CTD; 11278; -. DR GeneCards; KLF12; -. DR HGNC; HGNC:6346; KLF12. DR MIM; 607531; gene. DR neXtProt; NX_Q9Y4X4; -. DR PharmGKB; PA30132; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00760000118998; -. DR HOGENOM; HOG000232138; -. DR HOVERGEN; HBG003941; -. DR InParanoid; Q9Y4X4; -. DR KO; K09205; -. DR OMA; PYLHILH; -. DR OrthoDB; EOG747PJ4; -. DR PhylomeDB; Q9Y4X4; -. DR TreeFam; TF350556; -. DR SignaLink; Q9Y4X4; -. DR ChiTaRS; KLF12; human. DR GeneWiki; KLF12; -. DR GenomeRNAi; 11278; -. DR NextBio; 42933; -. DR PRO; PR:Q9Y4X4; -. DR Proteomes; UP000005640; Chromosome 13. DR Bgee; Q9Y4X4; -. DR CleanEx; HS_KLF12; -. DR ExpressionAtlas; Q9Y4X4; baseline and differential. DR Genevisible; Q9Y4X4; HS. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:MGI. DR GO; GO:0001227; F:transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:MGI. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.30.160.60; -; 3. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Pfam; PF00096; zf-C2H2; 1. DR SMART; SM00355; ZnF_C2H2; 3. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; DNA-binding; Metal-binding; KW Methylation; Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Repressor; Transcription; Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 402 Krueppel-like factor 12. FT /FTId=PRO_0000047182. FT ZN_FING 317 341 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 347 371 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 377 399 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT MOD_RES 202 202 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 313 313 N6-methylated lysine; by EHMT2. FT {ECO:0000269|PubMed:18438403}. FT VAR_SEQ 270 402 Missing (in isoform 2). FT {ECO:0000303|PubMed:11042152, FT ECO:0000303|Ref.4}. FT /FTId=VSP_006876. FT VAR_SEQ 290 309 CSISPFSIESTRRQRRSESP -> WRETLQVYLGRLHLEVR FT SFR (in isoform 3). FT {ECO:0000303|PubMed:23134681}. FT /FTId=VSP_047486. FT VAR_SEQ 310 402 Missing (in isoform 3). FT {ECO:0000303|PubMed:23134681}. FT /FTId=VSP_047487. FT CONFLICT 246 246 P -> L (in Ref. 1; CAB46982 and 2; FT AAK12082). {ECO:0000305}. SQ SEQUENCE 402 AA; 44240 MW; 9557E776878BAA8D CRC64; MNIHMKRKTI KNINTFENRM LMLDGMPAVR VKTELLESEQ GSPNVHNYPD MEAVPLLLNN VKGEPPEDSL SVDHFQTQTE PVDLSINKAR TSPTAVSSSP VSMTASASSP SSTSTSSSSS SRLASSPTVI TSVSSASSSS TVLTPGPLVA SASGVGGQQF LHIIHPVPPS SPMNLQSNKL SHVHRIPVVV QSVPVVYTAV RSPGNVNNTI VVPLLEDGRG HGKAQMDPRG LSPRQSKSDS DDDDLPNVTL DSVNETGSTA LSIARAVQEV HPSPVSRVRG NRMNNQKFPC SISPFSIEST RRQRRSESPD SRKRRIHRCD FEGCNKVYTK SSHLKAHRRT HTGEKPYKCT WEGCTWKFAR SDELTRHYRK HTGVKPFKCA DCDRSFSRSD HLALHRRRHM LV // ID KLF4_HUMAN Reviewed; 513 AA. AC O43474; B2R8S4; B3KT79; L0R3I6; L0R4N5; P78338; Q5T3J8; Q5T3J9; AC Q8N717; Q9UNP3; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 10-FEB-2009, sequence version 3. DT 11-NOV-2015, entry version 149. DE RecName: Full=Krueppel-like factor 4; DE AltName: Full=Epithelial zinc finger protein EZF; DE AltName: Full=Gut-enriched krueppel-like factor; GN Name=KLF4; Synonyms=EZF, GKLF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=9422764; DOI=10.1074/jbc.273.2.1026; RA Yet S.-F., McA'Nulty M.M., Folta S.C., Yen H.-W., Yoshizumi M., RA Hsieh C.-M., Layne M.D., Chin M.T., Wang H., Perrella M.A., Jain M.K., RA Lee M.-E.; RT "Human EZF, a Kruppel-like zinc finger protein, is expressed in RT vascular endothelial cells and contains transcriptional activation and RT repression domains."; RL J. Biol. Chem. 273:1026-1031(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=10392904; RA Foster K.W., Ren S., Louro I.D., Lobo-Ruppert S.M., McKie-Bell P., RA Grizzle W., Hayes M.R., Broker T.R., Chow L.T., Ruppert J.M.; RT "Oncogene expression cloning by retroviral transduction of adenovirus RT E1A-immortalized rat kidney RK3E cells: transformation of a host with RT epithelial features by c-MYC and the zinc finger protein GKLF."; RL Cell Growth Differ. 10:423-434(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 4 AND 5), AND ALTERNATIVE RP SPLICING. RX PubMed=23134681; DOI=10.1096/fj.12-220319; RA Camacho-Vanegas O., Till J., Miranda-Lorenzo I., Ozturk B., RA Camacho S.C., Martignetti J.A.; RT "Shaking the family tree: Identification of novel and biologically RT active alternatively spliced isoforms across the KLF family of RT transcription factors."; RL FASEB J. 27:432-436(2013). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS SER-315 AND RP PHE-321. RC TISSUE=Placenta; RA Garrett-Sinha L.A., de Crombrugghe B.; RL Submitted (SEP-1996) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Substantia nigra, and Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG SeattleSNPs variation discovery resource; RL Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., RA Rogers J., Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Cervix, and Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP INTERACTION WITH MUC1, AND FUNCTION. RX PubMed=17308127; DOI=10.1158/0008-5472.CAN-06-3063; RA Wei X., Xu H., Kufe D.; RT "Human mucin 1 oncoprotein represses transcription of the p53 tumor RT suppressor gene."; RL Cancer Res. 67:1853-1858(2007). RN [11] RP BIOTECHNOLOGY. RX PubMed=18035408; DOI=10.1016/j.cell.2007.11.019; RA Takahashi K., Tanabe K., Ohnuki M., Narita M., Ichisaka T., Tomoda K., RA Yamanaka S.; RT "Induction of pluripotent stem cells from adult human fibroblasts by RT defined factors."; RL Cell 131:861-872(2007). RN [12] RP DOMAIN. RX PubMed=17467953; DOI=10.1016/j.ygeno.2007.02.003; RA Piskacek S., Gregor M., Nemethova M., Grabner M., Kovarik P., RA Piskacek M.; RT "Nine-amino-acid transactivation domain: establishment and prediction RT utilities."; RL Genomics 89:756-768(2007). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [14] RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-32. RC TISSUE=Cervix carcinoma; RX PubMed=18655026; DOI=10.1002/pmic.200700887; RA Tan F., Lu L., Cai Y., Wang J., Xie Y., Wang L., Gong Y., Xu B.-E., RA Wu J., Luo Y., Qiang B., Yuan J., Sun X., Peng X.; RT "Proteomic analysis of ubiquitinated proteins in normal hepatocyte RT cell line Chang liver cells."; RL Proteomics 8:2885-2896(2008). RN [15] RP FUNCTION. RX PubMed=20071344; DOI=10.1074/jbc.M109.077958; RA Zhang P., Andrianakos R., Yang Y., Liu C., Lu W.; RT "Kruppel-like factor 4 (Klf4) prevents embryonic stem (ES) cell RT differentiation by regulating Nanog gene expression."; RL J. Biol. Chem. 285:9180-9189(2010). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-254, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [17] RP INTERACTION WITH PBX1 AND MEIS2. RX PubMed=21746878; DOI=10.1128/MCB.01456-10; RA Bjerke G.A., Hyman-Walsh C., Wotton D.; RT "Cooperative transcriptional activation by Klf4, Meis2, and Pbx1."; RL Mol. Cell. Biol. 31:3723-3733(2011). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). CC -!- FUNCTION: Transcription factor; can act both as activator and as CC repressor. Binds the 5'-CACCC-3' core sequence. Binds to the CC promoter region of its own gene and can activate its own CC transcription. Regulates the expression of key transcription CC factors during embryonic development. Plays an important role in CC maintaining embryonic stem cells, and in preventing their CC differentiation. Required for establishing the barrier function of CC the skin and for postnatal maturation and maintenance of the CC ocular surface. Involved in the differentiation of epithelial CC cells and may also function in skeletal and kidney development. CC Contributes to the down-regulation of p53/TP53 transcription. CC {ECO:0000269|PubMed:17308127, ECO:0000269|PubMed:20071344}. CC -!- SUBUNIT: Interacts with POU5F1/OCT4 and SOX2 (By similarity). CC Interacts with MUC1 (via the C-terminal domain). Interacts with CC MEIS2 isoform 4 and PBX1 isoform PBX1a. {ECO:0000250, CC ECO:0000269|PubMed:17308127, ECO:0000269|PubMed:21746878}. CC -!- INTERACTION: CC Q13363:CTBP1; NbExp=4; IntAct=EBI-7232405, EBI-908846; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=O43474-3; Sequence=Displayed; CC Name=2; CC IsoId=O43474-1; Sequence=VSP_036399; CC Name=3; CC IsoId=O43474-4; Sequence=VSP_040569, VSP_036399; CC Note=No experimental confirmation available.; CC Name=4; Synonyms=1a; CC IsoId=O43474-5; Sequence=VSP_047470, VSP_047473; CC Name=5; CC IsoId=O43474-6; Sequence=VSP_047471, VSP_047472; CC -!- DOMAIN: the 9aaTAD motif is a transactivation domain present in a CC large number of yeast and animal transcription factors. CC {ECO:0000269|PubMed:17467953}. CC -!- BIOTECHNOLOGY: POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four CC Yamanaka factors. When combined, these factors are sufficient to CC reprogram differentiated cells to an embryonic-like state CC designated iPS (induced pluripotent stem) cells. iPS cells exhibit CC the morphology and growth properties of ES cells and express ES CC cell marker genes. {ECO:0000269|PubMed:18035408}. CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 3 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB48399.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAC03462.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAD42165.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAH29923.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAH30811.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=ABG25917.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=BAG36271.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=EAW59020.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=EAW59021.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/KLF4ID44316ch9q31.html"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/klf4/"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF022184; AAC03462.1; ALT_INIT; mRNA. DR EMBL; AF105036; AAD42165.1; ALT_INIT; mRNA. DR EMBL; HF546201; CCO02787.1; -; mRNA. DR EMBL; HF546202; CCO02788.1; -; mRNA. DR EMBL; U70663; AAB48399.1; ALT_INIT; mRNA. DR EMBL; AK095134; BAG52991.1; -; mRNA. DR EMBL; AK313489; BAG36271.1; ALT_INIT; mRNA. DR EMBL; DQ658241; ABG25917.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL360218; CAI12254.2; -; Genomic_DNA. DR EMBL; CH471105; EAW59020.1; ALT_SEQ; Genomic_DNA. DR EMBL; CH471105; EAW59021.1; ALT_SEQ; Genomic_DNA. DR EMBL; BC029923; AAH29923.1; ALT_INIT; mRNA. DR EMBL; BC030811; AAH30811.1; ALT_INIT; mRNA. DR CCDS; CCDS6770.2; -. [O43474-1] DR RefSeq; NP_004226.3; NM_004235.4. [O43474-1] DR RefSeq; XP_005252362.1; XM_005252305.1. [O43474-3] DR UniGene; Hs.376206; -. DR ProteinModelPortal; O43474; -. DR SMR; O43474; 427-513. DR BioGrid; 114726; 22. DR DIP; DIP-57667N; -. DR IntAct; O43474; 2. DR MINT; MINT-7261942; -. DR PhosphoSite; O43474; -. DR BioMuta; KLF4; -. DR MaxQB; O43474; -. DR PRIDE; O43474; -. DR DNASU; 9314; -. DR Ensembl; ENST00000374672; ENSP00000363804; ENSG00000136826. [O43474-1] DR GeneID; 9314; -. DR KEGG; hsa:9314; -. DR UCSC; uc004bdf.2; human. [O43474-4] DR UCSC; uc004bdg.3; human. [O43474-1] DR UCSC; uc004bdh.3; human. [O43474-3] DR CTD; 9314; -. DR GeneCards; KLF4; -. DR HGNC; HGNC:6348; KLF4. DR HPA; HPA002926; -. DR MIM; 602253; gene. DR neXtProt; NX_O43474; -. DR PharmGKB; PA30138; -. DR GeneTree; ENSGT00760000118998; -. DR HOVERGEN; HBG006220; -. DR InParanoid; O43474; -. DR KO; K17846; -. DR OMA; CTVGRPL; -. DR PhylomeDB; O43474; -. DR TreeFam; TF350556; -. DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation. DR Reactome; R-HSA-422085; Synthesis, secretion, and deacylation of Ghrelin. DR Reactome; R-HSA-452723; Transcriptional regulation of pluripotent stem cells. DR SignaLink; O43474; -. DR ChiTaRS; KLF4; human. DR GeneWiki; KLF4; -. DR GenomeRNAi; 9314; -. DR NextBio; 34891; -. DR PRO; PR:O43474; -. DR Proteomes; UP000005640; Chromosome 9. DR Bgee; O43474; -. DR CleanEx; HS_KLF4; -. DR ExpressionAtlas; O43474; baseline and differential. DR Genevisible; O43474; HS. DR GO; GO:0000790; C:nuclear chromatin; IDA:BHF-UCL. DR GO; GO:0005719; C:nuclear euchromatin; IEA:Ensembl. DR GO; GO:0044798; C:nuclear transcription factor complex; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0001047; F:core promoter binding; IEA:Ensembl. DR GO; GO:0000987; F:core promoter proximal region sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0003690; F:double-stranded DNA binding; IEA:Ensembl. DR GO; GO:0035014; F:phosphatidylinositol 3-kinase regulator activity; IEA:Ensembl. DR GO; GO:0001085; F:RNA polymerase II transcription factor binding; IPI:BHF-UCL. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; NAS:UniProtKB. DR GO; GO:0001010; F:transcription factor activity, sequence-specific DNA binding transcription factor recruiting; ISS:BHF-UCL. DR GO; GO:0044212; F:transcription regulatory region DNA binding; ISS:UniProtKB. DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IMP:BHF-UCL. DR GO; GO:0001190; F:transcriptional activator activity, RNA polymerase II transcription factor binding; IDA:BHF-UCL. DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0071409; P:cellular response to cycloheximide; IEA:Ensembl. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:BHF-UCL. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; IMP:BHF-UCL. DR GO; GO:1901653; P:cellular response to peptide; IEA:Ensembl. DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl. DR GO; GO:0009913; P:epidermal cell differentiation; IEA:Ensembl. DR GO; GO:0048730; P:epidermis morphogenesis; IEA:Ensembl. DR GO; GO:0045444; P:fat cell differentiation; ISS:BHF-UCL. DR GO; GO:0007500; P:mesodermal cell fate determination; TAS:ProtInc. DR GO; GO:0090051; P:negative regulation of cell migration involved in sprouting angiogenesis; IDA:BHF-UCL. DR GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc. DR GO; GO:2000342; P:negative regulation of chemokine (C-X-C motif) ligand 2 production; IDA:BHF-UCL. DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:BHF-UCL. DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; IDA:BHF-UCL. DR GO; GO:0050728; P:negative regulation of inflammatory response; TAS:BHF-UCL. DR GO; GO:0045415; P:negative regulation of interleukin-8 biosynthetic process; IDA:BHF-UCL. DR GO; GO:0014740; P:negative regulation of muscle hyperplasia; IEA:Ensembl. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:BHF-UCL. DR GO; GO:0014067; P:negative regulation of phosphatidylinositol 3-kinase signaling; IEA:Ensembl. DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IEA:Ensembl. DR GO; GO:0060761; P:negative regulation of response to cytokine stimulus; IDA:BHF-UCL. DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0032270; P:positive regulation of cellular protein metabolic process; IMP:BHF-UCL. DR GO; GO:0046985; P:positive regulation of hemoglobin biosynthetic process; IMP:BHF-UCL. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:BHF-UCL. DR GO; GO:0051247; P:positive regulation of protein metabolic process; IGI:BHF-UCL. DR GO; GO:0051973; P:positive regulation of telomerase activity; IDA:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB. DR GO; GO:0031077; P:post-embryonic camera-type eye development; IEA:Ensembl. DR GO; GO:0035166; P:post-embryonic hemopoiesis; IMP:BHF-UCL. DR GO; GO:0045595; P:regulation of cell differentiation; ISS:UniProtKB. DR GO; GO:0035019; P:somatic stem cell population maintenance; TAS:Reactome. DR GO; GO:0019827; P:stem cell population maintenance; ISS:UniProtKB. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; ISS:BHF-UCL. DR Gene3D; 3.30.160.60; -; 3. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Pfam; PF00096; zf-C2H2; 1. DR SMART; SM00355; ZnF_C2H2; 3. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 3. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 3. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Complete proteome; DNA-binding; KW Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Ubl conjugation; Zinc; Zinc-finger. FT CHAIN 1 513 Krueppel-like factor 4. FT /FTId=PRO_0000047167. FT ZN_FING 430 454 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 460 484 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 490 512 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT REGION 473 504 Interaction with target DNA. FT {ECO:0000250}. FT MOTIF 101 109 9aaTAD. FT COMPBIAS 125 149 Ser-rich. FT COMPBIAS 179 415 Pro-rich. FT MOD_RES 254 254 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT CROSSLNK 32 32 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000269|PubMed:18655026}. FT VAR_SEQ 1 50 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_040569. FT VAR_SEQ 43 118 RWREELSHMKRLPPVLPGRPYDLAAATVATDLESGGAGAAC FT GGSNLAPLPRRETEEFNDLLDLDFILSNSLTHPPE -> SS FT CHPVPACQRSPSQRGEDDRGPGKGPPPTLVITRAAAKPTQR FT VPISRHTCEPTQVRNLTTVTGTAVDGNSPAQMN (in FT isoform 4). FT {ECO:0000303|PubMed:23134681}. FT /FTId=VSP_047470. FT VAR_SEQ 43 63 RWREELSHMKRLPPVLPGRPY -> VRNLTTVTGTAVDGNS FT PAQMN (in isoform 5). FT {ECO:0000303|PubMed:23134681}. FT /FTId=VSP_047471. FT VAR_SEQ 64 513 Missing (in isoform 5). FT {ECO:0000303|PubMed:23134681}. FT /FTId=VSP_047472. FT VAR_SEQ 119 513 Missing (in isoform 4). FT {ECO:0000303|PubMed:23134681}. FT /FTId=VSP_047473. FT VAR_SEQ 367 400 Missing (in isoform 2 and isoform 3). FT {ECO:0000303|PubMed:10392904, FT ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9422764, FT ECO:0000303|Ref.4}. FT /FTId=VSP_036399. FT VARIANT 315 315 T -> S (in dbSNP:rs1059913). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_059888. FT VARIANT 321 321 L -> F (in dbSNP:rs1059914). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_059889. FT CONFLICT 60 61 GR -> AG (in Ref. 1; AAC03462). FT {ECO:0000305}. FT CONFLICT 77 77 G -> A (in Ref. 1; AAC03462). FT {ECO:0000305}. FT CONFLICT 251 251 S -> T (in Ref. 1; AAC03462). FT {ECO:0000305}. FT CONFLICT 304 304 D -> N (in Ref. 4; AAB48399). FT {ECO:0000305}. FT CONFLICT 329 329 D -> E (in Ref. 4; AAB48399). FT {ECO:0000305}. SQ SEQUENCE 513 AA; 54671 MW; 3B6113A3EF333935 CRC64; MRQPPGESDM AVSDALLPSF STFASGPAGR EKTLRQAGAP NNRWREELSH MKRLPPVLPG RPYDLAAATV ATDLESGGAG AACGGSNLAP LPRRETEEFN DLLDLDFILS NSLTHPPESV AATVSSSASA SSSSSPSSSG PASAPSTCSF TYPIRAGNDP GVAPGGTGGG LLYGRESAPP PTAPFNLADI NDVSPSGGFV AELLRPELDP VYIPPQQPQP PGGGLMGKFV LKASLSAPGS EYGSPSVISV SKGSPDGSHP VVVAPYNGGP PRTCPKIKQE AVSSCTHLGA GPPLSNGHRP AAHDFPLGRQ LPSRTTPTLG LEEVLSSRDC HPALPLPPGF HPHPGPNYPS FLPDQMQPQV PPLHYQGQSR GFVARAGEPC VCWPHFGTHG MMLTPPSSPL ELMPPGSCMP EEPKPKRGRR SWPRKRTATH TCDYAGCGKT YTKSSHLKAH LRTHTGEKPY HCDWDGCGWK FARSDELTRH YRKHTGHRPF QCQKCDRAFS RSDHLALHMK RHF // ID LCORL_HUMAN Reviewed; 602 AA. AC Q8N3X6; Q96NK1; DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot. DT 13-NOV-2007, sequence version 4. DT 11-NOV-2015, entry version 103. DE RecName: Full=Ligand-dependent nuclear receptor corepressor-like protein; DE Short=LCoR-like protein; GN Name=LCORL; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP IDENTIFICATION. RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200; RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core RT fucosylated glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). CC -!- FUNCTION: May act as transcription activator that binds DNA CC elements with the sequence 5'-CCCTATCGATCGATCTCTACCT-3'. May play CC a role in spermatogenesis (By similarity). {ECO:0000250}. CC -!- INTERACTION: CC P43360:MAGEA6; NbExp=3; IntAct=EBI-7138654, EBI-1045155; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE- CC ProRule:PRU00320}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q8N3X6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8N3X6-2; Sequence=VSP_029287; CC Name=3; CC IsoId=Q8N3X6-3; Sequence=VSP_029288, VSP_029289; CC -!- SIMILARITY: Contains 1 HTH psq-type DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00320}. CC -!- CAUTION: A report observed N-glycosylation at Asn-493 CC (PubMed:19139490). However, as the protein is predicted to act as CC a DNA-binding transcription activator, additional evidences are CC required to confirm this result. {ECO:0000305|PubMed:19139490}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AK055258; BAB70892.1; -; mRNA. DR EMBL; AC005768; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC079399; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471069; EAW92786.1; -; Genomic_DNA. DR EMBL; BC037322; AAH37322.3; -; mRNA. DR CCDS; CCDS3425.1; -. [Q8N3X6-3] DR CCDS; CCDS54749.1; -. [Q8N3X6-1] DR RefSeq; NP_001159611.1; NM_001166139.1. [Q8N3X6-1] DR RefSeq; NP_710153.2; NM_153686.7. [Q8N3X6-3] DR UniGene; Hs.446201; -. DR UniGene; Hs.677572; -. DR ProteinModelPortal; Q8N3X6; -. DR SMR; Q8N3X6; 522-579. DR BioGrid; 129025; 2. DR IntAct; Q8N3X6; 2. DR MINT; MINT-8247449; -. DR STRING; 9606.ENSP00000371661; -. DR PhosphoSite; Q8N3X6; -. DR BioMuta; LCORL; -. DR DMDM; 160395582; -. DR MaxQB; Q8N3X6; -. DR PaxDb; Q8N3X6; -. DR PRIDE; Q8N3X6; -. DR DNASU; 254251; -. DR Ensembl; ENST00000326877; ENSP00000317566; ENSG00000178177. [Q8N3X6-3] DR Ensembl; ENST00000382226; ENSP00000371661; ENSG00000178177. [Q8N3X6-1] DR GeneID; 254251; -. DR KEGG; hsa:254251; -. DR UCSC; uc003gpq.3; human. [Q8N3X6-3] DR UCSC; uc021xmr.1; human. [Q8N3X6-1] DR CTD; 254251; -. DR GeneCards; LCORL; -. DR HGNC; HGNC:30776; LCORL. DR HPA; HPA028794; -. DR HPA; HPA028795; -. DR HPA; HPA060033; -. DR MIM; 611799; gene. DR neXtProt; NX_Q8N3X6; -. DR PharmGKB; PA145148507; -. DR eggNOG; KOG4565; Eukaryota. DR eggNOG; ENOG4111GCI; LUCA. DR GeneTree; ENSGT00520000055615; -. DR HOGENOM; HOG000253915; -. DR HOVERGEN; HBG108084; -. DR InParanoid; Q8N3X6; -. DR OMA; YKVKERS; -. DR OrthoDB; EOG7VHSXQ; -. DR PhylomeDB; Q8N3X6; -. DR TreeFam; TF319589; -. DR ChiTaRS; LCORL; human. DR GenomeRNAi; 254251; -. DR NextBio; 92303; -. DR PRO; PR:Q8N3X6; -. DR Proteomes; UP000005640; Chromosome 4. DR Bgee; Q8N3X6; -. DR CleanEx; HS_LCORL; -. DR ExpressionAtlas; Q8N3X6; baseline and differential. DR Genevisible; Q8N3X6; HS. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IEA:Ensembl. DR InterPro; IPR009057; Homeodomain-like. DR InterPro; IPR007889; HTH_Psq. DR Pfam; PF05225; HTH_psq; 2. DR SUPFAM; SSF46689; SSF46689; 2. DR PROSITE; PS50960; HTH_PSQ; 1. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Complete proteome; DNA-binding; KW Nucleus; Reference proteome; Transcription; Transcription regulation. FT CHAIN 1 602 Ligand-dependent nuclear receptor FT corepressor-like protein. FT /FTId=PRO_0000310463. FT DOMAIN 516 568 HTH psq-type. {ECO:0000255|PROSITE- FT ProRule:PRU00320}. FT DNA_BIND 544 564 H-T-H motif. {ECO:0000255|PROSITE- FT ProRule:PRU00320}. FT COMPBIAS 9 31 Ala-rich. FT VAR_SEQ 1 389 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_029287. FT VAR_SEQ 260 318 RLHRNREDYVERSAEFADGLLSKALKDIQSGALDINKAGIL FT YGIPQKTLLLHLEALPAG -> MLQVKTDEKLNVSDENTAS FT CPLSPIKMCLNRPIEWNLNLTTASLTSCTVHNQNLKSEEK FT (in isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_029288. FT VAR_SEQ 319 602 Missing (in isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_029289. FT CONFLICT 407 407 N -> S (in Ref. 1; BAB70892). FT {ECO:0000305}. SQ SEQUENCE 602 AA; 66964 MW; 05245F999E5A61D7 CRC64; MDKGRERMAA AAAAAAAAAA AAQCRSPRCA AERRGFRREL DSWRHRLMHC VGFESILEGL YGPRLRRDLS LFEDCEPEEL TDWSMDEKCS FCNLQREAVS DCIPSLDSSQ STPTEELSSQ GQSNTDKIEC QAENYLNALF RKKDLPQNCD PNIPLVAQEL MKKMIRQFAI EYISKSGKTQ ENRNGSIGPS IVCKSIQMNQ AENSLQEEQE GPLDLTVNRM QEQNTQQGDG VLDLSTKKTS IKSEESSICD PSSENSVAGR LHRNREDYVE RSAEFADGLL SKALKDIQSG ALDINKAGIL YGIPQKTLLL HLEALPAGKP ASFKNKTRDF HDSYSYKDSK ETCAVLQKVA LWARAQAERT EKSKLNLLET SEIKFPTAST YLHQLTLQKM VTQFKEKNES LQYETSNPTV QLKIPQLRVS SVSKSQPDGS GLLDVMYQVS KTSSVLEGSA LQKLKNILPK QNKIECSGPV THSSVDSYFL HGDLSPLCLN SKNGTVDGTS ENTEDGLDRK DSKQPRKKRG RYRQYDHEIM EEAIAMVMSG KMSVSKAQGI YGVPHSTLEY KVKERSGTLK TPPKKKLRLP DTGLYNMTDS GTGSCKNSSK PV // ID LCOR_HUMAN Reviewed; 433 AA. AC Q96JN0; D3DR47; Q5VW16; Q7Z723; Q86T32; Q86T33; Q8N3L6; DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 30-MAY-2006, sequence version 2. DT 11-NOV-2015, entry version 103. DE RecName: Full=Ligand-dependent corepressor; DE Short=LCoR; DE AltName: Full=Mblk1-related protein 2; GN Name=LCOR; Synonyms=KIAA1795, MLR2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=11347906; DOI=10.1093/dnares/8.2.85; RA Nagase T., Nakayama M., Nakajima D., Kikuno R., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XX. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 8:85-95(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Bone marrow, and Skeletal muscle; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION, INTERACTION WITH CTBP1; ESR1; ESR2; HDAC3 AND HDAC6, RP SUBCELLULAR LOCATION, MUTAGENESIS OF 56-LEU-LEU-57, AND TISSUE RP SPECIFICITY. RX PubMed=12535528; DOI=10.1016/S1097-2765(03)00014-5; RA Fernandes I., Bastien Y., Wai T., Nygard K., Lin R., Cormier O., RA Lee H.S., Eng F., Bertos N.R., Pelletier N., Mader S., Han V.K.M., RA Yang X.-J., White J.H.; RT "Ligand-dependent nuclear receptor corepressor LCoR functions by RT histone deacetylase-dependent and -independent mechanisms."; RL Mol. Cell 11:139-150(2003). RN [7] RP IDENTIFICATION IN A COREPRESSOR COMPLEX, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RX PubMed=12700765; DOI=10.1038/nature01550; RA Shi Y., Sawada J., Sui G., Affar E.B., Whetstine J.R., Lan F., RA Ogawa H., Luke M.P.-S., Nakatani Y., Shi Y.; RT "Coordinated histone modifications mediated by a CtBP co-repressor RT complex."; RL Nature 422:735-738(2003). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-63 AND SER-249, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [11] RP STRUCTURE BY NMR OF 343-405. RG RIKEN structural genomics initiative (RSGI); RT "Solution structures of the HTH domain of human LCOR protein."; RL Submitted (NOV-2005) to the PDB data bank. CC -!- FUNCTION: May act as transcription activator that binds DNA CC elements with the sequence 5'-CCCTATCGATCGATCTCTACCT-3' (By CC similarity). Repressor of ligand-dependent transcription CC activation by target nuclear receptors. Repressor of ligand- CC dependent transcription activation by ESR1, ESR2, NR3C1, PGR, CC RARA, RARB, RARG, RXRA and VDR. {ECO:0000250, CC ECO:0000269|PubMed:12535528}. CC -!- SUBUNIT: Interacts with ESR1 and ESR2 in the presence of CC estradiol. Interacts with CTBP1, HDAC3 and HDAC6. Component of a CC large corepressor complex that contains about 20 proteins, CC including CTBP1, CTBP2, HDAC1 and HDAC2. CC {ECO:0000269|PubMed:12535528, ECO:0000269|PubMed:12700765}. CC -!- INTERACTION: CC P56545:CTBP2; NbExp=3; IntAct=EBI-8833163, EBI-741533; CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-8833163, EBI-10171902; CC Q08379:GOLGA2; NbExp=3; IntAct=EBI-8833163, EBI-618309; CC Q13077:TRAF1; NbExp=3; IntAct=EBI-8833163, EBI-359224; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE- CC ProRule:PRU00320, ECO:0000269|PubMed:12535528}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96JN0-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96JN0-2; Sequence=VSP_018585, VSP_018586; CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:12535528}. CC -!- SIMILARITY: Contains 1 HTH psq-type DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00320}. CC -!- SEQUENCE CAUTION: CC Sequence=BAB47424.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AB058698; BAB47424.1; ALT_INIT; mRNA. DR EMBL; AL834245; CAD38921.2; -; mRNA. DR EMBL; AL832106; CAD91159.1; -; mRNA. DR EMBL; AL832044; CAD91160.1; -; mRNA. DR EMBL; AL442123; CAH70915.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49963.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49965.1; -; Genomic_DNA. DR EMBL; CH471066; EAW49966.1; -; Genomic_DNA. DR EMBL; BC053359; AAH53359.1; -; mRNA. DR CCDS; CCDS53561.1; -. [Q96JN0-2] DR CCDS; CCDS7451.1; -. [Q96JN0-1] DR RefSeq; NP_001164236.1; NM_001170765.1. [Q96JN0-1] DR RefSeq; NP_001164237.1; NM_001170766.1. [Q96JN0-2] DR RefSeq; NP_115816.2; NM_032440.3. [Q96JN0-1] DR RefSeq; XP_006718097.1; XM_006718034.2. [Q96JN0-1] DR UniGene; Hs.745068; -. DR PDB; 2COB; NMR; -; A=343-405. DR PDBsum; 2COB; -. DR ProteinModelPortal; Q96JN0; -. DR SMR; Q96JN0; 346-405. DR BioGrid; 124093; 23. DR IntAct; Q96JN0; 4. DR STRING; 9606.ENSP00000348298; -. DR PhosphoSite; Q96JN0; -. DR BioMuta; LCOR; -. DR DMDM; 108936028; -. DR MaxQB; Q96JN0; -. DR PaxDb; Q96JN0; -. DR PRIDE; Q96JN0; -. DR DNASU; 84458; -. DR Ensembl; ENST00000356016; ENSP00000348298; ENSG00000196233. [Q96JN0-1] DR Ensembl; ENST00000371097; ENSP00000360138; ENSG00000196233. [Q96JN0-1] DR Ensembl; ENST00000371103; ENSP00000360144; ENSG00000196233. [Q96JN0-1] DR Ensembl; ENST00000540664; ENSP00000443431; ENSG00000196233. [Q96JN0-2] DR GeneID; 84458; -. DR KEGG; hsa:84458; -. DR UCSC; uc001kmr.3; human. [Q96JN0-2] DR UCSC; uc001kms.2; human. [Q96JN0-1] DR CTD; 84458; -. DR GeneCards; LCOR; -. DR HGNC; HGNC:29503; LCOR. DR HPA; HPA031428; -. DR HPA; HPA031429; -. DR MIM; 607698; gene. DR neXtProt; NX_Q96JN0; -. DR PharmGKB; PA145148487; -. DR eggNOG; KOG4565; Eukaryota. DR eggNOG; ENOG4111GCI; LUCA. DR GeneTree; ENSGT00520000055615; -. DR HOVERGEN; HBG079596; -. DR InParanoid; Q96JN0; -. DR OMA; HYEFNFS; -. DR OrthoDB; EOG73RBBB; -. DR PhylomeDB; Q96JN0; -. DR TreeFam; TF319589; -. DR ChiTaRS; LCOR; human. DR EvolutionaryTrace; Q96JN0; -. DR GeneWiki; LCOR; -. DR GenomeRNAi; 84458; -. DR NextBio; 74251; -. DR PRO; PR:Q96JN0; -. DR Proteomes; UP000005640; Chromosome 10. DR Bgee; Q96JN0; -. DR CleanEx; HS_LCOR; -. DR Genevisible; Q96JN0; HS. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IEA:Ensembl. DR InterPro; IPR009057; Homeodomain-like. DR InterPro; IPR007889; HTH_Psq. DR Pfam; PF05225; HTH_psq; 1. DR SUPFAM; SSF46689; SSF46689; 1. DR PROSITE; PS50960; HTH_PSQ; 1. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Complete proteome; KW DNA-binding; Nucleus; Phosphoprotein; Reference proteome; Repressor; KW Transcription; Transcription regulation. FT CHAIN 1 433 Ligand-dependent corepressor. FT /FTId=PRO_0000236807. FT DOMAIN 340 392 HTH psq-type. {ECO:0000255|PROSITE- FT ProRule:PRU00320}. FT DNA_BIND 368 388 H-T-H motif. {ECO:0000255|PROSITE- FT ProRule:PRU00320}. FT MOTIF 53 57 Interaction with nuclear receptors. FT MOTIF 339 345 Nuclear localization signal. FT {ECO:0000255}. FT MOD_RES 63 63 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 249 249 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT VAR_SEQ 405 406 RS -> SG (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_018585. FT VAR_SEQ 407 433 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_018586. FT MUTAGEN 56 57 LL->AA: Loss of estradiol-dependent FT interaction with ESR1 and ESR2. FT {ECO:0000269|PubMed:12535528}. FT CONFLICT 6 6 Q -> P (in Ref. 2; CAD91159). FT {ECO:0000305}. FT CONFLICT 321 321 S -> P (in Ref. 2; CAD38921). FT {ECO:0000305}. FT HELIX 351 362 {ECO:0000244|PDB:2COB}. FT HELIX 368 375 {ECO:0000244|PDB:2COB}. FT HELIX 379 389 {ECO:0000244|PDB:2COB}. FT TURN 390 393 {ECO:0000244|PDB:2COB}. SQ SEQUENCE 433 AA; 47007 MW; 5F934FE687417740 CRC64; MQRMIQQFAA EYTSKNSSTQ DPSQPNSTKN QSLPKASPVT TSPTAATTQN PVLSKLLMAD QDSPLDLTVR KSQSEPSEQD GVLDLSTKKS PCAGSTSLSH SPGCSSTQGN GRPGRPSQYR PDGLRSGDGV PPRSLQDGTR EGFGHSTSLK VPLARSLQIS EELLSRNQLS TAASLGPSGL QNHGQHLILS REASWAKPHY EFNLSRMKFR GNGALSNISD LPFLAENSAF PKMALQAKQD GKKDVSHSSP VDLKIPQVRG MDLSWESRTG DQYSYSSLVM GSQTESALSK KLRAILPKQS RKSMLDAGPD SWGSDAEQST SGQPYPTSDQ EGDPGSKQPR KKRGRYRQYN SEILEEAISV VMSGKMSVSK AQSIYGIPHS TLEYKVKERL GTLKNPPKKK MKLMRSEGPD VSVKIELDPQ GEAAQSANES KNE // ID MDM2_HUMAN Reviewed; 491 AA. AC Q00987; A6NL51; A8K2S6; Q13226; Q13297; Q13298; Q13299; Q13300; AC Q13301; Q53XW0; Q71TW9; Q8WYJ1; Q8WYJ2; Q9UGI3; Q9UMT8; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1993, sequence version 1. DT 11-NOV-2015, entry version 205. DE RecName: Full=E3 ubiquitin-protein ligase Mdm2; DE EC=6.3.2.-; DE AltName: Full=Double minute 2 protein; DE Short=Hdm2; DE AltName: Full=Oncoprotein Mdm2; DE AltName: Full=p53-binding protein Mdm2; GN Name=MDM2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MDM2). RC TISSUE=Colon; RX PubMed=1614537; DOI=10.1038/358080a0; RA Oliner J.D., Kinzler K.W., Meltzer P.S., George D.L., Vogelstein B.; RT "Amplification of a gene encoding a p53-associated protein in human RT sarcomas."; RL Nature 358:80-83(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MDM2-A; MDM2-B; MDM2-C; MDM2-D RP AND MDM2-E). RC TISSUE=Ovarian carcinoma; RX PubMed=8705862; DOI=10.1038/nm0896-912; RA Sigalas I., Calvert A.H., Anderson J.J., Neal D.E., Lunec J.; RT "Alternatively spliced mdm2 transcripts with loss of p53 binding RT domain sequences: transforming ability and frequent detection in human RT cancer."; RL Nat. Med. 2:912-917(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MDM2-ALPHA). RX PubMed=10597303; DOI=10.1038/sj.onc.1203182; RA Veldhoen N., Metcalfe S., Milner J.; RT "A novel exon within the mdm2 gene modulates translation initiation in RT vitro and disrupts the p53-binding domain of mdm2 protein."; RL Oncogene 18:7026-7033(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MDM2-F AND MDM2-G), AND RP INTERACTION WITH TP53. RX PubMed=11351297; DOI=10.1002/ijc.1271; RA Tamborini E., Della Torre G., Lavarino C., Azzarelli A., RA Carpinelli P., Pierotti M.A., Pilotti S.; RT "Analysis of the molecular species generated by MDM2 gene RT amplification in liposarcomas."; RL Int. J. Cancer 92:790-796(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MDM2). RC TISSUE=Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM MDM2). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., RA Kucherlapati R., Weinstock G., Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 11). RC TISSUE=Rhabdomyosarcoma; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24. RX PubMed=7651818; DOI=10.1093/nar/23.14.2584; RA Zauberman A., Flusberg D., Haupt Y., Barak Y., Oren M.; RT "A functional p53-responsive intronic promoter is contained within the RT human mdm2 gene."; RL Nucleic Acids Res. 23:2584-2592(1995). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9. RX PubMed=9270029; RA Landers J.E., Cassel S.L., George D.L.; RT "Translational enhancement of mdm2 oncogene expression in human tumor RT cells containing a stabilized wild-type p53 protein."; RL Cancer Res. 57:3562-3568(1997). RN [12] RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-491 (ISOFORM MDM2-A1). RX PubMed=15315825; DOI=10.1016/j.gene.2004.05.015; RA Liang H., Atkins H., Abdel-Fattah R., Jones S.N., Lunec J.; RT "Genomic organisation of the human MDM2 oncogene and relationship to RT its alternatively spliced mRNAs."; RL Gene 338:217-223(2004). RN [13] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 301-481. RX PubMed=11087894; DOI=10.1016/S0027-5107(00)00112-3; RA Taubert H., Kappler M., Meye A., Bartel F., Schlott T., RA Lautenschlaeger C., Bache M., Schmidt H., Wuerl P.; RT "A MboII polymorphism in exon 11 of the human MDM2 gene occurring in RT normal blood donors and in soft tissue sarcoma patients: an indication RT for an increased cancer susceptibility?"; RL Mutat. Res. 456:39-44(2000). RN [14] RP SUBCELLULAR LOCATION, AND INTERACTION WITH TP53. RX PubMed=7689721; RA Olson D.C., Marechal V., Momand J., Chen J., Romocki C., Levine A.J.; RT "Identification and characterization of multiple mdm-2 proteins and RT mdm-2-p53 protein complexes."; RL Oncogene 8:2353-2360(1993). RN [15] RP MUTAGENESIS OF CYS-464. RX PubMed=9450543; DOI=10.1016/S0014-5793(97)01480-4; RA Honda R., Tanaka H., Yasuda H.; RT "Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53."; RL FEBS Lett. 420:25-27(1997). RN [16] RP MUTAGENESIS OF CYS-441 AND CYS-478. RX PubMed=10608892; DOI=10.1074/jbc.274.53.38189; RA Sharp D.A., Kratowicz S.A., Sank M.J., George D.L.; RT "Stabilization of the MDM2 oncoprotein by interaction with the RT structurally related MDMX protein."; RL J. Biol. Chem. 274:38189-38196(1999). RN [17] RP PHOSPHORYLATION BY ATM. RX PubMed=10611322; DOI=10.1073/pnas.96.26.14973; RA Khosravi R., Maya R., Gottlieb T., Oren M., Shiloh Y., Shkedy D.; RT "Rapid ATM-dependent phosphorylation of MDM2 precedes p53 accumulation RT in response to DNA damage."; RL Proc. Natl. Acad. Sci. U.S.A. 96:14973-14977(1999). RN [18] RP MUTAGENESIS. RX PubMed=10722742; DOI=10.1074/jbc.275.12.8945; RA Fang S., Jensen J.P., Ludwig R.L., Vousden K.H., Weissman A.M.; RT "Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself RT and p53."; RL J. Biol. Chem. 275:8945-8951(2000). RN [19] RP NUCLEOLAR LOCALIZATION SIGNAL. RX PubMed=10707090; DOI=10.1038/35004057; RA Lohrum M.A.E., Ashcroft M., Kubbutat M.H.G., Vousden K.H.; RT "Identification of a cryptic nucleolar-localization signal in MDM2."; RL Nat. Cell Biol. 2:179-181(2000). RN [20] RP MUTAGENESIS OF CYS-449. RX PubMed=10723139; DOI=10.1038/sj.onc.1203464; RA Honda R., Yasuda H.; RT "Activity of MDM2, a ubiquitin ligase, toward p53 or itself is RT dependent on the RING finger domain of the ligase."; RL Oncogene 19:1473-1476(2000). RN [21] RP PHOSPHORYLATION AT SER-240; SER-242; SER-246; SER-260 AND SER-262. RX PubMed=12167711; DOI=10.1128/MCB.22.17.6170-6182.2002; RA Blattner C., Hay T., Meek D.W., Lane D.P.; RT "Hypophosphorylation of Mdm2 augments p53 stability."; RL Mol. Cell. Biol. 22:6170-6182(2002). RN [22] RP INTERACTION WITH HIV-1 TAT. RX PubMed=12883554; DOI=10.1038/ncb1023; RA Bres V., Kiernan R.E., Linares L.K., Chable-Bessia C., Plechakova O., RA Treand C., Emiliani S., Peloponese J.-M., Jeang K.-T., Coux O., RA Scheffner M., Benkirane M.; RT "A non-proteolytic role for ubiquitin in Tat-mediated transactivation RT of the HIV-1 promoter."; RL Nat. Cell Biol. 5:754-761(2003). RN [23] RP FUNCTION IN UBIQUITINATION OF IGF1R, AND INTERACTION WITH IGF1R. RX PubMed=12821780; DOI=10.1073/pnas.1431613100; RA Girnita L., Girnita A., Larsson O.; RT "Mdm2-dependent ubiquitination and degradation of the insulin-like RT growth factor 1 receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 100:8247-8252(2003). RN [24] RP INTERACTION WITH FHIT. RX PubMed=15313915; DOI=10.1158/0008-5472.CAN-04-0195; RA Nishizaki M., Sasaki J., Fang B., Atkinson E.N., Minna J.D., RA Roth J.A., Ji L.; RT "Synergistic tumor suppression by coexpression of FHIT and p53 RT coincides with FHIT-mediated MDM2 inactivation and p53 stabilization RT in human non-small cell lung cancer cells."; RL Cancer Res. 64:5745-5752(2004). RN [25] RP INVOLVEMENT IN SUSCEPTIBILITY TO ACCELERATED TUMOR FORMATION. RX PubMed=15550242; DOI=10.1016/j.cell.2004.11.022; RA Bond G.L., Hu W., Bond E.E., Robins H., Lutzker S.G., Arva N.C., RA Bargonetti J., Bartel F., Taubert H., Wuerl P., Onel K., Yip L., RA Hwang S.J., Strong L.C., Lozano G., Levine A.J.; RT "A single nucleotide polymorphism in the MDM2 promoter attenuates the RT p53 tumor suppressor pathway and accelerates tumor formation in RT humans."; RL Cell 119:591-602(2004). RN [26] RP INTERACTION WITH DAXX. RX PubMed=15364927; DOI=10.1074/jbc.M406743200; RA Zhao L.Y., Liu J., Sidhu G.S., Niu Y., Liu Y., Wang R., Liao D.; RT "Negative regulation of p53 functions by Daxx and the involvement of RT MDM2."; RL J. Biol. Chem. 279:50566-50579(2004). RN [27] RP FUNCTION, INTERACTION WITH USP7, AND DEUBIQUITINATION BY USP7. RX PubMed=15053880; DOI=10.1016/S1097-2765(04)00157-1; RA Li M., Brooks C.L., Kon N., Gu W.; RT "A dynamic role of HAUSP in the p53-Mdm2 pathway."; RL Mol. Cell 13:879-886(2004). RN [28] RP FUNCTION, INTERACTION WITH PML AND RPL11, AND SUBCELLULAR LOCATION. RX PubMed=15195100; DOI=10.1038/ncb1147; RA Bernardi R., Scaglioni P.P., Bergmann S., Horn H.F., Vousden K.H., RA Pandolfi P.P.; RT "PML regulates p53 stability by sequestering Mdm2 to the nucleolus."; RL Nat. Cell Biol. 6:665-672(2004). RN [29] RP INTERACTION WITH ARRB1 AND ARRB2. RX PubMed=15878855; DOI=10.1074/jbc.M501129200; RA Girnita L., Shenoy S.K., Sehat B., Vasilcanu R., Girnita A., RA Lefkowitz R.J., Larsson O.; RT "{beta}-Arrestin is crucial for ubiquitination and down-regulation of RT the insulin-like growth factor-1 receptor by acting as adaptor for the RT MDM2 E3 ligase."; RL J. Biol. Chem. 280:24412-24419(2005). RN [30] RP INTERACTION WITH WWOX AND TP53. RX PubMed=16219768; DOI=10.1074/jbc.M505590200; RA Chang N.-S., Doherty J., Ensign A., Schultz L., Hsu L.-J., Hong Q.; RT "WOX1 is essential for tumor necrosis factor-, UV light-, RT staurosporine-, and p53-mediated cell death, and its tyrosine 33- RT phosphorylated form binds and stabilizes serine 46-phosphorylated RT p53."; RL J. Biol. Chem. 280:43100-43108(2005). RN [31] RP FUNCTION, AND INTERACTION WITH PSMA3. RX PubMed=16337594; DOI=10.1016/j.molcel.2005.10.017; RA Sdek P., Ying H., Chang D.L., Qiu W., Zheng H., Touitou R., RA Allday M.J., Xiao Z.X.; RT "MDM2 promotes proteasome-dependent ubiquitin-independent degradation RT of retinoblastoma protein."; RL Mol. Cell 20:699-708(2005). RN [32] RP FUNCTION, INTERACTION WITH MTBP, AND MUTAGENESIS OF CYS-464. RX PubMed=15632057; DOI=10.1128/MCB.25.2.545-553.2005; RA Brady M., Vlatkovic N., Boyd M.T.; RT "Regulation of p53 and MDM2 activity by MTBP."; RL Mol. Cell. Biol. 25:545-553(2005). RN [33] RP INTERACTION WITH CDK5RAP3 AND CDKN2A/ARF. RX PubMed=16173922; DOI=10.1042/BJ20050960; RA Wang J., He X., Luo Y., Yarbrough W.G.; RT "A novel ARF-binding protein (LZAP) alters ARF regulation of HDM2."; RL Biochem. J. 393:489-501(2006). RN [34] RP UBIQUITINATION, INTERACTION WITH PYHIN1, AND MUTAGENESIS OF CYS-464. RX PubMed=16479015; DOI=10.1128/MCB.26.5.1979-1996.2006; RA Ding Y., Lee J.-F., Lu H., Lee M.-H., Yan D.-H.; RT "Interferon-inducible protein IFIXalpha1 functions as a negative RT regulator of HDM2."; RL Mol. Cell. Biol. 26:1979-1996(2006). RN [35] RP IDENTIFICATION IN A COMPLEX WITH DAXX AND USP7, INTERACTION WITH DAXX, RP AND SUBCELLULAR LOCATION. RX PubMed=16845383; DOI=10.1038/ncb1442; RA Tang J., Qu L.K., Zhang J., Wang W., Michaelson J.S., Degenhardt Y.Y., RA El-Deiry W.S., Yang X.; RT "Critical role for Daxx in regulating Mdm2."; RL Nat. Cell Biol. 8:855-862(2006). RN [36] RP INTERACTION WITH CDKN2AIP. RX PubMed=17460193; DOI=10.1196/annals.1395.033; RA Kamrul H.M., Wadhwa R., Kaul S.C.; RT "CARF binds to three members (ARF, p53, and HDM2) of the p53 tumor- RT suppressor pathway."; RL Ann. N. Y. Acad. Sci. 1100:312-315(2007). RN [37] RP FUNCTION, INTERACTION WITH USP2, UBIQUITINATION, AND DEUBIQUITINATION RP BY USP2. RX PubMed=17290220; DOI=10.1038/sj.emboj.7601567; RA Stevenson L.F., Sparks A., Allende-Vega N., Xirodimas D.P., Lane D.P., RA Saville M.K.; RT "The deubiquitinating enzyme USP2a regulates the p53 pathway by RT targeting Mdm2."; RL EMBO J. 26:976-986(2007). RN [38] RP INVOLVEMENT IN SUSCEPTIBILITY TO ACCELERATED TUMOR FORMATION AND RP LI-FRAUMENI SYNDROME. RX PubMed=17003841; DOI=10.1038/sj.ejhg.5201715; RA Ruijs M.W., Schmidt M.K., Nevanlinna H., Tommiska J., Aittomaki K., RA Pruntel R., Verhoef S., Van't Veer L.J.; RT "The single-nucleotide polymorphism 309 in the MDM2 gene contributes RT to the Li-Fraumeni syndrome and related phenotypes."; RL Eur. J. Hum. Genet. 15:110-114(2007). RN [39] RP INTERACTION WITH TBRG1. RX PubMed=17110379; DOI=10.1074/jbc.M609612200; RA Tompkins V.S., Hagen J., Frazier A.A., Lushnikova T., Fitzgerald M.P., RA di Tommaso A.D., Ladeveze V., Domann F.E., Eischen C.M., Quelle D.E.; RT "A novel nuclear interactor of ARF and MDM2 (NIAM) that maintains RT chromosomal stability."; RL J. Biol. Chem. 282:1322-1333(2007). RN [40] RP INTERACTION WITH RBBP6. RX PubMed=17470788; DOI=10.1073/pnas.0701916104; RA Li L., Deng B., Xing G., Teng Y., Tian C., Cheng X., Yin X., Yang J., RA Gao X., Zhu Y., Sun Q., Zhang L., Yang X., He F.; RT "PACT is a negative regulator of p53 and essential for cell growth and RT embryonic development."; RL Proc. Natl. Acad. Sci. U.S.A. 104:7951-7956(2007). RN [41] RP INTERACTION WITH RFFL AND RNF34, AND AUTOUBIQUITINATION. RX PubMed=18382127; RA Yang W., Dicker D.T., Chen J., El-Deiry W.S.; RT "CARPs enhance p53 turnover by degrading 14-3-3sigma and stabilizing RT MDM2."; RL Cell Cycle 7:670-682(2008). RN [42] RP IDENTIFICATION IN A COMPLEX WITH DAXX; RASSF1 AND USP7, INTERACTION RP WITH RASSF1; USP7 AND DAXX, AND SUBCELLULAR LOCATION. RX PubMed=18566590; DOI=10.1038/emboj.2008.115; RA Song M.S., Song S.J., Kim S.Y., Oh H.J., Lim D.S.; RT "The tumour suppressor RASSF1A promotes MDM2 self-ubiquitination by RT disrupting the MDM2-DAXX-HAUSP complex."; RL EMBO J. 27:1863-1874(2008). RN [43] RP INTERACTION WITH UBXN6. RX PubMed=18768758; DOI=10.1091/mbc.E08-01-0067; RA Zweitzig D.R., Shcherbik N., Haines D.S.; RT "AAA ATPase p97 and adaptor UBXD1 suppress MDM2 ubiquitination and RT degradation and promote constitutive p53 turnover."; RL Mol. Biol. Cell 19:5029-5029(2008). RN [44] RP PHOSPHORYLATION AT SER-386; SER-395; SER-407; THR-419; SER-425 AND RP SER-429. RX PubMed=19816404; DOI=10.1038/emboj.2009.294; RA Cheng Q., Chen L., Li Z., Lane W.S., Chen J.; RT "ATM activates p53 by regulating MDM2 oligomerization and E3 RT processivity."; RL EMBO J. 28:3857-3867(2009). RN [45] RP FUNCTION, INTERACTION WITH RYBP, AND IDENTIFICATION IN A COMPLEX WITH RP RYBP AND TP53. RX PubMed=19098711; DOI=10.1038/embor.2008.231; RA Chen D., Zhang J., Li M., Rayburn E.R., Wang H., Zhang R.; RT "RYBP stabilizes p53 by modulating MDM2."; RL EMBO Rep. 10:166-172(2009). RN [46] RP FUNCTION, AND INTERACTION WITH MTA1. RX PubMed=19837670; DOI=10.1074/jbc.M109.056499; RA Li D.Q., Divijendra Natha Reddy S., Pakala S.B., Wu X., Zhang Y., RA Rayala S.K., Kumar R.; RT "MTA1 coregulator regulates p53 stability and function."; RL J. Biol. Chem. 284:34545-34552(2009). RN [47] RP PHOSPHORYLATION AT SER-166 BY SGK1. RX PubMed=19756449; DOI=10.1007/s00109-009-0525-5; RA Amato R., D'Antona L., Porciatti G., Agosti V., Menniti M., RA Rinaldo C., Costa N., Bellacchio E., Mattarocci S., Fuiano G., RA Soddu S., Paggi M.G., Lang F., Perrotti N.; RT "Sgk1 activates MDM2-dependent p53 degradation and affects cell RT proliferation, survival, and differentiation."; RL J. Mol. Med. 87:1221-1239(2009). RN [48] RP INTERACTION WITH HHV-8 PROTEIN VIRF4. RX PubMed=19369353; DOI=10.1128/JVI.02353-08; RA Lee H.R., Toth Z., Shin Y.C., Lee J.S., Chang H., Gu W., Oh T.K., RA Kim M.H., Jung J.U.; RT "Kaposi's sarcoma-associated herpesvirus viral interferon regulatory RT factor 4 targets MDM2 to deregulate the p53 tumor suppressor RT pathway."; RL J. Virol. 83:6739-6747(2009). RN [49] RP FUNCTION, INTERACTION WITH APEX1, AND MUTAGENESIS OF CYS-464. RX PubMed=19219073; DOI=10.1038/onc.2009.5; RA Busso C.S., Iwakuma T., Izumi T.; RT "Ubiquitination of mammalian AP endonuclease (APE1) regulated by the RT p53-MDM2 signaling pathway."; RL Oncogene 28:1616-1625(2009). RN [50] RP IDENTIFICATION. RX PubMed=19139490; DOI=10.1074/mcp.M800504-MCP200; RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., RA Zheng Z.B., Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., RA Zhang Y.K., Deng Y.L., Ying W.T., He S.M., Qian X.H.; RT "A strategy for precise and large scale identification of core RT fucosylated glycoproteins."; RL Mol. Cell. Proteomics 8:913-923(2009). RN [51] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-166, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [52] RP FUNCTION, AND INTERACTION WITH SNAI1. RX PubMed=20385133; DOI=10.1016/j.febslet.2010.04.006; RA Lim S.O., Kim H., Jung G.; RT "p53 inhibits tumor cell invasion via the degradation of snail protein RT in hepatocellular carcinoma."; RL FEBS Lett. 584:2231-2236(2010). RN [53] RP FUNCTION IN DYRK2 UBIQUITINATION, AND INTERACTION WITH DYRK2. RX PubMed=19965871; DOI=10.1074/jbc.M109.042341; RA Taira N., Yamamoto H., Yamaguchi T., Miki Y., Yoshida K.; RT "ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in the RT apoptotic response to DNA damage."; RL J. Biol. Chem. 285:4909-4919(2010). RN [54] RP INTERACTION WITH TRIM28 IN THE TRIM28/KAP1-ERBB4-MDM2 COMPLEX AND WITH RP TP53 IN THE TRIM28/KAP1-MDM2-P53/TP53 COMPLEX, FUNCTION, AND RP SUBCELLULAR LOCATION. RX PubMed=20858735; DOI=10.1158/1541-7786.MCR-10-0042; RA Gilmore-Hebert M., Ramabhadran R., Stern D.F.; RT "Interactions of ErbB4 and Kap1 connect the growth factor and DNA RT damage response pathways."; RL Mol. Cancer Res. 8:1388-1398(2010). RN [55] RP FUNCTION, INTERACTION WITH TP53 AND RFWD3, AND MUTAGENESIS OF CYS-464. RX PubMed=20173098; DOI=10.1073/pnas.0912094107; RA Fu X., Yucer N., Liu S., Li M., Yi P., Mu J.J., Yang T., Chu J., RA Jung S.Y., O'Malley B.W., Gu W., Qin J., Wang Y.; RT "RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53 RT stability in response to DNA damage."; RL Proc. Natl. Acad. Sci. U.S.A. 107:4579-4584(2010). RN [56] RP INTERACTION WITH USP2 AND MDM4. RX PubMed=19838211; DOI=10.1038/onc.2009.330; RA Allende-Vega N., Sparks A., Lane D.P., Saville M.K.; RT "MdmX is a substrate for the deubiquitinating enzyme USP2a."; RL Oncogene 29:432-441(2010). RN [57] RP FUNCTION, AND INTERACTION WITH SNAI1 AND NOTCH1. RX PubMed=22128911; DOI=10.1186/1741-7007-9-83; RA Lim S.O., Kim H.S., Quan X., Ahn S.M., Kim H., Hsieh D., Seong J.K., RA Jung G.; RT "Notch1 binds and induces degradation of Snail in hepatocellular RT carcinoma."; RL BMC Biol. 9:83-83(2011). RN [58] RP INTERACTION WITH TRIM13, AND UBIQUITINATION. RX PubMed=21333377; DOI=10.1016/j.ejcb.2010.12.001; RA Joo H.M., Kim J.Y., Jeong J.B., Seong K.M., Nam S.Y., Yang K.H., RA Kim C.S., Kim H.S., Jeong M., An S., Jin Y.W.; RT "Ret finger protein 2 enhances ionizing radiation-induced apoptosis RT via degradation of AKT and MDM2."; RL Eur. J. Cell Biol. 90:420-431(2011). RN [59] RP SUBCELLULAR LOCATION, AND INTERACTION WITH PML. RX PubMed=22869143; DOI=10.1038/onc.2012.332; RA Yang Q., Liao L., Deng X., Chen R., Gray N.S., Yates J.R. III, RA Lee J.D.; RT "BMK1 is involved in the regulation of p53 through disrupting the PML- RT MDM2 interaction."; RL Oncogene 32:3156-3164(2013). RN [60] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 25-109 IN COMPLEX WITH P53. RX PubMed=8875929; DOI=10.1126/science.274.5289.948; RA Kussie P.H., Gorina S., Marechal V., Elenbaas B., Moreau J., RA Levine A.J., Pavletich N.P.; RT "Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor RT transactivation domain."; RL Science 274:948-953(1996). RN [61] RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 224-232 IN COMPLEX WITH RP USP7, AND INTERACTION WITH USP7. RX PubMed=16402859; DOI=10.1371/journal.pbio.0040027; RA Hu M., Gu L., Li M., Jeffrey P.D., Gu W., Shi Y.; RT "Structural basis of competitive recognition of p53 and MDM2 by RT HAUSP/USP7: implications for the regulation of the p53-MDM2 pathway."; RL PLoS Biol. 4:228-239(2006). RN [62] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 145-150 IN COMPLEX WITH USP7, RP AND INTERACTION WITH USP7. RX PubMed=16474402; DOI=10.1038/nsmb1067; RA Sheng Y., Saridakis V., Sarkari F., Duan S., Wu T., Arrowsmith C.H., RA Frappier L.; RT "Molecular recognition of p53 and MDM2 by USP7/HAUSP."; RL Nat. Struct. Mol. Biol. 13:285-291(2006). CC -!- FUNCTION: E3 ubiquitin-protein ligase that mediates ubiquitination CC of p53/TP53, leading to its degradation by the proteasome. CC Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and CC apoptosis by binding its transcriptional activation domain. Also CC acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the CC nuclear export of p53/TP53. Promotes proteasome-dependent CC ubiquitin-independent degradation of retinoblastoma RB1 protein. CC Inhibits DAXX-mediated apoptosis by inducing its ubiquitination CC and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 CC complex involved in stabilizing p53/TP53. Also component of the CC TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA CC damage response pathways. Mediates ubiquitination and subsequent CC proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R CC and SNAI1 and promotes them to proteasomal degradation. CC {ECO:0000269|PubMed:12821780, ECO:0000269|PubMed:15053880, CC ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15632057, CC ECO:0000269|PubMed:16337594, ECO:0000269|PubMed:17290220, CC ECO:0000269|PubMed:19098711, ECO:0000269|PubMed:19219073, CC ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19965871, CC ECO:0000269|PubMed:20173098, ECO:0000269|PubMed:20385133, CC ECO:0000269|PubMed:20858735, ECO:0000269|PubMed:22128911}. CC -!- SUBUNIT: Interacts with p53/TP53, TP73/p73, RBL5 and RP11. Binds CC specifically to RNA. Can interact with RB1, E1A-associated protein CC EP300 and the E2F1 transcription factor. Forms a ternary complex CC with p53/TP53 and WWOX. Interacts with CDKN2AIP, RFWD3, USP7, CC PYHIN1, UBXN6, and RBBP6. Interacts with ARRB1 and ARRB2. CC Interacts with PSMA3. Found in a trimeric complex with MDM2, MDM4 CC and USP2. Interacts with USP2 (via N-terminus and C-terminus). CC Interacts with MDM4. Part of a complex with MDM2, DAXX, RASSF1 and CC USP7. Part of a complex with DAXX, MDM2 and USP7. Interacts CC directly with DAXX and USP7. Interacts (via C-terminus) with CC RASSF1 isoform A (via N-terminus); the interaction is independent CC of TP53. Interacts with APEX1; leading to its ubiquitination and CC degradation. Interacts with RYBP; this inhibits ubiquitination of CC TP53. Identified in a complex with RYBP and p53/TP53. Also CC component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in CC regulating p53/TP53 stabilization and activity. Binds directly CC both p53/TP53 and TRIM28. Component of the TRIM28/KAP1-ERBB4-MDM2 CC complex involved in connecting growth factor responses with DNA CC damage. Interacts directly with both TRIM28 and ERBB4 in the CC complex. Interacts with DYRK2. Interacts with IGF1R. Interacts CC with TRIM13; the interaction ubiquitinates MDM2 leading to its CC proteasomal degradation. Interacts with SNAI1; this interaction CC promotes SNAI1 ubiquitination. Interacts with NOTCH1 (via CC intracellular domain). Interacts with FHIT. Interacts with RFFL CC and RNF34; the interaction stabilizes MDM2. Interacts with CC CDK5RAP3 and CDKN2A/ARF; form a ternary complex involved in CC regulation of p53/TP53 (PubMed:16173922). Interacts with MTA1. CC Interacts with AARB2. Interacts with MTBP. Interacts with PML. CC Interacts with RPL11. Interacts with TBRG1. Interacts with herpes CC virus 8 protein v-IRF4. Interacts with and ubiquitinates HIV-1 CC Tat. {ECO:0000269|PubMed:11351297, ECO:0000269|PubMed:12821780, CC ECO:0000269|PubMed:12883554, ECO:0000269|PubMed:15053880, CC ECO:0000269|PubMed:15195100, ECO:0000269|PubMed:15313915, CC ECO:0000269|PubMed:15364927, ECO:0000269|PubMed:15632057, CC ECO:0000269|PubMed:15878855, ECO:0000269|PubMed:16173922, CC ECO:0000269|PubMed:16219768, ECO:0000269|PubMed:16337594, CC ECO:0000269|PubMed:16402859, ECO:0000269|PubMed:16474402, CC ECO:0000269|PubMed:16479015, ECO:0000269|PubMed:16845383, CC ECO:0000269|PubMed:17110379, ECO:0000269|PubMed:17290220, CC ECO:0000269|PubMed:17460193, ECO:0000269|PubMed:17470788, CC ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:18566590, CC ECO:0000269|PubMed:18768758, ECO:0000269|PubMed:19098711, CC ECO:0000269|PubMed:19219073, ECO:0000269|PubMed:19369353, CC ECO:0000269|PubMed:19837670, ECO:0000269|PubMed:19838211, CC ECO:0000269|PubMed:19965871, ECO:0000269|PubMed:20173098, CC ECO:0000269|PubMed:20385133, ECO:0000269|PubMed:20858735, CC ECO:0000269|PubMed:21333377, ECO:0000269|PubMed:22128911, CC ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:7689721, CC ECO:0000269|PubMed:8875929}. CC -!- INTERACTION: CC Self; NbExp=4; IntAct=EBI-389668, EBI-389668; CC P25098:ADRBK1; NbExp=4; IntAct=EBI-389668, EBI-3904795; CC P31749:AKT1; NbExp=4; IntAct=EBI-389668, EBI-296087; CC P10275:AR; NbExp=2; IntAct=EBI-389668, EBI-608057; CC Q9Y297:BTRC; NbExp=9; IntAct=EBI-389668, EBI-307461; CC P42574:CASP3; NbExp=2; IntAct=EBI-389668, EBI-524064; CC Q8N726:CDKN2A; NbExp=5; IntAct=EBI-389668, EBI-625922; CC P48729:CSNK1A1; NbExp=3; IntAct=EBI-389668, EBI-1383726; CC P48729-2:CSNK1A1; NbExp=3; IntAct=EBI-389668, EBI-2040168; CC P48730:CSNK1D; NbExp=6; IntAct=EBI-389668, EBI-751621; CC Q06486:Csnk1d (xeno); NbExp=2; IntAct=EBI-389668, EBI-2910316; CC P49674:CSNK1E; NbExp=3; IntAct=EBI-389668, EBI-749343; CC Q13616:CUL1; NbExp=3; IntAct=EBI-389668, EBI-359390; CC Q9UER7:DAXX; NbExp=18; IntAct=EBI-389668, EBI-77321; CC P78352:DLG4; NbExp=3; IntAct=EBI-389668, EBI-80389; CC P68104:EEF1A1; NbExp=9; IntAct=EBI-389668, EBI-352162; CC P03372:ESR1; NbExp=2; IntAct=EBI-389668, EBI-78473; CC P15311:EZR; NbExp=3; IntAct=EBI-389668, EBI-1056902; CC Q9UKB1:FBXW11; NbExp=4; IntAct=EBI-389668, EBI-355189; CC Q00688:FKBP3; NbExp=2; IntAct=EBI-389668, EBI-1044081; CC Q62446:Fkbp3 (xeno); NbExp=4; IntAct=EBI-389668, EBI-8313562; CC Q9BVP2:GNL3; NbExp=3; IntAct=EBI-389668, EBI-641642; CC Q9NVN8:GNL3L; NbExp=8; IntAct=EBI-389668, EBI-746682; CC Q5T7V8:GORAB; NbExp=6; IntAct=EBI-389668, EBI-3917143; CC P61978:HNRNPK; NbExp=2; IntAct=EBI-389668, EBI-304185; CC P08069:IGF1R; NbExp=2; IntAct=EBI-389668, EBI-475981; CC Q8N9B5:JMY; NbExp=2; IntAct=EBI-389668, EBI-866435; CC P05412:JUN; NbExp=3; IntAct=EBI-389668, EBI-852823; CC P17535:JUND; NbExp=3; IntAct=EBI-389668, EBI-2682803; CC O15151:MDM4; NbExp=8; IntAct=EBI-389668, EBI-398437; CC P19338:NCL; NbExp=8; IntAct=EBI-389668, EBI-346967; CC P06748:NPM1; NbExp=5; IntAct=EBI-389668, EBI-78579; CC Q61937:Npm1 (xeno); NbExp=2; IntAct=EBI-389668, EBI-626362; CC Q15466:NR0B2; NbExp=4; IntAct=EBI-389668, EBI-3910729; CC Q96FW1:OTUB1; NbExp=5; IntAct=EBI-389668, EBI-1058491; CC P53350:PLK1; NbExp=7; IntAct=EBI-389668, EBI-476768; CC P29590:PML; NbExp=6; IntAct=EBI-389668, EBI-295890; CC P29590-5:PML; NbExp=6; IntAct=EBI-389668, EBI-304008; CC O15297:PPM1D; NbExp=4; IntAct=EBI-389668, EBI-1551512; CC Q13362:PPP2R5C; NbExp=5; IntAct=EBI-389668, EBI-1266156; CC P25788:PSMA3; NbExp=2; IntAct=EBI-389668, EBI-348380; CC P61289:PSME3; NbExp=8; IntAct=EBI-389668, EBI-355546; CC Q9NS23:RASSF1; NbExp=5; IntAct=EBI-389668, EBI-367363; CC P06400:RB1; NbExp=4; IntAct=EBI-389668, EBI-491274; CC P62913:RPL11; NbExp=11; IntAct=EBI-389668, EBI-354380; CC P62829:RPL23; NbExp=3; IntAct=EBI-389668, EBI-353303; CC P46777:RPL5; NbExp=5; IntAct=EBI-389668, EBI-358018; CC P42677:RPS27; NbExp=5; IntAct=EBI-389668, EBI-356336; CC Q71UM5:RPS27L; NbExp=6; IntAct=EBI-389668, EBI-355126; CC P23396:RPS3; NbExp=8; IntAct=EBI-389668, EBI-351193; CC P62081:RPS7; NbExp=15; IntAct=EBI-389668, EBI-354360; CC Q8N488:RYBP; NbExp=11; IntAct=EBI-389668, EBI-752324; CC Q92736:RYR2; NbExp=2; IntAct=EBI-389668, EBI-1170425; CC P23297:S100A1; NbExp=2; IntAct=EBI-389668, EBI-743686; CC P29034:S100A2; NbExp=2; IntAct=EBI-389668, EBI-752230; CC P26447:S100A4; NbExp=3; IntAct=EBI-389668, EBI-717058; CC P06703:S100A6; NbExp=2; IntAct=EBI-389668, EBI-352877; CC P04271:S100B; NbExp=2; IntAct=EBI-389668, EBI-458391; CC Q01105:SET; NbExp=2; IntAct=EBI-389668, EBI-1053182; CC P04637:TP53; NbExp=65; IntAct=EBI-389668, EBI-366083; CC P0CG48:UBC; NbExp=6; IntAct=EBI-389668, EBI-3390054; CC O75604:USP2; NbExp=4; IntAct=EBI-389668, EBI-743272; CC Q93009:USP7; NbExp=18; IntAct=EBI-389668, EBI-302474; CC Q2HR73:vIRF-4 (xeno); NbExp=2; IntAct=EBI-389668, EBI-9001898; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm. Cytoplasm. Nucleus, CC nucleolus. Note=Expressed predominantly in the nucleoplasm. CC Interaction with ARF(P14) results in the localization of both CC proteins to the nucleolus. The nucleolar localization signals in CC both ARF(P14) and MDM2 may be necessary to allow efficient CC nucleolar localization of both proteins. Colocalizes with RASSF1 CC isoform A in the nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=11; CC Name=Mdm2; CC IsoId=Q00987-1; Sequence=Displayed; CC Name=Mdm2-A; CC IsoId=Q00987-2; Sequence=VSP_003208; CC Name=Mdm2-A1; CC IsoId=Q00987-3; Sequence=VSP_003208, VSP_003214; CC Name=Mdm2-B; CC IsoId=Q00987-4; Sequence=VSP_003209; CC Name=Mdm2-C; CC IsoId=Q00987-5; Sequence=VSP_003211; CC Name=Mdm2-D; CC IsoId=Q00987-6; Sequence=VSP_003210; CC Name=Mdm2-E; CC IsoId=Q00987-7; Sequence=VSP_003212, VSP_003213; CC Name=Mdm2-alpha; CC IsoId=Q00987-8; Sequence=VSP_003207; CC Name=Mdm2-F; CC IsoId=Q00987-9; Sequence=VSP_022578; CC Note=Does not interact with p53/TP53.; CC Name=Mdm2-G; CC IsoId=Q00987-10; Sequence=VSP_022579; CC Name=11; CC IsoId=Q00987-11; Sequence=VSP_037997; CC -!- TISSUE SPECIFICITY: Ubiquitous. Isoform Mdm2-A, isoform Mdm2-B, CC isoform Mdm2-C, isoform Mdm2-D, isoform Mdm2-E, isoform Mdm2-F and CC isoform Mdm2-G are observed in a range of cancers but absent in CC normal tissues. CC -!- INDUCTION: By DNA damage. CC -!- DOMAIN: Region I is sufficient for binding p53 and inhibiting its CC G1 arrest and apoptosis functions. It also binds p73 and E2F1. CC Region II contains most of a central acidic region required for CC interaction with ribosomal protein L5 and a putative C4-type zinc CC finger. The RING finger domain which coordinates two molecules of CC zinc interacts specifically with RNA whether or not zinc is CC present and mediates the heterooligomerization with MDM4. It is CC also essential for its ubiquitin ligase E3 activity toward p53 and CC itself. CC -!- PTM: Phosphorylation on Ser-166 by SGK1 activates ubiquitination CC of p53/TP53. Phosphorylated at multiple sites near the RING domain CC by ATM upon DNA damage; this prevents oligomerization and E3 CC ligase processivity and impedes constitutive p53/TP53 degradation. CC {ECO:0000269|PubMed:10611322, ECO:0000269|PubMed:12167711, CC ECO:0000269|PubMed:18382127, ECO:0000269|PubMed:19756449, CC ECO:0000269|PubMed:19816404}. CC -!- PTM: Autoubiquitination leads to proteasomal degradation; CC resulting in p53/TP53 activation it may be regulated by SFN. Also CC ubiquitinated by TRIM13. Deubiquitinated by USP2 leads to its CC accumulation and increases deubiquitination and degradation of CC p53/TP53. Deubiquitinated by USP7 leading to its stabilization. CC {ECO:0000269|PubMed:18382127}. CC -!- POLYMORPHISM: A polymorphism in the MDM2 promoter is associated CC with susceptibility to accelerated tumor formation in both CC hereditary and sporadic cancers [MIM:614401]. It also contributes CC to susceptibility to Li-Fraumeni syndrome, in patients carrying a CC TP53 germline mutation. CC -!- DISEASE: Note=Seems to be amplified in certain tumors (including CC soft tissue sarcomas, osteosarcomas and gliomas). A higher CC frequency of splice variants lacking p53 binding domain sequences CC was found in late-stage and high-grade ovarian and bladder CC carcinomas. Four of the splice variants show loss of p53 binding. CC -!- MISCELLANEOUS: MDM2 RING finger mutations that failed to CC ubiquitinate p53 in vitro did not target p53 for degradation when CC expressed in cells. CC -!- SIMILARITY: Belongs to the MDM2/MDM4 family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 RanBP2-type zinc finger. CC {ECO:0000255|PROSITE-ProRule:PRU00322}. CC -!- SIMILARITY: Contains 1 RING-type zinc finger. CC {ECO:0000255|PROSITE-ProRule:PRU00175}. CC -!- SIMILARITY: Contains 1 SWIB domain. {ECO:0000305}. CC -!- CAUTION: A report observed N-glycosylation at Asn-349 CC (PubMed:19139490). However, as the protein is not extracellular, CC additional evidences are required to confirm this result. CC {ECO:0000305|PubMed:19139490}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/MDM2ID115ch12q15.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/mdm2/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Mdm2 entry; CC URL="https://en.wikipedia.org/wiki/Mdm2"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M92424; AAA60568.1; -; mRNA. DR EMBL; Z12020; CAA78055.1; -; mRNA. DR EMBL; U33199; AAA75514.1; -; mRNA. DR EMBL; U33200; AAA75515.1; -; mRNA. DR EMBL; U33201; AAA75516.1; -; mRNA. DR EMBL; U33202; AAA75517.1; -; mRNA. DR EMBL; U33203; AAA75518.1; -; mRNA. DR EMBL; AF092844; AAL40179.1; -; mRNA. DR EMBL; AF092845; AAL40180.1; -; mRNA. DR EMBL; AK290341; BAF83030.1; -; mRNA. DR EMBL; BT007258; AAP35922.1; -; mRNA. DR EMBL; AF527840; AAM78554.1; -; Genomic_DNA. DR EMBL; AC025423; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC009893; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; U28935; AAA82237.1; -; Genomic_DNA. DR EMBL; U39736; AAA82061.1; -; Genomic_DNA. DR EMBL; AF201370; AAF42995.1; -; mRNA. DR EMBL; AJ251943; CAB64448.1; -; Genomic_DNA. DR CCDS; CCDS61189.1; -. [Q00987-5] DR CCDS; CCDS8986.2; -. [Q00987-11] DR PIR; S24354; S24354. DR RefSeq; NP_001138811.1; NM_001145339.2. DR RefSeq; NP_001265391.1; NM_001278462.1. [Q00987-5] DR RefSeq; NP_002383.2; NM_002392.5. [Q00987-11] DR RefSeq; XP_005268929.1; XM_005268872.3. [Q00987-1] DR RefSeq; XP_006719462.1; XM_006719399.2. [Q00987-8] DR UniGene; Hs.484551; -. DR UniGene; Hs.733536; -. DR PDB; 1RV1; X-ray; 2.30 A; A/B/C=25-109. DR PDB; 1T4E; X-ray; 2.60 A; A/B=17-111. DR PDB; 1T4F; X-ray; 1.90 A; M=17-125. DR PDB; 1YCR; X-ray; 2.60 A; A=17-125. DR PDB; 1Z1M; NMR; -; A=1-118. DR PDB; 2AXI; X-ray; 1.40 A; A=17-125. DR PDB; 2C6A; NMR; -; A=290-335. DR PDB; 2C6B; NMR; -; A=290-335. DR PDB; 2F1Y; X-ray; 1.70 A; A=224-232. DR PDB; 2FOP; X-ray; 2.10 A; B=145-150. DR PDB; 2GV2; X-ray; 1.80 A; A=17-125. DR PDB; 2HDP; NMR; -; A/B=429-491. DR PDB; 2LZG; NMR; -; A=1-125. DR PDB; 2M86; NMR; -; B=17-125. DR PDB; 2MPS; NMR; -; A=3-109. DR PDB; 2RUH; NMR; -; A=6-102. DR PDB; 2VJE; X-ray; 2.20 A; A/C=428-491. DR PDB; 2VJF; X-ray; 2.30 A; A/C=428-491. DR PDB; 3EQS; X-ray; 1.65 A; A=25-109. DR PDB; 3G03; X-ray; 1.80 A; A/C=18-125. DR PDB; 3IUX; X-ray; 1.65 A; A/C=25-109. DR PDB; 3IWY; X-ray; 1.93 A; A/C=25-109. DR PDB; 3JZK; X-ray; 2.10 A; A=17-111. DR PDB; 3JZR; X-ray; 2.10 A; A=17-125. DR PDB; 3JZS; X-ray; 1.78 A; A=24-109. DR PDB; 3LBK; X-ray; 2.30 A; A=18-111. DR PDB; 3LBL; X-ray; 1.60 A; A/C/E=18-111. DR PDB; 3LNJ; X-ray; 2.40 A; A/C/E=25-109. DR PDB; 3LNZ; X-ray; 1.95 A; A/C/E/G/I/K/M/O=25-109. DR PDB; 3MQS; X-ray; 2.40 A; D=394-403. DR PDB; 3TJ2; X-ray; 2.10 A; A/C=18-111. DR PDB; 3TPX; X-ray; 1.80 A; A/C/E=25-109. DR PDB; 3TU1; X-ray; 1.60 A; A=18-125. DR PDB; 3V3B; X-ray; 2.00 A; A/B=24-110. DR PDB; 3VBG; X-ray; 2.80 A; A/B/C/D=25-109. DR PDB; 3VZV; X-ray; 2.80 A; A/B=25-109. DR PDB; 3W69; X-ray; 1.90 A; A/B=25-109. DR PDB; 4DIJ; X-ray; 1.90 A; A/B=17-111. DR PDB; 4ERE; X-ray; 1.80 A; A/B=17-111. DR PDB; 4ERF; X-ray; 2.00 A; A/C/E=17-111. DR PDB; 4HBM; X-ray; 1.90 A; A/B/C/D/E/F/G/H=6-125. DR PDB; 4HFZ; X-ray; 2.69 A; A/C=17-125. DR PDB; 4HG7; X-ray; 1.60 A; A=17-108. DR PDB; 4JV7; X-ray; 2.20 A; A=18-111. DR PDB; 4JV9; X-ray; 2.50 A; A=18-111. DR PDB; 4JVE; X-ray; 2.30 A; A=18-111. DR PDB; 4JVR; X-ray; 1.70 A; A/C/E=18-111. DR PDB; 4JWR; X-ray; 2.35 A; A/B/C=17-111. DR PDB; 4MDN; X-ray; 1.90 A; A=18-110. DR PDB; 4MDQ; X-ray; 2.12 A; A=25-110. DR PDB; 4OAS; X-ray; 1.70 A; A/C/E=17-111. DR PDB; 4OBA; X-ray; 1.60 A; A/B/C=17-111. DR PDB; 4OCC; X-ray; 1.80 A; A/C/E=17-111. DR PDB; 4ODE; X-ray; 1.80 A; A=6-110. DR PDB; 4ODF; X-ray; 2.20 A; A=6-110. DR PDB; 4OGN; X-ray; 1.38 A; A=6-110. DR PDB; 4OGT; X-ray; 1.54 A; A=6-110. DR PDB; 4OGV; X-ray; 2.20 A; A/B/C=17-111. DR PDB; 4OQ3; X-ray; 2.30 A; A/B/C/D=17-111. DR PDB; 4QO4; X-ray; 1.70 A; A=17-111. DR PDB; 4QOC; X-ray; 1.70 A; A/C/E/G/I/K=17-111. DR PDB; 4UMN; X-ray; 1.99 A; A/B=6-125. DR PDB; 4WT2; X-ray; 1.42 A; A=6-110. DR PDB; 4XXB; X-ray; 2.40 A; B=290-437. DR PDB; 4ZYC; X-ray; 1.95 A; A/B/C=17-111. DR PDB; 4ZYF; X-ray; 1.80 A; A=17-111. DR PDB; 4ZYI; X-ray; 1.67 A; A=17-111. DR PDBsum; 1RV1; -. DR PDBsum; 1T4E; -. DR PDBsum; 1T4F; -. DR PDBsum; 1YCR; -. DR PDBsum; 1Z1M; -. DR PDBsum; 2AXI; -. DR PDBsum; 2C6A; -. DR PDBsum; 2C6B; -. DR PDBsum; 2F1Y; -. DR PDBsum; 2FOP; -. DR PDBsum; 2GV2; -. DR PDBsum; 2HDP; -. DR PDBsum; 2LZG; -. DR PDBsum; 2M86; -. DR PDBsum; 2MPS; -. DR PDBsum; 2RUH; -. DR PDBsum; 2VJE; -. DR PDBsum; 2VJF; -. DR PDBsum; 3EQS; -. DR PDBsum; 3G03; -. DR PDBsum; 3IUX; -. DR PDBsum; 3IWY; -. DR PDBsum; 3JZK; -. DR PDBsum; 3JZR; -. DR PDBsum; 3JZS; -. DR PDBsum; 3LBK; -. DR PDBsum; 3LBL; -. DR PDBsum; 3LNJ; -. DR PDBsum; 3LNZ; -. DR PDBsum; 3MQS; -. DR PDBsum; 3TJ2; -. DR PDBsum; 3TPX; -. DR PDBsum; 3TU1; -. DR PDBsum; 3V3B; -. DR PDBsum; 3VBG; -. DR PDBsum; 3VZV; -. DR PDBsum; 3W69; -. DR PDBsum; 4DIJ; -. DR PDBsum; 4ERE; -. DR PDBsum; 4ERF; -. DR PDBsum; 4HBM; -. DR PDBsum; 4HFZ; -. DR PDBsum; 4HG7; -. DR PDBsum; 4JV7; -. DR PDBsum; 4JV9; -. DR PDBsum; 4JVE; -. DR PDBsum; 4JVR; -. DR PDBsum; 4JWR; -. DR PDBsum; 4MDN; -. DR PDBsum; 4MDQ; -. DR PDBsum; 4OAS; -. DR PDBsum; 4OBA; -. DR PDBsum; 4OCC; -. DR PDBsum; 4ODE; -. DR PDBsum; 4ODF; -. DR PDBsum; 4OGN; -. DR PDBsum; 4OGT; -. DR PDBsum; 4OGV; -. DR PDBsum; 4OQ3; -. DR PDBsum; 4QO4; -. DR PDBsum; 4QOC; -. DR PDBsum; 4UMN; -. DR PDBsum; 4WT2; -. DR PDBsum; 4XXB; -. DR PDBsum; 4ZYC; -. DR PDBsum; 4ZYF; -. DR PDBsum; 4ZYI; -. DR DisProt; DP00334; -. DR ProteinModelPortal; Q00987; -. DR SMR; Q00987; 11-110, 290-335, 432-491. DR BioGrid; 110358; 742. DR DIP; DIP-392N; -. DR IntAct; Q00987; 181. DR MINT; MINT-101583; -. DR STRING; 9606.ENSP00000417281; -. DR BindingDB; Q00987; -. DR ChEMBL; CHEMBL5023; -. DR PhosphoSite; Q00987; -. DR DMDM; 266516; -. DR MaxQB; Q00987; -. DR PaxDb; Q00987; -. DR PRIDE; Q00987; -. DR DNASU; 4193; -. DR Ensembl; ENST00000258149; ENSP00000258149; ENSG00000135679. [Q00987-11] DR Ensembl; ENST00000299252; ENSP00000299252; ENSG00000135679. [Q00987-5] DR Ensembl; ENST00000356290; ENSP00000348637; ENSG00000135679. [Q00987-5] DR Ensembl; ENST00000360430; ENSP00000353611; ENSG00000135679. [Q00987-2] DR Ensembl; ENST00000393413; ENSP00000377065; ENSG00000135679. [Q00987-4] DR GeneID; 4193; -. DR UCSC; uc001sui.4; human. [Q00987-11] DR UCSC; uc001sun.5; human. [Q00987-5] DR UCSC; uc001suo.4; human. [Q00987-2] DR UCSC; uc009zqy.1; human. [Q00987-1] DR UCSC; uc009zrc.4; human. [Q00987-4] DR UCSC; uc009zrh.4; human. [Q00987-3] DR CTD; 4193; -. DR GeneCards; MDM2; -. DR HGNC; HGNC:6973; MDM2. DR HPA; CAB000086; -. DR HPA; CAB016303; -. DR MIM; 164785; gene. DR MIM; 614401; phenotype. DR neXtProt; NX_Q00987; -. DR Orphanet; 99970; Dedifferentiated liposarcoma. DR Orphanet; 524; Li-Fraumeni syndrome. DR Orphanet; 99971; Well-differentiated liposarcoma. DR PharmGKB; PA30718; -. DR eggNOG; ENOG410IGXG; Eukaryota. DR eggNOG; ENOG41125MP; LUCA. DR GeneTree; ENSGT00530000063539; -. DR HOVERGEN; HBG013472; -. DR InParanoid; Q00987; -. DR OMA; FEREETQ; -. DR OrthoDB; EOG7RRF7T; -. DR PhylomeDB; Q00987; -. DR TreeFam; TF105306; -. DR BRENDA; 6.3.2.19; 2681. DR Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol. DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence. DR Reactome; R-HSA-2559585; Oncogene Induced Senescence. DR Reactome; R-HSA-399719; Trafficking of AMPA receptors. DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer. DR Reactome; R-HSA-69541; Stabilization of p53. DR SignaLink; Q00987; -. DR ChiTaRS; MDM2; human. DR EvolutionaryTrace; Q00987; -. DR GeneWiki; Mdm2; -. DR GenomeRNAi; 4193; -. DR NextBio; 16526; -. DR PMAP-CutDB; Q00987; -. DR PRO; PR:Q00987; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; Q00987; -. DR ExpressionAtlas; Q00987; baseline and differential. DR Genevisible; Q00987; HS. DR GO; GO:0005737; C:cytoplasm; IMP:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030666; C:endocytic vesicle membrane; TAS:Reactome. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IMP:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0043234; C:protein complex; IDA:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0016874; F:ligase activity; IDA:UniProtKB. DR GO; GO:0002039; F:p53 binding; IPI:UniProtKB. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IMP:BHF-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0004842; F:ubiquitin-protein transferase activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0071456; P:cellular response to hypoxia; IEP:UniProtKB. DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IMP:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0045184; P:establishment of protein localization; IDA:BHF-UCL. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:InterPro. DR GO; GO:0071157; P:negative regulation of cell cycle arrest; IDA:BHF-UCL. DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IDA:BHF-UCL. DR GO; GO:1901797; P:negative regulation of signal transduction by p53 class mediator; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome. DR GO; GO:0018205; P:peptidyl-lysine modification; IMP:BHF-UCL. DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome. DR GO; GO:0008284; P:positive regulation of cell proliferation; TAS:BHF-UCL. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:BHF-UCL. DR GO; GO:0006461; P:protein complex assembly; IDA:UniProtKB. DR GO; GO:0031648; P:protein destabilization; IDA:BHF-UCL. DR GO; GO:0034504; P:protein localization to nucleus; IDA:BHF-UCL. DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB. DR GO; GO:0042787; P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IDA:UniProtKB. DR GO; GO:0042176; P:regulation of protein catabolic process; IDA:UniProtKB. DR GO; GO:0046677; P:response to antibiotic; IEP:UniProtKB. DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome. DR GO; GO:0007089; P:traversing start control point of mitotic cell cycle; IEA:Ensembl. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. DR Gene3D; 1.10.245.10; -; 1. DR Gene3D; 3.30.40.10; -; 1. DR InterPro; IPR028340; Mdm2. DR InterPro; IPR015459; MDM2_E3_ligase. DR InterPro; IPR016495; p53_neg-reg_MDM_2/4. DR InterPro; IPR003121; SWIB_MDM2_domain. DR InterPro; IPR001876; Znf_RanBP2. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR13844:SF15; PTHR13844:SF15; 1. DR Pfam; PF02201; SWIB; 1. DR Pfam; PF00641; zf-RanBP; 1. DR PIRSF; PIRSF500700; MDM2; 1. DR PIRSF; PIRSF006748; p53_MDM_2/4; 1. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF47592; SSF47592; 2. DR SUPFAM; SSF90209; SSF90209; 1. DR PROSITE; PS01358; ZF_RANBP2_1; 1. DR PROSITE; PS50199; ZF_RANBP2_2; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; KW Host-virus interaction; Ligase; Metal-binding; Nucleus; KW Phosphoprotein; Proto-oncogene; Reference proteome; Ubl conjugation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1 491 E3 ubiquitin-protein ligase Mdm2. FT /FTId=PRO_0000157332. FT DOMAIN 27 107 SWIB. FT ZN_FING 299 328 RanBP2-type. {ECO:0000255|PROSITE- FT ProRule:PRU00322}. FT ZN_FING 438 479 RING-type. {ECO:0000255|PROSITE- FT ProRule:PRU00175}. FT REGION 1 110 Necessary for interaction with USP2. FT REGION 150 230 Interaction with PYHIN1 and necessary for FT interaction with RFFL and RNF34. FT {ECO:0000269|PubMed:16479015, FT ECO:0000269|PubMed:18382127}. FT REGION 170 306 Interaction with MTBP. {ECO:0000250}. FT REGION 210 304 ARF-binding. FT REGION 223 232 Interaction with USP7. FT REGION 242 331 Region II. FT REGION 276 491 Necessary for interaction with USP2. FT MOTIF 179 185 Nuclear localization signal. FT {ECO:0000255}. FT MOTIF 190 202 Nuclear export signal. FT MOTIF 466 473 Nucleolar localization signal. FT {ECO:0000255}. FT COMPBIAS 210 215 Poly-Ser. FT COMPBIAS 243 301 Asp/Glu-rich (acidic). FT MOD_RES 166 166 Phosphoserine; by SGK1. FT {ECO:0000244|PubMed:19690332, FT ECO:0000269|PubMed:19756449}. FT MOD_RES 190 190 Phosphoserine. FT {ECO:0000250|UniProtKB:P23804}. FT MOD_RES 240 240 Phosphoserine. FT {ECO:0000269|PubMed:12167711}. FT MOD_RES 242 242 Phosphoserine. FT {ECO:0000269|PubMed:12167711}. FT MOD_RES 246 246 Phosphoserine. FT {ECO:0000269|PubMed:12167711}. FT MOD_RES 260 260 Phosphoserine. FT {ECO:0000269|PubMed:12167711}. FT MOD_RES 262 262 Phosphoserine. FT {ECO:0000269|PubMed:12167711}. FT MOD_RES 386 386 Phosphoserine; by ATM. FT {ECO:0000269|PubMed:19816404}. FT MOD_RES 395 395 Phosphoserine; by ATM. FT {ECO:0000269|PubMed:19816404}. FT MOD_RES 407 407 Phosphoserine; by ATM. FT {ECO:0000269|PubMed:19816404}. FT MOD_RES 419 419 Phosphothreonine; by ATM. FT {ECO:0000269|PubMed:19816404}. FT MOD_RES 425 425 Phosphoserine; by ATM. FT {ECO:0000269|PubMed:19816404}. FT MOD_RES 429 429 Phosphoserine; by ATM. FT {ECO:0000269|PubMed:19816404}. FT VAR_SEQ 1 61 Missing (in isoform Mdm2-alpha). FT {ECO:0000303|PubMed:10597303}. FT /FTId=VSP_003207. FT VAR_SEQ 1 1 M -> MVRSRQM (in isoform 11). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_037997. FT VAR_SEQ 28 300 Missing (in isoform Mdm2-B). FT {ECO:0000303|PubMed:8705862}. FT /FTId=VSP_003209. FT VAR_SEQ 28 222 Missing (in isoform Mdm2-A and isoform FT Mdm2-A1). {ECO:0000303|PubMed:15315825, FT ECO:0000303|PubMed:8705862}. FT /FTId=VSP_003208. FT VAR_SEQ 30 388 Missing (in isoform Mdm2-D). FT {ECO:0000303|PubMed:8705862}. FT /FTId=VSP_003210. FT VAR_SEQ 53 222 Missing (in isoform Mdm2-C). FT {ECO:0000303|PubMed:8705862}. FT /FTId=VSP_003211. FT VAR_SEQ 53 97 Missing (in isoform Mdm2-F). FT {ECO:0000303|PubMed:11351297}. FT /FTId=VSP_022578. FT VAR_SEQ 76 102 YCSNDLLGDLFGVPSFSVKEHRKIYTM -> NDCANLFPLV FT DLSIRELYISNYITLGI (in isoform Mdm2-E). FT {ECO:0000303|PubMed:8705862}. FT /FTId=VSP_003212. FT VAR_SEQ 103 491 Missing (in isoform Mdm2-E). FT {ECO:0000303|PubMed:8705862}. FT /FTId=VSP_003213. FT VAR_SEQ 115 169 Missing (in isoform Mdm2-G). FT {ECO:0000303|PubMed:11351297}. FT /FTId=VSP_022579. FT VAR_SEQ 275 300 Missing (in isoform Mdm2-A1). FT {ECO:0000303|PubMed:15315825}. FT /FTId=VSP_003214. FT MUTAGEN 305 305 C->S: No loss of ubiquitin ligase E3 FT activity. {ECO:0000269|PubMed:10722742}. FT MUTAGEN 374 374 C->T: No loss of ubiquitin ligase E3 FT activity. {ECO:0000269|PubMed:10722742}. FT MUTAGEN 438 438 C->L: No loss of ubiquitin ligase E3 FT activity. {ECO:0000269|PubMed:10722742}. FT MUTAGEN 441 441 C->G: Fails to interact with MDM4. FT {ECO:0000269|PubMed:10608892}. FT MUTAGEN 449 449 C->A: Loss of ubiquitin ligase E3 FT activity. {ECO:0000269|PubMed:10723139}. FT MUTAGEN 449 449 C->S: No substantial decrease of FT ubiquitin ligase E3 activity. FT {ECO:0000269|PubMed:10723139}. FT MUTAGEN 452 452 H->A: Loss of ubiquitin ligase E3 FT activity. {ECO:0000269|PubMed:10722742}. FT MUTAGEN 455 455 T->A: Significant decrease of ubiquitin FT ligase E3 activity. FT {ECO:0000269|PubMed:10722742}. FT MUTAGEN 457 457 H->S: Loss of ubiquitin ligase E3 FT activity. {ECO:0000269|PubMed:10722742}. FT MUTAGEN 461 461 C->S: Loss of ubiquitin ligase E3 FT activity. {ECO:0000269|PubMed:10722742}. FT MUTAGEN 464 464 C->A: Loss of ubiquitin ligase E3 FT activity, enhances protein stability. FT Does not inhibit interaction with APEX1, FT but inhibits its ubiquitin ligase E3 FT activity on APEX1. FT {ECO:0000269|PubMed:15632057, FT ECO:0000269|PubMed:16479015, FT ECO:0000269|PubMed:19219073, FT ECO:0000269|PubMed:20173098, FT ECO:0000269|PubMed:9450543}. FT MUTAGEN 475 475 C->G: Loss of ubiquitin ligase E3 FT activity. {ECO:0000269|PubMed:10722742}. FT MUTAGEN 478 478 C->R: Fails to interact with MDM4. FT {ECO:0000269|PubMed:10608892}. FT MUTAGEN 478 478 C->S: Loss of ubiquitin ligase E3 FT activity. {ECO:0000269|PubMed:10608892}. FT CONFLICT 17 17 S -> P (in Ref. 10; AAA82237). FT {ECO:0000305}. FT STRAND 7 10 {ECO:0000244|PDB:4WT2}. FT STRAND 13 15 {ECO:0000244|PDB:4WT2}. FT STRAND 17 19 {ECO:0000244|PDB:2LZG}. FT HELIX 23 25 {ECO:0000244|PDB:4OGN}. FT STRAND 27 30 {ECO:0000244|PDB:4OGN}. FT HELIX 32 40 {ECO:0000244|PDB:4OGN}. FT STRAND 46 49 {ECO:0000244|PDB:4OBA}. FT HELIX 50 63 {ECO:0000244|PDB:4OGN}. FT TURN 64 67 {ECO:0000244|PDB:4ODF}. FT HELIX 70 72 {ECO:0000244|PDB:4WT2}. FT STRAND 74 76 {ECO:0000244|PDB:4OGN}. FT STRAND 78 80 {ECO:0000244|PDB:3LBK}. FT HELIX 81 86 {ECO:0000244|PDB:4OGN}. FT STRAND 88 92 {ECO:0000244|PDB:4OGN}. FT HELIX 96 104 {ECO:0000244|PDB:4OGN}. FT STRAND 107 109 {ECO:0000244|PDB:4OGN}. FT STRAND 295 297 {ECO:0000244|PDB:2C6A}. FT HELIX 299 301 {ECO:0000244|PDB:4XXB}. FT TURN 306 308 {ECO:0000244|PDB:4XXB}. FT STRAND 314 318 {ECO:0000244|PDB:4XXB}. FT TURN 320 322 {ECO:0000244|PDB:4XXB}. FT HELIX 433 435 {ECO:0000244|PDB:2VJE}. FT TURN 439 441 {ECO:0000244|PDB:2VJE}. FT STRAND 442 444 {ECO:0000244|PDB:2VJE}. FT STRAND 448 452 {ECO:0000244|PDB:2VJE}. FT STRAND 455 460 {ECO:0000244|PDB:2VJE}. FT HELIX 462 470 {ECO:0000244|PDB:2VJE}. FT TURN 476 478 {ECO:0000244|PDB:2VJE}. FT STRAND 484 489 {ECO:0000244|PDB:2VJE}. SQ SEQUENCE 491 AA; 55233 MW; F37CE163876BC983 CRC64; MCNTNMSVPT DGAVTTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM KEVLFYLGQY IMTKRLYDEK QQHIVYCSND LLGDLFGVPS FSVKEHRKIY TMIYRNLVVV NQQESSDSGT SVSENRCHLE GGSDQKDLVQ ELQEEKPSSS HLVSRPSTSS RRRAISETEE NSDELSGERQ RKRHKSDSIS LSFDESLALC VIREICCERS SSSESTGTPS NPDLDAGVSE HSGDWLDQDS VSDQFSVEFE VESLDSEDYS LSEEGQELSD EDDEVYQVTV YQAGESDTDS FEEDPEISLA DYWKCTSCNE MNPPLPSHCN RCWALRENWL PEDKGKDKGE ISEKAKLENS TQAEEGFDVP DCKKTIVNDS RESCVEENDD KITQASQSQE SEDYSQPSTS SSIIYSSQED VKEFEREETQ DKEESVESSL PLNAIEPCVI CQGRPKNGCI VHGKTGHLMA CFTCAKKLKK RNKPCPVCRQ PIQMIVLTYF P // ID MK09_HUMAN Reviewed; 424 AA. AC P45984; A8K0S3; B5BU66; B5M0B4; D3DWQ8; D3DWQ9; Q15708; Q15710; AC Q15711; Q8N5C5; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2006, sequence version 2. DT 11-NOV-2015, entry version 173. DE RecName: Full=Mitogen-activated protein kinase 9; DE Short=MAP kinase 9; DE Short=MAPK 9; DE EC=2.7.11.24; DE AltName: Full=JNK-55; DE AltName: Full=Stress-activated protein kinase 1a; DE Short=SAPK1a; DE AltName: Full=Stress-activated protein kinase JNK2; DE AltName: Full=c-Jun N-terminal kinase 2; GN Name=MAPK9; Synonyms=JNK2, PRKM9, SAPK1A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=7969172; RA Sluss H.K., Barrett T., Derijard B., Davis R.J.; RT "Signal transduction by tumor necrosis factor mediated by JNK protein RT kinases."; RL Mol. Cell. Biol. 14:8376-8384(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8001819; DOI=10.1101/gad.8.24.2996; RA Kallunki T., Su B., Tsigelny I., Sluss H.K., Derijard B., Moore G., RA Davis R., Karin M.; RT "JNK2 contains a specificity-determining region responsible for RT efficient c-Jun binding and phosphorylation."; RL Genes Dev. 8:2996-3007(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING. RC TISSUE=Brain; RX PubMed=8654373; RA Gupta S., Barrett T., Whitmarsh A.J., Cavanagh J., Sluss H.K., RA Derijard B., Davis R.J.; RT "Selective interaction of JNK protein kinase isoforms with RT transcription factors."; RL EMBO J. 15:2760-2770(1996). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). RX PubMed=21110917; DOI=10.5483/BMBRep.2010.43.11.738; RA Wang P., Xiong Y., Ma C., Shi T., Ma D.; RT "Molecular cloning and characterization of novel human JNK2 (MAPK9) RT transcript variants that show different stimulation activities on AP- RT 1."; RL BMB Rep. 43:738-743(2010). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., RA Korn B., Zuo D., Hu Y., LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA-2). RC TISSUE=Amygdala; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-268. RG NIEHS SNPs program; RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-2). RX PubMed=19054851; DOI=10.1038/nmeth.1273; RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B., RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., RA Isogai T., Imai J., Watanabe S., Nomura N.; RT "Human protein factory for converting the transcriptome into an in RT vitro-expressed proteome."; RL Nat. Methods 5:1011-1017(2008). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15372022; DOI=10.1038/nature02919; RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S., RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., RA Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., RA Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., RA Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., RA Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., RA Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., RA Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., RA Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., RA Richardson P., Lucas S.M., Myers R.M., Rubin E.M.; RT "The DNA sequence and comparative analysis of human chromosome 5."; RL Nature 431:268-274(2004). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [12] RP INTERACTION WITH ATF7, AND FUNCTION. RX PubMed=10376527; DOI=10.1038/sj.onc.1202723; RA De Graeve F., Bahr A., Sabapathy K.T., Hauss C., Wagner E.F., RA Kedinger C., Chatton B.; RT "Role of the ATFa/JNK2 complex in Jun activation."; RL Oncogene 18:3491-3500(1999). RN [13] RP PHOSPHORYLATION AT THR-183 AND TYR-185, REGULATION BY MAP2K4 AND RP MAP2K7, AND COFACTOR. RX PubMed=11062067; DOI=10.1042/0264-6021:3520145; RA Fleming Y., Armstrong C.G., Morrice N., Paterson A., Goedert M., RA Cohen P.; RT "Synergistic activation of stress-activated protein kinase 1/c-Jun N- RT terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein RT kinase kinase 4 (MKK4) and MKK7."; RL Biochem. J. 352:145-154(2000). RN [14] RP INTERACTION WITH SPAG9. RX PubMed=15693750; DOI=10.1042/BJ20041577; RA Jagadish N., Rana R., Selvi R., Mishra D., Garg M., Yadav S., RA Herr J.C., Okumura K., Hasegawa A., Koyama K., Suri A.; RT "Characterization of a novel human sperm-associated antigen 9 (SPAG9) RT having structural homology with c-Jun N-terminal kinase-interacting RT protein."; RL Biochem. J. 389:73-82(2005). RN [15] RP FUNCTION IN PHOSPHORYLATION OF RRN3. RX PubMed=15805466; DOI=10.1101/gad.333205; RA Mayer C., Bierhoff H., Grummt I.; RT "The nucleolus as a stress sensor: JNK2 inactivates the transcription RT factor TIF-IA and down-regulates rRNA synthesis."; RL Genes Dev. 19:933-941(2005). RN [16] RP INTERACTION WITH NFATC4. RX PubMed=17875713; DOI=10.1158/0008-5472.CAN-06-4788; RA Yao K., Cho Y.-Y., Bergen H.R. III, Madden B.J., Choi B.Y., Ma W.-Y., RA Bode A.M., Dong Z.; RT "Nuclear factor of activated T3 is a negative regulator of Ras-JNK1/2- RT AP-1 induced cell transformation."; RL Cancer Res. 67:8725-8735(2007). RN [17] RP INTERACTION WITH BCL10. RX PubMed=17189706; DOI=10.1016/j.immuni.2006.11.008; RA Blonska M., Pappu B.P., Matsumoto R., Li H., Su B., Wang D., Lin X.; RT "The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase RT in the T cell receptor-signaling pathway."; RL Immunity 26:55-66(2007). RN [18] RP FUNCTION IN PHOSPHORYLATION OF TP53. RX PubMed=17525747; DOI=10.1038/sj.onc.1210526; RA Oleinik N.V., Krupenko N.I., Krupenko S.A.; RT "Cooperation between JNK1 and JNK2 in activation of p53 apoptotic RT pathway."; RL Oncogene 26:7222-7230(2007). RN [19] RP REVIEW ON FUNCTION. RX PubMed=19290929; DOI=10.1111/j.1600-065X.2008.00749.x; RA Blonska M., Lin X.; RT "CARMA1-mediated NF-kappaB and JNK activation in lymphocytes."; RL Immunol. Rev. 228:199-211(2009). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [21] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CTNNB1. RX PubMed=19675674; DOI=10.1371/journal.pone.0006640; RA Hu D., Bi X., Fang W., Han A., Yang W.; RT "GSK3beta is involved in JNK2-mediated beta-catenin inhibition."; RL PLoS ONE 4:E6640-E6640(2009). RN [22] RP FUNCTION. RX PubMed=20595622; DOI=10.1152/ajpgi.00265.2010; RA Samak G., Suzuki T., Bhargava A., Rao R.K.; RT "c-Jun NH2-terminal kinase-2 mediates osmotic stress-induced tight RT junction disruption in the intestinal epithelium."; RL Am. J. Physiol. 299:G572-G584(2010). RN [23] RP FUNCTION IN PHOSPHORYLATION OF YAP1. RX PubMed=21364637; DOI=10.1038/cddis.2010.7; RA Tomlinson V., Gudmundsdottir K., Luong P., Leung K.Y., Knebel A., RA Basu S.; RT "JNK phosphorylates Yes-associated protein (YAP) to regulate RT apoptosis."; RL Cell Death Dis. 1:E29-E29(2010). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [25] RP FUNCTION. RX PubMed=22441692; DOI=10.1038/embor.2012.37; RA Yoshitane H., Honma S., Imamura K., Nakajima H., Nishide S.Y., Ono D., RA Kiyota H., Shinozaki N., Matsuki H., Wada N., Doi H., Hamada T., RA Honma K., Fukada Y.; RT "JNK regulates the photic response of the mammalian circadian clock."; RL EMBO Rep. 13:455-461(2012). RN [26] RP X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS) OF 7-362. RX PubMed=18801372; DOI=10.1016/j.jmb.2008.08.086; RA Shaw D., Wang S.M., Villasenor A.G., Tsing S., Walter D., RA Browner M.F., Barnett J., Kuglstatter A.; RT "The crystal structure of JNK2 reveals conformational flexibility in RT the MAP kinase insert and indicates its involvement in the regulation RT of catalytic activity."; RL J. Mol. Biol. 383:885-893(2008). RN [27] RP VARIANTS [LARGE SCALE ANALYSIS] MET-13; ASN-56; THR-246 AND ILE-366. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). CC -!- FUNCTION: Serine/threonine-protein kinase involved in various CC processes such as cell proliferation, differentiation, migration, CC transformation and programmed cell death. Extracellular stimuli CC such as proinflammatory cytokines or physical stress stimulate the CC stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) CC signaling pathway. In this cascade, two dual specificity kinases CC MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2. CC In turn, MAPK9/JNK2 phosphorylates a number of transcription CC factors, primarily components of AP-1 such as JUN and ATF2 and CC thus regulates AP-1 transcriptional activity. In response to CC oxidative or ribotoxic stresses, inhibits rRNA synthesis by CC phosphorylating and inactivating the RNA polymerase 1-specific CC transcription initiation factor RRN3. Promotes stressed cell CC apoptosis by phosphorylating key regulatory factors including TP53 CC and YAP1. In T-cells, MAPK8 and MAPK9 are required for polarized CC differentiation of T-helper cells into Th1 cells. Upon T-cell CC receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 CC and MAP3K7/TAK1 to regulate JUN protein levels. Plays an important CC role in the osmotic stress-induced epithelial tight-junctions CC disruption. When activated, promotes beta-catenin/CTNNB1 CC degradation and inhibits the canonical Wnt signaling pathway. CC Participates also in neurite growth in spiral ganglion neurons. CC Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role CC in the regulation of the circadian clock (PubMed:22441692). CC {ECO:0000269|PubMed:22441692}. CC -!- FUNCTION: MAPK9 isoforms display different binding patterns: CC alpha-1 and alpha-2 preferentially bind to JUN, whereas beta-1 and CC beta-2 bind to ATF2. However, there is no correlation between CC binding and phosphorylation, which is achieved at about the same CC efficiency by all isoforms. JUNB is not a substrate for JNK2 CC alpha-2, and JUND binds only weakly to it. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:11062067}; CC -!- ENZYME REGULATION: Activated by threonine and tyrosine CC phosphorylation by either of two dual specificity kinases, MAP2K4 CC and MAP2K7. MAP2K4 shows a strong preference for Tyr-185 while CC MAP2K7 phosphorylates Tyr-183 preferentially. Inhibited by dual CC specificity phosphatases, such as DUSP1. CC -!- SUBUNIT: Interacts with MECOM and DCLK2 (By similarity). Binds to CC at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP- CC 2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins CC also bind other components of the JNK signaling pathway. Interacts CC with NFATC4. Interacts with ATF7; the interaction does not CC phosphorylate ATF7 but acts as a docking site for ATF7-associated CC partners such as JUN. Interacts with BCL10. Interacts with CTNNB1 CC and GSK3B. {ECO:0000250, ECO:0000269|PubMed:10376527, CC ECO:0000269|PubMed:15693750, ECO:0000269|PubMed:17189706, CC ECO:0000269|PubMed:17875713, ECO:0000269|PubMed:19675674}. CC -!- INTERACTION: CC P49407:ARRB1; NbExp=5; IntAct=EBI-713568, EBI-743313; CC P32121:ARRB2; NbExp=5; IntAct=EBI-713568, EBI-714559; CC P15336:ATF2; NbExp=5; IntAct=EBI-713568, EBI-1170906; CC Q6P1W5:C1orf94; NbExp=3; IntAct=EBI-713568, EBI-946029; CC Q9C0F1:CEP44; NbExp=4; IntAct=EBI-713568, EBI-744115; CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-713568, EBI-10171858; CC Q5JST6:EFHC2; NbExp=3; IntAct=EBI-713568, EBI-2349927; CC Q96JM7:L3MBTL3; NbExp=3; IntAct=EBI-713568, EBI-2686809; CC Q8TBB1:LNX1; NbExp=3; IntAct=EBI-713568, EBI-739832; CC P50221:MEOX1; NbExp=3; IntAct=EBI-713568, EBI-2864512; CC Q15427:SF3B4; NbExp=4; IntAct=EBI-713568, EBI-348469; CC P34896:SHMT1; NbExp=3; IntAct=EBI-713568, EBI-715117; CC A2RU48:SMCO3; NbExp=3; IntAct=EBI-713568, EBI-10173195; CC P40763:STAT3; NbExp=3; IntAct=EBI-713586, EBI-518675; CC Q8IYF3:TEX11; NbExp=3; IntAct=EBI-713568, EBI-742397; CC O43379:WDR62; NbExp=4; IntAct=EBI-713568, EBI-714790; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19675674}. CC Nucleus {ECO:0000269|PubMed:19675674}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=Alpha-2; CC IsoId=P45984-1; Sequence=Displayed; CC Name=Alpha-1; CC IsoId=P45984-2; Sequence=VSP_004835; CC Name=Beta-1; CC IsoId=P45984-3; Sequence=VSP_004834, VSP_004835; CC Name=Beta-2; CC IsoId=P45984-4; Sequence=VSP_004834; CC Name=5; CC IsoId=P45984-5; Sequence=VSP_041908, VSP_041909; CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues CC whose phosphorylation activates the MAP kinases. CC -!- PTM: Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K7 and CC MAP2K4, which activates the enzyme. Autophosphorylated in vitro. CC {ECO:0000269|PubMed:11062067}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC CC Ser/Thr protein kinase family. MAP kinase subfamily. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/JNK2ID426.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/mapk9/"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; L31951; AAA56831.1; -; mRNA. DR EMBL; U09759; AAA74740.1; -; mRNA. DR EMBL; U34821; AAC50606.1; -; mRNA. DR EMBL; U35002; AAC50608.1; -; mRNA. DR EMBL; U35003; AAC50609.1; -; mRNA. DR EMBL; EU927388; ACH57450.1; -; mRNA. DR EMBL; CR536580; CAG38817.1; -; mRNA. DR EMBL; AK289638; BAF82327.1; -; mRNA. DR EMBL; DQ066599; AAY46156.1; -; Genomic_DNA. DR EMBL; AB451302; BAG70116.1; -; mRNA. DR EMBL; AB451355; BAG70169.1; -; mRNA. DR EMBL; AC008610; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC104115; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471165; EAW53759.1; -; Genomic_DNA. DR EMBL; CH471165; EAW53757.1; -; Genomic_DNA. DR EMBL; CH471165; EAW53758.1; -; Genomic_DNA. DR EMBL; CH471165; EAW53762.1; -; Genomic_DNA. DR EMBL; BC032539; AAH32539.1; -; mRNA. DR CCDS; CCDS43409.1; -. [P45984-2] DR CCDS; CCDS43410.1; -. [P45984-3] DR CCDS; CCDS4453.1; -. [P45984-1] DR CCDS; CCDS4454.1; -. [P45984-4] DR CCDS; CCDS47356.1; -. [P45984-5] DR PIR; A55480; A55480. DR PIR; S71102; S71102. DR RefSeq; NP_001128516.1; NM_001135044.1. [P45984-5] DR RefSeq; NP_001295173.1; NM_001308244.1. DR RefSeq; NP_002743.3; NM_002752.4. [P45984-1] DR RefSeq; NP_620707.1; NM_139068.2. [P45984-2] DR RefSeq; NP_620708.1; NM_139069.2. [P45984-3] DR RefSeq; NP_620709.1; NM_139070.2. [P45984-4] DR RefSeq; XP_006714954.1; XM_006714891.1. [P45984-1] DR UniGene; Hs.484371; -. DR PDB; 3E7O; X-ray; 2.14 A; A/B=7-362. DR PDB; 3NPC; X-ray; 2.35 A; A/B=1-364. DR PDBsum; 3E7O; -. DR PDBsum; 3NPC; -. DR ProteinModelPortal; P45984; -. DR SMR; P45984; 7-363. DR BioGrid; 111587; 101. DR DIP; DIP-270N; -. DR DIP; DIP-281N; -. DR IntAct; P45984; 50. DR MINT; MINT-1400230; -. DR STRING; 9606.ENSP00000389338; -. DR BindingDB; P45984; -. DR ChEMBL; CHEMBL2096667; -. DR GuidetoPHARMACOLOGY; 1497; -. DR PhosphoSite; P45984; -. DR BioMuta; MAPK9; -. DR DMDM; 85700366; -. DR REPRODUCTION-2DPAGE; P45984; -. DR MaxQB; P45984; -. DR PaxDb; P45984; -. DR PRIDE; P45984; -. DR DNASU; 5601; -. DR Ensembl; ENST00000343111; ENSP00000345524; ENSG00000050748. [P45984-3] DR Ensembl; ENST00000393360; ENSP00000377028; ENSG00000050748. [P45984-2] DR Ensembl; ENST00000425491; ENSP00000397422; ENSG00000050748. [P45984-5] DR Ensembl; ENST00000452135; ENSP00000394560; ENSG00000050748. [P45984-1] DR Ensembl; ENST00000455781; ENSP00000389338; ENSG00000050748. [P45984-4] DR GeneID; 5601; -. DR KEGG; hsa:5601; -. DR UCSC; uc003mls.4; human. [P45984-1] DR UCSC; uc003mlt.4; human. [P45984-2] DR UCSC; uc003mlv.4; human. [P45984-3] DR UCSC; uc010jlc.3; human. [P45984-4] DR UCSC; uc011dgx.2; human. [P45984-5] DR CTD; 5601; -. DR GeneCards; MAPK9; -. DR HGNC; HGNC:6886; MAPK9. DR HPA; CAB008910; -. DR HPA; HPA045654; -. DR HPA; HPA055483; -. DR MIM; 602896; gene. DR neXtProt; NX_P45984; -. DR PharmGKB; PA30630; -. DR eggNOG; KOG0665; Eukaryota. DR eggNOG; ENOG410XSHI; LUCA. DR GeneTree; ENSGT00550000074271; -. DR HOGENOM; HOG000233024; -. DR HOVERGEN; HBG014652; -. DR InParanoid; P45984; -. DR KO; K04440; -. DR OMA; PSLEFMN; -. DR OrthoDB; EOG7PCJGV; -. DR PhylomeDB; P45984; -. DR TreeFam; TF105100; -. DR BRENDA; 2.7.11.24; 2681. DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence. DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation. DR Reactome; R-HSA-450321; JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1. DR Reactome; R-HSA-450341; Activation of the AP-1 family of transcription factors. DR SignaLink; P45984; -. DR ChiTaRS; MAPK9; human. DR EvolutionaryTrace; P45984; -. DR GeneWiki; Mitogen-activated_protein_kinase_9; -. DR GenomeRNAi; 5601; -. DR NextBio; 21752; -. DR PRO; PR:P45984; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; P45984; -. DR CleanEx; HS_MAPK9; -. DR ExpressionAtlas; P45984; baseline and differential. DR Genevisible; P45984; HS. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008656; F:cysteine-type endopeptidase activator activity involved in apoptotic process; IEA:Ensembl. DR GO; GO:0004705; F:JUN kinase activity; IDA:UniProtKB. DR GO; GO:0008134; F:transcription factor binding; IDA:UniProtKB. DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEA:Ensembl. DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl. DR GO; GO:0034644; P:cellular response to UV; IEA:Ensembl. DR GO; GO:0007417; P:central nervous system development; IEA:Ensembl. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0007254; P:JNK cascade; IDA:UniProtKB. DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0002756; P:MyD88-independent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0031175; P:neuron projection development; IEA:Ensembl. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0010770; P:positive regulation of cell morphogenesis involved in differentiation; IEA:Ensembl. DR GO; GO:0032722; P:positive regulation of chemokine production; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL. DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IMP:BHF-UCL. DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IEA:Ensembl. DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IEA:Ensembl. DR GO; GO:0031394; P:positive regulation of prostaglandin biosynthetic process; IEA:Ensembl. DR GO; GO:0032308; P:positive regulation of prostaglandin secretion; IEA:Ensembl. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IEA:Ensembl. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl. DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB. DR GO; GO:0006626; P:protein targeting to mitochondrion; IEA:Ensembl. DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:0046328; P:regulation of JNK cascade; IEA:Ensembl. DR GO; GO:0031396; P:regulation of protein ubiquitination; IEA:Ensembl. DR GO; GO:0051090; P:regulation of sequence-specific DNA binding transcription factor activity; TAS:Reactome. DR GO; GO:0001836; P:release of cytochrome c from mitochondria; IEA:Ensembl. DR GO; GO:0014075; P:response to amine; IEA:Ensembl. DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl. DR GO; GO:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0006950; P:response to stress; TAS:ProtInc. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome. DR GO; GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome. DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome. DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome. DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome. DR GO; GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome. DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome. DR GO; GO:0002224; P:toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome. DR GO; GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome. DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR003527; MAP_kinase_CS. DR InterPro; IPR008351; MAPK_JNK. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR Pfam; PF00069; Pkinase; 1. DR PRINTS; PR01772; JNKMAPKINASE. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; SSF56112; 1. DR PROSITE; PS01351; MAPK; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Biological rhythms; KW Complete proteome; Cytoplasm; Kinase; Nucleotide-binding; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1 424 Mitogen-activated protein kinase 9. FT /FTId=PRO_0000186273. FT DOMAIN 26 321 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 32 40 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOTIF 183 185 TXY. FT ACT_SITE 151 151 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10027}. FT BINDING 55 55 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 183 183 Phosphothreonine; by MAP2K7. FT {ECO:0000269|PubMed:11062067}. FT MOD_RES 185 185 Phosphotyrosine; by MAP2K4. FT {ECO:0000269|PubMed:11062067}. FT VAR_SEQ 216 230 GELVKGCVIFQGTDH -> AEMVLHKVLFPGRDY (in FT isoform Beta-1 and isoform Beta-2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_004834. FT VAR_SEQ 230 242 HIDQWNKVIEQLG -> RILPRDLGPAMLS (in FT isoform 5). FT {ECO:0000303|PubMed:21110917}. FT /FTId=VSP_041908. FT VAR_SEQ 243 424 Missing (in isoform 5). FT {ECO:0000303|PubMed:21110917}. FT /FTId=VSP_041909. FT VAR_SEQ 378 424 DAAVSSNATPSQSSSINDISSMSTEQTLASDTDSSLDASTG FT PLEGCR -> AQMQQ (in isoform Alpha-1 and FT isoform Beta-1). {ECO:0000305}. FT /FTId=VSP_004835. FT VARIANT 13 13 V -> M (in a colorectal adenocarcinoma FT sample; somatic mutation). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_042260. FT VARIANT 56 56 K -> N (in a head & Neck squamous cell FT carcinoma sample; somatic mutation). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_042261. FT VARIANT 246 246 A -> T (in dbSNP:rs35421153). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_042262. FT VARIANT 268 268 G -> A (in dbSNP:rs35693958). FT {ECO:0000269|Ref.7}. FT /FTId=VAR_025175. FT VARIANT 366 366 R -> I (in dbSNP:rs55736180). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_042263. FT CONFLICT 51 51 N -> S (in Ref. 1; AAA56831 and 3; FT AAC50606/AAC50608/AAC50609). FT {ECO:0000305}. FT CONFLICT 377 377 S -> P (in Ref. 2; AAA74740). FT {ECO:0000305}. FT STRAND 10 15 {ECO:0000244|PDB:3E7O}. FT STRAND 18 23 {ECO:0000244|PDB:3E7O}. FT STRAND 26 33 {ECO:0000244|PDB:3E7O}. FT STRAND 38 45 {ECO:0000244|PDB:3E7O}. FT TURN 46 49 {ECO:0000244|PDB:3E7O}. FT STRAND 50 58 {ECO:0000244|PDB:3E7O}. FT HELIX 64 79 {ECO:0000244|PDB:3E7O}. FT STRAND 88 92 {ECO:0000244|PDB:3E7O}. FT TURN 98 100 {ECO:0000244|PDB:3E7O}. FT STRAND 105 109 {ECO:0000244|PDB:3E7O}. FT STRAND 112 114 {ECO:0000244|PDB:3E7O}. FT HELIX 115 118 {ECO:0000244|PDB:3E7O}. FT HELIX 125 144 {ECO:0000244|PDB:3E7O}. FT HELIX 154 156 {ECO:0000244|PDB:3E7O}. FT STRAND 157 159 {ECO:0000244|PDB:3E7O}. FT STRAND 165 167 {ECO:0000244|PDB:3E7O}. FT TURN 176 178 {ECO:0000244|PDB:3NPC}. FT STRAND 180 183 {ECO:0000244|PDB:3NPC}. FT HELIX 189 191 {ECO:0000244|PDB:3NPC}. FT HELIX 194 197 {ECO:0000244|PDB:3E7O}. FT HELIX 206 220 {ECO:0000244|PDB:3E7O}. FT HELIX 232 241 {ECO:0000244|PDB:3E7O}. FT HELIX 246 250 {ECO:0000244|PDB:3E7O}. FT HELIX 254 261 {ECO:0000244|PDB:3E7O}. FT HELIX 271 274 {ECO:0000244|PDB:3E7O}. FT HELIX 277 279 {ECO:0000244|PDB:3E7O}. FT HELIX 286 301 {ECO:0000244|PDB:3E7O}. FT TURN 306 308 {ECO:0000244|PDB:3NPC}. FT HELIX 312 316 {ECO:0000244|PDB:3E7O}. FT HELIX 319 322 {ECO:0000244|PDB:3E7O}. FT HELIX 327 330 {ECO:0000244|PDB:3NPC}. FT TURN 341 343 {ECO:0000244|PDB:3NPC}. FT HELIX 349 360 {ECO:0000244|PDB:3E7O}. SQ SEQUENCE 424 AA; 48139 MW; 9C15DA79981290AF CRC64; MSDSKCDSQF YSVQVADSTF TVLKRYQQLK PIGSGAQGIV CAAFDTVLGI NVAVKKLSRP FQNQTHAKRA YRELVLLKCV NHKNIISLLN VFTPQKTLEE FQDVYLVMEL MDANLCQVIH MELDHERMSY LLYQMLCGIK HLHSAGIIHR DLKPSNIVVK SDCTLKILDF GLARTACTNF MMTPYVVTRY YRAPEVILGM GYKENVDIWS VGCIMGELVK GCVIFQGTDH IDQWNKVIEQ LGTPSAEFMK KLQPTVRNYV ENRPKYPGIK FEELFPDWIF PSESERDKIK TSQARDLLSK MLVIDPDKRI SVDEALRHPY ITVWYDPAEA EAPPPQIYDA QLEEREHAIE EWKELIYKEV MDWEERSKNG VVKDQPSDAA VSSNATPSQS SSINDISSMS TEQTLASDTD SSLDASTGPL EGCR // ID MYC_HUMAN Reviewed; 439 AA. AC P01106; A8WFE7; P01107; Q14026; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 13-AUG-1987, sequence version 1. DT 11-NOV-2015, entry version 207. DE RecName: Full=Myc proto-oncogene protein; DE AltName: Full=Class E basic helix-loop-helix protein 39; DE Short=bHLHe39; DE AltName: Full=Proto-oncogene c-Myc; DE AltName: Full=Transcription factor p64; GN Name=MYC; Synonyms=BHLHE39; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM RP 1). RX PubMed=6414718; DOI=10.1016/0092-8674(83)90534-2; RA Battey J., Moulding C., Taub R., Murphy W., Stewart T., Potter H., RA Lenoir G., Leder P.; RT "The human c-myc oncogene: structural consequences of translocation RT into the IgH locus in Burkitt lymphoma."; RL Cell 34:779-787(1983). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM RP 1). RX PubMed=6321164; RA Bernard O., Cory S., Gerondakis S., Webb E., Adams J.M.; RT "Sequence of the murine and human cellular myc oncogenes and two modes RT of myc transcription resulting from chromosome translocation in B RT lymphoid tumours."; RL EMBO J. 2:2375-2383(1983). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM RP 1). RX PubMed=6298632; DOI=10.1038/301722a0; RA Colby W.W., Chen E.Y., Smith D.H., Levinson A.D.; RT "Identification and nucleotide sequence of a human locus homologous to RT the v-myc oncogene of avian myelocytomatosis virus MC29."; RL Nature 301:722-725(1983). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=6304538; DOI=10.1038/303725a0; RA Watt R., Stanton L.W., Marcu K.B., Gallo R.C., Croce C.M., Rovera G.; RT "Nucleotide sequence of cloned cDNA of human c-myc oncogene."; RL Nature 303:725-728(1983). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ASP-39. RX PubMed=6419122; DOI=10.1038/306760a0; RA Rabbitts T.H., Hamlyn P.H., Baer R.; RT "Altered nucleotide sequences of a translocated c-myc gene in Burkitt RT lymphoma."; RL Nature 306:760-765(1983). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM RP 1). RX PubMed=6304729; DOI=10.1073/pnas.80.12.3642; RA Watson D.K., Psallidopoulos M.C., Samuel K.P., Dalla-Favera R., RA Papas T.S.; RT "Nucleotide sequence analysis of human c-myc locus, chicken homologue, RT and myelocytomatosis virus MC29 transforming gene reveals a highly RT conserved gene product."; RL Proc. Natl. Acad. Sci. U.S.A. 80:3642-3645(1983). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE RP [GENOMIC DNA] OF 1-252. RX PubMed=6547209; DOI=10.1038/309592a0; RA Rabbitts T.H., Forster A., Hamlyn P., Baer R.; RT "Effect of somatic mutation within translocated c-myc genes in RT Burkitt's lymphoma."; RL Nature 309:592-597(1984). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM RP 1). RX PubMed=6714223; RA Gazin C., Dupont S., de Dinechin D., Hampe A., Masson J.-M., RA Martin P., Stehelin D., Galibert F.; RT "Nucleotide sequence of the human c-myc locus: provocative open RT reading frame within the first exon."; RL EMBO J. 3:383-387(1984). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS RP 1 AND 2). RX PubMed=8444346; DOI=10.1016/0378-1119(93)90398-M; RA Tachibana K., Takayama N., Matsuo K., Kato S., Yamamoto K., Ohyama K., RA Umezawa A., Takano T.; RT "Allele-specific activation of the c-myc gene in an atypical Burkitt's RT lymphoma carrying the t(2;8) chromosomal translocation 250 kb RT downstream from c-myc."; RL Gene 124:231-237(1993). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-11; CYS-160; RP ILE-170 AND VAL-322. RG NIEHS SNPs program; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16421571; DOI=10.1038/nature04406; RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T., RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., RA Lander E.S.; RT "DNA sequence and analysis of human chromosome 8."; RL Nature 439:331-335(2006). RN [14] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [15] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Cervix, Placenta, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [16] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-170 (ISOFORM 1). RC TISSUE=Promyelocytic leukemia; RX PubMed=3540591; RA Bentley D.L., Groudine M.; RT "Novel promoter upstream of the human c-myc gene and regulation of c- RT myc expression in B-cell lymphomas."; RL Mol. Cell. Biol. 6:3481-3489(1986). RN [17] RP INVOLVEMENT IN BURKITT LYMPHOMA. RX PubMed=2166998; RA Magrath I.; RT "The pathogenesis of Burkitt's lymphoma."; RL Adv. Cancer Res. 55:133-270(1990). RN [18] RP PHOSPHORYLATION. RX PubMed=1597196; DOI=10.1111/j.1432-1033.1992.tb16964.x; RA Iijima S., Teraoka H., Date T., Tsukada K.; RT "DNA-activated protein kinase in Raji Burkitt's lymphoma cells. RT Phosphorylation of c-Myc oncoprotein."; RL Eur. J. Biochem. 206:595-603(1992). RN [19] RP INVOLVEMENT IN BURKITT LYMPHOMA, AND VARIANTS ASP-39; SER-57; ALA-59 RP AND THR-86. RX PubMed=8220424; DOI=10.1038/ng0993-56; RA Bhatia K., Huppi K., Spangler G., Siwarski D., Iyer R., Magrath I.; RT "Point mutations in the c-Myc transactivation domain are common in RT Burkitt's lymphoma and mouse plasmacytomas."; RL Nat. Genet. 5:56-61(1993). RN [20] RP PHOSPHORYLATION AT THR-58 AND SER-62. RX PubMed=8386367; DOI=10.1073/pnas.90.8.3216; RA Gupta S., Seth A., Davis R.J.; RT "Transactivation of gene expression by Myc is inhibited by mutation at RT the phosphorylation sites Thr-58 and Ser-62."; RL Proc. Natl. Acad. Sci. U.S.A. 90:3216-3220(1993). RN [21] RP GLYCOSYLATION AT THR-58. RX PubMed=7642555; DOI=10.1074/jbc.270.32.18961; RA Chou T.-Y., Hart G.W., Dang C.V.; RT "c-Myc is glycosylated at threonine 58, a known phosphorylation site RT and a mutational hot spot in lymphomas."; RL J. Biol. Chem. 270:18961-18965(1995). RN [22] RP PHOSPHORYLATION AT THR-8. RX PubMed=9315742; DOI=10.1016/S0014-5793(97)00992-7; RA Alexandrov I., Shlyakhova L., Vartanian A., Zajac-Kaye M., RA Alexandrova N.; RT "c-Raf kinase binds to N-terminal domain of c-Myc."; RL FEBS Lett. 414:465-470(1997). RN [23] RP UBIQUITINATION, INTERACTION WITH FBXW7, PHOSPHORYLATION AT THR-58 AND RP SER-62, AND MUTAGENESIS OF THR-58 AND SER-62. RX PubMed=15103331; DOI=10.1038/sj.emboj.7600217; RA Yada M., Hatakeyama S., Kamura T., Nishiyama M., Tsunematsu R., RA Imaki H., Ishida N., Okumura F., Nakayama K., Nakayama K.I.; RT "Phosphorylation-dependent degradation of c-Myc is mediated by the F- RT box protein Fbw7."; RL EMBO J. 23:2116-2125(2004). RN [24] RP ACETYLATION AT LYS-143; LYS-157; LYS-275; LYS-317; LYS-323 AND RP LYS-371, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=16126174; DOI=10.1016/j.bbrc.2005.08.075; RA Zhang K., Faiola F., Martinez E.; RT "Six lysine residues on c-Myc are direct substrates for acetylation by RT p300."; RL Biochem. Biophys. Res. Commun. 336:274-280(2005). RN [25] RP INTERACTION WITH TAF1C. RX PubMed=15723054; DOI=10.1038/ncb1224; RA Grandori C., Gomez-Roman N., Felton-Edkins Z.A., Ngouenet C., RA Galloway D.A., Eisenman R.N., White R.J.; RT "c-Myc binds to human ribosomal DNA and stimulates transcription of RT rRNA genes by RNA polymerase I."; RL Nat. Cell Biol. 7:311-318(2005). RN [26] RP INTERACTION WITH PARP10. RX PubMed=15674325; DOI=10.1038/sj.onc.1208410; RA Yu M., Schreek S., Cerni C., Schamberger C., Lesniewicz K., Poreba E., RA Vervoorts J., Walsemann G., Groetzinger J., Kremmer E., Mehraein Y., RA Mertsching J., Kraft R., Austen M., Luescher-Firzlaff J., Luescher B.; RT "PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) RT polymerase activity, inhibits transformation."; RL Oncogene 24:1982-1993(2005). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-58, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [28] RP BIOTECHNOLOGY. RX PubMed=18035408; DOI=10.1016/j.cell.2007.11.019; RA Takahashi K., Tanabe K., Ohnuki M., Narita M., Ichisaka T., Tomoda K., RA Yamanaka S.; RT "Induction of pluripotent stem cells from adult human fibroblasts by RT defined factors."; RL Cell 131:861-872(2007). RN [29] RP UBIQUITINATION, DEUBIQUITINATION BY USP28, AND INTERACTION WITH FBXW7. RX PubMed=17873522; RA Popov N., Herold S., Llamazares M., Schulein C., Eilers M.; RT "Fbw7 and Usp28 regulate myc protein stability in response to DNA RT damage."; RL Cell Cycle 6:2327-2331(2007). RN [30] RP INTERACTION WITH KDM5A AND KDM5B. RX PubMed=17311883; DOI=10.1101/gad.1523007; RA Secombe J., Li L., Carlos L., Eisenman R.N.; RT "The Trithorax group protein Lid is a trimethyl histone H3K4 RT demethylase required for dMyc-induced cell growth."; RL Genes Dev. 21:537-551(2007). RN [31] RP INTERACTION WITH NO66. RX PubMed=17308053; DOI=10.1158/1535-7163.MCT-06-0659; RA Suzuki C., Takahashi K., Hayama S., Ishikawa N., Kato T., Ito T., RA Tsuchiya E., Nakamura Y., Daigo Y.; RT "Identification of Myc-associated protein with JmjC domain as a novel RT therapeutic target oncogene for lung cancer."; RL Mol. Cancer Ther. 6:542-551(2007). RN [32] RP UBIQUITINATION, DEUBIQUITINATION BY USP28, INTERACTION WITH FBXW7, RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-58 AND SER-62, AND RP MUTAGENESIS OF THR-58 AND SER-62. RX PubMed=17558397; DOI=10.1038/ncb1601; RA Popov N., Wanzel M., Madiredjo M., Zhang D., Beijersbergen R., RA Bernards R., Moll R., Elledge S.J., Eilers M.; RT "The ubiquitin-specific protease USP28 is required for MYC RT stability."; RL Nat. Cell Biol. 9:765-774(2007). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-58; SER-62 AND SER-71, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [34] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [35] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-148, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [36] RP REVIEW ON SENESCENCE, PHOSPHORYLATION AT SER-62 BY CDK2, AND RP MUTAGENESIS OF THR-58 AND SER-62. RX PubMed=20713526; DOI=10.1158/0008-5472.CAN-10-1383; RA Hydbring P., Larsson L.-G.; RT "Tipping the balance: Cdk2 enables Myc to suppress senescence."; RL Cancer Res. 70:6687-6691(2010). RN [37] RP PHOSPHORYLATION AT SER-62 BY CDK2, AND MUTAGENESIS OF THR-58 AND RP SER-62. RX PubMed=19966300; DOI=10.1073/pnas.0900121106; RA Hydbring P., Bahram F., Su Y., Tronnersjoe S., Hoegstrand K., RA von der Lehr N., Sharifi H.R., Lilischkis R., Hein N., Wu S., RA Vervoorts J., Henriksson M., Grandien A., Luescher B., Larsson L.-G.; RT "Phosphorylation by Cdk2 is required for Myc to repress Ras-induced RT senescence in cotransformation."; RL Proc. Natl. Acad. Sci. U.S.A. 107:58-63(2010). RN [38] RP UBIQUITINATION. RX PubMed=20551172; DOI=10.1101/gad.1920310; RA Choi S.H., Wright J.B., Gerber S.A., Cole M.D.; RT "Myc protein is stabilized by suppression of a novel E3 ligase complex RT in cancer cells."; RL Genes Dev. 24:1236-1241(2010). RN [39] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-6 AND SER-161, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [40] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-58 AND SER-62, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [41] RP PHOSPHORYLATION AT SER-62, AND MUTAGENESIS OF SER-62. RX PubMed=22307329; DOI=10.1172/JCI60818; RA Taira N., Mimoto R., Kurata M., Yamaguchi T., Kitagawa M., Miki Y., RA Yoshida K.; RT "DYRK2 priming phosphorylation of c-Jun and c-Myc modulates cell cycle RT progression in human cancer cells."; RL J. Clin. Invest. 122:859-872(2012). RN [42] RP STRUCTURE BY NMR OF 402-434 IN COMPLEX WITH MAX. RX PubMed=9680483; DOI=10.1006/jmbi.1998.1914; RA Lavigne P., Crump M.P., Gagne S.M., Hodges R.S., Kay C.M., Sykes B.D.; RT "Insights into the mechanism of heterodimerization from the 1H-NMR RT solution structure of the c-Myc-Max heterodimeric leucine zipper."; RL J. Mol. Biol. 281:165-181(1998). CC -!- FUNCTION: Transcription factor that binds DNA in a non-specific CC manner, yet also specifically recognizes the core sequence 5'- CC CAC[GA]TG-3'. Activates the transcription of growth-related genes. CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another CC bHLH protein. Binds DNA as a heterodimer with MAX. Interacts with CC TAF1C and SPAG9. Interacts with PARP10. Interacts with KDM5A and CC KDM5B. Interacts (when phosphorylated at Thr-58 and Ser-62) with CC FBXW7. Interacts with PIM2. Interacts with NO66. The heterodimer CC MYC:MAX interacts with ABI1; the interaction may enhance MYC:MAX CC transcriptional activity. Interacts with TRIM6 (By similarity). CC {ECO:0000250|UniProtKB:P01108, ECO:0000269|PubMed:15103331, CC ECO:0000269|PubMed:15674325, ECO:0000269|PubMed:15723054, CC ECO:0000269|PubMed:17308053, ECO:0000269|PubMed:17311883, CC ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17873522, CC ECO:0000269|PubMed:9680483}. CC -!- INTERACTION: CC P03070:- (xeno); NbExp=2; IntAct=EBI-447544, EBI-617698; CC O15169:AXIN1; NbExp=10; IntAct=EBI-447544, EBI-710484; CC O00499-10:BIN1; NbExp=3; IntAct=EBI-447544, EBI-7689134; CC O00499-11:BIN1; NbExp=2; IntAct=EBI-447544, EBI-7689211; CC Q15059:BRD3; NbExp=3; IntAct=EBI-447544, EBI-1383460; CC Q8N163:CCAR2; NbExp=8; IntAct=EBI-447544, EBI-355410; CC P11802:CDK4; NbExp=2; IntAct=EBI-447544, EBI-295644; CC Q86XR8:CEP57; NbExp=3; IntAct=EBI-447544, EBI-308614; CC Q14839:CHD4; NbExp=2; IntAct=EBI-447544, EBI-372916; CC O15111:CHUK; NbExp=3; IntAct=EBI-447544, EBI-81249; CC P03129:E7 (xeno); NbExp=2; IntAct=EBI-447544, EBI-866453; CC P04020:E7 (xeno); NbExp=2; IntAct=EBI-447544, EBI-7005254; CC P06788:E7 (xeno); NbExp=5; IntAct=EBI-447544, EBI-1776887; CC P03204:EBNA6 (xeno); NbExp=11; IntAct=EBI-447544, EBI-9255985; CC Q15029:EFTUD2; NbExp=5; IntAct=EBI-447544, EBI-357897; CC Q969H0:FBXW7; NbExp=4; IntAct=EBI-447544, EBI-359574; CC Q8N3Y1:FBXW8; NbExp=3; IntAct=EBI-447544, EBI-914770; CC Q92769:HDAC2; NbExp=2; IntAct=EBI-447544, EBI-301821; CC O15379:HDAC3; NbExp=6; IntAct=EBI-447544, EBI-607682; CC Q9Y6K9:IKBKG; NbExp=3; IntAct=EBI-447544, EBI-81279; CC Q8TCG1:KIAA1524; NbExp=2; IntAct=EBI-447544, EBI-1379376; CC P61244:MAX; NbExp=23; IntAct=EBI-447544, EBI-751711; CC P52164:Max (xeno); NbExp=4; IntAct=EBI-447544, EBI-1184963; CC P33993:MCM7; NbExp=6; IntAct=EBI-447544, EBI-355924; CC O75928:PIAS2; NbExp=4; IntAct=EBI-447544, EBI-348555; CC P62913:RPL11; NbExp=3; IntAct=EBI-447544, EBI-354380; CC O75182:SIN3B; NbExp=7; IntAct=EBI-447544, EBI-540462; CC Q62141:Sin3b (xeno); NbExp=8; IntAct=EBI-447544, EBI-591450; CC Q96EB6:SIRT1; NbExp=4; IntAct=EBI-447544, EBI-1802965; CC Q8N6T7:SIRT6; NbExp=3; IntAct=EBI-447544, EBI-712415; CC Q13309:SKP2; NbExp=2; IntAct=EBI-447544, EBI-456291; CC Q8TAD8:SNIP1; NbExp=9; IntAct=EBI-447544, EBI-749336; CC P08047:SP1; NbExp=4; IntAct=EBI-447544, EBI-298336; CC P11387:TOP1; NbExp=2; IntAct=EBI-447544, EBI-876302; CC Q9Y4A5:TRRAP; NbExp=4; IntAct=EBI-447544, EBI-399128; CC P0CG48:UBC; NbExp=5; IntAct=EBI-447544, EBI-3390054; CC P17480:UBTF; NbExp=2; IntAct=EBI-447544, EBI-396235; CC Q13105:ZBTB17; NbExp=4; IntAct=EBI-447544, EBI-372156; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm CC {ECO:0000269|PubMed:17558397}. Nucleus, nucleolus CC {ECO:0000269|PubMed:17558397}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P01106-1; Sequence=Displayed; CC Name=2; CC IsoId=P01106-2; Sequence=VSP_037813; CC Note=Initiates from CTG codon. Ref.7 (BAA01374) sequence is in CC conflict in positions: 2:D->N, 6:V->E. {ECO:0000305}; CC -!- PTM: Phosphorylated by PRKDC. Phosphorylation at Ser-329 by PIM2 CC leads to the stabilization of MYC (By similarity). Phosphorylation CC at Ser-62 by CDK2 prevents Ras-induced senescence. Phosphorylated CC at Ser-62 by DYRK2; this primes the protein for subsequent CC phosphorylation by GSK3B at Thr-58. Phosphorylation at Thr-58 and CC Ser-62 by GSK3 is required for ubiquitination and degradation by CC the proteasome. {ECO:0000250, ECO:0000269|PubMed:15103331, CC ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:19966300, CC ECO:0000269|PubMed:20713526, ECO:0000269|PubMed:22307329, CC ECO:0000269|PubMed:8386367}. CC -!- PTM: Ubiquitinated by the SCF(FBXW7) complex when phosphorylated CC at Thr-58 and Ser-62, leading to its degradation by the CC proteasome. In the nucleoplasm, ubiquitination is counteracted by CC USP28, which interacts with isoform 1 of FBXW7 (FBW7alpha), CC leading to its deubiquitination and preventing degradation. In the CC nucleolus, however, ubiquitination is not counteracted by USP28, CC due to the lack of interaction between isoform 4 of FBXW7 CC (FBW7gamma) and USP28, explaining the selective MYC degradation in CC the nucleolus. Also polyubiquitinated by the DCX(TRUSS) complex. CC Ubiquitinated by TRIM6 in a phosphorylation-independent manner (By CC similarity). {ECO:0000250|UniProtKB:P01108, CC ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:17558397, CC ECO:0000269|PubMed:19966300, ECO:0000269|PubMed:20713526, CC ECO:0000269|PubMed:22307329, ECO:0000269|PubMed:8386367}. CC -!- DISEASE: Note=Overexpression of MYC is implicated in the etiology CC of a variety of hematopoietic tumors. CC -!- DISEASE: Note=A chromosomal aberration involving MYC may be a CC cause of a form of B-cell chronic lymphocytic leukemia. CC Translocation t(8;12)(q24;q22) with BTG1. CC -!- DISEASE: Burkitt lymphoma (BL) [MIM:113970]: A form of CC undifferentiated malignant lymphoma commonly manifested as a large CC osteolytic lesion in the jaw or as an abdominal mass. CC {ECO:0000269|PubMed:2166998, ECO:0000269|PubMed:8220424}. Note=The CC gene represented in this entry is involved in disease CC pathogenesis. Chromosomal aberrations involving MYC are usually CC found in Burkitt lymphoma. Translocations t(8;14), t(8;22) or CC t(2;8) which juxtapose MYC to one of the heavy or light chain CC immunoglobulin gene loci. CC -!- BIOTECHNOLOGY: POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four CC Yamanaka factors. When combined, these factors are sufficient to CC reprogram differentiated cells to an embryonic-like state CC designated iPS (induced pluripotent stem) cells. iPS cells exhibit CC the morphology and growth properties of ES cells and express ES CC cell marker genes. {ECO:0000269|PubMed:18035408}. CC -!- SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. CC {ECO:0000255|PROSITE-ProRule:PRU00981}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/MYCID27.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/myc/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Myc entry; CC URL="https://en.wikipedia.org/wiki/Myc"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; L00058; AAA59882.1; -; Genomic_DNA. DR EMBL; L00057; AAA59882.1; JOINED; Genomic_DNA. DR EMBL; K00535; AAA59880.1; -; Genomic_DNA. DR EMBL; K00534; AAA59880.1; JOINED; Genomic_DNA. DR EMBL; K00535; ABW69847.1; -; Genomic_DNA. DR EMBL; K00534; ABW69847.1; JOINED; Genomic_DNA. DR EMBL; X00196; CAA25015.2; -; Genomic_DNA. DR EMBL; X00198; CAA25015.2; JOINED; Genomic_DNA. DR EMBL; X00364; CAA25106.1; -; Genomic_DNA. DR EMBL; V00568; CAA23831.1; -; mRNA. DR EMBL; K01906; AAA59881.1; -; Genomic_DNA. DR EMBL; K01905; AAA59881.1; JOINED; Genomic_DNA. DR EMBL; K02276; AAA36340.1; -; mRNA. DR EMBL; X00676; CAA25288.1; -; Genomic_DNA. DR EMBL; D10493; BAA01374.2; -; Genomic_DNA. DR EMBL; D10493; BAA01375.1; -; Genomic_DNA. DR EMBL; BT019768; AAV38573.1; -; mRNA. DR EMBL; AY214166; AAO21131.1; -; Genomic_DNA. DR EMBL; AK312883; BAG35731.1; -; mRNA. DR EMBL; AC103819; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471060; EAW92098.1; -; Genomic_DNA. DR EMBL; BC000141; AAH00141.2; -; mRNA. DR EMBL; BC000917; AAH00917.2; -; mRNA. DR EMBL; BC058901; AAH58901.2; -; mRNA. DR EMBL; M13929; AAA88092.1; -; mRNA. DR CCDS; CCDS6359.2; -. [P01106-2] DR PIR; A01349; TVHUM. DR PIR; A01350; TVHUT. DR RefSeq; NP_002458.2; NM_002467.4. [P01106-2] DR UniGene; Hs.202453; -. DR PDB; 1A93; NMR; -; A=406-434. DR PDB; 1EE4; X-ray; 2.10 A; C/D/E/F=320-328. DR PDB; 1MV0; NMR; -; A=55-68. DR PDB; 1NKP; X-ray; 1.80 A; A/D=353-434. DR PDB; 2A93; NMR; -; A=406-434. DR PDB; 2OR9; X-ray; 2.70 A; P=410-419. DR PDB; 4Y7R; X-ray; 1.90 A; B=260-267. DR PDBsum; 1A93; -. DR PDBsum; 1EE4; -. DR PDBsum; 1MV0; -. DR PDBsum; 1NKP; -. DR PDBsum; 2A93; -. DR PDBsum; 2OR9; -. DR PDBsum; 4Y7R; -. DR DisProt; DP00260; -. DR ProteinModelPortal; P01106; -. DR SMR; P01106; 353-434. DR BioGrid; 110694; 569. DR DIP; DIP-28143N; -. DR IntAct; P01106; 674. DR MINT; MINT-257327; -. DR STRING; 9606.ENSP00000367207; -. DR BindingDB; P01106; -. DR ChEMBL; CHEMBL3301395; -. DR DrugBank; DB08813; Nadroparin. DR PhosphoSite; P01106; -. DR UniCarbKB; P01106; -. DR BioMuta; MYC; -. DR DMDM; 127619; -. DR SWISS-2DPAGE; P01106; -. DR MaxQB; P01106; -. DR PaxDb; P01106; -. DR PRIDE; P01106; -. DR DNASU; 4609; -. DR Ensembl; ENST00000377970; ENSP00000367207; ENSG00000136997. [P01106-1] DR GeneID; 4609; -. DR KEGG; hsa:4609; -. DR UCSC; uc003ysi.3; human. [P01106-2] DR UCSC; uc022bbe.1; human. [P01106-1] DR CTD; 4609; -. DR GeneCards; MYC; -. DR H-InvDB; HIX0007784; -. DR HGNC; HGNC:7553; MYC. DR HPA; CAB000084; -. DR HPA; CAB010307; -. DR MIM; 113970; phenotype. DR MIM; 190080; gene. DR neXtProt; NX_P01106; -. DR Orphanet; 543; Burkitt lymphoma. DR Orphanet; 99861; Precursor T-cell acute lymphoblastic leukemia. DR PharmGKB; PA31353; -. DR eggNOG; ENOG410IFSM; Eukaryota. DR eggNOG; ENOG41124Q3; LUCA. DR GeneTree; ENSGT00510000046414; -. DR HOGENOM; HOG000043075; -. DR HOVERGEN; HBG000472; -. DR InParanoid; P01106; -. DR KO; K04377; -. DR OrthoDB; EOG7GJ6CX; -. DR PhylomeDB; P01106; -. DR TreeFam; TF106001; -. DR BioCyc; MetaCyc:ENSG00000136997-MONOMER; -. DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription. DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription. DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants. DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants. DR Reactome; R-HSA-4411364; binding of TCF/LEF:CTNNB1 to target gene promoters. DR Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling. DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition. DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry. DR SignaLink; P01106; -. DR ChiTaRS; MYC; human. DR EvolutionaryTrace; P01106; -. DR GeneWiki; Myc; -. DR GenomeRNAi; 4609; -. DR NextBio; 17740; -. DR PRO; PR:P01106; -. DR Proteomes; UP000005640; Chromosome 8. DR Bgee; P01106; -. DR CleanEx; HS_MYC; -. DR ExpressionAtlas; P01106; baseline and differential. DR Genevisible; P01106; HS. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0043234; C:protein complex; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB. DR GO; GO:0070888; F:E-box binding; IDA:UniProtKB. DR GO; GO:0032403; F:protein complex binding; IDA:UniProtKB. DR GO; GO:0070491; F:repressing transcription factor binding; IPI:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:NTNU_SB. DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:UniProtKB. DR GO; GO:0007050; P:cell cycle arrest; IDA:UniProtKB. DR GO; GO:0006879; P:cellular iron ion homeostasis; IDA:UniProtKB. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB. DR GO; GO:0035690; P:cellular response to drug; IDA:UniProtKB. DR GO; GO:0034644; P:cellular response to UV; IEP:UniProtKB. DR GO; GO:0006338; P:chromatin remodeling; IDA:UniProtKB. DR GO; GO:0051276; P:chromosome organization; IDA:UniProtKB. DR GO; GO:0006112; P:energy reserve metabolic process; NAS:UniProtKB. DR GO; GO:0044346; P:fibroblast apoptotic process; TAS:UniProtKB. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0000165; P:MAPK cascade; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0051782; P:negative regulation of cell division; IDA:UniProtKB. DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IDA:UniProtKB. DR GO; GO:0045656; P:negative regulation of monocyte differentiation; IMP:UniProtKB. DR GO; GO:0032873; P:negative regulation of stress-activated MAPK cascade; ISS:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome. DR GO; GO:0015671; P:oxygen transport; NAS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell proliferation; IDA:MGI. DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB. DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IMP:UniProtKB. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:UniProtKB. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IDA:UniProtKB. DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISS:UniProtKB. DR GO; GO:0090096; P:positive regulation of metanephric cap mesenchymal cell proliferation; ISS:UniProtKB. DR GO; GO:2001022; P:positive regulation of response to DNA damage stimulus; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; IDA:MGI. DR GO; GO:0032204; P:regulation of telomere maintenance; IMP:BHF-UCL. DR GO; GO:0042493; P:response to drug; IEP:UniProtKB. DR GO; GO:0010332; P:response to gamma radiation; IDA:UniProtKB. DR GO; GO:0070848; P:response to growth factor; TAS:UniProtKB. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0006351; P:transcription, DNA-templated; TAS:Reactome. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome. DR Gene3D; 4.10.280.10; -; 1. DR InterPro; IPR011598; bHLH_dom. DR InterPro; IPR003327; Myc-LZ. DR InterPro; IPR002418; Tscrpt_reg_Myc. DR InterPro; IPR012682; Tscrpt_reg_Myc_N. DR Pfam; PF00010; HLH; 1. DR Pfam; PF02344; Myc-LZ; 1. DR Pfam; PF01056; Myc_N; 1. DR PIRSF; PIRSF001705; Myc_protein; 1. DR PRINTS; PR00044; LEUZIPPRMYC. DR SMART; SM00353; HLH; 1. DR SUPFAM; SSF47459; SSF47459; 1. DR PROSITE; PS50888; BHLH; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Chromosomal rearrangement; Complete proteome; DNA-binding; KW Glycoprotein; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; KW Reference proteome; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1 439 Myc proto-oncogene protein. FT /FTId=PRO_0000127293. FT DOMAIN 354 406 bHLH. {ECO:0000255|PROSITE- FT ProRule:PRU00981}. FT REGION 413 434 Leucine-zipper. FT COMPBIAS 33 37 Poly-Gln. FT COMPBIAS 88 91 Poly-Gly. FT MOD_RES 6 6 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 8 8 Phosphothreonine; by RAF; in vitro. FT {ECO:0000269|PubMed:9315742}. FT MOD_RES 58 58 Phosphothreonine; by GSK3; alternate. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:21406692, FT ECO:0000269|PubMed:15103331, FT ECO:0000269|PubMed:17558397, FT ECO:0000269|PubMed:8386367}. FT MOD_RES 62 62 Phosphoserine; by DYRK2, GSK3 and CDK2. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:21406692, FT ECO:0000269|PubMed:15103331, FT ECO:0000269|PubMed:17558397, FT ECO:0000269|PubMed:19966300, FT ECO:0000269|PubMed:20713526, FT ECO:0000269|PubMed:22307329, FT ECO:0000269|PubMed:8386367}. FT MOD_RES 71 71 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 143 143 N6-acetyllysine; by PCAF. FT {ECO:0000269|PubMed:16126174}. FT MOD_RES 148 148 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 157 157 N6-acetyllysine; by PCAF. FT {ECO:0000269|PubMed:16126174}. FT MOD_RES 161 161 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 275 275 N6-acetyllysine; by PCAF. FT {ECO:0000269|PubMed:16126174}. FT MOD_RES 317 317 N6-acetyllysine; by PCAF. FT {ECO:0000269|PubMed:16126174}. FT MOD_RES 323 323 N6-acetyllysine; by PCAF. FT {ECO:0000269|PubMed:16126174}. FT MOD_RES 329 329 Phosphoserine; by PIM2; in vitro. FT {ECO:0000250}. FT MOD_RES 371 371 N6-acetyllysine; by PCAF. FT {ECO:0000269|PubMed:16126174}. FT CARBOHYD 58 58 O-linked (GlcNAc); alternate. FT {ECO:0000269|PubMed:7642555}. FT /FTId=CAR_000033. FT VAR_SEQ 1 1 M -> MDFFRVVENQQPPATM (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_037813. FT VARIANT 11 11 N -> S (in dbSNP:rs4645959). FT {ECO:0000269|Ref.11}. FT /FTId=VAR_016327. FT VARIANT 39 39 E -> D (in a Burkitt lymphoma symple). FT {ECO:0000269|PubMed:6419122, FT ECO:0000269|PubMed:8220424}. FT /FTId=VAR_063384. FT VARIANT 57 57 P -> S (in a Burkitt lymphoma sample). FT {ECO:0000269|PubMed:8220424}. FT /FTId=VAR_063385. FT VARIANT 59 59 P -> A (in a Burkitt lymphoma sample). FT {ECO:0000269|PubMed:8220424}. FT /FTId=VAR_063386. FT VARIANT 86 86 N -> T (in a Burkitt lymphoma sample). FT {ECO:0000269|PubMed:8220424}. FT /FTId=VAR_063387. FT VARIANT 160 160 G -> C (in dbSNP:rs4645960). FT {ECO:0000269|Ref.11}. FT /FTId=VAR_016328. FT VARIANT 170 170 V -> I (in dbSNP:rs4645961). FT {ECO:0000269|Ref.11}. FT /FTId=VAR_016329. FT VARIANT 322 322 A -> V (in dbSNP:rs4645968). FT {ECO:0000269|Ref.11}. FT /FTId=VAR_016330. FT MUTAGEN 58 58 T->A: Impairs interaction with FBXW7 and FT subsequent degradation by the proteasome. FT Normal inhibition of Ras-induced FT senescence. {ECO:0000269|PubMed:15103331, FT ECO:0000269|PubMed:17558397, FT ECO:0000269|PubMed:19966300, FT ECO:0000269|PubMed:20713526}. FT MUTAGEN 62 62 S->A: Impairs interaction with FBXW7 and FT subsequent degradation by the proteasome. FT Impaired inhibition of Ras-induced FT senescence. Abolishes phosphorylation by FT DYRK2, and subsequent phosphorylation by FT GSK3B at Thr-58. FT {ECO:0000269|PubMed:15103331, FT ECO:0000269|PubMed:17558397, FT ECO:0000269|PubMed:19966300, FT ECO:0000269|PubMed:20713526, FT ECO:0000269|PubMed:22307329}. FT CONFLICT 6 7 SF -> TI (in Ref. 5; no nucleotide FT entry). {ECO:0000305}. FT CONFLICT 10 10 R -> K (in Ref. 5; no nucleotide entry). FT {ECO:0000305}. FT CONFLICT 56 56 L -> LL (in Ref. 5; no nucleotide entry). FT {ECO:0000305}. FT CONFLICT 62 62 S -> P (in Ref. 7; CAA25288). FT {ECO:0000305}. FT CONFLICT 88 88 G -> D (in Ref. 5; no nucleotide entry). FT {ECO:0000305}. FT CONFLICT 92 92 S -> N (in Ref. 5; no nucleotide entry). FT {ECO:0000305}. FT CONFLICT 114 114 S -> N (in Ref. 5; no nucleotide entry). FT {ECO:0000305}. FT CONFLICT 120 120 D -> G (in Ref. 5; no nucleotide entry). FT {ECO:0000305}. FT CONFLICT 171 171 C -> S (in Ref. 5; no nucleotide entry). FT {ECO:0000305}. FT CONFLICT 203 203 S -> R (in Ref. 5; no nucleotide entry). FT {ECO:0000305}. FT CONFLICT 230 230 S -> A (in Ref. 5; no nucleotide entry). FT {ECO:0000305}. FT CONFLICT 240 240 L -> F (in Ref. 5; no nucleotide entry). FT {ECO:0000305}. FT CONFLICT 245 245 P -> S (in Ref. 5; no nucleotide entry). FT {ECO:0000305}. FT HELIX 353 378 {ECO:0000244|PDB:1NKP}. FT HELIX 382 384 {ECO:0000244|PDB:1NKP}. FT HELIX 392 434 {ECO:0000244|PDB:1NKP}. SQ SEQUENCE 439 AA; 48804 MW; ED5C028029A4C5D1 CRC64; MPLNVSFTNR NYDLDYDSVQ PYFYCDEEEN FYQQQQQSEL QPPAPSEDIW KKFELLPTPP LSPSRRSGLC SPSYVAVTPF SLRGDNDGGG GSFSTADQLE MVTELLGGDM VNQSFICDPD DETFIKNIII QDCMWSGFSA AAKLVSEKLA SYQAARKDSG SPNPARGHSV CSTSSLYLQD LSAAASECID PSVVFPYPLN DSSSPKSCAS QDSSAFSPSS DSLLSSTESS PQGSPEPLVL HEETPPTTSS DSEEEQEDEE EIDVVSVEKR QAPGKRSESG SPSAGGHSKP PHSPLVLKRC HVSTHQHNYA APPSTRKDYP AAKRVKLDSV RVLRQISNNR KCTSPRSSDT EENVKRRTHN VLERQRRNEL KRSFFALRDQ IPELENNEKA PKVVILKKAT AYILSVQAEE QKLISEEDLL RKRREQLKHK LEQLRNSCA // ID NDKB_HUMAN Reviewed; 152 AA. AC P22392; A8MWA3; Q1WM23; Q6LCT6; DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1991, sequence version 1. DT 11-NOV-2015, entry version 189. DE RecName: Full=Nucleoside diphosphate kinase B; DE Short=NDK B; DE Short=NDP kinase B; DE EC=2.7.4.6; DE AltName: Full=C-myc purine-binding transcription factor PUF; DE AltName: Full=Histidine protein kinase NDKB; DE EC=2.7.13.3; DE AltName: Full=nm23-H2; GN Name=NME2; Synonyms=NM23B; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1988104; RA Stahl J.A., Leone A., Rosengard A.M., Porter L., Liotta L.A., RA Steeg P.S., King C.R.; RT "Identification of a second human nm23 gene, nm23-H2."; RL Cancer Res. 51:445-449(1991). RN [2] RP PROTEIN SEQUENCE (ISOFORM 1), SUBUNIT, AND ACTIVE SITE. RX PubMed=1851158; RA Gilles A.-M., Presecan E., Vonica A., Lascu I.; RT "Nucleoside diphosphate kinase from human erythrocytes. Structural RT characterization of the two polypeptide chains responsible for RT heterogeneity of the hexameric enzyme."; RL J. Biol. Chem. 266:8784-8789(1991). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8392752; DOI=10.1126/science.8392752; RA Postel E.H., Berberich S.J., Flint S.J., Ferrone C.A.; RT "Human c-myc transcription factor PuF identified as nm23-H2 nucleoside RT diphosphate kinase, a candidate suppressor of tumor metastasis."; RL Science 261:478-480(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION, AND RP TISSUE SPECIFICITY. RC TISSUE=Neuroblastoma; RX PubMed=16442775; DOI=10.1016/j.ygeno.2005.11.004; RA Valentijn L.J., Koster J., Versteeg R.; RT "Read-through transcript from NM23-H1 into the neighboring NM23-H2 RT gene encodes a novel protein, NM23-LV."; RL Genomics 87:483-489(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in RT the human lineage."; RL Nature 440:1045-1049(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-18. RX PubMed=7488060; DOI=10.1006/bbrc.1995.2550; RA Seifert M., Seib T., Engel M., Dooley S., Welter C.; RT "Characterization of the human nm23-H2 promoter region and RT localization of the microsatellite D17S396."; RL Biochem. Biophys. Res. Commun. 215:910-914(1995). RN [8] RP INTERACTION WITH ITGB1BP1, AND SUBCELLULAR LOCATION. RX PubMed=11919189; DOI=10.1074/jbc.M200200200; RA Fournier H.N., Dupe-Manet S., Bouvard D., Lacombe M.L., Marie C., RA Block M.R., Albiges-Rizo C.; RT "Integrin cytoplasmic domain-associated protein 1alpha (ICAP-1alpha) RT interacts directly with the metastasis suppressor nm23-H2, and both RT proteins are targeted to newly formed cell adhesion sites upon RT integrin engagement."; RL J. Biol. Chem. 277:20895-20902(2002). RN [9] RP FUNCTION, AND INTERACTION WITH AKAP13. RX PubMed=15249197; DOI=10.1016/j.bbrc.2004.06.067; RA Iwashita S., Fujii M., Mukai H., Ono Y., Miyamoto M.; RT "Lbc proto-oncogene product binds to and could be negatively regulated RT by metastasis suppressor nm23-H2."; RL Biochem. Biophys. Res. Commun. 320:1063-1068(2004). RN [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2 (ISOFORM 3), CLEAVAGE OF RP INITIATOR METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM 3), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-128, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [12] RP FUNCTION AS HISTIDINE PROTEIN KINASE. RX PubMed=20946858; DOI=10.1016/S0076-6879(10)71020-X; RA Wieland T., Hippe H.J., Ludwig K., Zhou X.B., Korth M., Klumpp S.; RT "Reversible histidine phosphorylation in mammalian cells: a teeter- RT totter formed by nucleoside diphosphate kinase and protein histidine RT phosphatase 1."; RL Methods Enzymol. 471:379-402(2010). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22905912; DOI=10.1021/pr300539b; RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., RA Fischer-Posovszky P., Mariman E.C., Renes J.; RT "Resveratrol-induced changes of the human adipocyte secretion RT profile."; RL J. Proteome Res. 11:4733-4743(2012). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS). RX PubMed=7658474; DOI=10.1006/jmbi.1995.0457; RA Webb P.A., Perisic O., Mendola C.E., Backer J.M., Williams R.L.; RT "The crystal structure of a human nucleoside diphosphate kinase, NM23- RT H2."; RL J. Mol. Biol. 251:574-587(1995). RN [18] RP X-RAY CRYSTALLOGRAPHY (2 ANGSTROMS). RX PubMed=8747457; DOI=10.1016/S0969-2126(01)00268-4; RA Morera S., Lacombe M.-L., Xu Y., Lebras G., Janin J.; RT "X-ray structure of human nucleoside diphosphate kinase B complexed RT with GDP at 2-A resolution."; RL Structure 3:1307-1314(1995). CC -!- FUNCTION: Major role in the synthesis of nucleoside triphosphates CC other than ATP. Negatively regulates Rho activity by interacting CC with AKAP13/LBC. Acts as a transcriptional activator of the MYC CC gene; binds DNA non-specifically (PubMed:8392752). Exhibits CC histidine protein kinase activity. {ECO:0000269|PubMed:15249197, CC ECO:0000269|PubMed:20946858, ECO:0000269|PubMed:8392752}. CC -!- CATALYTIC ACTIVITY: ATP + nucleoside diphosphate = ADP + CC nucleoside triphosphate. CC -!- CATALYTIC ACTIVITY: ATP + protein L-histidine = ADP + protein N- CC phospho-L-histidine. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- SUBUNIT: Hexamer of two different chains: A and B (A6, A5B, A4B2, CC A3B3, A2B4, AB5, B6). Interacts with CAPN8 (By similarity). CC Interacts with AKAP13. Interacts ITGB1BP1 (via C-terminal domain CC region). {ECO:0000250, ECO:0000269|PubMed:11919189, CC ECO:0000269|PubMed:15249197, ECO:0000269|PubMed:1851158}. CC -!- INTERACTION: CC O14713-1:ITGB1BP1; NbExp=7; IntAct=EBI-713693, EBI-2127367; CC P15531:NME1; NbExp=2; IntAct=EBI-713693, EBI-741141; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell projection, CC lamellipodium. Cell projection, ruffle. Note=Isoform 2 is mainly CC cytoplasmic and isoform 1 and isoform 2 are excluded from the CC nucleolus. Colocalizes with ITGB1 and ITGB1BP1 at the edge or CC peripheral ruffles and lamellipodia during the early stages of CC cell spreading on fibronectin or collagen but not on vitronectin CC or laminin substrates. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=NM23-H2; CC IsoId=P22392-1; Sequence=Displayed; CC Name=3; Synonyms=NM23-LV; CC IsoId=P22392-2; Sequence=VSP_036708; CC Note=Based on a naturally occurring readthrough transcript which CC produces an NME1-NME2 fusion protein. Initiator Met-1 is removed CC (By similarity). Contains a N-acetylalanine at position 2. CC {ECO:0000244|PubMed:19413330, ECO:0000250}; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC {ECO:0000269|PubMed:16442775}. CC -!- SIMILARITY: Belongs to the NDK family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X58965; CAB37870.1; -; mRNA. DR EMBL; M36981; AAA36369.1; -; mRNA. DR EMBL; L16785; AAA60228.1; -; mRNA. DR EMBL; DQ109675; AAZ82097.1; -; mRNA. DR EMBL; AC005839; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC002476; AAH02476.1; -; mRNA. DR EMBL; BC133029; AAI33030.1; -; mRNA. DR EMBL; BC133031; AAI33032.1; -; mRNA. DR EMBL; U29200; AAA86745.1; -; Genomic_DNA. DR CCDS; CCDS11580.1; -. [P22392-1] DR PIR; A49798; A49798. DR RefSeq; NP_001018146.1; NM_001018136.2. [P22392-2] DR RefSeq; NP_001018147.1; NM_001018137.2. [P22392-1] DR RefSeq; NP_001018148.1; NM_001018138.1. [P22392-1] DR RefSeq; NP_001018149.1; NM_001018139.2. [P22392-1] DR RefSeq; NP_002503.1; NM_002512.3. [P22392-1] DR UniGene; Hs.463456; -. DR PDB; 1NSK; X-ray; 2.80 A; L/N/O/R/T/U=1-152. DR PDB; 1NUE; X-ray; 2.00 A; A/B/C/D/E/F=2-152. DR PDB; 3BBB; X-ray; 1.30 A; A/B/C/D/E/F=2-152. DR PDB; 3BBC; X-ray; 1.70 A; A/B/C/D/E/F=2-152. DR PDB; 3BBF; X-ray; 1.70 A; A/B/C/D/E/F=2-152. DR PDBsum; 1NSK; -. DR PDBsum; 1NUE; -. DR PDBsum; 3BBB; -. DR PDBsum; 3BBC; -. DR PDBsum; 3BBF; -. DR ProteinModelPortal; P22392; -. DR SMR; P22392; 2-152. DR BioGrid; 110895; 53. DR BioGrid; 576341; 8. DR DIP; DIP-50179N; -. DR IntAct; P22392; 18. DR MINT; MINT-1429922; -. DR STRING; 9606.ENSP00000376886; -. DR ChEMBL; CHEMBL2160; -. DR DrugBank; DB00718; Adefovir Dipivoxil. DR DrugBank; DB00709; Lamivudine. DR DrugBank; DB00300; Tenofovir. DR PhosphoSite; P22392; -. DR BioMuta; NME2; -. DR DMDM; 127983; -. DR DOSAC-COBS-2DPAGE; P22392; -. DR OGP; P22392; -. DR UCD-2DPAGE; P22392; -. DR MaxQB; P22392; -. DR PaxDb; P22392; -. DR PRIDE; P22392; -. DR DNASU; 4831; -. DR DNASU; 654364; -. DR Ensembl; ENST00000393193; ENSP00000376889; ENSG00000011052. [P22392-2] DR GeneID; 4831; -. DR GeneID; 654364; -. DR KEGG; hsa:4831; -. DR KEGG; hsa:654364; -. DR UCSC; uc002itj.3; human. [P22392-2] DR UCSC; uc002itl.3; human. [P22392-1] DR CTD; 4831; -. DR CTD; 654364; -. DR GeneCards; NME2; -. DR HGNC; HGNC:7850; NME2. DR HPA; CAB002169; -. DR HPA; HPA041113; -. DR MIM; 156491; gene. DR neXtProt; NX_P22392; -. DR PharmGKB; PA162398077; -. DR eggNOG; KOG0888; Eukaryota. DR eggNOG; COG0105; LUCA. DR GeneTree; ENSGT00760000119146; -. DR HOGENOM; HOG000224564; -. DR HOVERGEN; HBG000423; -. DR InParanoid; P22392; -. DR KO; K00940; -. DR OrthoDB; EOG7GJ6FG; -. DR PhylomeDB; P22392; -. DR TreeFam; TF106373; -. DR BioCyc; MetaCyc:HS04463-MONOMER; -. DR Reactome; R-HSA-499943; Synthesis and interconversion of nucleotide di- and triphosphates. DR SignaLink; P22392; -. DR ChiTaRS; NME2; human. DR EvolutionaryTrace; P22392; -. DR GeneWiki; NME1-NME2; -. DR GeneWiki; NME2; -. DR NextBio; 18612; -. DR PRO; PR:P22392; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; P22392; -. DR ExpressionAtlas; P22392; baseline and differential. DR Genevisible; P22392; HS. DR GO; GO:0071944; C:cell periphery; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005622; C:intracellular; IBA:GO_Central. DR GO; GO:0030027; C:lamellipodium; IDA:HGNC. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0001726; C:ruffle; IDA:HGNC. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004550; F:nucleoside diphosphate kinase activity; IDA:UniProtKB. DR GO; GO:0004673; F:protein histidine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:UniProtKB. DR GO; GO:0007155; P:cell adhesion; TAS:HGNC. DR GO; GO:0006241; P:CTP biosynthetic process; IEA:InterPro. DR GO; GO:0006183; P:GTP biosynthetic process; IEA:InterPro. DR GO; GO:0007229; P:integrin-mediated signaling pathway; IDA:UniProtKB. DR GO; GO:0098779; P:mitophagy in response to mitochondrial depolarization; IGI:ParkinsonsUK-UCL. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:HGNC. DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome. DR GO; GO:0055086; P:nucleobase-containing small molecule metabolic process; TAS:Reactome. DR GO; GO:0009142; P:nucleoside triphosphate biosynthetic process; IDA:UniProtKB. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IMP:HGNC. DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IMP:HGNC. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0006163; P:purine nucleotide metabolic process; IBA:GO_Central. DR GO; GO:0006220; P:pyrimidine nucleotide metabolic process; IBA:GO_Central. DR GO; GO:0045682; P:regulation of epidermis development; IMP:HGNC. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:UniProtKB. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0006228; P:UTP biosynthetic process; IEA:InterPro. DR HAMAP; MF_00451; NDP_kinase; 1. DR InterPro; IPR001564; Nucleoside_diP_kinase. DR InterPro; IPR023005; Nucleoside_diP_kinase_AS. DR Pfam; PF00334; NDK; 1. DR PRINTS; PR01243; NUCDPKINASE. DR SMART; SM00562; NDK; 1. DR PROSITE; PS00469; NDP_KINASES; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW ATP-binding; Cell projection; Complete proteome; Cytoplasm; KW Direct protein sequencing; DNA-binding; Kinase; Magnesium; KW Metal-binding; Nucleotide metabolism; Nucleotide-binding; Nucleus; KW Reference proteome; Transcription; Transcription regulation; KW Transferase. FT CHAIN 1 152 Nucleoside diphosphate kinase B. FT /FTId=PRO_0000137117. FT REGION 1 66 Interaction with AKAP13. FT ACT_SITE 118 118 Pros-phosphohistidine intermediate. FT {ECO:0000269|PubMed:1851158}. FT BINDING 12 12 ATP. FT BINDING 60 60 ATP. FT BINDING 88 88 ATP. FT BINDING 94 94 ATP. FT BINDING 105 105 ATP. FT BINDING 115 115 ATP. FT MOD_RES 128 128 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT VAR_SEQ 1 1 M -> MANCERTFIAIKPDGVQRGLVGEIIKRFEQKGFRLV FT GLKFMQASEDLLKEHYVDLKDRPFFAGLVKYMHSGPVVAMV FT WEGLNVVKTGRVMLGETNPADSKPGTIRGDFCIQVGRTM FT (in isoform 3). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:16442775}. FT /FTId=VSP_036708. FT STRAND 6 11 {ECO:0000244|PDB:3BBB}. FT HELIX 13 17 {ECO:0000244|PDB:3BBB}. FT HELIX 21 31 {ECO:0000244|PDB:3BBB}. FT STRAND 34 41 {ECO:0000244|PDB:3BBB}. FT HELIX 45 51 {ECO:0000244|PDB:3BBB}. FT HELIX 53 55 {ECO:0000244|PDB:3BBB}. FT HELIX 61 68 {ECO:0000244|PDB:3BBB}. FT STRAND 73 80 {ECO:0000244|PDB:3BBB}. FT HELIX 83 91 {ECO:0000244|PDB:3BBB}. FT HELIX 96 98 {ECO:0000244|PDB:3BBB}. FT HELIX 104 108 {ECO:0000244|PDB:3BBB}. FT HELIX 112 114 {ECO:0000244|PDB:3BBC}. FT STRAND 117 119 {ECO:0000244|PDB:3BBB}. FT HELIX 123 133 {ECO:0000244|PDB:3BBB}. FT HELIX 136 138 {ECO:0000244|PDB:3BBB}. FT HELIX 147 150 {ECO:0000244|PDB:3BBB}. SQ SEQUENCE 152 AA; 17298 MW; 1A5C3F84D7AD272C CRC64; MANLERTFIA IKPDGVQRGL VGEIIKRFEQ KGFRLVAMKF LRASEEHLKQ HYIDLKDRPF FPGLVKYMNS GPVVAMVWEG LNVVKTGRVM LGETNPADSK PGTIRGDFCI QVGRNIIHGS DSVKSAEKEI SLWFKPEELV DYKSCAHDWV YE // ID NOL4L_HUMAN Reviewed; 436 AA. AC Q96MY1; Q5JYB7; Q6P0Y4; Q9BR34; Q9NQF6; DT 01-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-2003, sequence version 2. DT 11-NOV-2015, entry version 111. DE RecName: Full=Nucleolar protein 4-like; GN Name=NOL4L; Synonyms=C20orf112, C20orf113; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Neuron; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., RA Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). CC -!- INTERACTION: CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-6660790, EBI-10171858; CC P56545:CTBP2; NbExp=3; IntAct=EBI-6660790, EBI-741533; CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-6660790, EBI-10171902; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q96MY1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q96MY1-2; Sequence=VSP_014667, VSP_014668; CC Note=No experimental confirmation available.; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AK056286; BAB71138.1; -; mRNA. DR EMBL; AL034550; CAI42261.1; -; Genomic_DNA. DR EMBL; BC065370; AAH65370.1; -; mRNA. DR CCDS; CCDS13202.1; -. [Q96MY1-1] DR RefSeq; NP_001243727.1; NM_001256798.1. DR RefSeq; NP_542183.2; NM_080616.4. [Q96MY1-1] DR RefSeq; XP_005260345.1; XM_005260288.1. [Q96MY1-1] DR RefSeq; XP_005260346.1; XM_005260289.3. [Q96MY1-1] DR UniGene; Hs.516978; -. DR UniGene; Hs.729596; -. DR ProteinModelPortal; Q96MY1; -. DR BioGrid; 126651; 5. DR IntAct; Q96MY1; 4. DR STRING; 9606.ENSP00000352704; -. DR PhosphoSite; Q96MY1; -. DR BioMuta; C20orf112; -. DR DMDM; 28212212; -. DR MaxQB; Q96MY1; -. DR PaxDb; Q96MY1; -. DR PRIDE; Q96MY1; -. DR DNASU; 140688; -. DR Ensembl; ENST00000359676; ENSP00000352704; ENSG00000197183. [Q96MY1-1] DR GeneID; 140688; -. DR KEGG; hsa:140688; -. DR UCSC; uc002wxu.5; human. [Q96MY1-1] DR CTD; 140688; -. DR GeneCards; NOL4L; -. DR H-InvDB; HIX0015727; -. DR H-InvDB; HIX0015728; -. DR HGNC; HGNC:16106; NOL4L. DR HPA; HPA041768; -. DR HPA; HPA043600; -. DR neXtProt; NX_Q96MY1; -. DR PharmGKB; PA25652; -. DR eggNOG; ENOG410IHZD; Eukaryota. DR eggNOG; ENOG410YIBB; LUCA. DR GeneTree; ENSGT00390000017363; -. DR HOGENOM; HOG000220856; -. DR HOVERGEN; HBG031438; -. DR InParanoid; Q96MY1; -. DR PhylomeDB; Q96MY1; -. DR TreeFam; TF325594; -. DR ChiTaRS; C20orf112; human. DR GenomeRNAi; 140688; -. DR NextBio; 84231; -. DR PRO; PR:Q96MY1; -. DR Proteomes; UP000005640; Chromosome 20. DR Bgee; Q96MY1; -. DR CleanEx; HS_C20orf112; -. DR ExpressionAtlas; Q96MY1; baseline and differential. DR Genevisible; Q96MY1; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR InterPro; IPR026746; NOL4L. DR PANTHER; PTHR12449:SF19; PTHR12449:SF19; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Phosphoprotein; KW Reference proteome. FT CHAIN 1 436 Nucleolar protein 4-like. FT /FTId=PRO_0000079456. FT COMPBIAS 161 169 Poly-Asp. FT MOD_RES 130 130 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT VAR_SEQ 382 398 TPTPSSTSTSRPVPTAQ -> SALSGEPPTRRWGCSSV FT (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_014667. FT VAR_SEQ 399 436 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_014668. FT CONFLICT 215 215 K -> E (in Ref. 1; BAB71138). FT {ECO:0000305}. SQ SEQUENCE 436 AA; 47215 MW; 139A07537D875DF8 CRC64; MSDSTWMSAD PHLASSLSPS QDERMRSPQN LHSQEDDDSS SESGSGNGSS TLNPSTSSST QGDPAFPEMN GNGAVAPMDF TTAAEDQPIN LCDKLPPATA LGTASYPSDG CGADGLRSRV KYGVKTTPES PPYSSGSYDS IKTEVSGCPE DLTVGRAPTA DDDDDDHDDH EDNDKMNDSE GMDPERLKAF NMFVRLFVDE NLDRMVPISK QPKEKIQAII ESCSRQFPEF QERARKRIRT YLKSCRRMKK NGMEMTRPTP PHLTSAMAEN ILAAACESET RKAAKRMRLE IYQSSQDEPI ALDKQHSRDS AAITHSTYSL PASSYSQDPV YANGGLNYSY RGYGALSSNL QPPASLQTGN HSNGPTDLSM KGGASTTSTT PTPTPSSTST SRPVPTAQLS PTEISAVRQL IAGYRESAAF LLRSADELEN LILQQN // ID NOL4_HUMAN Reviewed; 638 AA. AC O94818; B4DSQ0; B7Z3Z7; F5H1E3; Q6IBS2; Q9BWF1; DT 26-APR-2004, integrated into UniProtKB/Swiss-Prot. DT 05-APR-2011, sequence version 2. DT 11-NOV-2015, entry version 108. DE RecName: Full=Nucleolar protein 4; DE AltName: Full=Nucleolar-localized protein; GN Name=NOL4; Synonyms=NOLP; ORFNames=HRIHFB2255; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, AND RP TISSUE SPECIFICITY. RC TISSUE=Fetal brain; RX PubMed=9813152; DOI=10.1006/bbrc.1998.9606; RA Ueki N., Kondo M., Seki N., Yano K., Oda T., Masuho Y., RA Muramatsu M.-A.; RT "NOLP: identification of a novel human nucleolar protein and RT determination of sequence requirements for its nucleolar RT localization."; RL Biochem. Biophys. Res. Commun. 252:97-102(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). RC TISSUE=Brain, and Thalamus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16177791; DOI=10.1038/nature03983; RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R., RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., RA O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.; RT "DNA sequence and analysis of human chromosome 18."; RL Nature 437:551-555(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 9-638 (ISOFORM 2). RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 115-638 (ISOFORM 2). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 115-638 (ISOFORM 2). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 336-638 (ISOFORM 1), AND RP SUBCELLULAR LOCATION. RC TISSUE=Fetal brain; RX PubMed=9853615; DOI=10.1038/4315; RA Ueki N., Oda T., Kondo M., Yano K., Noguchi T., Muramatsu M.-A.; RT "Selection system for genes encoding nuclear-targeted proteins."; RL Nat. Biotechnol. 16:1338-1342(1998). CC -!- INTERACTION: CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-10190763, EBI-10171858; CC P56545:CTBP2; NbExp=3; IntAct=EBI-10190763, EBI-741533; CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-10190763, EBI-10171902; CC Q8IZU0:FAM9B; NbExp=3; IntAct=EBI-10190763, EBI-10175124; CC O75971:SNAPC5; NbExp=3; IntAct=EBI-10190763, EBI-749483; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus CC {ECO:0000269|PubMed:9813152, ECO:0000269|PubMed:9853615}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=O94818-1; Sequence=Displayed; CC Name=2; CC IsoId=O94818-2; Sequence=VSP_010080; CC Name=3; CC IsoId=O94818-3; Sequence=VSP_043344; CC Note=No experimental confirmation available.; CC Name=4; CC IsoId=O94818-4; Sequence=VSP_045836; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed predominantly in fetal brain, adult CC brain and testis. {ECO:0000269|PubMed:9813152}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH00313.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305}; CC Sequence=BAA34576.1; Type=Erroneous termination; Positions=38; Note=Translated as Gln.; Evidence={ECO:0000305}; CC Sequence=BAA34576.1; Type=Frameshift; Positions=82; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AB017800; BAA34576.1; ALT_SEQ; mRNA. DR EMBL; AK296539; BAH12383.1; -; mRNA. DR EMBL; AK299850; BAG61712.1; -; mRNA. DR EMBL; AC010798; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC018972; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC087397; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC104985; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000313; AAH00313.1; ALT_SEQ; mRNA. DR EMBL; BT006763; AAP35409.1; -; mRNA. DR EMBL; CR456730; CAG33011.1; -; mRNA. DR EMBL; AB015339; BAA34797.1; -; mRNA. DR CCDS; CCDS11907.2; -. [O94818-1] DR CCDS; CCDS56058.1; -. [O94818-4] DR CCDS; CCDS56059.1; -. [O94818-3] DR CCDS; CCDS59308.1; -. [O94818-2] DR PIR; JE0335; JE0335. DR RefSeq; NP_001185475.1; NM_001198546.1. DR RefSeq; NP_001185476.1; NM_001198547.1. [O94818-3] DR RefSeq; NP_001185477.1; NM_001198548.1. [O94818-2] DR RefSeq; NP_001185478.1; NM_001198549.1. [O94818-4] DR RefSeq; NP_001269456.1; NM_001282527.1. DR RefSeq; NP_003778.2; NM_003787.4. [O94818-1] DR RefSeq; XP_006722626.1; XM_006722563.2. [O94818-1] DR RefSeq; XP_011524539.1; XM_011526237.1. [O94818-1] DR RefSeq; XP_011524540.1; XM_011526238.1. DR UniGene; Hs.514795; -. DR ProteinModelPortal; O94818; -. DR BioGrid; 114256; 9. DR IntAct; O94818; 8. DR MINT; MINT-1429799; -. DR STRING; 9606.ENSP00000261592; -. DR PhosphoSite; O94818; -. DR BioMuta; NOL4; -. DR PaxDb; O94818; -. DR PRIDE; O94818; -. DR DNASU; 8715; -. DR Ensembl; ENST00000261592; ENSP00000261592; ENSG00000101746. [O94818-1] DR Ensembl; ENST00000535384; ENSP00000445733; ENSG00000101746. [O94818-4] DR Ensembl; ENST00000538587; ENSP00000443472; ENSG00000101746. [O94818-3] DR Ensembl; ENST00000589544; ENSP00000465450; ENSG00000101746. [O94818-2] DR GeneID; 8715; -. DR KEGG; hsa:8715; -. DR UCSC; uc002kxt.4; human. [O94818-2] DR UCSC; uc010dmh.3; human. [O94818-3] DR UCSC; uc010dmi.3; human. [O94818-1] DR CTD; 8715; -. DR GeneCards; NOL4; -. DR HGNC; HGNC:7870; NOL4. DR HPA; HPA046740; -. DR MIM; 603577; gene. DR neXtProt; NX_O94818; -. DR PharmGKB; PA31674; -. DR eggNOG; ENOG410IEBQ; Eukaryota. DR eggNOG; ENOG411245F; LUCA. DR GeneTree; ENSGT00390000017363; -. DR HOGENOM; HOG000220856; -. DR HOVERGEN; HBG031438; -. DR InParanoid; O94818; -. DR OMA; SEYRIED; -. DR OrthoDB; EOG7JDR0F; -. DR PhylomeDB; O94818; -. DR TreeFam; TF325594; -. DR ChiTaRS; NOL4; human. DR GenomeRNAi; 8715; -. DR NextBio; 32683; -. DR PRO; PR:O94818; -. DR Proteomes; UP000005640; Chromosome 18. DR Bgee; O94818; -. DR CleanEx; HS_NOL4; -. DR ExpressionAtlas; O94818; baseline and differential. DR Genevisible; O94818; HS. DR GO; GO:0005730; C:nucleolus; TAS:ProtInc. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0003723; F:RNA binding; TAS:ProtInc. DR InterPro; IPR026747; NOL4. DR PANTHER; PTHR12449:SF17; PTHR12449:SF17; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Nucleus; Reference proteome. FT CHAIN 1 638 Nucleolar protein 4. FT /FTId=PRO_0000096935. FT VAR_SEQ 1 285 Missing (in isoform 4). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_045836. FT VAR_SEQ 1 87 MESERDMYRQFQDWCLRTYGDSGKTKTVTRKKYERIVQLLN FT GSESSSTDNAKFKFWVKSKGFQLGQPDEVRGGGGGAKQVLY FT VPVKT -> MADLMQETFLHHA (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_043344. FT VAR_SEQ 413 514 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|Ref.5, ECO:0000303|Ref.6}. FT /FTId=VSP_010080. FT CONFLICT 637 637 Q -> H (in Ref. 2; BAH12383). FT {ECO:0000305}. SQ SEQUENCE 638 AA; 71357 MW; 02DF0130F10E0B3F CRC64; MESERDMYRQ FQDWCLRTYG DSGKTKTVTR KKYERIVQLL NGSESSSTDN AKFKFWVKSK GFQLGQPDEV RGGGGGAKQV LYVPVKTTDG VGVDEKLSLR RVAVVEDFFD IIYSMHVETG PNGEQIRKHA GQKRTYKAIS ESYAFLPREA VTRFLMSCSE CQKRMHLNPD GTDHKDNGKP PTLVTSMIDY NMPITMAYMK HMKLQLLNSQ QDEDESSIES DEFDMSDSTR MSAVNSDLSS NLEERMQSPQ NLHGQQDDDS AAESFNGNET LGHSSIASGG THSREMGDSN SDGKTGLEQD EQPLNLSDSP LSAQLTSEYR IDDHNSNGKN KYKNLLISDL KMEREARENG SKSPAHSYSS YDSGKNESVD RGAEDLSLNR GDEDEDDHED HDDSEKVNET DGVEAERLKA FNMFVRLFVD ENLDRMVPIS KQPKEKIQAI IDSCRRQFPE YQERARKRIR TYLKSCRRMK RSGFEMSRPI PSHLTSAVAE SILASACESE SRNAAKRMRL ERQQDESAPA DKQCKPEATQ ATYSTSAVPG SQDVLYINGN GTYSYHSYRG LGGGLLNLND ASSSGPTDLS MKRQLATSSG SSSSSNSRPQ LSPTEINAVR QLVAGYRESA AFLLRSADEL ENLILQQN // ID NRIP1_HUMAN Reviewed; 1158 AA. AC P48552; Q8IWE8; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2000, sequence version 2. DT 11-NOV-2015, entry version 140. DE RecName: Full=Nuclear receptor-interacting protein 1; DE AltName: Full=Nuclear factor RIP140; DE AltName: Full=Receptor-interacting protein 140; GN Name=NRIP1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH ESR1, RP SUBCELLULAR LOCATION, AND VARIANT GLY-448. RC TISSUE=Mammary gland; RX PubMed=7641693; RA Cavailles V., Dauvois S., L'Horset F., Lopez G., Hoare S., RA Kushner P.J., Parker M.G.; RT "Nuclear factor RIP140 modulates transcriptional activation by the RT estrogen receptor."; RL EMBO J. 14:3741-3751(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10830953; DOI=10.1038/35012518; RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., RA Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., RA Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., RA Polley A., Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., RA Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., RA Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., RA Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., RA Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., RA Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., RA Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., RA Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., RA Lehrach H., Reinhardt R., Yaspo M.-L.; RT "The DNA sequence of human chromosome 21."; RL Nature 405:311-319(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH NR2C2. RX PubMed=9556573; DOI=10.1074/jbc.273.18.10948; RA Yan Z.H., Karam W.G., Staudinger J.L., Medvedev A., Ghanayem B.I., RA Jetten A.M.; RT "Regulation of peroxisome proliferator-activated receptor alpha- RT induced transactivation by the nuclear orphan receptor TAK1/TR4."; RL J. Biol. Chem. 273:10948-10957(1998). RN [5] RP FUNCTION, AND INTERACTION WITH NR3C1. RX PubMed=10364267; DOI=10.1074/jbc.274.25.18121; RA Subramaniam N., Treuter E., Okret S.; RT "Receptor interacting protein RIP140 inhibits both positive and RT negative gene regulation by glucocorticoids."; RL J. Biol. Chem. 274:18121-18127(1999). RN [6] RP FUNCTION, INTERACTION WITH CTBP1, MUTAGENESIS OF 440-PRO--LEU-443 AND RP LYS-446, AND ACETYLATION AT LYS-446. RX PubMed=11509661; DOI=10.1128/MCB.21.18.6181-6188.2001; RA Vo N., Fjeld C., Goodman R.H.; RT "Acetylation of nuclear hormone receptor-interacting protein RIP140 RT regulates binding of the transcriptional corepressor CtBP."; RL Mol. Cell. Biol. 21:6181-6188(2001). RN [7] RP INTERACTION WITH NR3C1 AND YWHAH, IDENTIFICATION IN A COMPLEX WITH RP NR3C1 AND YWHAH, AND SUBCELLULAR LOCATION. RX PubMed=11266503; DOI=10.1210/me.15.4.501; RA Zilliacus J., Holter E., Wakui H., Tazawa H., Treuter E., RA Gustafsson J.-A.; RT "Regulation of glucocorticoid receptor activity by 14-3-3-dependent RT intracellular relocalization of the corepressor RIP140."; RL Mol. Endocrinol. 15:501-511(2001). RN [8] RP FUNCTION, AND INTERACTION WITH NR3C2. RX PubMed=11518808; DOI=10.1210/me.15.9.1586; RA Zennaro M.-C., Souque A., Viengchareun S., Poisson E., Lombes M.; RT "A new human MR splice variant is a ligand-independent transactivator RT modulating corticosteroid action."; RL Mol. Endocrinol. 15:1586-1598(2001). RN [9] RP INTERACTION WITH NR3C1, AND SUBCELLULAR LOCATION. RX PubMed=12773562; DOI=10.1128/MCB.23.12.4187-4198.2003; RA Tazawa H., Osman W., Shoji Y., Treuter E., Gustafsson J.-A., RA Zilliacus J.; RT "Regulation of subnuclear localization is associated with a mechanism RT for nuclear receptor corepression by RIP140."; RL Mol. Cell. Biol. 23:4187-4198(2003). RN [10] RP FUNCTION, AND INTERACTION WITH ESR1; FOS AND JUN. RX PubMed=12554755; DOI=10.1210/me.2002-0324; RA Teyssier C., Belguise K., Galtier F., Cavailles V., Chalbos D.; RT "Receptor-interacting protein 140 binds c-Jun and inhibits estradiol- RT induced activator protein-1 activity by reversing glucocorticoid RT receptor-interacting protein 1 effect."; RL Mol. Endocrinol. 17:287-299(2003). RN [11] RP INTERACTION WITH CTBP1 AND CTBP2, MUTAGENESIS OF 442-ASP--LEU-443; RP 567-ASN--LEU-568 AND 948-ASP--LEU-949, AND IDENTIFICATION OF RP REPRESSION DOMAINS. RX PubMed=14736873; DOI=10.1074/jbc.M313906200; RA Christian M., Tullet J.M.A., Parker M.G.; RT "Characterization of four autonomous repression domains in the RT corepressor receptor interacting protein 140."; RL J. Biol. Chem. 279:15645-15651(2004). RN [12] RP FUNCTION, INTERACTION WITH CTBP1; CTBP2; HDAC1; HDAC2; HDAC5 AND RP HDAC6, MUTAGENESIS OF 442-ASP--LEU-443 AND 567-ASN--LEU-568, AND RP SUBCELLULAR LOCATION. RX PubMed=15060175; DOI=10.1093/nar/gkh524; RA Castet A., Boulahtouf A., Versini G., Bonnet S., Augereau P., RA Vignon F., Khochbin S., Jalaguier S., Cavailles V.; RT "Multiple domains of the receptor-interacting protein 140 contribute RT to transcription inhibition."; RL Nucleic Acids Res. 32:1957-1966(2004). RN [13] RP INTERACTION WITH NR2C2. RX PubMed=16887930; DOI=10.1074/mcp.M600180-MCP200; RA Huq M.D., Gupta P., Tsai N.P., Wei L.N.; RT "Modulation of testicular receptor 4 activity by mitogen-activated RT protein kinase-mediated phosphorylation."; RL Mol. Cell. Proteomics 5:2072-2082(2006). RN [14] RP INTERACTION WITH ZNF366. RX PubMed=17085477; DOI=10.1093/nar/gkl875; RA Lopez-Garcia J., Periyasamy M., Thomas R.S., Christian M., Leao M., RA Jat P., Kindle K.B., Heery D.M., Parker M.G., Buluwela L., RA Kamalati T., Ali S.; RT "ZNF366 is an estrogen receptor corepressor that acts through CtBP and RT histone deacetylases."; RL Nucleic Acids Res. 34:6126-6136(2006). RN [15] RP FUNCTION, INTERACTION WITH RORA, AND INDUCTION. RX PubMed=21628546; DOI=10.1177/0748730411401579; RA Poliandri A.H., Gamsby J.J., Christian M., Spinella M.J., Loros J.J., RA Dunlap J.C., Parker M.G.; RT "Modulation of clock gene expression by the transcriptional RT coregulator receptor interacting protein 140 (RIP140)."; RL J. Biol. Rhythms 26:187-199(2011). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-218; SER-671 AND RP SER-807, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [17] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-756 AND LYS-1105, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [18] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 366-390 IN COMPLEX WITH RP ESRRG. RX PubMed=16990259; DOI=10.1074/jbc.M608410200; RA Wang L., Zuercher W.J., Consler T.G., Lambert M.H., Miller A.B., RA Orband-Miller L.A., McKee D.D., Willson T.M., Nolte R.T.; RT "X-ray crystal structures of the estrogen-related receptor-gamma RT ligand binding domain in three functional states reveal the molecular RT basis of small molecule regulation."; RL J. Biol. Chem. 281:37773-37781(2006). RN [19] RP VARIANTS ARG-221; VAL-441; GLY-448; LEU-803 AND PHE-1079. RX PubMed=16131398; DOI=10.1186/1743-1050-2-11; RA Caballero V., Ruiz R., Sainz J.A., Cruz M., Lopez-Nevot M.A., RA Galan J.J., Real L.M., de Castro F., Lopez-Villaverde V., Ruiz A.; RT "Preliminary molecular genetic analysis of the receptor interacting RT protein 140 (RIP140) in women affected by endometriosis."; RL J. Exp. Clin. Assist. Reprod. 2:11-11(2005). CC -!- FUNCTION: Modulates transcriptional activation by steroid CC receptors such as NR3C1, NR3C2 and ESR1. Also modulates CC transcriptional repression by nuclear hormone receptors. Positive CC regulator of the circadian clock gene expression: stimulates CC transcription of ARNTL/BMAL1, CLOCK and CRY1 by acting as a CC coactivator for RORA and RORC. {ECO:0000269|PubMed:10364267, CC ECO:0000269|PubMed:11509661, ECO:0000269|PubMed:11518808, CC ECO:0000269|PubMed:12554755, ECO:0000269|PubMed:15060175, CC ECO:0000269|PubMed:21628546, ECO:0000269|PubMed:7641693}. CC -!- SUBUNIT: Interacts with RARA and RXRB homodimers and RARA/RXRB CC heterodimers in the presence of ligand. Interacts with HDAC1 and CC HDAC3 via its N-terminal domain. Interacts with NR2C1 (sumoylated CC form and via the ligand-binding domain); the interaction results CC in promoting the repressor activity of NR2C1 (By similarity). CC Interacts with CTBP1, CTBP2, ESR1, HDAC1, HDAC2, HDAC5, HDAC6, CC NR2C2, NR3C1, NR3C2, YWHAH, JUN and FOS. Found in a complex with CC both NR3C1 and YWHAH. Interacts with ZNF366. Interacts with RORA. CC {ECO:0000250|UniProtKB:Q8CBD1, ECO:0000269|PubMed:10364267, CC ECO:0000269|PubMed:11266503, ECO:0000269|PubMed:11509661, CC ECO:0000269|PubMed:11518808, ECO:0000269|PubMed:12554755, CC ECO:0000269|PubMed:12773562, ECO:0000269|PubMed:14736873, CC ECO:0000269|PubMed:15060175, ECO:0000269|PubMed:16887930, CC ECO:0000269|PubMed:16990259, ECO:0000269|PubMed:17085477, CC ECO:0000269|PubMed:21628546, ECO:0000269|PubMed:7641693, CC ECO:0000269|PubMed:9556573}. CC -!- INTERACTION: CC O15145:ARPC3; NbExp=3; IntAct=EBI-746484, EBI-351829; CC Q8NHQ1:CEP70; NbExp=3; IntAct=EBI-746484, EBI-739624; CC P26358:DNMT1; NbExp=3; IntAct=EBI-746484, EBI-719459; CC Q13642:FHL1; NbExp=6; IntAct=EBI-746484, EBI-912547; CC O15379:HDAC3; NbExp=2; IntAct=EBI-746484, EBI-607682; CC O95751:LDOC1; NbExp=3; IntAct=EBI-746484, EBI-740738; CC Q99873:PRMT1; NbExp=4; IntAct=EBI-746484, EBI-78738; CC P10276:RARA; NbExp=4; IntAct=EBI-746484, EBI-413374; CC P10276-2:RARA; NbExp=3; IntAct=EBI-746484, EBI-10197061; CC Q8N895:ZNF366; NbExp=2; IntAct=EBI-746484, EBI-2813661; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11266503, CC ECO:0000269|PubMed:12773562, ECO:0000269|PubMed:15060175, CC ECO:0000269|PubMed:7641693}. Note=Localized to discrete foci and CC redistributes to larger nuclear domains upon binding to ligand- CC bound NR3C1. CC -!- INDUCTION: Expressed in a circadian manner in the liver (at CC protein level). {ECO:0000269|PubMed:21628546}. CC -!- DOMAIN: Contains 9 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which have CC different affinities for nuclear receptors. The C-terminal CC LTKTNPILYYMLQK motif is required for ligand-dependent interaction CC with RAAR and RXRB homodimers and heterodimers, for the CC corepressor activity, and for the formation of an HDAC3 complex CC with RARA/RXRB (By similarity). Contains at least four autonomous CC repression domains (RD1-4). RD1 functions via a histone CC deacetylase (HDAC)-independent mechanism, whereas RD2, RD3 and RD4 CC can function by HDAC-dependent or independent mechanisms, CC depending on cell type. RD2 is dependent on CTBP binding. CC {ECO:0000250}. CC -!- PTM: Acetylation regulates its nuclear translocation and CC corepressive activity (By similarity). Acetylation abolishes CC interaction with CTBP1. Phosphorylation enhances interaction with CC YWHAH. {ECO:0000250, ECO:0000269|PubMed:11509661}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/NRIP1ID44067ch21q11.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X84373; CAA59108.1; -; mRNA. DR EMBL; AF248484; AAF62185.1; -; Genomic_DNA. DR EMBL; AF127577; AAF35255.1; -; Genomic_DNA. DR EMBL; AL163207; CAB90396.1; -; Genomic_DNA. DR EMBL; BC040361; AAH40361.1; -; mRNA. DR CCDS; CCDS13568.1; -. DR PIR; S57348; S57348. DR RefSeq; NP_003480.2; NM_003489.3. DR RefSeq; XP_005261120.1; XM_005261063.2. DR RefSeq; XP_005261122.1; XM_005261065.2. DR RefSeq; XP_011528049.1; XM_011529747.1. DR RefSeq; XP_011528050.1; XM_011529748.1. DR RefSeq; XP_011528051.1; XM_011529749.1. DR RefSeq; XP_011528052.1; XM_011529750.1. DR RefSeq; XP_011528053.1; XM_011529751.1. DR RefSeq; XP_011528054.1; XM_011529752.1. DR UniGene; Hs.155017; -. DR PDB; 2GPO; X-ray; 1.95 A; C=366-390. DR PDB; 2GPP; X-ray; 2.60 A; C/D=366-390. DR PDB; 4S14; X-ray; 3.54 A; C=499-510. DR PDB; 4S15; X-ray; 1.90 A; C/D=499-510. DR PDBsum; 2GPO; -. DR PDBsum; 2GPP; -. DR PDBsum; 4S14; -. DR PDBsum; 4S15; -. DR ProteinModelPortal; P48552; -. DR BioGrid; 113843; 56. DR DIP; DIP-5964N; -. DR IntAct; P48552; 22. DR MINT; MINT-192711; -. DR STRING; 9606.ENSP00000327213; -. DR PhosphoSite; P48552; -. DR BioMuta; NRIP1; -. DR DMDM; 9988061; -. DR MaxQB; P48552; -. DR PaxDb; P48552; -. DR PRIDE; P48552; -. DR DNASU; 8204; -. DR Ensembl; ENST00000318948; ENSP00000327213; ENSG00000180530. DR Ensembl; ENST00000400199; ENSP00000383060; ENSG00000180530. DR Ensembl; ENST00000400202; ENSP00000383063; ENSG00000180530. DR GeneID; 8204; -. DR KEGG; hsa:8204; -. DR UCSC; uc002yjx.2; human. DR CTD; 8204; -. DR GeneCards; NRIP1; -. DR H-InvDB; HIX0027827; -. DR HGNC; HGNC:8001; NRIP1. DR HPA; HPA046571; -. DR HPA; HPA060036; -. DR MIM; 602490; gene. DR neXtProt; NX_P48552; -. DR PharmGKB; PA31780; -. DR eggNOG; ENOG410IFW7; Eukaryota. DR eggNOG; ENOG410XPVS; LUCA. DR GeneTree; ENSGT00390000007999; -. DR HOGENOM; HOG000236277; -. DR HOVERGEN; HBG052667; -. DR InParanoid; P48552; -. DR KO; K17965; -. DR OMA; VEKDLRC; -. DR OrthoDB; EOG7H1JJQ; -. DR PhylomeDB; P48552; -. DR TreeFam; TF332210; -. DR Reactome; R-HSA-1368082; RORA activates gene expression. DR Reactome; R-HSA-1368108; BMAL1:CLOCK,NPAS2 activates circadian gene expression. DR Reactome; R-HSA-400253; Circadian Clock. DR SignaLink; P48552; -. DR ChiTaRS; NRIP1; human. DR EvolutionaryTrace; P48552; -. DR GeneWiki; NRIP1; -. DR GenomeRNAi; 8204; -. DR NextBio; 30914; -. DR PRO; PR:P48552; -. DR Proteomes; UP000005640; Chromosome 21. DR Bgee; P48552; -. DR CleanEx; HS_NRIP1; -. DR ExpressionAtlas; P48552; baseline and differential. DR Genevisible; P48552; HS. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0000118; C:histone deacetylase complex; IEA:Ensembl. DR GO; GO:0000790; C:nuclear chromatin; IDA:BHF-UCL. DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0050681; F:androgen receptor binding; NAS:UniProtKB. DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0030331; F:estrogen receptor binding; IPI:UniProtKB. DR GO; GO:0035259; F:glucocorticoid receptor binding; IPI:UniProtKB. DR GO; GO:0035257; F:nuclear hormone receptor binding; IPI:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB. DR GO; GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB. DR GO; GO:0071392; P:cellular response to estradiol stimulus; IDA:BHF-UCL. DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB. DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB. DR GO; GO:0019915; P:lipid storage; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0001543; P:ovarian follicle rupture; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; NAS:UniProtKB. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR InterPro; IPR026649; NRIP1. DR InterPro; IPR031405; NRIP1_RD1. DR InterPro; IPR031406; NRIP1_RD2. DR InterPro; IPR031407; NRIP1_RD3. DR InterPro; IPR031408; NRIP1_RD4. DR PANTHER; PTHR15088; PTHR15088; 1. DR Pfam; PF15687; NRIP1_repr_1; 1. DR Pfam; PF15688; NRIP1_repr_2; 1. DR Pfam; PF15689; NRIP1_repr_3; 1. DR Pfam; PF15690; NRIP1_repr_4; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Biological rhythms; KW Complete proteome; Isopeptide bond; Nucleus; Phosphoprotein; KW Polymorphism; Reference proteome; Repeat; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1 1158 Nuclear receptor-interacting protein 1. FT /FTId=PRO_0000057951. FT REGION 1 415 Interaction with ZNF366. FT REGION 78 333 Repression domain 1. FT REGION 410 700 Repression domain 2. FT REGION 431 472 Required for targeting to small nuclear FT foci. FT REGION 735 885 Repression domain 3. FT REGION 753 1158 Interaction with ZNF366. FT REGION 1118 1158 Repression domain 4. FT MOTIF 21 25 LXXLL motif 1. FT MOTIF 133 137 LXXLL motif 2. FT MOTIF 185 189 LXXLL motif 3. FT MOTIF 266 270 LXXLL motif 4. FT MOTIF 380 384 LXXLL motif 5. FT MOTIF 440 446 CTBP-binding; principal site. FT MOTIF 500 504 LXXLL motif 6. FT MOTIF 565 569 CTBP-binding. FT MOTIF 599 603 CTBP-binding. {ECO:0000255}. FT MOTIF 713 717 LXXLL motif 7. FT MOTIF 819 823 LXXLL motif 8. FT MOTIF 936 940 LXXLL motif 9. FT MOTIF 946 950 CTBP-binding. FT MOTIF 1061 1074 Ligand-dependent nuclear receptor FT binding. {ECO:0000250}. FT MOD_RES 104 104 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 111 111 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 158 158 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 207 207 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 218 218 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 286 286 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 310 310 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 356 356 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 378 378 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 446 446 N6-acetyllysine. FT {ECO:0000269|PubMed:11509661}. FT MOD_RES 481 481 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 487 487 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 518 518 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 528 528 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 542 542 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 606 606 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 671 671 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 807 807 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 931 931 N6-acetyllysine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT MOD_RES 1001 1001 Phosphoserine. FT {ECO:0000250|UniProtKB:Q8CBD1}. FT CROSSLNK 756 756 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 1105 1105 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT VARIANT 37 37 V -> I (in dbSNP:rs9941840). FT /FTId=VAR_051241. FT VARIANT 221 221 H -> R (in dbSNP:rs139263261). FT {ECO:0000269|PubMed:16131398}. FT /FTId=VAR_023706. FT VARIANT 315 315 Y -> F (in dbSNP:rs2228507). FT /FTId=VAR_034142. FT VARIANT 441 441 I -> V (in dbSNP:rs150468995). FT {ECO:0000269|PubMed:16131398}. FT /FTId=VAR_023707. FT VARIANT 448 448 R -> G (common polymorphism; FT dbSNP:rs2229742). FT {ECO:0000269|PubMed:16131398, FT ECO:0000269|PubMed:7641693}. FT /FTId=VAR_023708. FT VARIANT 567 567 N -> S (in dbSNP:rs9975169). FT /FTId=VAR_051242. FT VARIANT 803 803 S -> L (in dbSNP:rs61750208). FT {ECO:0000269|PubMed:16131398}. FT /FTId=VAR_023709. FT VARIANT 1079 1079 V -> F. {ECO:0000269|PubMed:16131398}. FT /FTId=VAR_023710. FT MUTAGEN 440 443 PIDL->AAAA: Abolishes interaction with FT CTBP1. {ECO:0000269|PubMed:11509661}. FT MUTAGEN 440 442 PID->AIA: Abolishes interaction with FT CTBP1 and attenuates nuclear hormone FT receptor-dependent transcription FT repression. FT MUTAGEN 442 443 DL->AA: Reduces, but does not completely FT abolish, interaction with CTBP. Reduces FT transcriptional repression. FT {ECO:0000269|PubMed:14736873, FT ECO:0000269|PubMed:15060175}. FT MUTAGEN 442 443 DL->AS: Disrupts interaction with CTBP1, FT and CTBP2 to a lesser extent. Disrupts FT transcriptional repression; when FT associated with 567-AS-568. FT {ECO:0000269|PubMed:14736873, FT ECO:0000269|PubMed:15060175}. FT MUTAGEN 446 446 K->Q: Disrupts interaction with CTBP1. FT Decreases lysine acetylation. Disrupts FT nuclear hormone receptor-dependent FT transcription repression. FT {ECO:0000269|PubMed:11509661}. FT MUTAGEN 446 446 K->R: Does not disrupt nuclear hormone FT receptor-dependent transcription FT repression. FT {ECO:0000269|PubMed:11509661}. FT MUTAGEN 567 568 NL->AA: Disrupts transcriptional FT repression. {ECO:0000269|PubMed:14736873, FT ECO:0000269|PubMed:15060175}. FT MUTAGEN 567 568 NL->AS: Disrupts interaction with CTBP1 FT and CTBP2. Disrupts transcriptional FT repression; when associated with 442-AS- FT 443. {ECO:0000269|PubMed:14736873, FT ECO:0000269|PubMed:15060175}. FT MUTAGEN 599 603 SMDLT->PIAAS: Does not further disrupt FT transcriptional repression; when FT associated with 442-AA-443 and 567-AA- FT 568. FT MUTAGEN 948 949 DL->AA: Abolishes CTBP binding but FT retains transcriptional repressor FT activity. {ECO:0000269|PubMed:14736873}. FT CONFLICT 124 124 P -> R (in Ref. 1; CAA59108). FT {ECO:0000305}. FT CONFLICT 721 726 NKGKSE -> TKGRVK (in Ref. 1; CAA59108). FT {ECO:0000305}. FT CONFLICT 954 954 S -> I (in Ref. 3; AAH40361). FT {ECO:0000305}. FT CONFLICT 1080 1080 T -> A (in Ref. 1; CAA59108). FT {ECO:0000305}. FT HELIX 379 385 {ECO:0000244|PDB:2GPO}. FT HELIX 500 505 {ECO:0000244|PDB:4S15}. SQ SEQUENCE 1158 AA; 126942 MW; 81FC424968E9A5F6 CRC64; MTHGEELGSD VHQDSIVLTY LEGLLMHQAA GGSGTAVDKK SAGHNEEDQN FNISGSAFPT CQSNGPVLNT HTYQGSGMLH LKKARLLQSS EDWNAAKRKR LSDSIMNLNV KKEALLAGMV DSVPKGKQDS TLLASLLQSF SSRLQTVALS QQIRQSLKEQ GYALSHDSLK VEKDLRCYGV ASSHLKTLLK KSKVKDQKPD TNLPDVTKNL IRDRFAESPH HVGQSGTKVM SEPLSCAARL QAVASMVEKR ASPATSPKPS VACSQLALLL SSEAHLQQYS REHALKTQNA NQAASERLAA MARLQENGQK DVGSYQLPKG MSSHLNGQAR TSSSKLMASK SSATVFQNPM GIIPSSPKNA GYKNSLERNN IKQAANNSLL LHLLKSQTIP KPMNGHSHSE RGSIFEESST PTTIDEYSDN NPSFTDDSSG DESSYSNCVP IDLSCKHRTE KSESDQPVSL DNFTQSLLNT WDPKVPDVDI KEDQDTSKNS KLNSHQKVTL LQLLLGHKNE ENVEKNTSPQ GVHNDVSKFN TQNYARTSVI ESPSTNRTTP VSTPPLLTSS KAGSPINLSQ HSLVIKWNSP PYVCSTQSEK LTNTASNHSM DLTKSKDPPG EKPAQNEGAQ NSATFSASKL LQNLAQCGMQ SSMSVEEQRP SKQLLTGNTD KPIGMIDRLN SPLLSNKTNA VEENKAFSSQ PTGPEPGLSG SEIENLLERR TVLQLLLGNP NKGKSEKKEK TPLRDESTQE HSERALSEQI LMVKIKSEPC DDLQIPNTNV HLSHDAKSAP FLGMAPAVQR SAPALPVSED FKSEPVSPQD FSFSKNGLLS RLLRQNQDSY LADDSDRSHR NNEMALLESK NLCMVPKKRK LYTEPLENPF KKMKNNIVDA ANNHSAPEVL YGSLLNQEEL KFSRNDLEFK YPAGHGSASE SEHRSWARES KSFNVLKQLL LSENCVRDLS PHRSNSVADS KKKGHKNNVT NSKPEFSISS LNGLMYSSTQ PSSCMDNRTF SYPGVVKTPV SPTFPEHLGC AGSRPESGLL NGCSMPSEKG PIKWVITDAE KNEYEKDSPR LTKTNPILYY MLQKGGNSVT SRETQDKDIW REASSAESVS QVTAKEELLP TAETKASFFN LRSPYNSHMG NNASRPHSAN GEVYGLLGSV LTIKKESE // ID ORC4_HUMAN Reviewed; 436 AA. AC O43929; B7Z3D0; B7Z5F1; D3DP86; F5H069; Q96C42; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 07-JUN-2005, sequence version 2. DT 11-NOV-2015, entry version 144. DE RecName: Full=Origin recognition complex subunit 4; GN Name=ORC4; Synonyms=ORC4L; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-78. RX PubMed=9353276; DOI=10.1074/jbc.272.45.28247; RA Quintana D.G., Hou Z.H., Thome K.C., Hendricks M., Saha P., Dutta A.; RT "Identification of HsORC4, a member of the human origin of replication RT recognition complex."; RL J. Biol. Chem. 272:28247-28251(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-78. RA Komrskova T., Yang H., Gavin K., Pappin D., Canas B., Kobayashi R., RA Hunt T., Stillman B.; RT "The Orc4p and Orc5p subunits of the Xenopus and human origin RT recognition complex are related to Orc1p and Cdc6p."; RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT SER-78. RA Dean F.B., O'Donnell M.; RT "cDNA cloning of a homolog for S. cerevisiae ORC4 from H. sapiens."; RL Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-56. RG NIEHS SNPs program; RL Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., RA Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., RA Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., RA Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J., RA Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., RA Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., RA Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., RA Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., RA Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., RA Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., RA Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., RA Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., RA Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., RA Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., RA Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., RA Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., RA Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., RA Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., RA McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., RA Waterston R.H., Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 RT and 4."; RL Nature 434:724-731(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT SER-78. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP IDENTIFICATION IN THE ORC COMPLEX, IDENTIFICATION BY MASS RP SPECTROMETRY, AND ASSEMBLY OF THE ORC COMPLEX. RX PubMed=12909626; DOI=10.1074/jbc.M307535200; RA Ohta S., Tatsumi Y., Fujita M., Tsurimoto T., Obuse C.; RT "The ORC1 cycle in human cells: II. Dynamic changes in the human ORC RT complex during the cell cycle."; RL J. Biol. Chem. 278:41535-41540(2003). RN [10] RP RECONSTITUTION OF THE ORC COMPLEX, DISASSEMBLY OF THE ORC COMPLEX, AND RP MUTAGENESIS OF LYS-73 AND 159-ASP-GLU-160. RX PubMed=17716973; DOI=10.1074/jbc.M705905200; RA Siddiqui K., Stillman B.; RT "ATP-dependent assembly of the human origin recognition complex."; RL J. Biol. Chem. 282:32370-32383(2007). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [13] RP FUNCTION, AND BINDING TO HISTONE H3 AND H4 TRIMETHYLATION MARKS. RX PubMed=22427655; DOI=10.1074/jbc.M111.337980; RA Chan K.M., Zhang Z.; RT "Leucine-rich repeat and WD repeat-containing protein 1 is recruited RT to pericentric heterochromatin by trimethylated lysine 9 of histone H3 RT and maintains heterochromatin silencing."; RL J. Biol. Chem. 287:15024-15033(2012). RN [14] RP INTERACTION WITH POLQ. RX PubMed=24989122; DOI=10.1038/ncomms5285; RA Fernandez-Vidal A., Guitton-Sert L., Cadoret J.C., Drac M., Schwob E., RA Baldacci G., Cazaux C., Hoffmann J.S.; RT "A role for DNA polymerase theta in the timing of DNA replication."; RL Nat. Commun. 5:4285-4285(2014). RN [15] RP VARIANT MGORS2 CYS-174. RX PubMed=21358632; DOI=10.1038/ng.775; RA Bicknell L.S., Bongers E.M., Leitch A., Brown S., Schoots J., RA Harley M.E., Aftimos S., Al-Aama J.Y., Bober M., Brown P.A., RA van Bokhoven H., Dean J., Edrees A.Y., Feingold M., Fryer A., RA Hoefsloot L.H., Kau N., Knoers N.V., Mackenzie J., Opitz J.M., RA Sarda P., Ross A., Temple I.K., Toutain A., Wise C.A., Wright M., RA Jackson A.P.; RT "Mutations in the pre-replication complex cause Meier-Gorlin RT syndrome."; RL Nat. Genet. 43:356-359(2011). RN [16] RP VARIANT MGORS2 CYS-174. RX PubMed=21358631; DOI=10.1038/ng.777; RA Guernsey D.L., Matsuoka M., Jiang H., Evans S., Macgillivray C., RA Nightingale M., Perry S., Ferguson M., LeBlanc M., Paquette J., RA Patry L., Rideout A.L., Thomas A., Orr A., McMaster C.R., RA Michaud J.L., Deal C., Langlois S., Superneau D.W., Parkash S., RA Ludman M., Skidmore D.L., Samuels M.E.; RT "Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin RT syndrome."; RL Nat. Genet. 43:360-364(2011). CC -!- FUNCTION: Component of the origin recognition complex (ORC) that CC binds origins of replication. DNA-binding is ATP-dependent. The CC specific DNA sequences that define origins of replication have not CC been identified yet. ORC is required to assemble the pre- CC replication complex necessary to initiate DNA replication. Binds CC histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and CC H4K20me3. {ECO:0000269|PubMed:22427655}. CC -!- SUBUNIT: Component of ORC, a complex composed of at least 6 CC subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated CC in a cell-cycle dependent manner. It is sequentially assembled at CC the exit from anaphase of mitosis and disassembled as cells enter CC S phase (PubMed:12909626, PubMed:17716973). Interacts with DBF4 CC (By similarity). Interacts with POLQ (PubMed:24989122). CC {ECO:0000250|UniProtKB:O88708, ECO:0000269|PubMed:12909626, CC ECO:0000269|PubMed:17716973, ECO:0000269|PubMed:24989122}. CC -!- INTERACTION: CC Q13416:ORC2; NbExp=6; IntAct=EBI-374889, EBI-374957; CC Q9UBD5:ORC3; NbExp=12; IntAct=EBI-374889, EBI-374916; CC O43913:ORC5; NbExp=2; IntAct=EBI-374889, EBI-374928; CC Q7LG56:RRM2B; NbExp=4; IntAct=EBI-374889, EBI-9009083; CC P15884:TCF4; NbExp=3; IntAct=EBI-374889, EBI-533224; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O43929-1; Sequence=Displayed; CC Name=2; CC IsoId=O43929-2; Sequence=VSP_045199; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=O43929-3; Sequence=VSP_046437; CC Note=No experimental confirmation available.; CC -!- DISEASE: Meier-Gorlin syndrome 2 (MGORS2) [MIM:613800]: A syndrome CC characterized by bilateral microtia, aplasia/hypoplasia of the CC patellae, and severe intrauterine and postnatal growth retardation CC with short stature and poor weight gain. Additional clinical CC findings include anomalies of cranial sutures, microcephaly, CC apparently low-set and simple ears, microstomia, full lips, highly CC arched or cleft palate, micrognathia, genitourinary tract CC anomalies, and various skeletal anomalies. While almost all cases CC have primordial dwarfism with substantial prenatal and postnatal CC growth retardation, not all cases have microcephaly, and microtia CC and absent/hypoplastic patella are absent in some. Despite the CC presence of microcephaly, intellect is usually normal. CC {ECO:0000269|PubMed:21358631, ECO:0000269|PubMed:21358632}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the ORC4 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/orc4l/"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF022108; AAC01957.1; -; mRNA. DR EMBL; AF047598; AAC80282.1; -; mRNA. DR EMBL; AF132596; AAD22110.1; -; mRNA. DR EMBL; AY600302; AAS94326.1; -; Genomic_DNA. DR EMBL; AK295721; BAH12166.1; -; mRNA. DR EMBL; AK298862; BAH12887.1; -; mRNA. DR EMBL; AC009480; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC019226; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471058; EAX11555.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11556.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11557.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11558.1; -; Genomic_DNA. DR EMBL; BC014847; AAH14847.1; -; mRNA. DR CCDS; CCDS2187.1; -. [O43929-1] DR CCDS; CCDS54404.1; -. [O43929-2] DR CCDS; CCDS54405.1; -. [O43929-3] DR RefSeq; NP_001177808.1; NM_001190879.2. [O43929-1] DR RefSeq; NP_001177810.1; NM_001190881.2. [O43929-2] DR RefSeq; NP_001177811.1; NM_001190882.2. [O43929-3] DR RefSeq; NP_002543.2; NM_002552.4. [O43929-1] DR RefSeq; NP_859525.1; NM_181741.3. [O43929-1] DR RefSeq; NP_859526.1; NM_181742.3. [O43929-1] DR RefSeq; XP_006712619.1; XM_006712556.2. [O43929-2] DR RefSeq; XP_011509557.1; XM_011511255.1. [O43929-1] DR UniGene; Hs.558364; -. DR ProteinModelPortal; O43929; -. DR SMR; O43929; 17-432. DR BioGrid; 111042; 39. DR DIP; DIP-29690N; -. DR IntAct; O43929; 22. DR MINT; MINT-1201591; -. DR STRING; 9606.ENSP00000264169; -. DR PhosphoSite; O43929; -. DR BioMuta; ORC4; -. DR MaxQB; O43929; -. DR PaxDb; O43929; -. DR PeptideAtlas; O43929; -. DR PRIDE; O43929; -. DR DNASU; 5000; -. DR Ensembl; ENST00000264169; ENSP00000264169; ENSG00000115947. [O43929-1] DR Ensembl; ENST00000392857; ENSP00000376597; ENSG00000115947. [O43929-1] DR Ensembl; ENST00000535373; ENSP00000441953; ENSG00000115947. [O43929-1] DR Ensembl; ENST00000536575; ENSP00000441502; ENSG00000115947. [O43929-2] DR Ensembl; ENST00000540442; ENSP00000438326; ENSG00000115947. [O43929-3] DR GeneID; 5000; -. DR KEGG; hsa:5000; -. DR UCSC; uc002twi.3; human. [O43929-1] DR CTD; 5000; -. DR GeneCards; ORC4; -. DR HGNC; HGNC:8490; ORC4. DR HPA; CAB015124; -. DR HPA; HPA063019; -. DR HPA; HPA064562; -. DR MIM; 603056; gene. DR MIM; 613800; phenotype. DR neXtProt; NX_O43929; -. DR Orphanet; 2554; Ear-patella-short stature syndrome. DR PharmGKB; PA32811; -. DR eggNOG; KOG2228; Eukaryota. DR eggNOG; ENOG410XSK0; LUCA. DR GeneTree; ENSGT00390000016542; -. DR HOGENOM; HOG000007226; -. DR HOVERGEN; HBG000253; -. DR InParanoid; O43929; -. DR KO; K02606; -. DR OMA; FQKFIQR; -. DR OrthoDB; EOG72NRPZ; -. DR PhylomeDB; O43929; -. DR TreeFam; TF101094; -. DR Reactome; R-HSA-113507; E2F-enabled inhibition of pre-replication complex formation. DR Reactome; R-HSA-176187; Activation of ATR in response to replication stress. DR Reactome; R-HSA-68616; Assembly of the ORC complex at the origin of replication. DR Reactome; R-HSA-68689; CDC6 association with the ORC:origin complex. DR Reactome; R-HSA-68827; CDT1 association with the CDC6:ORC:origin complex. DR Reactome; R-HSA-68867; Assembly of the pre-replicative complex. DR Reactome; R-HSA-68949; Orc1 removal from chromatin. DR Reactome; R-HSA-68962; Activation of the pre-replicative complex. DR Reactome; R-HSA-69298; Association of licensing factors with the pre-replicative complex. DR Reactome; R-HSA-69300; Removal of licensing factors from origins. DR ChiTaRS; ORC4; human. DR GeneWiki; ORC4; -. DR GeneWiki; ORC4L; -. DR GenomeRNAi; 5000; -. DR NextBio; 19248; -. DR PRO; PR:O43929; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; O43929; -. DR CleanEx; HS_ORC4L; -. DR ExpressionAtlas; O43929; baseline and differential. DR Genevisible; O43929; HS. DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0000784; C:nuclear chromosome, telomeric region; IDA:BHF-UCL. DR GO; GO:0005664; C:nuclear origin of replication recognition complex; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000808; C:origin recognition complex; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003688; F:DNA replication origin binding; IMP:UniProtKB. DR GO; GO:0000166; F:nucleotide binding; IDA:UniProtKB. DR GO; GO:0006260; P:DNA replication; TAS:Reactome. DR GO; GO:0006270; P:DNA replication initiation; IMP:UniProtKB. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome. DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR016527; ORC4. DR InterPro; IPR027417; P-loop_NTPase. DR PIRSF; PIRSF007858; ORC4; 1. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF52540; SSF52540; 1. PE 1: Evidence at protein level; KW Alternative splicing; ATP-binding; Complete proteome; KW Disease mutation; DNA replication; DNA-binding; Dwarfism; KW Nucleotide-binding; Nucleus; Polymorphism; Reference proteome. FT CHAIN 1 436 Origin recognition complex subunit 4. FT /FTId=PRO_0000127087. FT NP_BIND 67 74 ATP. {ECO:0000255}. FT VAR_SEQ 1 84 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_045199. FT VAR_SEQ 1 74 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_046437. FT VARIANT 56 56 L -> V (in dbSNP:rs2307397). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014523. FT VARIANT 78 78 N -> S (in dbSNP:rs2307394). FT {ECO:0000269|PubMed:9353276, FT ECO:0000269|Ref.2, ECO:0000269|Ref.3, FT ECO:0000269|Ref.7}. FT /FTId=VAR_019235. FT VARIANT 174 174 Y -> C (in MGORS2). FT {ECO:0000269|PubMed:21358631, FT ECO:0000269|PubMed:21358632}. FT /FTId=VAR_065486. FT MUTAGEN 73 73 K->A,E: Impairs ORC complex formation. FT {ECO:0000269|PubMed:17716973}. FT MUTAGEN 159 160 DE->AA: Impairs ORC complex formation. FT {ECO:0000269|PubMed:17716973}. FT CONFLICT 135 135 N -> S (in Ref. 5; BAH12887). FT {ECO:0000305}. SQ SEQUENCE 436 AA; 50377 MW; A7020B6690E30B4E CRC64; MSSRKSKSNS LIHTECLSQV QRILRERFCR QSPHSNLFGV QVQYKHLSEL LKRTALHGES NSVLIIGPRG SGKTMLINHA LKELMEIEEV SENVLQVHLN GLLQINDKIA LKEITRQLNL ENVVGDKVFG SFAENLSFLL EALKKGDRTS SCPVIFILDE FDLFAHHKNQ TLLYNLFDIS QSAQTPIAVI GLTCRLDILE LLEKRVKSRF SHRQIHLMNS FGFPQYVKIF KEQLSLPAEF PDKVFAEKWN ENVQYLSEDR SVQEVLQKHF NISKNLRSLH MLLMLALNRV TASHPFMTAV DLMEASQLCS MDSKANIVHG LSVLEICLII AMKHLNDIYE EEPFNFQMVY NEFQKFVQRK AHSVYNFEKP VVMKAFEHLQ QLELIKPMER TSGNSQREYQ LMKLLLDNTQ IMNALQKYPN CPTDVRQWAT SSLSWL // ID PLCB1_HUMAN Reviewed; 1216 AA. AC Q9NQ66; D3DW12; D3DW13; O60325; Q17RQ6; Q5TFF7; Q5TGC9; Q8IV93; AC Q9BQW2; Q9H4H2; Q9H8H5; Q9NQ65; Q9NQH9; Q9NTH4; Q9UJP6; Q9UM26; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 11-NOV-2015, entry version 164. DE RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1; DE EC=3.1.4.11; DE AltName: Full=PLC-154; DE AltName: Full=Phosphoinositide phospholipase C-beta-1; DE AltName: Full=Phospholipase C-I; DE Short=PLC-I; DE AltName: Full=Phospholipase C-beta-1; DE Short=PLC-beta-1; GN Name=PLCB1; Synonyms=KIAA0581; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B). RC TISSUE=Brain; RX PubMed=11118617; DOI=10.1016/S0167-4781(00)00260-8; RA Caricasole A., Sala C., Roncarati R., Formenti E., Terstappen G.C.; RT "Cloning and characterization of the human phosphoinositide-specific RT phospholipase C-beta 1 (PLCbeta1)."; RL Biochim. Biophys. Acta 1517:63-72(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). RC TISSUE=Brain; RX PubMed=10760467; DOI=10.1016/S1388-1981(00)00012-3; RA Peruzzi D., Calabrese G., Faenza I., Manzoli L., Matteucci A., RA Gianfrancesco F., Billi A.M., Stuppia L., Palka G., Cocco L.; RT "Identification and chromosomal localisation by fluorescence in situ RT hybridisation of human gene of phosphoinositide-specific phospholipase RT C beta 1."; RL Biochim. Biophys. Acta 1484:175-182(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). RC TISSUE=Brain; RX PubMed=9628581; DOI=10.1093/dnares/5.1.31; RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., RA Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. IX. RT The complete sequences of 100 new cDNA clones from brain which can RT code for large proteins in vitro."; RL DNA Res. 5:31-39(1998). RN [4] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., RA Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS A AND B). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 261-1216 (ISOFORM B). RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 417-1062 (ISOFORMS A AND B). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [10] RP INTERACTION WITH DGKQ. RX PubMed=12799190; DOI=10.1016/S0014-4827(03)00115-0; RA Tabellini G., Bortul R., Santi S., Riccio M., Baldini G., RA Cappellini A., Billi A.M., Berezney R., Ruggeri A., Cocco L., RA Martelli A.M.; RT "Diacylglycerol kinase-theta is localized in the speckle domains of RT the nucleus."; RL Exp. Cell Res. 287:143-154(2003). RN [11] RP INVOLVEMENT IN EIEE12. RX PubMed=20833646; DOI=10.1093/brain/awq238; RA Kurian M.A., Meyer E., Vassallo G., Morgan N.V., Prakash N., Pasha S., RA Hai N.A., Shuib S., Rahman F., Wassmer E., Cross J.H., RA O'Callaghan F.J., Osborne J.P., Scheffer I.E., Gissen P., Maher E.R.; RT "Phospholipase C beta 1 deficiency is associated with early-onset RT epileptic encephalopathy."; RL Brain 133:2964-2970(2010). RN [12] RP VARIANT [LARGE SCALE ANALYSIS] PRO-907. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: The production of the second messenger molecules CC diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is CC mediated by activated phosphatidylinositol-specific phospholipase CC C enzymes. CC -!- CATALYTIC ACTIVITY: 1-phosphatidyl-1D-myo-inositol 4,5- CC bisphosphate + H(2)O = 1D-myo-inositol 1,4,5-trisphosphate + CC diacylglycerol. CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; CC -!- SUBUNIT: Interacts with DGKQ. {ECO:0000269|PubMed:12799190}. CC -!- INTERACTION: CC Q8TAP6:CEP76; NbExp=3; IntAct=EBI-3396023, EBI-742887; CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-3396023, EBI-10171858; CC P56545:CTBP2; NbExp=3; IntAct=EBI-3396023, EBI-741533; CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-3396023, EBI-10171902; CC Q12800:TFCP2; NbExp=3; IntAct=EBI-3396023, EBI-717422; CC -!- SUBCELLULAR LOCATION: Nucleus membrane {ECO:0000250}. Cytoplasm CC {ECO:0000250}. Note=Colocalizes with the adrenergic receptors, CC ADREN1A and ADREN1B, at the nuclear membrane of cardiac myocytes. CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=A; CC IsoId=Q9NQ66-1; Sequence=Displayed; CC Name=B; CC IsoId=Q9NQ66-2; Sequence=VSP_004718; CC -!- DISEASE: Epileptic encephalopathy, early infantile, 12 (EIEE12) CC [MIM:613722]: A form of epilepsy characterized by frequent tonic CC seizures or spasms beginning in infancy with a specific EEG CC finding of suppression-burst patterns, characterized by high- CC voltage bursts alternating with almost flat suppression phases. CC Patients may progress to West syndrome, which is characterized by CC tonic spasms with clustering, arrest of psychomotor development, CC and hypsarrhythmia on EEG. {ECO:0000269|PubMed:20833646}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- MISCELLANEOUS: The receptor-mediated activation of PLC-beta-1 is CC mediated by two G-protein alpha subunits, alpha-Q and alpha-11. CC -!- SIMILARITY: Contains 1 C2 domain. {ECO:0000255|PROSITE- CC ProRule:PRU00041}. CC -!- SIMILARITY: Contains 1 PI-PLC X-box domain. {ECO:0000255|PROSITE- CC ProRule:PRU00270}. CC -!- SIMILARITY: Contains 1 PI-PLC Y-box domain. {ECO:0000255|PROSITE- CC ProRule:PRU00271}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA25507.3; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=BAB14641.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/PLCB1ID41742ch20p12.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AJ278313; CAB98142.1; -; mRNA. DR EMBL; AJ278314; CAB98143.1; -; mRNA. DR EMBL; AY004175; AAF86613.1; -; mRNA. DR EMBL; AB011153; BAA25507.3; ALT_INIT; mRNA. DR EMBL; AL031683; CAI43121.1; -; Genomic_DNA. DR EMBL; AL034551; CAI43121.1; JOINED; Genomic_DNA. DR EMBL; AL049593; CAI43121.1; JOINED; Genomic_DNA. DR EMBL; AL049632; CAI43121.1; JOINED; Genomic_DNA. DR EMBL; AL050315; CAI43121.1; JOINED; Genomic_DNA. DR EMBL; AL050323; CAI43121.1; JOINED; Genomic_DNA. DR EMBL; AL031683; CAI43122.1; -; Genomic_DNA. DR EMBL; AL034551; CAI43122.1; JOINED; Genomic_DNA. DR EMBL; AL050315; CAI43122.1; JOINED; Genomic_DNA. DR EMBL; AL049632; CAI43122.1; JOINED; Genomic_DNA. DR EMBL; AL050323; CAI43122.1; JOINED; Genomic_DNA. DR EMBL; AL034551; CAI21973.1; -; Genomic_DNA. DR EMBL; AL031683; CAI21973.1; JOINED; Genomic_DNA. DR EMBL; AL049593; CAI21973.1; JOINED; Genomic_DNA. DR EMBL; AL049632; CAI21973.1; JOINED; Genomic_DNA. DR EMBL; AL050315; CAI21973.1; JOINED; Genomic_DNA. DR EMBL; AL050323; CAI21973.1; JOINED; Genomic_DNA. DR EMBL; AL034551; CAI21974.1; -; Genomic_DNA. DR EMBL; AL031683; CAI21974.1; JOINED; Genomic_DNA. DR EMBL; AL050315; CAI21974.1; JOINED; Genomic_DNA. DR EMBL; AL049632; CAI21974.1; JOINED; Genomic_DNA. DR EMBL; AL050323; CAI21974.1; JOINED; Genomic_DNA. DR EMBL; AL049593; CAI22175.1; -; Genomic_DNA. DR EMBL; AL031683; CAI22175.1; JOINED; Genomic_DNA. DR EMBL; AL034551; CAI22175.1; JOINED; Genomic_DNA. DR EMBL; AL049632; CAI22175.1; JOINED; Genomic_DNA. DR EMBL; AL050315; CAI22175.1; JOINED; Genomic_DNA. DR EMBL; AL050323; CAI22175.1; JOINED; Genomic_DNA. DR EMBL; AL049632; CAI43151.1; -; Genomic_DNA. DR EMBL; AL031683; CAI43151.1; JOINED; Genomic_DNA. DR EMBL; AL034551; CAI43151.1; JOINED; Genomic_DNA. DR EMBL; AL049593; CAI43151.1; JOINED; Genomic_DNA. DR EMBL; AL050315; CAI43151.1; JOINED; Genomic_DNA. DR EMBL; AL050323; CAI43151.1; JOINED; Genomic_DNA. DR EMBL; AL049632; CAI43152.1; -; Genomic_DNA. DR EMBL; AL031683; CAI43152.1; JOINED; Genomic_DNA. DR EMBL; AL034551; CAI43152.1; JOINED; Genomic_DNA. DR EMBL; AL050315; CAI43152.1; JOINED; Genomic_DNA. DR EMBL; AL050323; CAI43152.1; JOINED; Genomic_DNA. DR EMBL; AL050315; CAI42238.1; -; Genomic_DNA. DR EMBL; AL031683; CAI42238.1; JOINED; Genomic_DNA. DR EMBL; AL034551; CAI42238.1; JOINED; Genomic_DNA. DR EMBL; AL049593; CAI42238.1; JOINED; Genomic_DNA. DR EMBL; AL049632; CAI42238.1; JOINED; Genomic_DNA. DR EMBL; AL050323; CAI42238.1; JOINED; Genomic_DNA. DR EMBL; AL050315; CAI42239.1; -; Genomic_DNA. DR EMBL; AL031683; CAI42239.1; JOINED; Genomic_DNA. DR EMBL; AL034551; CAI42239.1; JOINED; Genomic_DNA. DR EMBL; AL049632; CAI42239.1; JOINED; Genomic_DNA. DR EMBL; AL050323; CAI42239.1; JOINED; Genomic_DNA. DR EMBL; AL050323; CAI22830.1; -; Genomic_DNA. DR EMBL; AL031683; CAI22830.1; JOINED; Genomic_DNA. DR EMBL; AL034551; CAI22830.1; JOINED; Genomic_DNA. DR EMBL; AL049593; CAI22830.1; JOINED; Genomic_DNA. DR EMBL; AL049632; CAI22830.1; JOINED; Genomic_DNA. DR EMBL; AL050315; CAI22830.1; JOINED; Genomic_DNA. DR EMBL; AL050323; CAI22831.1; -; Genomic_DNA. DR EMBL; AL031683; CAI22831.1; JOINED; Genomic_DNA. DR EMBL; AL034551; CAI22831.1; JOINED; Genomic_DNA. DR EMBL; AL050315; CAI22831.1; JOINED; Genomic_DNA. DR EMBL; AL049632; CAI22831.1; JOINED; Genomic_DNA. DR EMBL; CH471133; EAX10372.1; -; Genomic_DNA. DR EMBL; CH471133; EAX10373.1; -; Genomic_DNA. DR EMBL; CH471133; EAX10374.1; -; Genomic_DNA. DR EMBL; CH471133; EAX10376.1; -; Genomic_DNA. DR EMBL; BC069420; AAH69420.1; -; mRNA. DR EMBL; BC117231; AAI17232.1; -; mRNA. DR EMBL; AL137267; CAB70666.1; -; mRNA. DR EMBL; AK023689; BAB14641.1; ALT_INIT; mRNA. DR CCDS; CCDS13102.1; -. [Q9NQ66-1] DR CCDS; CCDS13103.1; -. [Q9NQ66-2] DR RefSeq; NP_056007.1; NM_015192.3. [Q9NQ66-1] DR RefSeq; NP_877398.1; NM_182734.2. [Q9NQ66-2] DR UniGene; Hs.431173; -. DR ProteinModelPortal; Q9NQ66; -. DR SMR; Q9NQ66; 11-833. DR BioGrid; 116841; 15. DR IntAct; Q9NQ66; 6. DR MINT; MINT-5005654; -. DR STRING; 9606.ENSP00000338185; -. DR BindingDB; Q9NQ66; -. DR ChEMBL; CHEMBL4034; -. DR PhosphoSite; Q9NQ66; -. DR DMDM; 12643814; -. DR MaxQB; Q9NQ66; -. DR PaxDb; Q9NQ66; -. DR PRIDE; Q9NQ66; -. DR Ensembl; ENST00000338037; ENSP00000338185; ENSG00000182621. [Q9NQ66-1] DR Ensembl; ENST00000378637; ENSP00000367904; ENSG00000182621. [Q9NQ66-2] DR Ensembl; ENST00000378641; ENSP00000367908; ENSG00000182621. [Q9NQ66-2] DR GeneID; 23236; -. DR KEGG; hsa:23236; -. DR UCSC; uc002wna.4; human. [Q9NQ66-2] DR UCSC; uc002wnb.4; human. [Q9NQ66-1] DR CTD; 23236; -. DR GeneCards; PLCB1; -. DR HGNC; HGNC:15917; PLCB1. DR HPA; CAB004275; -. DR HPA; CAB005334; -. DR HPA; HPA034743; -. DR HPA; HPA057910; -. DR MIM; 607120; gene. DR MIM; 613722; phenotype. DR neXtProt; NX_Q9NQ66; -. DR Orphanet; 293181; Malignant migrating partial seizures of infancy. DR Orphanet; 3451; West syndrome. DR PharmGKB; PA33384; -. DR eggNOG; KOG0169; Eukaryota. DR eggNOG; ENOG410XPSW; LUCA. DR GeneTree; ENSGT00760000118936; -. DR HOVERGEN; HBG053609; -. DR InParanoid; Q9NQ66; -. DR KO; K05858; -. DR OMA; MMDFINL; -. DR OrthoDB; EOG7WDN1N; -. DR PhylomeDB; Q9NQ66; -. DR TreeFam; TF313216; -. DR BRENDA; 3.1.4.11; 2681. DR Reactome; R-HSA-112043; PLC beta mediated events. DR Reactome; R-HSA-1855204; Synthesis of IP3 and IP4 in the cytosol. DR Reactome; R-HSA-399997; Acetylcholine regulates insulin secretion. DR Reactome; R-HSA-4086398; Ca2+ pathway. DR Reactome; R-HSA-416476; G alpha (q) signalling events. DR Reactome; R-HSA-418217; G beta:gamma signalling through PLC beta. DR Reactome; R-HSA-434316; Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion. DR Reactome; R-HSA-500657; Presynaptic function of Kainate receptors. DR SignaLink; Q9NQ66; -. DR ChiTaRS; PLCB1; human. DR GeneWiki; PLCB1; -. DR GenomeRNAi; 23236; -. DR NextBio; 44882; -. DR PRO; PR:Q9NQ66; -. DR Proteomes; UP000005640; Chromosome 20. DR Bgee; Q9NQ66; -. DR ExpressionAtlas; Q9NQ66; baseline and differential. DR Genevisible; Q9NQ66; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0043209; C:myelin sheath; IEA:Ensembl. DR GO; GO:0000790; C:nuclear chromatin; ISS:BHF-UCL. DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell. DR GO; GO:0016607; C:nuclear speck; IDA:BHF-UCL. DR GO; GO:0005634; C:nucleus; NAS:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0005516; F:calmodulin binding; IPI:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0005096; F:GTPase activator activity; IDA:BHF-UCL. DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; ISS:AgBase. DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; ISS:BHF-UCL. DR GO; GO:0004871; F:signal transducer activity; IEA:UniProtKB-KW. DR GO; GO:0060466; P:activation of meiosis involved in egg activation; ISS:BHF-UCL. DR GO; GO:0021987; P:cerebral cortex development; ISS:BHF-UCL. DR GO; GO:0045444; P:fat cell differentiation; IEA:Ensembl. DR GO; GO:0007213; P:G-protein coupled acetylcholine receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; ISS:BHF-UCL. DR GO; GO:0007215; P:glutamate receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0043647; P:inositol phosphate metabolic process; TAS:Reactome. DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IDA:BHF-UCL. DR GO; GO:0035722; P:interleukin-12-mediated signaling pathway; IDA:BHF-UCL. DR GO; GO:0035723; P:interleukin-15-mediated signaling pathway; IDA:BHF-UCL. DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro. DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW. DR GO; GO:0007613; P:memory; ISS:BHF-UCL. DR GO; GO:2000438; P:negative regulation of monocyte extravasation; ISS:BHF-UCL. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:BHF-UCL. DR GO; GO:0046488; P:phosphatidylinositol metabolic process; ISS:BHF-UCL. DR GO; GO:2000344; P:positive regulation of acrosome reaction; ISS:BHF-UCL. DR GO; GO:2000560; P:positive regulation of CD24 biosynthetic process; ISS:BHF-UCL. DR GO; GO:0048639; P:positive regulation of developmental growth; ISS:BHF-UCL. DR GO; GO:0040019; P:positive regulation of embryonic development; ISS:BHF-UCL. DR GO; GO:1900087; P:positive regulation of G1/S transition of mitotic cell cycle; ISS:BHF-UCL. DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:GOC. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISS:BHF-UCL. DR GO; GO:0046330; P:positive regulation of JNK cascade; IDA:BHF-UCL. DR GO; GO:0045663; P:positive regulation of myoblast differentiation; ISS:BHF-UCL. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:BHF-UCL. DR GO; GO:0080154; P:regulation of fertilization; ISS:BHF-UCL. DR GO; GO:0008277; P:regulation of G-protein coupled receptor protein signaling pathway; ISS:BHF-UCL. DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR GO; GO:0007268; P:synaptic transmission; TAS:Reactome. DR Gene3D; 1.10.238.10; -; 1. DR Gene3D; 2.60.40.150; -; 1. DR Gene3D; 3.20.20.190; -; 2. DR InterPro; IPR000008; C2_dom. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR001192; PI-PLC_fam. DR InterPro; IPR016280; PLC-beta. DR InterPro; IPR028400; PLC-beta1. DR InterPro; IPR014815; PLC-beta_C. DR InterPro; IPR009535; PLC-beta_CS. DR InterPro; IPR017946; PLC-like_Pdiesterase_TIM-brl. DR InterPro; IPR015359; PLC_EF-hand-like. DR InterPro; IPR000909; PLipase_C_PInositol-sp_X_dom. DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y. DR PANTHER; PTHR10336; PTHR10336; 1. DR PANTHER; PTHR10336:SF12; PTHR10336:SF12; 1. DR Pfam; PF06631; DUF1154; 1. DR Pfam; PF09279; EF-hand_like; 1. DR Pfam; PF00388; PI-PLC-X; 1. DR Pfam; PF00387; PI-PLC-Y; 1. DR Pfam; PF08703; PLC-beta_C; 1. DR PIRSF; PIRSF000956; PLC-beta; 1. DR PRINTS; PR00390; PHPHLIPASEC. DR SMART; SM00239; C2; 1. DR SMART; SM00148; PLCXc; 1. DR SMART; SM00149; PLCYc; 1. DR SUPFAM; SSF49562; SSF49562; 1. DR SUPFAM; SSF51695; SSF51695; 1. DR PROSITE; PS50004; C2; 1. DR PROSITE; PS50007; PIPLC_X_DOMAIN; 1. DR PROSITE; PS50008; PIPLC_Y_DOMAIN; 1. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Complete proteome; Cytoplasm; Epilepsy; KW Hydrolase; Lipid degradation; Lipid metabolism; Membrane; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Transducer. FT CHAIN 1 1216 1-phosphatidylinositol 4,5-bisphosphate FT phosphodiesterase beta-1. FT /FTId=PRO_0000088486. FT DOMAIN 316 467 PI-PLC X-box. {ECO:0000255|PROSITE- FT ProRule:PRU00270}. FT DOMAIN 540 656 PI-PLC Y-box. {ECO:0000255|PROSITE- FT ProRule:PRU00271}. FT DOMAIN 663 761 C2. {ECO:0000255|PROSITE- FT ProRule:PRU00041}. FT ACT_SITE 331 331 {ECO:0000255|PROSITE-ProRule:PRU00270}. FT ACT_SITE 378 378 {ECO:0000255|PROSITE-ProRule:PRU00270}. FT MOD_RES 236 236 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9Z1B3}. FT MOD_RES 417 417 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9Z1B3}. FT MOD_RES 509 509 Phosphothreonine. FT {ECO:0000250|UniProtKB:Q9Z1B3}. FT MOD_RES 511 511 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9Z1B3}. FT MOD_RES 582 582 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9Z1B3}. FT MOD_RES 887 887 Phosphoserine; by PKC. {ECO:0000250}. FT MOD_RES 978 978 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9Z1B3}. FT MOD_RES 987 987 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9Z1B3}. FT MOD_RES 1199 1199 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9Z1B3}. FT MOD_RES 1200 1200 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9Z1B3}. FT VAR_SEQ 1142 1216 LQVELEQEYQDKFKRLPLEILEFVQEAMKGKISEDSNHGSA FT PLSLSSDPGKVNHKTPSSEELGGDIPGKEFDTPL -> GEG FT SSSFLSETCHEDPSVSPNFTPPNPQALKW (in isoform FT B). {ECO:0000303|PubMed:11118617, FT ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:17974005}. FT /FTId=VSP_004718. FT VARIANT 854 854 E -> K (in dbSNP:rs2076413). FT /FTId=VAR_050541. FT VARIANT 907 907 A -> P (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_036547. FT CONFLICT 1 34 MAGAQPGVHALQLKPVCVSDSLKKGTKFVKWDDD -> MGS FT LQGIATKILIRILSDALIRKETDLKS (in Ref. 2; FT AAF86613). {ECO:0000305}. FT CONFLICT 189 189 L -> M (in Ref. 2; AAF86613). FT {ECO:0000305}. FT CONFLICT 203 203 P -> L (in Ref. 2; AAF86613). FT {ECO:0000305}. FT CONFLICT 216 216 L -> F (in Ref. 2; AAF86613). FT {ECO:0000305}. FT CONFLICT 221 221 P -> L (in Ref. 2; AAF86613). FT {ECO:0000305}. FT CONFLICT 266 266 L -> P (in Ref. 2; AAF86613). FT {ECO:0000305}. FT CONFLICT 309 309 P -> T (in Ref. 2; AAF86613). FT {ECO:0000305}. FT CONFLICT 320 320 Q -> R (in Ref. 2; AAF86613). FT {ECO:0000305}. FT CONFLICT 352 352 V -> A (in Ref. 2; AAF86613). FT {ECO:0000305}. FT CONFLICT 366 366 K -> R (in Ref. 2; AAF86613). FT {ECO:0000305}. FT CONFLICT 393 393 E -> K (in Ref. 2; AAF86613). FT {ECO:0000305}. FT CONFLICT 983 983 P -> S (in Ref. 1; CAB98143). FT {ECO:0000305}. SQ SEQUENCE 1216 AA; 138567 MW; 6F4263D1A50C6FD1 CRC64; MAGAQPGVHA LQLKPVCVSD SLKKGTKFVK WDDDSTIVTP IILRTDPQGF FFYWTDQNKE TELLDLSLVK DARCGRHAKA PKDPKLRELL DVGNIGRLEQ RMITVVYGPD LVNISHLNLV AFQEEVAKEW TNEVFSLATN LLAQNMSRDA FLEKAYTKLK LQVTPEGRIP LKNIYRLFSA DRKRVETALE ACSLPSSRND SIPQEDFTPE VYRVFLNNLC PRPEIDNIFS EFGAKSKPYL TVDQMMDFIN LKQRDPRLNE ILYPPLKQEQ VQVLIEKYEP NNSLARKGQI SVDGFMRYLS GEENGVVSPE KLDLNEDMSQ PLSHYFINSS HNTYLTAGQL AGNSSVEMYR QVLLSGCRCV ELDCWKGRTA EEEPVITHGF TMTTEISFKE VIEAIAECAF KTSPFPILLS FENHVDSPKQ QAKMAEYCRL IFGDALLMEP LEKYPLESGV PLPSPMDLMY KILVKNKKKS HKSSEGSGKK KLSEQASNTY SDSSSMFEPS SPGAGEADTE SDDDDDDDDC KKSSMDEGTA GSEAMATEEM SNLVNYIQPV KFESFEISKK RNKSFEMSSF VETKGLEQLT KSPVEFVEYN KMQLSRIYPK GTRVDSSNYM PQLFWNAGCQ MVALNFQTMD LAMQINMGMY EYNGKSGYRL KPEFMRRPDK HFDPFTEGIV DGIVANTLSV KIISGQFLSD KKVGTYVEVD MFGLPVDTRR KAFKTKTSQG NAVNPVWEEE PIVFKKVVLP TLACLRIAVY EEGGKFIGHR ILPVQAIRPG YHYICLRNER NQPLTLPAVF VYIEVKDYVP DTYADVIEAL SNPIRYVNLM EQRAKQLAAL TLEDEEEVKK EADPGETPSE APSEARTTPA ENGVNHTTTL TPKPPSQALH SQPAPGSVKA PAKTEDLIQS VLTEVEAQTI EELKQQKSFV KLQKKHYKEM KDLVKRHHKK TTDLIKEHTT KYNEIQNDYL RRRAALEKSA KKDSKKKSEP SSPDHGSSTI EQDLAALDAE MTQKLIDLKD KQQQQLLNLR QEQYYSEKYQ KREHIKLLIQ KLTDVAEECQ NNQLKKLKEI CEKEKKELKK KMDKKRQEKI TEAKSKDKSQ MEEEKTEMIR SYIQEVVQYI KRLEEAQSKR QEKLVEKHKE IRQQILDEKP KLQVELEQEY QDKFKRLPLE ILEFVQEAMK GKISEDSNHG SAPLSLSSDP GKVNHKTPSS EELGGDIPGK EFDTPL // ID PR15A_HUMAN Reviewed; 674 AA. AC O75807; B4DKQ3; Q6IA96; Q9NVU6; DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 11-NOV-2015, entry version 110. DE RecName: Full=Protein phosphatase 1 regulatory subunit 15A; DE AltName: Full=Growth arrest and DNA damage-inducible protein GADD34; DE AltName: Full=Myeloid differentiation primary response protein MyD116 homolog; GN Name=PPP1R15A; Synonyms=GADD34; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INDUCTION. RX PubMed=9153226; DOI=10.1074/jbc.272.21.13731; RA Hollander M.C., Zhan Q., Bae I., Fornace A.J. Jr.; RT "Mammalian GADD34, an apoptosis- and DNA damage-inducible gene."; RL J. Biol. Chem. 272:13731-13737(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT RP THR-32. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND RP VARIANTS GLU-277; SER-312; PRO-316; SER-476 AND ALA-597. RC TISSUE=Umbilical cord blood; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION. RX PubMed=8139541; DOI=10.1128/MCB.14.4.2361; RA Zhan Q., Lord K.A., Alamo I. Jr., Hollander M.C., Carrier F., Ron D., RA Kohn K.W., Hoffman B., Liebermann D.A., Fornace A.J. Jr.; RT "The gadd and MyD genes define a novel set of mammalian genes encoding RT acidic proteins that synergistically suppress cell growth."; RL Mol. Cell. Biol. 14:2361-2371(1994). RN [7] RP INTERACTION WITH KMT2A/MLL1 AND SMARCB1, AND INDUCTION. RX PubMed=10490642; RA Adler H.T., Chinery R., Wu D.Y., Kussick S.J., Payne J.M., RA Fornace A.J. Jr., Tkachuk D.C.; RT "Leukemic HRX fusion proteins inhibit GADD34-induced apoptosis and RT associate with the GADD34 and hSNF5/INI1 proteins."; RL Mol. Cell. Biol. 19:7050-7060(1999). RN [8] RP INTERACTION WITH LYN, AND PHOSPHORYLATION. RX PubMed=11517336; DOI=10.1073/pnas.191130798; RA Grishin A.V., Azhipa O., Semenov I., Corey S.J.; RT "Interaction between growth arrest-DNA damage protein 34 and Src RT kinase Lyn negatively regulates genotoxic apoptosis."; RL Proc. Natl. Acad. Sci. U.S.A. 98:10172-10177(2001). RN [9] RP INTERACTION WITH PP1 AND PPP1R1A, AND FUNCTION. RX PubMed=11564868; DOI=10.1128/MCB.21.20.6841-6850.2001; RA Connor J.H., Weiser D.C., Li S., Hallenbeck J.M., Shenolikar S.; RT "Growth arrest and DNA damage-inducible protein GADD34 assembles a RT novel signaling complex containing protein phosphatase 1 and inhibitor RT 1."; RL Mol. Cell. Biol. 21:6841-6850(2001). RN [10] RP INTERACTION WITH SMARCB1 AND PP1, AND MUTAGENESIS OF 555-LYS--PHE-558. RX PubMed=12016208; DOI=10.1074/jbc.M200955200; RA Wu D.Y., Tkachuck D.C., Roberson R.S., Schubach W.H.; RT "The human SNF5/INI1 protein facilitates the function of the growth RT arrest and DNA damage-inducible protein (GADD34) and modulates GADD34- RT bound protein phosphatase-1 activity."; RL J. Biol. Chem. 277:27706-27715(2002). RN [11] RP INDUCTION. RX PubMed=12114539; DOI=10.1073/pnas.152327199; RA Sarkar D., Su Z.-Z., Lebedeva I.V., Sauane M., Gopalkrishnan R.V., RA Valerie K., Dent P., Fisher P.B.; RT "mda-7 (IL-24) Mediates selective apoptosis in human melanoma cells by RT inducing the coordinated overexpression of the GADD family of genes by RT means of p38 MAPK."; RL Proc. Natl. Acad. Sci. U.S.A. 99:10054-10059(2002). RN [12] RP FUNCTION. RX PubMed=14635196; DOI=10.1002/jcb.10711; RA Yagi A., Hasegawa Y., Xiao H., Haneda M., Kojima E., Nishikimi A., RA Hasegawa T., Shimokata K., Isobe K.; RT "GADD34 induces p53 phosphorylation and p21/WAF1 transcription."; RL J. Cell. Biochem. 90:1242-1249(2003). RN [13] RP FUNCTION, MUTAGENESIS OF 556-VAL--SER-558; ARG-612; ARG-614 AND RP ARG-618, AND SUBCELLULAR LOCATION. RX PubMed=12556489; DOI=10.1128/MCB.23.4.1292-1303.2003; RA Brush M.H., Weiser D.C., Shenolikar S.; RT "Growth arrest and DNA damage-inducible protein GADD34 targets protein RT phosphatase 1 alpha to the endoplasmic reticulum and promotes RT dephosphorylation of the alpha subunit of eukaryotic translation RT initiation factor 2."; RL Mol. Cell. Biol. 23:1292-1303(2003). RN [14] RP INTERACTION WITH BAG1. RX PubMed=12724406; DOI=10.1128/MCB.23.10.3477-3486.2003; RA Hung W.J., Roberson R.S., Taft J., Wu D.Y.; RT "Human BAG-1 proteins bind to the cellular stress response protein RT GADD34 and interfere with GADD34 functions."; RL Mol. Cell. Biol. 23:3477-3486(2003). RN [15] RP FUNCTION, AND INTERACTION WITH SMAD7. RX PubMed=14718519; DOI=10.1083/jcb.200307151; RA Shi W., Sun C., He B., Xiong W., Shi X., Yao D., Cao X.; RT "GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I RT receptor."; RL J. Cell Biol. 164:291-300(2004). RN [16] RP INTERACTION WITH PP1. RX PubMed=15705855; DOI=10.1126/science.1101902; RA Boyce M., Bryant K.F., Jousse C., Long K., Harding H.P., Scheuner D., RA Kaufman R.J., Ma D., Coen D.M., Ron D., Yuan J.; RT "A selective inhibitor of eIF2alpha dephosphorylation protects cells RT from ER stress."; RL Science 307:935-939(2005). RN [17] RP SUBCELLULAR LOCATION, TOPOLOGY, INTRAMEMBRANE REGION, AND MUTAGENESIS RP OF VAL-25 AND LEU-29. RX PubMed=21518769; DOI=10.1074/jbc.M110.212787; RA Zhou W., Brush M.H., Choy M.S., Shenolikar S.; RT "Association with endoplasmic reticulum promotes proteasomal RT degradation of GADD34 protein."; RL J. Biol. Chem. 286:21687-21696(2011). RN [18] RP PHOSPHORYLATION AT TYR-262; TYR-391; TYR-434 AND TYR-512, RP UBIQUITINATION, AND MUTAGENESIS OF TYR-262. RX PubMed=24092754; DOI=10.1074/jbc.M113.504407; RA Zhou W., Jeyaraman K., Yusoff P., Shenolikar S.; RT "Phosphorylation at tyrosine 262 promotes GADD34 protein turnover."; RL J. Biol. Chem. 288:33146-33155(2013). CC -!- FUNCTION: Recruits the serine/threonine-protein phosphatase PP1 to CC dephosphorylate the translation initiation factor eIF-2A/EIF2S1, CC thereby reversing the shut-off of protein synthesis initiated by CC stress-inducible kinases and facilitating recovery of cells from CC stress. Down-regulates the TGF-beta signaling pathway by promoting CC dephosphorylation of TGFB1 by PP1. May promote apoptosis by CC inducing TP53 phosphorylation on 'Ser-15'. CC {ECO:0000269|PubMed:11564868, ECO:0000269|PubMed:12556489, CC ECO:0000269|PubMed:14635196, ECO:0000269|PubMed:14718519, CC ECO:0000269|PubMed:8139541}. CC -!- SUBUNIT: Interacts with PCNA (By similarity). Interacts with LYN CC and KMT2A/MLL1. Interacts with PP1, PPP1R1A and SMARCB1. Interacts CC with SMAD7. Interacts with BAG1. {ECO:0000250, CC ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:11517336, CC ECO:0000269|PubMed:11564868, ECO:0000269|PubMed:12016208, CC ECO:0000269|PubMed:12724406, ECO:0000269|PubMed:14718519, CC ECO:0000269|PubMed:15705855}. CC -!- INTERACTION: CC P56545:CTBP2; NbExp=2; IntAct=EBI-714746, EBI-741533; CC Q13522:PPP1R1A; NbExp=4; IntAct=EBI-714746, EBI-1568511; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral CC membrane protein; Cytoplasmic side {ECO:0000269|PubMed:12556489, CC ECO:0000269|PubMed:21518769}. Mitochondrion outer membrane; CC Peripheral membrane protein; Cytoplasmic side CC {ECO:0000269|PubMed:21518769}. Note=Associates with membranes via CC an N-terminal amphipathic intramembrane region. CC {ECO:0000269|PubMed:21518769}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O75807-1; Sequence=Displayed; CC Name=2; CC IsoId=O75807-2; Sequence=VSP_057083, VSP_057084; CC Note=No experimental confirmation available.; CC -!- INDUCTION: By methyl methanesulfonate and ionizing irradiation. By CC IL24/interleukin-24 in melanoma cells; which induces apoptosis. CC {ECO:0000269|PubMed:10490642, ECO:0000269|PubMed:12114539, CC ECO:0000269|PubMed:9153226}. CC -!- PTM: Phosphorylated at multiple Ser/Thr residues. Phosphorylated CC on tyrosine by LYN; which impairs its antiproliferative activity. CC Phosphorylation at Tyr-262 enhances proteasomal degradation, this CC position is dephosphorylated by PTPN2. CC {ECO:0000269|PubMed:11517336, ECO:0000269|PubMed:24092754}. CC -!- PTM: Polyubiquitinated. Exhibits a rapid proteasomal degradation CC with a half-life under 1 hour, ubiquitination depends on CC endoplasmic reticulum association. {ECO:0000269|PubMed:24092754}. CC -!- MISCELLANEOUS: The phosphatase activity of the PPP1R15A-PP1 CC complex toward EIF2S1 is specifically inhibited by Salubrinal, a CC drug that protects cells from endoplasmic reticulum stress. CC -!- SIMILARITY: Belongs to the PPP1R15 family. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U83981; AAC25631.1; -; mRNA. DR EMBL; CR457259; CAG33540.1; -; mRNA. DR EMBL; AK001361; BAA91649.1; -; mRNA. DR EMBL; AK296668; BAG59265.1; -; mRNA. DR EMBL; CH471177; EAW52409.1; -; Genomic_DNA. DR EMBL; BC003067; AAH03067.1; -; mRNA. DR CCDS; CCDS12738.1; -. [O75807-1] DR RefSeq; NP_055145.3; NM_014330.3. [O75807-1] DR UniGene; Hs.631593; -. DR PDB; 4XPN; X-ray; 2.29 A; B/D=552-591. DR PDBsum; 4XPN; -. DR ProteinModelPortal; O75807; -. DR BioGrid; 117172; 30. DR IntAct; O75807; 12. DR MINT; MINT-1192304; -. DR STRING; 9606.ENSP00000200453; -. DR PhosphoSite; O75807; -. DR BioMuta; PPP1R15A; -. DR MaxQB; O75807; -. DR PaxDb; O75807; -. DR PRIDE; O75807; -. DR DNASU; 23645; -. DR Ensembl; ENST00000200453; ENSP00000200453; ENSG00000087074. [O75807-1] DR GeneID; 23645; -. DR KEGG; hsa:23645; -. DR UCSC; uc002pky.4; human. [O75807-1] DR CTD; 23645; -. DR GeneCards; PPP1R15A; -. DR H-InvDB; HIX0015305; -. DR H-InvDB; HIX0174313; -. DR HGNC; HGNC:14375; PPP1R15A. DR HPA; CAB018395; -. DR HPA; HPA020240; -. DR MIM; 611048; gene. DR neXtProt; NX_O75807; -. DR PharmGKB; PA33632; -. DR eggNOG; ENOG410ITE6; Eukaryota. DR eggNOG; ENOG410Y1YJ; LUCA. DR GeneTree; ENSGT00510000049287; -. DR HOGENOM; HOG000060154; -. DR HOVERGEN; HBG052542; -. DR InParanoid; O75807; -. DR KO; K14019; -. DR OMA; VRAWVYR; -. DR OrthoDB; EOG75QR48; -. DR PhylomeDB; O75807; -. DR TreeFam; TF105547; -. DR Reactome; R-HSA-2173788; Downregulation of TGF-beta receptor signaling. DR SignaLink; O75807; -. DR ChiTaRS; PPP1R15A; human. DR GeneWiki; PPP1R15A; -. DR GenomeRNAi; 23645; -. DR NextBio; 35472843; -. DR PRO; PR:O75807; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; O75807; -. DR CleanEx; HS_PPP1R15A; -. DR ExpressionAtlas; O75807; baseline and differential. DR Genevisible; O75807; HS. DR GO; GO:0005737; C:cytoplasm; IDA:ParkinsonsUK-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:ParkinsonsUK-UCL. DR GO; GO:0005789; C:endoplasmic reticulum membrane; NAS:ParkinsonsUK-UCL. DR GO; GO:0005794; C:Golgi apparatus; IDA:ParkinsonsUK-UCL. DR GO; GO:0016020; C:membrane; IDA:ParkinsonsUK-UCL. DR GO; GO:0005741; C:mitochondrial outer membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:ParkinsonsUK-UCL. DR GO; GO:0000164; C:protein phosphatase type 1 complex; IDA:ParkinsonsUK-UCL. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0008157; F:protein phosphatase 1 binding; IDA:ParkinsonsUK-UCL. DR GO; GO:0071862; F:protein phosphatase type 1 activator activity; IC:ParkinsonsUK-UCL. DR GO; GO:0008599; F:protein phosphatase type 1 regulator activity; IC:ParkinsonsUK-UCL. DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc. DR GO; GO:0007050; P:cell cycle arrest; TAS:ProtInc. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; TAS:ProtInc. DR GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IEA:Ensembl. DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; TAS:ParkinsonsUK-UCL. DR GO; GO:1903912; P:negative regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; IEA:Ensembl. DR GO; GO:1903898; P:negative regulation of PERK-mediated unfolded protein response; TAS:ParkinsonsUK-UCL. DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0035308; P:negative regulation of protein dephosphorylation; IDA:ParkinsonsUK-UCL. DR GO; GO:1990441; P:negative regulation of transcription from RNA polymerase II promoter in response to endoplasmic reticulum stress; IEA:Ensembl. DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; TAS:Reactome. DR GO; GO:0070262; P:peptidyl-serine dephosphorylation; IEA:Ensembl. DR GO; GO:1903917; P:positive regulation of endoplasmic reticulum stress-induced eIF2 alpha dephosphorylation; TAS:ParkinsonsUK-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ParkinsonsUK-UCL. DR GO; GO:1902310; P:positive regulation of peptidyl-serine dephosphorylation; IDA:ParkinsonsUK-UCL. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:ParkinsonsUK-UCL. DR GO; GO:0032516; P:positive regulation of phosphoprotein phosphatase activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0045943; P:positive regulation of transcription from RNA polymerase I promoter; IGI:ParkinsonsUK-UCL. DR GO; GO:0032058; P:positive regulation of translational initiation in response to stress; IC:ParkinsonsUK-UCL. DR GO; GO:0070972; P:protein localization to endoplasmic reticulum; IMP:ParkinsonsUK-UCL. DR GO; GO:0060734; P:regulation of endoplasmic reticulum stress-induced eIF2 alpha phosphorylation; IEA:Ensembl. DR GO; GO:0036496; P:regulation of translational initiation by eIF2 alpha dephosphorylation; IDA:ParkinsonsUK-UCL. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:ParkinsonsUK-UCL. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome. DR InterPro; IPR019523; Prot_Pase1_reg-su15A/B_C. DR Pfam; PF10488; PP1c_bdg; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Complete proteome; KW Endoplasmic reticulum; Membrane; Mitochondrion; KW Mitochondrion outer membrane; Phosphoprotein; Polymorphism; KW Reference proteome; Repeat; Stress response; Translation regulation; KW Ubl conjugation. FT CHAIN 1 674 Protein phosphatase 1 regulatory subunit FT 15A. FT /FTId=PRO_0000320518. FT TOPO_DOM 1 21 Cytoplasmic. FT {ECO:0000305|PubMed:21518769}. FT INTRAMEM 22 39 Helical. {ECO:0000305|PubMed:21518769}. FT TOPO_DOM 40 674 Cytoplasmic. FT {ECO:0000305|PubMed:21518769}. FT REPEAT 337 369 1. FT REPEAT 384 417 2. FT REPEAT 427 460 3. FT REPEAT 477 510 4. FT REGION 1 60 Required for localization in the FT endoplasmic reticulum. FT REGION 337 510 4 X 34 AA approximate repeats. FT REGION 337 510 Interaction with SMAD7. FT REGION 483 555 Interaction with KMT2A/MLL1. FT REGION 536 583 Interaction with SMARCB1. FT COMPBIAS 112 115 Poly-Asp. FT COMPBIAS 160 503 Glu-rich. FT COMPBIAS 518 521 Poly-Pro. FT COMPBIAS 661 666 Poly-Ala. FT MOD_RES 262 262 Phosphotyrosine. FT {ECO:0000269|PubMed:24092754}. FT MOD_RES 391 391 Phosphotyrosine. FT {ECO:0000269|PubMed:24092754}. FT MOD_RES 434 434 Phosphotyrosine. FT {ECO:0000269|PubMed:24092754}. FT MOD_RES 512 512 Phosphotyrosine. FT {ECO:0000269|PubMed:24092754}. FT VAR_SEQ 16 16 A -> D (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_057083. FT VAR_SEQ 17 175 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_057084. FT VARIANT 31 31 R -> H (in dbSNP:rs564196). FT /FTId=VAR_039186. FT VARIANT 32 32 A -> T (in dbSNP:rs3786734). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_039187. FT VARIANT 199 199 V -> A (in dbSNP:rs611251). FT /FTId=VAR_039188. FT VARIANT 251 251 R -> P (in dbSNP:rs557806). FT /FTId=VAR_039189. FT VARIANT 277 277 K -> E (in dbSNP:rs610308). FT {ECO:0000269|PubMed:14702039}. FT /FTId=VAR_039190. FT VARIANT 312 312 G -> S (in dbSNP:rs11541192). FT {ECO:0000269|PubMed:14702039}. FT /FTId=VAR_062226. FT VARIANT 316 316 A -> P (in dbSNP:rs556052). FT {ECO:0000269|PubMed:14702039}. FT /FTId=VAR_039191. FT VARIANT 381 381 A -> V (in dbSNP:rs1050166). FT /FTId=VAR_039192. FT VARIANT 476 476 R -> S (in dbSNP:rs35087747). FT {ECO:0000269|PubMed:14702039}. FT /FTId=VAR_039193. FT VARIANT 594 594 R -> C (in dbSNP:rs2270946). FT /FTId=VAR_039194. FT VARIANT 597 597 T -> A (in dbSNP:rs500079). FT {ECO:0000269|PubMed:14702039}. FT /FTId=VAR_039195. FT MUTAGEN 25 25 V->R: Localizes to cytoplasm, degraded FT more slowly. FT {ECO:0000269|PubMed:21518769}. FT MUTAGEN 29 29 L->R: Localizes to cytoplasm. FT {ECO:0000269|PubMed:21518769}. FT MUTAGEN 262 262 Y->F: Significantly reduced turnover. FT {ECO:0000269|PubMed:24092754}. FT MUTAGEN 555 558 KVRF->AAAA: Reduces interaction with FT SMARCB1. {ECO:0000269|PubMed:12016208}. FT MUTAGEN 556 558 VRF->ARA: Impairs PP1 activation. FT {ECO:0000269|PubMed:12556489}. FT MUTAGEN 612 612 R->K: Reduces PP1-binding; when FT associated with K-614. FT {ECO:0000269|PubMed:12556489}. FT MUTAGEN 614 614 R->K: Reduces PP1-binding; when FT associated with K-612. FT {ECO:0000269|PubMed:12556489}. FT MUTAGEN 618 618 R->D: Reduces PP1-binding. FT {ECO:0000269|PubMed:12556489}. FT CONFLICT 80 80 E -> G (in Ref. 3; BAA91649). FT {ECO:0000305}. FT CONFLICT 297 297 P -> L (in Ref. 2; CAG33540). FT {ECO:0000305}. FT CONFLICT 669 669 L -> P (in Ref. 3; BAG59265). FT {ECO:0000305}. FT STRAND 563 565 {ECO:0000244|PDB:4XPN}. SQ SEQUENCE 674 AA; 73478 MW; B257AA17456D1403 CRC64; MAPGQAPHQA TPWRDAHPFF LLSPVMGLLS RAWSRLRGLG PLEPWLVEAV KGAALVEAGL EGEARTPLAI PHTPWGRRPE EEAEDSGGPG EDRETLGLKT SSSLPEAWGL LDDDDGMYGE REATSVPRGQ GSQFADGQRA PLSPSLLIRT LQGSDKNPGE EKAEEEGVAE EEGVNKFSYP PSHRECCPAV EEEDDEEAVK KEAHRTSTSA LSPGSKPSTW VSCPGEEENQ ATEDKRTERS KGARKTSVSP RSSGSDPRSW EYRSGEASEE KEEKAHKETG KGEAAPGPQS SAPAQRPQLK SWWCQPSDEE EGEVKALGAA EKDGEAECPP CIPPPSAFLK AWVYWPGEDT EEEEDEEEDE DSDSGSDEEE GEAEASSSTP ATGVFLKSWV YQPGEDTEEE EDEDSDTGSA EDEREAETSA STPPASAFLK AWVYRPGEDT EEEEDEDVDS EDKEDDSEAA LGEAESDPHP SHPDQRAHFR GWGYRPGKET EEEEAAEDWG EAEPCPFRVA IYVPGEKPPP PWAPPRLPLR LQRRLKRPET PTHDPDPETP LKARKVRFSE KVTVHFLAVW AGPAQAARQG PWEQLARDRS RFARRITQAQ EELSPCLTPA ARARAWARLR NPPLAPIPAL TQTLPSSSVP SSPVQTTPLS QAVATPSRSS AAAAAALDLS GRRG // ID PROX1_HUMAN Reviewed; 737 AA. AC Q92786; A6NK29; A8K2B1; Q5SW76; Q8TB91; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 13-SEP-2005, sequence version 2. DT 11-NOV-2015, entry version 134. DE RecName: Full=Prospero homeobox protein 1; DE AltName: Full=Homeobox prospero-like protein PROX1; DE Short=PROX-1; GN Name=PROX1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC TISSUE=Embryonic brain; RX PubMed=8812486; DOI=10.1006/geno.1996.0392; RA Zinovieva R.D., Duncan M.K., Johnson T.R., Torres R., RA Polymeropoulos M.H., Tomarev S.I.; RT "Structure and chromosomal localization of the human homeobox gene RT Prox 1."; RL Genomics 35:517-522(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP REVIEW. RX PubMed=22733308; DOI=10.1007/s10555-012-9390-8; RA Elsir T., Smits A., Lindstroem M.S., Nister M.; RT "Transcription factor PROX1: its role in development and cancer."; RL Cancer Metastasis Rev. 31:793-805(2012). RN [7] RP FUNCTION. RX PubMed=23723244; DOI=10.1093/nar/gkt447; RA Takeda Y., Jetten A.M.; RT "Prospero-related homeobox 1 (Prox1) functions as a novel modulator of RT retinoic acid-related orphan receptors alpha- and gamma-mediated RT transactivation."; RL Nucleic Acids Res. 41:6992-7008(2013). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177; SER-199; SER-295 RP AND SER-557, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [9] RP STRUCTURE BY NMR OF 575-737. RX PubMed=22733734; DOI=10.1073/pnas.1203013109; RA Lange O.F., Rossi P., Sgourakis N.G., Song Y., Lee H.W., Aramini J.M., RA Ertekin A., Xiao R., Acton T.B., Montelione G.T., Baker D.; RT "Determination of solution structures of proteins up to 40 kDa using RT CS-Rosetta with sparse NMR data from deuterated samples."; RL Proc. Natl. Acad. Sci. U.S.A. 109:10873-10878(2012). CC -!- FUNCTION: Transcription factor involved in developmental processes CC such as cell fate determination, gene transcriptional regulation CC and progenitor cell regulation in a number of organs. Plays a CC critical role in embryonic development and functions as a key CC regulatory protein in neurogenesis and the development of the CC heart, eye lens, liver, pancreas and the lymphatic system. CC Involved in the regulation of the circadian rhythm. Represses: CC transcription of the retinoid-related orphan receptor RORG, CC transcriptional activator activity of RORA and RORG and the CC expression of RORA/G-target genes including core clock components: CC ARNTL/BMAL1, NPAS2 and CRY1 and metabolic genes: AVPR1A and CC ELOVL3. {ECO:0000269|PubMed:23723244, CC ECO:0000303|PubMed:22733308}. CC -!- SUBUNIT: Interacts with RORA and RORG (via AF-2 motif). CC {ECO:0000250|UniProtKB:P48437}. CC -!- INTERACTION: CC P56545:CTBP2; NbExp=2; IntAct=EBI-3912635, EBI-741533; CC P20823:HNF1A; NbExp=3; IntAct=EBI-3912635, EBI-636034; CC P41235:HNF4A; NbExp=3; IntAct=EBI-3912635, EBI-1049011; CC O00482-2:NR5A2; NbExp=9; IntAct=EBI-3912635, EBI-9257474; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P48437}. CC Note=RORG promotes its nuclear localization. CC {ECO:0000250|UniProtKB:P48437}. CC -!- TISSUE SPECIFICITY: Most actively expressed in the developing CC lens. Detected also in embryonic brain, lung, liver and kidney. In CC adult, it is more abundant in heart and liver than in brain, CC skeletal muscle, kidney and pancreas. CC {ECO:0000269|PubMed:8812486}. CC -!- DOMAIN: The prospero-type homeobox DNA-binding domain is essential CC for repression of RORG transcriptional activator activity. CC {ECO:0000250|UniProtKB:P48437}. CC -!- SIMILARITY: Belongs to the Prospero homeobox family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 Prospero-type homeobox DNA-binding domain. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAI15309.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U44060; AAC50656.1; -; mRNA. DR EMBL; AK290176; BAF82865.1; -; mRNA. DR EMBL; AL606537; CAI15309.1; ALT_SEQ; Genomic_DNA. DR EMBL; AC011700; CAI15309.1; JOINED; Genomic_DNA. DR EMBL; CH471100; EAW93360.1; -; Genomic_DNA. DR EMBL; BC024201; AAH24201.1; -; mRNA. DR CCDS; CCDS31021.1; -. DR RefSeq; NP_001257545.1; NM_001270616.1. DR RefSeq; NP_002754.2; NM_002763.4. DR RefSeq; XP_011508076.1; XM_011509774.1. DR UniGene; Hs.741808; -. DR UniGene; Hs.744931; -. DR PDB; 2LMD; NMR; -; A=575-737. DR PDBsum; 2LMD; -. DR ProteinModelPortal; Q92786; -. DR SMR; Q92786; 575-737. DR BioGrid; 111613; 16. DR IntAct; Q92786; 10. DR MINT; MINT-2813285; -. DR STRING; 9606.ENSP00000261454; -. DR PhosphoSite; Q92786; -. DR DMDM; 85702224; -. DR MaxQB; Q92786; -. DR PaxDb; Q92786; -. DR PRIDE; Q92786; -. DR DNASU; 5629; -. DR Ensembl; ENST00000261454; ENSP00000261454; ENSG00000117707. DR Ensembl; ENST00000366958; ENSP00000355925; ENSG00000117707. DR Ensembl; ENST00000435016; ENSP00000400694; ENSG00000117707. DR Ensembl; ENST00000498508; ENSP00000420283; ENSG00000117707. DR GeneID; 5629; -. DR KEGG; hsa:5629; -. DR UCSC; uc001hkg.2; human. DR CTD; 5629; -. DR GeneCards; PROX1; -. DR HGNC; HGNC:9459; PROX1. DR MIM; 601546; gene. DR neXtProt; NX_Q92786; -. DR PharmGKB; PA33812; -. DR eggNOG; KOG3779; Eukaryota. DR eggNOG; ENOG410ZE21; LUCA. DR GeneTree; ENSGT00530000063507; -. DR HOGENOM; HOG000115708; -. DR HOVERGEN; HBG053693; -. DR InParanoid; Q92786; -. DR OMA; GNVQMPS; -. DR OrthoDB; EOG7MSMNK; -. DR PhylomeDB; Q92786; -. DR TreeFam; TF316638; -. DR ChiTaRS; PROX1; human. DR GeneWiki; PROX1; -. DR GenomeRNAi; 5629; -. DR NextBio; 21878; -. DR PRO; PR:Q92786; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; Q92786; -. DR CleanEx; HS_PROX1; -. DR ExpressionAtlas; Q92786; baseline and differential. DR Genevisible; Q92786; HS. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; ISS:UniProtKB. DR GO; GO:0050692; F:DBD domain binding; IPI:BHF-UCL. DR GO; GO:0003677; F:DNA binding; IMP:BHF-UCL. DR GO; GO:0050693; F:LBD domain binding; IPI:BHF-UCL. DR GO; GO:0016922; F:ligand-dependent nuclear receptor binding; IPI:BHF-UCL. DR GO; GO:0003714; F:transcription corepressor activity; IDA:BHF-UCL. DR GO; GO:0003705; F:transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; ISS:BHF-UCL. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IC:BHF-UCL. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IBA:GO_Central. DR GO; GO:0090425; P:acinar cell differentiation; IEA:Ensembl. DR GO; GO:0060414; P:aorta smooth muscle tissue morphogenesis; ISS:BHF-UCL. DR GO; GO:0055009; P:atrial cardiac muscle tissue morphogenesis; ISS:BHF-UCL. DR GO; GO:0007420; P:brain development; IEP:BHF-UCL. DR GO; GO:0061114; P:branching involved in pancreas morphogenesis; IEA:Ensembl. DR GO; GO:0055007; P:cardiac muscle cell differentiation; IBA:GO_Central. DR GO; GO:0001709; P:cell fate determination; IEA:Ensembl. DR GO; GO:0021707; P:cerebellar granule cell differentiation; ISS:BHF-UCL. DR GO; GO:0007623; P:circadian rhythm; IEA:Ensembl. DR GO; GO:0021542; P:dentate gyrus development; ISS:BHF-UCL. DR GO; GO:0021516; P:dorsal spinal cord development; ISS:BHF-UCL. DR GO; GO:0060059; P:embryonic retina morphogenesis in camera-type eye; IEP:BHF-UCL. DR GO; GO:0060214; P:endocardium formation; ISS:BHF-UCL. DR GO; GO:0002194; P:hepatocyte cell migration; IEA:Ensembl. DR GO; GO:0070365; P:hepatocyte differentiation; IEP:BHF-UCL. DR GO; GO:0072574; P:hepatocyte proliferation; IEA:Ensembl. DR GO; GO:0001822; P:kidney development; IEP:BHF-UCL. DR GO; GO:0002088; P:lens development in camera-type eye; IEP:BHF-UCL. DR GO; GO:0070309; P:lens fiber cell morphogenesis; IEP:BHF-UCL. DR GO; GO:0001889; P:liver development; IEP:BHF-UCL. DR GO; GO:0030324; P:lung development; IEP:BHF-UCL. DR GO; GO:0001946; P:lymphangiogenesis; IDA:BHF-UCL. DR GO; GO:0060836; P:lymphatic endothelial cell differentiation; IDA:BHF-UCL. DR GO; GO:0070858; P:negative regulation of bile acid biosynthetic process; IMP:BHF-UCL. DR GO; GO:0008285; P:negative regulation of cell proliferation; IMP:BHF-UCL. DR GO; GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB. DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:BHF-UCL. DR GO; GO:0021915; P:neural tube development; ISS:BHF-UCL. DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central. DR GO; GO:0097150; P:neuronal stem cell population maintenance; ISS:BHF-UCL. DR GO; GO:0030910; P:olfactory placode formation; ISS:BHF-UCL. DR GO; GO:0046619; P:optic placode formation involved in camera-type eye formation; ISS:BHF-UCL. DR GO; GO:0043049; P:otic placode formation; ISS:BHF-UCL. DR GO; GO:0031016; P:pancreas development; IEP:BHF-UCL. DR GO; GO:0045787; P:positive regulation of cell cycle; ISS:BHF-UCL. DR GO; GO:1901978; P:positive regulation of cell cycle checkpoint; IEA:Ensembl. DR GO; GO:0008284; P:positive regulation of cell proliferation; IDA:BHF-UCL. DR GO; GO:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:BHF-UCL. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:BHF-UCL. DR GO; GO:2000979; P:positive regulation of forebrain neuron differentiation; ISS:BHF-UCL. DR GO; GO:0060421; P:positive regulation of heart growth; ISS:BHF-UCL. DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; ISS:BHF-UCL. DR GO; GO:0060298; P:positive regulation of sarcomere organization; ISS:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IBA:GO_Central. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:BHF-UCL. DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB. DR GO; GO:0010468; P:regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0060849; P:regulation of transcription involved in lymphatic endothelial cell fate commitment; IMP:BHF-UCL. DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl. DR GO; GO:0060042; P:retina morphogenesis in camera-type eye; ISS:BHF-UCL. DR GO; GO:0030240; P:skeletal muscle thin filament assembly; ISS:BHF-UCL. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0048845; P:venous blood vessel morphogenesis; ISS:BHF-UCL. DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISS:BHF-UCL. DR GO; GO:0055005; P:ventricular cardiac myofibril assembly; ISS:BHF-UCL. DR GO; GO:0060412; P:ventricular septum morphogenesis; ISS:BHF-UCL. DR Gene3D; 1.10.10.500; -; 1. DR InterPro; IPR023082; Homeo_prospero_dom. DR InterPro; IPR009057; Homeodomain-like. DR Pfam; PF05044; HPD; 1. DR SUPFAM; SSF46689; SSF46689; 1. PE 1: Evidence at protein level; KW 3D-structure; Biological rhythms; Complete proteome; KW Developmental protein; DNA-binding; Homeobox; Nucleus; Phosphoprotein; KW Polymorphism; Reference proteome; Repressor; Transcription; KW Transcription regulation. FT CHAIN 1 737 Prospero homeobox protein 1. FT /FTId=PRO_0000208880. FT DNA_BIND 573 635 Prospero-type homeobox. FT REGION 1 28 Interaction with RORG. FT {ECO:0000250|UniProtKB:P48437}. FT REGION 636 737 Prospero-like. FT REGION 723 729 Essential for nuclear localization, FT interaction with RORG, repression of RORG FT transcriptional activator activity. FT {ECO:0000250|UniProtKB:P48437}. FT COMPBIAS 215 219 Poly-Gln. FT MOD_RES 177 177 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 179 179 Phosphoserine. FT {ECO:0000250|UniProtKB:P48437}. FT MOD_RES 199 199 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 291 291 Phosphoserine. FT {ECO:0000250|UniProtKB:P48437}. FT MOD_RES 295 295 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 511 511 Phosphoserine. FT {ECO:0000250|UniProtKB:P48437}. FT MOD_RES 514 514 Phosphoserine. FT {ECO:0000250|UniProtKB:P48437}. FT MOD_RES 557 557 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT VARIANT 584 584 H -> R (in dbSNP:rs12121210). FT /FTId=VAR_049362. FT CONFLICT 251 253 RQL -> LHV (in Ref. 1; AAC50656). FT {ECO:0000305}. FT CONFLICT 455 457 PAA -> LV (in Ref. 1; AAC50656). FT {ECO:0000305}. FT CONFLICT 724 724 I -> F (in Ref. 1; AAC50656). FT {ECO:0000305}. FT HELIX 582 592 {ECO:0000244|PDB:2LMD}. FT HELIX 599 606 {ECO:0000244|PDB:2LMD}. FT HELIX 614 645 {ECO:0000244|PDB:2LMD}. FT HELIX 650 652 {ECO:0000244|PDB:2LMD}. FT STRAND 653 656 {ECO:0000244|PDB:2LMD}. FT HELIX 660 669 {ECO:0000244|PDB:2LMD}. FT HELIX 679 698 {ECO:0000244|PDB:2LMD}. FT HELIX 705 715 {ECO:0000244|PDB:2LMD}. FT HELIX 728 730 {ECO:0000244|PDB:2LMD}. FT HELIX 732 734 {ECO:0000244|PDB:2LMD}. SQ SEQUENCE 737 AA; 83203 MW; D243CEB421B313CA CRC64; MPDHDSTALL SRQTKRRRVD IGVKRTVGTA SAFFAKARAT FFSAMNPQGS EQDVEYSVVQ HADGEKSNVL RKLLKRANSY EDAMMPFPGA TIISQLLKNN MNKNGGTEPS FQASGLSSTG SEVHQEDICS NSSRDSPPEC LSPFGRPTMS QFDMDRLCDE HLRAKRARVE NIIRGMSHSP SVALRGNENE REMAPQSVSP RESYRENKRK QKLPQQQQQS FQQLVSARKE QKREERRQLK QQLEDMQKQL RQLQEKFYQI YDSTDSENDE DGNLSEDSMR SEILDARAQD SVGRSDNEMC ELDPGQFIDR ARALIREQEM AENKPKREGN NKERDHGPNS LQPEGKHLAE TLKQELNTAM SQVVDTVVKV FSAKPSRQVP QVFPPLQIPQ ARFAVNGENH NFHTANQRLQ CFGDVIIPNP LDTFGNVQMA SSTDQTEALP LVVRKNSSDQ SASGPAAGGH HQPLHQSPLS ATTGFTTSTF RHPFPLPLMA YPFQSPLGAP SGSFSGKDRA SPESLDLTRD TTSLRTKMSS HHLSHHPCSP AHPPSTAEGL SLSLIKSECG DLQDMSEISP YSGSAMQEGL SPNHLKKAKL MFFYTRYPSS NMLKTYFSDV KFNRCITSQL IKWFSNFREF YYIQMEKYAR QAINDGVTST EELSITRDCE LYRALNMHYN KANDFEVPER FLEVAQITLR EFFNAIIAGK DVDPSWKKAI YKVICKLDSE VPEIFKSPNC LQELLHE // ID PYRG2_HUMAN Reviewed; 586 AA. AC Q9NRF8; B3KWM2; Q9BRI0; Q9H809; Q9H8K9; DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 11-NOV-2015, entry version 129. DE RecName: Full=CTP synthase 2; DE EC=6.3.4.2; DE AltName: Full=CTP synthetase 2; DE AltName: Full=UTP--ammonia ligase 2; GN Name=CTPS2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RX PubMed=10899599; DOI=10.1016/S0167-4781(00)00141-X; RA van Kuilenburg A.B.P., Meinsma R., Vreken P., Waterham H.R., RA van Gennip A.H.; RT "Identification of a cDNA encoding an isoform of human CTP RT synthetase."; RL Biochim. Biophys. Acta 1492:548-552(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta, and Retinoblastoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP FUNCTION. RX PubMed=16179339; DOI=10.1074/jbc.M509622200; RA Han G.-S., Sreenivas A., Choi M.-G., Chang Y.-F., Martin S.S., RA Baldwin E.P., Carman G.M.; RT "Expression of human CTP synthetase in Saccharomyces cerevisiae RT reveals phosphorylation by protein kinase A."; RL J. Biol. Chem. 280:38328-38336(2005). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-571, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568; SER-571 AND RP SER-574, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568; SER-571 AND RP SER-574, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568 AND SER-571, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-568; SER-571 AND RP SER-574, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). CC -!- FUNCTION: Catalyzes the ATP-dependent amination of UTP to CTP with CC either L-glutamine or ammonia as the source of nitrogen. CC Constitutes the rate-limiting enzyme in the synthesis of cytosine CC nucleotides. {ECO:0000269|PubMed:10899599, CC ECO:0000269|PubMed:16179339}. CC -!- CATALYTIC ACTIVITY: ATP + UTP + L-glutamine = ADP + phosphate + CC CTP + L-glutamate. CC -!- PATHWAY: Pyrimidine metabolism; CTP biosynthesis via de novo CC pathway; CTP from UDP: step 2/2. CC -!- INTERACTION: CC Q9NZD8:SPG21; NbExp=4; IntAct=EBI-740874, EBI-742688; CC -!- SIMILARITY: Belongs to the CTP synthase family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 glutamine amidotransferase type-1 domain. CC {ECO:0000255|PROSITE-ProRule:PRU00605}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF226667; AAF91241.1; -; mRNA. DR EMBL; AK023549; BAB14607.1; -; mRNA. DR EMBL; AK024070; BAB14814.1; -; mRNA. DR EMBL; AK125332; BAG54184.1; -; mRNA. DR EMBL; AK125348; BAG54188.1; -; mRNA. DR EMBL; AL445467; CAI40086.1; -; Genomic_DNA. DR EMBL; AC073909; CAI40086.1; JOINED; Genomic_DNA. DR EMBL; CH471074; EAW98912.1; -; Genomic_DNA. DR EMBL; BC006256; AAH06256.2; -; mRNA. DR EMBL; BC034986; AAH34986.1; -; mRNA. DR CCDS; CCDS14175.1; -. DR RefSeq; NP_001137474.1; NM_001144002.1. DR RefSeq; NP_062831.3; NM_019857.4. DR RefSeq; NP_787055.1; NM_175859.2. DR RefSeq; XP_005274619.1; XM_005274562.2. DR RefSeq; XP_006724566.1; XM_006724503.2. DR RefSeq; XP_011543848.1; XM_011545546.1. DR UniGene; Hs.227049; -. DR PDB; 2V4U; X-ray; 2.30 A; A=297-562. DR PDB; 2VKT; X-ray; 2.50 A; A=297-562. DR PDB; 3IHL; X-ray; 2.80 A; A/B=1-275. DR PDBsum; 2V4U; -. DR PDBsum; 2VKT; -. DR PDBsum; 3IHL; -. DR ProteinModelPortal; Q9NRF8; -. DR SMR; Q9NRF8; 1-273, 297-562. DR BioGrid; 121144; 27. DR IntAct; Q9NRF8; 6. DR MINT; MINT-1443035; -. DR STRING; 9606.ENSP00000352222; -. DR MEROPS; C26.964; -. DR PhosphoSite; Q9NRF8; -. DR BioMuta; CTPS2; -. DR DMDM; 74752919; -. DR MaxQB; Q9NRF8; -. DR PaxDb; Q9NRF8; -. DR PRIDE; Q9NRF8; -. DR DNASU; 56474; -. DR Ensembl; ENST00000359276; ENSP00000352222; ENSG00000047230. DR Ensembl; ENST00000380241; ENSP00000369590; ENSG00000047230. DR Ensembl; ENST00000443824; ENSP00000401264; ENSG00000047230. DR GeneID; 56474; -. DR KEGG; hsa:56474; -. DR UCSC; uc004cxk.3; human. DR CTD; 56474; -. DR GeneCards; CTPS2; -. DR HGNC; HGNC:2520; CTPS2. DR HPA; HPA017437; -. DR MIM; 300380; gene. DR neXtProt; NX_Q9NRF8; -. DR PharmGKB; PA27021; -. DR eggNOG; KOG2387; Eukaryota. DR eggNOG; COG0504; LUCA. DR GeneTree; ENSGT00390000012473; -. DR HOGENOM; HOG000077514; -. DR HOVERGEN; HBG002243; -. DR InParanoid; Q9NRF8; -. DR KO; K01937; -. DR OMA; YASIFES; -. DR OrthoDB; EOG7M3HZZ; -. DR PhylomeDB; Q9NRF8; -. DR TreeFam; TF300379; -. DR BioCyc; MetaCyc:HS00585-MONOMER; -. DR BRENDA; 6.3.4.2; 2681. DR Reactome; R-HSA-499943; Synthesis and interconversion of nucleotide di- and triphosphates. DR UniPathway; UPA00159; UER00277. DR ChiTaRS; CTPS2; human. DR EvolutionaryTrace; Q9NRF8; -. DR GeneWiki; CTPS2; -. DR GenomeRNAi; 56474; -. DR NextBio; 62001; -. DR PRO; PR:Q9NRF8; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; Q9NRF8; -. DR CleanEx; HS_CTPS2; -. DR ExpressionAtlas; Q9NRF8; baseline and differential. DR Genevisible; Q9NRF8; HS. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003883; F:CTP synthase activity; EXP:Reactome. DR GO; GO:0044210; P:'de novo' CTP biosynthetic process; IEA:UniProtKB-UniPathway. DR GO; GO:0006541; P:glutamine metabolic process; IEA:UniProtKB-KW. DR GO; GO:0015949; P:nucleobase-containing small molecule interconversion; TAS:Reactome. DR GO; GO:0055086; P:nucleobase-containing small molecule metabolic process; TAS:Reactome. DR GO; GO:0006220; P:pyrimidine nucleotide metabolic process; TAS:ProtInc. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR Gene3D; 3.40.50.300; -; 1. DR Gene3D; 3.40.50.880; -; 1. DR InterPro; IPR029062; Class_I_gatase-like. DR InterPro; IPR004468; CTP_synthase. DR InterPro; IPR017456; CTP_synthase_N. DR InterPro; IPR017926; GATASE. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR11550; PTHR11550; 1. DR Pfam; PF06418; CTP_synth_N; 1. DR Pfam; PF00117; GATase; 1. DR SUPFAM; SSF52317; SSF52317; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR TIGRFAMs; TIGR00337; PyrG; 1. DR PROSITE; PS51273; GATASE_TYPE_1; 1. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Complete proteome; KW Glutamine amidotransferase; Ligase; Nucleotide-binding; KW Phosphoprotein; Pyrimidine biosynthesis; Reference proteome. FT CHAIN 1 586 CTP synthase 2. FT /FTId=PRO_0000247033. FT DOMAIN 300 554 Glutamine amidotransferase type-1. FT {ECO:0000255|PROSITE-ProRule:PRU00605}. FT ACT_SITE 399 399 For GATase activity. FT {ECO:0000255|PROSITE-ProRule:PRU00605}. FT ACT_SITE 526 526 For GATase activity. FT {ECO:0000255|PROSITE-ProRule:PRU00605}. FT ACT_SITE 528 528 For GATase activity. FT {ECO:0000255|PROSITE-ProRule:PRU00605}. FT MOD_RES 568 568 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 571 571 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 574 574 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:24275569}. FT CONFLICT 220 220 T -> S (in Ref. 2; BAB14814). FT {ECO:0000305}. FT CONFLICT 233 233 F -> L (in Ref. 2; BAB14607). FT {ECO:0000305}. FT CONFLICT 304 304 V -> A (in Ref. 2; BAB14607). FT {ECO:0000305}. FT STRAND 2 8 {ECO:0000244|PDB:3IHL}. FT STRAND 10 15 {ECO:0000244|PDB:3IHL}. FT HELIX 16 28 {ECO:0000244|PDB:3IHL}. FT TURN 29 31 {ECO:0000244|PDB:3IHL}. FT STRAND 34 40 {ECO:0000244|PDB:3IHL}. FT STRAND 48 50 {ECO:0000244|PDB:3IHL}. FT STRAND 58 60 {ECO:0000244|PDB:3IHL}. FT STRAND 87 89 {ECO:0000244|PDB:3IHL}. FT HELIX 90 102 {ECO:0000244|PDB:3IHL}. FT TURN 103 108 {ECO:0000244|PDB:3IHL}. FT HELIX 113 129 {ECO:0000244|PDB:3IHL}. FT STRAND 141 147 {ECO:0000244|PDB:3IHL}. FT HELIX 154 156 {ECO:0000244|PDB:3IHL}. FT HELIX 157 169 {ECO:0000244|PDB:3IHL}. FT HELIX 172 174 {ECO:0000244|PDB:3IHL}. FT STRAND 175 182 {ECO:0000244|PDB:3IHL}. FT TURN 187 189 {ECO:0000244|PDB:3IHL}. FT HELIX 195 206 {ECO:0000244|PDB:3IHL}. FT STRAND 212 220 {ECO:0000244|PDB:3IHL}. FT HELIX 224 233 {ECO:0000244|PDB:3IHL}. FT HELIX 238 240 {ECO:0000244|PDB:3IHL}. FT STRAND 241 245 {ECO:0000244|PDB:3IHL}. FT HELIX 252 259 {ECO:0000244|PDB:3IHL}. FT HELIX 262 270 {ECO:0000244|PDB:3IHL}. FT STRAND 297 306 {ECO:0000244|PDB:2V4U}. FT HELIX 312 314 {ECO:0000244|PDB:2V4U}. FT HELIX 315 327 {ECO:0000244|PDB:2V4U}. FT STRAND 330 338 {ECO:0000244|PDB:2V4U}. FT HELIX 339 342 {ECO:0000244|PDB:2V4U}. FT HELIX 344 349 {ECO:0000244|PDB:2V4U}. FT HELIX 351 363 {ECO:0000244|PDB:2V4U}. FT STRAND 365 369 {ECO:0000244|PDB:2V4U}. FT HELIX 378 390 {ECO:0000244|PDB:2V4U}. FT STRAND 395 398 {ECO:0000244|PDB:2V4U}. FT HELIX 400 413 {ECO:0000244|PDB:2V4U}. FT STRAND 419 422 {ECO:0000244|PDB:2V4U}. FT STRAND 429 435 {ECO:0000244|PDB:2V4U}. FT STRAND 449 458 {ECO:0000244|PDB:2V4U}. FT HELIX 463 467 {ECO:0000244|PDB:2V4U}. FT STRAND 472 480 {ECO:0000244|PDB:2V4U}. FT STRAND 482 484 {ECO:0000244|PDB:2V4U}. FT HELIX 486 488 {ECO:0000244|PDB:2V4U}. FT HELIX 490 492 {ECO:0000244|PDB:2V4U}. FT STRAND 495 503 {ECO:0000244|PDB:2V4U}. FT STRAND 508 518 {ECO:0000244|PDB:2V4U}. FT STRAND 520 526 {ECO:0000244|PDB:2V4U}. FT HELIX 527 530 {ECO:0000244|PDB:2V4U}. FT HELIX 538 548 {ECO:0000244|PDB:2V4U}. FT HELIX 551 556 {ECO:0000244|PDB:2V4U}. SQ SEQUENCE 586 AA; 65678 MW; AC1CF2E67D89741B CRC64; MKYILVTGGV ISGIGKGIIA SSIGTILKSC GLRVTAIKID PYINIDAGTF SPYEHGEVFV LNDGGEVDLD LGNYERFLDI NLYKDNNITT GKIYQHVINK ERRGDYLGKT VQVVPHITDA VQEWVMNQAK VPVDGNKEEP QICVIELGGT IGDIEGMPFV EAFRQFQFKA KRENFCNIHV SLVPQLSATG EQKTKPTQNS VRALRGLGLS PDLIVCRSST PIEMAVKEKI SMFCHVNPEQ VICIHDVSST YRVPVLLEEQ SIVKYFKERL HLPIGDSASN LLFKWRNMAD RYERLQKICS IALVGKYTKL RDCYASVFKA LEHSALAINH KLNLMYIDSI DLEKITETED PVKFHEAWQK LCKADGILVP GGFGIRGTLG KLQAISWART KKIPFLGVCL GMQLAVIEFA RNCLNLKDAD STEFRPNAPV PLVIDMPEHN PGNLGGTMRL GIRRTVFKTE NSILRKLYGD VPFIEERHRH RFEVNPNLIK QFEQNDLSFV GQDVDGDRME IIELANHPYF VGVQFHPEFS SRPMKPSPPY LGLLLAATGN LNAYLQQGCK LSSSDRYSDA SDDSFSEPRI AELEIS // ID RAI2_HUMAN Reviewed; 530 AA. AC Q9Y5P3; B1B1K2; B4DQM9; E7EMN4; Q8N6X7; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 02-SEP-2008, sequence version 2. DT 11-NOV-2015, entry version 103. DE RecName: Full=Retinoic acid-induced protein 2; GN Name=RAI2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-252. RX PubMed=10049581; DOI=10.1006/geno.1998.5667; RA Walpole S.M., Hiriyana K.T., Nicolaou A., Bingham E.L., Durham J., RA Vaudin M., Ross M.T., Yates J.R.W., Sieving P.A., Trump D.; RT "Identification and characterization of the human homologue (RAI2) of RT a mouse retinoic acid-induced gene in Xp22."; RL Genomics 55:275-283(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT RP VAL-252. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS RP VAL-252 AND PRO-342. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). CC -!- INTERACTION: CC P56545:CTBP2; NbExp=4; IntAct=EBI-746228, EBI-741533; CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-746228, EBI-10171902; CC Q14192:FHL2; NbExp=3; IntAct=EBI-746228, EBI-701903; CC Q96EQ0:SGTB; NbExp=4; IntAct=EBI-746228, EBI-744081; CC Q9NRR5:UBQLN4; NbExp=3; IntAct=EBI-746228, EBI-711226; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9Y5P3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y5P3-2; Sequence=VSP_047524; CC Note=No experimental confirmation available.; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF136587; AAD33688.1; -; Genomic_DNA. DR EMBL; AK298873; BAG60991.1; -; mRNA. DR EMBL; Z93242; CAI42725.1; -; Genomic_DNA. DR EMBL; BC027937; AAH27937.1; -; mRNA. DR CCDS; CCDS14183.1; -. [Q9Y5P3-1] DR CCDS; CCDS55374.1; -. [Q9Y5P3-2] DR RefSeq; NP_001166203.1; NM_001172732.1. DR RefSeq; NP_001166210.1; NM_001172739.1. DR RefSeq; NP_001166214.1; NM_001172743.1. DR RefSeq; NP_068557.3; NM_021785.4. DR RefSeq; XP_006724522.1; XM_006724459.2. [Q9Y5P3-1] DR RefSeq; XP_006724523.1; XM_006724460.1. [Q9Y5P3-1] DR RefSeq; XP_011543741.1; XM_011545439.1. [Q9Y5P3-1] DR RefSeq; XP_011543742.1; XM_011545440.1. [Q9Y5P3-1] DR RefSeq; XP_011543743.1; XM_011545441.1. [Q9Y5P3-1] DR UniGene; Hs.446680; -. DR ProteinModelPortal; Q9Y5P3; -. DR BioGrid; 115965; 7. DR IntAct; Q9Y5P3; 12. DR MINT; MINT-1447745; -. DR STRING; 9606.ENSP00000333456; -. DR PhosphoSite; Q9Y5P3; -. DR BioMuta; RAI2; -. DR DMDM; 205371817; -. DR PaxDb; Q9Y5P3; -. DR PRIDE; Q9Y5P3; -. DR DNASU; 10742; -. DR Ensembl; ENST00000331511; ENSP00000333456; ENSG00000131831. [Q9Y5P3-1] DR Ensembl; ENST00000360011; ENSP00000353106; ENSG00000131831. [Q9Y5P3-1] DR Ensembl; ENST00000415486; ENSP00000392578; ENSG00000131831. [Q9Y5P3-2] DR Ensembl; ENST00000451717; ENSP00000401323; ENSG00000131831. [Q9Y5P3-1] DR Ensembl; ENST00000545871; ENSP00000444210; ENSG00000131831. [Q9Y5P3-1] DR GeneID; 10742; -. DR KEGG; hsa:10742; -. DR UCSC; uc004cyf.3; human. [Q9Y5P3-1] DR CTD; 10742; -. DR GeneCards; RAI2; -. DR HGNC; HGNC:9835; RAI2. DR HPA; HPA051054; -. DR MIM; 300217; gene. DR neXtProt; NX_Q9Y5P3; -. DR PharmGKB; PA34193; -. DR eggNOG; ENOG410IE37; Eukaryota. DR eggNOG; ENOG4110FZK; LUCA. DR GeneTree; ENSGT00730000111296; -. DR HOGENOM; HOG000133031; -. DR HOVERGEN; HBG017703; -. DR InParanoid; Q9Y5P3; -. DR OMA; KSVPWLK; -. DR OrthoDB; EOG7DZ8JT; -. DR PhylomeDB; Q9Y5P3; -. DR TreeFam; TF331261; -. DR GeneWiki; RAI2; -. DR GenomeRNAi; 10742; -. DR NextBio; 35499484; -. DR PRO; PR:Q9Y5P3; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; Q9Y5P3; -. DR CleanEx; HS_RAI2; -. DR ExpressionAtlas; Q9Y5P3; baseline and differential. DR Genevisible; Q9Y5P3; HS. DR GO; GO:0009790; P:embryo development; NAS:UniProtKB. DR InterPro; IPR026092; RAI2/SOBP. DR PANTHER; PTHR23186; PTHR23186; 1. DR Pfam; PF15279; SOBP; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Polymorphism; KW Reference proteome. FT CHAIN 1 530 Retinoic acid-induced protein 2. FT /FTId=PRO_0000097161. FT COMPBIAS 200 253 Pro-rich. FT VAR_SEQ 46 95 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_047524. FT VARIANT 252 252 M -> V (in dbSNP:rs6527818). FT {ECO:0000269|PubMed:10049581, FT ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334}. FT /FTId=VAR_046100. FT VARIANT 342 342 A -> P (in dbSNP:rs17855524). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_046101. SQ SEQUENCE 530 AA; 57180 MW; F5BEE12367961C9A CRC64; MDDLQSQNLS MDMTDSPPAL ANNRLENGMA QLITTEAWNI NSTDLVKKAL VTVPAPSILN PPAESQSGMA LKVAATVLQP LCLGESPVVM PIHMQVEGSS APELNPNGNA TYVMTTQGPV QLPVVLEQHV FQHLNSPLVL PQEAPCSSST IHNNLFQGAE DPEAQPQLLD LRIPSQPQEP TLPFEAVLQN LFPSQGTLGP PPCQPPPGYA PVPPQPFSSP LSPLVPPATL LVPYPVIVPL PVPVPIPIPI PMPQSSESKF SSSFPKPPSS FGLHPFKGTQ TPLEKDELKP FDILQPKEYF QLSRHTVIKM GSENEALDLS MKSVPWLKAG EVSPPIFQED AALDLSVAAH RKSEPPPETL YDSGASVDSS GHTVMEKLPS GMEISFAPAT SHEAPAMMDS HISSSDAATE MLSQPNHPSG EVKAENNIEM VGESQAAKVI VSVEDAVPTI FCGKIKGLSG VSTKNFSFKR EDSVLQGYDI NSQGEESMGN AEPLRKPIKN RSIKLKKVNS QEIHMLPIKK QRLATFFPRK // ID RBBP5_HUMAN Reviewed; 538 AA. AC Q15291; A8K272; Q7Z6D8; Q8NDZ7; DT 18-OCT-2001, integrated into UniProtKB/Swiss-Prot. DT 14-OCT-2008, sequence version 2. DT 11-NOV-2015, entry version 147. DE RecName: Full=Retinoblastoma-binding protein 5; DE Short=RBBP-5; DE AltName: Full=Retinoblastoma-binding protein RBQ-3; GN Name=RBBP5; Synonyms=RBQ3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION AT THR-252 AND RP SER-497, AND CHARACTERIZATION. RC TISSUE=Lung carcinoma, and Testis; RX PubMed=7558034; DOI=10.1006/geno.1995.1084; RA Saijo M., Sakai Y., Kishino T., Niikawa N., Matsuura Y., Morino K., RA Tamai K., Taya Y.; RT "Molecular cloning of a human protein that binds to the retinoblastoma RT protein and chromosomal mapping."; RL Genomics 27:511-519(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Thalamus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Brain, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP IDENTIFICATION IN THE MEN1-ASSOCIATED HISTONE METHYLTRANSFERASE RP COMPLEX. RX PubMed=14992727; DOI=10.1016/S1097-2765(04)00081-4; RA Hughes C.M., Rozenblatt-Rosen O., Milne T.A., Copeland T.D., RA Levine S.S., Lee J.C., Hayes D.N., Shanmugam K.S., Bhattacharjee A., RA Biondi C.A., Kay G.F., Hayward N.K., Hess J.L., Meyerson M.; RT "Menin associates with a trithorax family histone methyltransferase RT complex and with the hoxc8 locus."; RL Mol. Cell 13:587-597(2004). RN [7] RP IDENTIFICATION IN THE MLL-LIKE COMPLEX. RX PubMed=15199122; DOI=10.1128/MCB.24.13.5639-5649.2004; RA Yokoyama A., Wang Z., Wysocka J., Sanyal M., Aufiero D.J., RA Kitabayashi I., Herr W., Cleary M.L.; RT "Leukemia proto-oncoprotein MLL forms a SET1-like histone RT methyltransferase complex with menin to regulate Hox gene RT expression."; RL Mol. Cell. Biol. 24:5639-5649(2004). RN [8] RP IDENTIFICATION IN THE MLL1/MLL COMPLEX. RX PubMed=15960975; DOI=10.1016/j.cell.2005.04.031; RA Dou Y., Milne T.A., Tackett A.J., Smith E.R., Fukuda A., Wysocka J., RA Allis C.D., Chait B.T., Hess J.L., Roeder R.G.; RT "Physical association and coordinate function of the H3 K4 RT methyltransferase MLL1 and the H4 K16 acetyltransferase MOF."; RL Cell 121:873-885(2005). RN [9] RP IDENTIFICATION IN THE SET1 COMPLEX. RX PubMed=16253997; DOI=10.1074/jbc.M508312200; RA Lee J.-H., Skalnik D.G.; RT "CpG-binding protein (CXXC finger protein 1) is a component of the RT mammalian Set1 histone H3-Lys4 methyltransferase complex, the analogue RT of the yeast Set1/COMPASS complex."; RL J. Biol. Chem. 280:41725-41731(2005). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [11] RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE SET1 COMPLEX. RX PubMed=17355966; DOI=10.1074/jbc.M609809200; RA Lee J.-H., Tate C.M., You J.-S., Skalnik D.G.; RT "Identification and characterization of the human Set1B histone H3- RT Lys4 methyltransferase complex."; RL J. Biol. Chem. 282:13419-13428(2007). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MLL2/3 RP COMPLEX. RX PubMed=17500065; DOI=10.1074/jbc.M701574200; RA Cho Y.-W., Hong T., Hong S., Guo H., Yu H., Kim D., Guszczynski T., RA Dressler G.R., Copeland T.D., Kalkum M., Ge K.; RT "PTIP associates with MLL3- and MLL4-containing histone H3 lysine 4 RT methyltransferase complex."; RL J. Biol. Chem. 282:20395-20406(2007). RN [13] RP IDENTIFICATION IN SET1 COMPLEX, AND INTERACTION WITH SETD1A. RX PubMed=17998332; DOI=10.1128/MCB.01356-07; RA Lee J.H., Skalnik D.G.; RT "Wdr82 is a C-terminal domain-binding protein that recruits the Setd1A RT Histone H3-Lys4 methyltransferase complex to transcription start sites RT of transcribed human genes."; RL Mol. Cell. Biol. 28:609-618(2008). RN [14] RP IDENTIFICATION IN SET1 COMPLEX, AND INTERACTION WITH WDR82. RX PubMed=18838538; DOI=10.1128/MCB.00976-08; RA Wu M., Wang P.F., Lee J.S., Martin-Brown S., Florens L., Washburn M., RA Shilatifard A.; RT "Molecular regulation of H3K4 trimethylation by Wdr82, a component of RT human Set1/COMPASS."; RL Mol. Cell. Biol. 28:7337-7344(2008). RN [15] RP IDENTIFICATION IN A COMPLEX WITH HCFC1; MKI67; C11ORF30; MATR3; HSPA8; RP ZNF335; CCAR2; ASCL2; ZNF335 AND WDR5. RX PubMed=19131338; DOI=10.1074/jbc.M805872200; RA Garapaty S., Xu C.F., Trojer P., Mahajan M.A., Neubert T.A., RA Samuels H.H.; RT "Identification and characterization of a novel nuclear protein RT complex involved in nuclear hormone receptor-mediated gene RT regulation."; RL J. Biol. Chem. 284:7542-7552(2009). RN [16] RP FUNCTION, CHARACTERIZATION OF THE MLL1/MLL COMPLEX, AND INTERACTION RP WITH WDR5 AND ASH2L. RX PubMed=19556245; DOI=10.1074/jbc.M109.014498; RA Patel A., Dharmarajan V., Vought V.E., Cosgrove M.S.; RT "On the mechanism of multiple lysine methylation by the human mixed RT lineage leukemia protein-1 (MLL1) core complex."; RL J. Biol. Chem. 284:24242-24256(2009). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-388 AND SER-389, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-525, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [20] RP INTERACTION WITH ZNF335. RX PubMed=23178126; DOI=10.1016/j.cell.2012.10.043; RA Yang Y.J., Baltus A.E., Mathew R.S., Murphy E.A., Evrony G.D., RA Gonzalez D.M., Wang E.P., Marshall-Walker C.A., Barry B.J., Murn J., RA Tatarakis A., Mahajan M.A., Samuels H.H., Shi Y., Golden J.A., RA Mahajnah M., Shenhav R., Walsh C.A.; RT "Microcephaly gene links trithorax and REST/NRSF to control neural RT stem cell proliferation and differentiation."; RL Cell 151:1097-1112(2012). CC -!- FUNCTION: In embryonic stem (ES) cells, plays a crucial role in CC the differentiation potential, particularly along the neural CC lineage, regulating gene induction and H3 'Lys-4' methylation at CC key developmental loci, including that mediated by retinoic acid CC (By similarity). As part of the MLL1/MLL complex, involved in CC mono-, di- and trimethylation at 'Lys-4' of histone H3. Histone H3 CC 'Lys-4' methylation represents a specific tag for epigenetic CC transcriptional activation. {ECO:0000250, CC ECO:0000269|PubMed:19556245}. CC -!- SUBUNIT: Component of the SET1 complex, at least composed of the CC catalytic subunit (SETD1A or SETD1B), WDR5, WDR82, RBBP5, CC ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30. Core component of several CC methyltransferase-containing complexes including MLL1/MLL, MLL2/3 CC (also named ASCOM complex) and MLL4/WBP7. Each complex is at least CC composed of ASH2L, RBBP5, WDR5, DPY30, one or more specific CC histone methyltransferases (KMT2A/MLL1, KMT2D/MLL2, KMT2C/MLL3 and CC KMT2B/MLL4), and the facultative components PAGR1, BAP18, CHD8, CC E2F6, HCFC1, HCFC2, HSP70, INO80C, KDM6A, KANSL1, LAS1L, MAX, CC MCRS1, MEN1, MGA, MYST1/MOF, NCOA6, PAXIP1/PTIP, PELP1, PHF20, CC PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, CC TAF7, TAF9, TEX10 and alpha- and beta-tubulin. Interacts with WDR5 CC and ASH2L; the interaction is direct. Interacts with WDR82 and CC SETD1A. Part of a complex composed at least of ASCL2, CC C11orf30/EMSY, HCFC1, HSPA8, CCAR2, MATR3, MKI67, RBBP5, TUBB2A, CC WDR5 and ZNF335; this complex may have a histone H3-specific CC methyltransferase activity (By similarity). {ECO:0000250}. CC -!- INTERACTION: CC Q9UBL3:ASH2L; NbExp=18; IntAct=EBI-592823, EBI-540797; CC Q9HCK8:CHD8; NbExp=2; IntAct=EBI-592823, EBI-1169146; CC Q13619:CUL4A; NbExp=3; IntAct=EBI-592823, EBI-456106; CC Q9P0U4:CXXC1; NbExp=5; IntAct=EBI-592823, EBI-949911; CC Q03164:KMT2A; NbExp=6; IntAct=EBI-592823, EBI-591370; CC O15047:SETD1A; NbExp=3; IntAct=EBI-592823, EBI-540779; CC P61964:WDR5; NbExp=6; IntAct=EBI-592823, EBI-540834; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17355966}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q15291-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15291-2; Sequence=VSP_035583; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. CC -!- SIMILARITY: Contains 6 WD repeats. {ECO:0000255|PROSITE- CC ProRule:PRU00221}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X85134; CAA59446.1; -; mRNA. DR EMBL; AK290137; BAF82826.1; -; mRNA. DR EMBL; AL583832; CAI15286.1; -; Genomic_DNA. DR EMBL; AC093422; CAI15286.1; JOINED; Genomic_DNA. DR EMBL; AL583832; CAI15287.1; -; Genomic_DNA. DR EMBL; AC093422; CAI15287.1; JOINED; Genomic_DNA. DR EMBL; CH471067; EAW91537.1; -; Genomic_DNA. DR EMBL; CH471067; EAW91538.1; -; Genomic_DNA. DR EMBL; BC037284; AAH37284.1; -; mRNA. DR EMBL; BC053856; AAH53856.1; -; mRNA. DR EMBL; BC075059; AAH75059.1; -; mRNA. DR EMBL; BC075060; AAH75060.1; -; mRNA. DR CCDS; CCDS30983.1; -. [Q15291-1] DR CCDS; CCDS53463.1; -. [Q15291-2] DR PIR; A57624; A57624. DR RefSeq; NP_001180201.1; NM_001193272.1. [Q15291-2] DR RefSeq; NP_001180202.1; NM_001193273.1. DR RefSeq; NP_005048.2; NM_005057.3. [Q15291-1] DR UniGene; Hs.519230; -. DR PDB; 3P4F; X-ray; 2.35 A; B=371-381. DR PDB; 4X8N; X-ray; 2.10 A; B=347-356. DR PDB; 4X8P; X-ray; 2.20 A; B=344-355. DR PDBsum; 3P4F; -. DR PDBsum; 4X8N; -. DR PDBsum; 4X8P; -. DR ProteinModelPortal; Q15291; -. DR SMR; Q15291; 30-320. DR BioGrid; 111864; 64. DR DIP; DIP-29224N; -. DR IntAct; Q15291; 24. DR MINT; MINT-3031197; -. DR STRING; 9606.ENSP00000264515; -. DR ChEMBL; CHEMBL3137282; -. DR PhosphoSite; Q15291; -. DR BioMuta; RBBP5; -. DR DMDM; 209572664; -. DR MaxQB; Q15291; -. DR PaxDb; Q15291; -. DR PRIDE; Q15291; -. DR DNASU; 5929; -. DR Ensembl; ENST00000264515; ENSP00000264515; ENSG00000117222. [Q15291-1] DR Ensembl; ENST00000367164; ENSP00000356132; ENSG00000117222. [Q15291-2] DR GeneID; 5929; -. DR KEGG; hsa:5929; -. DR UCSC; uc001hbu.2; human. [Q15291-1] DR UCSC; uc001hbv.2; human. [Q15291-2] DR CTD; 5929; -. DR GeneCards; RBBP5; -. DR H-InvDB; HIX0023636; -. DR HGNC; HGNC:9888; RBBP5. DR HPA; HPA049042; -. DR HPA; HPA058085; -. DR MIM; 600697; gene. DR neXtProt; NX_Q15291; -. DR PharmGKB; PA34252; -. DR eggNOG; KOG1273; Eukaryota. DR eggNOG; ENOG410XTA2; LUCA. DR GeneTree; ENSGT00530000064100; -. DR HOVERGEN; HBG054324; -. DR InParanoid; Q15291; -. DR KO; K14961; -. DR OMA; EQGVIEW; -. DR OrthoDB; EOG7S21X6; -. DR PhylomeDB; Q15291; -. DR TreeFam; TF313289; -. DR Reactome; R-HSA-201722; formation of the beta-catenin:TCF transactivating complex. DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines. DR Reactome; R-HSA-3769402; deactivation of the beta-catenin transactivating complex. DR SignaLink; Q15291; -. DR GeneWiki; RBBP5; -. DR GenomeRNAi; 5929; -. DR NextBio; 23098; -. DR PRO; PR:Q15291; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; Q15291; -. DR CleanEx; HS_RBBP5; -. DR ExpressionAtlas; Q15291; baseline and differential. DR Genevisible; Q15291; HS. DR GO; GO:0035097; C:histone methyltransferase complex; IDA:UniProtKB. DR GO; GO:0071339; C:MLL1 complex; IDA:UniProtKB. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0048188; C:Set1C/COMPASS complex; IDA:UniProtKB. DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:UniProtKB. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:MGI. DR GO; GO:0006325; P:chromatin organization; TAS:Reactome. DR GO; GO:0051568; P:histone H3-K4 methylation; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0043627; P:response to estrogen; IDA:UniProtKB. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 2.130.10.10; -; 1. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom. DR InterPro; IPR001680; WD40_repeat. DR InterPro; IPR017986; WD40_repeat_dom. DR Pfam; PF00400; WD40; 1. DR SMART; SM00320; WD40; 5. DR PROSITE; PS50082; WD_REPEATS_2; 1. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromatin regulator; KW Complete proteome; Nucleus; Phosphoprotein; Reference proteome; KW Repeat; Transcription; Transcription regulation; WD repeat. FT CHAIN 1 538 Retinoblastoma-binding protein 5. FT /FTId=PRO_0000051194. FT REPEAT 22 63 WD 1. FT REPEAT 64 103 WD 2. FT REPEAT 148 188 WD 3. FT REPEAT 196 235 WD 4. FT REPEAT 249 291 WD 5. FT REPEAT 293 331 WD 6. FT MOD_RES 252 252 Phosphothreonine; by CDK1. FT {ECO:0000269|PubMed:7558034}. FT MOD_RES 350 350 Phosphoserine. FT {ECO:0000244|PubMed:17081983}. FT MOD_RES 388 388 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 389 389 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 497 497 Phosphoserine; by CDK1. FT {ECO:0000269|PubMed:7558034}. FT MOD_RES 525 525 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT VAR_SEQ 492 529 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_035583. FT CONFLICT 206 206 F -> Y (in Ref. 2; BAF82826). FT {ECO:0000305}. FT CONFLICT 244 244 K -> E (in Ref. 1; CAA59446). FT {ECO:0000305}. FT CONFLICT 351 351 E -> G (in Ref. 1; CAA59446). FT {ECO:0000305}. FT TURN 349 352 {ECO:0000244|PDB:4X8N}. SQ SEQUENCE 538 AA; 59153 MW; 095CCB41613CBED9 CRC64; MNLELLESFG QNYPEEADGT LDCISMALTC TFNRWGTLLA VGCNDGRIVI WDFLTRGIAK IISAHIHPVC SLCWSRDGHK LVSASTDNIV SQWDVLSGDC DQRFRFPSPI LKVQYHPRDQ NKVLVCPMKS APVMLTLSDS KHVVLPVDDD SDLNVVASFD RRGEYIYTGN AKGKILVLKT DSQDLVASFR VTTGTSNTTA IKSIEFARKG SCFLINTADR IIRVYDGREI LTCGRDGEPE PMQKLQDLVN RTPWKKCCFS GDGEYIVAGS ARQHALYIWE KSIGNLVKIL HGTRGELLLD VAWHPVRPII ASISSGVVSI WAQNQVENWS AFAPDFKELD ENVEYEERES EFDIEDEDKS EPEQTGADAA EDEEVDVTSV DPIAAFCSSD EELEDSKALL YLPIAPEVED PEENPYGPPP DAVQTSLMDE GASSEKKRQS SADGSQPPKK KPKTTNIELQ GVPNDEVHPL LGVKGDGKSK KKQAGRPKGS KGKEKDSPFK PKLYKGDRGL PLEGSAKGKV QAELSQPLTA GGAISELL // ID RIM3A_HUMAN Reviewed; 1639 AA. AC Q9UFD9; Q8IYP7; Q9BY94; Q9UFQ5; DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot. DT 21-MAR-2012, sequence version 4. DT 11-NOV-2015, entry version 113. DE RecName: Full=RIMS-binding protein 3A; DE Short=RIM-BP3.A; DE AltName: Full=RIMS-binding protein 3.1; DE Short=RIM-BP3.1; GN Name=RIMBP3; Synonyms=KIAA1666, RIMBP3A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J., RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., RA Khan A.S., Lane L., Tilahun Y., Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 50-1639, AND VARIANT RP CYS-1513. RC TISSUE=Brain; RX PubMed=11258795; DOI=10.1093/dnares/8.1.1; RA Hirosawa M., Nagase T., Murahashi Y., Kikuno R., Ohara O.; RT "Identification of novel transcribed sequences on human chromosome 22 RT by expressed sequence tag mapping."; RL DNA Res. 8:1-9(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 473-1639. RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 753-1639, AND VARIANT RP CYS-1513. RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP STRUCTURE BY NMR OF 1572-1639. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the third SH3 domain from human KIAA1666 RT protein."; RL Submitted (AUG-2007) to the PDB data bank. CC -!- INTERACTION: CC Q08117:AES; NbExp=3; IntAct=EBI-10182375, EBI-717810; CC P29972:AQP1; NbExp=3; IntAct=EBI-10182375, EBI-745213; CC Q8NEC5:CATSPER1; NbExp=3; IntAct=EBI-10182375, EBI-744545; CC Q02930-3:CREB5; NbExp=3; IntAct=EBI-10182375, EBI-10192698; CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-10182375, EBI-10171902; CC Q9BY27:DGCR6L; NbExp=3; IntAct=EBI-10182375, EBI-742953; CC Q4ZH49:DTX2; NbExp=3; IntAct=EBI-10182375, EBI-10192429; CC Q9NW38:FANCL; NbExp=3; IntAct=EBI-10182375, EBI-2339898; CC Q86UR1:NOXA1; NbExp=3; IntAct=EBI-10182375, EBI-949814; CC O15160:POLR1C; NbExp=3; IntAct=EBI-10182375, EBI-1055079; CC Q9Y3C6:PPIL1; NbExp=3; IntAct=EBI-10182375, EBI-2557649; CC Q13131:PRKAA1; NbExp=3; IntAct=EBI-10182375, EBI-1181405; CC O43741:PRKAB2; NbExp=3; IntAct=EBI-10182375, EBI-1053424; CC O43734:TRAF3IP2; NbExp=3; IntAct=EBI-10182375, EBI-744798; CC Q96MN9:ZNF488; NbExp=3; IntAct=EBI-10182375, EBI-948288; CC -!- SIMILARITY: Belongs to the RIMBP family. {ECO:0000305}. CC -!- SIMILARITY: Contains 2 fibronectin type-III domains. CC {ECO:0000255|PROSITE-ProRule:PRU00316}. CC -!- SIMILARITY: Contains 3 SH3 domains. {ECO:0000255|PROSITE- CC ProRule:PRU00192}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH35246.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=BAB33336.1; Type=Frameshift; Positions=652; Evidence={ECO:0000305}; CC Sequence=CAB61362.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AC023490; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB051453; BAB33336.1; ALT_FRAME; mRNA. DR EMBL; AL117509; CAB55970.1; -; mRNA. DR EMBL; AL133030; CAB61362.2; ALT_INIT; mRNA. DR EMBL; BC035246; AAH35246.2; ALT_INIT; mRNA. DR CCDS; CCDS46665.1; -. DR PIR; T17280; T17280. DR PIR; T42704; T42704. DR RefSeq; NP_056487.1; NM_015672.1. DR UniGene; Hs.115429; -. DR PDB; 2EGE; NMR; -; A=1572-1639. DR PDBsum; 2EGE; -. DR ProteinModelPortal; Q9UFD9; -. DR SMR; Q9UFD9; 833-900, 1572-1639. DR BioGrid; 124503; 18. DR IntAct; Q9UFD9; 15. DR STRING; 9606.ENSP00000391564; -. DR PhosphoSite; Q9UFD9; -. DR BioMuta; RIMBP3; -. DR DMDM; 380865484; -. DR MaxQB; Q9UFD9; -. DR PaxDb; Q9UFD9; -. DR PRIDE; Q9UFD9; -. DR Ensembl; ENST00000619918; ENSP00000483386; ENSG00000275793. DR GeneID; 85376; -. DR KEGG; hsa:85376; -. DR UCSC; uc002zsd.4; human. DR CTD; 85376; -. DR GeneCards; RIMBP3; -. DR H-InvDB; HIX0016277; -. DR H-InvDB; HIX0041402; -. DR H-InvDB; HIX0197170; -. DR HGNC; HGNC:29344; RIMBP3. DR HPA; HPA001183; -. DR MIM; 612699; gene. DR neXtProt; NX_Q9UFD9; -. DR eggNOG; KOG3632; Eukaryota. DR eggNOG; ENOG410XZ8W; LUCA. DR GeneTree; ENSGT00390000017228; -. DR HOGENOM; HOG000090231; -. DR HOVERGEN; HBG096074; -. DR InParanoid; Q9UFD9; -. DR OMA; WETMSST; -. DR PhylomeDB; Q9UFD9; -. DR TreeFam; TF316230; -. DR EvolutionaryTrace; Q9UFD9; -. DR GenomeRNAi; 85376; -. DR NextBio; 75918; -. DR PRO; PR:Q9UFD9; -. DR Proteomes; UP000005640; Chromosome 22. DR Bgee; Q9UFD9; -. DR CleanEx; HS_RIMBP3; -. DR Genevisible; Q9UFD9; HS. DR Gene3D; 2.60.40.10; -; 1. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR011511; SH3_2. DR InterPro; IPR001452; SH3_domain. DR Pfam; PF07653; SH3_2; 1. DR Pfam; PF14604; SH3_9; 1. DR SMART; SM00060; FN3; 2. DR SMART; SM00326; SH3; 3. DR SUPFAM; SSF49265; SSF49265; 1. DR SUPFAM; SSF50044; SSF50044; 3. DR PROSITE; PS50853; FN3; 2. DR PROSITE; PS50002; SH3; 2. PE 1: Evidence at protein level; KW 3D-structure; Coiled coil; Complete proteome; Phosphoprotein; KW Polymorphism; Reference proteome; Repeat. FT CHAIN 1 1639 RIMS-binding protein 3A. FT /FTId=PRO_0000259597. FT DOMAIN 832 899 SH3 1. {ECO:0000255|PROSITE- FT ProRule:PRU00192}. FT DOMAIN 995 1083 Fibronectin type-III 1. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 1088 1184 Fibronectin type-III 2. FT {ECO:0000255|PROSITE-ProRule:PRU00316}. FT DOMAIN 1452 1520 SH3 2. {ECO:0000255|PROSITE- FT ProRule:PRU00192}. FT DOMAIN 1569 1636 SH3 3. {ECO:0000255|PROSITE- FT ProRule:PRU00192}. FT COILED 21 143 {ECO:0000255}. FT COILED 409 442 {ECO:0000255}. FT COILED 480 619 {ECO:0000255}. FT COMPBIAS 30 137 Arg-rich. FT COMPBIAS 312 366 Pro-rich. FT MOD_RES 260 260 Phosphoserine. FT {ECO:0000250|UniProtKB:Q3V0F0}. FT MOD_RES 284 284 Phosphoserine. FT {ECO:0000250|UniProtKB:Q3V0F0}. FT VARIANT 1513 1513 R -> C (in dbSNP:rs469096). FT {ECO:0000269|PubMed:11258795, FT ECO:0000269|PubMed:15489334}. FT /FTId=VAR_028969. FT CONFLICT 396 396 A -> E (in Ref. 2; BAB33336). FT {ECO:0000305}. FT CONFLICT 437 437 K -> E (in Ref. 2; BAB33336). FT {ECO:0000305}. FT CONFLICT 653 653 S -> P (in Ref. 2; BAB33336). FT {ECO:0000305}. FT CONFLICT 882 882 E -> D (in Ref. 2; BAB33336). FT {ECO:0000305}. FT CONFLICT 1307 1307 P -> T (in Ref. 4; AAH35246). FT {ECO:0000305}. FT CONFLICT 1314 1314 S -> Y (in Ref. 3; CAB61362 and 4; FT AAH35246). {ECO:0000305}. FT CONFLICT 1391 1391 W -> R (in Ref. 4; AAH35246). FT {ECO:0000305}. FT CONFLICT 1484 1484 R -> K (in Ref. 2; BAB33336). FT {ECO:0000305}. FT CONFLICT 1536 1536 N -> H (in Ref. 2; BAB33336, 3; CAB55970 FT and 4; AAH35246). {ECO:0000305}. FT STRAND 1572 1578 {ECO:0000244|PDB:2EGE}. FT TURN 1582 1585 {ECO:0000244|PDB:2EGE}. FT STRAND 1589 1591 {ECO:0000244|PDB:2EGE}. FT STRAND 1602 1607 {ECO:0000244|PDB:2EGE}. FT STRAND 1614 1621 {ECO:0000244|PDB:2EGE}. FT STRAND 1623 1627 {ECO:0000244|PDB:2EGE}. FT TURN 1628 1630 {ECO:0000244|PDB:2EGE}. FT STRAND 1631 1633 {ECO:0000244|PDB:2EGE}. SQ SEQUENCE 1639 AA; 180717 MW; B1A465ECFDBE7903 CRC64; MAKDSPSPLG ASPKKPGCSS PAAAVLENQR RELEKLRAEL EAERAGWRAE RRRFAARERQ LREEAERERR QLADRLRSKW EAQRSRELRQ LQEEMQRERE AEIRQLLRWK EAEQRQLQQL LHRERDGVVR QARELQRQLA EELVNRGHCS RPGASEVSAA QCRCRLQEVL AQLRWQTDGE QAARIRYLQA ALEVERQLFL KYILAHFRGH PALSGSPDPQ AVHSLEEPLP QTSSGSCHAP KPACQLGSLD SLSAEVGVRS RSLGLVSSAC SSSPDGLLST HASSLDCFAP ACSRSLDSTR SLPKASKSEE RPSSPDTSTP GSRRLSPPPS PLPPPPPPSA HRKLSNPRGG EGSESQPCEV LTPSPPGLGH HELIKLNWLL AKALWVLARR CYTLQAENKQ LRRAGCPYQA DEKVKRLKVK RAELTGLARR LADRARKLQE TNLRAVSAPI PGESCAGLEL CQVFARQRAR DLSEQASAPL AKDKQIEELR QECHLLQARV ASGPCSDLHT GRGGPCTQWL NVRDLDRLQR ESQREVLRLQ RQLMLQQGNG GAWPEAGGQS ATCEEVRRQM LALERELDQR RRECQELGAQ AAPARRRGEE AETQLQAALL KNAWLAEENG RLQAKTDWVR KVEAENSEVR GHLGRACQER DASGLIAEQL LQQAARGQDR QQQLQRDPQK ALCDLHPSWK EIQALQCRPG HPPEQPWETS QMPESQVKGS RRPKFHARPE DYAVSQPNRD IQEKREASLE ESPVALGESA SVPQVSETVP ASQPLSKKTS SQSNSSSEGS MWATVPSSPT LDRDTASEVD DLEPDSVSLA LEMGGSAAPA APKLKIFMAQ YNYNPFEGPN DHPEGELPLT AGDYIYIFGD MDEDGFYEGE LEDGRRGLVP SNFVEQIPDS YIPGCLPAKS PDLGPSQLPA GQDEALEEDS LLSGKAQGVV DRGLCQMVRV GSKTEVATEI LDTKTEACQL GLLQSMGKQG LSRPLLGTKG VLRMAPMQLH LQNVTATSAN ITWVYSSHRH PHVVYLDDRE HALTPAGVSC YTFQGLCPGT HYRARVEVRL PRDLLQVYWG TMSSTVTFDT LLAGPPYPPL DVLVERHASP GVLVVSWLPV TIDSAGSSNG VQVTGYAVYA DGLKVCEVAD ATAGSTLLEF SQLQVPLTWQ KVSVRTMSLC GESLDSVPAQ IPEDFFMCHR WPETPPFSYT CGDPSTYRVT FPVCPQKLSL APPSAKASPH NPGSCGEPQA KFLEAFFEEP PRRQSPVSNL GSEGECPSSG AGSQAQELAE AWEGCRKDLL FQKSPQNHRP PSVSDQPGEK ENCSQHMGTS KSPAPGFIHL RTECGPRKEP CQEKAALERV LRQKQDAQGF TPPQLGASQQ YASDFHNVLK EEQEALCLDL WGTERREERR EPEPHSRQGQ ALGVKRGCQL HEPSSALCPA PSAKVIKMPR GGPQQLGTGA NTPARVFVAL SDYNPLVMSA NLKAAEEELV FQKRQLLRVW GSQDTHDFYL SECNRQVGNI PGRLVAEMEV GTEQTDRRWR SPAQGNLPSV AHLEDFQGLT IPQGSSLVLQ GNSKRLPLWT PKIMIAALDY DPGDGQMGGQ GKGRLALRAG DVVMVYGPMD DQGFYYGELG GHRGLVPAHL LDHMSLHGH // ID RL17_HUMAN Reviewed; 184 AA. AC P18621; B2R4H3; B4E3C2; B5ME31; J3QL51; Q3KQW2; Q6NZ54; Q7M4M5; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 11-NOV-2015, entry version 165. DE RecName: Full=60S ribosomal protein L17; DE AltName: Full=60S ribosomal protein L23; DE AltName: Full=PD-1; GN Name=RPL17; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Blood; RX PubMed=2402465; DOI=10.1093/nar/18.17.5301; RA Mager D.L., Freeman J.D.; RT "A human gene related to the ribosomal protein L23 gene of RT Halobacterium marismortui."; RL Nucleic Acids Res. 18:5301-5301(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC TISSUE=Pancreatic tumor; RX PubMed=1793733; RA Batra S.K., Metzgar R.S., Hollingsworth M.A.; RT "Isolation and characterization of a complementary DNA (PD-1) RT differentially expressed by human pancreatic ductal cell tumors."; RL Cell Growth Differ. 2:385-390(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11875025; DOI=10.1101/gr.214202; RA Yoshihama M., Uechi T., Asakawa S., Kawasaki K., Kato S., Higa S., RA Maeda N., Minoshima S., Tanaka T., Shimizu N., Kenmochi N.; RT "The human ribosomal protein genes: sequencing and comparative RT analysis of 73 genes."; RL Genome Res. 12:379-390(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Neuroblastoma; RA Li W.B., Gruber C., Jessee J., Polayes D.; RL Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16177791; DOI=10.1038/nature03983; RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R., RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., RA O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.; RT "DNA sequence and analysis of human chromosome 18."; RL Nature 437:551-555(2005). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Hypothalamus, Lung, Prostate, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP PROTEIN SEQUENCE OF 2-10, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=12962325; DOI=10.1023/A:1025068419698; RA Odintsova T.I., Muller E.C., Ivanov A.V., Egorov T.A., Bienert R., RA Vladimirov S.N., Kostka S., Otto A., Wittmann-Liebold B., RA Karpova G.G.; RT "Characterization and analysis of posttranslational modifications of RT the human large cytoplasmic ribosomal subunit proteins by mass RT spectrometry and Edman sequencing."; RL J. Protein Chem. 22:249-258(2003). RN [10] RP PROTEIN SEQUENCE OF 2-13; 31-42; 47-55; 75-82; 86-96 AND 106-124, RP CLEAVAGE OF INITIATOR METHIONINE, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Cervix carcinoma; RA Bienvenut W.V., Calvo F., Kolch W.; RL Submitted (FEB-2008) to UniProtKB. RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 170-183. RX PubMed=9582194; RA Kenmochi N., Kawaguchi T., Rozen S., Davis E., Goodman N., RA Hudson T.J., Tanaka T., Page D.C.; RT "A map of 75 human ribosomal protein genes."; RL Genome Res. 8:509-523(1998). RN [12] RP STRUCTURE BY ELECTRON MICROSCOPY (5.0 ANGSTROMS). RX PubMed=23636399; DOI=10.1038/nature12104; RA Anger A.M., Armache J.P., Berninghausen O., Habeck M., Subklewe M., RA Wilson D.N., Beckmann R.; RT "Structures of the human and Drosophila 80S ribosome."; RL Nature 497:80-85(2013). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P18621-1; Sequence=Displayed; CC Name=2; CC IsoId=P18621-2; Sequence=VSP_045445; CC Name=3; CC IsoId=P18621-3; Sequence=VSP_046965; CC -!- TISSUE SPECIFICITY: Expressed in pancreas, lung, colon, cystic CC duct, gall bladder, kidney and liver. Expressed at high levels in CC the well differentiated pancreatic tumor cell lines HPAF, COLO 357 CC and Capan-1, the moderately differentiated pancreatic tumor cell CC lines T3M-4, AsPc-1 and BxPc-3, the poorly differentiated CC pancreatic tumor cell line MIA PaCa-2, and the pancreatic tumor CC cell lines of undefined differentiation status such as SW979. CC Expressed at lower levels in the poorly differentiated pancreatic CC tumor cell lines HCG-25 and PANC-1. {ECO:0000269|PubMed:1793733}. CC -!- SIMILARITY: Belongs to the ribosomal protein L22P family. CC {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X53777; CAA37793.1; -; mRNA. DR EMBL; AB061824; BAB79462.1; -; Genomic_DNA. DR EMBL; AC100778; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AK304659; BAG65434.1; -; mRNA. DR EMBL; AK311828; BAG34770.1; -; mRNA. DR EMBL; BX393840; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; CH471096; EAW62940.1; -; Genomic_DNA. DR EMBL; BC000502; AAH00502.1; -; mRNA. DR EMBL; BC017831; AAH17831.1; -; mRNA. DR EMBL; BC066323; AAH66323.1; -; mRNA. DR EMBL; BC066324; AAH66324.1; -; mRNA. DR EMBL; BC106031; AAI06032.1; -; mRNA. DR EMBL; AB007174; BAA25834.1; -; Genomic_DNA. DR CCDS; CCDS45865.1; -. [P18621-1] DR CCDS; CCDS56070.1; -. [P18621-2] DR PIR; A61192; A61192. DR PIR; S11218; R5HU22. DR RefSeq; NP_000976.1; NM_000985.4. [P18621-1] DR RefSeq; NP_001030178.1; NM_001035006.2. [P18621-1] DR RefSeq; NP_001186269.1; NM_001199340.1. [P18621-1] DR RefSeq; NP_001186270.1; NM_001199341.1. [P18621-1] DR RefSeq; NP_001186271.1; NM_001199342.1. [P18621-1] DR RefSeq; NP_001186272.1; NM_001199343.1. [P18621-1] DR RefSeq; NP_001186273.1; NM_001199344.1. [P18621-1] DR RefSeq; NP_001186274.1; NM_001199345.1. [P18621-2] DR UniGene; Hs.293653; -. DR UniGene; Hs.374588; -. DR UniGene; Hs.485081; -. DR PDB; 4UG0; EM; -; LP=1-184. DR PDB; 4V6X; EM; 5.00 A; CP=1-184. DR PDB; 5AJ0; EM; 3.50 A; AP=1-184. DR PDBsum; 4UG0; -. DR PDBsum; 4V6X; -. DR PDBsum; 5AJ0; -. DR ProteinModelPortal; P18621; -. DR SMR; P18621; 1-153. DR BioGrid; 112059; 112. DR IntAct; P18621; 30. DR MINT; MINT-1393841; -. DR STRING; 9606.ENSP00000462023; -. DR PhosphoSite; P18621; -. DR BioMuta; RPL17; -. DR DMDM; 132799; -. DR MaxQB; P18621; -. DR PaxDb; P18621; -. DR PRIDE; P18621; -. DR DNASU; 6139; -. DR Ensembl; ENST00000418495; ENSP00000397798; ENSG00000265681. [P18621-1] DR Ensembl; ENST00000579248; ENSP00000462023; ENSG00000265681. [P18621-1] DR Ensembl; ENST00000579408; ENSP00000463842; ENSG00000265681. [P18621-1] DR Ensembl; ENST00000580261; ENSP00000462385; ENSG00000265681. [P18621-1] DR Ensembl; ENST00000581373; ENSP00000462944; ENSG00000265681. [P18621-2] DR Ensembl; ENST00000618613; ENSP00000480555; ENSG00000265681. [P18621-1] DR Ensembl; ENST00000618619; ENSP00000482577; ENSG00000265681. [P18621-1] DR GeneID; 6139; -. DR KEGG; hsa:6139; -. DR UCSC; uc002ldm.2; human. DR UCSC; uc002ldp.3; human. [P18621-1] DR CTD; 6139; -. DR GeneCards; RPL17; -. DR HGNC; HGNC:10307; RPL17. DR HPA; HPA043724; -. DR HPA; HPA046385; -. DR MIM; 603661; gene. DR neXtProt; NX_P18621; -. DR PharmGKB; PA34676; -. DR eggNOG; KOG3353; Eukaryota. DR eggNOG; COG0091; LUCA. DR GeneTree; ENSGT00390000014873; -. DR HOGENOM; HOG000205045; -. DR HOVERGEN; HBG000955; -. DR InParanoid; P18621; -. DR KO; K02880; -. DR OMA; RDINAFF; -. DR OrthoDB; EOG70GMHF; -. DR PhylomeDB; P18621; -. DR TreeFam; TF300042; -. DR Reactome; R-HSA-156827; L13a-mediated translational silencing of Ceruloplasmin expression. DR Reactome; R-HSA-156902; Peptide chain elongation. DR Reactome; R-HSA-1799339; SRP-dependent cotranslational protein targeting to membrane. DR Reactome; R-HSA-192823; Viral mRNA Translation. DR Reactome; R-HSA-72689; Formation of a pool of free 40S subunits. DR Reactome; R-HSA-72706; GTP hydrolysis and joining of the 60S ribosomal subunit. DR Reactome; R-HSA-72764; Eukaryotic Translation Termination. DR Reactome; R-HSA-975956; Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC). DR Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC). DR GeneWiki; RPL17; -. DR NextBio; 23849; -. DR PRO; PR:P18621; -. DR Proteomes; UP000005640; Chromosome 18. DR Bgee; P18621; -. DR CleanEx; HS_RPL17; -. DR ExpressionAtlas; P18621; baseline and differential. DR Genevisible; P18621; HS. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0022625; C:cytosolic large ribosomal subunit; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0003735; F:structural constituent of ribosome; NAS:UniProtKB. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0002181; P:cytoplasmic translation; IBA:GO_Central. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome. DR GO; GO:0006614; P:SRP-dependent cotranslational protein targeting to membrane; TAS:Reactome. DR GO; GO:0006412; P:translation; NAS:UniProtKB. DR GO; GO:0006414; P:translational elongation; TAS:Reactome. DR GO; GO:0006413; P:translational initiation; TAS:Reactome. DR GO; GO:0006415; P:translational termination; TAS:Reactome. DR GO; GO:0019058; P:viral life cycle; TAS:Reactome. DR GO; GO:0016032; P:viral process; TAS:Reactome. DR GO; GO:0019083; P:viral transcription; TAS:Reactome. DR Gene3D; 3.90.470.10; -; 1. DR HAMAP; MF_01331_A; Ribosomal_L22_A; 1. DR InterPro; IPR001063; Ribosomal_L22. DR InterPro; IPR018260; Ribosomal_L22/L17_CS. DR InterPro; IPR005721; Ribosomal_L22/L17_euk/arc. DR PANTHER; PTHR11593; PTHR11593; 1. DR Pfam; PF00237; Ribosomal_L22; 1. DR SUPFAM; SSF54843; SSF54843; 1. DR TIGRFAMs; TIGR01038; uL22_arch_euk; 1. DR PROSITE; PS00464; RIBOSOMAL_L22; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; KW Direct protein sequencing; Reference proteome; Ribonucleoprotein; KW Ribosomal protein. FT INIT_MET 1 1 Removed. {ECO:0000269|PubMed:12962325, FT ECO:0000269|Ref.10}. FT CHAIN 2 184 60S ribosomal protein L17. FT /FTId=PRO_0000125331. FT VAR_SEQ 1 38 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_045445. FT VAR_SEQ 170 184 ISQKKLKKQKLMARE -> LRSSSLGKWCAFLVSSFQFCSG FT STKNSWSHIYTLWFPPSLVVYGLRKQYKNPMIQTKAK (in FT isoform 3). {ECO:0000303|Ref.5}. FT /FTId=VSP_046965. FT CONFLICT 133 133 H -> R (in Ref. 8; AAH66324). FT {ECO:0000305}. SQ SEQUENCE 184 AA; 21397 MW; 2FC595DD74ED1CA0 CRC64; MVRYSLDPEN PTKSCKSRGS NLRVHFKNTR ETAQAIKGMH IRKATKYLKD VTLQKQCVPF RRYNGGVGRC AQAKQWGWTQ GRWPKKSAEF LLHMLKNAES NAELKGLDVD SLVIEHIQVN KAPKMRRRTY RAHGRINPYM SSPCHIEMIL TEKEQIVPKP EEEVAQKKKI SQKKLKKQKL MARE // ID RL7A_HUMAN Reviewed; 266 AA. AC P62424; P11518; Q5T8U4; DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 11-NOV-2015, entry version 123. DE RecName: Full=60S ribosomal protein L7a; DE AltName: Full=PLA-X polypeptide; DE AltName: Full=Surfeit locus protein 3; GN Name=RPL7A; Synonyms=SURF-3, SURF3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RX PubMed=2966065; RA Kozma S.C., Redmond S.M.S., Saurer S.M., Groner B., Hynes N.E.; RT "Activation of the receptor kinase domain of the trk oncogene by RT recombination with two different cellular sequences."; RL EMBO J. 7:147-154(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1756182; DOI=10.1016/0167-4781(91)90218-B; RA Colombo P., Yon J., Fried M.; RT "The organization and expression of the human L7a ribosomal protein RT gene."; RL Biochim. Biophys. Acta 1129:93-95(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8482538; DOI=10.1016/0378-1119(93)90371-9; RA De Falco S., Russo G., Angiolillo A., Pietropaolo C.; RT "Human L7a ribosomal protein: sequence, structural organization, and RT expression of a functional gene."; RL Gene 126:227-235(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1696715; DOI=10.1073/pnas.87.16.6039; RA Ben-Ishai R., Scharf R., Sharon R., Kapten I.; RT "A human cellular sequence implicated in trk oncogene activation is RT DNA damage inducible."; RL Proc. Natl. Acad. Sci. U.S.A. 87:6039-6043(1990). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cerebellum; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164053; DOI=10.1038/nature02465; RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., RA Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., RA Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., RA Babbage A.K., Babbage S., Bagguley C.L., Bailey J., Banerjee R., RA Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., RA Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., RA Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., RA Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., RA Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., RA Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., RA Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., RA Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., RA Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., RA McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., RA Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., RA Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., RA Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., RA Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., RA Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., RA Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., RA Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., RA Rogers J., Dunham I.; RT "DNA sequence and analysis of human chromosome 9."; RL Nature 429:369-374(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=B-cell, Eye, Lung, Placenta, Skin, and Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-34; LYS-97 AND LYS-217, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [13] RP STRUCTURE BY ELECTRON MICROSCOPY (5.0 ANGSTROMS). RX PubMed=23636399; DOI=10.1038/nature12104; RA Anger A.M., Armache J.P., Berninghausen O., Habeck M., Subklewe M., RA Wilson D.N., Beckmann R.; RT "Structures of the human and Drosophila 80S ribosome."; RL Nature 497:80-85(2013). CC -!- SUBUNIT: Interacts with CRY1. {ECO:0000250|UniProtKB:P12970}. CC -!- INTERACTION: CC O95793:STAU1; NbExp=2; IntAct=EBI-354172, EBI-358174; CC -!- DISEASE: Note=Chromosomal recombination involving RPL7A activates CC the receptor kinase domain of the TRK oncogene. CC -!- SIMILARITY: Belongs to the ribosomal protein L7Ae family. CC {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X06705; CAA29889.1; -; mRNA. DR EMBL; X52138; CAA36383.1; -; Genomic_DNA. DR EMBL; X61923; CAA43925.1; -; Genomic_DNA. DR EMBL; M36072; AAA60282.1; -; mRNA. DR EMBL; AK291123; BAF83812.1; -; mRNA. DR EMBL; AK311743; BAG34686.1; -; mRNA. DR EMBL; AL158826; CAI12832.1; -; Genomic_DNA. DR EMBL; CH471090; EAW88063.1; -; Genomic_DNA. DR EMBL; BC005128; AAH05128.1; -; mRNA. DR EMBL; BC021979; AAH21979.1; -; mRNA. DR EMBL; BC023594; AAH23594.1; -; mRNA. DR EMBL; BC023624; AAH23624.1; -; mRNA. DR EMBL; BC071900; AAH71900.1; -; mRNA. DR EMBL; BC071901; AAH71901.1; -; mRNA. DR EMBL; BC073802; AAH73802.1; -; mRNA. DR EMBL; BC105290; AAI05291.1; -; mRNA. DR CCDS; CCDS6965.1; -. DR PIR; S19717; R5HU7A. DR RefSeq; NP_000963.1; NM_000972.2. DR UniGene; Hs.499839; -. DR PDB; 4UG0; EM; -; LG=1-266. DR PDB; 4V6X; EM; 5.00 A; CG=1-266. DR PDB; 5AJ0; EM; 3.50 A; AG=1-266. DR PDBsum; 4UG0; -. DR PDBsum; 4V6X; -. DR PDBsum; 5AJ0; -. DR ProteinModelPortal; P62424; -. DR SMR; P62424; 136-223. DR BioGrid; 112050; 145. DR DIP; DIP-31502N; -. DR IntAct; P62424; 29. DR MINT; MINT-1149515; -. DR STRING; 9606.ENSP00000361076; -. DR PhosphoSite; P62424; -. DR BioMuta; RPL7A; -. DR DMDM; 54039239; -. DR SWISS-2DPAGE; P62424; -. DR PaxDb; P62424; -. DR PRIDE; P62424; -. DR DNASU; 6130; -. DR Ensembl; ENST00000323345; ENSP00000361076; ENSG00000148303. DR Ensembl; ENST00000630979; ENSP00000487443; ENSG00000280858. DR GeneID; 6130; -. DR KEGG; hsa:6130; -. DR UCSC; uc004cde.1; human. DR CTD; 6130; -. DR GeneCards; RPL7A; -. DR HGNC; HGNC:10364; RPL7A. DR HPA; HPA046794; -. DR MIM; 185640; gene. DR neXtProt; NX_P62424; -. DR PharmGKB; PA34760; -. DR eggNOG; KOG3166; Eukaryota. DR eggNOG; COG1358; LUCA. DR GeneTree; ENSGT00390000004753; -. DR HOGENOM; HOG000216644; -. DR HOVERGEN; HBG002936; -. DR InParanoid; P62424; -. DR KO; K02936; -. DR OMA; TCTCVAF; -. DR PhylomeDB; P62424; -. DR TreeFam; TF300788; -. DR Reactome; R-HSA-156827; L13a-mediated translational silencing of Ceruloplasmin expression. DR Reactome; R-HSA-156902; Peptide chain elongation. DR Reactome; R-HSA-1799339; SRP-dependent cotranslational protein targeting to membrane. DR Reactome; R-HSA-192823; Viral mRNA Translation. DR Reactome; R-HSA-72689; Formation of a pool of free 40S subunits. DR Reactome; R-HSA-72706; GTP hydrolysis and joining of the 60S ribosomal subunit. DR Reactome; R-HSA-72764; Eukaryotic Translation Termination. DR Reactome; R-HSA-975956; Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC). DR Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC). DR ChiTaRS; RPL7A; human. DR GeneWiki; RPL7A; -. DR GenomeRNAi; 6130; -. DR NextBio; 23809; -. DR PRO; PR:P62424; -. DR Proteomes; UP000005640; Chromosome 9. DR Bgee; P62424; -. DR CleanEx; HS_RPL7A; -. DR ExpressionAtlas; P62424; baseline and differential. DR Genevisible; P62424; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0022625; C:cytosolic large ribosomal subunit; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:BHF-UCL. DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0042788; C:polysomal ribosome; IDA:HGNC. DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0003723; F:RNA binding; TAS:ProtInc. DR GO; GO:0003735; F:structural constituent of ribosome; NAS:UniProtKB. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome. DR GO; GO:0042254; P:ribosome biogenesis; IEA:InterPro. DR GO; GO:0006614; P:SRP-dependent cotranslational protein targeting to membrane; TAS:Reactome. DR GO; GO:0006412; P:translation; NAS:UniProtKB. DR GO; GO:0006414; P:translational elongation; TAS:Reactome. DR GO; GO:0006413; P:translational initiation; TAS:Reactome. DR GO; GO:0006415; P:translational termination; TAS:Reactome. DR GO; GO:0019058; P:viral life cycle; TAS:Reactome. DR GO; GO:0016032; P:viral process; TAS:Reactome. DR GO; GO:0019083; P:viral transcription; TAS:Reactome. DR Gene3D; 3.30.1330.30; -; 1. DR InterPro; IPR029064; L30e-like. DR InterPro; IPR001921; Ribosomal_L7A/L8. DR InterPro; IPR004038; Ribosomal_L7Ae/L30e/S12e/Gad45. DR InterPro; IPR018492; Ribosomal_L7Ae/L8/Nhp2. DR InterPro; IPR004037; Ribosomal_L7Ae_CS. DR Pfam; PF01248; Ribosomal_L7Ae; 1. DR PRINTS; PR00881; L7ARS6FAMILY. DR PRINTS; PR00882; RIBOSOMALL7A. DR SUPFAM; SSF55315; SSF55315; 1. DR PROSITE; PS01082; RIBOSOMAL_L7AE; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Chromosomal rearrangement; KW Complete proteome; Polymorphism; Reference proteome; KW Ribonucleoprotein; Ribosomal protein. FT INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:P62425}. FT CHAIN 2 266 60S ribosomal protein L7a. FT /FTId=PRO_0000136747. FT MOD_RES 34 34 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 97 97 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 217 217 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT VARIANT 24 24 A -> V (in dbSNP:rs12295). FT /FTId=VAR_014721. SQ SEQUENCE 266 AA; 29996 MW; 54EF43F221D9F704 CRC64; MPKGKKAKGK KVAPAPAVVK KQEAKKVVNP LFEKRPKNFG IGQDIQPKRD LTRFVKWPRY IRLQRQRAIL YKRLKVPPAI NQFTQALDRQ TATQLLKLAH KYRPETKQEK KQRLLARAEK KAAGKGDVPT KRPPVLRAGV NTVTTLVENK KAQLVVIAHD VDPIELVVFL PALCRKMGVP YCIIKGKARL GRLVHRKTCT TVAFTQVNSE DKGALAKLVE AIRTNYNDRY DEIRRHWGGN VLGPKSVARI AKLEKAKAKE LATKLG // ID RS28_HUMAN Reviewed; 69 AA. AC P62857; P25112; DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 16-AUG-2004, sequence version 1. DT 11-NOV-2015, entry version 117. DE RecName: Full=40S ribosomal protein S28; GN Name=RPS28; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Bhat K.S.; RL Submitted (NOV-1992) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Kim J.M., Bae Y.S.; RL Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11875025; DOI=10.1101/gr.214202; RA Yoshihama M., Uechi T., Asakawa S., Kawasaki K., Kato S., Higa S., RA Maeda N., Minoshima S., Tanaka T., Shimizu N., Kenmochi N.; RT "The human ribosomal protein genes: sequencing and comparative RT analysis of 73 genes."; RL Genome Res. 12:379-390(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=B-cell, Muscle, and Prostate; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 48-68. RC TISSUE=Placenta; RX PubMed=8706699; DOI=10.1111/j.1432-1033.1996.0144u.x; RA Vladimirov S.N., Ivanov A.V., Karpova G.G., Musolyamov A.K., RA Egorov T.A., Thiede B., Wittmann-Liebold B., Otto A.; RT "Characterization of the human small-ribosomal-subunit proteins by N- RT terminal and internal sequencing, and mass spectrometry."; RL Eur. J. Biochem. 239:144-149(1996). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 54-69. RX PubMed=9582194; RA Kenmochi N., Kawaguchi T., Rozen S., Davis E., Goodman N., RA Hudson T.J., Tanaka T., Page D.C.; RT "A map of 75 human ribosomal protein genes."; RL Genome Res. 8:509-523(1998). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [9] RP INVOLVEMENT IN DBA15. RX PubMed=24942156; DOI=10.1002/ajmg.a.36633; RG UW Center for Mendelian Genomics; RA Gripp K.W., Curry C., Olney A.H., Sandoval C., Fisher J., Chong J.X., RA Pilchman L., Sahraoui R., Stabley D.L., Sol-Church K.; RT "Diamond-Blackfan anemia with mandibulofacial dystostosis is RT heterogeneous, including the novel DBA genes TSR2 and RPS28."; RL Am. J. Med. Genet. A 164A:2240-2249(2014). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [12] RP STRUCTURE BY ELECTRON MICROSCOPY (5.0 ANGSTROMS). RX PubMed=23636399; DOI=10.1038/nature12104; RA Anger A.M., Armache J.P., Berninghausen O., Habeck M., Subklewe M., RA Wilson D.N., Beckmann R.; RT "Structures of the human and Drosophila 80S ribosome."; RL Nature 497:80-85(2013). CC -!- INTERACTION: CC O95273:CCNDBP1; NbExp=3; IntAct=EBI-353027, EBI-748961; CC P60409:KRTAP10-7; NbExp=3; IntAct=EBI-353027, EBI-10172290; CC P60410:KRTAP10-8; NbExp=3; IntAct=EBI-353027, EBI-10171774; CC P0C7H8:KRTAP2-3; NbExp=3; IntAct=EBI-353027, EBI-10196781; CC Q7Z3S9:NOTCH2NL; NbExp=3; IntAct=EBI-353027, EBI-945833; CC -!- DISEASE: Diamond-Blackfan anemia 15, with mandibulofacial CC dysostosis (DBA15) [MIM:606164]: A form of Diamond-Blackfan CC anemia, a congenital non-regenerative hypoplastic anemia that CC usually presents early in infancy. Diamond-Blackfan anemia is CC characterized by a moderate to severe macrocytic anemia, CC erythroblastopenia, and an increased risk of malignancy. 30 to 40% CC of Diamond-Blackfan anemia patients present with short stature and CC congenital anomalies, the most frequent being craniofacial CC (Pierre-Robin syndrome and cleft palate), thumb and urogenital CC anomalies. {ECO:0000269|PubMed:24942156}. Note=The disease is CC caused by mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ribosomal protein S28e family. CC {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; L05091; AAC15855.1; -; mRNA. DR EMBL; U58682; AAB07066.1; -; mRNA. DR EMBL; AB061846; BAB79484.1; -; Genomic_DNA. DR EMBL; CR457055; CAG33336.1; -; mRNA. DR EMBL; BC000354; AAH00354.1; -; mRNA. DR EMBL; BC021239; AAH21239.1; -; mRNA. DR EMBL; BC070217; AAH70217.1; -; mRNA. DR EMBL; BC070218; AAH70218.1; -; mRNA. DR EMBL; AB007164; BAA28594.1; -; Genomic_DNA. DR CCDS; CCDS45953.1; -. DR PIR; S68914; S68914. DR RefSeq; NP_001022.1; NM_001031.4. DR UniGene; Hs.153177; -. DR UniGene; Hs.322473; -. DR PDB; 4UG0; EM; -; Sc=1-69. DR PDB; 4V6X; EM; 5.00 A; Ac=1-69. DR PDB; 5A2Q; EM; 3.90 A; c=8-68. DR PDB; 5AJ0; EM; 3.50 A; Bc=1-69. DR PDBsum; 4UG0; -. DR PDBsum; 4V6X; -. DR PDBsum; 5A2Q; -. DR PDBsum; 5AJ0; -. DR ProteinModelPortal; P62857; -. DR SMR; P62857; 8-68. DR BioGrid; 112148; 106. DR IntAct; P62857; 17. DR MINT; MINT-5000390; -. DR STRING; 9606.ENSP00000472469; -. DR PhosphoSite; P62857; -. DR BioMuta; RPS28; -. DR DMDM; 51338652; -. DR MaxQB; P62857; -. DR PaxDb; P62857; -. DR PRIDE; P62857; -. DR DNASU; 6234; -. DR Ensembl; ENST00000600659; ENSP00000472469; ENSG00000233927. DR GeneID; 6234; -. DR KEGG; hsa:6234; -. DR UCSC; uc002mjn.3; human. DR CTD; 6234; -. DR GeneCards; RPS28; -. DR HGNC; HGNC:10418; RPS28. DR HPA; HPA047132; -. DR MIM; 603685; gene. DR MIM; 606164; phenotype. DR neXtProt; NX_P62857; -. DR Orphanet; 124; Blackfan-Diamond anemia. DR PharmGKB; PA34825; -. DR eggNOG; KOG3502; Eukaryota. DR eggNOG; COG2053; LUCA. DR GeneTree; ENSGT00390000003580; -. DR HOVERGEN; HBG000219; -. DR InParanoid; P62857; -. DR KO; K02979; -. DR OMA; ILCLLET; -. DR OrthoDB; EOG7SN8GQ; -. DR PhylomeDB; P62857; -. DR TreeFam; TF300136; -. DR Reactome; R-HSA-156827; L13a-mediated translational silencing of Ceruloplasmin expression. DR Reactome; R-HSA-156902; Peptide chain elongation. DR Reactome; R-HSA-1799339; SRP-dependent cotranslational protein targeting to membrane. DR Reactome; R-HSA-192823; Viral mRNA Translation. DR Reactome; R-HSA-72649; Translation initiation complex formation. DR Reactome; R-HSA-72689; Formation of a pool of free 40S subunits. DR Reactome; R-HSA-72695; Formation of the ternary complex, and subsequently, the 43S complex. DR Reactome; R-HSA-72702; Ribosomal scanning and start codon recognition. DR Reactome; R-HSA-72706; GTP hydrolysis and joining of the 60S ribosomal subunit. DR Reactome; R-HSA-72764; Eukaryotic Translation Termination. DR Reactome; R-HSA-975956; Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC). DR Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC). DR GeneWiki; RPS28; -. DR GenomeRNAi; 6234; -. DR NextBio; 24201; -. DR PRO; PR:P62857; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; P62857; -. DR CleanEx; HS_RPS28; -. DR ExpressionAtlas; P62857; baseline and differential. DR Genevisible; P62857; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0022627; C:cytosolic small ribosomal subunit; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0015935; C:small ribosomal subunit; IDA:UniProtKB. DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0003735; F:structural constituent of ribosome; IBA:GO_Central. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome. DR GO; GO:0042274; P:ribosomal small subunit biogenesis; IMP:UniProtKB. DR GO; GO:0042254; P:ribosome biogenesis; IMP:UniProtKB. DR GO; GO:0006407; P:rRNA export from nucleus; IBA:GO_Central. DR GO; GO:0006364; P:rRNA processing; IMP:UniProtKB. DR GO; GO:0006614; P:SRP-dependent cotranslational protein targeting to membrane; TAS:Reactome. DR GO; GO:0006412; P:translation; IC:UniProtKB. DR GO; GO:0006414; P:translational elongation; TAS:Reactome. DR GO; GO:0006413; P:translational initiation; TAS:Reactome. DR GO; GO:0006415; P:translational termination; TAS:Reactome. DR GO; GO:0019058; P:viral life cycle; TAS:Reactome. DR GO; GO:0016032; P:viral process; TAS:Reactome. DR GO; GO:0019083; P:viral transcription; TAS:Reactome. DR Gene3D; 2.40.50.140; -; 1. DR HAMAP; MF_00292; Ribosomal_S28e; 1. DR InterPro; IPR012340; NA-bd_OB-fold. DR InterPro; IPR000289; Ribosomal_S28e. DR InterPro; IPR028626; Ribosomal_S28e_CS. DR PANTHER; PTHR10769; PTHR10769; 1. DR Pfam; PF01200; Ribosomal_S28e; 1. DR ProDom; PD005541; Ribosomal_S28e; 1. DR SUPFAM; SSF50249; SSF50249; 1. DR PROSITE; PS00961; RIBOSOMAL_S28E; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Diamond-Blackfan anemia; KW Direct protein sequencing; Reference proteome; Ribonucleoprotein; KW Ribosomal protein. FT CHAIN 1 69 40S ribosomal protein S28. FT /FTId=PRO_0000136822. FT CONFLICT 66 66 R -> P (in Ref. 6; AA sequence). FT {ECO:0000305}. SQ SEQUENCE 69 AA; 7841 MW; 49902FE9376EB74F CRC64; MDTSRVQPIK LARVTKVLGR TGSQGQCTQV RVEFMDDTSR SIIRNVKGPV REGDVLTLLE SEREARRLR // ID RS29_HUMAN Reviewed; 56 AA. AC P62273; A8MZ73; P30054; DT 05-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 11-NOV-2015, entry version 115. DE RecName: Full=40S ribosomal protein S29; GN Name=RPS29; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Colon; RX PubMed=7772601; DOI=10.1016/0167-4781(95)00045-I; RA Frigerio J.-M., Dagorn J.-C., Iovanna J.L.; RT "Cloning, sequencing and expression of the L5, L21, L27a, L28, S5, S9, RT S10 and S29 human ribosomal protein mRNAs."; RL Biochim. Biophys. Acta 1262:64-68(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Colon; RX PubMed=8781548; DOI=10.1016/0167-4889(96)00052-3; RA Kondoh N., Noda M., Fisher R.J., Schweinfest C.W., Papas T.S., RA Kondoh A., Samuel K.P., Oikawa T.; RT "The S29 ribosomal protein increases tumor suppressor activity of K RT rev-1 gene on v-K ras-transformed NIH3T3 cells."; RL Biochim. Biophys. Acta 1313:41-46(1996). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). RX PubMed=11875025; DOI=10.1101/gr.214202; RA Yoshihama M., Uechi T., Asakawa S., Kawasaki K., Kato S., Higa S., RA Maeda N., Minoshima S., Tanaka T., Shimizu N., Kenmochi N.; RT "The human ribosomal protein genes: sequencing and comparative RT analysis of 73 genes."; RL Genome Res. 12:379-390(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12508121; DOI=10.1038/nature01348; RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., RA Quetier F., Waterston R., Hood L., Weissenbach J.; RT "The DNA sequence and analysis of human chromosome 14."; RL Nature 421:601-607(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Blood, Bone marrow, and Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 2-11. RC TISSUE=Placenta; RX PubMed=8706699; DOI=10.1111/j.1432-1033.1996.0144u.x; RA Vladimirov S.N., Ivanov A.V., Karpova G.G., Musolyamov A.K., RA Egorov T.A., Thiede B., Wittmann-Liebold B., Otto A.; RT "Characterization of the human small-ribosomal-subunit proteins by N- RT terminal and internal sequencing, and mass spectrometry."; RL Eur. J. Biochem. 239:144-149(1996). RN [7] RP PROTEIN SEQUENCE OF 2-12 AND 49-56, CLEAVAGE OF INITIATOR METHIONINE, RP AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Colon adenocarcinoma; RA Bienvenut W.V., Murray L., Brunton V.G., Frame M.C.; RL Submitted (FEB-2008) to UniProtKB. RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 29-54. RX PubMed=9582194; RA Kenmochi N., Kawaguchi T., Rozen S., Davis E., Goodman N., RA Hudson T.J., Tanaka T., Page D.C.; RT "A map of 75 human ribosomal protein genes."; RL Genome Res. 8:509-523(1998). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-48, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [12] RP STRUCTURE BY ELECTRON MICROSCOPY (5.0 ANGSTROMS). RX PubMed=23636399; DOI=10.1038/nature12104; RA Anger A.M., Armache J.P., Berninghausen O., Habeck M., Subklewe M., RA Wilson D.N., Beckmann R.; RT "Structures of the human and Drosophila 80S ribosome."; RL Nature 497:80-85(2013). RN [13] RP INVOLVEMENT IN DBA13, VARIANTS DBA13 PHE-31 AND THR-50, AND RP CHARACTERIZATION OF VARIANTS DBA13 PHE-31 AND THR-50. RX PubMed=24829207; DOI=10.1182/blood-2013-11-540278; RA Mirabello L., Macari E.R., Jessop L., Ellis S.R., Myers T., Giri N., RA Taylor A.M., McGrath K.E., Humphries J.M., Ballew B.J., Yeager M., RA Boland J.F., He J., Hicks B.D., Burdett L., Alter B.P., Zon L., RA Savage S.A.; RT "Whole-exome sequencing and functional studies identify RPS29 as a RT novel gene mutated in multicase Diamond-Blackfan anemia families."; RL Blood 124:24-32(2014). CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000305}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000305}; CC -!- INTERACTION: CC Q9NY93:DDX56; NbExp=1; IntAct=EBI-1054121, EBI-372376; CC O60739:EIF1B; NbExp=1; IntAct=EBI-1054121, EBI-1043343; CC Q14240:EIF4A2; NbExp=1; IntAct=EBI-1054121, EBI-73473; CC Q93063:EXT2; NbExp=1; IntAct=EBI-1054121, EBI-1047761; CC Q9Y6J8:STYXL1; NbExp=1; IntAct=EBI-1054121, EBI-1044511; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P62273-1; Sequence=Displayed; CC Name=2; CC IsoId=P62273-2; Sequence=VSP_042844; CC -!- DISEASE: Diamond-Blackfan anemia 13 (DBA13) [MIM:615909]: A form CC of Diamond-Blackfan anemia, a congenital non-regenerative CC hypoplastic anemia that usually presents early in infancy. CC Diamond-Blackfan anemia is characterized by a moderate to severe CC macrocytic anemia, erythroblastopenia, and an increased risk of CC malignancy. 30 to 40% of Diamond-Blackfan anemia patients present CC with short stature and congenital anomalies, the most frequent CC being craniofacial (Pierre-Robin syndrome and cleft palate), thumb CC and urogenital anomalies. {ECO:0000269|PubMed:24829207}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- SIMILARITY: Belongs to the ribosomal protein S14P family. CC {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U14973; AAA85661.1; -; mRNA. DR EMBL; L31610; AAB27426.1; -; mRNA. DR EMBL; AB061847; BAB79485.1; -; Genomic_DNA. DR EMBL; AL139099; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC015974; AAH15974.2; -; mRNA. DR EMBL; BC032813; AAH32813.1; -; mRNA. DR EMBL; BC035313; AAH35313.1; -; mRNA. DR EMBL; AB007165; BAA25827.1; -; Genomic_DNA. DR CCDS; CCDS32072.1; -. [P62273-2] DR CCDS; CCDS9685.1; -. [P62273-1] DR PIR; S55919; S55919. DR RefSeq; NP_001023.1; NM_001032.4. [P62273-1] DR RefSeq; NP_001025172.1; NM_001030001.2. [P62273-2] DR UniGene; Hs.156367; -. DR PDB; 4UG0; EM; -; Sd=1-56. DR PDB; 4V6X; EM; 5.00 A; Ad=1-56. DR PDB; 5A2Q; EM; 3.90 A; d=2-56. DR PDB; 5AJ0; EM; 3.50 A; Bd=1-56. DR PDBsum; 4UG0; -. DR PDBsum; 4V6X; -. DR PDBsum; 5A2Q; -. DR PDBsum; 5AJ0; -. DR ProteinModelPortal; P62273; -. DR SMR; P62273; 2-56. DR BioGrid; 112149; 51. DR IntAct; P62273; 7. DR MINT; MINT-4133209; -. DR STRING; 9606.ENSP00000379339; -. DR PhosphoSite; P62273; -. DR DMDM; 50403626; -. DR MaxQB; P62273; -. DR PaxDb; P62273; -. DR PRIDE; P62273; -. DR DNASU; 6235; -. DR Ensembl; ENST00000245458; ENSP00000245458; ENSG00000213741. [P62273-1] DR Ensembl; ENST00000396020; ENSP00000379339; ENSG00000213741. [P62273-2] DR Ensembl; ENST00000611563; ENSP00000479892; ENSG00000213741. [P62273-1] DR GeneID; 6235; -. DR KEGG; hsa:6235; -. DR UCSC; uc001wwl.4; human. [P62273-2] DR UCSC; uc001wwm.4; human. [P62273-1] DR CTD; 6235; -. DR GeneCards; RPS29; -. DR HGNC; HGNC:10419; RPS29. DR HPA; HPA004107; -. DR MIM; 603633; gene. DR MIM; 615909; phenotype. DR neXtProt; NX_P62273; -. DR Orphanet; 124; Blackfan-Diamond anemia. DR PharmGKB; PA34826; -. DR eggNOG; KOG3506; Eukaryota. DR eggNOG; COG0199; LUCA. DR GeneTree; ENSGT00390000005814; -. DR HOVERGEN; HBG004459; -. DR InParanoid; P62273; -. DR KO; K02980; -. DR OMA; CFREKAA; -. DR OrthoDB; EOG78D7P4; -. DR PhylomeDB; P62273; -. DR TreeFam; TF300217; -. DR Reactome; R-HSA-156827; L13a-mediated translational silencing of Ceruloplasmin expression. DR Reactome; R-HSA-156902; Peptide chain elongation. DR Reactome; R-HSA-1799339; SRP-dependent cotranslational protein targeting to membrane. DR Reactome; R-HSA-192823; Viral mRNA Translation. DR Reactome; R-HSA-72649; Translation initiation complex formation. DR Reactome; R-HSA-72689; Formation of a pool of free 40S subunits. DR Reactome; R-HSA-72695; Formation of the ternary complex, and subsequently, the 43S complex. DR Reactome; R-HSA-72702; Ribosomal scanning and start codon recognition. DR Reactome; R-HSA-72706; GTP hydrolysis and joining of the 60S ribosomal subunit. DR Reactome; R-HSA-72764; Eukaryotic Translation Termination. DR Reactome; R-HSA-975956; Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC). DR Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC). DR GeneWiki; RPS29; -. DR GenomeRNAi; 6235; -. DR NextBio; 24205; -. DR PRO; PR:P62273; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; P62273; -. DR CleanEx; HS_RPS29; -. DR ExpressionAtlas; P62273; baseline and differential. DR Genevisible; P62273; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0022627; C:cytosolic small ribosomal subunit; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0015935; C:small ribosomal subunit; IDA:UniProtKB. DR GO; GO:0003735; F:structural constituent of ribosome; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome. DR GO; GO:0006614; P:SRP-dependent cotranslational protein targeting to membrane; TAS:Reactome. DR GO; GO:0006412; P:translation; IC:UniProtKB. DR GO; GO:0006414; P:translational elongation; TAS:Reactome. DR GO; GO:0006413; P:translational initiation; TAS:Reactome. DR GO; GO:0006415; P:translational termination; TAS:Reactome. DR GO; GO:0019058; P:viral life cycle; TAS:Reactome. DR GO; GO:0016032; P:viral process; TAS:Reactome. DR GO; GO:0019083; P:viral transcription; TAS:Reactome. DR InterPro; IPR001209; Ribosomal_S14. DR InterPro; IPR018271; Ribosomal_S14_CS. DR Pfam; PF00253; Ribosomal_S14; 1. DR PROSITE; PS00527; RIBOSOMAL_S14; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Complete proteome; KW Diamond-Blackfan anemia; Direct protein sequencing; Disease mutation; KW Metal-binding; Reference proteome; Ribonucleoprotein; KW Ribosomal protein; Zinc. FT INIT_MET 1 1 Removed. {ECO:0000269|PubMed:8706699, FT ECO:0000269|Ref.7}. FT CHAIN 2 56 40S ribosomal protein S29. FT /FTId=PRO_0000131019. FT METAL 21 21 Zinc. {ECO:0000255}. FT METAL 24 24 Zinc. {ECO:0000255}. FT METAL 39 39 Zinc. {ECO:0000255}. FT METAL 42 42 Zinc. {ECO:0000255}. FT MOD_RES 48 48 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT VAR_SEQ 54 56 KLD -> KKDLSCLPWHCLWR (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_042844. FT VARIANT 31 31 I -> F (in DBA13; results in reduced FT protein expression; results in pre-rRNA FT processing defect). FT {ECO:0000269|PubMed:24829207}. FT /FTId=VAR_071328. FT VARIANT 50 50 I -> T (in DBA13; results in reduced FT protein expression; results in pre-rRNA FT processing defect). FT {ECO:0000269|PubMed:24829207}. FT /FTId=VAR_071329. SQ SEQUENCE 56 AA; 6677 MW; 41325122B493EFF9 CRC64; MGHQQLYWSH PRKFGQGSRS CRVCSNRHGL IRKYGLNMCR QCFRQYAKDI GFIKLD // ID RS4X_HUMAN Reviewed; 263 AA. AC P62701; P12631; P12750; P27576; P55831; Q14727; Q6IPY4; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 11-NOV-2015, entry version 120. DE RecName: Full=40S ribosomal protein S4, X isoform; DE AltName: Full=SCR10; DE AltName: Full=Single copy abundant mRNA protein; GN Name=RPS4X; Synonyms=CCG2, RPS4, SCAR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2124517; DOI=10.1016/0092-8674(90)90416-C; RA Fisher E.M.C., Beer-Romero P., Brown L.G., Ridley A., McNeil J.A., RA Lawrence J.B., Willard H.F., Bieber F.R., Page D.C.; RT "Homologous ribosomal protein genes on the human X and Y chromosomes: RT escape from X inactivation and possible implications for Turner RT syndrome."; RL Cell 63:1205-1218(1990). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=1795030; RA Watanabe M., Furuno N., Goebl M., Go M., Miyauchi K., Sekiguchi T., RA Basilico C., Nishimoto T.; RT "Molecular cloning of the human gene, CCG2, that complements the BHK- RT derived temperature-sensitive cell cycle mutant tsBN63: identity of RT CCG2 with the human X chromosomal SCAR/RPS4X gene."; RL J. Cell Sci. 100:35-43(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Zuo L., Baybayan P., Kuang W.-J., Brown L., Page D., Chen E.; RL Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Muscle; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-59. RC TISSUE=Brain; RA Dmitrenko V.V., Garifulin O.M., Kavsan V.M.; RT "Characterization of different mRNA types expressed in human brain."; RL Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases. RN [7] RP PROTEIN SEQUENCE OF 2-11. RC TISSUE=Placenta; RX PubMed=8706699; DOI=10.1111/j.1432-1033.1996.0144u.x; RA Vladimirov S.N., Ivanov A.V., Karpova G.G., Musolyamov A.K., RA Egorov T.A., Thiede B., Wittmann-Liebold B., Otto A.; RT "Characterization of the human small-ribosomal-subunit proteins by N- RT terminal and internal sequencing, and mass spectrometry."; RL Eur. J. Biochem. 239:144-149(1996). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 19-263. RX PubMed=2829364; DOI=10.1007/BF01535047; RA Wiles M.V., Alexander C.M., Goodfellow P.N.; RT "Isolation of an abundantly expressed sequence from the human X RT chromosome by differential screening."; RL Somat. Cell Mol. Genet. 14:31-39(1988). RN [9] RP IDENTIFICATION IN A MRNP GRANULE COMPLEX, IDENTIFICATION BY MASS RP SPECTROMETRY, AND SUBCELLULAR LOCATION. RX PubMed=17289661; DOI=10.1074/mcp.M600346-MCP200; RA Joeson L., Vikesaa J., Krogh A., Nielsen L.K., Hansen T., Borup R., RA Johnsen A.H., Christiansen J., Nielsen F.C.; RT "Molecular composition of IMP1 ribonucleoprotein granules."; RL Mol. Cell. Proteomics 6:798-811(2007). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [13] RP STRUCTURE BY ELECTRON MICROSCOPY (5.0 ANGSTROMS). RX PubMed=23636399; DOI=10.1038/nature12104; RA Anger A.M., Armache J.P., Berninghausen O., Habeck M., Subklewe M., RA Wilson D.N., Beckmann R.; RT "Structures of the human and Drosophila 80S ribosome."; RL Nature 497:80-85(2013). CC -!- SUBUNIT: Identified in a IGF2BP1-dependent mRNP granule complex CC containing untranslated mRNAs. {ECO:0000269|PubMed:17289661}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17289661}. CC Note=Localized in cytoplasmic mRNP granules containing CC untranslated mRNAs. CC -!- SIMILARITY: Belongs to the ribosomal protein S4e family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 S4 RNA-binding domain. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M58458; AAA63255.1; -; mRNA. DR EMBL; AF041428; AAB96968.1; -; Genomic_DNA. DR EMBL; CR456735; CAG33016.1; -; mRNA. DR EMBL; BC000472; AAH00472.1; -; mRNA. DR EMBL; BC071662; AAH71662.1; -; mRNA. DR EMBL; BC100903; AAI00904.1; -; mRNA. DR EMBL; BC100904; AAI00905.1; -; mRNA. DR EMBL; Z70767; CAA94808.1; -; mRNA. DR EMBL; M22146; AAA36597.1; -; mRNA. DR CCDS; CCDS14418.1; -. DR PIR; B36338; R3HU4X. DR RefSeq; NP_000998.1; NM_001007.4. DR UniGene; Hs.118076; -. DR PDB; 4UG0; EM; -; SE=1-263. DR PDB; 4V6X; EM; 5.00 A; AE=1-263. DR PDB; 5A2Q; EM; 3.90 A; E=1-263. DR PDBsum; 4UG0; -. DR PDBsum; 4V6X; -. DR PDBsum; 5A2Q; -. DR ProteinModelPortal; P62701; -. DR SMR; P62701; 2-263. DR BioGrid; 112105; 174. DR IntAct; P62701; 28. DR MINT; MINT-1159032; -. DR STRING; 9606.ENSP00000362744; -. DR PhosphoSite; P62701; -. DR BioMuta; RPS4X; -. DR DMDM; 50403628; -. DR SWISS-2DPAGE; P62701; -. DR MaxQB; P62701; -. DR PaxDb; P62701; -. DR PeptideAtlas; P62701; -. DR PRIDE; P62701; -. DR DNASU; 6191; -. DR Ensembl; ENST00000316084; ENSP00000362744; ENSG00000198034. DR GeneID; 6191; -. DR KEGG; hsa:6191; -. DR UCSC; uc004ear.3; human. DR CTD; 6191; -. DR GeneCards; RPS4X; -. DR HGNC; HGNC:10424; RPS4X. DR HPA; HPA000857; -. DR MIM; 312760; gene. DR neXtProt; NX_P62701; -. DR PharmGKB; PA34839; -. DR eggNOG; KOG0378; Eukaryota. DR eggNOG; COG1471; LUCA. DR GeneTree; ENSGT00390000005569; -. DR HOVERGEN; HBG000935; -. DR InParanoid; P62701; -. DR KO; K02987; -. DR OMA; HIQLNLH; -. DR OrthoDB; EOG77WWD1; -. DR PhylomeDB; P62701; -. DR TreeFam; TF300612; -. DR Reactome; R-HSA-156827; L13a-mediated translational silencing of Ceruloplasmin expression. DR Reactome; R-HSA-156902; Peptide chain elongation. DR Reactome; R-HSA-1799339; SRP-dependent cotranslational protein targeting to membrane. DR Reactome; R-HSA-192823; Viral mRNA Translation. DR Reactome; R-HSA-72649; Translation initiation complex formation. DR Reactome; R-HSA-72689; Formation of a pool of free 40S subunits. DR Reactome; R-HSA-72695; Formation of the ternary complex, and subsequently, the 43S complex. DR Reactome; R-HSA-72702; Ribosomal scanning and start codon recognition. DR Reactome; R-HSA-72706; GTP hydrolysis and joining of the 60S ribosomal subunit. DR Reactome; R-HSA-72764; Eukaryotic Translation Termination. DR Reactome; R-HSA-975956; Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC). DR Reactome; R-HSA-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC). DR ChiTaRS; RPS4X; human. DR GeneWiki; RPS4X; -. DR GenomeRNAi; 6191; -. DR NextBio; 24041; -. DR PMAP-CutDB; P62701; -. DR PRO; PR:P62701; -. DR Proteomes; UP000005640; Chromosome X. DR Bgee; P62701; -. DR CleanEx; HS_RPS4X; -. DR ExpressionAtlas; P62701; baseline and differential. DR Genevisible; P62701; HS. DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:ParkinsonsUK-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0022627; C:cytosolic small ribosomal subunit; IDA:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005844; C:polysome; IDA:UniProtKB. DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:UniProtKB. DR GO; GO:0005840; C:ribosome; IDA:UniProtKB. DR GO; GO:0015935; C:small ribosomal subunit; IDA:MGI. DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0019843; F:rRNA binding; IEA:UniProtKB-KW. DR GO; GO:0003735; F:structural constituent of ribosome; IMP:UniProtKB. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0007275; P:multicellular organismal development; IMP:UniProtKB. DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; TAS:Reactome. DR GO; GO:0008284; P:positive regulation of cell proliferation; IMP:UniProtKB. DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB. DR GO; GO:0006614; P:SRP-dependent cotranslational protein targeting to membrane; TAS:Reactome. DR GO; GO:0006412; P:translation; IMP:UniProtKB. DR GO; GO:0006414; P:translational elongation; TAS:Reactome. DR GO; GO:0006413; P:translational initiation; TAS:Reactome. DR GO; GO:0006415; P:translational termination; TAS:Reactome. DR GO; GO:0019058; P:viral life cycle; TAS:Reactome. DR GO; GO:0016032; P:viral process; TAS:Reactome. DR GO; GO:0019083; P:viral transcription; TAS:Reactome. DR HAMAP; MF_00485; Ribosomal_S4e; 1. DR InterPro; IPR032277; 40S_S4_C. DR InterPro; IPR005824; KOW. DR InterPro; IPR000876; Ribosomal_S4e. DR InterPro; IPR013845; Ribosomal_S4e_central_region. DR InterPro; IPR013843; Ribosomal_S4e_N. DR InterPro; IPR018199; Ribosomal_S4e_N_CS. DR InterPro; IPR002942; S4_RNA-bd. DR PANTHER; PTHR11581; PTHR11581; 1. DR Pfam; PF16121; 40S_S4_C; 1. DR Pfam; PF00467; KOW; 1. DR Pfam; PF00900; Ribosomal_S4e; 1. DR Pfam; PF08071; RS4NT; 1. DR Pfam; PF01479; S4; 1. DR PIRSF; PIRSF002116; Ribosomal_S4; 1. DR ProDom; PD002667; Ribosomal_S4e_central; 1. DR SMART; SM00363; S4; 1. DR PROSITE; PS00528; RIBOSOMAL_S4E; 1. DR PROSITE; PS50889; S4; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; Cytoplasm; Direct protein sequencing; KW Reference proteome; Ribonucleoprotein; Ribosomal protein; RNA-binding; KW rRNA-binding. FT INIT_MET 1 1 Removed. {ECO:0000269|PubMed:8706699}. FT CHAIN 2 263 40S ribosomal protein S4, X isoform. FT /FTId=PRO_0000130805. FT DOMAIN 42 104 S4 RNA-binding. FT CONFLICT 33 33 Missing (in Ref. 8; AAA36597). FT {ECO:0000305}. FT CONFLICT 57 59 TGD -> DRR (in Ref. 6; CAA94808). FT {ECO:0000305}. SQ SEQUENCE 263 AA; 29598 MW; 87200E545A8958B0 CRC64; MARGPKKHLK RVAAPKHWML DKLTGVFAPR PSTGPHKLRE CLPLIIFLRN RLKYALTGDE VKKICMQRFI KIDGKVRTDI TYPAGFMDVI SIDKTGENFR LIYDTKGRFA VHRITPEEAK YKLCKVRKIF VGTKGIPHLV THDARTIRYP DPLIKVNDTI QIDLETGKIT DFIKFDTGNL CMVTGGANLG RIGVITNRER HPGSFDVVHV KDANGNSFAT RLSNIFVIGK GNKPWISLPR GKGIRLTIAE ERDKRLAAKQ SSG // ID SOBP_HUMAN Reviewed; 873 AA. AC A7XYQ1; B0QZ12; Q5BJD4; Q8N2B2; DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot. DT 23-SEP-2008, sequence version 2. DT 11-NOV-2015, entry version 67. DE RecName: Full=Sine oculis-binding protein homolog; DE AltName: Full=Jackson circler protein 1; GN Name=SOBP {ECO:0000312|EMBL:AAH91526.2}; GN Synonyms=JXC1 {ECO:0000312|EMBL:ABF72848.1}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] {ECO:0000312|EMBL:ABF72848.1} RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLY-683. RA Chen Z., Noben-Trauth K.; RT "Mutations in Jxc1 cause deafness, vestibular deficits and cochlear RT malformation in the Jackson circler (jc) mutant mouse."; RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases. RN [2] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [3] {ECO:0000312|EMBL:BAC03537.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-224. RC TISSUE=Amygdala {ECO:0000312|EMBL:BAC03537.1}; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] {ECO:0000312|EMBL:AAH91526.2} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-140. RC TISSUE=Brain {ECO:0000312|EMBL:AAH91526.2}; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP INVOLVEMENT IN MRAMS. RX PubMed=21035105; DOI=10.1016/j.ajhg.2010.10.005; RA Birk E., Har-Zahav A., Manzini C.M., Pasmanik-Chor M., Kornreich L., RA Walsh C.A., Noben-Trauth K., Albin A., Simon A.J., Colleaux L., RA Morad Y., Rainshtein L., Tischfield D.J., Wang P., Magal N., Maya I., RA Shoshani N., Rechavi G., Gothelf D., Maydan G., Shohat M., RA Basel-Vanagaite L.; RT "SOBP is mutated in syndromic and nonsyndromic intellectual disability RT and is highly expressed in the brain limbic system."; RL Am. J. Hum. Genet. 87:694-700(2010). RN [6] RP IDENTIFICATION OF REPEAT SUMO-INTERACTING MOTIF, AND INTERACTION WITH RP SUMO1 AND SUMO2. RX PubMed=23086935; DOI=10.1074/jbc.M112.410985; RA Sun H., Hunter T.; RT "PolySUMO-binding proteins identified through a string search."; RL J. Biol. Chem. 287:42071-42083(2012). CC -!- FUNCTION: Implicated in development of the cochlea. CC {ECO:0000250|UniProtKB:Q0P5V2}. CC -!- SUBUNIT: Interacts (via SIM domains) with SUMO1 and SUMO2. CC {ECO:0000269|PubMed:23086935}. CC -!- DISEASE: Mental retardation, anterior maxillary protrusion, and CC strabismus (MRAMS) [MIM:613671]: A syndrome characterized by CC severe mental retardation, strabismus and dysmorphic features such CC as anterior maxillary protrusion with vertical maxillary excess, CC open bite and prominent crowded teeth. Some patients may lack CC dysmorphic features and manifest temporal lobe epilepsy and CC psychosis. Esotropia and amblyopia are present in some CC individuals. {ECO:0000269|PubMed:21035105}. Note=The disease is CC caused by mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the SOBP family. {ECO:0000255}. CC -!- SIMILARITY: Contains 2 FCS-type zinc fingers. {ECO:0000255}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH91526.2; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; CC Sequence=BAC03537.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; DQ507800; ABF72848.1; -; mRNA. DR EMBL; AL096816; CAQ08124.1; -; Genomic_DNA. DR EMBL; AL121957; CAQ08124.1; JOINED; Genomic_DNA. DR EMBL; AL671934; CAQ08124.1; JOINED; Genomic_DNA. DR EMBL; AL671934; CAQ10205.1; -; Genomic_DNA. DR EMBL; AL096816; CAQ10205.1; JOINED; Genomic_DNA. DR EMBL; AL121957; CAQ10205.1; JOINED; Genomic_DNA. DR EMBL; AL121957; CAQ10380.1; -; Genomic_DNA. DR EMBL; AL096816; CAQ10380.1; JOINED; Genomic_DNA. DR EMBL; AL671934; CAQ10380.1; JOINED; Genomic_DNA. DR EMBL; AK090879; BAC03537.1; ALT_SEQ; mRNA. DR EMBL; BC091526; AAH91526.2; ALT_SEQ; mRNA. DR CCDS; CCDS43488.1; -. DR RefSeq; NP_060483.3; NM_018013.3. DR UniGene; Hs.445244; -. DR ProteinModelPortal; A7XYQ1; -. DR BioGrid; 120399; 3. DR IntAct; A7XYQ1; 2. DR MINT; MINT-6778579; -. DR STRING; 9606.ENSP00000318900; -. DR PhosphoSite; A7XYQ1; -. DR BioMuta; SOBP; -. DR MaxQB; A7XYQ1; -. DR PaxDb; A7XYQ1; -. DR PRIDE; A7XYQ1; -. DR Ensembl; ENST00000317357; ENSP00000318900; ENSG00000112320. DR GeneID; 55084; -. DR KEGG; hsa:55084; -. DR UCSC; uc003prx.3; human. DR CTD; 55084; -. DR GeneCards; SOBP; -. DR H-InvDB; HIX0006109; -. DR HGNC; HGNC:29256; SOBP. DR HPA; HPA029242; -. DR MIM; 613667; gene. DR MIM; 613671; phenotype. DR neXtProt; NX_A7XYQ1; -. DR PharmGKB; PA162404346; -. DR eggNOG; ENOG410IEAE; Eukaryota. DR eggNOG; ENOG4111QQS; LUCA. DR GeneTree; ENSGT00730000111043; -. DR HOGENOM; HOG000008673; -. DR HOVERGEN; HBG062766; -. DR InParanoid; A7XYQ1; -. DR OMA; EHGRSEV; -. DR OrthoDB; EOG7F7W8D; -. DR PhylomeDB; A7XYQ1; -. DR TreeFam; TF324359; -. DR ChiTaRS; SOBP; human. DR GeneWiki; Sobp; -. DR GenomeRNAi; 55084; -. DR NextBio; 58645; -. DR PRO; PR:A7XYQ1; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; A7XYQ1; -. DR CleanEx; HS_SOBP; -. DR ExpressionAtlas; A7XYQ1; baseline and differential. DR Genevisible; A7XYQ1; HS. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0050890; P:cognition; IMP:HGNC. DR GO; GO:0042472; P:inner ear morphogenesis; IEA:Ensembl. DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl. DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl. DR InterPro; IPR026092; RAI2/SOBP. DR PANTHER; PTHR23186; PTHR23186; 2. DR Pfam; PF15279; SOBP; 1. PE 1: Evidence at protein level; KW Complete proteome; Mental retardation; Metal-binding; Phosphoprotein; KW Polymorphism; Reference proteome; Repeat; Zinc; Zinc-finger. FT CHAIN 1 873 Sine oculis-binding protein homolog. FT /FTId=PRO_0000312232. FT ZN_FING 142 180 FCS-type 1. {ECO:0000255}. FT ZN_FING 216 256 FCS-type 2. {ECO:0000255}. FT MOTIF 620 624 SUMO interaction motif 1 (SIM); mediates FT the binding to polysumoylated substrates. FT MOTIF 653 657 SUMO interaction motif 2 (SIM); mediates FT the binding to polysumoylated substrates. FT COMPBIAS 346 552 Pro-rich. {ECO:0000255}. FT COMPBIAS 740 763 Pro-rich. {ECO:0000255}. FT MOD_RES 629 629 Phosphoserine. FT {ECO:0000250|UniProtKB:Q0P5V2}. FT MOD_RES 699 699 Phosphoserine. FT {ECO:0000250|UniProtKB:Q0P5V2}. FT VARIANT 683 683 S -> G (in dbSNP:rs9486659). FT {ECO:0000269|Ref.1}. FT /FTId=VAR_062215. FT CONFLICT 623 623 L -> M (in Ref. 1; ABF72848). FT {ECO:0000305}. FT CONFLICT 646 646 L -> M (in Ref. 1; ABF72848). FT {ECO:0000305}. SQ SEQUENCE 873 AA; 92658 MW; 894DEF718F6E0CB0 CRC64; MAEMEKEGRP PENKRSRKPA HPVKREINEE MKNFAENTMN ELLGWYGYDK VELKDGEDIE FRSYPTDGES RQHISVLKEN SLPKPKLPED SVISPYNIST GYSGLATGNG LSDSPAGSKD HGSVPIIVPL IPPPFIKPPA EDDVSNVQIM CAWCQKVGIK RYSLSMGSEV KSFCSEKCFA ACRRAYFKRN KARDEDGHAE NFPQQHYAKE TPRLAFKNNC ELLVCDWCKH IRHTKEYLDF GDGERRLQFC SAKCLNQYKM DIFYKETQAN LPAGLCSTLH PPMENKAEGT GVQLLTPDSW NIPLTDARRK APSPVATAGQ SQGPGPSAST TVSPSDTANC SVTKIPTPVP KSIPISETPN IPPVSVQPPA SIGPPLGVPP RSPPMVMTNR GPVPLPIFME QQIMQQIRPP FIRGPPHHAS NPNSPLSNPM LPGIGPPPGG PRNLGPTSSP MHRPMLSPHI HPPSTPTMPG NPPGLLPPPP PGAPLPSLPF PPVSMMPNGP MPVPQMMNFG LPSLAPLVPP PTLLVPYPVI VPLPVPIPIP IPIPHVSDSK PPNGFSSNGE NFIPNAPGDS AAAGGKPSGH SLSPRDSKQG SSKSADSPPG CSGQALSLAP TPAEHGRSEV VDLTRRAGSP PGPPGAGGQL GFPGVLQGPQ DGVIDLTVGH RARLHNVIHR ALHAHVKAER EPSAAERRTC GGCRDGHCSP PAAGDPGPGA PAGPEAAAAC NVIVNGTRGA AAEGAKSAEP PPEQPPPPPP PAPPKKLLSP EEPAVSELES VKENNCASNC HLDGEAAKKL MGEEALAGGD KSDPNLNNPA DEDHAYALRM LPKTGCVIQP VPKPAEKAAM APCIISSPML SAGPEDLEPP LKRRCLRIRN QNK // ID SOX13_HUMAN Reviewed; 622 AA. AC Q9UN79; B4E2B0; O95275; O95826; Q3KQV7; Q5SXX1; Q9UHW7; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 09-FEB-2010, sequence version 3. DT 11-NOV-2015, entry version 141. DE RecName: Full=Transcription factor SOX-13; DE AltName: Full=Islet cell antigen 12; DE AltName: Full=SRY (Sex determining region Y)-box 13; DE AltName: Full=Type 1 diabetes autoantigen ICA12; GN Name=SOX13; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Kidney; RX PubMed=9421502; DOI=10.1093/nar/26.2.469; RA Roose J., Korver W., Oving E., Wilson A., Wagenaar G., Markman M., RA Lamers W., Clevers H.; RT "High expression of the HMG box factor sox-13 in arterial walls during RT embryonic development."; RL Nucleic Acids Res. 26:469-476(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Pancreatic islet; RA LaGasse J.M., Gleason S., Rabin D.U., Michaels D., Kletter G., RA Pihoker K., Mahoney P., Valle T., Nguyen C., Hagopian W.A.; RT "ICA12: a novel autoantigen in type I diabetes."; RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Pancreas, and Placenta; RA Kasimiotis H., Myers M.A., Mertin S., Argentaro A., Fida S., Ferro T., RA Olsson J.E., Rowley M.J., Harley V.R.; RT "SOX13 encodes an autoimmune antigen in type 1 diabetes."; RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Argentaro A., Olsson J., Critcher R., McDowall S.G., Harley V.R.; RT "Genomic structure and precise chromosomal localization of human RT SOX13."; RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Trachea; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-335 AND SER-382, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-386, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-386 AND SER-613, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). CC -!- FUNCTION: Binds to the sequence 5'-AACAAT-3'. {ECO:0000250}. CC -!- INTERACTION: CC P56545:CTBP2; NbExp=2; IntAct=EBI-3928516, EBI-741533; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE- CC ProRule:PRU00267}. CC -!- TISSUE SPECIFICITY: Highly expressed in kidney, lung, and liver CC and low expression in thymus, brain, spleen, and muscle. CC -!- SIMILARITY: Contains 1 HMG box DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00267}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC83687.1; Type=Miscellaneous discrepancy; Note=Several frameshifts.; Evidence={ECO:0000305}; CC Sequence=AAF23875.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAG65072.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAI16596.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF083105; AAC83687.1; ALT_SEQ; mRNA. DR EMBL; AF098915; AAD16237.1; -; mRNA. DR EMBL; AF116571; AAF23875.1; ALT_INIT; mRNA. DR EMBL; AK304192; BAG65072.1; ALT_INIT; mRNA. DR EMBL; AF149301; AAD50120.1; -; Genomic_DNA. DR EMBL; AL592146; CAI16596.1; ALT_INIT; Genomic_DNA. DR EMBL; CH471067; EAW91500.1; -; Genomic_DNA. DR EMBL; BC106038; AAI06039.1; -; mRNA. DR CCDS; CCDS44299.1; -. DR RefSeq; NP_005677.2; NM_005686.2. DR UniGene; Hs.201671; -. DR ProteinModelPortal; Q9UN79; -. DR SMR; Q9UN79; 423-491. DR BioGrid; 114948; 7. DR IntAct; Q9UN79; 3. DR MINT; MINT-1179847; -. DR STRING; 9606.ENSP00000356172; -. DR PhosphoSite; Q9UN79; -. DR BioMuta; SOX13; -. DR DMDM; 288558840; -. DR MaxQB; Q9UN79; -. DR PaxDb; Q9UN79; -. DR PRIDE; Q9UN79; -. DR DNASU; 9580; -. DR Ensembl; ENST00000367204; ENSP00000356172; ENSG00000143842. DR Ensembl; ENST00000618875; ENSP00000478239; ENSG00000143842. DR GeneID; 9580; -. DR KEGG; hsa:9580; -. DR UCSC; uc001ham.3; human. DR CTD; 9580; -. DR GeneCards; SOX13; -. DR HGNC; HGNC:11192; SOX13. DR MIM; 604748; gene. DR neXtProt; NX_Q9UN79; -. DR PharmGKB; PA36029; -. DR eggNOG; KOG0528; Eukaryota. DR eggNOG; ENOG410YZNG; LUCA. DR GeneTree; ENSGT00760000119274; -. DR HOVERGEN; HBG003915; -. DR InParanoid; Q9UN79; -. DR KO; K09269; -. DR OMA; CDVDGSR; -. DR OrthoDB; EOG7R56S9; -. DR PhylomeDB; Q9UN79; -. DR TreeFam; TF320471; -. DR Reactome; R-HSA-3769402; deactivation of the beta-catenin transactivating complex. DR SignaLink; Q9UN79; -. DR ChiTaRS; SOX13; human. DR GeneWiki; SOX13; -. DR GenomeRNAi; 9580; -. DR NextBio; 35933; -. DR PRO; PR:Q9UN79; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; Q9UN79; -. DR CleanEx; HS_SOX13; -. DR ExpressionAtlas; Q9UN79; baseline and differential. DR Genevisible; Q9UN79; HS. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc. DR GO; GO:0045586; P:regulation of gamma-delta T cell differentiation; IEA:Ensembl. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 1.10.30.10; -; 1. DR InterPro; IPR009071; HMG_box_dom. DR InterPro; IPR029547; SOX-13. DR PANTHER; PTHR10270:SF233; PTHR10270:SF233; 1. DR Pfam; PF00505; HMG_box; 1. DR SMART; SM00398; HMG; 1. DR SUPFAM; SSF47095; SSF47095; 1. DR PROSITE; PS50118; HMG_BOX_2; 1. PE 1: Evidence at protein level; KW Complete proteome; DNA-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Transcription; Transcription regulation. FT CHAIN 1 622 Transcription factor SOX-13. FT /FTId=PRO_0000048756. FT DNA_BIND 424 492 HMG box. {ECO:0000255|PROSITE- FT ProRule:PRU00267}. FT COMPBIAS 184 221 Gln-rich. FT COMPBIAS 225 340 Pro-rich. FT MOD_RES 335 335 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 382 382 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 386 386 Phosphoserine. FT {ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 613 613 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT VARIANT 532 532 P -> S (in dbSNP:rs34758764). FT /FTId=VAR_062671. FT CONFLICT 91 91 V -> A (in Ref. 2; AAD16237). FT {ECO:0000305}. FT CONFLICT 259 259 V -> G (in Ref. 4; AAD50120). FT {ECO:0000305}. FT CONFLICT 270 270 P -> L (in Ref. 4; AAD50120). FT {ECO:0000305}. FT CONFLICT 491 491 Y -> C (in Ref. 4; AAD50120). FT {ECO:0000305}. FT CONFLICT 515 515 A -> G (in Ref. 4; AAD50120). FT {ECO:0000305}. SQ SEQUENCE 622 AA; 69228 MW; F8C102AF63128C06 CRC64; MSMRSPISAQ LALDGVGTMV NCTIKSEEKK EPCHEAPQGS ATAAEPQPGD PARASQDSAD PQAPAQGNFR GSWDCSSPEG NGSPEPKRPG VSEAASGSQE KLDFNRNLKE VVPAIEKLLS SDWKERFLGR NSMEAKDVKG TQESLAEKEL QLLVMIHQLS TLRDQLLTAH SEQKNMAAML FEKQQQQMEL ARQQQEQIAK QQQQLIQQQH KINLLQQQIQ QVNMPYVMIP AFPPSHQPLP VTPDSQLALP IQPIPCKPVE YPLQLLHSPP APVVKRPGAM ATHHPLQEPS QPLNLTAKPK APELPNTSSS PSLKMSSCVP RPPSHGGPTR DLQSSPPSLP LGFLGEGDAV TKAIQDARQL LHSHSGALDG SPNTPFRKDL ISLDSSPAKE RLEDGCVHPL EEAMLSCDMD GSRHFPESRN SSHIKRPMNA FMVWAKDERR KILQAFPDMH NSSISKILGS RWKSMTNQEK QPYYEEQARL SRQHLEKYPD YKYKPRPKRT CIVEGKRLRV GEYKALMRTR RQDARQSYVI PPQAGQVQMS SSDVLYPRAA GMPLAQPLVE HYVPRSLDPN MPVIVNTCSL REEGEGTDDR HSVADGEMYR YSEDEDSEGE EKSDGELVVL TD // ID STX11_HUMAN Reviewed; 287 AA. AC O75558; E1P598; O75378; O95148; Q5TCL6; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1998, sequence version 1. DT 11-NOV-2015, entry version 136. DE RecName: Full=Syntaxin-11; GN Name=STX11; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9571206; DOI=10.1006/bbrc.1998.8490; RA Tang B.L., Low D.Y.H., Hong W.; RT "Syntaxin 11: a member of the syntaxin family without a carboxyl RT terminal transmembrane domain."; RL Biochem. Biophys. Res. Commun. 245:627-632(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9553086; DOI=10.1074/jbc.273.17.10317; RA Advani R.J., Bae H.-R., Bock J.B., Chao D.S., Doung Y.-C., RA Prekeris R., Yoo J.-S., Scheller R.H.; RT "Seven novel mammalian SNARE proteins localize to distinct membrane RT compartments."; RL J. Biol. Chem. 273:10317-10324(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RX PubMed=10036234; RA Valdez A.C., Cabaniols J.-P., Brown M.J., Roche P.A.; RT "Syntaxin 11 is associated with SNAP-23 on late endosomes and the RT trans-Golgi network."; RL J. Cell Sci. 112:845-854(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP INVOLVEMENT IN FHL4. RX PubMed=15703195; DOI=10.1093/hmg/ddi076; RA zur Stadt U., Schmidt S., Kasper B., Beutel K., Diler A.S., RA Henter J.-I., Kabisch H., Schneppenheim R., Nuernberg P., Janka G., RA Hennies H.C.; RT "Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type-4 RT to chromosome 6q24 and identification of mutations in syntaxin 11."; RL Hum. Mol. Genet. 14:827-834(2005). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). CC -!- FUNCTION: SNARE that acts to regulate protein transport between CC late endosomes and the trans-Golgi network. CC -!- SUBUNIT: Interacts with the SNARE proteins SNAP-23 and VAMP. CC -!- INTERACTION: CC A8KAD6:-; NbExp=3; IntAct=EBI-714135, EBI-10174974; CC Q08117:AES; NbExp=3; IntAct=EBI-714135, EBI-717810; CC Q9UL45:BLOC1S6; NbExp=3; IntAct=EBI-714135, EBI-465781; CC Q13895:BYSL; NbExp=5; IntAct=EBI-714135, EBI-358049; CC Q9NX04:C1orf109; NbExp=3; IntAct=EBI-714135, EBI-8643161; CC Q9H257:CARD9; NbExp=3; IntAct=EBI-714135, EBI-751319; CC Q6UXH8:CCBE1; NbExp=3; IntAct=EBI-714135, EBI-3923278; CC Q52MB2:CCDC184; NbExp=3; IntAct=EBI-714135, EBI-10179526; CC Q96GN5:CDCA7L; NbExp=3; IntAct=EBI-714135, EBI-5278764; CC Q8N9N8:EIF1AD; NbExp=3; IntAct=EBI-714135, EBI-750700; CC Q9BQ89:FAM110A; NbExp=3; IntAct=EBI-714135, EBI-1752811; CC Q3B820:FAM161A; NbExp=3; IntAct=EBI-714135, EBI-719941; CC Q5TZK3:FAM74A6; NbExp=3; IntAct=EBI-714135, EBI-10247271; CC Q86YD7:FAM90A1; NbExp=3; IntAct=EBI-714135, EBI-6658203; CC O95363:FARS2; NbExp=3; IntAct=EBI-714135, EBI-2513774; CC Q0D2H9:GOLGA8DP; NbExp=3; IntAct=EBI-714135, EBI-10181276; CC Q08AF8:GOLGA8G; NbExp=3; IntAct=EBI-714135, EBI-10181260; CC Q96CS2:HAUS1; NbExp=3; IntAct=EBI-714135, EBI-2514791; CC Q9UKT9:IKZF3; NbExp=3; IntAct=EBI-714135, EBI-747204; CC Q92993:KAT5; NbExp=3; IntAct=EBI-714135, EBI-399080; CC Q7L273:KCTD9; NbExp=3; IntAct=EBI-714135, EBI-4397613; CC Q6P597:KLC3; NbExp=3; IntAct=EBI-714135, EBI-1643885; CC Q96BZ8:LENG1; NbExp=3; IntAct=EBI-714135, EBI-726510; CC Q17RB8:LONRF1; NbExp=3; IntAct=EBI-714135, EBI-2341787; CC Q9NS73-5:MBIP; NbExp=3; IntAct=EBI-714135, EBI-10182361; CC A4D127:MEOX2; NbExp=3; IntAct=EBI-714135, EBI-10172134; CC P55081:MFAP1; NbExp=3; IntAct=EBI-714135, EBI-1048159; CC Q9UJV3-2:MID2; NbExp=3; IntAct=EBI-714135, EBI-10172526; CC O14777:NDC80; NbExp=3; IntAct=EBI-714135, EBI-715849; CC Q6NYC8:PPP1R18; NbExp=3; IntAct=EBI-714135, EBI-2557469; CC O43741:PRKAB2; NbExp=3; IntAct=EBI-714135, EBI-1053424; CC F1T0A5:PRPF31; NbExp=3; IntAct=EBI-714135, EBI-10177194; CC Q06455-4:RUNX1T1; NbExp=3; IntAct=EBI-714135, EBI-10224192; CC Q9H788:SH2D4A; NbExp=3; IntAct=EBI-714135, EBI-747035; CC Q969G3:SMARCE1; NbExp=3; IntAct=EBI-714135, EBI-455078; CC A8K287:SNAP23; NbExp=3; IntAct=EBI-714135, EBI-10188497; CC O00161:SNAP23; NbExp=5; IntAct=EBI-714135, EBI-745000; CC P61764:STXBP1; NbExp=3; IntAct=EBI-714135, EBI-960169; CC P15884:TCF4; NbExp=3; IntAct=EBI-714135, EBI-533224; CC Q8N6Y0:USHBP1; NbExp=3; IntAct=EBI-714135, EBI-739895; CC Q8N1B4:VPS52; NbExp=3; IntAct=EBI-714135, EBI-2799833; CC Q96HA8:WDYHV1; NbExp=3; IntAct=EBI-714135, EBI-741158; CC Q8TBK6:ZCCHC10; NbExp=4; IntAct=EBI-714135, EBI-597063; CC Q8TAU3:ZNF417; NbExp=3; IntAct=EBI-714135, EBI-740727; CC Q96SQ5:ZNF587; NbExp=3; IntAct=EBI-714135, EBI-6427977; CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Peripheral membrane CC protein {ECO:0000305}. Golgi apparatus, trans-Golgi network CC membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. CC -!- DISEASE: Familial hemophagocytic lymphohistiocytosis 4 (FHL4) CC [MIM:603552]: A rare disorder characterized by immune CC dysregulation with hypercytokinemia, defective function of natural CC killer cell, and massive infiltration of several organs by CC activated lymphocytes and macrophages. The clinical features of CC the disease include fever, hepatosplenomegaly, cytopenia, and less CC frequently neurological abnormalities ranging from irritability CC and hypotonia to seizures, cranial nerve deficits and ataxia. CC {ECO:0000269|PubMed:15703195}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the syntaxin family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 t-SNARE coiled-coil homology domain. CC {ECO:0000255|PROSITE-ProRule:PRU00202}. CC -!- WEB RESOURCE: Name=STX11base; Note=STX11 mutation db; CC URL="http://structure.bmc.lu.se/idbase/STX11base/"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF038898; AAD02107.1; -; mRNA. DR EMBL; AF044309; AAC24031.1; -; mRNA. DR EMBL; AF071504; AAC24004.1; -; mRNA. DR EMBL; AL135917; CAI22980.1; -; Genomic_DNA. DR EMBL; CH471051; EAW47849.1; -; Genomic_DNA. DR EMBL; CH471051; EAW47850.1; -; Genomic_DNA. DR EMBL; BC033519; AAH33519.1; -; mRNA. DR CCDS; CCDS5205.1; -. DR PIR; JE0094; JE0094. DR RefSeq; NP_003755.2; NM_003764.3. DR RefSeq; XP_011534516.1; XM_011536214.1. DR RefSeq; XP_011534517.1; XM_011536215.1. DR RefSeq; XP_011534518.1; XM_011536216.1. DR RefSeq; XP_011534519.1; XM_011536217.1. DR RefSeq; XP_011534520.1; XM_011536218.1. DR UniGene; Hs.118958; -. DR ProteinModelPortal; O75558; -. DR SMR; O75558; 38-259. DR BioGrid; 114224; 103. DR IntAct; O75558; 59. DR MINT; MINT-1398569; -. DR STRING; 9606.ENSP00000356540; -. DR PhosphoSite; O75558; -. DR BioMuta; STX11; -. DR OGP; O75558; -. DR MaxQB; O75558; -. DR PaxDb; O75558; -. DR PRIDE; O75558; -. DR DNASU; 8676; -. DR Ensembl; ENST00000367568; ENSP00000356540; ENSG00000135604. DR GeneID; 8676; -. DR KEGG; hsa:8676; -. DR UCSC; uc003qks.4; human. DR CTD; 8676; -. DR GeneCards; STX11; -. DR GeneReviews; STX11; -. DR HGNC; HGNC:11429; STX11. DR HPA; HPA007992; -. DR MIM; 603552; phenotype. DR MIM; 605014; gene. DR neXtProt; NX_O75558; -. DR Orphanet; 540; Familial hemophagocytic lymphohistiocytosis. DR PharmGKB; PA36229; -. DR eggNOG; KOG0810; Eukaryota. DR eggNOG; COG5074; LUCA. DR GeneTree; ENSGT00760000119200; -. DR HOGENOM; HOG000286023; -. DR HOVERGEN; HBG099780; -. DR InParanoid; O75558; -. DR KO; K08487; -. DR OMA; KNPCRTL; -. DR OrthoDB; EOG7X9G7R; -. DR PhylomeDB; O75558; -. DR TreeFam; TF313763; -. DR ChiTaRS; STX11; human. DR GeneWiki; STX11; -. DR GenomeRNAi; 8676; -. DR NextBio; 32547; -. DR PRO; PR:O75558; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; O75558; -. DR CleanEx; HS_STX11; -. DR Genevisible; O75558; HS. DR GO; GO:0012505; C:endomembrane system; IBA:GO_Central. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central. DR GO; GO:0031201; C:SNARE complex; IBA:GO_Central. DR GO; GO:0008021; C:synaptic vesicle; IBA:GO_Central. DR GO; GO:0005484; F:SNAP receptor activity; TAS:ProtInc. DR GO; GO:0000149; F:SNARE binding; IBA:GO_Central. DR GO; GO:0043316; P:cytotoxic T cell degranulation; IEA:Ensembl. DR GO; GO:0006887; P:exocytosis; IBA:GO_Central. DR GO; GO:0006886; P:intracellular protein transport; IBA:GO_Central. DR GO; GO:0061025; P:membrane fusion; TAS:ProtInc. DR GO; GO:0043320; P:natural killer cell degranulation; IEA:Ensembl. DR GO; GO:0043312; P:neutrophil degranulation; IEA:Ensembl. DR GO; GO:0031629; P:synaptic vesicle fusion to presynaptic membrane; IBA:GO_Central. DR GO; GO:0048278; P:vesicle docking; IBA:GO_Central. DR InterPro; IPR028672; STX11. DR InterPro; IPR006012; Syntaxin/epimorphin_CS. DR InterPro; IPR006011; Syntaxin_N. DR InterPro; IPR010989; t-SNARE. DR InterPro; IPR000727; T_SNARE_dom. DR PANTHER; PTHR19957:SF30; PTHR19957:SF30; 1. DR Pfam; PF00804; Syntaxin; 1. DR SMART; SM00503; SynN; 1. DR SMART; SM00397; t_SNARE; 1. DR SUPFAM; SSF47661; SSF47661; 1. DR PROSITE; PS00914; SYNTAXIN; 1. DR PROSITE; PS50192; T_SNARE; 1. PE 1: Evidence at protein level; KW Coiled coil; Complete proteome; KW Familial hemophagocytic lymphohistiocytosis; Golgi apparatus; KW Membrane; Polymorphism; Protein transport; Reference proteome; KW Transport. FT CHAIN 1 287 Syntaxin-11. FT /FTId=PRO_0000210221. FT DOMAIN 204 266 t-SNARE coiled-coil homology. FT {ECO:0000255|PROSITE-ProRule:PRU00202}. FT COILED 41 71 {ECO:0000255}. FT VARIANT 31 31 E -> Q (in dbSNP:rs1802414). FT /FTId=VAR_011995. FT VARIANT 49 49 R -> Q (in dbSNP:rs17073498). FT /FTId=VAR_029769. FT VARIANT 204 204 L -> H (in dbSNP:rs1133248). FT /FTId=VAR_011996. FT VARIANT 277 277 T -> A (in dbSNP:rs9496891). FT /FTId=VAR_029770. FT CONFLICT 61 61 D -> N (in Ref. 1; AAD02107). FT {ECO:0000305}. FT CONFLICT 93 94 IK -> FR (in Ref. 2; AAC24031). FT {ECO:0000305}. FT CONFLICT 96 97 RG -> PP (in Ref. 1; AAD02107). FT {ECO:0000305}. FT CONFLICT 103 104 KL -> NV (in Ref. 1; AAD02107). FT {ECO:0000305}. FT CONFLICT 121 126 HSAVAR -> ALGSGG (in Ref. 1; AAD02107). FT {ECO:0000305}. FT CONFLICT 200 220 ARAALNEIESRHRELLRLESR -> RGPPTTRSRAATANCC FT AWRAA (in Ref. 2; AAC24031). FT {ECO:0000305}. FT CONFLICT 200 200 A -> V (in Ref. 1; AAD02107). FT {ECO:0000305}. FT CONFLICT 215 215 L -> V (in Ref. 1; AAD02107). FT {ECO:0000305}. FT CONFLICT 220 220 R -> A (in Ref. 1; AAD02107). FT {ECO:0000305}. SQ SEQUENCE 287 AA; 33196 MW; 18E8B43BA987D891 CRC64; MKDRLAELLD LSKQYDQQFP DGDDEFDSPH EDIVFETDHI LESLYRDIRD IQDENQLLVA DVKRLGKQNA RFLTSMRRLS SIKRDTNSIA KAIKARGEVI HCKLRAMKEL SEAAEAQHGP HSAVARISRA QYNALTLTFQ RAMHDYNQAE MKQRDNCKIR IQRQLEIMGK EVSGDQIEDM FEQGKWDVFS ENLLADVKGA RAALNEIESR HRELLRLESR IRDVHELFLQ MAVLVEKQAD TLNVIELNVQ KTVDYTGQAK AQVRKAVQYE EKNPCRTLCC FCCPCLK // ID TEAD3_HUMAN Reviewed; 435 AA. AC Q99594; O95910; Q5BJG7; Q8N6Y4; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 11-NOV-2015, entry version 144. DE RecName: Full=Transcriptional enhancer factor TEF-5; DE AltName: Full=DTEF-1; DE AltName: Full=TEA domain family member 3; DE Short=TEAD-3; GN Name=TEAD3; Synonyms=TEAD5, TEF5; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9148898; DOI=10.1074/jbc.272.20.12928; RA Jacquemin P., Martial J.A., Davidson I.; RT "Human TEF-5 is preferentially expressed in placenta and binds to RT multiple functional elements of the human chorionic somatomammotropin- RT B gene enhancer."; RL J. Biol. Chem. 272:12928-12937(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung, and PNS; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP FUNCTION, AND INTERACTION WITH YAP1. RX PubMed=18579750; DOI=10.1101/gad.1664408; RA Zhao B., Ye X., Yu J., Li L., Li W., Li S., Yu J., Lin J.D., RA Wang C.Y., Chinnaiyan A.M., Lai Z.C., Guan K.L.; RT "TEAD mediates YAP-dependent gene induction and growth control."; RL Genes Dev. 22:1962-1971(2008). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH RP WWTR1. RX PubMed=19324877; DOI=10.1074/jbc.M900843200; RA Zhang H., Liu C.Y., Zha Z.Y., Zhao B., Yao J., Zhao S., Xiong Y., RA Lei Q.Y., Guan K.L.; RT "TEAD transcription factors mediate the function of TAZ in cell growth RT and epithelial-mesenchymal transition."; RL J. Biol. Chem. 284:13355-13362(2009). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [7] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). CC -!- FUNCTION: Transcription factor which plays a key role in the Hippo CC signaling pathway, a pathway involved in organ size control and CC tumor suppression by restricting proliferation and promoting CC apoptosis. The core of this pathway is composed of a kinase CC cascade wherein MST1/MST2, in complex with its regulatory protein CC SAV1, phosphorylates and activates LATS1/2 in complex with its CC regulatory protein MOB1, which in turn phosphorylates and CC inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene CC expression of YAP1 and WWTR1/TAZ, thereby regulating cell CC proliferation, migration and epithelial mesenchymal transition CC (EMT) induction. Binds to multiple functional elements of the CC human chorionic somatomammotropin-B gene enhancer. CC {ECO:0000269|PubMed:18579750, ECO:0000269|PubMed:19324877}. CC -!- SUBUNIT: Interacts with YAP1 and WWTR1/TAZ. CC {ECO:0000269|PubMed:18579750, ECO:0000269|PubMed:19324877}. CC -!- INTERACTION: CC Q8N8G2:VGLL2; NbExp=3; IntAct=EBI-746720, EBI-10267981; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- TISSUE SPECIFICITY: Preferentially expressed in the placenta. CC -!- SIMILARITY: Contains 1 TEA DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00505}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH27877.1; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ATA isoleucine codon.; Evidence={ECO:0000305}; CC Sequence=AAH91488.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ATA isoleucine codon.; Evidence={ECO:0000305}; CC Sequence=CAA64213.2; Type=Miscellaneous discrepancy; Note=Unusual initiator. The initiator methionine is coded by a non-canonical ATA isoleucine codon.; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X94439; CAA64213.2; ALT_SEQ; mRNA. DR EMBL; AL022721; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC027877; AAH27877.1; ALT_SEQ; mRNA. DR EMBL; BC091488; AAH91488.2; ALT_SEQ; mRNA. DR CCDS; CCDS47414.1; -. DR RefSeq; NP_003205.2; NM_003214.3. DR UniGene; Hs.485205; -. DR ProteinModelPortal; Q99594; -. DR SMR; Q99594; 27-104, 218-434. DR BioGrid; 112864; 19. DR IntAct; Q99594; 15. DR STRING; 9606.ENSP00000345772; -. DR PhosphoSite; Q99594; -. DR BioMuta; TEAD3; -. DR DMDM; 2501157; -. DR MaxQB; Q99594; -. DR PaxDb; Q99594; -. DR PRIDE; Q99594; -. DR DNASU; 7005; -. DR Ensembl; ENST00000338863; ENSP00000345772; ENSG00000007866. DR GeneID; 7005; -. DR KEGG; hsa:7005; -. DR UCSC; uc003okt.3; human. DR CTD; 7005; -. DR GeneCards; TEAD3; -. DR HGNC; HGNC:11716; TEAD3. DR HPA; HPA028906; -. DR MIM; 603170; gene. DR neXtProt; NX_Q99594; -. DR PharmGKB; PA36434; -. DR eggNOG; KOG3841; Eukaryota. DR eggNOG; ENOG410XQMP; LUCA. DR HOGENOM; HOG000253933; -. DR HOVERGEN; HBG056905; -. DR InParanoid; Q99594; -. DR KO; K09448; -. DR PhylomeDB; Q99594; -. DR TreeFam; TF313443; -. DR Reactome; R-HSA-1989781; PPARA activates gene expression. DR Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression. DR ChiTaRS; TEAD3; human. DR GeneWiki; TEAD3; -. DR GenomeRNAi; 7005; -. DR NextBio; 27362; -. DR PRO; PR:Q99594; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; Q99594; -. DR CleanEx; HS_TEAD3; -. DR ExpressionAtlas; Q99594; baseline and differential. DR Genevisible; Q99594; HS. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005667; C:transcription factor complex; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0001085; F:RNA polymerase II transcription factor binding; IPI:WormBase. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0007565; P:female pregnancy; TAS:ProtInc. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0035329; P:hippo signaling; IDA:UniProtKB. DR GO; GO:1902459; P:positive regulation of stem cell population maintenance; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR InterPro; IPR000818; TEA/ATTS. DR InterPro; IPR027253; TEF-5. DR InterPro; IPR016361; TEF_metazoa. DR PANTHER; PTHR11834; PTHR11834; 1. DR Pfam; PF01285; TEA; 1. DR PIRSF; PIRSF002603; TEF; 1. DR PIRSF; PIRSF500720; TEF-5; 1. DR PRINTS; PR00065; TEADOMAIN. DR SMART; SM00426; TEA; 1. DR PROSITE; PS00554; TEA_1; 1. DR PROSITE; PS51088; TEA_2; 1. PE 1: Evidence at protein level; KW Acetylation; Activator; Complete proteome; DNA-binding; Nucleus; KW Polymorphism; Reference proteome; Transcription; KW Transcription regulation. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:21406692}. FT CHAIN 2 435 Transcriptional enhancer factor TEF-5. FT /FTId=PRO_0000205934. FT DNA_BIND 30 97 TEA. {ECO:0000255|PROSITE- FT ProRule:PRU00505}. FT REGION 173 435 Transcriptional activation. FT {ECO:0000255}. FT COMPBIAS 146 213 Pro-rich. FT MOD_RES 2 2 N-acetylalanine. FT {ECO:0000244|PubMed:21406692}. FT VARIANT 254 254 T -> M (in dbSNP:rs35080860). FT /FTId=VAR_052278. SQ SEQUENCE 435 AA; 48676 MW; 9F8E7900EB13D4DC CRC64; MASNSWNASS SPGEAREDGP EGLDKGLDND AEGVWSPDIE QSFQEALAIY PPCGRRKIIL SDEGKMYGRN ELIARYIKLR TGKTRTRKQV SSHIQVLARK KVREYQVGIK AMNLDQVSKD KALQSMASMS SAQIVSASVL QNKFSPPSPL PQAVFSTSSR FWSSPPLLGQ QPGPSQDIKP FAQPAYPIQP PLPPTLSSYE PLAPLPSAAA SVPVWQDRTI ASSRLRLLEY SAFMEVQRDP DTYSKHLFVH IGQTNPAFSD PPLEAVDVRQ IYDKFPEKKG GLKELYEKGP PNAFFLVKFW ADLNSTIQEG PGAFYGVSSQ YSSADSMTIS VSTKVCSFGK QVVEKVETEY ARLENGRFVY RIHRSPMCEY MINFIHKLKH LPEKYMMNSV LENFTILQVV TSRDSQETLL VIAFVFEVST SEHGAQHHVY KLVKD // ID TGIF1_HUMAN Reviewed; 401 AA. AC Q15583; A6NE42; A6NLU7; F8VZB6; Q6ICR0; Q8N5X9; Q9NRS0; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 3. DT 11-NOV-2015, entry version 169. DE RecName: Full=Homeobox protein TGIF1; DE AltName: Full=5'-TG-3'-interacting factor 1; GN Name=TGIF1; Synonyms=TGIF; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Liver; RX PubMed=8537382; DOI=10.1074/jbc.270.52.31178; RA Bertolino E., Reimund B., Wildt-Perinic D., Clerc R.G.; RT "A novel homeobox protein which recognizes a TGT core and functionally RT interferes with a retinoid-responsive motif."; RL J. Biol. Chem. 270:31178-31188(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANT SER-292. RC TISSUE=Brain; RX PubMed=10764806; DOI=10.1074/jbc.M908382199; RA Yang Y., Hwang C.K., D'Souza U.M., Lee S.-H., Junn E., Mouradian M.M.; RT "Three-amino acid extension loop homeodomain proteins Meis2 and TGIF RT differentially regulate transcription."; RL J. Biol. Chem. 275:20734-20741(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT RP SER-292. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16177791; DOI=10.1038/nature03983; RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R., RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., RA O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.; RT "DNA sequence and analysis of human chromosome 18."; RL Nature 437:551-555(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-137 (ISOFORM 4). RC TISSUE=Brain, Placenta, and Rhabdomyosarcoma; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP STRUCTURE BY NMR OF 171-248. RG Northeast structural genomics consortium (NESG); RT "Solution NMR structure of homeobox domain (171-248) of human homeobox RT protein TGIF1, northeast structural genomics consortium target RT hr4411b."; RL Submitted (OCT-2011) to the PDB data bank. RN [9] RP VARIANTS HPE4 CYS-157; ARG-192; ALA-280 AND PHE-291. RX PubMed=10835638; DOI=10.1038/76074; RA Gripp K.W., Wotton D., Edwards M.C., Roessler E., Ades L., RA Meinecke P., Richieri-Costa A., Zackai E.H., Massague J., Muenke M., RA Elledge S.J.; RT "Mutations in TGIF cause holoprosencephaly and link NODAL signalling RT to human neural axis determination."; RL Nat. Genet. 25:205-208(2000). RN [10] RP VARIANT HPE4 LEU-236. RX PubMed=15221788; DOI=10.1002/humu.20056; RA Dubourg C., Lazaro L., Pasquier L., Bendavid C., Blayau M., RA Le Duff F., Durou M.-R., Odent S., David V.; RT "Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients RT with features of holoprosencephaly spectrum: mutation review and RT genotype-phenotype correlations."; RL Hum. Mutat. 24:43-51(2004). CC -!- FUNCTION: Binds to a retinoid X receptor (RXR) responsive element CC from the cellular retinol-binding protein II promoter (CRBPII- CC RXRE). Inhibits the 9-cis-retinoic acid-dependent RXR alpha CC transcription activation of the retinoic acid responsive element. CC Active transcriptional corepressor of SMAD2. Links the nodal CC signaling pathway to the bifurcation of the forebrain and the CC establishment of ventral midline structures. May participate in CC the transmission of nuclear signals during development and in the CC adult, as illustrated by the down-modulation of the RXR alpha CC activities. CC -!- SUBUNIT: Interacts with CTBP, SMAD2, SMAD3 and HDAC1. CC -!- INTERACTION: CC Q13363-2:CTBP1; NbExp=3; IntAct=EBI-714215, EBI-10171858; CC P56545:CTBP2; NbExp=5; IntAct=EBI-714215, EBI-741533; CC O00214:LGALS8; NbExp=10; IntAct=EBI-714215, EBI-740058; CC Q99750:MDFI; NbExp=4; IntAct=EBI-714215, EBI-724076; CC P29590:PML; NbExp=3; IntAct=EBI-714215, EBI-295890; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q15583-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15583-2; Sequence=VSP_013020, VSP_013021; CC Name=3; CC IsoId=Q15583-3; Sequence=VSP_043108, VSP_043109; CC Name=4; CC IsoId=Q15583-4; Sequence=VSP_046848; CC Note=No experimental confirmation available.; CC -!- DISEASE: Holoprosencephaly 4 (HPE4) [MIM:142946]: A structural CC anomaly of the brain, in which the developing forebrain fails to CC correctly separate into right and left hemispheres. CC Holoprosencephaly is genetically heterogeneous and associated with CC several distinct facies and phenotypic variability. CC {ECO:0000269|PubMed:10835638, ECO:0000269|PubMed:15221788}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the TALE/TGIF homeobox family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00108}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X89750; CAA61897.1; -; mRNA. DR EMBL; AF179900; AAF81643.1; -; mRNA. DR EMBL; CR450333; CAG29329.1; -; mRNA. DR EMBL; AK291112; BAF83801.1; -; mRNA. DR EMBL; AP001025; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471113; EAX01672.1; -; Genomic_DNA. DR EMBL; BC000814; AAH00814.1; -; mRNA. DR EMBL; BC031268; AAH31268.1; -; mRNA. DR EMBL; BE296707; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS11832.1; -. [Q15583-3] DR CCDS; CCDS11833.1; -. [Q15583-2] DR CCDS; CCDS11834.1; -. [Q15583-1] DR CCDS; CCDS11835.1; -. [Q15583-4] DR RefSeq; NP_001265611.1; NM_001278682.1. DR RefSeq; NP_001265613.1; NM_001278684.1. [Q15583-2] DR RefSeq; NP_001265615.1; NM_001278686.1. [Q15583-4] DR RefSeq; NP_003235.1; NM_003244.3. [Q15583-2] DR RefSeq; NP_733796.2; NM_170695.3. [Q15583-1] DR RefSeq; NP_775299.1; NM_173207.2. [Q15583-3] DR RefSeq; NP_775300.1; NM_173208.2. [Q15583-2] DR RefSeq; NP_775301.1; NM_173209.2. [Q15583-4] DR RefSeq; NP_775302.1; NM_173210.2. [Q15583-4] DR RefSeq; NP_775303.1; NM_173211.1. [Q15583-4] DR RefSeq; NP_777480.1; NM_174886.2. [Q15583-4] DR RefSeq; XP_011524037.1; XM_011525735.1. [Q15583-4] DR UniGene; Hs.373550; -. DR PDB; 2LK2; NMR; -; A=171-248. DR PDBsum; 2LK2; -. DR ProteinModelPortal; Q15583; -. DR SMR; Q15583; 171-248. DR BioGrid; 112908; 21. DR IntAct; Q15583; 9. DR MINT; MINT-145985; -. DR STRING; 9606.ENSP00000327959; -. DR PhosphoSite; Q15583; -. DR BioMuta; TGIF1; -. DR DMDM; 215274200; -. DR MaxQB; Q15583; -. DR PaxDb; Q15583; -. DR PRIDE; Q15583; -. DR Ensembl; ENST00000330513; ENSP00000327959; ENSG00000177426. [Q15583-1] DR Ensembl; ENST00000343820; ENSP00000339631; ENSG00000177426. [Q15583-2] DR Ensembl; ENST00000345133; ENSP00000343969; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000400167; ENSP00000383031; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000401449; ENSP00000385206; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000405385; ENSP00000384970; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000407501; ENSP00000384133; ENSG00000177426. [Q15583-2] DR Ensembl; ENST00000472042; ENSP00000449501; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000548489; ENSP00000447747; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000551541; ENSP00000450025; ENSG00000177426. [Q15583-4] DR Ensembl; ENST00000618001; ENSP00000483499; ENSG00000177426. [Q15583-3] DR GeneID; 7050; -. DR KEGG; hsa:7050; -. DR UCSC; uc002klu.3; human. [Q15583-1] DR UCSC; uc002klv.3; human. [Q15583-3] DR UCSC; uc002klw.3; human. [Q15583-2] DR CTD; 7050; -. DR GeneCards; TGIF1; -. DR GeneReviews; TGIF1; -. DR H-InvDB; HIX0174209; -. DR HGNC; HGNC:11776; TGIF1. DR HPA; CAB004596; -. DR HPA; HPA062160; -. DR MIM; 142946; phenotype. DR MIM; 602630; gene. DR neXtProt; NX_Q15583; -. DR Orphanet; 93925; Alobar holoprosencephaly. DR Orphanet; 93924; Lobar holoprosencephaly. DR Orphanet; 280200; Microform holoprosencephaly. DR Orphanet; 93926; Midline interhemispheric variant of holoprosencephaly. DR Orphanet; 220386; Semilobar holoprosencephaly. DR Orphanet; 280195; Septopreoptic holoprosencephaly. DR PharmGKB; PA36489; -. DR eggNOG; KOG0773; Eukaryota. DR eggNOG; ENOG410XPMQ; LUCA. DR GeneTree; ENSGT00550000074260; -. DR HOGENOM; HOG000232039; -. DR HOVERGEN; HBG001143; -. DR InParanoid; Q15583; -. DR KO; K19383; -. DR OMA; IAANNFT; -. DR PhylomeDB; Q15583; -. DR TreeFam; TF318093; -. DR Reactome; R-HSA-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity. DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription. DR SignaLink; Q15583; -. DR EvolutionaryTrace; Q15583; -. DR GeneWiki; Homeobox_protein_TGIF1; -. DR GenomeRNAi; 7050; -. DR NextBio; 27551; -. DR PRO; PR:Q15583; -. DR Proteomes; UP000005640; Chromosome 18. DR Bgee; Q15583; -. DR CleanEx; HS_TGIF1; -. DR ExpressionAtlas; Q15583; baseline and differential. DR Genevisible; Q15583; HS. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:NTNU_SB. DR GO; GO:0007368; P:determination of left/right symmetry; IEA:Ensembl. DR GO; GO:0009953; P:dorsal/ventral pattern formation; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0007275; P:multicellular organismal development; TAS:ProtInc. DR GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:NTNU_SB. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0038092; P:nodal signaling pathway; IEA:Ensembl. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IEA:Ensembl. DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:0010470; P:regulation of gastrulation; IEA:Ensembl. DR GO; GO:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0060041; P:retina development in camera-type eye; IEA:Ensembl. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0006351; P:transcription, DNA-templated; TAS:Reactome. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome. DR Gene3D; 1.10.10.60; -; 1. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR008422; Homeobox_KN_domain. DR InterPro; IPR009057; Homeodomain-like. DR Pfam; PF05920; Homeobox_KN; 1. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; SSF46689; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; KW Disease mutation; DNA-binding; Holoprosencephaly; Homeobox; Nucleus; KW Polymorphism; Reference proteome; Repressor; Transcription; KW Transcription regulation. FT CHAIN 1 401 Homeobox protein TGIF1. FT /FTId=PRO_0000049318. FT DNA_BIND 164 226 Homeobox; TALE-type. FT {ECO:0000255|PROSITE-ProRule:PRU00108}. FT MOTIF 153 157 CTBP-binding motif. FT COMPBIAS 165 168 Poly-Arg. FT VAR_SEQ 1 149 Missing (in isoform 4). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_046848. FT VAR_SEQ 1 129 Missing (in isoform 2). FT {ECO:0000303|PubMed:10764806, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:8537382, FT ECO:0000303|Ref.3}. FT /FTId=VSP_013020. FT VAR_SEQ 1 115 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_043108. FT VAR_SEQ 116 134 PSQGAQGPAPRRRLLETMK -> MTCSGKSCALARSSLTSS FT Q (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_043109. FT VAR_SEQ 130 133 LETM -> MKGK (in isoform 2). FT {ECO:0000303|PubMed:10764806, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:8537382, FT ECO:0000303|Ref.3}. FT /FTId=VSP_013021. FT VARIANT 157 157 S -> C (in HPE4). FT {ECO:0000269|PubMed:10835638}. FT /FTId=VAR_009961. FT VARIANT 192 192 P -> R (in HPE4). FT {ECO:0000269|PubMed:10835638}. FT /FTId=VAR_009962. FT VARIANT 236 236 Q -> L (in HPE4). FT {ECO:0000269|PubMed:15221788}. FT /FTId=VAR_023803. FT VARIANT 280 280 T -> A (in HPE4). FT {ECO:0000269|PubMed:10835638}. FT /FTId=VAR_009963. FT VARIANT 289 289 P -> S (in dbSNP:rs11571512). FT /FTId=VAR_047363. FT VARIANT 291 291 S -> F (in HPE4). FT {ECO:0000269|PubMed:10835638}. FT /FTId=VAR_009964. FT VARIANT 292 292 P -> L (in dbSNP:rs2229333). FT /FTId=VAR_020151. FT VARIANT 292 292 P -> S (in dbSNP:rs4468717). FT {ECO:0000269|PubMed:10764806, FT ECO:0000269|Ref.3}. FT /FTId=VAR_061268. FT CONFLICT 96 96 P -> Q (in Ref. 7; AAH31268). FT {ECO:0000305}. FT HELIX 173 185 {ECO:0000244|PDB:2LK2}. FT HELIX 188 190 {ECO:0000244|PDB:2LK2}. FT HELIX 194 203 {ECO:0000244|PDB:2LK2}. FT STRAND 204 206 {ECO:0000244|PDB:2LK2}. FT HELIX 208 230 {ECO:0000244|PDB:2LK2}. SQ SEQUENCE 401 AA; 43013 MW; 4D9C76AFB37A29F0 CRC64; MVLAQSRVSA GVGSPHCSGS GGGGSDSFPW PASHPGNPQC SFSTAFLASP RLSRGTLAYL PPAPWSSLAT PSALLGSSCA PPPPPARCPQ PRALSPELGT KAGPRRPHRW ELPRSPSQGA QGPAPRRRLL ETMKGIVAAS GSETEDEDSM DIPLDLSSSA GSGKRRRRGN LPKESVQILR DWLYEHRYNA YPSEQEKALL SQQTHLSTLQ VCNWFINARR RLLPDMLRKD GKDPNQFTIS RRGAKISETS SVESVMGIKN FMPALEETPF HSCTAGPNPT LGRPLSPKPS SPGSVLARPS VICHTTVTAL KDVPFSLCQS VGVGQNTDIQ QIAAKNFTDT SLMYPEDTCK SGPSTNTQSG LFNTPPPTPP DLNQDFSGFQ LLVDVALKRA AEMELQAKLT A // ID THA11_HUMAN Reviewed; 314 AA. AC Q96EK4; A4UCT5; A8K002; O94795; DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot. DT 14-OCT-2008, sequence version 2. DT 11-NOV-2015, entry version 124. DE RecName: Full=THAP domain-containing protein 11; GN Name=THAP11; ORFNames=HRIHFB2206; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Neuroblastoma; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 44-197. RA Santana-Roman H., Curiel-Quesada E., Tapia-Ramirez J.; RT "Searching for interaction partners of the transcription factor RT REST/NRSF by two-hybrid screening."; RL Submitted (OCT-2006) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 226-313, AND SUBCELLULAR RP LOCATION. RC TISSUE=Brain; RX PubMed=9853615; DOI=10.1038/4315; RA Ueki N., Oda T., Kondo M., Yano K., Noguchi T., Muramatsu M.-A.; RT "Selection system for genes encoding nuclear-targeted proteins."; RL Nat. Biotechnol. 16:1338-1342(1998). RN [5] RP TRIPLET REPEAT EXPANSION. RX PubMed=15368101; DOI=10.1007/s10038-004-0194-8; RA Pandey N., Mittal U., Srivastava A.K., Mukerji M.; RT "SMARCA2 and THAP11: potential candidates for polyglutamine disorders RT as evidenced from polymorphism and protein-folding simulation RT studies."; RL J. Hum. Genet. 49:596-602(2004). RN [6] RP STRUCTURE BY NMR OF 1-81 IN COMPLEX WITH ZINC ION, AND DNA-BINDING. RX PubMed=23306615; DOI=10.1007/s10858-012-9699-1; RA Gervais V., Campagne S., Durand J., Muller I., Milon A.; RT "NMR studies of a new family of DNA binding proteins: the THAP RT proteins."; RL J. Biomol. NMR 56:3-15(2013). CC -!- FUNCTION: Transcriptional repressor that plays a central role for CC embryogenesis and the pluripotency of embryonic stem (ES) cells. CC Sequence-specific DNA-binding factor that represses gene CC expression in pluripotent ES cells by directly binding to key CC genetic loci and recruiting epigenetic modifiers (By similarity). CC {ECO:0000250}. CC -!- SUBUNIT: Interacts (via coiled coil domain) with HCFC1. CC {ECO:0000250}. CC -!- INTERACTION: CC P70677:Casp3 (xeno); NbExp=2; IntAct=EBI-1790529, EBI-1790419; CC Q13363:CTBP1; NbExp=2; IntAct=EBI-1790529, EBI-908846; CC P51610:HCFC1; NbExp=2; IntAct=EBI-1790529, EBI-396176; CC Q15365:PCBP1; NbExp=4; IntAct=EBI-1790529, EBI-946095; CC Q8N1B4:VPS52; NbExp=3; IntAct=EBI-1790529, EBI-2799833; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9853615}. CC Cytoplasm {ECO:0000250}. Note=May be regulated by shuttling of the CC protein between the cytoplasm and nucleus. {ECO:0000250}. CC -!- POLYMORPHISM: The length of the poly-Gln region is variable in the CC population. CC -!- SIMILARITY: Belongs to the THAP11 family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 THAP-type zinc finger. CC {ECO:0000255|PROSITE-ProRule:PRU00309}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AK289367; BAF82056.1; -; mRNA. DR EMBL; BC012182; AAH12182.1; -; mRNA. DR EMBL; EF036502; ABO65088.1; -; mRNA. DR EMBL; AB015338; BAA34796.1; -; mRNA. DR CCDS; CCDS10847.1; -. DR RefSeq; NP_065190.2; NM_020457.2. DR UniGene; Hs.632200; -. DR PDB; 2LAU; NMR; -; A=2-80. DR PDBsum; 2LAU; -. DR ProteinModelPortal; Q96EK4; -. DR SMR; Q96EK4; 2-80. DR BioGrid; 121453; 30. DR IntAct; Q96EK4; 12. DR MINT; MINT-8362103; -. DR STRING; 9606.ENSP00000304689; -. DR PhosphoSite; Q96EK4; -. DR BioMuta; THAP11; -. DR DMDM; 209572685; -. DR MaxQB; Q96EK4; -. DR PaxDb; Q96EK4; -. DR PRIDE; Q96EK4; -. DR DNASU; 57215; -. DR Ensembl; ENST00000303596; ENSP00000304689; ENSG00000168286. DR GeneID; 57215; -. DR KEGG; hsa:57215; -. DR UCSC; uc002euo.3; human. DR CTD; 57215; -. DR GeneCards; THAP11; -. DR HGNC; HGNC:23194; THAP11. DR HPA; HPA041434; -. DR HPA; HPA042189; -. DR MIM; 609119; gene. DR neXtProt; NX_Q96EK4; -. DR PharmGKB; PA134979842; -. DR eggNOG; ENOG410IFX3; Eukaryota. DR eggNOG; ENOG4111FSQ; LUCA. DR GeneTree; ENSGT00390000006585; -. DR HOGENOM; HOG000154562; -. DR HOVERGEN; HBG062269; -. DR InParanoid; Q96EK4; -. DR OMA; TGHRVCS; -. DR OrthoDB; EOG7WQ7TG; -. DR PhylomeDB; Q96EK4; -. DR TreeFam; TF331359; -. DR GenomeRNAi; 57215; -. DR NextBio; 63333; -. DR PRO; PR:Q96EK4; -. DR Proteomes; UP000005640; Chromosome 16. DR Bgee; Q96EK4; -. DR CleanEx; HS_THAP11; -. DR Genevisible; Q96EK4; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0045171; C:intercellular bridge; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR InterPro; IPR006612; Znf_C2CH. DR Pfam; PF05485; THAP; 1. DR SMART; SM00692; DM3; 1. DR SMART; SM00980; THAP; 1. DR PROSITE; PS50950; ZF_THAP; 1. PE 1: Evidence at protein level; KW 3D-structure; Coiled coil; Complete proteome; Cytoplasm; DNA-binding; KW Metal-binding; Nucleus; Reference proteome; Repressor; Transcription; KW Transcription regulation; Triplet repeat expansion; Zinc; Zinc-finger. FT CHAIN 1 314 THAP domain-containing protein 11. FT /FTId=PRO_0000068653. FT ZN_FING 1 80 THAP-type. {ECO:0000255|PROSITE- FT ProRule:PRU00309}. FT COILED 255 305 {ECO:0000255}. FT MOTIF 243 246 HCFC1-binding motif (HBM). {ECO:0000250}. FT COMPBIAS 95 100 Poly-Ala. FT COMPBIAS 104 146 Gln-rich. FT COMPBIAS 197 221 Ala-rich. FT CONFLICT 132 132 Missing (in Ref. 2; AAH12182). FT {ECO:0000305}. FT STRAND 9 13 {ECO:0000244|PDB:2LAU}. FT STRAND 15 17 {ECO:0000244|PDB:2LAU}. FT HELIX 30 40 {ECO:0000244|PDB:2LAU}. FT HELIX 62 64 {ECO:0000244|PDB:2LAU}. FT STRAND 65 71 {ECO:0000244|PDB:2LAU}. SQ SEQUENCE 314 AA; 34455 MW; 25235D20CB54D8C2 CRC64; MPGFTCCVPG CYNNSHRDKA LHFYTFPKDA ELRRLWLKNV SRAGVSGCFS TFQPTTGHRL CSVHFQGGRK TYTVRVPTIF PLRGVNERKV ARRPAGAAAA RRRQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ QQSSPSASTA QTAQLQPNLV SASAAVLLTL QATVDSSQAP GSVQPAPITP TGEDVKPIDL TVQVEFAAAE GAAAAAAASE LQAATAGLEA AECPMGPQLV VVGEEGFPDT GSDHSYSLSS GTTEEELLRK LNEQRDILAL MEVKMKEMKG SIRHLRLTEA KLREELREKD RLLAMAVIRK KHGM // ID TSH3_HUMAN Reviewed; 1081 AA. AC Q63HK5; Q9H0G6; Q9P254; DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot. DT 10-JAN-2006, sequence version 2. DT 11-NOV-2015, entry version 121. DE RecName: Full=Teashirt homolog 3; DE AltName: Full=Zinc finger protein 537; GN Name=TSHZ3; Synonyms=KIAA1474, TSH3, ZNF537; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLY-469. RC TISSUE=Endometrial tumor; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 3-1081. RC TISSUE=Brain; RX PubMed=10819331; DOI=10.1093/dnares/7.2.143; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVII. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 7:143-150(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 176-1081. RC TISSUE=Testis; RX PubMed=11230166; DOI=10.1101/gr.GR1547R; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D., RA Wambutt R., Korn B., Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and RT analysis of 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [4] RP TISSUE SPECIFICITY. RX PubMed=18776146; DOI=10.1242/dev.022442; RA Caubit X., Lye C.M., Martin E., Core N., Long D.A., Vola C., RA Jenkins D., Garratt A.N., Skaer H., Woolf A.S., Fasano L.; RT "Teashirt 3 is necessary for ureteral smooth muscle differentiation RT downstream of SHH and BMP4."; RL Development 135:3301-3310(2008). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [6] RP FUNCTION, INTERACTION WITH APBB1; HDAC1 AND HDAC2, IDENTIFICATION IN A RP TRIMERIC COMPLEX WITH APBB1 AND HDAC1, CHROMATIN-BINDING, MUTAGENESIS RP OF 953-VAL--TYR-955, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=19343227; DOI=10.1371/journal.pone.0005071; RA Kajiwara Y., Akram A., Katsel P., Haroutunian V., Schmeidler J., RA Beecham G., Haines J.L., Pericak-Vance M.A., Buxbaum J.D.; RT "FE65 binds Teashirt, inhibiting expression of the primate-specific RT caspase-4."; RL PLoS ONE 4:E5071-E5071(2009). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-682, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [9] RP VARIANT GLY-469, AND DEVELOPMENTAL STAGE. RX PubMed=19745106; DOI=10.1093/ndt/gfp453; RA Jenkins D., Caubit X., Dimovski A., Matevska N., Lye C.M., Cabuk F., RA Gucev Z., Tasic V., Fasano L., Woolf A.S.; RT "Analysis of TSHZ2 and TSHZ3 genes in congenital pelvi-ureteric RT junction obstruction."; RL Nephrol. Dial. Transplant. 25:54-60(2010). RN [10] RP STRUCTURE BY NMR OF 200-303. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the first and the second ZF-C2H2-like domains RT of human teashirt homolog 3."; RL Submitted (OCT-2006) to the PDB data bank. CC -!- FUNCTION: Transcriptional regulator involved in developmental CC processes. Function in association with APBB1, SET and HDAC CC factors as a transcriptional repressor, that inhibits the CC expression of CASP4. TSHZ3-mediated transcription repression CC involves the recruitment of histone deacetylases HDAC1 and HDAC2. CC Associates with chromatin in a region surrounding the CASP4 CC transcriptional start site(s). Regulates the development of CC neurons involved in both respiratory rhythm and airflow control. CC Promotes maintenance of nucleus ambiguus (nA) motoneurons, which CC govern upper airway function, and establishes a respiratory rhythm CC generator (RRG) activity compatible with survival at birth. CC Involved in the differentiation of the proximal uretic smooth CC muscle cells during developmental processes. Involved in the up- CC regulation of myocardin, that directs the expression of smooth CC muscle cells in the proximal ureter. CC {ECO:0000269|PubMed:19343227}. CC -!- SUBUNIT: Interacts (via homeobox domain) with APBB1 (via PID CC domain 1). Interacts (via N-terminus) with HDAC1 and HDAC2; the CC interaction is direct. Found in a trimeric complex with APBB1 and CC HDAC1; the interaction between HDAC1 and APBB1 is mediated by CC TSHZ3. {ECO:0000269|PubMed:19343227}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE- CC ProRule:PRU00108, ECO:0000269|PubMed:19343227}. Cell projection, CC growth cone {ECO:0000250}. Note=Colocalizes with APBB1 in axonal CC growth cone (By similarity). Colocalizes with APBB1 in the CC nucleus. {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Expressed in brain; strongly reduced in post- CC mortem elderly subjects with Alzheimer disease. CC {ECO:0000269|PubMed:18776146, ECO:0000269|PubMed:19343227}. CC -!- DEVELOPMENTAL STAGE: Expressed in peri-urothelial cells of the CC proximal ureter and renal pelvis at 9 weeks of gestation. CC {ECO:0000269|PubMed:19745106}. CC -!- SIMILARITY: Belongs to the teashirt C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 5 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00108}. CC -!- SEQUENCE CAUTION: CC Sequence=CAB66739.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Life's first breath - CC Issue 122 of October 2010; CC URL="http://web.expasy.org/spotlight/back_issues/122"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; BX648745; CAH56184.1; -; mRNA. DR EMBL; AB040907; BAA95998.1; -; mRNA. DR EMBL; AL136805; CAB66739.1; ALT_INIT; mRNA. DR CCDS; CCDS12421.2; -. DR RefSeq; NP_065907.2; NM_020856.2. DR UniGene; Hs.278436; -. DR PDB; 2DMI; NMR; -; A=202-303. DR PDBsum; 2DMI; -. DR ProteinModelPortal; Q63HK5; -. DR SMR; Q63HK5; 200-303. DR BioGrid; 121663; 21. DR IntAct; Q63HK5; 1. DR MINT; MINT-4725267; -. DR STRING; 9606.ENSP00000240587; -. DR PhosphoSite; Q63HK5; -. DR BioMuta; TSHZ3; -. DR DMDM; 85541971; -. DR MaxQB; Q63HK5; -. DR PaxDb; Q63HK5; -. DR PRIDE; Q63HK5; -. DR DNASU; 57616; -. DR Ensembl; ENST00000240587; ENSP00000240587; ENSG00000121297. DR GeneID; 57616; -. DR KEGG; hsa:57616; -. DR UCSC; uc002nsy.4; human. DR CTD; 57616; -. DR GeneCards; TSHZ3; -. DR HGNC; HGNC:30700; TSHZ3. DR HPA; HPA008834; -. DR MIM; 614119; gene. DR neXtProt; NX_Q63HK5; -. DR PharmGKB; PA134887020; -. DR eggNOG; ENOG410IFDT; Eukaryota. DR eggNOG; ENOG410XQQR; LUCA. DR GeneTree; ENSGT00390000014977; -. DR HOGENOM; HOG000231480; -. DR HOVERGEN; HBG079626; -. DR InParanoid; Q63HK5; -. DR KO; K09236; -. DR OMA; YIMSDLS; -. DR OrthoDB; EOG7NPFSF; -. DR PhylomeDB; Q63HK5; -. DR TreeFam; TF328447; -. DR ChiTaRS; TSHZ3; human. DR EvolutionaryTrace; Q63HK5; -. DR GeneWiki; TSHZ3; -. DR GenomeRNAi; 57616; -. DR NextBio; 64282; -. DR PRO; PR:Q63HK5; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; Q63HK5; -. DR CleanEx; HS_TSHZ3; -. DR ExpressionAtlas; Q63HK5; baseline and differential. DR Genevisible; Q63HK5; HS. DR GO; GO:0030426; C:growth cone; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0007275; P:multicellular organismal development; IEA:UniProtKB-KW. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0002087; P:regulation of respiratory gaseous exchange by neurological system process; ISS:UniProtKB. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR027008; Teashirt_fam. DR InterPro; IPR026810; Tshz3. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR PANTHER; PTHR12487; PTHR12487; 1. DR PANTHER; PTHR12487:SF5; PTHR12487:SF5; 1. DR SMART; SM00389; HOX; 1. DR SMART; SM00355; ZnF_C2H2; 5. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 2. PE 1: Evidence at protein level; KW 3D-structure; Cell projection; Coiled coil; Complete proteome; KW Developmental protein; DNA-binding; Homeobox; Metal-binding; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; Repressor; KW Transcription; Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 1081 Teashirt homolog 3. FT /FTId=PRO_0000047066. FT ZN_FING 214 238 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 275 299 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 386 404 C2H2-type 3; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT DNA_BIND 891 961 Homeobox; atypical. {ECO:0000255|PROSITE- FT ProRule:PRU00108}. FT ZN_FING 976 998 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 1041 1064 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT COILED 606 630 {ECO:0000255}. FT COMPBIAS 142 164 Ser-rich. FT COMPBIAS 493 496 Poly-Glu. FT MOD_RES 682 682 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT VARIANT 469 469 E -> G (in dbSNP:rs143453460). FT {ECO:0000269|PubMed:17974005, FT ECO:0000269|PubMed:19745106}. FT /FTId=VAR_063635. FT VARIANT 687 687 P -> L (in dbSNP:rs4805664). FT /FTId=VAR_052708. FT MUTAGEN 953 955 VKY->ATA: Does not inhibit interaction FT with APBB1. FT {ECO:0000269|PubMed:19343227}. FT STRAND 213 220 {ECO:0000244|PDB:2DMI}. FT STRAND 222 225 {ECO:0000244|PDB:2DMI}. FT HELIX 226 235 {ECO:0000244|PDB:2DMI}. FT STRAND 278 280 {ECO:0000244|PDB:2DMI}. FT HELIX 287 296 {ECO:0000244|PDB:2DMI}. FT TURN 297 301 {ECO:0000244|PDB:2DMI}. SQ SEQUENCE 1081 AA; 118566 MW; B4E0A4347B04E74A CRC64; MPRRKQQAPR RAAAYVSEEL KAAALVDEGL DPEEHTADGE PSAKYMCPEK ELARACPSYQ NSPAAEFSCH EMDSESHISE TSDRMADFES GSIKNEEETK EVTVPLEDTT VSDSLEQMKA VYNNFLSNSY WSNLNLNLHQ PSSEKNNGSS SSSSSSSSSC GSGSFDWHQS AMAKTLQQVS QSRMLPEPSL FSTVQLYRQS SKLYGSIFTG ASKFRCKDCS AAYDTLVELT VHMNETGHYR DDNHETDNNN PKRWSKPRKR SLLEMEGKED AQKVLKCMYC GHSFESLQDL SVHMIKTKHY QKVPLKEPVT PVAAKIIPAT RKKASLELEL PSSPDSTGGT PKATISDTND ALQKNSNPYI TPNNRYGHQN GASYAWHFEA RKSQILKCME CGSSHDTLQE LTAHMMVTGH FIKVTNSAMK KGKPIVETPV TPTITTLLDE KVQSVPLAAT TFTSPSNTPA SISPKLNVEV KKEVDKEKAV TDEKPKQKDK PGEEEEKCDI SSKYHYLTEN DLEESPKGGL DILKSLENTV TSAINKAQNG TPSWGGYPSI HAAYQLPNMM KLSLGSSGKS TPLKPMFGNS EIVSPTKNQT LVSPPSSQTS PMPKTNFHAM EELVKKVTEK VAKVEEKMKE PDGKLSPPKR ATPSPCSSEV GEPIKMEASS DGGFRSQENS PSPPRDGCKD GSPLAEPVEN GKELVKPLAS SLSGSTAIIT DHPPEQPFVN PLSALQSVMN IHLGKAAKPS LPALDPMSML FKMSNSLAEK AAVATPPPLQ SKKADHLDRY FYHVNNDQPI DLTKGKSDKG CSLGSVLLSP TSTAPATSSS TVTTAKTSAV VSFMSNSPLR ENALSDISDM LKNLTESHTS KSSTPSSISE KSDIDGATLE EAEESTPAQK RKGRQSNWNP QHLLILQAQF AASLRQTSEG KYIMSDLSPQ ERMHISRFTG LSMTTISHWL ANVKYQLRRT GGTKFLKNLD TGHPVFFCND CASQIRTPST YISHLESHLG FRLRDLSKLS TEQINSQIAQ TKSPSEKMVT SSPEEDLGTS YQCKLCNRTF ASKHAVKLHL SKTHGKSPED HLLYVSELEK Q // ID UBC9_HUMAN Reviewed; 158 AA. AC P63279; D3DU69; P50550; Q15698; Q59GX1; Q86VB3; DT 11-OCT-2004, integrated into UniProtKB/Swiss-Prot. DT 11-OCT-2004, sequence version 1. DT 11-NOV-2015, entry version 139. DE RecName: Full=SUMO-conjugating enzyme UBC9; DE EC=6.3.2.-; DE AltName: Full=SUMO-protein ligase; DE AltName: Full=Ubiquitin carrier protein 9; DE AltName: Full=Ubiquitin carrier protein I; DE AltName: Full=Ubiquitin-conjugating enzyme E2 I; DE AltName: Full=Ubiquitin-protein ligase I; DE AltName: Full=p18; GN Name=UBE2I; Synonyms=UBC9, UBCE9; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION. RX PubMed=8668529; DOI=10.1093/nar/24.11.2005; RA Yasugi T., Howley P.M.; RT "Identification of the structural and functional human homolog of the RT yeast ubiquitin conjugating enzyme UBC9."; RL Nucleic Acids Res. 24:2005-2010(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9067428; RA Tachibana M., Iwata N., Watanabe A., Nobukuni Y., Ploplis B., RA Kajigaya S.; RT "Assignment of the gene for a ubiquitin-conjugating enzyme (UBE2I) to RT human chromosome band 16p13.3 by in situ hybridization."; RL Cytogenet. Cell Genet. 75:222-223(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Fetal brain; RX PubMed=8565643; RA Watanabe T.K., Fujiwara T., Kawai A., Shimizu F., Takami S., RA Hirano H., Okuno S., Ozaki K., Takeda S., Shimada Y., Nagata M., RA Takaichi A., Takahashi E., Nakamura Y., Shin S.; RT "Cloning, expression, and mapping of UBE2I, a novel gene encoding a RT human homologue of yeast ubiquitin-conjugating enzymes which are RT critical for regulating the cell cycle."; RL Cytogenet. Cell Genet. 72:86-89(1996). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH PARP. RX PubMed=9197546; DOI=10.1016/S0378-1119(97)00015-2; RA Masson M., Menissier-de Murcia J., Mattei M.-G., de Murcia G.M., RA Niedergang C.P.; RT "Poly(ADP-ribose) polymerase interacts with a novel human ubiquitin RT conjugating enzyme: hUbc9."; RL Gene 190:287-296(1997). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RX PubMed=8610150; DOI=10.1073/pnas.93.7.2958; RA Kovalenko O.V., Plug A.W., Haaf T., Gonda D.K., Ashley T., Ward D.C., RA Radding C.M., Golub E.I.; RT "Mammalian ubiquitin-conjugating enzyme Ubc9 interacts with Rad51 RT recombination protein and localizes in synaptonemal complexes."; RL Proc. Natl. Acad. Sci. U.S.A. 93:2958-2963(1996). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8668125; DOI=10.1007/BF02172913; RA Jiang W., Koltin Y.; RT "Two-hybrid interaction of a human UBC9 homolog with centromere RT proteins of Saccharomyces cerevisiae."; RL Mol. Gen. Genet. 251:153-160(1996). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RX PubMed=8798754; DOI=10.1074/jbc.271.40.24811; RA Wang Z.-Y., Qiu Q., Seufert W., Taguchi T., Testa J.R., Whitmore S.A., RA Callen D.F., Welsh D., Shenk T., Deuel T.F.; RT "Molecular cloning of the cDNA and chromosome localization of the gene RT for human ubiquitin-conjugating enzyme 9."; RL J. Biol. Chem. 271:24811-24816(1996). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Shen Z.; RL Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=9333025; DOI=10.1038/sj.onc.1201301; RA Hahn S.L., Criqui-Filipe P., Wasylyk B.; RT "Modulation of ETS-1 transcriptional activity by huUBC9, a ubiquitin- RT conjugating enzyme."; RL Oncogene 15:1489-1495(1997). RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., RA Ohara O., Nagase T., Kikuno R.F.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11157797; DOI=10.1093/hmg/10.4.339; RA Daniels R.J., Peden J.F., Lloyd C., Horsley S.W., Clark K., RA Tufarelli C., Kearney L., Buckle V.J., Doggett N.A., Flint J., RA Higgs D.R.; RT "Sequence, structure and pathology of the fully annotated terminal 2 RT Mb of the short arm of human chromosome 16."; RL Hum. Mol. Genet. 10:339-352(2001). RN [13] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [14] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., RA Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [15] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [16] RP INTERACTION WITH ADENOVIRUS E1A. RX PubMed=8824223; DOI=10.1074/jbc.271.42.25906; RA Hateboer G., Hijmans E.M., Nooij J.B.D., Schlenker S., Jentsch S., RA Bernards R.; RT "mUBC9, a novel adenovirus E1A-interacting protein that complements a RT yeast cell cycle defect."; RL J. Biol. Chem. 271:25906-25911(1996). RN [17] RP INTERACTION WITH SIAH1. RX PubMed=9334332; DOI=10.1101/gad.11.20.2701; RA Hu G., Zhang S., Vidal M., Baer J.L., Xu T., Fearon E.R.; RT "Mammalian homologs of seven in absentia regulate DCC via the RT ubiquitin-proteasome pathway."; RL Genes Dev. 11:2701-2714(1997). RN [18] RP INTERACTION WITH AR. RX PubMed=10383460; DOI=10.1074/jbc.274.27.19441; RA Poukka H., Aarnisalo P., Karvonen U., Palvimo J.J., Jaenne O.A.; RT "Ubc9 interacts with the androgen receptor and activates receptor- RT dependent transcription."; RL J. Biol. Chem. 274:19441-19446(1999). RN [19] RP INTERACTION WITH FHIT. RX PubMed=11085938; DOI=10.1042/0264-6021:3520443; RA Shi Y., Zou M., Farid N.R., Paterson M.C.; RT "Association of FHIT (fragile histidine triad), a candidate tumour RT suppressor gene, with the ubiquitin-conjugating enzyme hUBC9."; RL Biochem. J. 352:443-448(2000). RN [20] RP FUNCTION. RX PubMed=11451954; DOI=10.1074/jbc.M104214200; RA Tatham M.H., Jaffray E., Vaughan O.A., Desterro J.M.P., Botting C.H., RA Naismith J.H., Hay R.T.; RT "Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein RT substrates by SAE1/SAE2 and Ubc9."; RL J. Biol. Chem. 276:35368-35374(2001). RN [21] RP INTERACTION WITH TFAP2A; TFAP2B AND TFAP2C. RX PubMed=12072434; DOI=10.1074/jbc.M202780200; RA Eloranta J.J., Hurst H.C.; RT "Transcription factor AP-2 interacts with the SUMO-conjugating enzyme RT UBC9 and is sumolated in vivo."; RL J. Biol. Chem. 277:30798-30804(2002). RN [22] RP MUTAGENESIS OF 100-ASP-LYS-101. RX PubMed=12641448; DOI=10.1021/bi026861x; RA Tatham M.H., Chen Y., Hay R.T.; RT "Role of two residues proximal to the active site of Ubc9 in substrate RT recognition by the Ubc9.SUMO-1 thiolester complex."; RL Biochemistry 42:3168-3179(2003). RN [23] RP INTERACTION WITH SUMO1; SUMO2; SUMO3 AND THE UBLE1A-UBLE1B E1 COMPLEX, RP AND MUTAGENESIS OF 13-ARG-LYS-14 AND 17-ARG-LYS-18. RX PubMed=12924945; DOI=10.1021/bi0345283; RA Tatham M.H., Kim S., Yu B., Jaffray E., Song J., Zheng J., RA Rodriguez M.S., Hay R.T., Chen Y.; RT "Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and RT conjugation."; RL Biochemistry 42:9959-9969(2003). RN [24] RP INTERACTION WITH RANBP2. RX PubMed=15378033; DOI=10.1038/nsmb834; RA Pichler A., Knipscheer P., Saitoh H., Sixma T.K., Melchior F.; RT "The RanBP2 SUMO E3 ligase is neither HECT- nor RING-type."; RL Nat. Struct. Mol. Biol. 11:984-991(2004). RN [25] RP INTERACTION WITH THE PML-RARALPHA ONCOPROTEIN, AND FUNCTION. RX PubMed=15809060; DOI=10.1016/j.bbrc.2005.03.052; RA Kim Y.E., Kim D.Y., Lee J.M., Kim S.T., Han T.H., Ahn J.H.; RT "Requirement of the coiled-coil domain of PML-RARalpha oncoprotein for RT localization, sumoylation, and inhibition of monocyte RT differentiation."; RL Biochem. Biophys. Res. Commun. 330:746-754(2005). RN [26] RP INTERACTION WITH RANBP2, AND MUTAGENESIS OF PHE-22; VAL-25; VAL-27; RP GLU-42; LYS-48; GLU-54; LEU-57; LYS-59 AND ARG-61. RX PubMed=15608651; DOI=10.1038/nsmb878; RA Tatham M.H., Kim S., Jaffray E., Song J., Chen Y., Hay R.T.; RT "Unique binding interactions among Ubc9, SUMO and RanBP2 reveal a RT mechanism for SUMO paralog selection."; RL Nat. Struct. Mol. Biol. 12:67-74(2005). RN [27] RP IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=16620772; DOI=10.1016/j.abb.2006.03.002; RA Li T., Santockyte R., Shen R.-F., Tekle E., Wang G., Yang D.C.H., RA Chock P.B.; RT "A general approach for investigating enzymatic pathways and RT substrates for ubiquitin-like modifiers."; RL Arch. Biochem. Biophys. 453:70-74(2006). RN [28] RP SUBCELLULAR LOCATION, AND INTERACTION WITH SOX4. RX PubMed=16631117; DOI=10.1016/j.bbrc.2006.03.194; RA Pan X., Li H., Zhang P., Jin B., Man J., Tian L., Su G., Zhao J., RA Li W., Liu H., Gong W., Zhou T., Zhang X.; RT "Ubc9 interacts with SOX4 and represses its transcriptional RT activity."; RL Biochem. Biophys. Res. Commun. 344:727-734(2006). RN [29] RP INTERACTION WITH HERPESVIRUS 6 IE2. RX PubMed=17005699; DOI=10.1128/JVI.00375-06; RA Tomoiu A., Gravel A., Tanguay R.M., Flamand L.; RT "Functional interaction between human herpesvirus 6 immediate-early 2 RT protein and ubiquitin-conjugating enzyme 9 in the absence of RT sumoylation."; RL J. Virol. 80:10218-10228(2006). RN [30] RP INTERACTION WITH RWDD3, AND SUBCELLULAR LOCATION. RX PubMed=17956732; DOI=10.1016/j.cell.2007.07.044; RA Carbia-Nagashima A., Gerez J., Perez-Castro C., Paez-Pereda M., RA Silberstein S., Stalla G.K., Holsboer F., Arzt E.; RT "RSUME, a small RWD-containing protein, enhances SUMO conjugation and RT stabilizes HIF-1alpha during hypoxia."; RL Cell 131:309-323(2007). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION OF RP KAT5-UBE2I-SENP6 COMPLEX. RX PubMed=17704809; DOI=10.1038/sj.onc.1210710; RA Cheng Z., Ke Y., Ding X., Wang F., Wang H., Wang W., Ahmed K., Liu Z., RA Xu Y., Aikhionbare F., Yan H., Liu J., Xue Y., Yu J., Powell M., RA Liang S., Wu Q., Reddy S.E., Hu R., Huang H., Jin C., Yao X.; RT "Functional characterization of TIP60 sumoylation in UV-irradiated DNA RT damage response."; RL Oncogene 27:931-941(2008). RN [32] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [33] RP INTERACTION WITH DNMT1. RX PubMed=19450230; DOI=10.1042/BJ20090142; RA Lee B., Muller M.T.; RT "SUMOylation enhances DNA methyltransferase 1 activity."; RL Biochem. J. 421:449-461(2009). RN [34] RP INTERACTION WITH FOXL2, ROLE IN FOXL2 SUMOYLATION, AND SUBCELLULAR RP LOCATION. RX PubMed=19744555; DOI=10.1016/j.cellsig.2009.09.001; RA Kuo F.T., Bentsi-Barnes I.K., Barlow G.M., Bae J., Pisarska M.D.; RT "Sumoylation of forkhead L2 by Ubc9 is required for its activity as a RT transcriptional repressor of the steroidogenic acute regulatory RT gene."; RL Cell. Signal. 21:1935-1944(2009). RN [35] RP INTERACTION WITH DNM1L, AND FUNCTION IN DNM1L SUMOYLATION. RX PubMed=19638400; DOI=10.1096/fj.09-136630; RA Figueroa-Romero C., Iniguez-Lluhi J.A., Stadler J., Chang C.R., RA Arnoult D., Keller P.J., Hong Y., Blackstone C., Feldman E.L.; RT "SUMOylation of the mitochondrial fission protein Drp1 occurs at RT multiple nonconsensus sites within the B domain and is linked to its RT activity cycle."; RL FASEB J. 23:3917-3927(2009). RN [36] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-65, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [37] RP INTERACTION WITH HUMAN ADENOVIRUS EARLY E1A PROTEIN. RX PubMed=20543865; DOI=10.1038/onc.2010.226; RA Yousef A.F., Fonseca G.J., Pelka P., Ablack J.N., Walsh C., Dick F.A., RA Bazett-Jones D.P., Shaw G.S., Mymryk J.S.; RT "Identification of a molecular recognition feature in the E1A RT oncoprotein that binds the SUMO conjugase UBC9 and likely interferes RT with polySUMOylation."; RL Oncogene 29:4693-4704(2010). RN [38] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [39] RP INTERACTION WITH MTA1. RX PubMed=21965678; DOI=10.1074/jbc.M111.267237; RA Cong L., Pakala S.B., Ohshiro K., Li D.Q., Kumar R.; RT "SUMOylation and SUMO-interacting motif (SIM) of metastasis tumor RT antigen 1 (MTA1) synergistically regulate its transcriptional RT repressor function."; RL J. Biol. Chem. 286:43793-43808(2011). RN [40] RP INTERACTION WITH EPSTEIN-BARR VIRUS LMP1. RX PubMed=21795333; DOI=10.1128/JVI.05035-11; RA Bentz G.L., Whitehurst C.B., Pagano J.S.; RT "Epstein-Barr virus latent membrane protein 1 (LMP1) C-terminal- RT activating region 3 contributes to LMP1-mediated cellular migration RT via its interaction with Ubc9."; RL J. Virol. 85:10144-10153(2011). RN [41] RP SUBCELLULAR LOCATION. RX PubMed=22214662; DOI=10.4161/cc.11.2.18999; RA Bennett R.L., Pan Y., Christian J., Hui T., May W.S. Jr.; RT "The RAX/PACT-PKR stress response pathway promotes p53 sumoylation and RT activation, leading to G(1) arrest."; RL Cell Cycle 11:407-417(2012). RN [42] RP PHOSPHORYLATION AT SER-71. RX PubMed=22509284; DOI=10.1371/journal.pone.0034250; RA Su Y.F., Yang T., Huang H., Liu L.F., Hwang J.; RT "Phosphorylation of Ubc9 by Cdk1 enhances SUMOylation activity."; RL PLoS ONE 7:E34250-E34250(2012). RN [43] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [44] RP INTERACTION WITH SETX. RX PubMed=24105744; DOI=10.1101/gad.224923.113; RA Richard P., Feng S., Manley J.L.; RT "A SUMO-dependent interaction between Senataxin and the exosome, RT disrupted in the neurodegenerative disease AOA2, targets the exosome RT to sites of transcription-induced DNA damage."; RL Genes Dev. 27:2227-2232(2013). RN [45] RP INTERACTION WITH UHRF2. RX PubMed=23404503; DOI=10.1074/jbc.M112.438234; RA Oh Y., Chung K.C.; RT "UHRF2, a ubiquitin E3 ligase, acts as a small ubiquitin-like modifier RT E3 ligase for zinc finger protein 131."; RL J. Biol. Chem. 288:9102-9111(2013). RN [46] RP INTERACTION WITH NR3C1. RX PubMed=23508108; DOI=10.1128/MCB.01470-12; RA Druker J., Liberman A.C., Antunica-Noguerol M., Gerez J., RA Paez-Pereda M., Rein T., Iniguez-Lluhi J.A., Holsboer F., Arzt E.; RT "RSUME enhances glucocorticoid receptor SUMOylation and RT transcriptional activity."; RL Mol. Cell. Biol. 33:2116-2127(2013). RN [47] RP INTERACTION WITH RWDD3. RX PubMed=23469069; DOI=10.1371/journal.pone.0057795; RA Gerez J., Fuertes M., Tedesco L., Silberstein S., Sevlever G., RA Paez-Pereda M., Holsboer F., Turjanski A.G., Arzt E.; RT "In silico structural and functional characterization of the RSUME RT splice variants."; RL PLoS ONE 8:E57795-E57795(2013). RN [48] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [49] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-49, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [50] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [51] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS). RX PubMed=9261152; DOI=10.1074/jbc.272.34.21381; RA Tong H., Hateboer G., Perrakis A., Bernards R., Sixma T.K.; RT "Crystal structure of murine/human Ubc9 provides insight into the RT variability of the ubiquitin-conjugating system."; RL J. Biol. Chem. 272:21381-21387(1997). RN [52] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH RANGAP1. RX PubMed=11853669; DOI=10.1016/S0092-8674(02)00630-X; RA Bernier-Villamor V., Sampson D.A., Matunis M.J., Lima C.D.; RT "Structural basis for E2-mediated SUMO conjugation revealed by a RT complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1."; RL Cell 108:345-356(2002). RN [53] RP X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) IN COMPLEX WITH SUMO1; RANGAP1 RP AND RANBP2. RX PubMed=15931224; DOI=10.1038/nature03588; RA Reverter D., Lima C.D.; RT "Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9- RT Nup358 complex."; RL Nature 435:687-692(2005). RN [54] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) IN COMPLEX WITH RANGAP1, AND RP MUTAGENESIS OF ASN-85; TYR-87 AND ASP-127. RX PubMed=16732283; DOI=10.1038/nsmb1104; RA Yunus A.A., Lima C.D.; RT "Lysine activation and functional analysis of E2-mediated conjugation RT in the SUMO pathway."; RL Nat. Struct. Mol. Biol. 13:491-499(2006). RN [55] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH SUMO1, RP INTERACTION WITH SUMO1; SUMO2 AND SUMO3, AND FUNCTION. RX PubMed=17466333; DOI=10.1016/j.jmb.2007.04.006; RA Capili A.D., Lima C.D.; RT "Structure and analysis of a complex between SUMO and Ubc9 illustrates RT features of a conserved E2-Ubl interaction."; RL J. Mol. Biol. 369:608-618(2007). RN [56] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) IN COMPLEX WITH NFATC2IP/NIP45, RP INTERACTION WITH NFATC2IP, AND FUNCTION. RX PubMed=20077568; DOI=10.1002/prot.22667; RA Sekiyama N., Arita K., Ikeda Y., Hashiguchi K., Ariyoshi M., RA Tochio H., Saitoh H., Shirakawa M.; RT "Structural basis for regulation of poly-SUMO chain by a SUMO-like RT domain of Nip45."; RL Proteins 78:1491-1502(2010). RN [57] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH IPO13. RX PubMed=21139563; DOI=10.1038/emboj.2010.320; RA Grunwald M., Bono F.; RT "Structure of Importin13-Ubc9 complex: nuclear import and release of a RT key regulator of sumoylation."; RL EMBO J. 30:427-438(2011). CC -!- FUNCTION: Accepts the ubiquitin-like proteins SUMO1, SUMO2, SUMO3 CC and SUMO4 from the UBLE1A-UBLE1B E1 complex and catalyzes their CC covalent attachment to other proteins with the help of an E3 CC ligase such as RANBP2 or CBX4. Can catalyze the formation of poly- CC SUMO chains. Necessary for sumoylation of FOXL2 and KAT5. CC Essential for nuclear architecture and chromosome segregation. CC Sumoylates p53/TP53 at 'Lys-386'. {ECO:0000269|PubMed:11451954, CC ECO:0000269|PubMed:15809060, ECO:0000269|PubMed:17466333, CC ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:19744555, CC ECO:0000269|PubMed:20077568, ECO:0000269|PubMed:8668529}. CC -!- CATALYTIC ACTIVITY: ATP + SUMO + protein lysine = AMP + CC diphosphate + protein N-SUMOyllysine. CC -!- PATHWAY: Protein modification; protein sumoylation. CC -!- SUBUNIT: Interacts with SETX (PubMed:24105744). Interacts with CC HIPK1, HIPK2, PPM1J, RASD2 and TCF3 Interacts with NR2C1; the CC interaction promotes its sumoylation (By similarity). Forms a CC tight complex with RANGAP1 and RANBP2. Interacts with SIAH1 and CC PARP. Interacts with various transcription factors such as TFAP2A, CC TFAP2B, TFAP2C, AR, ETS1 and SOX4. Interacts with RWDD3; the CC interaction enhances the sumoylation of a number of proteins such CC as HIF1A and I-kappa-B. Interacts with DNMT1. Interacts with CC FOXL2. Forms a complex with SENP6 and UBE2I in response to UV CC irradiation. Interacts with human herpesvirus 6 IE2. Interacts CC with human adenovirus early E1A protein; this interaction CC interferes with polysumoylation (Probable). Interacts with DNM1l CC (via its GTPase and B domains); the interaction promotes CC sumoylation of DNM1L, mainly in its B domain. Interacts with PML- CC RARA oncoprotein (via the coiled-colied domain); the interaction CC is required for sumoylation of the PML-RARA oncoprotein. Interacts CC with IPO13. Interacts with NFATC2IP; this inhibits formation of CC poly-SUMO chains. Interacts with FHIT. Interacts with PRKRA and CC p53/TP53 (By similarity). Interacts with UHRF2. Interacts with CC NR3C1 and this interaction is enhanced in the presence of RWDD3. CC Interacts with MTA1. Interacts with Epstein-barr virus protein CC LMP1. {ECO:0000250, ECO:0000269|PubMed:10383460, CC ECO:0000269|PubMed:11085938, ECO:0000269|PubMed:11853669, CC ECO:0000269|PubMed:12072434, ECO:0000269|PubMed:12924945, CC ECO:0000269|PubMed:15378033, ECO:0000269|PubMed:15608651, CC ECO:0000269|PubMed:15809060, ECO:0000269|PubMed:15931224, CC ECO:0000269|PubMed:16631117, ECO:0000269|PubMed:16732283, CC ECO:0000269|PubMed:17005699, ECO:0000269|PubMed:17466333, CC ECO:0000269|PubMed:17956732, ECO:0000269|PubMed:19450230, CC ECO:0000269|PubMed:19638400, ECO:0000269|PubMed:19744555, CC ECO:0000269|PubMed:20077568, ECO:0000269|PubMed:20543865, CC ECO:0000269|PubMed:21139563, ECO:0000269|PubMed:21795333, CC ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:23404503, CC ECO:0000269|PubMed:23469069, ECO:0000269|PubMed:23508108, CC ECO:0000269|PubMed:24105744, ECO:0000269|PubMed:8824223, CC ECO:0000269|PubMed:9197546, ECO:0000269|PubMed:9334332, CC ECO:0000305}. CC -!- INTERACTION: CC G2XKQ0:-; NbExp=3; IntAct=EBI-80168, EBI-10175576; CC P29991:- (xeno); NbExp=3; IntAct=EBI-80168, EBI-8826488; CC O14503:BHLHE40; NbExp=3; IntAct=EBI-80168, EBI-711810; CC Q9UER7:DAXX; NbExp=3; IntAct=EBI-80168, EBI-77321; CC Q9UBC3:DNMT3B; NbExp=3; IntAct=EBI-80168, EBI-80125; CC P03116:E1 (xeno); NbExp=2; IntAct=EBI-80168, EBI-7015985; CC Q8WWZ3:EDARADD; NbExp=3; IntAct=EBI-80168, EBI-2949647; CC P19419:ELK1; NbExp=7; IntAct=EBI-80168, EBI-726632; CC Q08379:GOLGA2; NbExp=3; IntAct=EBI-80168, EBI-618309; CC P56524:HDAC4; NbExp=3; IntAct=EBI-80168, EBI-308629; CC O94829:IPO13; NbExp=6; IntAct=EBI-80168, EBI-747310; CC P03230:LMP1 (xeno); NbExp=5; IntAct=EBI-80168, EBI-6973030; CC O75928:PIAS2; NbExp=8; IntAct=EBI-80168, EBI-348555; CC P46060:RANGAP1; NbExp=5; IntAct=EBI-80168, EBI-396091; CC Q6ZNA4:RNF111; NbExp=5; IntAct=EBI-80168, EBI-2129175; CC Q9Y3V2:RWDD3; NbExp=5; IntAct=EBI-80168, EBI-1549885; CC Q7Z333:SETX; NbExp=3; IntAct=EBI-80168, EBI-1220123; CC Q13485:SMAD4; NbExp=4; IntAct=EBI-80168, EBI-347263; CC P56693:SOX10; NbExp=2; IntAct=EBI-80168, EBI-1167533; CC P63165:SUMO1; NbExp=5; IntAct=EBI-80168, EBI-80140; CC P61956:SUMO2; NbExp=6; IntAct=EBI-80168, EBI-473220; CC P05549:TFAP2A; NbExp=4; IntAct=EBI-80168, EBI-347351; CC Q92754:TFAP2C; NbExp=5; IntAct=EBI-80168, EBI-937309; CC P22314:UBA1; NbExp=2; IntAct=EBI-80168, EBI-709688; CC Q9HCK0:ZBTB26; NbExp=3; IntAct=EBI-80168, EBI-3918996; CC Q8N3Z6:ZCCHC7; NbExp=3; IntAct=EBI-80168, EBI-7265024; CC Q9Y4E5:ZNF451; NbExp=3; IntAct=EBI-80168, EBI-747230; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Mainly nuclear. In CC spermatocytes, localizes in synaptonemal complexes. Recruited by CC BCL11A into the nuclear body (By similarity). {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Expressed in heart, skeletal muscle, pancreas, CC kidney, liver, lung, placenta and brain. Also expressed in testis CC and thymus. {ECO:0000269|PubMed:8610150}. CC -!- PTM: Phosphorylation at Ser-71 significantly enhances SUMOylation CC activity. {ECO:0000269|PubMed:22509284}. CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. CC {ECO:0000255|PROSITE-ProRule:PRU00388}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH51289.3; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=BAD92225.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X96427; CAA65287.1; -; mRNA. DR EMBL; U45328; AAA86662.1; -; mRNA. DR EMBL; D45050; BAA08091.1; -; mRNA. DR EMBL; U29092; AAC51361.1; -; mRNA. DR EMBL; U31933; AAB02181.1; -; mRNA. DR EMBL; U31882; AAC50603.1; -; mRNA. DR EMBL; U66867; AAC50716.1; -; mRNA. DR EMBL; U66818; AAC50715.1; -; mRNA. DR EMBL; U38785; AAB09410.1; -; mRNA. DR EMBL; AJ002385; CAA05359.1; -; mRNA. DR EMBL; BT006932; AAP35578.1; -; mRNA. DR EMBL; AB208988; BAD92225.1; ALT_INIT; mRNA. DR EMBL; AE006466; AAK61274.1; -; Genomic_DNA. DR EMBL; AL031714; CAB45853.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85673.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85676.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85677.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85678.1; -; Genomic_DNA. DR EMBL; CH471112; EAW85679.1; -; Genomic_DNA. DR EMBL; BC000427; AAH00427.1; -; mRNA. DR EMBL; BC004429; AAH04429.1; -; mRNA. DR EMBL; BC051289; AAH51289.3; ALT_INIT; mRNA. DR CCDS; CCDS10433.1; -. DR PIR; JC6056; JC6056. DR RefSeq; NP_003336.1; NM_003345.4. DR RefSeq; NP_919235.1; NM_194259.2. DR RefSeq; NP_919236.1; NM_194260.2. DR RefSeq; NP_919237.1; NM_194261.2. DR UniGene; Hs.302903; -. DR PDB; 1A3S; X-ray; 2.80 A; A=1-158. DR PDB; 1KPS; X-ray; 2.50 A; A/C=1-158. DR PDB; 1Z5Q; Model; -; A=1-158. DR PDB; 1Z5S; X-ray; 3.01 A; A=1-158. DR PDB; 2GRN; X-ray; 1.80 A; A=1-158. DR PDB; 2GRO; X-ray; 1.70 A; A=1-158. DR PDB; 2GRP; X-ray; 2.05 A; A=1-158. DR PDB; 2GRQ; X-ray; 1.70 A; A=1-158. DR PDB; 2GRR; X-ray; 1.30 A; A=1-158. DR PDB; 2O25; X-ray; 2.60 A; C/D=1-158. DR PDB; 2PE6; X-ray; 2.40 A; A=1-158. DR PDB; 2PX9; NMR; -; B=1-158. DR PDB; 2XWU; X-ray; 2.80 A; A=1-158. DR PDB; 3A4S; X-ray; 2.70 A; A/B=1-158. DR PDB; 3UIN; X-ray; 2.60 A; A=1-158. DR PDB; 3UIO; X-ray; 2.60 A; A=1-158. DR PDB; 3UIP; X-ray; 2.29 A; A=1-158. DR PDB; 4W5V; X-ray; 2.50 A; A=1-158. DR PDB; 4Y1L; X-ray; 2.70 A; A/B=1-158. DR PDBsum; 1A3S; -. DR PDBsum; 1KPS; -. DR PDBsum; 1Z5Q; -. DR PDBsum; 1Z5S; -. DR PDBsum; 2GRN; -. DR PDBsum; 2GRO; -. DR PDBsum; 2GRP; -. DR PDBsum; 2GRQ; -. DR PDBsum; 2GRR; -. DR PDBsum; 2O25; -. DR PDBsum; 2PE6; -. DR PDBsum; 2PX9; -. DR PDBsum; 2XWU; -. DR PDBsum; 3A4S; -. DR PDBsum; 3UIN; -. DR PDBsum; 3UIO; -. DR PDBsum; 3UIP; -. DR PDBsum; 4W5V; -. DR PDBsum; 4Y1L; -. DR ProteinModelPortal; P63279; -. DR SMR; P63279; 1-157. DR BioGrid; 113177; 404. DR DIP; DIP-29078N; -. DR IntAct; P63279; 154. DR MINT; MINT-137807; -. DR STRING; 9606.ENSP00000324897; -. DR BindingDB; P63279; -. DR ChEMBL; CHEMBL3137290; -. DR TCDB; 3.A.20.1.1; the peroxisomal protein importer (ppi) family. DR PhosphoSite; P63279; -. DR BioMuta; UBE2I; -. DR DMDM; 54039791; -. DR MaxQB; P63279; -. DR PaxDb; P63279; -. DR PeptideAtlas; P63279; -. DR PRIDE; P63279; -. DR DNASU; 7329; -. DR Ensembl; ENST00000325437; ENSP00000324897; ENSG00000103275. DR Ensembl; ENST00000355803; ENSP00000348056; ENSG00000103275. DR Ensembl; ENST00000397514; ENSP00000380649; ENSG00000103275. DR Ensembl; ENST00000397515; ENSP00000380650; ENSG00000103275. DR Ensembl; ENST00000403747; ENSP00000385009; ENSG00000103275. DR Ensembl; ENST00000406620; ENSP00000384568; ENSG00000103275. DR Ensembl; ENST00000566587; ENSP00000457064; ENSG00000103275. DR GeneID; 7329; -. DR KEGG; hsa:7329; -. DR UCSC; uc002clc.2; human. DR CTD; 7329; -. DR GeneCards; UBE2I; -. DR HGNC; HGNC:12485; UBE2I. DR HPA; CAB009021; -. DR HPA; HPA003909; -. DR MIM; 601661; gene. DR neXtProt; NX_P63279; -. DR PharmGKB; PA37134; -. DR eggNOG; KOG0424; Eukaryota. DR eggNOG; COG5078; LUCA. DR GeneTree; ENSGT00550000075088; -. DR HOGENOM; HOG000233454; -. DR HOVERGEN; HBG063308; -. DR InParanoid; P63279; -. DR KO; K10577; -. DR OMA; DLKRWEC; -. DR OrthoDB; EOG7B8S5F; -. DR PhylomeDB; P63279; -. DR TreeFam; TF101122; -. DR Reactome; R-HSA-1221632; Meiotic synapsis. DR Reactome; R-HSA-3065678; SUMO is transferred from E1 to E2 (UBE2I, UBC9). DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins. DR SignaLink; P63279; -. DR UniPathway; UPA00886; -. DR ChiTaRS; UBE2I; human. DR EvolutionaryTrace; P63279; -. DR GeneWiki; UBE2I; -. DR GenomeRNAi; 7329; -. DR NextBio; 28682; -. DR PRO; PR:P63279; -. DR Proteomes; UP000005640; Chromosome 16. DR Bgee; P63279; -. DR CleanEx; HS_UBE2I; -. DR ExpressionAtlas; P63279; baseline and differential. DR Genevisible; P63279; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:1990356; C:sumoylated E2 ligase complex; IC:BHF-UCL. DR GO; GO:0000795; C:synaptonemal complex; TAS:ProtInc. DR GO; GO:1990234; C:transferase complex; IDA:BHF-UCL. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW. DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0071535; F:RING-like zinc finger domain binding; IPI:UniProtKB. DR GO; GO:0061656; F:SUMO conjugating enzyme activity; IDA:BHF-UCL. DR GO; GO:0019789; F:SUMO transferase activity; EXP:Reactome. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0006464; P:cellular protein modification process; TAS:ProtInc. DR GO; GO:0007059; P:chromosome segregation; IEA:UniProtKB-KW. DR GO; GO:0007067; P:mitotic nuclear division; IEA:UniProtKB-KW. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:BHF-UCL. DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl. DR GO; GO:1903755; P:positive regulation of SUMO transferase activity; IDA:BHF-UCL. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:0016925; P:protein sumoylation; IDA:BHF-UCL. DR GO; GO:0016567; P:protein ubiquitination; IBA:GO_Central. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; TAS:ProtInc. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. DR Gene3D; 3.10.110.10; -; 1. DR InterPro; IPR027230; Ubc9. DR InterPro; IPR000608; UBQ-conjugat_E2. DR InterPro; IPR023313; UBQ-conjugating_AS. DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD. DR PANTHER; PTHR24067:SF51; PTHR24067:SF51; 1. DR Pfam; PF00179; UQ_con; 1. DR SUPFAM; SSF54495; SSF54495; 1. DR PROSITE; PS00183; UBIQUITIN_CONJUGAT_1; 1. DR PROSITE; PS50127; UBIQUITIN_CONJUGAT_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division; KW Chromosome partition; Complete proteome; Cytoplasm; KW Host-virus interaction; Isopeptide bond; Ligase; Mitosis; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Ubl conjugation; Ubl conjugation pathway. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22814378}. FT CHAIN 2 158 SUMO-conjugating enzyme UBC9. FT /FTId=PRO_0000082454. FT REGION 13 18 Interaction with SUMO1. FT ACT_SITE 93 93 Glycyl thioester intermediate. FT SITE 4 4 Interaction with RANBP2. FT SITE 25 25 Interaction with RANBP2. FT SITE 57 57 Interaction with RANBP2. FT SITE 100 101 Substrate binding. FT MOD_RES 2 2 N-acetylserine. FT {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22814378}. FT MOD_RES 65 65 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 71 71 Phosphoserine; by CDK1. FT {ECO:0000269|PubMed:22509284}. FT CROSSLNK 18 18 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT CROSSLNK 49 49 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT MUTAGEN 13 14 RK->AA: Impairs binding to SUMO1 and FT catalytic activity. FT {ECO:0000269|PubMed:12924945}. FT MUTAGEN 17 18 RK->AA: Impairs binding to SUMO1 and FT catalytic activity. FT {ECO:0000269|PubMed:12924945}. FT MUTAGEN 22 22 F->A: Impairs binding to RANBP2. FT {ECO:0000269|PubMed:15608651}. FT MUTAGEN 25 25 V->A: Impairs binding to RANBP2. FT {ECO:0000269|PubMed:15608651}. FT MUTAGEN 27 27 V->A: Impairs binding to RANBP2. FT {ECO:0000269|PubMed:15608651}. FT MUTAGEN 42 42 E->A: Slightly impairs binding to RANBP2. FT {ECO:0000269|PubMed:15608651}. FT MUTAGEN 48 48 K->A: Slightly impairs binding to RANBP2. FT {ECO:0000269|PubMed:15608651}. FT MUTAGEN 54 54 E->A: Slightly impairs binding to RANBP2. FT {ECO:0000269|PubMed:15608651}. FT MUTAGEN 57 57 L->A: Impairs binding to RANBP2. FT {ECO:0000269|PubMed:15608651}. FT MUTAGEN 59 59 K->A: Impairs binding to RANBP2. FT {ECO:0000269|PubMed:15608651}. FT MUTAGEN 61 61 R->A: Slightly impairs binding to RANBP2. FT {ECO:0000269|PubMed:15608651}. FT MUTAGEN 85 85 N->Q: Impairs catalytic activity. FT {ECO:0000269|PubMed:16732283}. FT MUTAGEN 87 87 Y->A: Impairs catalytic activity. FT {ECO:0000269|PubMed:16732283}. FT MUTAGEN 93 93 C->S: Loss of enhancement of sumoylation FT by RWDD3. No effect on RWDD3 protein FT levels. FT MUTAGEN 100 101 DK->AA: Impairs catalytic activity. FT {ECO:0000269|PubMed:12641448}. FT MUTAGEN 127 127 D->A: Impairs catalytic activity. FT {ECO:0000269|PubMed:16732283}. FT MUTAGEN 127 127 D->S: No effect on catalytic activity. FT {ECO:0000269|PubMed:16732283}. FT CONFLICT 18 18 K -> P (in Ref. 6; AAC50603). FT {ECO:0000305}. FT CONFLICT 86 89 VYPS -> GVPF (in Ref. 6; AAC50603). FT {ECO:0000305}. FT HELIX 3 18 {ECO:0000244|PDB:2GRR}. FT STRAND 25 30 {ECO:0000244|PDB:2GRR}. FT STRAND 32 34 {ECO:0000244|PDB:2PE6}. FT STRAND 36 46 {ECO:0000244|PDB:2GRR}. FT TURN 52 55 {ECO:0000244|PDB:2GRR}. FT STRAND 57 63 {ECO:0000244|PDB:2GRR}. FT TURN 66 69 {ECO:0000244|PDB:2GRR}. FT STRAND 74 79 {ECO:0000244|PDB:2GRR}. FT STRAND 90 92 {ECO:0000244|PDB:2GRR}. FT HELIX 95 97 {ECO:0000244|PDB:2GRR}. FT TURN 99 102 {ECO:0000244|PDB:2GRR}. FT HELIX 109 121 {ECO:0000244|PDB:2GRR}. FT HELIX 131 139 {ECO:0000244|PDB:2GRR}. FT HELIX 141 154 {ECO:0000244|PDB:2GRR}. SQ SEQUENCE 158 AA; 18007 MW; E2C826E9C8D0683D CRC64; MSGIALSRLA QERKAWRKDH PFGFVAVPTK NPDGTMNLMN WECAIPGKKG TPWEGGLFKL RMLFKDDYPS SPPKCKFEPP LFHPNVYPSG TVCLSILEED KDWRPAITIK QILLGIQELL NEPNIQDPAQ AEAYTIYCQN RVEYEKRVRA QAKKFAPS // ID VDR_HUMAN Reviewed; 427 AA. AC P11473; B2R5Q1; G3V1V9; Q5PSV3; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1989, sequence version 1. DT 11-NOV-2015, entry version 194. DE RecName: Full=Vitamin D3 receptor; DE Short=VDR; DE AltName: Full=1,25-dihydroxyvitamin D3 receptor; DE AltName: Full=Nuclear receptor subfamily 1 group I member 1; GN Name=VDR; Synonyms=NR1I1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2835767; DOI=10.1073/pnas.85.10.3294; RA Baker A.R., McDonnell D.P., Hughes M., Crisp T.M., Mangelsdorf D.J., RA Haussler M.R., Pike J.W., Shine J., O'Malley B.W.; RT "Cloning and expression of full-length cDNA encoding human vitamin D RT receptor."; RL Proc. Natl. Acad. Sci. U.S.A. 85:3294-3298(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1324736; DOI=10.1016/0167-4781(92)90063-6; RA Goto H., Chen K.S., Prahl J.M., Deluca H.F.; RT "A single receptor identical with that from intestine/T47D cells RT mediates the action of 1,25-dihydroxyvitamin D-3 in HL-60 cells."; RL Biochim. Biophys. Acta 1132:103-108(1992). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Lens epithelium; RA Rae J.L., Shepard A.R.; RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9212063; DOI=10.1210/me.11.8.1165; RA Miyamoto K., Kesterson R.A., Yamamoto H., Taketani Y., Nishiwaki E., RA Tatsumi S., Inoue Y., Morita K., Takeda E., Pike J.W.; RT "Structural organization of the human vitamin D receptor chromosomal RT gene and its promoter."; RL Mol. Endocrinol. 11:1165-1179(1997). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-230 AND ILE-362. RG NIEHS SNPs program; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., RA Kucherlapati R., Weinstock G., Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP NUCLEOTIDE SEQUENCE [MRNA] OF 24-90 (ISOFORM 1/2). RC TISSUE=Peripheral blood; RX PubMed=1850412; RA Yu X.-P., Mocharla H., Hustmyer F.G., Manolagas S.C.; RT "Vitamin D receptor expression in human lymphocytes. Signal RT requirements and characterization by western blots and DNA RT sequencing."; RL J. Biol. Chem. 266:7588-7595(1991). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 343-427. RX PubMed=16252240; DOI=10.1086/497438; RA Fang Y., van Meurs J.B., d'Alesio A., Jhamai M., Zhao H., RA Rivadeneira F., Hofman A., van Leeuwen J.P., Jehan F., Pols H.A., RA Uitterlinden A.G.; RT "Promoter and 3'-untranslated-region haplotypes in the vitamin D RT receptor gene predispose to osteoporotic fracture: the Rotterdam RT study."; RL Am. J. Hum. Genet. 77:807-823(2005). RN [12] RP INTERACTION WITH NCOA3. RX PubMed=9267036; DOI=10.1016/S0092-8674(00)80516-4; RA Chen H., Lin R.J., Schiltz R.L., Chakravarti D., Nash A., Nagy L., RA Privalsky M.L., Nakatani Y., Evans R.M.; RT "Nuclear receptor coactivator ACTR is a novel histone RT acetyltransferase and forms a multimeric activation complex with P/CAF RT and CBP/p300."; RL Cell 90:569-580(1997). RN [13] RP INTERACTION WITH SNW1. RX PubMed=9632709; DOI=10.1074/jbc.273.26.16434; RA Baudino T.A., Kraichely D.M., Jefcoat S.C. Jr., Winchester S.K., RA Partridge N.C., Macdonald P.N.; RT "Isolation and characterization of a novel coactivator protein, NCoA- RT 62, involved in vitamin D-mediated transcription."; RL J. Biol. Chem. 273:16434-16441(1998). RN [14] RP INTERACTION WITH NCOA6. RX PubMed=10866662; DOI=10.1128/MCB.20.14.5048-5063.2000; RA Mahajan M.A., Samuels H.H.; RT "A new family of nuclear receptor coregulators that integrates nuclear RT receptor signaling through CBP."; RL Mol. Cell. Biol. 20:5048-5063(2000). RN [15] RP FUNCTION, AND INTERACTION WITH BAZ1B. RX PubMed=16252006; DOI=10.1038/sj.emboj.7600853; RA Fujiki R., Kim M.-S., Sasaki Y., Yoshimura K., Kitagawa H., Kato S.; RT "Ligand-induced transrepression by VDR through association of WSTF RT with acetylated histones."; RL EMBO J. 24:3881-3894(2005). RN [16] RP INTERACTION WITH IRX4. RC TISSUE=Prostate; RX PubMed=22323358; DOI=10.1093/hmg/dds025; RA Nguyen H.H., Takata R., Akamatsu S., Shigemizu D., Tsunoda T., RA Furihata M., Takahashi A., Kubo M., Kamatani N., Ogawa O., Fujioka T., RA Nakamura Y., Nakagawa H.; RT "IRX4 at 5p15 suppresses prostate cancer growth through the RT interaction with vitamin D receptor, conferring prostate cancer RT susceptibility."; RL Hum. Mol. Genet. 21:2076-2085(2012). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 118-427 IN COMPLEX WITH RP DIHYDROXYVITAMIN D3, IDENTIFICATION BY MASS SPECTROMETRY, AND RP FUNCTION. RX PubMed=10678179; DOI=10.1016/S1097-2765(00)80413-X; RA Rochel N., Wurtz J.-M., Mitschler A., Klaholz B., Moras D.; RT "The crystal structure of the nuclear receptor for vitamin D bound to RT its natural ligand."; RL Mol. Cell 5:173-179(2000). RN [18] RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 118-427 IN COMPLEXES WITH RP VITAMIN D3 AND VITAMIN D3 ANALOGS. RX PubMed=11344298; DOI=10.1073/pnas.091018698; RA Tocchini-Valentini G., Rochel N., Wurtz J.-M., Mitschler A., Moras D.; RT "Crystal structures of the vitamin D receptor complexed to RT superagonist 20-epi ligands."; RL Proc. Natl. Acad. Sci. U.S.A. 98:5491-5496(2001). RN [19] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 16-125 IN COMPLEX WITH DNA, RP MUTAGENESIS OF 61-PRO-PHE-62 AND HIS-75, AND SUBUNIT. RX PubMed=11980721; DOI=10.1093/emboj/21.9.2242; RA Shaffer P.L., Gewirth D.T.; RT "Structural basis of VDR-DNA interactions on direct repeat response RT elements."; RL EMBO J. 21:2242-2252(2002). RN [20] RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 188-427 IN COMPLEXES WITH RP VITAMIN D3 ANALOGS. RX PubMed=15055995; DOI=10.1021/jm0310582; RA Tocchini-Valentini G., Rochel N., Wurtz J.-M., Moras D.; RT "Crystal structures of the vitamin D nuclear receptor liganded with RT the vitamin D side chain analogues calcipotriol and seocalcitol, RT receptor agonists of clinical importance. Insights into a structural RT basis for the switching of calcipotriol to a receptor antagonist by RT further side chain modification."; RL J. Med. Chem. 47:1956-1961(2004). RN [21] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 16-125 OF MUTANT RP ALA-61/ALA-62/ALA-75 IN COMPLEX WITH RXRA AND DNA, AND SUBUNIT. RX PubMed=15225774; DOI=10.1016/j.jsbmb.2004.03.084; RA Shaffer P.L., Gewirth D.T.; RT "Structural analysis of RXR-VDR interactions on DR3 DNA."; RL J. Steroid Biochem. Mol. Biol. 89:215-219(2004). RN [22] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 188-427 IN COMPLEX WITH RP VITAMIN D3 ANALOG, IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND RP INTERACTION WITH NCOA1; NCOA2 AND MED1. RX PubMed=15728261; DOI=10.1124/mol.104.008730; RA Eelen G., Verlinden L., Rochel N., Claessens F., De Clercq P., RA Vandewalle M., Tocchini-Valentini G., Moras D., Bouillon R., RA Verstuyf A.; RT "Superagonistic action of 14-epi-analogs of 1,25-dihydroxyvitamin D RT explained by vitamin D receptor-coactivator interaction."; RL Mol. Pharmacol. 67:1566-1573(2005). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 188-427 IN COMPLEXES WITH RP DIHYDROXYVITAMIN D3 AND VITAMIN D3 ANALOGS, AND FUNCTION. RX PubMed=16913708; DOI=10.1021/jm0604070; RA Hourai S., Fujishima T., Kittaka A., Suhara Y., Takayama H., RA Rochel N., Moras D.; RT "Probing a water channel near the A-ring of receptor-bound 1 alpha,25- RT dihydroxyvitamin D3 with selected 2 alpha-substituted analogues."; RL J. Med. Chem. 49:5199-5205(2006). RN [24] RP VARIANTS VDDR2A ASP-33 AND GLN-73. RX PubMed=2849209; DOI=10.1126/science.2849209; RA Hughes M.R., Malloy P.J., Kieback D.G., Kesterson R.A., Pike J.W., RA Feldman D., O'Malley B.W.; RT "Point mutations in the human vitamin D receptor gene associated with RT hypocalcemic rickets."; RL Science 242:1702-1705(1988). RN [25] RP VARIANT VDDR2A GLN-35. RX PubMed=8381803; DOI=10.1210/jcem.76.2.8381803; RA Yagi H., Ozono K., Miyake H., Nagashima K., Kuroume T., Pike J.W.; RT "A new point mutation in the deoxyribonucleic acid-binding domain of RT the vitamin D receptor in a kindred with hereditary 1,25- RT dihydroxyvitamin D-resistant rickets."; RL J. Clin. Endocrinol. Metab. 76:509-512(1993). RN [26] RP VARIANT VDDR2A GLN-50. RX PubMed=1652893; RA Saijo T., Ito M., Takeda E., Mahbubul Huq A.H.M., Naito E., Yokota I., RA Sone T., Pike J.W., Kuroda Y.; RT "A unique mutation in the vitamin D receptor gene in three Japanese RT patients with vitamin D-dependent rickets type II: utility of single- RT strand conformation polymorphism analysis for heterozygous carrier RT detection."; RL Am. J. Hum. Genet. 49:668-673(1991). RN [27] RP VARIANT VDDR2A GLN-80. RX PubMed=2177843; DOI=10.1210/mend-4-4-623; RA Sone T., Marx S.J., Liberman U.A., Pike J.W.; RT "A unique point mutation in the human vitamin D receptor chromosomal RT gene confers hereditary resistance to 1,25-dihydroxyvitamin D3."; RL Mol. Endocrinol. 4:623-631(1990). RN [28] RP VARIANT VDDR2A GLN-80. RX PubMed=8106618; DOI=10.1210/jc.78.2.313; RA Malloy P.J., Weisman Y., Feldman D.; RT "Hereditary 1 alpha,25-dihydroxyvitamin D-resistant rickets resulting RT from a mutation in the vitamin D receptor deoxyribonucleic acid- RT binding domain."; RL J. Clin. Endocrinol. Metab. 78:313-316(1994). RN [29] RP VARIANT VDDR2A LEU-274. RX PubMed=8392085; DOI=10.1172/JCI116539; RA Kristjansson K., Rut A.R., Hewison M., O'Riordan J.L.H., Hughes M.R.; RT "Two mutations in the hormone binding domain of the vitamin D receptor RT cause tissue resistance to 1,25 dihydroxyvitamin D3."; RL J. Clin. Invest. 92:12-16(1993). RN [30] RP VARIANTS VDDR2A GLU-45 AND ILE-47. RX PubMed=7828346; DOI=10.1111/j.1365-2265.1994.tb01822.x; RA Rut A.R., Hewison M., Kristjansson K., Luisi B., Hughes M.R., RA O'Riordan J.L.H.; RT "Two mutations causing vitamin D resistant rickets: modelling on the RT basis of steroid hormone receptor DNA-binding domain crystal RT structures."; RL Clin. Endocrinol. (Oxf.) 41:581-590(1994). RN [31] RP VARIANT VDDR2A ASP-46. RX PubMed=8675579; DOI=10.1210/jc.81.7.2564; RA Lin U.-T., Malloy P.J., Sakati N., Al-Ashwal A., Feldman D.; RT "A novel mutation in the deoxyribonucleic acid-binding domain of the RT vitamin D receptor causes hereditary 1,25-dihydroxyvitamin D-resistant RT rickets."; RL J. Clin. Endocrinol. Metab. 81:2564-2569(1996). RN [32] RP VARIANTS VDDR2A SER-314 AND CYS-391. RX PubMed=8961271; DOI=10.1210/me.10.12.1617; RA Whitfield G.K., Selznick S.H., Haussler C.A., Hsieh J.-C., RA Galligan M.A., Jurutka P.W., Thompson P.D., Lee S.M., Zerwekh J.E., RA Haussler M.R.; RT "Vitamin D receptors from patients with resistance to 1,25- RT dihydroxyvitamin D(3): point mutations confer reduced transactivation RT in response to ligand and impaired interaction with the retinoid X RT receptor heterodimeric partner."; RL Mol. Endocrinol. 10:1617-1631(1996). RN [33] RP VARIANT VDDR2A GLN-305. RX PubMed=9005998; DOI=10.1172/JCI119158; RA Malloy P.J., Eccleshall T.R., Gross C., van Maldergem L., Bouillon R., RA Feldman D.; RT "Hereditary vitamin D resistant rickets caused by a novel mutation in RT the vitamin D receptor that results in decreased affinity for hormone RT and cellular hyporesponsiveness."; RL J. Clin. Invest. 99:297-304(1997). RN [34] RP INVOLVEMENT IN MYCOBACTERIUM TUBERCULOSIS SUSCEPTIBILITY. RX PubMed=15032981; DOI=10.1111/j..2004.00183.x; RA Selvaraj P., Kurian S.M., Chandra G., Reetha A.M., Charles N., RA Narayanan P.R.; RT "Vitamin D receptor gene variants of BsmI, ApaI, TaqI, and FokI RT polymorphisms in spinal tuberculosis."; RL Clin. Genet. 65:73-76(2004). CC -!- FUNCTION: Nuclear hormone receptor. Transcription factor that CC mediates the action of vitamin D3 by controlling the expression of CC hormone sensitive genes. Recruited to promoters via its CC interaction with BAZ1B/WSTF which mediates the interaction with CC acetylated histones, an essential step for VDR-promoter CC association. Plays a central role in calcium homeostasis. CC {ECO:0000269|PubMed:10678179, ECO:0000269|PubMed:15728261, CC ECO:0000269|PubMed:16252006, ECO:0000269|PubMed:16913708}. CC -!- SUBUNIT: Homodimer in the absence of bound vitamin D3. Heterodimer CC with RXRA after vitamin D3 binding. Interacts with SMAD3. CC Interacts with MED1, NCOA1, NCOA2, NCOA3 and NCOA6 coactivators, CC leading to a strong increase of transcription of target genes. CC Interacts (in a ligand-dependent manner) with BAZ1B/WSTF. CC Interacts with SNW1. Interacts with IRX4, the interaction doesn't CC affect its transactivation activity. {ECO:0000269|PubMed:10678179, CC ECO:0000269|PubMed:10866662, ECO:0000269|PubMed:11980721, CC ECO:0000269|PubMed:15225774, ECO:0000269|PubMed:15728261, CC ECO:0000269|PubMed:16252006, ECO:0000269|PubMed:22323358, CC ECO:0000269|PubMed:9267036, ECO:0000269|PubMed:9632709}. CC -!- INTERACTION: CC Q09472:EP300; NbExp=3; IntAct=EBI-286357, EBI-447295; CC Q9JLI4:Ncoa6 (xeno); NbExp=2; IntAct=EBI-286357, EBI-286271; CC P26045:PTPN3; NbExp=4; IntAct=EBI-286357, EBI-1047946; CC Q13573:SNW1; NbExp=5; IntAct=EBI-286357, EBI-632715; CC P04637:TP53; NbExp=6; IntAct=EBI-286357, EBI-366083; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P11473-1; Sequence=Displayed; CC Name=2; CC IsoId=P11473-2; Sequence=VSP_047218; CC Note=No experimental confirmation available.; CC -!- DOMAIN: Composed of three domains: a modulating N-terminal domain, CC a DNA-binding domain and a C-terminal ligand-binding domain. CC -!- POLYMORPHISM: Genetic variations in VDR may determine CC Mycobacterium tuberculosis susceptibility [MIM:607948]. CC -!- DISEASE: Rickets vitamin D-dependent 2A (VDDR2A) [MIM:277440]: A CC disorder of vitamin D metabolism resulting in severe rickets, CC hypocalcemia and secondary hyperparathyroidism. Most patients have CC total alopecia in addition to rickets. CC {ECO:0000269|PubMed:1652893, ECO:0000269|PubMed:2177843, CC ECO:0000269|PubMed:2849209, ECO:0000269|PubMed:7828346, CC ECO:0000269|PubMed:8106618, ECO:0000269|PubMed:8381803, CC ECO:0000269|PubMed:8392085, ECO:0000269|PubMed:8675579, CC ECO:0000269|PubMed:8961271, ECO:0000269|PubMed:9005998}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- SIMILARITY: Belongs to the nuclear hormone receptor family. NR1 CC subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 nuclear receptor DNA-binding domain. CC {ECO:0000255|PROSITE-ProRule:PRU00407}. CC -!- CAUTION: It is uncertain whether Met-1 or Met-4 is the initiator. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH60832.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAP88938.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/vdr/"; CC -!- WEB RESOURCE: Name=SHMPD; Note=The Singapore human mutation and CC polymorphism database; CC URL="http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=VDR"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; J03258; AAA61273.1; -; mRNA. DR EMBL; X67482; CAA47824.1; -; mRNA. DR EMBL; AF026260; AAB95155.1; -; mRNA. DR EMBL; AB002168; BAA83389.1; -; Genomic_DNA. DR EMBL; AY342401; AAP88938.1; ALT_SEQ; Genomic_DNA. DR EMBL; AK312267; BAG35198.1; -; mRNA. DR EMBL; AC004466; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC121338; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471111; EAW57960.1; -; Genomic_DNA. DR EMBL; CH471111; EAW57961.1; -; Genomic_DNA. DR EMBL; BC060832; AAH60832.1; ALT_INIT; mRNA. DR EMBL; M65208; AAA61274.1; -; mRNA. DR EMBL; AY827087; AAV85448.1; -; Genomic_DNA. DR CCDS; CCDS55820.1; -. [P11473-2] DR CCDS; CCDS8757.1; -. [P11473-1] DR PIR; A28200; A28200. DR RefSeq; NP_000367.1; NM_000376.2. [P11473-1] DR RefSeq; NP_001017535.1; NM_001017535.1. [P11473-1] DR RefSeq; NP_001017536.1; NM_001017536.1. [P11473-2] DR RefSeq; XP_006719650.1; XM_006719587.2. [P11473-1] DR RefSeq; XP_011537022.1; XM_011538720.1. [P11473-1] DR UniGene; Hs.524368; -. DR PDB; 1DB1; X-ray; 1.80 A; A=118-427. DR PDB; 1IE8; X-ray; 1.52 A; A=118-427. DR PDB; 1IE9; X-ray; 1.40 A; A=118-427. DR PDB; 1KB2; X-ray; 2.70 A; A/B=16-125. DR PDB; 1KB4; X-ray; 2.80 A; A/B=16-125. DR PDB; 1KB6; X-ray; 2.70 A; A/B=16-125. DR PDB; 1S0Z; X-ray; 2.50 A; A=118-427. DR PDB; 1S19; X-ray; 2.10 A; A=118-427. DR PDB; 1TXI; X-ray; 1.90 A; A=118-427. DR PDB; 1YNW; X-ray; 3.00 A; A=16-125. DR PDB; 2HAM; X-ray; 1.90 A; A=118-427. DR PDB; 2HAR; X-ray; 1.90 A; A=118-427. DR PDB; 2HAS; X-ray; 1.96 A; A=118-427. DR PDB; 2HB7; X-ray; 1.80 A; A=118-427. DR PDB; 2HB8; X-ray; 2.00 A; A=118-427. DR PDB; 3A2I; X-ray; 3.27 A; A=118-427. DR PDB; 3A2J; X-ray; 2.70 A; A=118-427. DR PDB; 3A3Z; X-ray; 1.72 A; X=118-427. DR PDB; 3A40; X-ray; 1.45 A; X=118-427. DR PDB; 3A78; X-ray; 1.90 A; A=118-427. DR PDB; 3AUQ; X-ray; 2.64 A; A=118-427. DR PDB; 3AUR; X-ray; 2.21 A; A=118-427. DR PDB; 3AX8; X-ray; 2.60 A; A=118-427. DR PDB; 3AZ1; X-ray; 1.50 A; A=120-423. DR PDB; 3AZ2; X-ray; 1.69 A; A=120-423. DR PDB; 3AZ3; X-ray; 1.36 A; A=120-423. DR PDB; 3B0T; X-ray; 1.30 A; A=120-423. DR PDB; 3CS4; X-ray; 2.00 A; A=118-427. DR PDB; 3CS6; X-ray; 1.80 A; A=118-427. DR PDB; 3KPZ; X-ray; 1.90 A; A=118-427. DR PDB; 3M7R; X-ray; 1.80 A; A=120-423. DR PDB; 3OGT; X-ray; 1.75 A; A=118-427. DR PDB; 3P8X; X-ray; 1.70 A; A=118-164, A=217-427. DR PDB; 3TKC; X-ray; 1.75 A; A=118-427. DR PDB; 3VHW; X-ray; 2.43 A; A=118-427. DR PDB; 3W0A; X-ray; 1.80 A; A=120-423. DR PDB; 3W0C; X-ray; 1.90 A; A=120-423. DR PDB; 3W0Y; X-ray; 1.98 A; A=120-423. DR PDB; 3WGP; X-ray; 2.00 A; A=120-423. DR PDB; 3WWR; X-ray; 3.18 A; A=118-427. DR PDB; 4G2I; X-ray; 1.80 A; A=118-427. DR PDB; 4ITE; X-ray; 2.49 A; A=118-427. DR PDB; 4ITF; X-ray; 2.84 A; A=118-427. DR PDB; 4PA2; X-ray; 2.00 A; A=118-427. DR PDBsum; 1DB1; -. DR PDBsum; 1IE8; -. DR PDBsum; 1IE9; -. DR PDBsum; 1KB2; -. DR PDBsum; 1KB4; -. DR PDBsum; 1KB6; -. DR PDBsum; 1S0Z; -. DR PDBsum; 1S19; -. DR PDBsum; 1TXI; -. DR PDBsum; 1YNW; -. DR PDBsum; 2HAM; -. DR PDBsum; 2HAR; -. DR PDBsum; 2HAS; -. DR PDBsum; 2HB7; -. DR PDBsum; 2HB8; -. DR PDBsum; 3A2I; -. DR PDBsum; 3A2J; -. DR PDBsum; 3A3Z; -. DR PDBsum; 3A40; -. DR PDBsum; 3A78; -. DR PDBsum; 3AUQ; -. DR PDBsum; 3AUR; -. DR PDBsum; 3AX8; -. DR PDBsum; 3AZ1; -. DR PDBsum; 3AZ2; -. DR PDBsum; 3AZ3; -. DR PDBsum; 3B0T; -. DR PDBsum; 3CS4; -. DR PDBsum; 3CS6; -. DR PDBsum; 3KPZ; -. DR PDBsum; 3M7R; -. DR PDBsum; 3OGT; -. DR PDBsum; 3P8X; -. DR PDBsum; 3TKC; -. DR PDBsum; 3VHW; -. DR PDBsum; 3W0A; -. DR PDBsum; 3W0C; -. DR PDBsum; 3W0Y; -. DR PDBsum; 3WGP; -. DR PDBsum; 3WWR; -. DR PDBsum; 4G2I; -. DR PDBsum; 4ITE; -. DR PDBsum; 4ITF; -. DR PDBsum; 4PA2; -. DR DisProt; DP00184; -. DR ProteinModelPortal; P11473; -. DR SMR; P11473; 21-425. DR BioGrid; 113264; 96. DR DIP; DIP-32624N; -. DR IntAct; P11473; 19. DR MINT; MINT-236408; -. DR STRING; 9606.ENSP00000447173; -. DR BindingDB; P11473; -. DR ChEMBL; CHEMBL1977; -. DR DrugBank; DB01436; Alfacalcidol. DR DrugBank; DB00146; Calcidiol. DR DrugBank; DB02300; Calcipotriol. DR DrugBank; DB00136; Calcitriol. DR DrugBank; DB00169; Cholecalciferol. DR DrugBank; DB01070; Dihydrotachysterol. DR DrugBank; DB00153; Ergocalciferol. DR DrugBank; DB00910; Paricalcitol. DR GuidetoPHARMACOLOGY; 605; -. DR PhosphoSite; P11473; -. DR BioMuta; VDR; -. DR DMDM; 137617; -. DR MaxQB; P11473; -. DR PaxDb; P11473; -. DR PRIDE; P11473; -. DR DNASU; 7421; -. DR Ensembl; ENST00000229022; ENSP00000229022; ENSG00000111424. [P11473-1] DR Ensembl; ENST00000395324; ENSP00000378734; ENSG00000111424. [P11473-1] DR Ensembl; ENST00000549336; ENSP00000449573; ENSG00000111424. [P11473-1] DR Ensembl; ENST00000550325; ENSP00000447173; ENSG00000111424. [P11473-2] DR GeneID; 7421; -. DR KEGG; hsa:7421; -. DR UCSC; uc001rql.3; human. DR UCSC; uc001rqm.3; human. [P11473-1] DR CTD; 7421; -. DR GeneCards; VDR; -. DR HGNC; HGNC:12679; VDR. DR MIM; 277440; phenotype. DR MIM; 601769; gene. DR MIM; 607948; phenotype. DR neXtProt; NX_P11473; -. DR Orphanet; 93160; Hypocalcemic vitamin D-resistant rickets. DR PharmGKB; PA37301; -. DR eggNOG; KOG3575; Eukaryota. DR eggNOG; ENOG410XRZC; LUCA. DR GeneTree; ENSGT00810000125350; -. DR HOGENOM; HOG000220844; -. DR HOVERGEN; HBG108655; -. DR InParanoid; P11473; -. DR KO; K08539; -. DR OMA; FCQFRPP; -. DR PhylomeDB; P11473; -. DR TreeFam; TF316304; -. DR Reactome; R-HSA-383280; Nuclear Receptor transcription pathway. DR SignaLink; P11473; -. DR ChiTaRS; VDR; human. DR EvolutionaryTrace; P11473; -. DR GeneWiki; Calcitriol_receptor; -. DR GenomeRNAi; 7421; -. DR NextBio; 29054; -. DR PRO; PR:P11473; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; P11473; -. DR CleanEx; HS_VDR; -. DR ExpressionAtlas; P11473; baseline and differential. DR Genevisible; P11473; HS. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0043235; C:receptor complex; IDA:BHF-UCL. DR GO; GO:0090575; C:RNA polymerase II transcription factor complex; IDA:BHF-UCL. DR GO; GO:1902098; F:calcitriol binding; IDA:UniProtKB. DR GO; GO:0008434; F:calcitriol receptor activity; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:1902121; F:lithocholic acid binding; IDA:UniProtKB. DR GO; GO:0038186; F:lithocholic acid receptor activity; IDA:UniProtKB. DR GO; GO:0046965; F:retinoid X receptor binding; IPI:BHF-UCL. DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro. DR GO; GO:0003707; F:steroid hormone receptor activity; IEA:InterPro. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0038183; P:bile acid signaling pathway; IDA:UniProtKB. DR GO; GO:0006816; P:calcium ion transport; IEA:Ensembl. DR GO; GO:0000902; P:cell morphogenesis; IMP:UniProtKB. DR GO; GO:0006874; P:cellular calcium ion homeostasis; IEA:Ensembl. DR GO; GO:0046697; P:decidualization; IEP:BHF-UCL. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0050892; P:intestinal absorption; IEA:Ensembl. DR GO; GO:0007595; P:lactation; IEA:Ensembl. DR GO; GO:0060745; P:mammary gland branching involved in pregnancy; IEA:Ensembl. DR GO; GO:0008285; P:negative regulation of cell proliferation; IDA:BHF-UCL. DR GO; GO:0010839; P:negative regulation of keratinocyte proliferation; IMP:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI. DR GO; GO:0060058; P:positive regulation of apoptotic process involved in mammary gland involution; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB. DR GO; GO:0010980; P:positive regulation of vitamin D 24-hydroxylase activity; IDA:BHF-UCL. DR GO; GO:0060558; P:regulation of calcidiol 1-monooxygenase activity; ISS:BHF-UCL. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0070561; P:vitamin D receptor signaling pathway; IDA:BHF-UCL. DR Gene3D; 1.10.565.10; -; 2. DR Gene3D; 3.30.50.10; -; 1. DR InterPro; IPR000536; Nucl_hrmn_rcpt_lig-bd. DR InterPro; IPR001723; Nuclear_hrmn_rcpt. DR InterPro; IPR000324; VitD_rcpt. DR InterPro; IPR001628; Znf_hrmn_rcpt. DR InterPro; IPR013088; Znf_NHR/GATA. DR Pfam; PF00104; Hormone_recep; 1. DR Pfam; PF00105; zf-C4; 1. DR PRINTS; PR00398; STRDHORMONER. DR PRINTS; PR00047; STROIDFINGER. DR PRINTS; PR00350; VITAMINDR. DR SMART; SM00430; HOLI; 1. DR SMART; SM00399; ZnF_C4; 1. DR SUPFAM; SSF48508; SSF48508; 1. DR PROSITE; PS00031; NUCLEAR_REC_DBD_1; 1. DR PROSITE; PS51030; NUCLEAR_REC_DBD_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Complete proteome; KW Disease mutation; DNA-binding; Metal-binding; Nucleus; Polymorphism; KW Receptor; Reference proteome; Transcription; Transcription regulation; KW Zinc; Zinc-finger. FT CHAIN 1 427 Vitamin D3 receptor. FT /FTId=PRO_0000053542. FT DNA_BIND 21 96 Nuclear receptor. {ECO:0000255|PROSITE- FT ProRule:PRU00407}. FT ZN_FING 24 44 NR C4-type. {ECO:0000255|PROSITE- FT ProRule:PRU00407}. FT ZN_FING 60 84 NR C4-type. {ECO:0000255|PROSITE- FT ProRule:PRU00407}. FT REGION 97 191 Hinge. FT REGION 192 427 Ligand-binding. FT REGION 227 237 Vitamin D3 binding. FT REGION 271 278 Vitamin D3 binding. FT BINDING 143 143 Vitamin D3. FT BINDING 305 305 Vitamin D3. FT BINDING 397 397 Vitamin D3. FT VAR_SEQ 1 1 M -> MEWRNKKRSDWLSMVLRTAGVEEAFGSEVSVRPHRR FT APLGSTYLPPAPSGM (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_047218. FT VARIANT 33 33 G -> D (in VDDR2A). FT {ECO:0000269|PubMed:2849209}. FT /FTId=VAR_004656. FT VARIANT 35 35 H -> Q (in VDDR2A). FT {ECO:0000269|PubMed:8381803}. FT /FTId=VAR_004657. FT VARIANT 45 45 K -> E (in VDDR2A). FT {ECO:0000269|PubMed:7828346}. FT /FTId=VAR_004658. FT VARIANT 46 46 G -> D (in VDDR2A). FT {ECO:0000269|PubMed:8675579}. FT /FTId=VAR_004659. FT VARIANT 47 47 F -> I (in VDDR2A). FT {ECO:0000269|PubMed:7828346}. FT /FTId=VAR_004660. FT VARIANT 50 50 R -> Q (in VDDR2A). FT {ECO:0000269|PubMed:1652893}. FT /FTId=VAR_004661. FT VARIANT 73 73 R -> Q (in VDDR2A). FT {ECO:0000269|PubMed:2849209}. FT /FTId=VAR_004662. FT VARIANT 80 80 R -> Q (in VDDR2A). FT {ECO:0000269|PubMed:2177843, FT ECO:0000269|PubMed:8106618}. FT /FTId=VAR_004663. FT VARIANT 230 230 L -> V (in dbSNP:rs11574090). FT {ECO:0000269|Ref.5}. FT /FTId=VAR_029309. FT VARIANT 274 274 R -> L (in VDDR2A; decreases affinity for FT ligand by a factor of 1000). FT {ECO:0000269|PubMed:8392085}. FT /FTId=VAR_004664. FT VARIANT 305 305 H -> Q (in VDDR2A). FT {ECO:0000269|PubMed:9005998}. FT /FTId=VAR_004665. FT VARIANT 314 314 I -> S (in VDDR2A). FT {ECO:0000269|PubMed:8961271}. FT /FTId=VAR_004666. FT VARIANT 362 362 T -> I (in dbSNP:rs11574115). FT {ECO:0000269|Ref.5}. FT /FTId=VAR_029310. FT VARIANT 391 391 R -> C (in VDDR2A). FT {ECO:0000269|PubMed:8961271}. FT /FTId=VAR_004667. FT MUTAGEN 61 62 PF->AA: Promotes heterodimerization with FT RXRA; when associated with A-75. FT {ECO:0000269|PubMed:11980721}. FT MUTAGEN 75 75 H->A: Promotes heterodimerization with FT RXRA; when associated with A-61 and A-62. FT {ECO:0000269|PubMed:11980721}. FT TURN 25 27 {ECO:0000244|PDB:1KB2}. FT STRAND 33 35 {ECO:0000244|PDB:1KB2}. FT STRAND 38 40 {ECO:0000244|PDB:1KB6}. FT HELIX 42 53 {ECO:0000244|PDB:1KB2}. FT STRAND 61 64 {ECO:0000244|PDB:1KB4}. FT TURN 70 75 {ECO:0000244|PDB:1KB2}. FT HELIX 77 86 {ECO:0000244|PDB:1KB2}. FT HELIX 91 93 {ECO:0000244|PDB:1KB2}. FT HELIX 97 107 {ECO:0000244|PDB:1KB2}. FT STRAND 108 110 {ECO:0000244|PDB:1KB6}. FT TURN 111 113 {ECO:0000244|PDB:1KB6}. FT HELIX 115 119 {ECO:0000244|PDB:1KB6}. FT HELIX 126 142 {ECO:0000244|PDB:3B0T}. FT HELIX 150 152 {ECO:0000244|PDB:3B0T}. FT HELIX 217 223 {ECO:0000244|PDB:3B0T}. FT HELIX 227 247 {ECO:0000244|PDB:3B0T}. FT HELIX 251 253 {ECO:0000244|PDB:3B0T}. FT HELIX 256 274 {ECO:0000244|PDB:3B0T}. FT HELIX 275 277 {ECO:0000244|PDB:3B0T}. FT TURN 281 284 {ECO:0000244|PDB:3B0T}. FT STRAND 285 287 {ECO:0000244|PDB:3B0T}. FT HELIX 291 293 {ECO:0000244|PDB:3B0T}. FT HELIX 297 301 {ECO:0000244|PDB:3B0T}. FT TURN 302 304 {ECO:0000244|PDB:3B0T}. FT HELIX 307 321 {ECO:0000244|PDB:3B0T}. FT TURN 322 324 {ECO:0000244|PDB:2HAR}. FT HELIX 327 338 {ECO:0000244|PDB:3B0T}. FT STRAND 341 343 {ECO:0000244|PDB:3AUQ}. FT HELIX 349 370 {ECO:0000244|PDB:3B0T}. FT TURN 373 378 {ECO:0000244|PDB:3B0T}. FT HELIX 379 404 {ECO:0000244|PDB:3B0T}. FT HELIX 410 413 {ECO:0000244|PDB:3B0T}. FT HELIX 416 422 {ECO:0000244|PDB:3B0T}. SQ SEQUENCE 427 AA; 48289 MW; F95F300D042C4CB7 CRC64; MEAMAASTSL PDPGDFDRNV PRICGVCGDR ATGFHFNAMT CEGCKGFFRR SMKRKALFTC PFNGDCRITK DNRRHCQACR LKRCVDIGMM KEFILTDEEV QRKREMILKR KEEEALKDSL RPKLSEEQQR IIAILLDAHH KTYDPTYSDF CQFRPPVRVN DGGGSHPSRP NSRHTPSFSG DSSSSCSDHC ITSSDMMDSS SFSNLDLSEE DSDDPSVTLE LSQLSMLPHL ADLVSYSIQK VIGFAKMIPG FRDLTSEDQI VLLKSSAIEV IMLRSNESFT MDDMSWTCGN QDYKYRVSDV TKAGHSLELI EPLIKFQVGL KKLNLHEEEH VLLMAICIVS PDRPGVQDAA LIEAIQDRLS NTLQTYIRCR HPPPGSHLLY AKMIQKLADL RSLNEEHSKQ YRCLSFQPEC SMKLTPLVLE VFGNEIS // ID XRCC6_HUMAN Reviewed; 609 AA. AC P12956; B1AHC8; Q6FG89; Q9UCQ2; Q9UCQ3; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 2. DT 11-NOV-2015, entry version 193. DE RecName: Full=X-ray repair cross-complementing protein 6; DE EC=3.6.4.-; DE EC=4.2.99.-; DE AltName: Full=5'-deoxyribose-5-phosphate lyase Ku70; DE Short=5'-dRP lyase Ku70; DE AltName: Full=70 kDa subunit of Ku antigen; DE AltName: Full=ATP-dependent DNA helicase 2 subunit 1; DE AltName: Full=ATP-dependent DNA helicase II 70 kDa subunit; DE AltName: Full=CTC box-binding factor 75 kDa subunit; DE Short=CTC75; DE Short=CTCBF; DE AltName: Full=DNA repair protein XRCC6; DE AltName: Full=Lupus Ku autoantigen protein p70; DE Short=Ku70; DE AltName: Full=Thyroid-lupus autoantigen; DE Short=TLAA; DE AltName: Full=X-ray repair complementing defective repair in Chinese hamster cells 6; GN Name=XRCC6; Synonyms=G22P1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=2917966; RA Chan J.Y., Lerman M.I., Prabhakar B.S., Isozaki O., Santisteban P., RA Kuppers R.C., Oates E.L., Notkins A.L., Kohn L.D.; RT "Cloning and characterization of a cDNA that encodes a 70-kDa novel RT human thyroid autoantigen."; RL J. Biol. Chem. 264:3651-3654(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND RP ROLE IN LUPUS ERYTHEMATOSUS. RX PubMed=2466842; RA Reeves W.H., Sthoeger Z.M.; RT "Molecular cloning of cDNA encoding the p70 (Ku) lupus autoantigen."; RL J. Biol. Chem. 264:5047-5052(1989). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1608402; DOI=10.1007/BF00419754; RA Griffith A.J., Craft J., Evans J., Mimori T., Hardin J.A.; RT "Nucleotide sequence and genomic structure analyses of the p70 subunit RT of the human Ku autoantigen: evidence for a family of genes encoding RT Ku (p70)-related polypeptides."; RL Mol. Biol. Rep. 16:91-97(1992). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Kidney; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., RA Korn B., Zuo D., Hu Y., LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J., RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., RA Khan A.S., Lane L., Tilahun Y., Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain, Kidney, Lung, Placenta, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [10] RP PROTEIN SEQUENCE OF 10-30 AND 299-317. RX PubMed=1537839; RA Wedrychowski A., Henzel W., Huston L., Paslidis N., Ellerson D., RA McRae M., Seong D., Howard O.M.Z., Deisseroth A.; RT "Identification of proteins binding to interferon-inducible RT transcriptional enhancers in hematopoietic cells."; RL J. Biol. Chem. 267:4533-4540(1992). RN [11] RP PROTEIN SEQUENCE OF 101-114 AND 116-125, AND DEVELOPMENTAL STAGE. RC TISSUE=Cervix carcinoma; RX PubMed=8605992; DOI=10.1016/0014-5793(96)00189-5; RA Oderwald H., Hughes M.J., Jost J.-P.; RT "Non-histone protein 1 (NHP1) is a member of the Ku protein family RT which is upregulated in differentiating mouse myoblasts and human RT promyelocytes."; RL FEBS Lett. 382:313-318(1996). RN [12] RP PROTEIN SEQUENCE OF 288-293 AND 300-312, FUNCTION, AND INTERACTION RP WITH APEX1. RX PubMed=8621488; DOI=10.1074/jbc.271.15.8593; RA Chung U., Igarashi T., Nishishita T., Iwanari H., Iwamatsu A., RA Suwa A., Mimori T., Hata K., Ebisu S., Ogata E., Fujita T., RA Okazaki T.; RT "The interaction between Ku antigen and REF1 protein mediates negative RT gene regulation by extracellular calcium."; RL J. Biol. Chem. 271:8593-8598(1996). RN [13] RP PROTEIN SEQUENCE OF 301-308 AND 556-565. RX PubMed=7882982; RA Genersch E., Eckerskorn C., Lottspeich F., Herzog C., Kuehn K., RA Poeschl E.; RT "Purification of the sequence-specific transcription factor CTCBF, RT involved in the control of human collagen IV genes: subunits with RT homology to Ku antigen."; RL EMBO J. 14:791-800(1995). RN [14] RP PROTEIN SEQUENCE OF 346-352, AND FUNCTION. RX PubMed=7957065; RA Tuteja N., Tuteja R., Ochem A., Taneja P., Huang N.W., Simoncsits A., RA Susic S., Rahman K., Marusic L., Chen J., Zhang J., Wang S., RA Pongor S., Falaschi A.; RT "Human DNA helicase II: a novel DNA unwinding enzyme identified as the RT Ku autoantigen."; RL EMBO J. 13:4991-5001(1994). RN [15] RP PHOSPHORYLATION AT SER-51. RX PubMed=9362500; DOI=10.1093/emboj/16.22.6874; RA Jin S., Weaver D.T.; RT "Double-strand break repair by Ku70 requires heterodimerization with RT Ku80 and DNA binding functions."; RL EMBO J. 16:6874-6885(1997). RN [16] RP FUNCTION, AND INTERACTION WITH PRKDC. RX PubMed=9742108; RA West R.B., Yaneva M., Lieber M.R.; RT "Productive and nonproductive complexes of Ku and DNA-dependent RT protein kinase at DNA termini."; RL Mol. Cell. Biol. 18:5908-5920(1998). RN [17] RP PHOSPHORYLATION AT SER-6. RX PubMed=10026262; DOI=10.1021/bi982584b; RA Chan D.W., Ye R., Veillette C.J., Lees-Miller S.P.; RT "DNA-dependent protein kinase phosphorylation sites in Ku 70/80 RT heterodimer."; RL Biochemistry 38:1819-1828(1999). RN [18] RP REVIEW. RX PubMed=10377944; DOI=10.1016/S0921-8777(99)00006-3; RA Featherstone C., Jackson S.P.; RT "Ku, a DNA repair protein with multiple cellular functions?"; RL Mutat. Res. 434:3-15(1999). RN [19] RP INTERACTION WITH XRCC6BP1. RC TISSUE=Liver; RX PubMed=10219089; DOI=10.1093/nar/27.10.2165; RA Yang C.-R., Yeh S.-Y., Leskov K., Odegaard E., Hsu H.L., Chang C., RA Kinsella T.J., Chen D.J., Boothman D.A.; RT "Isolation of Ku70-binding proteins (KUBs)."; RL Nucleic Acids Res. 27:2165-2174(1999). RN [20] RP INTERACTION WITH PRKDC. RX PubMed=12509254; DOI=10.1016/S1568-7864(01)00018-0; RA Hsu H.-L., Yannone S.M., Chen D.J.; RT "Defining interactions between DNA-PK and ligase IV/XRCC4."; RL DNA Repair 1:225-235(2002). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, AND INTERACTION WITH RP NAA15; MSX2; RUNX2 AND DLX5. RC TISSUE=Heart, and Osteoblast; RX PubMed=12145306; DOI=10.1074/jbc.M206482200; RA Willis D.M., Loewy A.P., Charlton-Kachigian N., Shao J.-S., RA Ornitz D.M., Towler D.A.; RT "Regulation of osteocalcin gene expression by a novel Ku antigen RT transcription factor complex."; RL J. Biol. Chem. 277:37280-37291(2002). RN [22] RP IDENTIFICATION IN A COMPLEX WITH G22P2; PRKDC AND XRCC4, AND RP PHOSPHORYLATION. RX PubMed=12547193; DOI=10.1016/S0022-2836(02)01328-1; RA Calsou P., Delteil C., Frit P., Drouet J., Salles B.; RT "Coordinated assembly of Ku and p460 subunits of the DNA-dependent RT protein kinase on DNA ends is necessary for XRCC4-ligase IV RT recruitment."; RL J. Mol. Biol. 326:93-103(2003). RN [23] RP INTERACTION WITH ELF3. RX PubMed=15075319; DOI=10.1074/jbc.M401356200; RA Wang H., Fang R., Cho J.-Y., Libermann T.A., Oettgen P.; RT "Positive and negative modulation of the transcriptional activity of RT the ETS factor ESE-1 through interaction with p300, CREB-binding RT protein, and Ku 70/86."; RL J. Biol. Chem. 279:25241-25250(2004). RN [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-477, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [25] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-520, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [27] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-31; LYS-331; LYS-338 AND RP LYS-461, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [28] RP FUNCTION IN DNA REPAIR, AND INTERACTION WITH CDK9. RX PubMed=20493174; DOI=10.1016/j.bbrc.2010.05.092; RA Liu H., Herrmann C.H., Chiang K., Sung T.L., Moon S.H., RA Donehower L.A., Rice A.P.; RT "55K isoform of CDK9 associates with Ku70 and is involved in DNA RT repair."; RL Biochem. Biophys. Res. Commun. 397:245-250(2010). RN [29] RP FUNCTION AS A 5'-DRP LYASE, AND MUTAGENESIS OF LYS-31; LYS-160 AND RP LYS-164. RX PubMed=20383123; DOI=10.1038/nature08926; RA Roberts S.A., Strande N., Burkhalter M.D., Strom C., Havener J.M., RA Hasty P., Ramsden D.A.; RT "Ku is a 5'-dRP/AP lyase that excises nucleotide damage near broken RT ends."; RL Nature 464:1214-1217(2010). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-455 AND SER-550, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [31] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-455, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [33] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.M111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., RA Meinnel T., Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [34] RP DNA-BINDING, IDENTIFICATION IN A COMPLEX WITH DEAF1 AND XRCC5, RP INTERACTION WITH DEAF1, SUBCELLULAR LOCATION, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=22442688; DOI=10.1371/journal.pone.0033404; RA Jensik P.J., Huggenvik J.I., Collard M.W.; RT "Deformed epidermal autoregulatory factor-1 (DEAF1) interacts with the RT Ku70 subunit of the DNA-dependent protein kinase complex."; RL PLoS ONE 7:E33404-E33404(2012). RN [35] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [36] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-556, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [37] RP INTERACTION WITH NR4A3. RX PubMed=25852083; DOI=10.1093/cvr/cvv126; RA Medunjanin S., Daniel J.M., Weinert S., Dutzmann J., Burgbacher F., RA Brecht S., Bruemmer D., Kaehne T., Naumann M., Sedding D.G., RA Zuschratter W., Braun-Dullaeus R.C.; RT "DNA-dependent protein kinase (DNA-PK) permits vascular smooth muscle RT cell proliferation through phosphorylation of the orphan nuclear RT receptor NOR1."; RL Cardiovasc. Res. 106:488-497(2015). RN [38] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [39] RP INTERACTION WITH C9ORF142. RX PubMed=25574025; DOI=10.1126/science.1261971; RA Ochi T., Blackford A.N., Coates J., Jhujh S., Mehmood S., Tamura N., RA Travers J., Wu Q., Draviam V.M., Robinson C.V., Blundell T.L., RA Jackson S.P.; RT "DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to RT promote DNA double-strand break repair."; RL Science 347:185-188(2015). RN [40] RP STRUCTURE BY NMR OF 557-610. RX PubMed=11457852; DOI=10.1074/jbc.M105238200; RA Zhang Z., Zhu L., Lin D., Chen F., Chen D.J., Chen Y.; RT "The three-dimensional structure of the C-terminal DNA-binding domain RT of human Ku70."; RL J. Biol. Chem. 276:38231-38236(2001). RN [41] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 36-609 IN COMPLEX WITH G22P2. RX PubMed=11493912; DOI=10.1038/35088000; RA Walker J.R., Corpina R.A., Goldberg J.; RT "Structure of the Ku heterodimer bound to DNA and its implications for RT double-strand break repair."; RL Nature 412:607-614(2001). CC -!- FUNCTION: Single-stranded DNA-dependent ATP-dependent helicase. CC Has a role in chromosome translocation. The DNA helicase II CC complex binds preferentially to fork-like ends of double-stranded CC DNA in a cell cycle-dependent manner. It works in the 3'-5' CC direction. Binding to DNA may be mediated by XRCC6. Involved in CC DNA non-homologous end joining (NHEJ) required for double-strand CC break repair and V(D)J recombination. The XRCC5/6 dimer acts as CC regulatory subunit of the DNA-dependent protein kinase complex CC DNA-PK by increasing the affinity of the catalytic subunit PRKDC CC to DNA by 100-fold. The XRCC5/6 dimer is probably involved in CC stabilizing broken DNA ends and bringing them together. The CC assembly of the DNA-PK complex to DNA ends is required for the CC NHEJ ligation step. Required for osteocalcin gene expression. CC Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP CC lyase), by catalyzing the beta-elimination of the 5' deoxyribose- CC 5-phosphate at an abasic site near double-strand breaks. 5'-dRP CC lyase activity allows to 'clean' the termini of abasic sites, a CC class of nucleotide damage commonly associated with strand breaks, CC before such broken ends can be joined. The XRCC5/6 dimer together CC with APEX1 acts as a negative regulator of transcription. CC {ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:20383123, CC ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:2466842, CC ECO:0000269|PubMed:7957065, ECO:0000269|PubMed:8621488, CC ECO:0000269|PubMed:9742108}. CC -!- SUBUNIT: Heterodimer of a 70 kDa (XRCC6) and a 80 kDa (XRCC5) CC subunit. The dimer associates in a DNA-dependent manner with PRKDC CC to form the DNA-dependent protein kinase complex DNA-PK, and with CC the LIG4-XRCC4 complex. The dimer also associates with NAA15, and CC this complex binds to the osteocalcin promoter and activates CC osteocalcin expression. In addition, XRCC6 interacts with the CC osteoblast-specific transcription factors MSX2, RUNX2 and DLX5. CC Interacts with ELF3. Interacts with XRCC6BP1. The XRCC5/6 dimer CC associates in a DNA-dependent manner with APEX1. Binds to CDK9 CC isoform 2. Identified in a complex with DEAF1 and XRCC5. Interacts CC with DEAF1 (via the SAND domain); the interaction is direct and CC may be inhibited by DNA-binding (PubMed:10219089, PubMed:11493912, CC PubMed:12145306, PubMed:12509254, PubMed:12547193, CC PubMed:15075319, PubMed:20493174, PubMed:22442688, PubMed:8621488, CC PubMed:9742108). Interacts with C9orf142/PAXX (PubMed:25574025). CC Interacts with CLU (By similarity). Interacts with NR4A3; the DNA- CC dependent protein kinase complex DNA-PK phosphorylates and CC activates NR4A3 and prevents NR4A3 ubiquitinylation and CC degradation (PubMed:25852083). {ECO:0000250|UniProtKB:P23475, CC ECO:0000269|PubMed:10219089, ECO:0000269|PubMed:11493912, CC ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:12509254, CC ECO:0000269|PubMed:12547193, ECO:0000269|PubMed:15075319, CC ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:22442688, CC ECO:0000269|PubMed:25574025, ECO:0000269|PubMed:25852083, CC ECO:0000269|PubMed:8621488, ECO:0000269|PubMed:9742108}. CC -!- INTERACTION: CC Q96P48:ARAP1; NbExp=2; IntAct=EBI-353208, EBI-710003; CC Q07812:BAX; NbExp=2; IntAct=EBI-353208, EBI-516580; CC P38432:COIL; NbExp=3; IntAct=EBI-353208, EBI-945751; CC Q6NT76:HMBOX1; NbExp=2; IntAct=EBI-353208, EBI-2549423; CC P42858:HTT; NbExp=3; IntAct=EBI-353208, EBI-466029; CC Q92597:NDRG1; NbExp=2; IntAct=EBI-353208, EBI-716486; CC Q08752:PPID; NbExp=4; IntAct=EBI-353208, EBI-716596; CC P78527:PRKDC; NbExp=5; IntAct=EBI-353208, EBI-352053; CC Q96EB6:SIRT1; NbExp=7; IntAct=EBI-353208, EBI-1802965; CC Q9NQB0:TCF7L2; NbExp=9; IntAct=EBI-353208, EBI-924724; CC P04637:TP53; NbExp=2; IntAct=EBI-353208, EBI-366083; CC Q14191:WRN; NbExp=4; IntAct=EBI-353208, EBI-368417; CC P13010:XRCC5; NbExp=9; IntAct=EBI-353208, EBI-357997; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22442688}. CC Chromosome {ECO:0000269|PubMed:22442688}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P12956-1; Sequence=Displayed; CC Name=2; CC IsoId=P12956-2; Sequence=VSP_056030; CC Note=No experimental confirmation available.; CC -!- DEVELOPMENTAL STAGE: Expression does not increase during CC promyelocyte differentiation. {ECO:0000269|PubMed:8605992}. CC -!- INDUCTION: In osteoblasts, by FGF2. CC -!- PTM: Phosphorylation by PRKDC may enhance helicase activity. CC Phosphorylation of Ser-51 does not affect DNA repair. CC {ECO:0000269|PubMed:10026262, ECO:0000269|PubMed:12547193, CC ECO:0000269|PubMed:9362500}. CC -!- MISCELLANEOUS: Individuals with systemic lupus erythematosus (SLE) CC and related disorders produce extremely large amounts of CC autoantibodies to XRCC5 and XRCC6. Existence of a major CC autoantigenic epitope or epitopes on the C-terminal 190 amino CC acids of XRCC6 containing the leucine repeat. The majority of CC autoantibodies to XRCC6 in most sera from patients with SLE seem CC to be reactive with this region. CC -!- SIMILARITY: Belongs to the ku70 family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 Ku domain. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 SAP domain. {ECO:0000255|PROSITE- CC ProRule:PRU00186}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/g22p1/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/XRCC6ID246ch22q13.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; J04607; AAA61177.1; -; mRNA. DR EMBL; J04611; AAA51733.1; -; mRNA. DR EMBL; M32865; AAA36155.1; -; mRNA. DR EMBL; S38729; AAB22381.1; -; mRNA. DR EMBL; AK055786; BAG51575.1; -; mRNA. DR EMBL; CR542219; CAG47015.1; -; mRNA. DR EMBL; AY870329; AAW34364.1; -; Genomic_DNA. DR EMBL; Z83840; CAB46206.1; -; Genomic_DNA. DR EMBL; CH471095; EAW60448.1; -; Genomic_DNA. DR EMBL; BC008343; AAH08343.1; -; mRNA. DR EMBL; BC010034; AAH10034.1; -; mRNA. DR EMBL; BC012154; AAH12154.1; -; mRNA. DR EMBL; BC018259; AAH18259.1; -; mRNA. DR EMBL; BC072449; AAH72449.1; -; mRNA. DR CCDS; CCDS14021.1; -. [P12956-1] DR CCDS; CCDS74870.1; -. [P12956-2] DR PIR; A30299; A30894. DR RefSeq; NP_001275905.1; NM_001288976.1. [P12956-1] DR RefSeq; NP_001275906.1; NM_001288977.1. [P12956-2] DR RefSeq; NP_001460.1; NM_001469.4. [P12956-1] DR UniGene; Hs.292493; -. DR UniGene; Hs.730702; -. DR PDB; 1JEQ; X-ray; 2.70 A; A=1-609. DR PDB; 1JEY; X-ray; 2.50 A; A=1-609. DR PDB; 1JJR; NMR; -; A=556-609. DR PDB; 3RZX; X-ray; 2.61 A; B=537-558. DR PDBsum; 1JEQ; -. DR PDBsum; 1JEY; -. DR PDBsum; 1JJR; -. DR PDBsum; 3RZX; -. DR ProteinModelPortal; P12956; -. DR SMR; P12956; 34-609. DR BioGrid; 108822; 247. DR DIP; DIP-24188N; -. DR IntAct; P12956; 132. DR MINT; MINT-1416738; -. DR STRING; 9606.ENSP00000352257; -. DR PhosphoSite; P12956; -. DR DMDM; 125729; -. DR SWISS-2DPAGE; P12956; -. DR MaxQB; P12956; -. DR PaxDb; P12956; -. DR PRIDE; P12956; -. DR DNASU; 2547; -. DR Ensembl; ENST00000359308; ENSP00000352257; ENSG00000196419. [P12956-1] DR Ensembl; ENST00000360079; ENSP00000353192; ENSG00000196419. [P12956-1] DR Ensembl; ENST00000402580; ENSP00000384941; ENSG00000196419. [P12956-2] DR Ensembl; ENST00000405878; ENSP00000384257; ENSG00000196419. [P12956-1] DR GeneID; 2547; -. DR KEGG; hsa:2547; -. DR UCSC; uc003bao.1; human. [P12956-1] DR UCSC; uc003bap.1; human. DR CTD; 2547; -. DR GeneCards; XRCC6; -. DR HGNC; HGNC:4055; XRCC6. DR HPA; CAB004254; -. DR HPA; HPA047549; -. DR HPA; HPA062226; -. DR MIM; 152690; gene. DR neXtProt; NX_P12956; -. DR PharmGKB; PA28467; -. DR eggNOG; KOG2327; Eukaryota. DR eggNOG; ENOG410XNXU; LUCA. DR GeneTree; ENSGT00390000001422; -. DR HOGENOM; HOG000006588; -. DR HOVERGEN; HBG006236; -. DR InParanoid; P12956; -. DR KO; K10884; -. DR OMA; RKAYKFG; -. DR OrthoDB; EOG7QG43F; -. DR PhylomeDB; P12956; -. DR TreeFam; TF315101; -. DR Reactome; R-HSA-164843; 2-LTR circle formation. DR Reactome; R-HSA-1834949; Cytosolic sensors of pathogen-associated DNA. DR Reactome; R-HSA-3270619; IRF3-mediated induction of type I IFN. DR Reactome; R-HSA-73889; Nonhomologous End-Joining (NHEJ). DR Reactome; R-HSA-75924; Processing of DNA ends prior to end rejoining. DR ChiTaRS; XRCC6; human. DR EvolutionaryTrace; P12956; -. DR GeneWiki; Ku70; -. DR GenomeRNAi; 2547; -. DR NextBio; 10043; -. DR PMAP-CutDB; P12956; -. DR PRO; PR:P12956; -. DR Proteomes; UP000005640; Chromosome 22. DR Bgee; P12956; -. DR CleanEx; HS_XRCC6; -. DR ExpressionAtlas; P12956; baseline and differential. DR Genevisible; P12956; HS. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043564; C:Ku70:Ku80 complex; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0070419; C:nonhomologous end joining complex; IDA:UniProtKB. DR GO; GO:0000784; C:nuclear chromosome, telomeric region; IDA:BHF-UCL. DR GO; GO:0000783; C:nuclear telomere cap complex; TAS:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0005667; C:transcription factor complex; IDA:UniProtKB. DR GO; GO:0051575; F:5'-deoxyribose-5-phosphate lyase activity; IMP:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004003; F:ATP-dependent DNA helicase activity; TAS:ProtInc. DR GO; GO:0003684; F:damaged DNA binding; IBA:GO_Central. DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; TAS:ProtInc. DR GO; GO:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB. DR GO; GO:0042162; F:telomeric DNA binding; IEA:InterPro. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL. DR GO; GO:0071480; P:cellular response to gamma radiation; IBA:GO_Central. DR GO; GO:0071481; P:cellular response to X-ray; IBA:GO_Central. DR GO; GO:0032508; P:DNA duplex unwinding; TAS:GOC. DR GO; GO:0006266; P:DNA ligation; TAS:ProtInc. DR GO; GO:0006310; P:DNA recombination; IBA:GO_Central. DR GO; GO:0006281; P:DNA repair; TAS:Reactome. DR GO; GO:0006302; P:double-strand break repair; TAS:Reactome. DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:UniProtKB. DR GO; GO:0075713; P:establishment of integrated proviral latency; TAS:Reactome. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome. DR GO; GO:0048660; P:regulation of smooth muscle cell proliferation; IMP:UniProtKB. DR GO; GO:0000723; P:telomere maintenance; TAS:BHF-UCL. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0016032; P:viral process; TAS:Reactome. DR Gene3D; 1.10.1600.10; -; 1. DR Gene3D; 1.10.720.30; -; 1. DR Gene3D; 2.40.290.10; -; 1. DR Gene3D; 3.40.50.410; -; 1. DR Gene3D; 4.10.970.10; -; 1. DR InterPro; IPR006165; Ku70. DR InterPro; IPR006164; Ku70/Ku80_beta-barrel_dom. DR InterPro; IPR027388; Ku70_bridge/pillars_dom. DR InterPro; IPR005160; Ku_C. DR InterPro; IPR005161; Ku_N. DR InterPro; IPR003034; SAP_dom. DR InterPro; IPR016194; SPOC-like_C_dom. DR InterPro; IPR002035; VWF_A. DR Pfam; PF02735; Ku; 1. DR Pfam; PF03730; Ku_C; 1. DR Pfam; PF03731; Ku_N; 1. DR Pfam; PF02037; SAP; 1. DR PIRSF; PIRSF003033; Ku70; 1. DR SMART; SM00559; Ku78; 1. DR SMART; SM00513; SAP; 1. DR SUPFAM; SSF100939; SSF100939; 1. DR SUPFAM; SSF53300; SSF53300; 1. DR TIGRFAMs; TIGR00578; ku70; 1. DR PROSITE; PS50800; SAP; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW ATP-binding; Chromosome; Complete proteome; Direct protein sequencing; KW DNA damage; DNA recombination; DNA repair; DNA-binding; Helicase; KW Hydrolase; Isopeptide bond; Lyase; Multifunctional enzyme; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Systemic lupus erythematosus; Transcription; Transcription regulation; KW Ubl conjugation. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22223895}. FT CHAIN 2 609 X-ray repair cross-complementing protein FT 6. FT /FTId=PRO_0000210179. FT DOMAIN 261 468 Ku. FT DOMAIN 573 607 SAP. {ECO:0000255|PROSITE- FT ProRule:PRU00186}. FT REGION 550 609 Interaction with DEAF1. FT COMPBIAS 2 61 Ser-rich (potentially targets for FT phosphorylation). FT COMPBIAS 11 29 Asp/Glu-rich (acidic). FT COMPBIAS 330 342 Asp/Glu-rich (acidic). FT ACT_SITE 31 31 Schiff-base intermediate with DNA; for FT 5'-deoxyribose-5-phosphate lyase FT activity. {ECO:0000305}. FT MOD_RES 2 2 N-acetylserine. FT {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22223895}. FT MOD_RES 6 6 Phosphoserine; by PRKDC. FT {ECO:0000269|PubMed:10026262}. FT MOD_RES 31 31 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 51 51 Phosphoserine; by PRKDC. FT {ECO:0000269|PubMed:9362500}. FT MOD_RES 331 331 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 338 338 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 455 455 Phosphothreonine. FT {ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 461 461 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 477 477 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 520 520 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 550 550 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT CROSSLNK 556 556 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT VAR_SEQ 65 105 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_056030. FT MUTAGEN 31 31 K->A: Diminishes the ability to form a FT Schiff base. Abolishes adduct formation; FT when associated with A-160 and A-164. FT {ECO:0000269|PubMed:20383123}. FT MUTAGEN 160 160 K->A: Abolishes adduct formation; when FT associated with A-31 and A-160. FT {ECO:0000269|PubMed:20383123}. FT MUTAGEN 164 164 K->A: Abolishes adduct formation; when FT associated with A-31 and A-164. FT {ECO:0000269|PubMed:20383123}. FT CONFLICT 20 20 Q -> D (in Ref. 10; AA sequence). FT {ECO:0000305}. FT CONFLICT 101 101 N -> K (in Ref. 11; AA sequence). FT {ECO:0000305}. FT CONFLICT 103 103 Y -> L (in Ref. 11; AA sequence). FT {ECO:0000305}. FT CONFLICT 116 116 I -> S (in Ref. 11; AA sequence). FT {ECO:0000305}. FT CONFLICT 125 125 Q -> S (in Ref. 11; AA sequence). FT {ECO:0000305}. FT CONFLICT 181 181 A -> T (in Ref. 5; CAG47015). FT {ECO:0000305}. FT STRAND 35 43 {ECO:0000244|PDB:1JEY}. FT HELIX 46 49 {ECO:0000244|PDB:1JEY}. FT STRAND 53 56 {ECO:0000244|PDB:1JEY}. FT HELIX 59 76 {ECO:0000244|PDB:1JEY}. FT STRAND 82 89 {ECO:0000244|PDB:1JEY}. FT STRAND 102 109 {ECO:0000244|PDB:1JEY}. FT HELIX 113 120 {ECO:0000244|PDB:1JEY}. FT HELIX 124 135 {ECO:0000244|PDB:1JEY}. FT HELIX 143 155 {ECO:0000244|PDB:1JEY}. FT STRAND 161 171 {ECO:0000244|PDB:1JEY}. FT TURN 175 178 {ECO:0000244|PDB:1JEY}. FT HELIX 180 196 {ECO:0000244|PDB:1JEY}. FT STRAND 198 205 {ECO:0000244|PDB:1JEY}. FT TURN 213 216 {ECO:0000244|PDB:1JEY}. FT HELIX 217 219 {ECO:0000244|PDB:1JEY}. FT HELIX 239 250 {ECO:0000244|PDB:1JEY}. FT STRAND 256 266 {ECO:0000244|PDB:1JEY}. FT STRAND 268 274 {ECO:0000244|PDB:1JEY}. FT STRAND 286 289 {ECO:0000244|PDB:1JEY}. FT TURN 290 292 {ECO:0000244|PDB:1JEY}. FT STRAND 295 304 {ECO:0000244|PDB:1JEY}. FT TURN 305 307 {ECO:0000244|PDB:1JEY}. FT HELIX 313 315 {ECO:0000244|PDB:1JEY}. FT STRAND 316 322 {ECO:0000244|PDB:1JEY}. FT STRAND 325 329 {ECO:0000244|PDB:1JEY}. FT HELIX 331 336 {ECO:0000244|PDB:1JEY}. FT STRAND 343 352 {ECO:0000244|PDB:1JEY}. FT HELIX 353 355 {ECO:0000244|PDB:1JEY}. FT HELIX 358 360 {ECO:0000244|PDB:1JEY}. FT STRAND 366 370 {ECO:0000244|PDB:1JEY}. FT TURN 372 374 {ECO:0000244|PDB:1JEY}. FT HELIX 378 391 {ECO:0000244|PDB:1JEY}. FT STRAND 394 401 {ECO:0000244|PDB:1JEY}. FT STRAND 403 405 {ECO:0000244|PDB:1JEY}. FT STRAND 409 416 {ECO:0000244|PDB:1JEY}. FT STRAND 426 428 {ECO:0000244|PDB:1JEY}. FT STRAND 430 436 {ECO:0000244|PDB:1JEY}. FT HELIX 440 442 {ECO:0000244|PDB:1JEY}. FT HELIX 456 468 {ECO:0000244|PDB:1JEY}. FT HELIX 481 494 {ECO:0000244|PDB:1JEY}. FT HELIX 511 518 {ECO:0000244|PDB:1JEY}. FT HELIX 521 529 {ECO:0000244|PDB:1JEY}. FT HELIX 561 569 {ECO:0000244|PDB:1JEQ}. FT HELIX 573 575 {ECO:0000244|PDB:1JEQ}. FT HELIX 578 587 {ECO:0000244|PDB:1JEQ}. FT HELIX 596 607 {ECO:0000244|PDB:1JEQ}. SQ SEQUENCE 609 AA; 69843 MW; BBD3CD434526DFCB CRC64; MSGWESYYKT EGDEEAEEEQ EENLEASGDY KYSGRDSLIF LVDASKAMFE SQSEDELTPF DMSIQCIQSV YISKIISSDR DLLAVVFYGT EKDKNSVNFK NIYVLQELDN PGAKRILELD QFKGQQGQKR FQDMMGHGSD YSLSEVLWVC ANLFSDVQFK MSHKRIMLFT NEDNPHGNDS AKASRARTKA GDLRDTGIFL DLMHLKKPGG FDISLFYRDI ISIAEDEDLR VHFEESSKLE DLLRKVRAKE TRKRALSRLK LKLNKDIVIS VGIYNLVQKA LKPPPIKLYR ETNEPVKTKT RTFNTSTGGL LLPSDTKRSQ IYGSRQIILE KEETEELKRF DDPGLMLMGF KPLVLLKKHH YLRPSLFVYP EESLVIGSST LFSALLIKCL EKEVAALCRY TPRRNIPPYF VALVPQEEEL DDQKIQVTPP GFQLVFLPFA DDKRKMPFTE KIMATPEQVG KMKAIVEKLR FTYRSDSFEN PVLQQHFRNL EALALDLMEP EQAVDLTLPK VEAMNKRLGS LVDEFKELVY PPDYNPEGKV TKRKHDNEGS GSKRPKVEYS EEELKTHISK GTLGKFTVPM LKEACRAYGL KSGLKKQELL EALTKHFQD // ID Z512B_HUMAN Reviewed; 892 AA. AC Q96KM6; Q08AK9; Q9ULM4; DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 11-NOV-2015, entry version 126. DE RecName: Full=Zinc finger protein 512B; GN Name=ZNF512B; Synonyms=KIAA1196; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., RA Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 42-892. RC TISSUE=Brain; RX PubMed=10574462; DOI=10.1093/dnares/6.5.337; RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XV. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 6:337-345(1999). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 425-892. RC TISSUE=Testis; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-409, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-686, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [8] RP STRUCTURE BY NMR OF 493-577. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the two ZF-C2H2-like domains (493-575) of human RT zinc finger protein KIAA1196."; RL Submitted (OCT-2006) to the PDB data bank. CC -!- FUNCTION: May be involved in transcriptional regulation. CC -!- INTERACTION: CC Q13643:FHL3; NbExp=3; IntAct=EBI-1049952, EBI-741101; CC Q8IUQ4:SIAH1; NbExp=3; IntAct=EBI-1049952, EBI-747107; CC Q13077:TRAF1; NbExp=3; IntAct=EBI-1049952, EBI-359224; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 7 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AL118506; CAC15498.3; -; Genomic_DNA. DR EMBL; BC125128; AAI25129.1; -; mRNA. DR EMBL; BC125129; AAI25130.1; -; mRNA. DR EMBL; AB033022; BAA86510.1; -; mRNA. DR EMBL; AL834525; CAD39181.1; -; mRNA. DR CCDS; CCDS13548.1; -. DR RefSeq; NP_065764.1; NM_020713.2. DR RefSeq; XP_011527231.1; XM_011528929.1. DR UniGene; Hs.740578; -. DR PDB; 2GQJ; NMR; -; A=493-577. DR PDBsum; 2GQJ; -. DR ProteinModelPortal; Q96KM6; -. DR SMR; Q96KM6; 134-169, 497-577, 587-616, 623-661, 741-775, 784-810. DR BioGrid; 121543; 65. DR IntAct; Q96KM6; 63. DR MINT; MINT-1180628; -. DR STRING; 9606.ENSP00000217130; -. DR PhosphoSite; Q96KM6; -. DR DMDM; 23822331; -. DR MaxQB; Q96KM6; -. DR PaxDb; Q96KM6; -. DR PRIDE; Q96KM6; -. DR Ensembl; ENST00000217130; ENSP00000217130; ENSG00000196700. DR Ensembl; ENST00000369888; ENSP00000358904; ENSG00000196700. DR Ensembl; ENST00000450537; ENSP00000393795; ENSG00000196700. DR GeneID; 57473; -. DR KEGG; hsa:57473; -. DR UCSC; uc002yhl.2; human. DR CTD; 57473; -. DR GeneCards; ZNF512B; -. DR HGNC; HGNC:29212; ZNF512B. DR HPA; HPA006688; -. DR neXtProt; NX_Q96KM6; -. DR PharmGKB; PA162410181; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00490000043365; -. DR HOGENOM; HOG000070202; -. DR HOVERGEN; HBG081832; -. DR InParanoid; Q96KM6; -. DR OMA; ISRHTPP; -. DR OrthoDB; EOG7T1R9K; -. DR PhylomeDB; Q96KM6; -. DR TreeFam; TF331185; -. DR ChiTaRS; ZNF512B; human. DR EvolutionaryTrace; Q96KM6; -. DR GenomeRNAi; 57473; -. DR NextBio; 63707; -. DR PRO; PR:Q96KM6; -. DR Proteomes; UP000005640; Chromosome 20. DR Bgee; Q96KM6; -. DR CleanEx; HS_ZNF512B; -. DR Genevisible; Q96KM6; HS. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR SMART; SM00355; ZnF_C2H2; 6. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; DNA-binding; Metal-binding; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; KW Transcription; Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 892 Zinc finger protein 512B. FT /FTId=PRO_0000047779. FT ZN_FING 105 129 C2H2-type 1; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT ZN_FING 140 163 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 540 563 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 594 618 C2H2-type 4; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT ZN_FING 630 653 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 750 774 C2H2-type 6; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT ZN_FING 784 807 C2H2-type 7. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT MOD_RES 409 409 Phosphoserine. FT {ECO:0000244|PubMed:17081983}. FT MOD_RES 686 686 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT VARIANT 288 288 V -> M (in dbSNP:rs45486695). FT /FTId=VAR_061954. FT VARIANT 372 372 M -> V (in dbSNP:rs817326). FT /FTId=VAR_024226. FT VARIANT 453 453 A -> T (in dbSNP:rs6062599). FT /FTId=VAR_024227. FT HELIX 499 502 {ECO:0000244|PDB:2GQJ}. FT TURN 503 507 {ECO:0000244|PDB:2GQJ}. FT TURN 513 515 {ECO:0000244|PDB:2GQJ}. FT HELIX 524 540 {ECO:0000244|PDB:2GQJ}. FT STRAND 543 545 {ECO:0000244|PDB:2GQJ}. FT HELIX 552 562 {ECO:0000244|PDB:2GQJ}. SQ SEQUENCE 892 AA; 97264 MW; 50449C476DFCE4DF CRC64; MTDPFCVGGR RLPGSSKSGP GKDGSRKEVR LPMLHDPPKM GMPVVRGGQT VPGQAPLCFD PGSPASDKTE GKKKGRPKAE NQALRDIPLS LMNDWKDEFK AHSRVKCPNS GCWLEFPSIY GLKYHYQRCQ GGAISDRLAF PCPFCEAAFT SKTQLEKHRI WNHMDRPLPA SKPGPISRPV TISRPVGVSK PIGVSKPVTI GKPVGVSKPI GISKPVSVGR PMPVTKAIPV TRPVPVTKPV TVSRPMPVTK AMPVTKPITV TKSVPVTKPV PVTKPITVTK LVTVTKPVPV TKPVTVSRPI VVSKPVTVSR PIAISRHTPP CKMVLLTRSE NKAPRATGRN SGKKRAADSL DTCPIPPKQA RPENGEYGPS SMGQSSAFQL SADTSSGSLS PGSRPSGGME ALKAAGPASP PEEDPERTKH RRKQKTPKKF TGEQPSISGT FGLKGLVKAE DKARVHRSKK QEGPGPEDAR KKVPAAPITV SKEAPAPVAH PAPGGPEEQW QRAIHERGEA VCPTCNVVTR KTLVGLKKHM EVCQKLQDAL KCQHCRKQFK SKAGLNYHTM AEHSAKPSDA EASEGGEQEE RERLRKVLKQ MGRLRCPQEG CGAAFSSLMG YQYHQRRCGK PPCEVDSPSF PCTHCGKTYR SKAGHDYHVR SEHTAPPPEE PTDKSPEAED PLGVERTPSG RVRRTSAQVA VFHLQEIAED ELARDWTKRR MKDDLVPETA RLNYTRPGLP TLNPQLLEAW KNEVKEKGHV NCPNDCCEAI YSSVSGLKAH LASCSKGAHL AGKYRCLLCP KEFSSESGVK YHILKTHAEN WFRTSADPPP KHRSQDSLVP KKEKKKNLAG GKKRGRKPKE RTPEEPVAKL PPRRDDWPPG CRDKGARGST GRKVGVSKAP EK // ID ZBT18_HUMAN Reviewed; 522 AA. AC Q99592; A8K5U3; Q13397; Q5VU40; Q8N463; Q9UD99; DT 21-FEB-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 11-NOV-2015, entry version 151. DE RecName: Full=Zinc finger and BTB domain-containing protein 18; DE AltName: Full=58 kDa repressor protein; DE AltName: Full=Transcriptional repressor RP58; DE AltName: Full=Translin-associated zinc finger protein 1; DE Short=TAZ-1; DE AltName: Full=Zinc finger protein 238; DE AltName: Full=Zinc finger protein C2H2-171; GN Name=ZBTB18; Synonyms=RP58, TAZ1, ZNF238; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT GLY-132. RC TISSUE=Hippocampus; RX PubMed=7633419; DOI=10.1093/hmg/4.4.685; RA Becker K.G., Nagle J.W., Canning R.D., Biddison W.E., Ozato K., RA Drew P.D.; RT "Rapid isolation and characterization of 118 novel C2H2-type zinc RT finger cDNAs expressed in human brain."; RL Hum. Mol. Genet. 4:685-691(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND DNA-BINDING. RC TISSUE=Spleen; RX PubMed=9756912; DOI=10.1074/jbc.273.41.26698; RA Aoki K., Meng G., Suzuki K., Takashi T., Kameoka Y., Nakahara K., RA Ishida R., Kasai M.; RT "RP58 associates with condensed chromatin and mediates a sequence- RT specific transcriptional repression."; RL J. Biol. Chem. 273:26698-26704(1998). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Placenta; RX PubMed=10721697; DOI=10.1016/S0378-1119(99)00477-1; RA Meng G., Inazawa J., Ishida R., Tokura K., Nakahara K., Aoki K., RA Kasai M.; RT "Structural analysis of the gene encoding RP58, a sequence-specific RT transrepressor associated with heterochromatin."; RL Gene 242:59-64(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-75 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=8358434; DOI=10.1038/ng0793-256; RA Adams M.D., Kerlavage A.R., Fields C., Venter J.C.; RT "3,400 new expressed sequence tags identify diversity of transcripts RT in human brain."; RL Nat. Genet. 4:256-267(1993). RN [8] RP INTERACTION WITH DNMT3A. RX PubMed=11350943; DOI=10.1093/emboj/20.10.2536; RA Fuks F., Burgers W.A., Godin N., Kasai M., Kouzarides T.; RT "Dnmt3a binds deacetylases and is recruited by a sequence-specific RT repressor to silence transcription."; RL EMBO J. 20:2536-2544(2001). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-516 AND SER-517, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.; RT "ATM and ATR substrate analysis reveals extensive protein networks RT responsive to DNA damage."; RL Science 316:1160-1166(2007). RN [10] RP INVOLVEMENT IN MRD22. RX PubMed=24193349; DOI=10.1038/ejhg.2013.249; RA de Munnik S.A., Garcia-Minaur S., Hoischen A., van Bon B.W., RA Boycott K.M., Schoots J., Hoefsloot L.H., Knoers N.V., Bongers E.M., RA Brunner H.G.; RT "A de novo non-sense mutation in ZBTB18 in a patient with features of RT the 1q43q44 microdeletion syndrome."; RL Eur. J. Hum. Genet. 22:844-846(2014). CC -!- FUNCTION: Transcriptional repressor that plays a role in various CC developmental processes such as myogenesis and brain development. CC Plays a key role in myogenesis by directly repressing the CC expression of ID2 and ID3, 2 inhibitors of skeletal myogenesis. CC Also involved in controlling cell division of progenitor cells and CC regulating the survival of postmitotic cortical neurons. CC Specifically binds the consensus DNA sequence 5'- CC [AC]ACATCTG[GT][AC]-3' which contains the E box core, and acts by CC recruiting chromatin remodeling multiprotein complexes. May also CC play a role in the organization of chromosomes in the nucleus. CC {ECO:0000269|PubMed:9756912}. CC -!- SUBUNIT: Interacts with DNMT3A. {ECO:0000269|PubMed:11350943}. CC -!- INTERACTION: CC Q8IY44:CTBP2; NbExp=3; IntAct=EBI-3232046, EBI-10171902; CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Associates with condensed CC chromatin. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q99592-1; Sequence=Displayed; CC Name=2; CC IsoId=Q99592-2; Sequence=VSP_035381; CC -!- TISSUE SPECIFICITY: Lymphoid tissues, testis, heart, brain, CC skeletal muscle, and pancreas and, at much lower level, other CC tissues. CC -!- DISEASE: Mental retardation, autosomal dominant 22 (MRD22) CC [MIM:612337]: A disorder characterized by significantly below CC average general intellectual functioning associated with CC impairments in adaptive behavior and manifested during the CC developmental period. Additional MRD22 patients have limited or no CC speech, and variable but characteristic facial features, including CC round face, prominent forehead, flat nasal bridge, hypertelorism, CC epicanthal folds, and low-set ears. Other features may include CC hypotonia, poor growth, microcephaly, agenesis of the corpus CC callosum, and seizures. {ECO:0000269|PubMed:24193349}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein CC family. ZBTB18 subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 BTB (POZ) domain. {ECO:0000255|PROSITE- CC ProRule:PRU00037}. CC -!- SIMILARITY: Contains 4 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U38896; AAA81368.1; -; mRNA. DR EMBL; X95072; CAA64468.1; -; mRNA. DR EMBL; AJ001388; CAA04718.1; -; mRNA. DR EMBL; AJ223321; CAA11262.1; -; Genomic_DNA. DR EMBL; AK291408; BAF84097.1; -; mRNA. DR EMBL; AL590483; CAH71954.2; -; Genomic_DNA. DR EMBL; BC036677; AAH36677.2; -; mRNA. DR CCDS; CCDS1622.1; -. [Q99592-2] DR PIR; I39200; I39200. DR RefSeq; NP_001265125.1; NM_001278196.1. [Q99592-1] DR RefSeq; NP_006343.2; NM_006352.4. [Q99592-1] DR RefSeq; NP_991331.1; NM_205768.2. [Q99592-2] DR RefSeq; XP_005273063.1; XM_005273006.2. [Q99592-1] DR UniGene; Hs.69997; -. DR ProteinModelPortal; Q99592; -. DR SMR; Q99592; 2-127, 370-489. DR BioGrid; 115735; 15. DR IntAct; Q99592; 4. DR STRING; 9606.ENSP00000351539; -. DR PhosphoSite; Q99592; -. DR BioMuta; ZBTB18; -. DR DMDM; 20141020; -. DR PaxDb; Q99592; -. DR PRIDE; Q99592; -. DR DNASU; 10472; -. DR Ensembl; ENST00000358704; ENSP00000351539; ENSG00000179456. [Q99592-2] DR Ensembl; ENST00000622512; ENSP00000481278; ENSG00000179456. [Q99592-1] DR GeneID; 10472; -. DR KEGG; hsa:10472; -. DR UCSC; uc001iad.5; human. [Q99592-2] DR UCSC; uc001iae.4; human. [Q99592-1] DR CTD; 10472; -. DR GeneCards; ZBTB18; -. DR HGNC; HGNC:13030; ZBTB18. DR MIM; 608433; gene. DR MIM; 612337; phenotype. DR neXtProt; NX_Q99592; -. DR Orphanet; 36367; Distal monosomy 1q. DR PharmGKB; PA37608; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00800000124025; -. DR HOGENOM; HOG000234147; -. DR HOVERGEN; HBG059113; -. DR InParanoid; Q99592; -. DR OMA; DGSSHMP; -. DR OrthoDB; EOG73FQM8; -. DR PhylomeDB; Q99592; -. DR TreeFam; TF337437; -. DR SignaLink; Q99592; -. DR GeneWiki; ZNF238; -. DR GenomeRNAi; 10472; -. DR NextBio; 39714; -. DR PRO; PR:Q99592; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; Q99592; -. DR CleanEx; HS_ZNF238; -. DR Genevisible; Q99592; HS. DR GO; GO:0045171; C:intercellular bridge; IDA:HPA. DR GO; GO:0015630; C:microtubule cytoskeleton; IDA:HPA. DR GO; GO:0000228; C:nuclear chromosome; TAS:ProtInc. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; TAS:UniProtKB. DR GO; GO:0003677; F:DNA binding; TAS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0021549; P:cerebellum development; IEA:Ensembl. DR GO; GO:0021987; P:cerebral cortex development; IEA:Ensembl. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0048872; P:homeostasis of number of cells; IEA:Ensembl. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; ISS:UniProtKB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB. DR GO; GO:0048666; P:neuron development; IEA:Ensembl. DR GO; GO:0051302; P:regulation of cell division; IEA:Ensembl. DR GO; GO:0007519; P:skeletal muscle tissue development; ISS:UniProtKB. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.30.160.60; -; 3. DR InterPro; IPR000210; BTB/POZ_dom. DR InterPro; IPR011333; POZ_dom. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Pfam; PF00651; BTB; 1. DR SMART; SM00225; BTB; 1. DR SMART; SM00355; ZnF_C2H2; 4. DR SUPFAM; SSF54695; SSF54695; 1. DR PROSITE; PS50097; BTB; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 4. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 4. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Developmental protein; KW DNA-binding; Mental retardation; Metal-binding; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; Repressor; KW Transcription; Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 522 Zinc finger and BTB domain-containing FT protein 18. FT /FTId=PRO_0000047477. FT DOMAIN 24 91 BTB. {ECO:0000255|PROSITE- FT ProRule:PRU00037}. FT ZN_FING 370 392 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 410 432 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 438 460 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 466 489 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT REGION 310 427 Interaction with DNMT3A. FT MOD_RES 157 157 Phosphoserine. FT {ECO:0000250|UniProtKB:Q9JKY3}. FT MOD_RES 516 516 Phosphoserine. FT {ECO:0000244|PubMed:17525332}. FT MOD_RES 517 517 Phosphoserine. FT {ECO:0000244|PubMed:17525332}. FT VAR_SEQ 1 1 M -> MCPKGYEDSM (in isoform 2). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_035381. FT VARIANT 132 132 E -> G (in dbSNP:rs1048824). FT {ECO:0000269|PubMed:7633419}. FT /FTId=VAR_012768. FT CONFLICT 51 51 L -> I (in Ref. 6; AAH36677). FT {ECO:0000305}. FT CONFLICT 166 262 KLNILPSKRDLAAEPGNMWMRLPSDSAGIPQAGGEAEPHAT FT AAGKTVASPCSSTESLSQRSVTSVRDSADVDCVLDLSVKSS FT LSGVENLNSSYFSSQ -> IEHPAQQKGLGGRAWEHVDAIA FT LRLSRHPPGWRRGRATRHSSWKNSSQPLQLNRVFVPE (in FT Ref. 1; AAA81368). {ECO:0000305}. SQ SEQUENCE 522 AA; 58354 MW; DE024B66E02DCE75 CRC64; MEFPDHSRHL LQCLSEQRHQ GFLCDCTVLV GDAQFRAHRA VLASCSMYFH LFYKDQLDKR DIVHLNSDIV TAPAFALLLE FMYEGKLQFK DLPIEDVLAA ASYLHMYDIV KVCKKKLKEK ATTEADSTKK EEDASSCSDK VESLSDGSSH IAGDLPSDED EGEDEKLNIL PSKRDLAAEP GNMWMRLPSD SAGIPQAGGE AEPHATAAGK TVASPCSSTE SLSQRSVTSV RDSADVDCVL DLSVKSSLSG VENLNSSYFS SQDVLRSNLV QVKVEKEASC DESDVGTNDY DMEHSTVKES VSTNNRVQYE PAHLAPLRED SVLRELDRED KASDDEMMTP ESERVQVEGG MESSLLPYVS NILSPAGQIF MCPLCNKVFP SPHILQIHLS THFREQDGIR SKPAADVNVP TCSLCGKTFS CMYTLKRHER THSGEKPYTC TQCGKSFQYS HNLSRHAVVH TREKPHACKW CERRFTQSGD LYRHIRKFHC ELVNSLSVKS EALSLPTVRD WTLEDSSQEL WK // ID ZEB1_HUMAN Reviewed; 1124 AA. AC P37275; B4DJV0; B4DUW9; E9PCM7; F5H4I8; Q12924; Q13800; Q2KJ05; AC Q5T968; Q5VZ84; Q8NB68; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1999, sequence version 2. DT 11-NOV-2015, entry version 164. DE RecName: Full=Zinc finger E-box-binding homeobox 1; DE AltName: Full=NIL-2-A zinc finger protein; DE AltName: Full=Negative regulator of IL2; DE AltName: Full=Transcription factor 8; DE Short=TCF-8; GN Name=ZEB1; Synonyms=AREB6, TCF8; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8138542; RA Watanabe Y., Kawakami K., Hirayama Y., Nagano K.; RT "Transcription factors positively and negatively regulating the Na,K- RT ATPase alpha 1 subunit gene."; RL J. Biochem. 114:849-855(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Bachman N.J., Scarpulla R.C.; RT "A human zinc finger homeodomain protein homologous to the chicken RT delta-crystallin enhancer binding protein, delta EF1."; RL Submitted (JUL-1994) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-798 (ISOFORM 5). RC TISSUE=Brain, and Thalamus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., RA Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 390-1124. RX PubMed=1840704; DOI=10.1126/science.1840704; RA Williams T.M., Moolten D., Burlein J., Romano J., Bhaerman R., RA Godillot A., Mellon M., Rauscher F.J. III, Kant J.A.; RT "Identification of a zinc finger protein that inhibits IL-2 gene RT expression."; RL Science 254:1791-1794(1991). RN [8] RP INVOLVEMENT IN PPCD3. RX PubMed=16252232; DOI=10.1086/497348; RA Krafchak C.M., Pawar H., Moroi S.E., Sugar A., Lichter P.R., RA Mackey D.A., Mian S., Nairus T., Elner V., Schteingart M.T., RA Downs C.A., Kijek T.G., Johnson J.M., Trager E.H., Rozsa F.W., RA Mandal M.N.A., Epstein M.P., Vollrath D., Ayyagari R., Boehnke M., RA Richards J.E.; RT "Mutations in TCF8 cause posterior polymorphous corneal dystrophy and RT ectopic expression of COL4A3 by corneal endothelial cells."; RL Am. J. Hum. Genet. 77:694-708(2005). RN [9] RP SUMOYLATION AT LYS-347 AND LYS-774. RX PubMed=16061479; DOI=10.1074/jbc.M504477200; RA Long J., Zuo D., Park M.; RT "Pc2-mediated sumoylation of Smad-interacting protein 1 attenuates RT transcriptional repression of E-cadherin."; RL J. Biol. Chem. 280:35477-35489(2005). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-322, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [13] RP FUNCTION. RX PubMed=19935649; DOI=10.1038/ncb1998; RA Wellner U., Schubert J., Burk U.C., Schmalhofer O., Zhu F., RA Sonntag A., Waldvogel B., Vannier C., Darling D., zur Hausen A., RA Brunton V.G., Morton J., Sansom O., Schuler J., Stemmler M.P., RA Herzberger C., Hopt U., Keck T., Brabletz S., Brabletz T.; RT "The EMT-activator ZEB1 promotes tumorigenicity by repressing RT stemness-inhibiting microRNAs."; RL Nat. Cell Biol. 11:1487-1495(2009). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-642; SER-679 AND RP THR-702, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP FUNCTION. RX PubMed=20175752; DOI=10.1042/BJ20091578; RA Papadopoulou V., Postigo A., Sanchez-Tillo E., Porter A.C., RA Wagner S.D.; RT "ZEB1 and CtBP form a repressive complex at a distal promoter element RT of the BCL6 locus."; RL Biochem. J. 427:541-550(2010). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SMARCA4, AND TISSUE RP SPECIFICITY. RX PubMed=20418909; DOI=10.1038/onc.2010.102; RA Sanchez-Tillo E., Lazaro A., Torrent R., Cuatrecasas M., Vaquero E.C., RA Castells A., Engel P., Postigo A.; RT "ZEB1 represses E-cadherin and induces an EMT by recruiting the RT SWI/SNF chromatin-remodeling protein BRG1."; RL Oncogene 29:3490-3500(2010). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-679, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-493; LYS-504 AND LYS-515, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [20] RP STRUCTURE BY NMR OF 583-642. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the homeobox domain from human NIL-2-A zinc RT finger protein, transcription factor 8."; RL Submitted (APR-2007) to the PDB data bank. RN [21] RP VARIANTS FECD6 THR-78; ALA-649; PRO-810; PRO-840 AND THR-905. RX PubMed=20036349; DOI=10.1016/j.ajhg.2009.12.001; RA Riazuddin S.A., Zaghloul N.A., Al-Saif A., Davey L., Diplas B.H., RA Meadows D.N., Eghrari A.O., Minear M.A., Li Y.J., Klintworth G.K., RA Afshari N., Gregory S.G., Gottsch J.D., Katsanis N.; RT "Missense mutations in TCF8 cause late-onset Fuchs corneal dystrophy RT and interact with FCD4 on chromosome 9p."; RL Am. J. Hum. Genet. 86:45-53(2010). RN [22] RP INVOLVEMENT IN FECD6 AND PPCD3, VARIANT FECD6 HIS-640, RP CHARACTERIZATION OF VARIANTS FECD6 THR-78 AND HIS-640, AND VARIANT RP GLU-525. RX PubMed=23599324; DOI=10.1167/iovs.13-11781; RA Lechner J., Dash D.P., Muszynska D., Hosseini M., Segev F., George S., RA Frazer D.G., Moore J.E., Kaye S.B., Young T., Simpson D.A., RA Churchill A.J., Heon E., Willoughby C.E.; RT "Mutational spectrum of the ZEB1 gene in corneal dystrophies supports RT a genotype-phenotype correlation."; RL Invest. Ophthalmol. Vis. Sci. 54:3215-3223(2013). RN [23] RP VARIANTS FECD6 THR-78; ALA-649; SER-696; PRO-810; PRO-840 AND GLY-905, RP CHARACTERIZATION OF VARIANTS FECD6 THR-78; ALA-649; SER-696; PRO-810; RP PRO-840 AND GLY-905, AND SUBCELLULAR LOCATION. RX PubMed=25190660; DOI=10.1167/iovs.14-15247; RA Chung D.W., Frausto R.F., Ann L.B., Jang M.S., Aldave A.J.; RT "Functional impact of ZEB1 mutations associated with posterior RT polymorphous and Fuchs' endothelial corneal dystrophies."; RL Invest. Ophthalmol. Vis. Sci. 55:6159-6166(2014). CC -!- FUNCTION: Acts as a transcriptional repressor. Inhibits CC interleukin-2 (IL-2) gene expression. Enhances or represses the CC promoter activity of the ATP1A1 gene depending on the quantity of CC cDNA and on the cell type. Represses E-cadherin promoter and CC induces an epithelial-mesenchymal transition (EMT) by recruiting CC SMARCA4/BRG1. Represses BCL6 transcription in the presence of the CC corepressor CTBP1. Positively regulates neuronal differentiation. CC Represses RCOR1 transcription activation during neurogenesis. CC Represses transcription by binding to the E box (5'-CANNTG-3'). CC Promotes tumorigenicity by repressing stemness-inhibiting CC microRNAs. {ECO:0000269|PubMed:19935649, CC ECO:0000269|PubMed:20175752, ECO:0000269|PubMed:20418909}. CC -!- SUBUNIT: Interacts (via N-terminus) with SMARCA4/BRG1. CC {ECO:0000269|PubMed:20418909}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20418909, CC ECO:0000269|PubMed:25190660}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=P37275-1; Sequence=Displayed; CC Name=2; CC IsoId=P37275-2; Sequence=VSP_045184; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=P37275-3; Sequence=VSP_047280; CC Name=4; CC IsoId=P37275-4; Sequence=VSP_047281; CC Name=5; CC IsoId=P37275-5; Sequence=VSP_047279, VSP_045184; CC -!- TISSUE SPECIFICITY: Colocalizes with SMARCA4/BRG1 in E-cadherin- CC negative cells from established lines, and stroma of normal colon CC as well as in de-differentiated epithelial cells at the invasion CC front of colorectal carcinomas (at protein level). Expressed in CC heart and skeletal muscle, but not in liver, spleen, or pancreas. CC {ECO:0000269|PubMed:20418909}. CC -!- DISEASE: Corneal dystrophy, posterior polymorphous, 3 (PPCD3) CC [MIM:609141]: A subtype of posterior corneal dystrophy, a disease CC characterized by alterations of Descemet membrane presenting as CC vesicles, opacities or band-like lesions on slit-lamp examination CC and specular microscopy. Affected patient typically are CC asymptomatic. {ECO:0000269|PubMed:16252232, CC ECO:0000269|PubMed:23599324}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Corneal dystrophy, Fuchs endothelial, 6 (FECD6) CC [MIM:613270]: A corneal disease caused by loss of endothelium of CC the central cornea. It is characterized by focal wart-like guttata CC that arise from Descemet membrane and develop in the central CC cornea, epithelial blisters, reduced vision and pain. Descemet CC membrane is thickened by abnormal collagenous deposition. CC {ECO:0000269|PubMed:20036349, ECO:0000269|PubMed:23599324}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 7 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC -!- SIMILARITY: Contains 1 homeobox DNA-binding domain. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAG62481.1; Type=Frameshift; Positions=177; Evidence={ECO:0000305}; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; D15050; BAA03646.1; -; mRNA. DR EMBL; U12170; AAA20602.1; -; mRNA. DR EMBL; AK091478; BAC03673.1; -; mRNA. DR EMBL; AK296244; BAG58962.1; -; mRNA. DR EMBL; AK300830; BAG62481.1; ALT_FRAME; mRNA. DR EMBL; AL158080; CAI17320.1; -; Genomic_DNA. DR EMBL; AL117340; CAI17320.1; JOINED; Genomic_DNA. DR EMBL; AL161935; CAI17320.1; JOINED; Genomic_DNA. DR EMBL; AL355148; CAI17320.1; JOINED; Genomic_DNA. DR EMBL; AL161935; CAH74132.1; -; Genomic_DNA. DR EMBL; AL117340; CAH74132.1; JOINED; Genomic_DNA. DR EMBL; AL158080; CAH74132.1; JOINED; Genomic_DNA. DR EMBL; AL355148; CAH74132.1; JOINED; Genomic_DNA. DR EMBL; AL117340; CAI12550.1; -; Genomic_DNA. DR EMBL; AL158080; CAI12550.1; JOINED; Genomic_DNA. DR EMBL; AL161935; CAI12550.1; JOINED; Genomic_DNA. DR EMBL; AL355148; CAI12550.1; JOINED; Genomic_DNA. DR EMBL; AL355148; CAI15108.1; -; Genomic_DNA. DR EMBL; AL117340; CAI15108.1; JOINED; Genomic_DNA. DR EMBL; AL158080; CAI15108.1; JOINED; Genomic_DNA. DR EMBL; AL161935; CAI15108.1; JOINED; Genomic_DNA. DR EMBL; CH471072; EAW85989.1; -; Genomic_DNA. DR EMBL; BC112392; AAI12393.1; -; mRNA. DR EMBL; M81699; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS44370.1; -. [P37275-5] DR CCDS; CCDS53505.1; -. [P37275-2] DR CCDS; CCDS53506.1; -. [P37275-4] DR CCDS; CCDS53507.1; -. [P37275-3] DR CCDS; CCDS7169.1; -. [P37275-1] DR PIR; JX0293; JX0293. DR RefSeq; NP_001121600.1; NM_001128128.2. [P37275-5] DR RefSeq; NP_001167564.1; NM_001174093.1. [P37275-4] DR RefSeq; NP_001167565.1; NM_001174094.1. DR RefSeq; NP_001167566.1; NM_001174095.1. [P37275-3] DR RefSeq; NP_001167567.1; NM_001174096.1. [P37275-2] DR RefSeq; NP_110378.3; NM_030751.5. [P37275-1] DR UniGene; Hs.124503; -. DR PDB; 2E19; NMR; -; A=586-642. DR PDBsum; 2E19; -. DR ProteinModelPortal; P37275; -. DR SMR; P37275; 583-642. DR BioGrid; 112796; 22. DR IntAct; P37275; 2. DR MINT; MINT-94525; -. DR STRING; 9606.ENSP00000354487; -. DR PhosphoSite; P37275; -. DR BioMuta; ZEB1; -. DR DMDM; 6166575; -. DR MaxQB; P37275; -. DR PaxDb; P37275; -. DR PRIDE; P37275; -. DR Ensembl; ENST00000320985; ENSP00000319248; ENSG00000148516. [P37275-1] DR Ensembl; ENST00000361642; ENSP00000354487; ENSG00000148516. [P37275-2] DR Ensembl; ENST00000446923; ENSP00000391612; ENSG00000148516. [P37275-5] DR Ensembl; ENST00000542815; ENSP00000444891; ENSG00000148516. [P37275-3] DR Ensembl; ENST00000560721; ENSP00000452787; ENSG00000148516. [P37275-4] DR GeneID; 6935; -. DR KEGG; hsa:6935; -. DR UCSC; uc001ivr.4; human. [P37275-1] DR UCSC; uc001ivu.4; human. DR CTD; 6935; -. DR GeneCards; ZEB1; -. DR HGNC; HGNC:11642; ZEB1. DR HPA; CAB058686; -. DR HPA; HPA027524; -. DR MIM; 189909; gene. DR MIM; 609141; phenotype. DR MIM; 613270; phenotype. DR neXtProt; NX_P37275; -. DR Orphanet; 98974; Fuchs endothelial corneal dystrophy. DR Orphanet; 98973; Posterior polymorphous corneal dystrophy. DR PharmGKB; PA162409589; -. DR eggNOG; KOG3623; Eukaryota. DR eggNOG; ENOG410ZFMZ; LUCA. DR GeneTree; ENSGT00630000089829; -. DR HOGENOM; HOG000264256; -. DR HOVERGEN; HBG004697; -. DR InParanoid; P37275; -. DR KO; K09299; -. DR OMA; ECEKPQG; -. DR OrthoDB; EOG790G0D; -. DR PhylomeDB; P37275; -. DR TreeFam; TF331759; -. DR SignaLink; P37275; -. DR ChiTaRS; ZEB1; human. DR EvolutionaryTrace; P37275; -. DR GeneWiki; ZEB1; -. DR GenomeRNAi; 6935; -. DR NextBio; 27137; -. DR PRO; PR:P37275; -. DR Proteomes; UP000005640; Chromosome 10. DR Bgee; P37275; -. DR CleanEx; HS_ZEB1; -. DR ExpressionAtlas; P37275; baseline and differential. DR Genevisible; P37275; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005667; C:transcription factor complex; IEA:Ensembl. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; TAS:ProtInc. DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0001227; F:transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding; IDA:HGNC. DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc. DR GO; GO:0051216; P:cartilage development; IEA:Ensembl. DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl. DR GO; GO:0007417; P:central nervous system development; IEA:Ensembl. DR GO; GO:0090103; P:cochlea morphogenesis; IEA:Ensembl. DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IEA:Ensembl. DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IEA:Ensembl. DR GO; GO:0006955; P:immune response; TAS:ProtInc. DR GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0030857; P:negative regulation of epithelial cell differentiation; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:HGNC. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0007389; P:pattern specification process; IEA:Ensembl. DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0010464; P:regulation of mesenchymal cell proliferation; IEA:Ensembl. DR GO; GO:0051150; P:regulation of smooth muscle cell differentiation; IEA:Ensembl. DR GO; GO:0033081; P:regulation of T cell differentiation in thymus; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc. DR GO; GO:0017015; P:regulation of transforming growth factor beta receptor signaling pathway; IEA:Ensembl. DR GO; GO:0048752; P:semicircular canal morphogenesis; IEA:Ensembl. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 1.10.10.60; -; 1. DR Gene3D; 3.30.160.60; -; 5. DR InterPro; IPR008598; Di19_Zn_binding_dom. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR009057; Homeodomain-like. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Pfam; PF00046; Homeobox; 1. DR Pfam; PF05605; zf-Di19; 1. DR SMART; SM00389; HOX; 1. DR SMART; SM00355; ZnF_C2H2; 7. DR SUPFAM; SSF46689; SSF46689; 1. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Complete proteome; KW Corneal dystrophy; Differentiation; Disease mutation; DNA-binding; KW Homeobox; Isopeptide bond; Metal-binding; Neurogenesis; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; Repressor; KW Transcription; Transcription regulation; Ubl conjugation; Zinc; KW Zinc-finger. FT CHAIN 1 1124 Zinc finger E-box-binding homeobox 1. FT /FTId=PRO_0000047231. FT ZN_FING 170 193 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 200 222 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 240 262 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 268 292 C2H2-type 4; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT DNA_BIND 581 640 Homeobox; atypical. FT ZN_FING 904 926 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 932 954 C2H2-type 6. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 960 981 C2H2-type 7; atypical. FT {ECO:0000255|PROSITE-ProRule:PRU00042}. FT COMPBIAS 989 1124 Glu-rich (acidic). FT MOD_RES 31 31 Phosphoserine. FT {ECO:0000250|UniProtKB:Q62947}. FT MOD_RES 33 33 Phosphoserine. FT {ECO:0000250|UniProtKB:Q62947}. FT MOD_RES 313 313 Phosphoserine. FT {ECO:0000250|UniProtKB:Q64318}. FT MOD_RES 322 322 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 642 642 Phosphoserine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 679 679 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231}. FT MOD_RES 686 686 Phosphoserine. FT {ECO:0000250|UniProtKB:Q64318}. FT MOD_RES 693 693 Phosphoserine. FT {ECO:0000250|UniProtKB:Q64318}. FT MOD_RES 700 700 Phosphoserine. FT {ECO:0000250|UniProtKB:Q64318}. FT MOD_RES 702 702 Phosphothreonine. FT {ECO:0000244|PubMed:19690332}. FT MOD_RES 704 704 Phosphoserine. FT {ECO:0000250|UniProtKB:Q64318}. FT CROSSLNK 347 347 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT CROSSLNK 493 493 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 504 504 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 515 515 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 774 774 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT VAR_SEQ 1 19 MADGPRCKRRKQANPRRNN -> MK (in isoform 5). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_047279. FT VAR_SEQ 20 87 VTNYNTVVETNSDSDDEDKLHIVEEESVTDAADCEGVPEDD FT LPTDQTVLPGRSSEREGNAKNCWEDDR -> G (in FT isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_047280. FT VAR_SEQ 87 107 RKEGQEILGPEAQADEAGCTV -> I (in isoform FT 4). {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_047281. FT VAR_SEQ 87 87 R -> TG (in isoform 2 and isoform 5). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334}. FT /FTId=VSP_045184. FT VARIANT 78 78 N -> T (in FECD6; no effect on protein FT expression; no effect on nuclear FT localization; dbSNP:rs80194531). FT {ECO:0000269|PubMed:20036349, FT ECO:0000269|PubMed:23599324, FT ECO:0000269|PubMed:25190660}. FT /FTId=VAR_063759. FT VARIANT 90 90 G -> R (in dbSNP:rs12217419). FT /FTId=VAR_052731. FT VARIANT 525 525 G -> E (found in a patient with FECD6). FT {ECO:0000269|PubMed:23599324}. FT /FTId=VAR_072897. FT VARIANT 553 553 K -> R (in dbSNP:rs35753967). FT /FTId=VAR_031824. FT VARIANT 640 640 Q -> H (in FECD6; down-regulation of FT several collagen genes expression). FT {ECO:0000269|PubMed:23599324}. FT /FTId=VAR_072898. FT VARIANT 649 649 P -> A (in FECD6; no effect on protein FT expression; no effect on nuclear FT localization). FT {ECO:0000269|PubMed:20036349, FT ECO:0000269|PubMed:25190660}. FT /FTId=VAR_063760. FT VARIANT 696 696 N -> S (in FECD6; no effect on protein FT expression; no effect on nuclear FT localization). FT {ECO:0000269|PubMed:25190660}. FT /FTId=VAR_072899. FT VARIANT 810 810 Q -> P (in FECD6; no effect on protein FT expression; no effect on nuclear FT localization). FT {ECO:0000269|PubMed:20036349, FT ECO:0000269|PubMed:25190660}. FT /FTId=VAR_063761. FT VARIANT 840 840 Q -> P (in FECD6; no effect on protein FT expression; no effect on nuclear FT localization; dbSNP:rs118020901). FT {ECO:0000269|PubMed:20036349, FT ECO:0000269|PubMed:25190660}. FT /FTId=VAR_063762. FT VARIANT 905 905 A -> G (in FECD6; no effect on protein FT expression; no effect on nuclear FT localization). FT {ECO:0000269|PubMed:25190660}. FT /FTId=VAR_072900. FT VARIANT 905 905 A -> T (in FECD6). FT {ECO:0000269|PubMed:20036349}. FT /FTId=VAR_063763. FT CONFLICT 12 12 Q -> R (in Ref. 3; BAC03673). FT {ECO:0000305}. FT CONFLICT 81 81 N -> S (in Ref. 3; BAC03673). FT {ECO:0000305}. FT CONFLICT 84 84 E -> K (in Ref. 3; BAC03673). FT {ECO:0000305}. FT CONFLICT 220 220 T -> A (in Ref. 3; BAG62481). FT {ECO:0000305}. FT CONFLICT 390 390 M -> T (in Ref. 3; BAG62481). FT {ECO:0000305}. FT CONFLICT 420 420 V -> I (in Ref. 2; AAA20602). FT {ECO:0000305}. FT CONFLICT 472 472 K -> R (in Ref. 3; BAG58962). FT {ECO:0000305}. FT CONFLICT 609 609 E -> Q (in Ref. 7; M81699). FT {ECO:0000305}. FT CONFLICT 654 654 I -> T (in Ref. 2; AAA20602). FT {ECO:0000305}. FT CONFLICT 672 672 D -> H (in Ref. 7; M81699). FT {ECO:0000305}. FT CONFLICT 681 681 L -> S (in Ref. 7; M81699). FT {ECO:0000305}. FT CONFLICT 775 775 K -> T (in Ref. 3; BAG62481). FT {ECO:0000305}. FT CONFLICT 793 794 IP -> KY (in Ref. 3; BAG58962). FT {ECO:0000305}. FT CONFLICT 797 797 A -> N (in Ref. 3; BAG58962). FT {ECO:0000305}. FT CONFLICT 818 818 A -> V (in Ref. 3; BAG62481). FT {ECO:0000305}. FT CONFLICT 838 838 I -> T (in Ref. 3; BAC03673). FT {ECO:0000305}. FT CONFLICT 1066 1066 E -> G (in Ref. 3; BAC03673). FT {ECO:0000305}. FT HELIX 590 600 {ECO:0000244|PDB:2E19}. FT HELIX 608 618 {ECO:0000244|PDB:2E19}. FT HELIX 622 634 {ECO:0000244|PDB:2E19}. SQ SEQUENCE 1124 AA; 124074 MW; 0A2714CC37C848D1 CRC64; MADGPRCKRR KQANPRRNNV TNYNTVVETN SDSDDEDKLH IVEEESVTDA ADCEGVPEDD LPTDQTVLPG RSSEREGNAK NCWEDDRKEG QEILGPEAQA DEAGCTVKDD ECESDAENEQ NHDPNVEEFL QQQDTAVIFP EAPEEDQRQG TPEASGHDEN GTPDAFSQLL TCPYCDRGYK RFTSLKEHIK YRHEKNEDNF SCSLCSYTFA YRTQLERHMT SHKSGRDQRH VTQSGCNRKF KCTECGKAFK YKHHLKEHLR IHSGEKPYEC PNCKKRFSHS GSYSSHISSK KCISLIPVNG RPRTGLKTSQ CSSPSLSASP GSPTRPQIRQ KIENKPLQEQ LSVNQIKTEP VDYEFKPIVV ASGINCSTPL QNGVFTGGGP LQATSSPQGM VQAVVLPTVG LVSPISINLS DIQNVLKVAV DGNVIRQVLE NNQANLASKE QETINASPIQ QGGHSVISAI SLPLVDQDGT TKIIINYSLE QPSQLQVVPQ NLKKENPVAT NSCKSEKLPE DLTVKSEKDK SFEGGVNDST CLLCDDCPGD INALPELKHY DLKQPTQPPP LPAAEAEKPE SSVSSATGDG NLSPSQPPLK NLLSLLKAYY ALNAQPSAEE LSKIADSVNL PLDVVKKWFE KMQAGQISVQ SSEPSSPEPG KVNIPAKNND QPQSANANEP QDSTVNLQSP LKMTNSPVLP VGSTTNGSRS STPSPSPLNL SSSRNTQGYL YTAEGAQEEP QVEPLDLSLP KQQGELLERS TITSVYQNSV YSVQEEPLNL SCAKKEPQKD SCVTDSEPVV NVIPPSANPI NIAIPTVTAQ LPTIVAIADQ NSVPCLRALA ANKQTILIPQ VAYTYSTTVS PAVQEPPLKV IQPNGNQDER QDTSSEGVSN VEDQNDSDST PPKKKMRKTE NGMYACDLCD KIFQKSSSLL RHKYEHTGKR PHECGICKKA FKHKHHLIEH MRLHSGEKPY QCDKCGKRFS HSGSYSQHMN HRYSYCKREA EERDSTEQEE AGPEILSNEH VGARASPSQG DSDERESLTR EEDEDSEKEE EEEDKEMEEL QEEKECEKPQ GDEEEEEEEE EVEEEEVEEA ENEGEEAKTE GLMKDDRAES QASSLGQKVG ESSEQVSEEK TNEA // ID ZN219_HUMAN Reviewed; 722 AA. AC Q9P2Y4; D3DS16; Q53Y57; Q8IYC1; Q9BW28; DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 23-NOV-2004, sequence version 2. DT 11-NOV-2015, entry version 138. DE RecName: Full=Zinc finger protein 219; GN Name=ZNF219; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION. RC TISSUE=Testis; RX PubMed=10819330; DOI=10.1093/dnares/7.2.137; RA Sakai T., Toyoda A., Hashimoto K., Maeda H.; RT "Isolation and characterization of a novel zinc finger gene, ZNF219, RT and mapping to the human chromosome 14q11 region."; RL DNA Res. 7:137-141(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-260. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-260. RC TISSUE=Brain, and Kidney; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). CC -!- FUNCTION: May be involved in transcriptional regulation. CC -!- INTERACTION: CC P25800:LMO1; NbExp=3; IntAct=EBI-3937106, EBI-8639312; CC Q5I0X7:TTC32; NbExp=3; IntAct=EBI-3937106, EBI-8636434; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- SIMILARITY: Belongs to the krueppel C2H2-type zinc-finger protein CC family. {ECO:0000305}. CC -!- SIMILARITY: Contains 6 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AB015427; BAA90526.1; -; mRNA. DR EMBL; BT006956; AAP35602.1; -; mRNA. DR EMBL; CH471078; EAW66404.1; -; Genomic_DNA. DR EMBL; CH471078; EAW66405.1; -; Genomic_DNA. DR EMBL; CH471078; EAW66406.1; -; Genomic_DNA. DR EMBL; CH471078; EAW66407.1; -; Genomic_DNA. DR EMBL; BC000694; AAH00694.1; -; mRNA. DR EMBL; BC036105; AAH36105.1; -; mRNA. DR CCDS; CCDS9568.1; -. DR RefSeq; NP_001095142.1; NM_001101672.1. DR RefSeq; NP_001095924.1; NM_001102454.1. DR RefSeq; NP_057507.2; NM_016423.2. DR RefSeq; XP_006720226.1; XM_006720163.2. DR RefSeq; XP_006720227.1; XM_006720164.2. DR UniGene; Hs.250493; -. DR ProteinModelPortal; Q9P2Y4; -. DR SMR; Q9P2Y4; 57-210, 269-331, 393-429, 498-549, 635-675. DR BioGrid; 119387; 41. DR IntAct; Q9P2Y4; 10. DR MINT; MINT-8247371; -. DR STRING; 9606.ENSP00000354206; -. DR PhosphoSite; Q9P2Y4; -. DR BioMuta; ZNF219; -. DR DMDM; 55977885; -. DR MaxQB; Q9P2Y4; -. DR PaxDb; Q9P2Y4; -. DR PRIDE; Q9P2Y4; -. DR DNASU; 51222; -. DR Ensembl; ENST00000360947; ENSP00000354206; ENSG00000165804. DR Ensembl; ENST00000421093; ENSP00000392401; ENSG00000165804. DR Ensembl; ENST00000451119; ENSP00000388558; ENSG00000165804. DR GeneID; 51222; -. DR KEGG; hsa:51222; -. DR UCSC; uc001vzr.2; human. DR CTD; 51222; -. DR GeneCards; ZNF219; -. DR HGNC; HGNC:13011; ZNF219. DR HPA; HPA030761; -. DR HPA; HPA056168; -. DR MIM; 605036; gene. DR neXtProt; NX_Q9P2Y4; -. DR PharmGKB; PA37590; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00530000063100; -. DR HOGENOM; HOG000140857; -. DR HOVERGEN; HBG054187; -. DR InParanoid; Q9P2Y4; -. DR OMA; DASPPYA; -. DR OrthoDB; EOG7D59N5; -. DR PhylomeDB; Q9P2Y4; -. DR TreeFam; TF332241; -. DR ChiTaRS; ZNF219; human. DR GeneWiki; ZNF219; -. DR GenomeRNAi; 51222; -. DR NextBio; 54298; -. DR PRO; PR:Q9P2Y4; -. DR Proteomes; UP000005640; Chromosome 14. DR Bgee; Q9P2Y4; -. DR CleanEx; HS_ZNF219; -. DR ExpressionAtlas; Q9P2Y4; baseline and differential. DR Genevisible; Q9P2Y4; HS. DR GO; GO:0016021; C:integral component of membrane; IEA:InterPro. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0004969; F:histamine receptor activity; IEA:InterPro. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:NTNU_SB. DR GO; GO:0007275; P:multicellular organismal development; IBA:GO_Central. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:NTNU_SB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0001505; P:regulation of neurotransmitter levels; IEA:InterPro. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:UniProtKB. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR GO; GO:0006351; P:transcription, DNA-templated; IDA:UniProtKB. DR Gene3D; 3.30.160.60; -; 6. DR InterPro; IPR003980; Histamine_H3_rcpt. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR PRINTS; PR01471; HISTAMINEH3R. DR SMART; SM00355; ZnF_C2H2; 9. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 5. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 6. PE 1: Evidence at protein level; KW Complete proteome; DNA-binding; Metal-binding; Nucleus; Polymorphism; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Zinc; Zinc-finger. FT CHAIN 1 722 Zinc finger protein 219. FT /FTId=PRO_0000047461. FT ZN_FING 57 79 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 85 107 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 163 186 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 274 296 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 302 324 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 498 520 C2H2-type 6. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT VARIANT 260 260 P -> T (in dbSNP:rs17853549). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.2}. FT /FTId=VAR_067624. FT CONFLICT 232 233 Missing (in Ref. 4; AAH00694). FT {ECO:0000305}. FT CONFLICT 436 436 E -> Q (in Ref. 1; BAA90526). FT {ECO:0000305}. SQ SEQUENCE 722 AA; 76877 MW; AB2B6B37904FC14B CRC64; MEGSRPRAPS GHLAPSPPAF DGELDLQRYS NGPAVSAGSL GMGAVSWSES RAGERRFPCP VCGKRFRFNS ILALHLRAHP GAQAFQCPHC GHRAAQRALL RSHLRTHQPE RPRSPAARLL LELEERALLR EARLGRARSS GGMQATPATE GLARPQAPSS SAFRCPYCKG KFRTSAERER HLHILHRPWK CGLCSFGSSQ EEELLHHSLT AHGAPERPLA ATSAAPPPQP QPQPPPQPEP RSVPQPEPEP EPEREATPTP APAAPEEPPA PPEFRCQVCG QSFTQSWFLK GHMRKHKASF DHACPVCGRC FKEPWFLKNH MKVHASKLGP LRAPGPASGP ARAPQPPDLG LLAYEPLGPA LLLAPAPTPA ERREPPSLLG YLSLRAGEGR PNGEGAEPGP GRSFGGFRPL SSALPARARR HRAEEPEEEE EVVEAEEETW ARGRSLGSLA SLHPRPGEGP GHSASAAGAQ ARSTATQEEN GLLVGGTRPE GGRGATGKDC PFCGKSFRSA HHLKVHLRVH TGERPYKCPH CDYAGTQSGS LKYHLQRHHR EQRSGAGPGP PPEPPPPSQR GSAPQSGAKP SPQPATWVEG ASSPRPPSSG AGPGSRRKPA SPGRTLRNGR GGEAEPLDLS LRAGPGGEAG PGGALHRCLF CPFATGAPEL MALHLQVHHS RRARGRRPPQ ADASPPYARV PSGETPPSPS QEGEEGSGLS RPGEAGLGGQ ER // ID ZN366_HUMAN Reviewed; 744 AA. AC Q8N895; Q5HYI9; Q7RTV4; DT 12-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2002, sequence version 1. DT 11-NOV-2015, entry version 113. DE RecName: Full=Zinc finger protein 366; GN Name=ZNF366; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Spleen; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Heart; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., RA Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., RA Ottenwaelder B., Poustka A., Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP IDENTIFICATION. RX PubMed=12234665; DOI=10.1016/S0378-1119(02)00793-X; RA Gilligan P., Brenner S., Venkatesh B.; RT "Fugu and human sequence comparison identifies novel human genes and RT conserved non-coding sequences."; RL Gene 294:35-44(2002). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ESR1; NRIP1 AND RP CTBP1, AND MUTAGENESIS OF PRO-590; ASP-592; PRO-645 AND ASP-647. RX PubMed=17085477; DOI=10.1093/nar/gkl875; RA Lopez-Garcia J., Periyasamy M., Thomas R.S., Christian M., Leao M., RA Jat P., Kindle K.B., Heery D.M., Parker M.G., Buluwela L., RA Kamalati T., Ali S.; RT "ZNF366 is an estrogen receptor corepressor that acts through CtBP and RT histone deacetylases."; RL Nucleic Acids Res. 34:6126-6136(2006). CC -!- FUNCTION: Has transcriptional repression activity. Acts as CC corepressor of ESR1; the function seems to involve CTBP1 and CC histone deacetylases. {ECO:0000269|PubMed:17085477}. CC -!- SUBUNIT: Interacts with ESR1, NRIP1 and CTBP1. CC {ECO:0000269|PubMed:17085477}. CC -!- INTERACTION: CC Q8NHQ1:CEP70; NbExp=3; IntAct=EBI-2813661, EBI-739624; CC Q13363:CTBP1; NbExp=5; IntAct=EBI-2813661, EBI-908846; CC P03372:ESR1; NbExp=6; IntAct=EBI-2813661, EBI-78473; CC P48552:NRIP1; NbExp=2; IntAct=EBI-2813661, EBI-746484; CC P25788:PSMA3; NbExp=3; IntAct=EBI-2813661, EBI-348380; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:17085477}. CC -!- SIMILARITY: Contains 11 C2H2-type zinc fingers. CC {ECO:0000255|PROSITE-ProRule:PRU00042}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AK097115; BAC04954.1; -; mRNA. DR EMBL; BX647592; CAI46096.1; -; mRNA. DR EMBL; CH471084; EAW95707.1; -; Genomic_DNA. DR EMBL; BC121053; AAI21054.1; -; mRNA. DR EMBL; BK000210; DAA00066.1; -; mRNA. DR CCDS; CCDS4015.1; -. DR RefSeq; NP_689838.1; NM_152625.2. DR UniGene; Hs.224794; -. DR UniGene; Hs.370303; -. DR ProteinModelPortal; Q8N895; -. DR SMR; Q8N895; 251-557. DR BioGrid; 127947; 2. DR IntAct; Q8N895; 7. DR STRING; 9606.ENSP00000313158; -. DR PhosphoSite; Q8N895; -. DR BioMuta; ZNF366; -. DR DMDM; 28380235; -. DR PaxDb; Q8N895; -. DR PRIDE; Q8N895; -. DR DNASU; 167465; -. DR Ensembl; ENST00000318442; ENSP00000313158; ENSG00000178175. DR GeneID; 167465; -. DR KEGG; hsa:167465; -. DR UCSC; uc003kce.1; human. DR CTD; 167465; -. DR GeneCards; ZNF366; -. DR HGNC; HGNC:18316; ZNF366. DR HPA; HPA023128; -. DR HPA; HPA023526; -. DR MIM; 610159; gene. DR neXtProt; NX_Q8N895; -. DR PharmGKB; PA38314; -. DR eggNOG; KOG1721; Eukaryota. DR eggNOG; COG5048; LUCA. DR GeneTree; ENSGT00750000117653; -. DR HOGENOM; HOG000138030; -. DR HOVERGEN; HBG055962; -. DR InParanoid; Q8N895; -. DR OMA; HMMQHSE; -. DR OrthoDB; EOG7MPRDM; -. DR PhylomeDB; Q8N895; -. DR TreeFam; TF331510; -. DR ChiTaRS; ZNF366; human. DR GeneWiki; ZNF366; -. DR GenomeRNAi; 167465; -. DR NextBio; 88674; -. DR PRO; PR:Q8N895; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; Q8N895; -. DR CleanEx; HS_ZNF366; -. DR ExpressionAtlas; Q8N895; baseline and differential. DR Genevisible; Q8N895; HS. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0030331; F:estrogen receptor binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB. DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0043627; P:response to estrogen; IDA:UniProtKB. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.30.160.60; -; 10. DR InterPro; IPR007087; Znf_C2H2. DR InterPro; IPR015880; Znf_C2H2-like. DR InterPro; IPR013087; Znf_C2H2/integrase_DNA-bd. DR Pfam; PF00096; zf-C2H2; 1. DR SMART; SM00355; ZnF_C2H2; 11. DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 11. DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 11. PE 1: Evidence at protein level; KW Complete proteome; DNA-binding; Metal-binding; Nucleus; Polymorphism; KW Reference proteome; Repeat; Repressor; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 744 Zinc finger protein 366. FT /FTId=PRO_0000047548. FT ZN_FING 253 275 C2H2-type 1. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 281 303 C2H2-type 2. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 309 331 C2H2-type 3. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 337 359 C2H2-type 4. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 365 387 C2H2-type 5. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 393 415 C2H2-type 6. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 421 443 C2H2-type 7. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 449 471 C2H2-type 8. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 477 499 C2H2-type 9. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 505 527 C2H2-type 10. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT ZN_FING 533 556 C2H2-type 11. {ECO:0000255|PROSITE- FT ProRule:PRU00042}. FT REGION 455 744 Interaction with NRIP1. FT REGION 558 744 Interaction with CTBP1. FT VARIANT 739 739 A -> G (in dbSNP:rs13188519). FT /FTId=VAR_033564. FT MUTAGEN 590 590 P->A: Abolishes interaction with CTBP1 FT and in part relieves transcription FT repression; when associated with A-592. FT {ECO:0000269|PubMed:17085477}. FT MUTAGEN 592 592 D->A: Abolishes interaction with CTBP1 FT and in part relieves transcription FT repression; when associated with A-590. FT {ECO:0000269|PubMed:17085477}. FT MUTAGEN 645 645 P->A: Decreases interaction with CTBP1; FT when associated with A-647. FT {ECO:0000269|PubMed:17085477}. FT MUTAGEN 647 647 D->A: Decreases interaction with CTBP1; FT when associated with A-645. FT {ECO:0000269|PubMed:17085477}. SQ SEQUENCE 744 AA; 85107 MW; D4E12259280727B1 CRC64; MQKEMKMIKD EDVHFDLAVK KTPSFPHCLQ PVASRGKAPQ RHPFPEALRG PFSQFRYEPP PGDLDGFPGV FEGAGSRKRK SMPTKMPYNH PAEEVTLALH SEENKNHGLP NLPLLFPQPP RPKYDSQMID LCNVGFQFYR SLEHFGGKPV KQEPIKPSAV WPQPTPTPFL PTPYPYYPKV HPGLMFPFFV PSSSPFPFSR HTFLPKQPPE PLLPRKAEPQ ESEETKQKVE RVDVNVQIDD SYYVDVGGSQ KRWQCPTCEK SYTSKYNLVT HILGHSGIKP HACTHCGKLF KQLSHLHTHM LTHQGTRPHK CQVCHKAFTQ TSHLKRHMMQ HSEVKPHNCR VCGRGFAYPS ELKAHEAKHA SGRENICVEC GLDFPTLAQL KRHLTTHRGP IQYNCSECDK TFQYPSQLQN HMMKHKDIRP YICSECGMEF VQPHHLKQHS LTHKGVKEHK CGICGREFTL LANMKRHVLI HTNIRAYQCH LCYKSFVQKQ TLKAHMIVHS DVKPFKCKLC GKEFNRMHNL MGHMHLHSDS KPFKCLYCPS KFTLKGNLTR HMKVKHGVME RGLHSQGLGR GRIALAQTAG VLRSLEQEEP FDLSQKRRAK VPVFQSDGES AQGSHCHEEE EEDNCYEVEP YSPGLAPQSQ QLCTPEDLST KSEHAPEVLE EACKEEKEDA SKGEWEKRSK GDLGAEGGQE RDCAGRDECL SLRAFQSTRR GPSFSDYLYF KHRDESLKEL LERKMEKQAV LLGI // ID ZN750_HUMAN Reviewed; 723 AA. AC Q32MQ0; Q9H899; DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot. DT 06-DEC-2005, sequence version 1. DT 11-NOV-2015, entry version 84. DE RecName: Full=Zinc finger protein 750; GN Name=ZNF750; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Thyroid; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16625196; DOI=10.1038/nature04689; RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., RA Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., RA Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., RA Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., RA Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., RA Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., RA Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., RA Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.; RT "DNA sequence of human chromosome 17 and analysis of rearrangement in RT the human lineage."; RL Nature 440:1045-1049(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INVOLVEMENT IN SLDP, AND TISSUE SPECIFICITY. RX PubMed=16751772; DOI=10.1038/ng1813; RA Birnbaum R.Y., Zvulunov A., Hallel-Halevy D., Cagnano E., Finer G., RA Ofir R., Geiger D., Silberstein E., Feferman Y., Birk O.S.; RT "Seborrhea-like dermatitis with psoriasiform elements caused by a RT mutation in ZNF750, encoding a putative C2H2 zinc finger protein."; RL Nat. Genet. 38:749-751(2006). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, DNA-BINDING, INDUCTION BY TP63, AND RP MUTAGENESIS OF CYS-27; CYS-30; HIS-39 AND HIS-43. RX PubMed=22364861; DOI=10.1016/j.devcel.2011.12.001; RA Sen G.L., Boxer L.D., Webster D.E., Bussat R.T., Qu K., Zarnegar B.J., RA Johnston D., Siprashvili Z., Khavari P.A.; RT "ZNF750 is a p63 target gene that induces KLF4 to drive terminal RT epidermal differentiation."; RL Dev. Cell 22:669-677(2012). CC -!- FUNCTION: Transcription factor involved in epidermis CC differentiation. Required for terminal epidermal differentiation: CC acts downstream of p63/TP63 and activates expression of late CC epidermal differentiation genes. Specifically binds to the CC promoter of KLF4 and promotes its expression. CC {ECO:0000269|PubMed:22364861}. CC -!- INTERACTION: CC P56545:CTBP2; NbExp=3; IntAct=EBI-10240029, EBI-741533; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22364861}. CC -!- TISSUE SPECIFICITY: Expressed in the skin, prostate, lung, CC placenta and thymus, and at low level in T-cells. Not expressed in CC peripheral blood leukocytes, pancreas and brain. Clearly expressed CC in primary keratinocytes but not in fibroblasts. CC {ECO:0000269|PubMed:16751772}. CC -!- INDUCTION: During epidermal differentiation: expression is CC activated by p63/TP63. {ECO:0000269|PubMed:22364861}. CC -!- DISEASE: Seborrhea-like dermatitis with psoriasiform elements CC (SLDP) [MIM:610227]: Characterized by a chronic fine diffuse scaly CC erythematous rash on the face, particularly on the chin, CC nasolabial folds and eyebrows, around earlobes and over the scalp. CC The rash exacerbate in the winter, with emotional stress and after CC strenuous physical activity. Hyperkeratosis of skin over the CC elbows, knees, palms, soles and metacarpophalangeal joints is CC evident. There is no arthralgia, arthritis or neurological CC disorders. {ECO:0000269|PubMed:16751772}. Note=The disease is CC caused by mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Contains 1 C2H2-type zinc finger. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AK023903; BAB14718.1; -; mRNA. DR EMBL; AC068584; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC109036; AAI09037.1; -; mRNA. DR EMBL; BC109037; AAI09038.1; -; mRNA. DR CCDS; CCDS11819.1; -. DR RefSeq; NP_078978.2; NM_024702.2. DR UniGene; Hs.464391; -. DR UniGene; Hs.653124; -. DR ProteinModelPortal; Q32MQ0; -. DR BioGrid; 122866; 1. DR IntAct; Q32MQ0; 1. DR STRING; 9606.ENSP00000269394; -. DR PhosphoSite; Q32MQ0; -. DR BioMuta; ZNF750; -. DR DMDM; 110825759; -. DR PaxDb; Q32MQ0; -. DR PRIDE; Q32MQ0; -. DR Ensembl; ENST00000269394; ENSP00000269394; ENSG00000141579. DR GeneID; 79755; -. DR KEGG; hsa:79755; -. DR UCSC; uc002kga.3; human. DR CTD; 79755; -. DR GeneCards; ZNF750; -. DR HGNC; HGNC:25843; ZNF750. DR HPA; HPA021573; -. DR HPA; HPA023012; -. DR MIM; 610226; gene. DR MIM; 610227; phenotype. DR neXtProt; NX_Q32MQ0; -. DR Orphanet; 168606; Seborrhea-like dermatitis with psoriasiform elements. DR PharmGKB; PA145149939; -. DR eggNOG; ENOG410IF50; Eukaryota. DR eggNOG; ENOG410ZK89; LUCA. DR GeneTree; ENSGT00530000063870; -. DR HOGENOM; HOG000049178; -. DR HOVERGEN; HBG080198; -. DR InParanoid; Q32MQ0; -. DR OMA; HYRFFQQ; -. DR OrthoDB; EOG7G1V5J; -. DR PhylomeDB; Q32MQ0; -. DR TreeFam; TF331381; -. DR Reactome; R-HSA-212436; Generic Transcription Pathway. DR GenomeRNAi; 79755; -. DR NextBio; 69211; -. DR PRO; PR:Q32MQ0; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; Q32MQ0; -. DR CleanEx; HS_ZNF750; -. DR ExpressionAtlas; Q32MQ0; baseline and differential. DR Genevisible; Q32MQ0; HS. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0001046; F:core promoter sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:UniProtKB. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0008544; P:epidermis development; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IDA:GOC. DR InterPro; IPR015880; Znf_C2H2-like. DR SMART; SM00355; ZnF_C2H2; 1. PE 1: Evidence at protein level; KW Activator; Complete proteome; Differentiation; Metal-binding; Nucleus; KW Polymorphism; Reference proteome; Transcription; KW Transcription regulation; Zinc; Zinc-finger. FT CHAIN 1 723 Zinc finger protein 750. FT /FTId=PRO_0000247070. FT ZN_FING 25 46 C2H2-type; degenerate. FT VARIANT 235 235 M -> V (in dbSNP:rs8074277). FT /FTId=VAR_027062. FT VARIANT 288 288 P -> L (in dbSNP:rs35653278). FT /FTId=VAR_051502. FT VARIANT 392 392 Q -> R (in dbSNP:rs34687659). FT /FTId=VAR_051503. FT MUTAGEN 27 27 C->A: Abolishes the ability to induce FT epidermal terminal differentiation; when FT associated with A-30. FT {ECO:0000269|PubMed:22364861}. FT MUTAGEN 30 30 C->A: Abolishes the ability to induce FT epidermal terminal differentiation; when FT associated with A-27. FT {ECO:0000269|PubMed:22364861}. FT MUTAGEN 39 39 H->A: Abolishes the ability to induce FT epidermal terminal differentiation; when FT associated with A-43. FT {ECO:0000269|PubMed:22364861}. FT MUTAGEN 43 43 H->A: Abolishes the ability to induce FT epidermal terminal differentiation; when FT associated with A-39. FT {ECO:0000269|PubMed:22364861}. FT CONFLICT 178 178 A -> P (in Ref. 1; BAB14718). FT {ECO:0000305}. SQ SEQUENCE 723 AA; 77361 MW; 890E7DB46DD0F5FF CRC64; MSLLKERKPK KPHYIPRPPG KPFKYKCFQC PFTCNEKSHL FNHMKYGLCK NSITLVSEQD RVPKCPKSNS LDPKQTNQPD ATAKPASSKS VANGLSAFDS KLQHSSARED IKENLELQAR GTHRCLGQKP ALHRASPCKS PAPEAALGAQ PALEGAARPS AFVPVGEHRL KGPDNAEAPE TLALHNPTAK AVSFHTKSAF HTPGYPWKAG SPFLPPEFPH KISSTKGLGA ISPYMHPTIP EYPPHFYTEH GLATIYSPYL LAGSSPECDA PLLSVYGTQD PRHFLPHPGP IPKHLAPSPA TYDHYRFFQQ YPSNLPIPYG FYRPESAFSS YGLRLPPVTG LTRDQSSHLL EEATLVYPAS SPSRLNPSDP NRKHVEFESP IPEAKDSSKA GQRDTEGSKM SPRAGSAATG SPGRPSPTDF MQTSQTCEGL YDLSNKAASS ALGRLYPPEQ SLTAFRPVKK STECLPAQAA ETTAESPVSL NVVNGDPPAP TGSASLVSEA APSSPDDSSG MGPLNLSKKS EINLAATHEP TYQGSPQAET ASFSELQDLP LNLSVKDPCN TQAPRPAFPG RPRAAEPAAA VPQKTGTEGS EDGPSHPETK PGSLDGDGAP PTGPGEEAPD ACAVDSSEEQ KQTAAVALCQ LAAYSPRNIR VGDGDAAAPE PACRQDTPTL SSMESQEAQC DLRPKGQKRT SLRDAGKSQQ GAKKAKLQDT ARVFTLRRRA RVS //