ID ATX1L_HUMAN Reviewed; 689 AA. AC P0C7T5; DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot. DT 22-JUL-2008, sequence version 1. DT 11-NOV-2015, entry version 66. DE RecName: Full=Ataxin-1-like; DE AltName: Full=Brother of ataxin-1; DE Short=Brother of ATXN1; GN Name=ATXN1L; Synonyms=BOAT, BOAT1; 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=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 [2] RP INTERACTION WITH NCOR2 AND ATXN1, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=16121196; DOI=10.1038/sj.emboj.7600785; RA Mizutani A., Wang L., Rajan H., Vig P.J.S., Alaynick W.A., RA Thaler J.P., Tsai C.-C.; RT "Boat, an AXH domain protein, suppresses the cytotoxicity of mutant RT ataxin-1."; RL EMBO J. 24:3339-3351(2005). RN [3] 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 [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, 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 [5] RP FUNCTION, AND INTERACTION WITH RBPJ. RX PubMed=21475249; DOI=10.1038/embor.2011.49; RA Tong X., Gui H., Jin F., Heck B.W., Lin P., Ma J., Fondell J.D., RA Tsai C.C.; RT "Ataxin-1 and Brother of ataxin-1 are components of the Notch RT signalling pathway."; RL EMBO Rep. 12:428-435(2011). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361, 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: Chromatin-binding factor that repress Notch signaling in CC the absence of Notch intracellular domain by acting as a CBF1 CC corepressor. Binds to the HEY promoter and might assist, along CC with NCOR2, RBPJ-mediated repression. Can suppress ATXN1 CC cytotoxicity in spinocerebellar ataxia type 1 (SCA1) (By CC similarity). {ECO:0000250}. CC -!- SUBUNIT: Homodimer. Interacts with CIC (By similarity). Interacts CC (via AXH domain) with NCOR2. Interacts with ATXN1. Directly CC interacts with RBPJ; this interaction is disrupted in the presence CC of Notch intracellular domain. Competes with ATXN1 for RBPJ- CC binding. {ECO:0000250, ECO:0000269|PubMed:16121196, CC ECO:0000269|PubMed:21475249}. CC -!- INTERACTION: CC Q06330:RBPJ; NbExp=7; IntAct=EBI-8624731, EBI-632552; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16121196}. Cell CC projection, dendrite {ECO:0000269|PubMed:16121196}. Note=Forms CC nuclear foci. Colocalizes with NCOR2 and HDAC3. Distributed beyond CC the nucleus into the cell body and dendrites in Purkinje cells and CC in inferior olive cells. CC -!- TISSUE SPECIFICITY: Expressed in cerebellum and cerebral cortex. CC {ECO:0000269|PubMed:16121196}. CC -!- SIMILARITY: Belongs to the ATXN1 family. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 AXH domain. {ECO:0000255|PROSITE- CC ProRule:PRU00496}. 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; AC010653; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BX537575; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS45523.1; -. DR RefSeq; NP_001131147.1; NM_001137675.3. DR UniGene; Hs.743239; -. DR ProteinModelPortal; P0C7T5; -. DR SMR; P0C7T5; 468-582. DR BioGrid; 131172; 67. DR IntAct; P0C7T5; 4. DR MINT; MINT-8176805; -. DR STRING; 9606.ENSP00000415822; -. DR PhosphoSite; P0C7T5; -. DR DMDM; 206557834; -. DR MaxQB; P0C7T5; -. DR PaxDb; P0C7T5; -. DR PRIDE; P0C7T5; -. DR Ensembl; ENST00000427980; ENSP00000415822; ENSG00000224470. DR GeneID; 342371; -. DR KEGG; hsa:342371; -. DR UCSC; uc002fbd.3; human. DR CTD; 342371; -. DR GeneCards; ATXN1L; -. DR H-InvDB; HIX0013220; -. DR HGNC; HGNC:33279; ATXN1L. DR MIM; 614301; gene. DR neXtProt; NX_P0C7T5; -. DR PharmGKB; PA162377321; -. DR eggNOG; KOG4053; Eukaryota. DR eggNOG; ENOG410XSNX; LUCA. DR GeneTree; ENSGT00390000005939; -. DR HOGENOM; HOG000034225; -. DR HOVERGEN; HBG100955; -. DR InParanoid; P0C7T5; -. DR OMA; TSCSTNH; -. DR OrthoDB; EOG7PGDQ2; -. DR PhylomeDB; P0C7T5; -. DR TreeFam; TF350643; -. DR ChiTaRS; ATXN1L; human. DR GenomeRNAi; 342371; -. DR NextBio; 98271; -. DR PRO; PR:P0C7T5; -. DR Proteomes; UP000005640; Chromosome 16. DR Bgee; P0C7T5; -. DR CleanEx; HS_ATXN1L; -. DR Genevisible; P0C7T5; HS. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0003723; F:RNA binding; IEA:InterPro. DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl. DR GO; GO:0048286; P:lung alveolus development; IEA:Ensembl. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:1902035; P:positive regulation of hematopoietic stem cell proliferation; IEA:Ensembl. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 2.170.16.10; -; 1. DR InterPro; IPR013723; Ataxin-1_HBP1. DR InterPro; IPR028992; Hedgehog/Intein_dom. DR Pfam; PF08517; AXH; 1. DR SUPFAM; SSF102031; SSF102031; 1. DR PROSITE; PS51148; AXH; 1. PE 1: Evidence at protein level; KW Cell projection; Complete proteome; DNA-binding; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Repressor; KW Transcription; Transcription regulation. FT CHAIN 1 689 Ataxin-1-like. FT /FTId=PRO_0000343709. FT DOMAIN 457 588 AXH. {ECO:0000255|PROSITE- FT ProRule:PRU00496}. FT REGION 20 197 Interaction with NCOR2 and ATXN1. FT REGION 20 197 Self-association. FT COMPBIAS 88 256 Pro-rich. FT MOD_RES 284 284 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 361 361 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT VARIANT 313 313 S -> P (in dbSNP:rs7194407). FT /FTId=VAR_044496. SQ SEQUENCE 689 AA; 73306 MW; 9C5D3938EF91F2C7 CRC64; MKPVHERSQE CLPPKKRDLP VTSEDMGRTT SCSTNHTPSS DASEWSRGVV VAGQSQAGAR VSLGGDGAEA ITGLTVDQYG MLYKVAVPPA TFSPTGLPSV VNMSPLPPTF NVASSLIQHP GIHYPPLHYA QLPSTSLQFI GSPYSLPYAV PPNFLPSPLL SPSANLATSH LPHFVPYASL LAEGATPPPQ APSPAHSFNK APSATSPSGQ LPHHSSTQPL DLAPGRMPIY YQMSRLPAGY TLHETPPAGA SPVLTPQESQ SALEAAAANG GQRPRERNLV RRESEALDSP NSKGEGQGLV PVVECVVDGQ LFSGSQTPRV EVAAPAHRGT PDTDLEVQRV VGALASQDYR VVAAQRKEEP SPLNLSHHTP DHQGEGRGSA RNPAELAEKS QARGFYPQSH QEPVKHRPLP KAMVVANGNL VPTGTDSGLL PVGSEILVAS SLDVQARATF PDKEPTPPPI TSSHLPSHFM KGAIIQLATG ELKRVEDLQT QDFVRSAEVS GGLKIDSSTV VDIQESQWPG FVMLHFVVGE QQSKVSIEVP PEHPFFVYGQ GWSSCSPGRT TQLFSLPCHR LQVGDVCISI SLQSLNSNSV SQASCAPPSQ LGPPRERPER TVLGSRELCD SEGKSQPAGE GSRVVEPSQP ESGAQACWPA PSFQRYSMQG EEARAALLRP SFIPQEVKLS IEGRSNAGK // ID BRCA1_HUMAN Reviewed; 1863 AA. AC P38398; E9PFZ0; O15129; Q1RMC1; Q3LRJ0; Q3LRJ6; Q6IN79; Q7KYU9; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 2. DT 11-NOV-2015, entry version 209. DE RecName: Full=Breast cancer type 1 susceptibility protein; DE EC=6.3.2.-; DE AltName: Full=RING finger protein 53; GN Name=BRCA1; Synonyms=RNF53; 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 BC ARG-1775. RX PubMed=7545954; DOI=10.1126/science.7545954; RA Miki Y., Swensen J., Shattuck-Eidens D., Futreal P.A., Harshman K., RA Tavtigian S., Liu Q., Cochran C., Bennett L.M., Ding W., Bell R., RA Rosenthal J., Hussey C., Tran T., McClure M., Frye C., Hattier T., RA Phelps R., Haugen-Strano A., Katcher H., Yakumo K., Gholami Z., RA Shaffer D., Stone S., Bayer S., Wray C., Bogden R., Dayananth P., RA Ward J., Tonin P., Narod S., Bristow P.K., Norris F.H., Helvering L., RA Morrison P., Rosteck P., Lai M., Barrett J.C., Lewis C., Neuhausen S., RA Cannon-Albright L., Godlgar D., Wiseman R., Kamb A., Skolnick M.H.; RT "A strong candidate for the breast and ovarian cancer susceptibility RT gene BRCA1."; RL Science 266:66-71(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8938427; DOI=10.1101/gr.6.11.1029; RA Smith T.M., Lee M.K., Szabo C.I., Jerome N., McEuen M., Taylor M., RA Hood L., King M.-C.; RT "Complete genomic sequence and analysis of 117 kb of human DNA RT containing the gene BRCA1."; RL Genome Res. 6:1029-1049(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), SUBCELLULAR LOCATION (ISOFORM RP 2), VARIANTS ARG-239 AND GLY-1613, AND TISSUE SPECIFICITY (ISOFORMS 1 RP AND 3). RC TISSUE=Mammary gland; RX PubMed=9010228; DOI=10.1038/sj.onc.1200924; RA Wilson C.A., Payton M.N., Elliott G.S., Buaas F.W., Cajulis E.E., RA Grosshans D., Ramos L., Reese D.M., Slamon D.J., Calzone F.J.; RT "Differential subcellular localization, expression and biological RT toxicity of BRCA1 and the splice variant BRCA1-delta11b."; RL Oncogene 14:1-16(1997). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RC TISSUE=Testis; RA Holt J.T., Robinson-Benion C.; RL Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-356. RA Raymond C.K., Paddock M., Subramanian S., Deodato C., Zhou Y., RA Haugen E., Kaul R., Olson M.V.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-275; ARG-356; RP ASN-693; LEU-871; GLY-1038; ASN-1040; GLY-1140; ARG-1183; GLY-1613 AND RP ALA-1620. RG NIEHS SNPs program; RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases. RN [7] 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 6 AND 7), AND RP VARIANTS LEU-871; GLY-1038; ARG-1183; GLY-1613 AND ILE-1652. RC TISSUE=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 [9] RP PROTEIN SEQUENCE OF 6-18 (ISOFORM 1), PROTEIN SEQUENCE OF 18-26 RP (ISOFORM 4), AND ALTERNATIVE INITIATION (ISOFORM 4). RX PubMed=10851077; DOI=10.1038/sj.onc.1203599; RA Liu J., Prolla G., Rostagno A., Chiarle R., Feiner H., Inghirami G.; RT "Initiation of translation from a downstream in-frame AUG codon on RT BRCA1 can generate the novel isoform protein DeltaBRCA1(17aa)."; RL Oncogene 19:2767-2773(2000). RN [10] RP ALTERNATIVE SPLICING (ISOFORM 5), AND SUBCELLULAR LOCATION (ISOFORM RP 5). RX PubMed=8972225; RA Thakur S., Zhang H.B., Peng Y., Le H., Carroll B., Ward T., Yao J., RA Farid L.M., Couch F.J., Wilson R.B., Weber B.L.; RT "Localization of BRCA1 and a splice variant identifies the nuclear RT localization signal."; RL Mol. Cell. Biol. 17:444-452(1997). RN [11] RP INTERACTION WITH BAP1, SUBCELLULAR LOCATION, VARIANTS GLY-61 AND RP GLY-64, AND MUTAGENESIS OF ARG-71. RX PubMed=9528852; DOI=10.1038/sj.onc.1201861; RA Jensen D.E., Proctor M., Marquis S.T., Gardner H.P., Ha S.I., RA Chodosh L.A., Ishov A.M., Tommerup N., Vissing H., Sekido Y., RA Minna J., Borodovsky A., Schultz D.C., Wilkinson K.D., Maul G.G., RA Barlev N., Berger S., Prendergast G.C., Rauscher F.J. III; RT "BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING RT finger and enhances BRCA1-mediated cell growth suppression."; RL Oncogene 16:1097-1112(1998). RN [12] RP INTERACTION WITH RBBP8. RX PubMed=9811458; DOI=10.1038/sj.onc.1202150; RA Wong A.K., Ormonde P.A., Pero R., Chen Y., Lian L., Salada G., RA Berry S., Lawrence Q., Dayananth P., Ha P., Tavtigian S.V., Teng D.H., RA Bartel P.L.; RT "Characterization of a carboxy-terminal BRCA1 interacting protein."; RL Oncogene 17:2279-2285(1998). RN [13] RP FUNCTION AS AN E2-DEPENDENT UBIQUITIN-PROTEIN LIGASE. RX PubMed=10500182; DOI=10.1073/pnas.96.20.11364; RA Lorick K.L., Jensen J.P., Fang S., Ong A.M., Hatakeyama S., RA Weissman A.M.; RT "RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent RT ubiquitination."; RL Proc. Natl. Acad. Sci. U.S.A. 96:11364-11369(1999). RN [14] RP IDENTIFICATION IN THE BASC COMPLEX. RX PubMed=10783165; DOI=10.1101/gad.827000; RA Wang Y., Cortez D., Yazdi P., Neff N., Elledge S.J., Qin J.; RT "BASC, a super complex of BRCA1-associated proteins involved in the RT recognition and repair of aberrant DNA structures."; RL Genes Dev. 14:927-939(2000). RN [15] RP PHOSPHORYLATION AT SER-1143; SER-1280; SER-1387; THR-1394; SER-1423 RP AND SER-1457, MUTAGENESIS OF SER-1143; SER-1239; SER-1280; SER-1298; RP SER-1330; SER-1387; THR-1394; SER-1423; SER-1457; SER-1466; SER-1524 RP AND SER-1755, AND CHARACTERIZATION OF VARIANT BC ALA-1720. RX PubMed=11114888; DOI=10.1101/gad.851000; RA Tibbetts R.S., Cortez D., Brumbaugh K.M., Scully R., Livingston D., RA Elledge S.J., Abraham R.T.; RT "Functional interactions between BRCA1 and the checkpoint kinase ATR RT during genotoxic stress."; RL Genes Dev. 14:2989-3002(2000). RN [16] RP FUNCTION IN DNA DAMAGE RESPONSE, PHOSPHORYLATION AT SER-988 BY CHEK2, RP AND INTERACTION WITH CHEK2. RX PubMed=10724175; DOI=10.1038/35004614; RA Lee J.S., Collins K.M., Brown A.L., Lee C.H., Chung J.H.; RT "hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage RT response."; RL Nature 404:201-204(2000). RN [17] RP INTERACTION WITH BRIP1, CHARACTERIZATION OF VARIANT OVARIAN CANCER RP ARG-1749, AND CHARACTERIZATION OF VARIANT BC ARG-1775. RX PubMed=11301010; DOI=10.1016/S0092-8674(01)00304-X; RA Cantor S.B., Bell D.W., Ganesan S., Kass E.M., Drapkin R., RA Grossman S., Wahrer D.C.R., Sgroi D.C., Lane W.S., Haber D.A., RA Livingston D.M.; RT "BACH1, a novel helicase-like protein, interacts directly with BRCA1 RT and contributes to its DNA repair function."; RL Cell 105:149-160(2001). RN [18] RP INTERACTION WITH NELFB. RX PubMed=11739404; DOI=10.1083/jcb.200108049; RA Ye Q., Hu Y.-F., Zhong H., Nye A.C., Belmont A.S., Li R.; RT "BRCA1-induced large-scale chromatin unfolding and allele-specific RT effects of cancer-predisposing mutations."; RL J. Cell Biol. 155:911-921(2001). RN [19] RP INTERACTION WITH FANCD2. RX PubMed=11239454; DOI=10.1016/S1097-2765(01)00173-3; RA Garcia-Higuera I., Taniguchi T., Ganesan S., Meyn M.S., Timmers C., RA Hejna J., Grompe M., D'Andrea A.D.; RT "Interaction of the Fanconi anemia proteins and BRCA1 in a common RT pathway."; RL Mol. Cell 7:249-262(2001). RN [20] RP PHOSPHORYLATION BY ATM, AND MUTAGENESIS OF SER-1387; SER-1423 AND RP SER-1524. RX PubMed=12183412; RA Xu B., O'Donnell A.H., Kim S.-T., Kastan M.B.; RT "Phosphorylation of serine 1387 in BRCA1 is specifically required for RT the Atm-mediated S-phase checkpoint after ionizing irradiation."; RL Cancer Res. 62:4588-4591(2002). RN [21] RP INTERACTION WITH H2AFX. RX PubMed=12419185; DOI=10.1016/S0960-9822(02)01259-9; RA Kobayashi J., Tauchi H., Sakamoto S., Nakamura A., Morishima K., RA Matsuura S., Kobayashi T., Tamai K., Tanimoto K., Komatsu K.; RT "NBS1 localizes to gamma-H2AX foci through interaction with the RT FHA/BRCT domain."; RL Curr. Biol. 12:1846-1851(2002). RN [22] RP INTERACTION WITH SMC1A. RX PubMed=11877377; DOI=10.1101/gad.970702; RA Yazdi P.T., Wang Y., Zhao S., Patel N., Lee E.Y.-H.P., Qin J.; RT "SMC1 is a downstream effector in the ATM/NBS1 branch of the human S- RT phase checkpoint."; RL Genes Dev. 16:571-582(2002). RN [23] 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 [24] RP FUNCTION, AND INTERACTION WITH CHEK1. RX PubMed=11836499; DOI=10.1038/ng837; RA Yarden R.I., Pardo-Reoyo S., Sgagias M., Cowan K.H., Brody L.C.; RT "BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon RT DNA damage."; RL Nat. Genet. 30:285-289(2002). RN [25] RP INTERACTION WITH ACACA. RX PubMed=12360400; DOI=10.1038/sj.onc.1205915; RA Magnard C., Bachelier R., Vincent A., Jaquinod M., Kieffer S., RA Lenoir G.M., Venezia N.D.; RT "BRCA1 interacts with acetyl-CoA carboxylase through its tandem of RT BRCT domains."; RL Oncogene 21:6729-6739(2002). RN [26] RP FUNCTION, UBIQUITINATION, AND INTERACTION WITH BARD1. RX PubMed=12890688; DOI=10.1074/jbc.C300249200; RA Wu-Baer F., Lagrazon K., Yuan W., Baer R.; RT "The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an RT unconventional linkage involving lysine residue K6 of ubiquitin."; RL J. Biol. Chem. 278:34743-34746(2003). RN [27] RP FUNCTION. RX PubMed=12887909; DOI=10.1016/S1097-2765(03)00281-8; RA Vandenberg C.J., Gergely F., Ong C.Y., Pace P., Mallery D.L., Hiom K., RA Patel K.J.; RT "BRCA1-independent ubiquitination of FANCD2."; RL Mol. Cell 12:247-254(2003). RN [28] RP INTERACTION WITH BRCC3. RX PubMed=14636569; DOI=10.1016/S1097-2765(03)00424-6; RA Dong Y., Hakimi M.-A., Chen X., Kumaraswamy E., Cooch N.S., RA Godwin A.K., Shiekhattar R.; RT "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, RT by a signalosome-like subunit and its role in DNA repair."; RL Mol. Cell 12:1087-1099(2003). RN [29] RP FUNCTION, AND INTERACTION WITH BARD1. RX PubMed=14976165; DOI=10.1093/hmg/ddh095; RA Morris J.R., Solomon E.; RT "BRCA1:BARD1 induces the formation of conjugated ubiquitin structures, RT dependent on K6 of ubiquitin, in cells during DNA replication and RT repair."; RL Hum. Mol. Genet. 13:807-817(2004). RN [30] RP INTERACTION WITH AURKA, FUNCTION, MUTAGENESIS OF SER-308, AND RP PHOSPHORYLATION AT SER-308. RX PubMed=14990569; DOI=10.1074/jbc.M311780200; RA Ouchi M., Fujiuchi N., Sasai K., Katayama H., Minamishima Y.A., RA Ongusaha P.P., Deng C., Sen S., Lee S.W., Ouchi T.; RT "BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M RT transition."; RL J. Biol. Chem. 279:19643-19648(2004). RN [31] RP INTERACTION WITH DCLRE1C. RX PubMed=15456891; DOI=10.1128/MCB.24.20.9207-9220.2004; RA Zhang X., Succi J., Feng Z., Prithivirajsingh S., Story M.D., RA Legerski R.J.; RT "Artemis is a phosphorylation target of ATM and ATR and is involved in RT the G2/M DNA damage checkpoint response."; RL Mol. Cell. Biol. 24:9207-9220(2004). RN [32] RP INTERACTION WITH CLSPN. RX PubMed=15096610; DOI=10.1073/pnas.0401847101; RA Lin S.-Y., Li K., Stewart G.S., Elledge S.J.; RT "Human claspin works with BRCA1 to both positively and negatively RT regulate cell proliferation."; RL Proc. Natl. Acad. Sci. U.S.A. 101:6484-6489(2004). RN [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1336, 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 [34] RP FUNCTION, INTERACTION WITH RBBP8, AND MUTAGENESIS OF ILE-26. 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 [35] RP FUNCTION, AND INTERACTION WITH ACACA. RX PubMed=16326698; DOI=10.1074/jbc.M504652200; RA Moreau K., Dizin E., Ray H., Luquain C., Lefai E., Foufelle F., RA Billaud M., Lenoir G.M., Venezia N.D.; RT "BRCA1 affects lipid synthesis through its interaction with acetyl-CoA RT carboxylase."; RL J. Biol. Chem. 281:3172-3181(2006). RN [36] RP INTERACTION WITH ACACA. RX PubMed=16698035; DOI=10.1016/j.jmb.2006.04.010; RA Ray H., Moreau K., Dizin E., Callebaut I., Venezia N.D.; RT "ACCA phosphopeptide recognition by the BRCT repeats of BRCA1."; RL J. Mol. Biol. 359:973-982(2006). RN [37] RP FUNCTION, PHOSPHORYLATION BY AURKA, AND ENZYME REGULATION. RX PubMed=18056443; DOI=10.1158/0008-5472.CAN-07-2578; RA Sankaran S., Crone D.E., Palazzo R.E., Parvin J.D.; RT "Aurora-A kinase regulates breast cancer associated gene 1 inhibition RT of centrosome-dependent microtubule nucleation."; RL Cancer Res. 67:11186-11194(2007). RN [38] RP INTERACTION WITH FAM175A. RX PubMed=17643122; DOI=10.1038/nsmb1277; RA Kim H., Huang J., Chen J.; RT "CCDC98 is a BRCA1-BRCT domain-binding protein involved in the DNA RT damage response."; RL Nat. Struct. Mol. Biol. 14:710-715(2007). RN [39] RP INTERACTION WITH FAM175A. RX PubMed=17643121; DOI=10.1038/nsmb1279; RA Liu Z., Wu J., Yu X.; RT "CCDC98 targets BRCA1 to DNA damage sites."; RL Nat. Struct. Mol. Biol. 14:716-720(2007). RN [40] 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 [41] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH FAM175A. RX PubMed=17525340; DOI=10.1126/science.1139476; RA Wang B., Matsuoka S., Ballif B.A., Zhang D., Smogorzewska A., Giyi S., RA Elledge S.J.; RT "Abraxas and RAP80 form a BRCA1 protein complex required for the DNA RT damage response."; RL Science 316:1194-1198(2007). RN [42] RP INVOLVEMENT IN PNCA4. RX PubMed=18762988; DOI=10.1007/s00439-008-0554-0; RA Al-Sukhni W., Rothenmund H., Borgida A.E., Zogopoulos G., O'Shea A.M., RA Pollett A., Gallinger S.; RT "Germline BRCA1 mutations predispose to pancreatic adenocarcinoma."; RL Hum. Genet. 124:271-278(2008). RN [43] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395; SER-398; SER-753; RP SER-1211; SER-1217 AND SER-1218, AND IDENTIFICATION BY MASS RP 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 [44] RP FUNCTION, AND IDENTIFICATION IN THE BRCA1-A COMPLEX. RX PubMed=19261748; DOI=10.1101/gad.1770609; RA Feng L., Huang J., Chen J.; RT "MERIT40 facilitates BRCA1 localization and DNA damage repair."; RL Genes Dev. 23:719-728(2009). RN [45] RP IDENTIFICATION IN THE BRCA1-A COMPLEX. RX PubMed=19261749; DOI=10.1101/gad.1770309; RA Wang B., Hurov K., Hofmann K., Elledge S.J.; RT "NBA1, a new player in the Brca1 A complex, is required for DNA damage RT resistance and checkpoint control."; RL Genes Dev. 23:729-739(2009). RN [46] RP IDENTIFICATION IN THE BRCA1-A COMPLEX. RX PubMed=19261746; DOI=10.1101/gad.1739609; RA Shao G., Patterson-Fortin J., Messick T.E., Feng D., Shanbhag N., RA Wang Y., Greenberg R.A.; RT "MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA RT double-strand breaks."; RL Genes Dev. 23:740-754(2009). RN [47] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH PALB2, RP IDENTIFICATION IN A BRCA COMPLEX WITH BRCA1 AND PALB2, AND RP CHARACTERIZATION OF VARIANT OVARIAN CANCER 1411-THR. RX PubMed=19369211; DOI=10.1073/pnas.0811159106; RA Sy S.M., Huen M.S., Chen J.; RT "PALB2 is an integral component of the BRCA complex required for RT homologous recombination repair."; RL Proc. Natl. Acad. Sci. U.S.A. 106:7155-7160(2009). RN [48] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-395 AND SER-398, 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 [49] RP FUNCTION, INTERACTION WITH CCAR2, AND SUBCELLULAR LOCATION. RX PubMed=20160719; DOI=10.1038/sj.bjc.6605577; RA Hiraike H., Wada-Hiraike O., Nakagawa S., Koyama S., Miyamoto Y., RA Sone K., Tanikawa M., Tsuruga T., Nagasaka K., Matsumoto Y., Oda K., RA Shoji K., Fukuhara H., Saji S., Nakagawa K., Kato S., Yano T., RA Taketani Y.; RT "Identification of DBC1 as a transcriptional repressor for BRCA1."; RL Br. J. Cancer 102:1061-1067(2010). RN [50] RP FUNCTION, INTERACTION WITH BARD1 AND UBXN1, UBIQUITINATION, AND RP MUTAGENESIS OF ILE-26. RX PubMed=20351172; DOI=10.1128/MCB.01056-09; RA Wu-Baer F., Ludwig T., Baer R.; RT "The UBXN1 protein associates with autoubiquitinated forms of the RT BRCA1 tumor suppressor and inhibits its enzymatic function."; RL Mol. Cell. Biol. 30:2787-2798(2010). RN [51] RP FUNCTION IN CHROMOSOMAL STABILITY, AND PHOSPHORYLATION AT SER-988 BY RP CHEK2. RX PubMed=20364141; DOI=10.1038/ncb2051; RA Stolz A., Ertych N., Kienitz A., Vogel C., Schneider V., Fritz B., RA Jacob R., Dittmar G., Weichert W., Petersen I., Bastians H.; RT "The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal RT stability in human somatic cells."; RL Nat. Cell Biol. 12:492-499(2010). RN [52] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114; SER-423; SER-694; RP SER-1328; SER-1336 AND SER-1342, AND IDENTIFICATION BY MASS RP 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 [53] RP PHOSPHORYLATION AT SER-1524, AND SUBCELLULAR LOCATION. RX PubMed=21144835; DOI=10.1016/j.bbrc.2010.12.005; RA Kang Y., Cheong H.M., Lee J.H., Song P.I., Lee K.H., Kim S.Y., RA Jun J.Y., You H.J.; RT "Protein phosphatase 5 is necessary for ATR-mediated DNA repair."; RL Biochem. Biophys. Res. Commun. 404:476-481(2011). RN [54] RP INTERACTION WITH KIAA0101. RX PubMed=21673012; DOI=10.1158/1541-7786.MCR-10-0503; RA Kais Z., Barsky S.H., Mathsyaraja H., Zha A., Ransburgh D.J., He G., RA Pilarski R.T., Shapiro C.L., Huang K., Parvin J.D.; RT "KIAA0101 interacts with BRCA1 and regulates centrosome number."; RL Mol. Cancer Res. 9:1091-1099(2011). RN [55] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-114; SER-1218; SER-1336 RP AND SER-1342, 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 [56] 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 [57] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-339; LYS-459; LYS-583; RP LYS-654; LYS-734 AND LYS-739, AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [58] RP STRUCTURE BY NMR OF 1-110 IN COMPLEX WITH ZINC IONS AND BARD1, AND RP SUBUNIT. RX PubMed=11573085; DOI=10.1038/nsb1001-833; RA Brzovic P.S., Rajagopal P., Hoyt D.W., King M.C., Klevit R.E.; RT "Structure of a BRCA1-BARD1 heterodimeric RING-RING complex."; RL Nat. Struct. Biol. 8:833-837(2001). RN [59] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1646-1859, PARTIAL PROTEIN RP SEQUENCE, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=11573086; DOI=10.1038/nsb1001-838; RA Williams R.S., Green R., Glover J.N.; RT "Crystal structure of the BRCT repeat region from the breast cancer- RT associated protein BRCA1."; RL Nat. Struct. Biol. 8:838-842(2001). RN [60] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 1646-1859 OF VARIANT BC RP ARG-1775, CHARACTERIZATION OF VARIANT BC ARG-1775, AND CIRCULAR RP DICHROISM. RX PubMed=12427738; DOI=10.1074/jbc.M210019200; RA Williams R.S., Glover J.N.; RT "Structural consequences of a cancer-causing BRCA1-BRCT missense RT mutation."; RL J. Biol. Chem. 278:2630-2635(2003). RN [61] RP STRUCTURE BY NMR OF 1755-1863. RX PubMed=15609993; DOI=10.1021/bi049550q; RA Gaiser O.J., Ball L.J., Schmieder P., Leitner D., Strauss H., Wahl M., RA Kuhne R., Oschkinat H., Heinemann U.; RT "Solution structure, backbone dynamics, and association behavior of RT the C-terminal BRCT domain from the breast cancer-associated protein RT BRCA1."; RL Biochemistry 43:15983-15995(2004). RN [62] RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 1649-1859 IN COMPLEX WITH RP WITH PHOSPHORYLATED BRIP1 PEPTIDE, MUTAGENESIS OF SER-1655; LYS-1702 RP AND GLY-1738, CHARACTERIZATION OF VARIANT OVARIAN CANCER ARG-1749, RP CHARACTERIZATION OF VARIANT BC ARG-1775, SUBCELLULAR LOCATION, AND RP INTERACTION WITH PHOSPHORYLATED BRIP1. RX PubMed=15133502; DOI=10.1038/nsmb775; RA Clapperton J.A., Manke I.A., Lowery D.M., Ho T., Haire L.F., RA Yaffe M.B., Smerdon S.J.; RT "Structure and mechanism of BRCA1 BRCT domain recognition of RT phosphorylated BACH1 with implications for cancer."; RL Nat. Struct. Mol. Biol. 11:512-518(2004). RN [63] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 1646-1859 IN COMPLEX WITH RP PHOSPHORYLATED RBBP8 PEPTIDE, AND SUBUNIT. RX PubMed=16101277; DOI=10.1021/bi0509651; RA Varma A.K., Brown R.S., Birrane G., Ladias J.A.; RT "Structural basis for cell cycle checkpoint control by the BRCA1-CtIP RT complex."; RL Biochemistry 44:10941-10946(2005). RN [64] RP X-RAY CRYSTALLOGRAPHY (3.21 ANGSTROMS) OF 1646-1859 IN COMPLEX WITH RP PHOSPHORYLATED ACACA PEPTIDE, AND SUBUNIT. RX PubMed=18452305; DOI=10.1021/bi800314m; RA Shen Y., Tong L.; RT "Structural evidence for direct interactions between the BRCT domains RT of human BRCA1 and a phospho-peptide from human ACC1."; RL Biochemistry 47:5767-5773(2008). RN [65] RP X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 1649-1859 OF VARIANT BC RP LYS-1775, VARIANT BC LYS-1775, AND CHARACTERIZATION OF VARIANT BC RP LYS-1775. RX PubMed=18285836; DOI=10.1038/ejhg.2008.13; RA Tischkowitz M., Hamel N., Carvalho M.A., Birrane G., Soni A., RA van Beers E.H., Joosse S.A., Wong N., Novak D., Quenneville L.A., RA Grist S.A., Nederlof P.M., Goldgar D.E., Tavtigian S.V., RA Monteiro A.N., Ladias J.A., Foulkes W.D.; RT "Pathogenicity of the BRCA1 missense variant M1775K is determined by RT the disruption of the BRCT phosphopeptide-binding pocket: a multi- RT modal approach."; RL Eur. J. Hum. Genet. 16:820-832(2008). RN [66] RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 1646-1859 IN COMPLEX WITH RP PHOSPHORYLATED PEPTIDES, AND DOMAIN. RX PubMed=20159462; DOI=10.1016/j.str.2009.12.008; RA Campbell S.J., Edwards R.A., Glover J.N.; RT "Comparison of the structures and peptide binding specificities of the RT BRCT domains of MDC1 and BRCA1."; RL Structure 18:167-176(2010). RN [67] RP REVIEW ON VARIANTS. RX PubMed=8807330; DOI=10.1002/humu.1380080102; RA Couch F.J., Weber B.L.; RT "Mutations and polymorphisms in the familial early-onset breast cancer RT (BRCA1) gene."; RL Hum. Mutat. 8:8-18(1996). RN [68] RP VARIANT BC ARG-1775, AND VARIANTS LEU-1637 AND GLU-1708. RX PubMed=7939630; DOI=10.1126/science.7939630; RA Futreal P.A., Liu Q., Shattuck-Eidens D., Cochran C., Harshman K., RA Tavtigian S., Bennett L.M., Haugen-Strano A., Swensen J., Miki Y., RA Eddington K., McClure M., Frye C., Weaver-Felhaus J., Ding W., RA Gholami Z., Soederkvist P., Terry L., Jhanwar S., Berchuk A., RA Iglehart J.D., Marks J., Ballinger D.G., Barrett J.C., Skolnick M.H., RA Kamb A., Wiseman R.; RT "BRCA1 mutations in primary breast and ovarian carcinomas."; RL Science 266:120-122(1994). RN [69] RP VARIANT BC GLY-64, AND VARIANTS ALA-772; ASN-1040 AND GLY-1443. RX PubMed=7894491; DOI=10.1038/ng1294-387; RA Castilla L.H., Couch F.J., Erdos M.R., Hoskins K.F., Calzone K., RA Garber J.E., Boyd J., Lubin M.B., Deshano M.L., Brody L.C., RA Collins F.S., Weber B.L.; RT "Mutations in the BRCA1 gene in families with early-onset breast and RT ovarian cancer."; RL Nat. Genet. 8:387-391(1994). RN [70] RP VARIANT BC GLY-61, AND VARIANTS ARG-356; GLY-1038; ASN-1040; ARG-1183 RP AND GLY-1613. RX PubMed=7894493; DOI=10.1038/ng1294-399; RA Friedman L.S., Ostermeyer E.A., Szabo C.I., Dowd P., Lynch E.D., RA Rowell S.E., King M.-C.; RT "Confirmation of BRCA1 by analysis of germline mutations linked to RT breast and ovarian cancer in ten families."; RL Nat. Genet. 8:399-404(1994). RN [71] RP VARIANT BC GLY-61. RX PubMed=8554067; RA Serova O., Montagna M., Torchard D., Narod S.A., Tonin P., Sylla B., RA Lynch H.T., Feunteun J., Lenoir G.M.; RT "A high incidence of BRCA1 mutations in 20 breast-ovarian cancer RT families."; RL Am. J. Hum. Genet. 58:42-51(1996). RN [72] RP VARIANT BROVCA1 TRP-841. RX PubMed=8968716; RX DOI=10.1002/(SICI)1098-2272(1996)13:6<595::AID-GEPI5>3.3.CO;2-0; RA Barker D.F., Almeida E.F.A., Casey G., Fain P.R., Liao S.-Y., RA Masunaka I., Noble B., Kurosaki T., Anton-Culver H.; RT "BRCA1 R841W: a strong candidate for a common mutation with moderate RT phenotype."; RL Genet. Epidemiol. 13:595-604(1996). RN [73] RP VARIANTS BC AND BROVCA1. RX PubMed=8776600; DOI=10.1093/hmg/5.6.835; RA Durocher F., Shattuck-Eidens D., McClure M., Labrie F., Skolnick M.H., RA Goldgar D.E., Simard J.; RT "Comparison of BRCA1 polymorphisms, rare sequence variants and/or RT missense mutations in unaffected and breast/ovarian cancer RT populations."; RL Hum. Mol. Genet. 5:835-842(1996). RN [74] RP VARIANTS BC MET-271 AND SER-1150. RX PubMed=8723683; RX DOI=10.1002/(SICI)1098-1004(1996)7:4<334::AID-HUMU7>3.3.CO;2-K; RA Katagiri T., Emi M., Ito I., Kobayashi K., Yoshimoto M., Iwase T., RA Kasumi F., Miki Y., Skolnick M.H., Nakamura Y.; RT "Mutations in the BRCA1 gene in Japanese breast cancer patients."; RL Hum. Mutat. 7:334-339(1996). RN [75] RP VARIANT BC GLY-61, AND VARIANTS ARG-239; TRP-841 AND ILE-1512. RX PubMed=9760198; DOI=10.1007/s004390050799; RA Dong J., Chang-Claude J., Wu Y., Schumacher V., Debatin I., Tonin P., RA Royer-Pokora B.; RT "A high proportion of mutations in the BRCA1 gene in German RT breast/ovarian cancer families with clustering of mutations in the 3' RT third of the gene."; RL Hum. Genet. 103:154-161(1998). RN [76] RP VARIANT BC GLY-64, AND VARIANTS ALA-772; GLU-820; ASN-1040; GLY-1443; RP ILE-1512; LEU-1637 AND ILE-1652. RX PubMed=9482581; RX DOI=10.1002/(SICI)1098-1004(1998)11:2<166::AID-HUMU10>3.0.CO;2-X; RA Andersen T.I., Eiken H.G., Couch F., Kaada G., Skrede M., Johnsen H., RA Aloysius T.A., Tveit K.M., Tranebjaerg L., Doerum A., Moeller P., RA Weber B.L., Boerresen-Dale A.-L.; RT "Constant denaturant gel electrophoresis (CDGE) in BRCA1 mutation RT screening."; RL Hum. Mutat. 11:166-174(1998). RN [77] RP VARIANTS BC SER-22; LEU-461; ASP-465; VAL-552; SER-892; ASP-960; RP ILE-1025 AND ALA-1047. RX PubMed=9609997; DOI=10.1007/s100380050035; RA Katagiri T., Kasumi F., Yoshimoto M., Nomizu T., Asaishi K., Abe R., RA Tsuchiya A., Sugano M., Takai S., Yoneda M., Fukutomi T., Nanba K., RA Makita M., Okazaki H., Hirata K., Okazaki M., Furutsuma Y., RA Morishita Y., Iino Y., Karino T., Ayabe H., Hara S., Kajiwara T., RA Houga S., Shimizu T., Toda M., Yamazaki Y., Uchida T., Kunitomo K., RA Sonoo H., Kurebayashi J., Shimotsuma K., Nakamura Y., Miki Y.; RT "High proportion of missense mutations of the BRCA1 and BRCA2 genes in RT Japanese breast cancer families."; RL J. Hum. Genet. 43:42-48(1998). RN [78] RP VARIANT OVARIAN CANCER ARG-1749. RX PubMed=10486320; DOI=10.1086/302583; RA Gayther S.A., Russell P., Harrington P., Antoniou A.C., Easton D.F., RA Ponder B.A.J.; RT "The contribution of germline BRCA1 and BRCA2 mutations to familial RT ovarian cancer: no evidence for other ovarian cancer-susceptibility RT genes."; RL Am. J. Hum. Genet. 65:1021-1029(1999). RN [79] RP VARIANT BC SER-346, AND VARIANTS LEU-871; GLY-1038; ARG-1183 AND RP GLY-1613. RX PubMed=10323242; DOI=10.1007/s004390050936; RA Li S.S.-L., Tseng H.-M., Yang T.-P., Liu C.-H., Teng S.-J., RA Huang H.-W., Chen L.-M., Kao H.-W., Chen J.H., Tseng J.-N., Chen A., RA Hou M.-F., Huang T.-J., Chang H.-T., Mok K.-T., Tsai J.-H.; RT "Molecular characterization of germline mutations in the BRCA1 and RT BRCA2 genes from breast cancer families in Taiwan."; RL Hum. Genet. 104:201-204(1999). RN [80] RP VARIANTS OVARIAN CANCER, AND VARIANTS. RX PubMed=10196379; DOI=10.1093/hmg/8.5.889; RA Janezic S.A., Ziogas A., Krumroy L.M., Krasner M., Plummer S.J., RA Cohen P., Gildea M., Barker D., Haile R., Casey G., Anton-Culver H.; RT "Germline BRCA1 alterations in a population-based series of ovarian RT cancer cases."; RL Hum. Mol. Genet. 8:889-897(1999). RN [81] RP VARIANTS GLY-1347; ILE-1512 AND ILE-1652. RX PubMed=12215251; DOI=10.1089/10906570260199375; RA Deffenbaugh A.M., Frank T.S., Hoffman M., Cannon-Albright L., RA Neuhausen S.L.; RT "Characterization of common BRCA1 and BRCA2 variants."; RL Genet. Test. 6:119-121(2002). RN [82] RP VARIANTS ILE-656; LEU-871 AND GLY-1613. RX PubMed=12442274; DOI=10.1002/humu.9083; RA Zhi X., Szabo C., Chopin S., Suter N., Wang Q.-S., Ostrander E.A., RA Sinilnikova O.M., Lenoir G.M., Goldgar D., Shi Y.-R.; RT "BRCA1 and BRCA2 sequence variants in Chinese breast cancer RT families."; RL Hum. Mutat. 20:474-474(2002). RN [83] RP VARIANT BC TYR-749. RX PubMed=12442275; DOI=10.1002/humu.9084; RA Ruiz-Flores P., Sinilnikova O.M., Badzioch M., RA Calderon-Garciduenas A.L., Chopin S., Fabrice O., RA Gonzalez-Guerrero J.F., Szabo C., Lenoir G., Goldgar D.E., RA Barrera-Saldana H.A.; RT "BRCA1 and BRCA2 mutation analysis of early-onset and familial breast RT cancer cases in Mexico."; RL Hum. Mutat. 20:474-475(2002). RN [84] RP VARIANTS BC GLY-61; LYS-71; GLN-866; TYR-888; ILE-1139; GLY-1210 AND RP PRO-1297, AND VARIANTS BROVCA1 TYR-835 AND PRO-1786. RX PubMed=12938098; DOI=10.1002/humu.9174; RA Meyer P., Voigtlaender T., Bartram C.R., Klaes R.; RT "Twenty-three novel BRCA1 and BRCA2 sequence alterations in breast RT and/or ovarian cancer families in Southern Germany."; RL Hum. Mutat. 22:259-259(2003). RN [85] RP VARIANTS ASN-693; ASN-1040; ALA-1060 AND MET-1665. RX PubMed=15026808; DOI=10.1038/sj.bjc.6601656; RA Claes K., Poppe B., Coene I., De Paepe A., Messiaen L.; RT "BRCA1 and BRCA2 germline mutation spectrum and frequencies in Belgian RT breast/ovarian cancer families."; RL Br. J. Cancer 90:1244-1251(2004). RN [86] RP VARIANTS OVARIAN CANCER GLY-61; THR-1411; ARG-1697 AND TRP-1699. RX PubMed=14746861; DOI=10.1016/j.ejca.2003.09.016; RA Malander S., Ridderheim M., Masbaeck A., Loman N., Kristoffersson U., RA Olsson H., Nilbert M., Borg A.; RT "One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2 RT mutations: results of a prospective study in Southern Sweden."; RL Eur. J. Cancer 40:422-428(2004). RN [87] RP VARIANTS BC/BROVCA1 LYS-10; LYS-23; ILE-1187; HIS-1200 AND TYR-1217, RP VARIANTS BC ILE-1204 AND ASN-1207, VARIANTS BROVCA1 LEU-1226 AND RP GLY-1243, AND VARIANT ARG-1183. RX PubMed=14722926; DOI=10.1002/humu.9213; RA Valarmathi M.T., Sawhney M., Deo S.S.V., Shukla N.K., Das S.N.; RT "Novel germline mutations in the BRCA1 and BRCA2 genes in Indian RT breast and breast-ovarian cancer families."; RL Hum. Mutat. 23:205-205(2004). RN [88] RP VARIANTS HIS-856; LEU-871; GLY-1038; ARG-1183; THR-1628; GLN-1690 AND RP GLY-1713. RX PubMed=15365993; DOI=10.1002/humu.9275; RA Seo J.H., Cho D.-Y., Ahn S.-H., Yoon K.-S., Kang C.-S., Cho H.M., RA Lee H.S., Choe J.J., Choi C.W., Kim B.S., Shin S.W., Kim Y.H., RA Kim J.S., Son G.-S., Lee J.-B., Koo B.H.; RT "BRCA1 and BRCA2 germline mutations in Korean patients with sporadic RT breast cancer."; RL Hum. Mutat. 24:350-350(2004). RN [89] RP VARIANTS [LARGE SCALE ANALYSIS] PHE-30; PHE-758 AND CYS-778. 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). RN [90] RP VARIANTS THR-18; MET-1495; GLY-1623; ILE-1685; ALA-1685; ARG-1689; RP TRP-1699; GLU-1706; GLU-1708; ARG-1715; ARG-1738; PRO-1764; SER-1766 RP AND VAL-1788. RX PubMed=17924331; DOI=10.1086/521032; RA Easton D.F., Deffenbaugh A.M., Pruss D., Frye C., Wenstrup R.J., RA Allen-Brady K., Tavtigian S.V., Monteiro A.N.A., Iversen E.S., RA Couch F.J., Goldgar D.E.; RT "A systematic genetic assessment of 1,433 sequence variants of unknown RT clinical significance in the BRCA1 and BRCA2 breast cancer- RT predisposition genes."; RL Am. J. Hum. Genet. 81:873-883(2007). RN [91] RP CHARACTERIZATION OF VARIANTS GLY-1623 AND ILE-1685. RX PubMed=20513136; DOI=10.1002/humu.21267; RA Walker L.C., Whiley P.J., Couch F.J., Farrugia D.J., Healey S., RA Eccles D.M., Lin F., Butler S.A., Goff S.A., Thompson B.A., RA Lakhani S.R., Da Silva L.M., Tavtigian S.V., Goldgar D.E., Brown M.A., RA Spurdle A.B.; RT "Detection of splicing aberrations caused by BRCA1 and BRCA2 sequence RT variants encoding missense substitutions: implications for prediction RT of pathogenicity."; RL Hum. Mutat. 31:E1484-E1505(2010). RN [92] RP CHARACTERIZATION OF VARIANTS BC PHE-4; THR-18; GLN-45; GLY-61; GLY-64; RP TYR-67; LYS-132; HIS-142; PHE-147; PRO-165; TRP-170; TYR-186; ILE-191; RP MET-231; VAL-245; VAL-246; LEU-271; PHE-668; ASN-695; LEU-798; RP TYR-810; LYS-826; GLN-841; HIS-856; ASN-1101; ASN-1140; GLY-1140; RP LYS-1214; LYS-1236; SER-1267; VAL-1282; SER-1297 DEL; ARG-1301; RP LYS-1346; ILE-1378; VAL-1400; PRO-1407; THR-1411; GLY-1443; GLY-1448; RP CYS-1486; MET-1534; PRO-1589; THR-1628; PRO-1651; PHE-1651; PHE-1655; RP ARG-1686; GLN-1686; VAL-1688 DEL; ILE-1691; TRP-1699; GLN-1699; RP GLU-1706; ALA-1706; GLU-1708; CYS-1718; ALA-1720; LYS-1735; ALA-1736; RP GLY-1739; VAL-1739; GLN-1746; THR-1753; PRO-1764; SER-1767; VAL-1770; RP CYS-1782; THR-1789; ASP-1794; ASP-1804; ARG-1812; ARG-1837 AND RP LEU-1862, AND VARIANTS CYS-105; CYS-866; ALA-1060; LYS-1250 AND RP ILE-1652. RX PubMed=23867111; DOI=10.1158/2159-8290.CD-13-0094; RA Bouwman P., van der Gulden H., van der Heijden I., Drost R., RA Klijn C.N., Prasetyanti P., Pieterse M., Wientjens E., Seibler J., RA Hogervorst F.B., Jonkers J.; RT "A high-throughput functional complementation assay for classification RT of BRCA1 missense variants."; RL Cancer Discov. 3:1142-1155(2013). CC -!- FUNCTION: E3 ubiquitin-protein ligase that specifically mediates CC the formation of 'Lys-6'-linked polyubiquitin chains and plays a CC central role in DNA repair by facilitating cellular responses to CC DNA damage. It is unclear whether it also mediates the formation CC of other types of polyubiquitin chains. The E3 ubiquitin-protein CC ligase activity is required for its tumor suppressor function. The CC BRCA1-BARD1 heterodimer coordinates a diverse range of cellular CC pathways such as DNA damage repair, ubiquitination and CC transcriptional regulation to maintain genomic stability. CC Regulates centrosomal microtubule nucleation. Required for normal CC cell cycle progression from G2 to mitosis. Required for CC appropriate cell cycle arrests after ionizing irradiation in both CC the S-phase and the G2 phase of the cell cycle. Involved in CC transcriptional regulation of P21 in response to DNA damage. CC Required for FANCD2 targeting to sites of DNA damage. May function CC as a transcriptional regulator. Inhibits lipid synthesis by CC binding to inactive phosphorylated ACACA and preventing its CC dephosphorylation. Contributes to homologous recombination repair CC (HRR) via its direct interaction with PALB2, fine-tunes CC recombinational repair partly through its modulatory role in the CC PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA CC breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 CC activation and controls cell cycle G2/M checkpoints on DNA damage CC via BRCA1-mediated ubiquitination of RBBP8. Acts as a CC transcriptional activator (PubMed:20160719). CC {ECO:0000269|PubMed:10500182, ECO:0000269|PubMed:10724175, CC ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12887909, CC ECO:0000269|PubMed:12890688, ECO:0000269|PubMed:14976165, CC ECO:0000269|PubMed:14990569, ECO:0000269|PubMed:16326698, CC ECO:0000269|PubMed:16818604, ECO:0000269|PubMed:17525340, CC ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:19261748, CC ECO:0000269|PubMed:19369211, ECO:0000269|PubMed:20160719, CC ECO:0000269|PubMed:20351172, ECO:0000269|PubMed:20364141}. CC -!- ENZYME REGULATION: The E3 ubiquitin-protein ligase activity is CC inhibited by phosphorylation by AURKA. Activity is increased by CC phosphatase treatment. {ECO:0000269|PubMed:18056443}. CC -!- PATHWAY: Protein modification; protein ubiquitination. CC -!- SUBUNIT: Heterodimer with BARD1. Part of the BRCA1-associated CC genome surveillance complex (BASC), which contains BRCA1, MSH2, CC MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) CC complex. This association could be a dynamic process changing CC throughout the cell cycle and within subnuclear domains. Component CC of the BRCA1-A complex, at least composed of the BRCA1, BARD1, CC UIMC1, BRCC3, BRE and BABAM1. Interacts (via the BRCT domains) CC with FAM175A. Component of the BRCA1-RBBP8 complex. Interacts (via CC the BRCT domains) with RBBP8 ('Ser-327' phosphorylated form); the CC interaction ubiquitinates RBBP8, regulates CHEK1 activation, and CC involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA CC damage. Associates with RNA polymerase II holoenzyme. Interacts CC with SMC1A, COBRA1, DCLRE1C, CLSPN. CHEK1, CHEK2, BAP1, BRCC3, CC AURKA, UBXN1 and KIAA0101/PAF15. Interacts (via BRCT domains) with CC BRIP1 (phosphorylated form). Interacts with FANCD2 (ubiquitinated CC form). Interacts with H2AFX (phosphorylated on 'Ser-140'). CC Interacts (via the BRCT domains) with ACACA (phosphorylated form); CC the interaction prevents dephosphorylation of ACACA. Part of a CC BRCA complex containing BRCA1, BRCA2 and PALB2. Interacts directly CC with PALB2; the interaction is essential for its function in HRR. CC Interacts directly with BRCA2; the interaction occurs only in the CC presence of PALB2 which serves as the bridging protein. Interacts CC (via the BRCT domains) with LMO4; the interaction represses the CC transcriptional activity of BRCA1. Interacts (via the BRCT CC domains) with CCAR2 (via N-terminus); the interaction represses CC the transcriptional activator activity of BRCA1. CC {ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:10783165, CC ECO:0000269|PubMed:11239454, ECO:0000269|PubMed:11301010, CC ECO:0000269|PubMed:11573085, ECO:0000269|PubMed:11739404, CC ECO:0000269|PubMed:11751867, ECO:0000269|PubMed:11836499, CC ECO:0000269|PubMed:11877377, ECO:0000269|PubMed:12360400, CC ECO:0000269|PubMed:12419185, ECO:0000269|PubMed:12890688, CC ECO:0000269|PubMed:14636569, ECO:0000269|PubMed:14976165, CC ECO:0000269|PubMed:14990569, ECO:0000269|PubMed:15096610, CC ECO:0000269|PubMed:15133502, ECO:0000269|PubMed:15456891, CC ECO:0000269|PubMed:16101277, ECO:0000269|PubMed:16326698, CC ECO:0000269|PubMed:16698035, ECO:0000269|PubMed:16818604, CC ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, CC ECO:0000269|PubMed:17643122, ECO:0000269|PubMed:18452305, CC ECO:0000269|PubMed:19261746, ECO:0000269|PubMed:19261748, CC ECO:0000269|PubMed:19261749, ECO:0000269|PubMed:19369211, CC ECO:0000269|PubMed:20159462, ECO:0000269|PubMed:20160719, CC ECO:0000269|PubMed:20351172, ECO:0000269|PubMed:21673012, CC ECO:0000269|PubMed:9528852, ECO:0000269|PubMed:9811458}. CC -!- INTERACTION: CC Q13085:ACACA; NbExp=2; IntAct=EBI-349905, EBI-717681; CC Q92560:BAP1; NbExp=3; IntAct=EBI-349905, EBI-1791447; CC Q99728:BARD1; NbExp=9; IntAct=EBI-349905, EBI-473181; CC P10415:BCL2; NbExp=6; IntAct=EBI-349905, EBI-77694; CC Q7Z569:BRAP; NbExp=3; IntAct=EBI-349905, EBI-349900; CC Q6PJG6:BRAT1; NbExp=6; IntAct=EBI-349905, EBI-10826195; CC Q9BX63:BRIP1; NbExp=12; IntAct=EBI-349905, EBI-3509650; CC P24385:CCND1; NbExp=3; IntAct=EBI-349905, EBI-375001; CC P24864:CCNE1; NbExp=2; IntAct=EBI-349905, EBI-519526; CC O14757:CHEK1; NbExp=3; IntAct=EBI-349905, EBI-974488; CC P03372:ESR1; NbExp=12; IntAct=EBI-349905, EBI-78473; CC Q61188:Ezh2 (xeno); NbExp=5; IntAct=EBI-349905, EBI-904311; CC Q6UWZ7:FAM175A; NbExp=10; IntAct=EBI-349905, EBI-1263451; CC Q14192:FHL2; NbExp=6; IntAct=EBI-349905, EBI-701903; CC P78347:GTF2I; NbExp=5; IntAct=EBI-349905, EBI-359622; CC P16104:H2AFX; NbExp=4; IntAct=EBI-349905, EBI-494830; CC P10809:HSPD1; NbExp=2; IntAct=EBI-349905, EBI-352528; CC Q16666:IFI16; NbExp=9; IntAct=EBI-349905, EBI-2867186; CC P52292:KPNA2; NbExp=3; IntAct=EBI-349905, EBI-349938; CC Q8WX92:NELFB; NbExp=5; IntAct=EBI-349905, EBI-347721; CC P62136:PPP1CA; NbExp=2; IntAct=EBI-349905, EBI-357253; CC P62140:PPP1CB; NbExp=3; IntAct=EBI-349905, EBI-352350; CC P36873:PPP1CC; NbExp=2; IntAct=EBI-349905, EBI-356283; CC Q99708:RBBP8; NbExp=9; IntAct=EBI-349905, EBI-745715; CC Q9Y4A5:TRRAP; NbExp=8; IntAct=EBI-349905, EBI-399128; CC Q96RL1:UIMC1; NbExp=9; IntAct=EBI-349905, EBI-725300; CC Q6NZY4:ZCCHC8; NbExp=2; IntAct=EBI-349905, EBI-1263058; CC Q9GZX5:ZNF350; NbExp=3; IntAct=EBI-349905, EBI-396421; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15133502, CC ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:20160719, CC ECO:0000269|PubMed:21144835, ECO:0000269|PubMed:9528852}. CC Chromosome {ECO:0000250|UniProtKB:P48754}. Cytoplasm CC {ECO:0000269|PubMed:20160719}. Note=Localizes at sites of DNA CC damage at double-strand breaks (DSBs); recruitment to DNA damage CC sites is mediated by the BRCA1-A complex. Translocated to the CC cytoplasm during UV-induced apoptosis. CC {ECO:0000269|PubMed:20160719}. CC -!- SUBCELLULAR LOCATION: Isoform 3: Cytoplasm. CC -!- SUBCELLULAR LOCATION: Isoform 5: Cytoplasm CC {ECO:0000269|PubMed:8972225}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing, Alternative initiation; Named isoforms=8; CC Name=1; CC IsoId=P38398-1; Sequence=Displayed; CC Name=2; CC IsoId=P38398-2; Sequence=VSP_047891; CC Note=May be produced at very low levels due to a premature stop CC codon in the mRNA, leading to nonsense-mediated mRNA decay.; CC Name=3; Synonyms=Delta11b; CC IsoId=P38398-3; Sequence=VSP_035399, VSP_043797; CC Name=4; Synonyms=DeltaBRCA1(17aa); CC IsoId=P38398-4; Sequence=VSP_035396; CC Note=Produced by alternative initiation at Met-18 of isoform 1.; CC Name=5; Synonyms=Delta11, Delta772-3095; CC IsoId=P38398-5; Sequence=VSP_035398; CC Name=6; CC IsoId=P38398-6; Sequence=VSP_035399, VSP_043797, VSP_043798; CC Note=No experimental confirmation available.; CC Name=7; CC IsoId=P38398-7; Sequence=VSP_055404; CC Note=No experimental confirmation available. Ref.8 (AAI15038) CC sequence is in conflict in position: 1461:N->D. {ECO:0000305}; CC Name=8; CC IsoId=P38398-8; Sequence=VSP_057569; CC Note=No experimental confirmation available. The N-terminus is CC confirmed by several cDNAs. {ECO:0000305}; CC -!- TISSUE SPECIFICITY: Isoform 1 and isoform 3 are widely expressed. CC Isoform 3 is reduced or absent in several breast and ovarian CC cancer cell lines. CC -!- DOMAIN: The BRCT domains recognize and bind phosphorylated pSXXF CC motif on proteins. The interaction with the phosphorylated pSXXF CC motif of FAM175A/Abraxas, recruits BRCA1 at DNA damage sites. CC {ECO:0000269|PubMed:20159462}. CC -!- DOMAIN: The RING-type zinc finger domain interacts with BAP1. CC {ECO:0000269|PubMed:20159462}. CC -!- PTM: Phosphorylation at Ser-308 by AURKA is required for normal CC cell cycle progression from G2 to mitosis. Phosphorylated in CC response to IR, UV, and various stimuli that cause checkpoint CC activation, probably by ATM or ATR. Phosphorylation at Ser-988 by CC CHEK2 regulates mitotic spindle assembly. CC {ECO:0000269|PubMed:10724175, ECO:0000269|PubMed:11114888, CC ECO:0000269|PubMed:12183412, ECO:0000269|PubMed:14990569, CC ECO:0000269|PubMed:18056443, ECO:0000269|PubMed:20364141, CC ECO:0000269|PubMed:21144835}. CC -!- PTM: Autoubiquitinated, undergoes 'Lys-6'-linked CC polyubiquitination. 'Lys-6'-linked polyubiquitination does not CC promote degradation. {ECO:0000269|PubMed:12890688, CC ECO:0000269|PubMed:20351172}. CC -!- POLYMORPHISM: There is evidence that the presence of the rare form CC of Gln-356-Arg and Leu-871-Pro polymorphisms may be associated CC with an increased risk for developing ovarian cancer. CC -!- DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy CC originating from breast epithelial tissue. Breast neoplasms can be CC distinguished by their histologic pattern. Invasive ductal CC carcinoma is by far the most common type. Breast cancer is CC etiologically and genetically heterogeneous. Important genetic CC factors have been indicated by familial occurrence and bilateral CC involvement. Mutations at more than one locus can be involved in CC different families or even in the same case. CC {ECO:0000269|PubMed:10323242, ECO:0000269|PubMed:12442275, CC ECO:0000269|PubMed:12938098, ECO:0000269|PubMed:14722926, CC ECO:0000269|PubMed:18285836, ECO:0000269|PubMed:7545954, CC ECO:0000269|PubMed:7894491, ECO:0000269|PubMed:7894493, CC ECO:0000269|PubMed:7939630, ECO:0000269|PubMed:8554067, CC ECO:0000269|PubMed:8723683, ECO:0000269|PubMed:8776600, CC ECO:0000269|PubMed:9482581, ECO:0000269|PubMed:9609997, CC ECO:0000269|PubMed:9760198}. Note=Disease susceptibility is CC associated with variations affecting the gene represented in this CC entry. Mutations in BRCA1 are thought to be responsible for 45% of CC inherited breast cancer. Moreover, BRCA1 carriers have a 4-fold CC increased risk of colon cancer, whereas male carriers face a 3- CC fold increased risk of prostate cancer. Cells lacking BRCA1 show CC defects in DNA repair by homologous recombination. CC -!- DISEASE: Breast-ovarian cancer, familial, 1 (BROVCA1) CC [MIM:604370]: A condition associated with familial predisposition CC to cancer of the breast and ovaries. Characteristic features in CC affected families are an early age of onset of breast cancer CC (often before age 50), increased chance of bilateral cancers CC (cancer that develop in both breasts, or both ovaries, CC independently), frequent occurrence of breast cancer among men, CC increased incidence of tumors of other specific organs, such as CC the prostate. {ECO:0000269|PubMed:12938098, CC ECO:0000269|PubMed:14722926, ECO:0000269|PubMed:8968716}. CC Note=Disease susceptibility is associated with variations CC affecting the gene represented in this entry. Mutations in BRCA1 CC are thought to be responsible for more than 80% of inherited CC breast-ovarian cancer. CC -!- DISEASE: Ovarian cancer (OC) [MIM:167000]: The term ovarian cancer CC defines malignancies originating from ovarian tissue. Although CC many histologic types of ovarian tumors have been described, CC epithelial ovarian carcinoma is the most common form. Ovarian CC cancers are often asymptomatic and the recognized signs and CC symptoms, even of late-stage disease, are vague. Consequently, CC most patients are diagnosed with advanced disease. CC {ECO:0000269|PubMed:10196379, ECO:0000269|PubMed:10486320, CC ECO:0000269|PubMed:14746861}. Note=Disease susceptibility is CC associated with variations affecting the gene represented in this CC entry. CC -!- DISEASE: Pancreatic cancer 4 (PNCA4) [MIM:614320]: A malignant CC neoplasm of the pancreas. Tumors can arise from both the exocrine CC and endocrine portions of the pancreas, but 95% of them develop CC from the exocrine portion, including the ductal epithelium, acinar CC cells, connective tissue, and lymphatic tissue. CC {ECO:0000269|PubMed:18762988}. Note=Disease susceptibility is CC associated with variations affecting the gene represented in this CC entry. CC -!- SIMILARITY: Contains 2 BRCT domains. {ECO:0000255|PROSITE- CC ProRule:PRU00033}. CC -!- SIMILARITY: Contains 1 RING-type zinc finger. CC {ECO:0000255|PROSITE-ProRule:PRU00175}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB61673.1; Type=Erroneous translation; Note=Wrong choice of CDS.; Evidence={ECO:0000305}; CC Sequence=AAI15038.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; CC Sequence=AAI15038.1; Type=Erroneous termination; Positions=526; Note=Translated as Gln.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/BRCA1ID163ch17q21.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/brca1/"; 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=BRCA1"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=BRCA1 entry; CC URL="https://en.wikipedia.org/wiki/BRCA1"; 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; U14680; AAA73985.1; -; mRNA. DR EMBL; L78833; AAC37594.1; -; Genomic_DNA. DR EMBL; U64805; AAC00049.1; -; mRNA. DR EMBL; AF005068; AAB61673.1; ALT_SEQ; mRNA. DR EMBL; DQ190450; ABA29208.1; -; Genomic_DNA. DR EMBL; DQ190451; ABA29211.1; -; Genomic_DNA. DR EMBL; DQ190452; ABA29214.1; -; Genomic_DNA. DR EMBL; DQ190453; ABA29217.1; -; Genomic_DNA. DR EMBL; DQ190454; ABA29220.1; -; Genomic_DNA. DR EMBL; DQ190455; ABA29223.1; -; Genomic_DNA. DR EMBL; DQ190456; ABA29226.1; -; Genomic_DNA. DR EMBL; AY273801; AAP12647.1; -; Genomic_DNA. DR EMBL; AC060780; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC135721; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC072418; AAH72418.1; -; mRNA. DR EMBL; BC115037; AAI15038.1; ALT_SEQ; mRNA. DR CCDS; CCDS11453.1; -. [P38398-1] DR CCDS; CCDS11454.2; -. [P38398-3] DR CCDS; CCDS11455.2; -. [P38398-6] DR CCDS; CCDS11456.2; -. [P38398-7] DR CCDS; CCDS11459.2; -. [P38398-8] DR PIR; A58881; A58881. DR RefSeq; NP_009225.1; NM_007294.3. [P38398-1] DR RefSeq; NP_009228.2; NM_007297.3. [P38398-8] DR RefSeq; NP_009229.2; NM_007298.3. [P38398-3] DR RefSeq; NP_009230.2; NM_007299.3. [P38398-6] DR RefSeq; NP_009231.2; NM_007300.3. [P38398-7] DR UniGene; Hs.194143; -. DR PDB; 1JM7; NMR; -; A=1-110. DR PDB; 1JNX; X-ray; 2.50 A; X=1646-1859. DR PDB; 1N5O; X-ray; 2.80 A; X=1646-1859. DR PDB; 1OQA; NMR; -; A=1755-1863. DR PDB; 1T15; X-ray; 1.85 A; A=1646-1859. DR PDB; 1T29; X-ray; 2.30 A; A=1646-1859. DR PDB; 1T2U; X-ray; 2.80 A; A=1646-1859. DR PDB; 1T2V; X-ray; 3.30 A; A/B/C/D/E=1646-1859. DR PDB; 1Y98; X-ray; 2.50 A; A=1646-1859. DR PDB; 2ING; X-ray; 3.60 A; X=1649-1859. DR PDB; 3COJ; X-ray; 3.21 A; A/B/C/D/E/F/G/X=1646-1859. DR PDB; 3K0H; X-ray; 2.70 A; A=1646-1859. DR PDB; 3K0K; X-ray; 2.70 A; A=1646-1859. DR PDB; 3K15; X-ray; 2.80 A; A=1646-1859. DR PDB; 3K16; X-ray; 3.00 A; A=1646-1859. DR PDB; 3PXA; X-ray; 2.55 A; A=1646-1859. DR PDB; 3PXB; X-ray; 2.50 A; A=1646-1859. DR PDB; 3PXC; X-ray; 2.80 A; X=1646-1859. DR PDB; 3PXD; X-ray; 2.80 A; A=1646-1859. DR PDB; 3PXE; X-ray; 2.85 A; A/B/C/D=1646-1859. DR PDB; 4IFI; X-ray; 2.20 A; A=1646-1859. DR PDB; 4IGK; X-ray; 1.75 A; A/B=1646-1859. DR PDB; 4JLU; X-ray; 3.50 A; A=1649-1859. DR PDB; 4OFB; X-ray; 3.05 A; A=1646-1859. DR PDB; 4U4A; X-ray; 3.51 A; A/B/C=1646-1859. DR PDBsum; 1JM7; -. DR PDBsum; 1JNX; -. DR PDBsum; 1N5O; -. DR PDBsum; 1OQA; -. DR PDBsum; 1T15; -. DR PDBsum; 1T29; -. DR PDBsum; 1T2U; -. DR PDBsum; 1T2V; -. DR PDBsum; 1Y98; -. DR PDBsum; 2ING; -. DR PDBsum; 3COJ; -. DR PDBsum; 3K0H; -. DR PDBsum; 3K0K; -. DR PDBsum; 3K15; -. DR PDBsum; 3K16; -. DR PDBsum; 3PXA; -. DR PDBsum; 3PXB; -. DR PDBsum; 3PXC; -. DR PDBsum; 3PXD; -. DR PDBsum; 3PXE; -. DR PDBsum; 4IFI; -. DR PDBsum; 4IGK; -. DR PDBsum; 4JLU; -. DR PDBsum; 4OFB; -. DR PDBsum; 4U4A; -. DR DisProt; DP00238; -. DR ProteinModelPortal; P38398; -. DR SMR; P38398; 1-103, 1649-1859. DR BioGrid; 107140; 561. DR DIP; DIP-5971N; -. DR IntAct; P38398; 74. DR MINT; MINT-90433; -. DR STRING; 9606.ENSP00000418960; -. DR BindingDB; P38398; -. DR ChEMBL; CHEMBL5990; -. DR PhosphoSite; P38398; -. DR BioMuta; BRCA1; -. DR DMDM; 728984; -. DR MaxQB; P38398; -. DR PaxDb; P38398; -. DR PRIDE; P38398; -. DR DNASU; 672; -. DR Ensembl; ENST00000352993; ENSP00000312236; ENSG00000012048. [P38398-5] DR Ensembl; ENST00000357654; ENSP00000350283; ENSG00000012048. [P38398-1] DR Ensembl; ENST00000461221; ENSP00000418548; ENSG00000012048. [P38398-2] DR Ensembl; ENST00000461798; ENSP00000417988; ENSG00000012048. [P38398-2] DR Ensembl; ENST00000468300; ENSP00000417148; ENSG00000012048. [P38398-6] DR Ensembl; ENST00000471181; ENSP00000418960; ENSG00000012048. [P38398-7] DR Ensembl; ENST00000491747; ENSP00000420705; ENSG00000012048. [P38398-3] DR Ensembl; ENST00000493795; ENSP00000418775; ENSG00000012048. [P38398-8] DR GeneID; 672; -. DR KEGG; hsa:672; -. DR UCSC; uc002icp.4; human. [P38398-2] DR UCSC; uc002icq.3; human. [P38398-1] DR UCSC; uc002icu.3; human. [P38398-6] DR UCSC; uc010whq.1; human. [P38398-3] DR CTD; 672; -. DR GeneCards; BRCA1; -. DR GeneReviews; BRCA1; -. DR HGNC; HGNC:1100; BRCA1. DR HPA; CAB001946; -. DR HPA; CAB018369; -. DR HPA; HPA034966; -. DR MIM; 113705; gene. DR MIM; 114480; phenotype. DR MIM; 167000; phenotype. DR MIM; 604370; phenotype. DR MIM; 614320; phenotype. DR neXtProt; NX_P38398; -. DR Orphanet; 1333; Familial pancreatic carcinoma. DR Orphanet; 1331; Familial prostate cancer. DR Orphanet; 145; Hereditary breast and ovarian cancer syndrome. DR Orphanet; 227535; Hereditary breast cancer. DR Orphanet; 213524; Hereditary site-specific ovarian cancer syndrome. DR Orphanet; 168829; Primary peritoneal carcinoma. DR PharmGKB; PA25411; -. DR eggNOG; ENOG410ITQ4; Eukaryota. DR eggNOG; ENOG4112BIH; LUCA. DR GeneTree; ENSGT00440000034289; -. DR HOGENOM; HOG000230969; -. DR HOVERGEN; HBG050730; -. DR InParanoid; P38398; -. DR KO; K10605; -. DR OMA; FQHLLFG; -. DR OrthoDB; EOG79CXXK; -. DR PhylomeDB; P38398; -. DR BRENDA; 6.3.2.19; 2681. DR Reactome; R-HSA-1221632; Meiotic synapsis. DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins. DR Reactome; R-HSA-419524; Fanconi Anemia pathway. DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint. DR Reactome; R-HSA-75148; ATM mediated phosphorylation of repair proteins. DR Reactome; R-HSA-75154; Recruitment of repair and signaling proteins to double-strand breaks. DR Reactome; R-HSA-912446; Meiotic recombination. DR SignaLink; P38398; -. DR UniPathway; UPA00143; -. DR ChiTaRS; BRCA1; human. DR EvolutionaryTrace; P38398; -. DR GeneWiki; BRCA1; -. DR GenomeRNAi; 672; -. DR NextBio; 2752; -. DR PMAP-CutDB; P38398; -. DR PRO; PR:P38398; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; P38398; -. DR CleanEx; HS_BRCA1; -. DR ExpressionAtlas; P38398; baseline and differential. DR Genevisible; P38398; HS. DR GO; GO:0070531; C:BRCA1-A complex; IDA:UniProtKB. DR GO; GO:0031436; C:BRCA1-BARD1 complex; IDA:UniProtKB. DR GO; GO:0005694; C:chromosome; ISS:UniProtKB. DR GO; GO:0000794; C:condensed nuclear chromosome; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0008274; C:gamma-tubulin ring complex; NAS:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL. DR GO; GO:0043234; C:protein complex; IDA:UniProtKB. DR GO; GO:0030529; C:ribonucleoprotein complex; IDA:MGI. DR GO; GO:0000151; C:ubiquitin ligase complex; NAS:UniProtKB. DR GO; GO:0050681; F:androgen receptor binding; NAS:UniProtKB. DR GO; GO:0003684; F:damaged DNA binding; IEA:Ensembl. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW. DR GO; GO:0003723; F:RNA binding; IDA:MGI. DR GO; GO:0003713; F:transcription coactivator activity; NAS:UniProtKB. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL. DR GO; GO:0015631; F:tubulin binding; NAS:UniProtKB. 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; TAS:ProtInc. DR GO; GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB. DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; TAS:ProtInc. DR GO; GO:0071681; P:cellular response to indole-3-methanol; IDA:UniProtKB. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:BHF-UCL. DR GO; GO:0007098; P:centrosome cycle; IEA:Ensembl. DR GO; GO:0043009; P:chordate embryonic development; IBA:GO_Central. DR GO; GO:0031052; P:chromosome breakage; IEA:Ensembl. DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB. DR GO; GO:0006978; P:DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator; TAS:UniProtKB. DR GO; GO:0006281; P:DNA repair; TAS:Reactome. DR GO; GO:0006260; P:DNA replication; IEA:Ensembl. DR GO; GO:0009048; P:dosage compensation by inactivation of X chromosome; IBA:GO_Central. DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:HGNC. DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW. DR GO; GO:0031572; P:G2 DNA damage checkpoint; IMP:UniProtKB. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:MGI. DR GO; GO:0046600; P:negative regulation of centriole replication; NAS:UniProtKB. DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IMP:BHF-UCL. DR GO; GO:0045717; P:negative regulation of fatty acid biosynthetic process; IMP:UniProtKB. DR GO; GO:0035067; P:negative regulation of histone acetylation; IBA:GO_Central. DR GO; GO:0051572; P:negative regulation of histone H3-K4 methylation; IEA:Ensembl. DR GO; GO:0051573; P:negative regulation of histone H3-K9 methylation; IDA:BHF-UCL. DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IMP:CACAO. DR GO; GO:2000378; P:negative regulation of reactive oxygen species metabolic process; IMP:BHF-UCL. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:BHF-UCL. DR GO; GO:0071158; P:positive regulation of cell cycle arrest; IDA:BHF-UCL. DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL. DR GO; GO:0035066; P:positive regulation of histone acetylation; IDA:BHF-UCL. DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; IDA:BHF-UCL. DR GO; GO:2000617; P:positive regulation of histone H3-K9 acetylation; IDA:BHF-UCL. DR GO; GO:0051574; P:positive regulation of histone H3-K9 methylation; IEA:Ensembl. DR GO; GO:2000620; P:positive regulation of histone H4-K16 acetylation; IDA:BHF-UCL. DR GO; GO:0070512; P:positive regulation of histone H4-K20 methylation; IDA:BHF-UCL. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; 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:0010575; P:positive regulation of vascular endothelial growth factor production; IMP:BHF-UCL. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:0006301; P:postreplication repair; IDA:HGNC. DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB. DR GO; GO:0085020; P:protein K6-linked ubiquitination; IDA:UniProtKB. DR GO; GO:0016925; P:protein sumoylation; TAS:Reactome. DR GO; GO:0016567; P:protein ubiquitination; IDA:HGNC. DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB. DR GO; GO:0042127; P:regulation of cell proliferation; TAS:UniProtKB. DR GO; GO:0044030; P:regulation of DNA methylation; IEA:Ensembl. DR GO; GO:0006349; P:regulation of gene expression by genetic imprinting; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; TAS:ProtInc. DR GO; GO:0006359; P:regulation of transcription from RNA polymerase III promoter; TAS:UniProtKB. DR GO; GO:0043627; P:response to estrogen; IDA:UniProtKB. DR GO; GO:0010212; P:response to ionizing radiation; IMP:UniProtKB. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.30.40.10; -; 1. DR Gene3D; 3.40.50.10190; -; 2. DR InterPro; IPR011364; BRCA1. DR InterPro; IPR031099; BRCA1-associated. DR InterPro; IPR025994; BRCA1_serine_dom. DR InterPro; IPR001357; BRCT_dom. DR InterPro; IPR018957; Znf_C3HC4_RING-type. DR InterPro; IPR001841; Znf_RING. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR InterPro; IPR017907; Znf_RING_CS. DR PANTHER; PTHR13763; PTHR13763; 1. DR PANTHER; PTHR13763:SF0; PTHR13763:SF0; 1. DR Pfam; PF00533; BRCT; 2. DR Pfam; PF12820; BRCT_assoc; 1. DR Pfam; PF00097; zf-C3HC4; 1. DR PIRSF; PIRSF001734; BRCA1; 1. DR PRINTS; PR00493; BRSTCANCERI. DR SMART; SM00292; BRCT; 2. DR SMART; SM00184; RING; 1. DR SUPFAM; SSF52113; SSF52113; 2. DR PROSITE; PS50172; BRCT; 2. DR PROSITE; PS00518; ZF_RING_1; 1. DR PROSITE; PS50089; ZF_RING_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative initiation; KW Alternative splicing; Cell cycle; Chromosome; Complete proteome; KW Cytoplasm; Direct protein sequencing; Disease mutation; DNA damage; KW DNA recombination; DNA repair; DNA-binding; Fatty acid biosynthesis; KW Fatty acid metabolism; Isopeptide bond; Ligase; Lipid biosynthesis; KW Lipid metabolism; Metal-binding; Nucleus; Phosphoprotein; KW Polymorphism; Reference proteome; Repeat; Transcription; KW Transcription regulation; Tumor suppressor; Ubl conjugation; KW Ubl conjugation pathway; Zinc; Zinc-finger. FT CHAIN 1 1863 Breast cancer type 1 susceptibility FT protein. FT /FTId=PRO_0000055830. FT DOMAIN 1642 1736 BRCT 1. {ECO:0000255|PROSITE- FT ProRule:PRU00033}. FT DOMAIN 1756 1855 BRCT 2. {ECO:0000255|PROSITE- FT ProRule:PRU00033}. FT ZN_FING 24 65 RING-type. {ECO:0000255|PROSITE- FT ProRule:PRU00175}. FT REGION 1397 1424 Interaction with PALB2. FT COMPBIAS 651 654 Poly-Lys. FT MOD_RES 1 1 N-acetylmethionine. FT {ECO:0000244|PubMed:22814378}. FT MOD_RES 114 114 Phosphoserine. FT {ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 308 308 Phosphoserine; by AURKA. FT {ECO:0000269|PubMed:14990569}. FT MOD_RES 395 395 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332}. FT MOD_RES 398 398 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332}. FT MOD_RES 423 423 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 694 694 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 725 725 Phosphoserine. FT {ECO:0000250|UniProtKB:P48754}. FT MOD_RES 753 753 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 840 840 Phosphoserine. FT {ECO:0000250|UniProtKB:P48754}. FT MOD_RES 988 988 Phosphoserine; by CHEK2. FT {ECO:0000269|PubMed:10724175, FT ECO:0000269|PubMed:20364141}. FT MOD_RES 1143 1143 Phosphoserine; by ATR; in vitro. FT {ECO:0000269|PubMed:11114888}. FT MOD_RES 1211 1211 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 1217 1217 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 1218 1218 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 1280 1280 Phosphoserine; by ATR; in vitro. FT {ECO:0000269|PubMed:11114888}. FT MOD_RES 1328 1328 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 1336 1336 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 1342 1342 Phosphoserine. FT {ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 1387 1387 Phosphoserine; by ATM and ATR. FT {ECO:0000269|PubMed:11114888}. FT MOD_RES 1394 1394 Phosphothreonine; by ATR; in vitro. FT {ECO:0000269|PubMed:11114888}. FT MOD_RES 1423 1423 Phosphoserine; by ATM and ATR. FT {ECO:0000269|PubMed:11114888}. FT MOD_RES 1457 1457 Phosphoserine; by ATR; in vitro. FT {ECO:0000269|PubMed:11114888}. FT MOD_RES 1524 1524 Phosphoserine; by ATM. FT {ECO:0000269|PubMed:21144835}. FT CROSSLNK 339 339 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 459 459 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 583 583 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 654 654 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 734 734 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 739 739 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT VAR_SEQ 1 47 Missing (in isoform 8). FT /FTId=VSP_057569. FT VAR_SEQ 1 17 Missing (in isoform 4). {ECO:0000305}. FT /FTId=VSP_035396. FT VAR_SEQ 64 1863 Missing (in isoform 2). FT {ECO:0000303|Ref.4}. FT /FTId=VSP_047891. FT VAR_SEQ 224 1365 Missing (in isoform 5). {ECO:0000305}. FT /FTId=VSP_035398. FT VAR_SEQ 264 1366 Missing (in isoform 3 and isoform 6). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9010228}. FT /FTId=VSP_035399. FT VAR_SEQ 1453 1453 Missing (in isoform 3 and isoform 6). FT {ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:9010228}. FT /FTId=VSP_043797. FT VAR_SEQ 1453 1453 A -> DSHIHGQRNNSMFSKRPREHIS (in isoform FT 7). {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_055404. FT VAR_SEQ 1778 1863 DQLEWMVQLCGASVVKELSSFTLGTGVHPIVVVQPDAWTED FT NGFHAIGQMCEAPVVTREWVLDSVALYQCQELDTYLIPQIP FT HSHY -> GCPPNCGCAARCLDRGQWLPCNWADV (in FT isoform 6). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_043798. FT VARIANT 4 4 S -> F (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070458. FT VARIANT 10 10 E -> K (in BC and BROVCA1). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020679. FT VARIANT 11 11 V -> A (found in breast-ovarian cancer FT patients; unknown pathological FT significance; dbSNP:rs80357017). FT /FTId=VAR_007754. FT VARIANT 18 18 M -> T (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:23867111}. FT /FTId=VAR_063899. FT VARIANT 21 21 I -> V (found in breast-ovarian cancer FT patients; unknown pathological FT significance; dbSNP:rs80357406). FT /FTId=VAR_007755. FT VARIANT 22 22 L -> S (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_007756. FT VARIANT 23 23 E -> K (in BC and BROVCA1). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020680. FT VARIANT 30 30 L -> F (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_035947. FT VARIANT 45 45 K -> Q (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070459. FT VARIANT 61 61 C -> G (in BC and ovarian cancer; no FT interaction with BAP1; dbSNP:rs28897672). FT {ECO:0000269|PubMed:12938098, FT ECO:0000269|PubMed:14746861, FT ECO:0000269|PubMed:23867111, FT ECO:0000269|PubMed:7894493, FT ECO:0000269|PubMed:8554067, FT ECO:0000269|PubMed:9528852, FT ECO:0000269|PubMed:9760198}. FT /FTId=VAR_007757. FT VARIANT 64 64 C -> G (in BC; no interaction with BAP1). FT {ECO:0000269|PubMed:23867111, FT ECO:0000269|PubMed:7894491, FT ECO:0000269|PubMed:9482581, FT ECO:0000269|PubMed:9528852}. FT /FTId=VAR_007758. FT VARIANT 64 64 C -> Y (in dbSNP:rs55851803). FT /FTId=VAR_007759. FT VARIANT 67 67 D -> Y (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070460. FT VARIANT 71 71 R -> K (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12938098}. FT /FTId=VAR_020681. FT VARIANT 105 105 Y -> C. {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070461. FT VARIANT 132 132 N -> K (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070462. FT VARIANT 142 142 P -> H (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070463. FT VARIANT 147 147 L -> F (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070464. FT VARIANT 153 153 S -> R (in dbSNP:rs28897674). FT /FTId=VAR_052077. FT VARIANT 165 165 L -> P (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070465. FT VARIANT 170 170 R -> W (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070466. FT VARIANT 186 186 S -> Y (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070467. FT VARIANT 191 191 V -> I (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070468. FT VARIANT 227 227 E -> K (in ovarian cancer; unknown FT pathological significance). FT /FTId=VAR_008759. FT VARIANT 231 231 T -> M (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070469. FT VARIANT 239 239 H -> R. {ECO:0000269|PubMed:9010228, FT ECO:0000269|PubMed:9760198}. FT /FTId=VAR_007760. FT VARIANT 245 245 D -> V (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070470. FT VARIANT 246 246 L -> V (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070471. FT VARIANT 271 271 V -> L (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070472. FT VARIANT 271 271 V -> M (in BC; dbSNP:rs80357244). FT {ECO:0000269|PubMed:8723683}. FT /FTId=VAR_007761. FT VARIANT 275 275 G -> S (in dbSNP:rs8176153). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_019944. FT VARIANT 346 346 P -> S (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:10323242}. FT /FTId=VAR_008760. FT VARIANT 356 356 Q -> R (common polymorphism; FT dbSNP:rs1799950). FT {ECO:0000269|PubMed:7894493, FT ECO:0000269|Ref.5, ECO:0000269|Ref.6}. FT /FTId=VAR_007762. FT VARIANT 369 369 Missing (in BC). FT /FTId=VAR_007763. FT VARIANT 379 379 I -> M (in dbSNP:rs56128296). FT /FTId=VAR_007764. FT VARIANT 461 461 F -> L (in BC; dbSNP:rs56046357). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_007765. FT VARIANT 465 465 Y -> D (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_007766. FT VARIANT 507 507 R -> I (found in breast-ovarian cancer FT patients; unknown pathological FT significance; dbSNP:rs80357224). FT /FTId=VAR_007767. FT VARIANT 552 552 G -> V (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_007768. FT VARIANT 656 656 N -> I. {ECO:0000269|PubMed:12442274}. FT /FTId=VAR_020682. FT VARIANT 668 668 L -> F (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070473. FT VARIANT 693 693 D -> N (rare polymorphism; FT dbSNP:rs4986850). FT {ECO:0000269|PubMed:15026808, FT ECO:0000269|Ref.6}. FT /FTId=VAR_007769. FT VARIANT 695 695 D -> N (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070474. FT VARIANT 723 723 N -> D (in dbSNP:rs4986845). FT /FTId=VAR_020110. FT VARIANT 749 749 D -> Y (in BC). FT {ECO:0000269|PubMed:12442275}. FT /FTId=VAR_020683. FT VARIANT 758 758 L -> F (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_035948. FT VARIANT 772 772 V -> A (rare polymorphism). FT {ECO:0000269|PubMed:7894491, FT ECO:0000269|PubMed:9482581}. FT /FTId=VAR_007770. FT VARIANT 778 778 G -> C (in a breast cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_035949. FT VARIANT 798 798 P -> L (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070475. FT VARIANT 810 810 N -> Y (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070476. FT VARIANT 820 820 K -> E (rare polymorphism; FT dbSNP:rs56082113). FT {ECO:0000269|PubMed:9482581}. FT /FTId=VAR_007771. FT VARIANT 826 826 T -> K (in BC; unknown pathological FT significance; functionally neutral in FT vitro; dbSNP:rs28897683). FT {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_007772. FT VARIANT 835 835 H -> Y (in BROVCA1; unknown pathological FT significance). FT {ECO:0000269|PubMed:12938098}. FT /FTId=VAR_020684. FT VARIANT 841 841 R -> Q (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070477. FT VARIANT 841 841 R -> W (in BROVCA1; unknown pathological FT significance; dbSNP:rs1800709). FT {ECO:0000269|PubMed:8968716, FT ECO:0000269|PubMed:9760198}. FT /FTId=VAR_007773. FT VARIANT 856 856 Y -> H (in a patient with sporadic breast FT cancer; unknown pathological FT significance; dbSNP:rs80356892). FT {ECO:0000269|PubMed:15365993, FT ECO:0000269|PubMed:23867111}. FT /FTId=VAR_020685. FT VARIANT 866 866 R -> C. {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070478. FT VARIANT 866 866 R -> Q (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12938098}. FT /FTId=VAR_020686. FT VARIANT 871 871 P -> L (common polymorphism; FT dbSNP:rs799917). FT {ECO:0000269|PubMed:10323242, FT ECO:0000269|PubMed:12442274, FT ECO:0000269|PubMed:15365993, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|Ref.6}. FT /FTId=VAR_007774. FT VARIANT 888 888 H -> Y (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12938098}. FT /FTId=VAR_020687. FT VARIANT 892 892 L -> S (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_007775. FT VARIANT 925 925 I -> L (in dbSNP:rs4986847). FT /FTId=VAR_021913. FT VARIANT 960 960 G -> D (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_007776. FT VARIANT 989 989 F -> S (in dbSNP:rs4986848). FT /FTId=VAR_020111. FT VARIANT 1008 1008 M -> I (common polymorphism; FT dbSNP:rs1800704). FT /FTId=VAR_007777. FT VARIANT 1025 1025 T -> I (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_007778. FT VARIANT 1038 1038 E -> G (common polymorphism; FT dbSNP:rs16941). FT {ECO:0000269|PubMed:10323242, FT ECO:0000269|PubMed:15365993, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7894493, FT ECO:0000269|Ref.6}. FT /FTId=VAR_007779. FT VARIANT 1040 1040 S -> N (rare polymorphism; FT dbSNP:rs4986852). FT {ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:7894491, FT ECO:0000269|PubMed:7894493, FT ECO:0000269|PubMed:9482581, FT ECO:0000269|Ref.6}. FT /FTId=VAR_007780. FT VARIANT 1047 1047 V -> A (in BC). FT {ECO:0000269|PubMed:9609997}. FT /FTId=VAR_007781. FT VARIANT 1060 1060 E -> A. {ECO:0000269|PubMed:15026808, FT ECO:0000269|PubMed:23867111}. FT /FTId=VAR_020688. FT VARIANT 1101 1101 S -> N (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070479. FT VARIANT 1139 1139 S -> I (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12938098}. FT /FTId=VAR_020689. FT VARIANT 1140 1140 S -> G (in BC; unknown pathological FT significance; functionally neutral in FT vitro; dbSNP:rs2227945). FT {ECO:0000269|PubMed:23867111, FT ECO:0000269|Ref.6}. FT /FTId=VAR_019945. FT VARIANT 1140 1140 S -> N (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070480. FT VARIANT 1150 1150 P -> S (in BC; dbSNP:rs80357272). FT {ECO:0000269|PubMed:8723683}. FT /FTId=VAR_007782. FT VARIANT 1183 1183 K -> R (common polymorphism; FT dbSNP:rs16942). FT {ECO:0000269|PubMed:10323242, FT ECO:0000269|PubMed:14722926, FT ECO:0000269|PubMed:15365993, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7894493, FT ECO:0000269|Ref.6}. FT /FTId=VAR_007783. FT VARIANT 1187 1187 S -> I (in BC and BROVCA1). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020690. FT VARIANT 1200 1200 Q -> H (in BC and BROVCA1; FT dbSNP:rs56214134). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020691. FT VARIANT 1204 1204 R -> I (in BC). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020692. FT VARIANT 1207 1207 K -> N (in BC). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020693. FT VARIANT 1210 1210 E -> G (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12938098}. FT /FTId=VAR_020694. FT VARIANT 1214 1214 E -> K (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070481. FT VARIANT 1217 1217 S -> Y (in BC and BROVCA1). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020695. FT VARIANT 1219 1219 E -> D (found in breast-ovarian cancer FT patients; unknown pathological FT significance; dbSNP:rs80356876). FT /FTId=VAR_007784. FT VARIANT 1226 1226 F -> L (in BROVCA1). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020696. FT VARIANT 1236 1236 N -> K (in BC; unknown pathological FT significance; functionally neutral in FT vitro; dbSNP:rs28897687). FT {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_052078. FT VARIANT 1243 1243 R -> G (in BROVCA1). FT {ECO:0000269|PubMed:14722926}. FT /FTId=VAR_020697. FT VARIANT 1250 1250 E -> K (in dbSNP:rs28897686). FT {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_052079. FT VARIANT 1267 1267 L -> S (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070482. FT VARIANT 1282 1282 E -> V (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070483. FT VARIANT 1297 1297 S -> P (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:12938098}. FT /FTId=VAR_020698. FT VARIANT 1297 1297 Missing (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070484. FT VARIANT 1301 1301 S -> R (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070485. FT VARIANT 1346 1346 E -> K (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070486. FT VARIANT 1347 1347 R -> G (in dbSNP:rs28897689). FT {ECO:0000269|PubMed:12215251}. FT /FTId=VAR_007785. FT VARIANT 1378 1378 V -> I (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070487. FT VARIANT 1400 1400 M -> V (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070488. FT VARIANT 1406 1406 K -> N (polymorphism; dbSNP:rs1800707). FT /FTId=VAR_008761. FT VARIANT 1407 1407 L -> P (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070489. FT VARIANT 1411 1411 M -> T (in BC and ovarian cancer; unknown FT pathological significance; decreased FT interaction with PALB2). FT {ECO:0000269|PubMed:14746861, FT ECO:0000269|PubMed:23867111}. FT /FTId=VAR_020699. FT VARIANT 1431 1431 S -> P. FT /FTId=VAR_007786. FT VARIANT 1443 1443 R -> G (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111, FT ECO:0000269|PubMed:7894491, FT ECO:0000269|PubMed:9482581}. FT /FTId=VAR_007787. FT VARIANT 1443 1443 R -> Q (in dbSNP:rs4986849). FT /FTId=VAR_020112. FT VARIANT 1448 1448 S -> G (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070490. FT VARIANT 1486 1486 S -> C (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070491. FT VARIANT 1495 1495 R -> M (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331}. FT /FTId=VAR_063900. FT VARIANT 1512 1512 S -> I (in dbSNP:rs1800744). FT {ECO:0000269|PubMed:12215251, FT ECO:0000269|PubMed:9482581, FT ECO:0000269|PubMed:9760198}. FT /FTId=VAR_007788. FT VARIANT 1534 1534 V -> M (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070492. FT VARIANT 1561 1561 T -> I (found in breast cancer; unknown FT pathological significance; FT dbSNP:rs56158747). FT /FTId=VAR_007789. FT VARIANT 1589 1589 R -> P (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070493. FT VARIANT 1606 1606 K -> E (found in breast cancer; unknown FT pathological significance). FT /FTId=VAR_007790. FT VARIANT 1613 1613 S -> G (common polymorphism; FT dbSNP:rs1799966). FT {ECO:0000269|PubMed:10323242, FT ECO:0000269|PubMed:12442274, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7894493, FT ECO:0000269|PubMed:9010228, FT ECO:0000269|Ref.6}. FT /FTId=VAR_007791. FT VARIANT 1620 1620 T -> A (in dbSNP:rs8176219). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_019946. FT VARIANT 1623 1623 A -> G (could be associated with cancer FT susceptibility; major splicing aberration FT identified with this mutant). FT {ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:20513136}. FT /FTId=VAR_063901. FT VARIANT 1628 1628 M -> T (in some patients with sporadic FT breast cancer; unknown pathological FT significance; dbSNP:rs4986854). FT {ECO:0000269|PubMed:15365993, FT ECO:0000269|PubMed:23867111}. FT /FTId=VAR_007793. FT VARIANT 1628 1628 M -> V (found in breast and ovarian FT cancer patients; unknown pathological FT significance; dbSNP:rs80357465). FT /FTId=VAR_007792. FT VARIANT 1637 1637 P -> L (rare polymorphism). FT {ECO:0000269|PubMed:7939630, FT ECO:0000269|PubMed:9482581}. FT /FTId=VAR_007794. FT VARIANT 1641 1641 A -> P (in ovarian cancer; unknown FT pathological significance; FT dbSNP:rs1800726). FT /FTId=VAR_008762. FT VARIANT 1651 1651 S -> F (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070494. FT VARIANT 1651 1651 S -> P (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070495. FT VARIANT 1652 1652 M -> I (rare polymorphism; FT dbSNP:rs1799967). FT {ECO:0000269|PubMed:12215251, FT ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:23867111, FT ECO:0000269|PubMed:9482581}. FT /FTId=VAR_007795. FT VARIANT 1655 1655 S -> F (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070496. FT VARIANT 1662 1662 F -> C (in dbSNP:rs28897695). FT /FTId=VAR_052080. FT VARIANT 1665 1665 V -> M. {ECO:0000269|PubMed:15026808}. FT /FTId=VAR_020700. FT VARIANT 1685 1685 T -> A (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331}. FT /FTId=VAR_063902. FT VARIANT 1685 1685 T -> I (could be associated with cancer FT susceptibility; multifactorial likelihood FT analysis provides evidence for FT pathogenicity). FT {ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:20513136}. FT /FTId=VAR_063903. FT VARIANT 1686 1686 H -> Q (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070497. FT VARIANT 1686 1686 H -> R (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070498. FT VARIANT 1688 1688 Missing (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070499. FT VARIANT 1689 1689 M -> R (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331}. FT /FTId=VAR_063904. FT VARIANT 1690 1690 K -> Q (in some patients with sporadic FT breast cancer; unknown pathological FT significance). FT {ECO:0000269|PubMed:15365993}. FT /FTId=VAR_020701. FT VARIANT 1691 1691 T -> I (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070500. FT VARIANT 1692 1692 D -> N (in ovarian cancer; unknown FT pathological significance). FT /FTId=VAR_008763. FT VARIANT 1697 1697 C -> R (in ovarian cancer). FT {ECO:0000269|PubMed:14746861}. FT /FTId=VAR_020702. FT VARIANT 1699 1699 R -> Q (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070501. FT VARIANT 1699 1699 R -> W (in BC and ovarian cancer; FT functionally impaired in vitro). FT {ECO:0000269|PubMed:14746861, FT ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:23867111}. FT /FTId=VAR_020703. FT VARIANT 1706 1706 G -> A (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070502. FT VARIANT 1706 1706 G -> E (in BC; unknown pathological FT significance; dbSNP:rs80356860). FT {ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:23867111}. FT /FTId=VAR_063905. FT VARIANT 1708 1708 A -> E (in BC; abolishes ACACA binding; FT dbSNP:rs28897696). FT {ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:23867111, FT ECO:0000269|PubMed:7939630}. FT /FTId=VAR_007796. FT VARIANT 1713 1713 V -> G. {ECO:0000269|PubMed:15365993}. FT /FTId=VAR_007797. FT VARIANT 1715 1715 S -> R (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331}. FT /FTId=VAR_063906. FT VARIANT 1718 1718 W -> C (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070503. FT VARIANT 1720 1720 T -> A (in BC; unknown pathological FT significance; functionally neutral in FT vitro; no effect on in vitro FT phosphorylation by ATR). FT {ECO:0000269|PubMed:11114888, FT ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070504. FT VARIANT 1735 1735 E -> K (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070505. FT VARIANT 1736 1736 V -> A (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070506. FT VARIANT 1738 1738 G -> R (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331}. FT /FTId=VAR_063907. FT VARIANT 1739 1739 D -> G (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070507. FT VARIANT 1739 1739 D -> V (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070508. FT VARIANT 1746 1746 H -> Q (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070509. FT VARIANT 1749 1749 P -> R (in ovarian cancer; unknown FT pathological significance; abolishes FT ACACA binding and strongly reduces BRIP1 FT binding). {ECO:0000269|PubMed:10486320, FT ECO:0000269|PubMed:11301010, FT ECO:0000269|PubMed:15133502}. FT /FTId=VAR_007798. FT VARIANT 1753 1753 R -> T (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070510. FT VARIANT 1764 1764 L -> P (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:17924331, FT ECO:0000269|PubMed:23867111}. FT /FTId=VAR_063908. FT VARIANT 1766 1766 I -> S (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331}. FT /FTId=VAR_063909. FT VARIANT 1767 1767 C -> S (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070511. FT VARIANT 1770 1770 G -> V (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070512. FT VARIANT 1775 1775 M -> K (in BC; strongly reduced FT transcription transactivation; abolishes FT interaction with BRIP1 and RBBP8). FT {ECO:0000269|PubMed:18285836}. FT /FTId=VAR_063212. FT VARIANT 1775 1775 M -> R (in BC; alters protein stability FT and abolishes ACACA and BRIP1 binding). FT {ECO:0000269|PubMed:11301010, FT ECO:0000269|PubMed:12427738, FT ECO:0000269|PubMed:15133502, FT ECO:0000269|PubMed:7545954, FT ECO:0000269|PubMed:7939630}. FT /FTId=VAR_007799. FT VARIANT 1776 1776 P -> S (in ovarian cancer; unknown FT pathological significance; FT dbSNP:rs1800757). FT /FTId=VAR_008764. FT VARIANT 1782 1782 W -> C (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070513. FT VARIANT 1786 1786 L -> P (in BROVCA1; unknown pathological FT significance). FT {ECO:0000269|PubMed:12938098}. FT /FTId=VAR_020704. FT VARIANT 1788 1788 G -> V (in BC; unknown pathological FT significance). FT {ECO:0000269|PubMed:17924331}. FT /FTId=VAR_063910. FT VARIANT 1789 1789 A -> T (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070514. FT VARIANT 1794 1794 E -> D (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070515. FT VARIANT 1804 1804 V -> D (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070516. FT VARIANT 1812 1812 P -> R (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070517. FT VARIANT 1812 1812 P -> S (in ovarian cancer; unknown FT pathological significance; FT dbSNP:rs1800751). FT /FTId=VAR_008765. FT VARIANT 1837 1837 W -> R (in BC; unknown pathological FT significance; functionally impaired in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070518. FT VARIANT 1862 1862 H -> L (in BC; unknown pathological FT significance; functionally neutral in FT vitro). {ECO:0000269|PubMed:23867111}. FT /FTId=VAR_070519. FT MUTAGEN 26 26 I->A: Disrupts the interaction with E2 FT enzymes, thereby abolishing the E3 FT ubiquitin-protein ligase activity. FT {ECO:0000269|PubMed:16818604, FT ECO:0000269|PubMed:20351172}. FT MUTAGEN 26 26 I->E: No ubiquitination of RBBP8. No FT restoration RBBP8-mediated focus FT formation or G2/M checkpoint control upon FT DNA damage. {ECO:0000269|PubMed:16818604, FT ECO:0000269|PubMed:20351172}. FT MUTAGEN 71 71 R->G: No effect on interaction with BAP1. FT {ECO:0000269|PubMed:9528852}. FT MUTAGEN 308 308 S->N: Abolishes phosphorylation by AURKA FT and interferes with cell cycle FT progression from G2 to mitosis. FT {ECO:0000269|PubMed:14990569}. FT MUTAGEN 1143 1143 S->A: Reduces in vitro phosphorylation by FT ATR. {ECO:0000269|PubMed:11114888}. FT MUTAGEN 1239 1239 S->A: No effect on in vitro FT phosphorylation by ATR. FT {ECO:0000269|PubMed:11114888}. FT MUTAGEN 1280 1280 S->A: Reduces in vitro phosphorylation by FT ATR. {ECO:0000269|PubMed:11114888}. FT MUTAGEN 1298 1298 S->A: No effect on in vitro FT phosphorylation by ATR. FT {ECO:0000269|PubMed:11114888}. FT MUTAGEN 1330 1330 S->A: No effect on in vitro FT phosphorylation by ATR. FT {ECO:0000269|PubMed:11114888}. FT MUTAGEN 1387 1387 S->A: Loss of IR-induced S-phase FT checkpoint. Reduces in vitro FT phosphorylation by ATR. FT {ECO:0000269|PubMed:11114888, FT ECO:0000269|PubMed:12183412}. FT MUTAGEN 1394 1394 T->A: Reduces in vitro phosphorylation by FT ATR. {ECO:0000269|PubMed:11114888}. FT MUTAGEN 1423 1423 S->A: Inhibition of the infrared-induced FT G2 arrest. Reduces phosphorylation by FT ATR. {ECO:0000269|PubMed:11114888, FT ECO:0000269|PubMed:12183412}. FT MUTAGEN 1457 1457 S->A: Reduces in vitro phosphorylation by FT ATR. {ECO:0000269|PubMed:11114888}. FT MUTAGEN 1466 1466 S->A: No effect on in vitro FT phosphorylation by ATR. FT {ECO:0000269|PubMed:11114888}. FT MUTAGEN 1524 1524 S->A: No change in infrared S-phase FT delay; when associated with A-1387. No FT effect on in vitro phosphorylation by FT ATR. {ECO:0000269|PubMed:11114888, FT ECO:0000269|PubMed:12183412}. FT MUTAGEN 1655 1655 S->A: Abolishes interaction with BRIP1. FT {ECO:0000269|PubMed:15133502}. FT MUTAGEN 1702 1702 K->M: Abolishes interaction with BRIP1. FT {ECO:0000269|PubMed:15133502}. FT MUTAGEN 1738 1738 G->E: Abolishes interaction with BRIP1. FT {ECO:0000269|PubMed:15133502}. FT MUTAGEN 1755 1755 S->A: No effect on in vitro FT phosphorylation by ATR. FT {ECO:0000269|PubMed:11114888}. FT CONFLICT 89 89 I -> T (in Ref. 4; AAB61673). FT {ECO:0000305}. FT CONFLICT 148 148 Missing (in Ref. 4; AAB61673). FT {ECO:0000305}. FT CONFLICT 253 253 A -> V (in Ref. 3; AAC00049). FT {ECO:0000305}. FT CONFLICT 713 713 S -> P (in Ref. 8; AAI15038). FT {ECO:0000305}. FT CONFLICT 1077 1077 G -> R (in Ref. 4; AAB61673). FT {ECO:0000305}. FT CONFLICT 1426 1426 S -> P (in Ref. 3; AAC00049). FT {ECO:0000305}. FT CONFLICT 1527 1527 E -> G (in Ref. 8; AAI15038). FT {ECO:0000305}. FT HELIX 3 5 {ECO:0000244|PDB:1JM7}. FT HELIX 8 21 {ECO:0000244|PDB:1JM7}. FT STRAND 25 27 {ECO:0000244|PDB:1JM7}. FT HELIX 46 53 {ECO:0000244|PDB:1JM7}. FT STRAND 54 58 {ECO:0000244|PDB:1JM7}. FT TURN 62 64 {ECO:0000244|PDB:1JM7}. FT TURN 70 72 {ECO:0000244|PDB:1JM7}. FT STRAND 78 80 {ECO:0000244|PDB:1JM7}. FT HELIX 81 96 {ECO:0000244|PDB:1JM7}. FT STRAND 1651 1656 {ECO:0000244|PDB:4IGK}. FT HELIX 1659 1671 {ECO:0000244|PDB:4IGK}. FT STRAND 1675 1679 {ECO:0000244|PDB:1T29}. FT STRAND 1686 1689 {ECO:0000244|PDB:4IGK}. FT STRAND 1695 1697 {ECO:0000244|PDB:4IGK}. FT HELIX 1701 1708 {ECO:0000244|PDB:4IGK}. FT STRAND 1712 1715 {ECO:0000244|PDB:4IGK}. FT HELIX 1717 1725 {ECO:0000244|PDB:4IGK}. FT HELIX 1731 1734 {ECO:0000244|PDB:4IGK}. FT TURN 1740 1742 {ECO:0000244|PDB:4IGK}. FT STRAND 1743 1745 {ECO:0000244|PDB:1T29}. FT HELIX 1748 1754 {ECO:0000244|PDB:4IGK}. FT TURN 1755 1757 {ECO:0000244|PDB:1T29}. FT TURN 1760 1763 {ECO:0000244|PDB:4IGK}. FT STRAND 1765 1768 {ECO:0000244|PDB:4IGK}. FT STRAND 1770 1772 {ECO:0000244|PDB:1T2V}. FT STRAND 1773 1775 {ECO:0000244|PDB:4IGK}. FT HELIX 1777 1786 {ECO:0000244|PDB:4IGK}. FT STRAND 1790 1794 {ECO:0000244|PDB:4IGK}. FT HELIX 1795 1797 {ECO:0000244|PDB:4IGK}. FT STRAND 1801 1803 {ECO:0000244|PDB:4IGK}. FT STRAND 1806 1810 {ECO:0000244|PDB:4IGK}. FT HELIX 1812 1814 {ECO:0000244|PDB:4IGK}. FT STRAND 1817 1819 {ECO:0000244|PDB:1OQA}. FT HELIX 1820 1822 {ECO:0000244|PDB:4IGK}. FT HELIX 1824 1827 {ECO:0000244|PDB:4IGK}. FT STRAND 1828 1830 {ECO:0000244|PDB:3PXE}. FT STRAND 1832 1834 {ECO:0000244|PDB:4IGK}. FT HELIX 1835 1844 {ECO:0000244|PDB:4IGK}. FT HELIX 1851 1853 {ECO:0000244|PDB:4IGK}. SQ SEQUENCE 1863 AA; 207721 MW; 89C6D83FF56312AF CRC64; MDLSALRVEE VQNVINAMQK ILECPICLEL IKEPVSTKCD HIFCKFCMLK LLNQKKGPSQ CPLCKNDITK RSLQESTRFS QLVEELLKII CAFQLDTGLE YANSYNFAKK ENNSPEHLKD EVSIIQSMGY RNRAKRLLQS EPENPSLQET SLSVQLSNLG TVRTLRTKQR IQPQKTSVYI ELGSDSSEDT VNKATYCSVG DQELLQITPQ GTRDEISLDS AKKAACEFSE TDVTNTEHHQ PSNNDLNTTE KRAAERHPEK YQGSSVSNLH VEPCGTNTHA SSLQHENSSL LLTKDRMNVE KAEFCNKSKQ PGLARSQHNR WAGSKETCND RRTPSTEKKV DLNADPLCER KEWNKQKLPC SENPRDTEDV PWITLNSSIQ KVNEWFSRSD ELLGSDDSHD GESESNAKVA DVLDVLNEVD EYSGSSEKID LLASDPHEAL ICKSERVHSK SVESNIEDKI FGKTYRKKAS LPNLSHVTEN LIIGAFVTEP QIIQERPLTN KLKRKRRPTS GLHPEDFIKK ADLAVQKTPE MINQGTNQTE QNGQVMNITN SGHENKTKGD SIQNEKNPNP IESLEKESAF KTKAEPISSS ISNMELELNI HNSKAPKKNR LRRKSSTRHI HALELVVSRN LSPPNCTELQ IDSCSSSEEI KKKKYNQMPV RHSRNLQLME GKEPATGAKK SNKPNEQTSK RHDSDTFPEL KLTNAPGSFT KCSNTSELKE FVNPSLPREE KEEKLETVKV SNNAEDPKDL MLSGERVLQT ERSVESSSIS LVPGTDYGTQ ESISLLEVST LGKAKTEPNK CVSQCAAFEN PKGLIHGCSK DNRNDTEGFK YPLGHEVNHS RETSIEMEES ELDAQYLQNT FKVSKRQSFA PFSNPGNAEE ECATFSAHSG SLKKQSPKVT FECEQKEENQ GKNESNIKPV QTVNITAGFP VVGQKDKPVD NAKCSIKGGS RFCLSSQFRG NETGLITPNK HGLLQNPYRI PPLFPIKSFV KTKCKKNLLE ENFEEHSMSP EREMGNENIP STVSTISRNN IRENVFKEAS SSNINEVGSS TNEVGSSINE IGSSDENIQA ELGRNRGPKL NAMLRLGVLQ PEVYKQSLPG SNCKHPEIKK QEYEEVVQTV NTDFSPYLIS DNLEQPMGSS HASQVCSETP DDLLDDGEIK EDTSFAENDI KESSAVFSKS VQKGELSRSP SPFTHTHLAQ GYRRGAKKLE SSEENLSSED EELPCFQHLL FGKVNNIPSQ STRHSTVATE CLSKNTEENL LSLKNSLNDC SNQVILAKAS QEHHLSEETK CSASLFSSQC SELEDLTANT NTQDPFLIGS SKQMRHQSES QGVGLSDKEL VSDDEERGTG LEENNQEEQS MDSNLGEAAS GCESETSVSE DCSGLSSQSD ILTTQQRDTM QHNLIKLQQE MAELEAVLEQ HGSQPSNSYP SIISDSSALE DLRNPEQSTS EKAVLTSQKS SEYPISQNPE GLSADKFEVS ADSSTSKNKE PGVERSSPSK CPSLDDRWYM HSCSGSLQNR NYPSQEELIK VVDVEEQQLE ESGPHDLTET SYLPRQDLEG TPYLESGISL FSDDPESDPS EDRAPESARV GNIPSSTSAL KVPQLKVAES AQSPAAAHTT DTAGYNAMEE SVSREKPELT ASTERVNKRM SMVVSGLTPE EFMLVYKFAR KHHITLTNLI TEETTHVVMK TDAEFVCERT LKYFLGIAGG KWVVSYFWVT QSIKERKMLN EHDFEVRGDV VNGRNHQGPK RARESQDRKI FRGLEICCYG PFTNMPTDQL EWMVQLCGAS VVKELSSFTL GTGVHPIVVV QPDAWTEDNG FHAIGQMCEA PVVTREWVLD SVALYQCQEL DTYLIPQIPH SHY // ID CBX4_HUMAN Reviewed; 560 AA. AC O00257; B1PJR7; Q6TPI8; Q96C04; DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot. DT 28-JUL-2009, sequence version 3. DT 11-NOV-2015, entry version 153. DE RecName: Full=E3 SUMO-protein ligase CBX4; DE EC=6.3.2.-; DE AltName: Full=Chromobox protein homolog 4; DE AltName: Full=Polycomb 2 homolog; DE Short=Pc2; DE Short=hPc2; GN Name=CBX4; 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=Fetal brain; RX PubMed=9315667; RA Satijn D.P.E., Olson D.J., van der Vlag J., Hamer K.M., Lambrechts C., RA Masselink H., Gunster M.J., Sewalt R.G.A.B., van Driel R., Otte A.P.; RT "Interference with the expression of a novel human polycomb protein, RT hPc2, results in cellular transformation and apoptosis."; RL Mol. Cell. Biol. 17:6076-6086(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND SUBCELLULAR LOCATION. RX PubMed=19266028; DOI=10.1371/journal.pgen.1000397; RA Salichs E., Ledda A., Mularoni L., Alba M.M., de la Luna S.; RT "Genome-wide analysis of histidine repeats reveals their role in the RT localization of human proteins to the nuclear speckles compartment."; RL PLoS Genet. 5:E1000397-E1000397(2009). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Liu M., Cheng J., Wang L.; RT "Cloning and identification of NS5ATP1-binding protein 16."; RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases. RN [4] 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 457-560 (ISOFORM 1). RX PubMed=9199346; RA Satijn D.P.E., Gunster M.J., van der Vlag J., Hamer K.M., Schul W., RA Alkema M.J., Saurin A.J., Freemont P.S., van Driel R., Otte A.P.; RT "RING1 is associated with the polycomb group protein complex and acts RT as a transcriptional repressor."; RL Mol. Cell. Biol. 17:4105-4113(1997). RN [7] RP INTERACTION WITH SUV39H1. RX PubMed=12101246; DOI=10.1128/MCB.22.15.5539-5553.2002; RA Sewalt R.G.A.B., Lachner M., Vargas M., Hamer K.M., den Blaauwen J.L., RA Hendrix T., Melcher M., Schweizer D., Jenuwein T., Otte A.P.; RT "Selective interactions between vertebrate polycomb homologs and the RT SUV39H1 histone lysine methyltransferase suggest that histone H3-K9 RT methylation contributes to chromosomal targeting of Polycomb group RT proteins."; RL Mol. Cell. Biol. 22:5539-5553(2002). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN A PRC1-LIKE RP HPRC-H COMPLEX WITH BMI1; CBX2; CBX8; PHC1; PHC2; PHC3; RING1 AND RP RNF2. RX PubMed=12167701; DOI=10.1128/MCB.22.17.6070-6078.2002; RA Levine S.S., Weiss A., Erdjument-Bromage H., Shao Z., Tempst P., RA Kingston R.E.; RT "The core of the polycomb repressive complex is compositionally and RT functionally conserved in flies and humans."; RL Mol. Cell. Biol. 22:6070-6078(2002). RN [9] RP FUNCTION, SUMOYLATION, 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 [10] RP SUMOYLATION AT LYS-494. RX PubMed=15592428; DOI=10.1038/sj.emboj.7600506; RA Kagey M.H., Melhuish T.A., Powers S.E., Wotton D.; RT "Multiple activities contribute to Pc2 E3 function."; RL EMBO J. 24:108-119(2005). RN [11] RP FUNCTION. 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 [12] RP FUNCTION, INTERACTION WITH HIPK2, SUMOYLATION, SUBCELLULAR LOCATION, RP AND PHOSPHORYLATION AT THR-497. RX PubMed=17018294; DOI=10.1016/j.molcel.2006.08.004; RA Roscic A., Moeller A., Calzado M.A., Renner F., Wimmer V.C., RA Gresko E., Luedi K.S., Schmitz M.L.; RT "Phosphorylation-dependent control of Pc2 SUMO E3 ligase activity by RT its substrate protein HIPK2."; RL Mol. Cell 24:77-89(2006). 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 IDENTIFICATION IN A PRC1-LIKE COMPLEX. RX PubMed=19636380; DOI=10.1371/journal.pone.0006380; RA Maertens G.N., El Messaoudi-Aubert S., Racek T., Stock J.K., RA Nicholls J., Rodriguez-Niedenfuhr M., Gil J., Peters G.; RT "Several distinct polycomb complexes regulate and co-localize on the RT INK4a tumor suppressor locus."; RL PLoS ONE 4:E6380-E6380(2009). RN [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-149, 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 [16] RP FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY (ISOFORM 2), RP IDENTIFICATION IN A PRC1-LIKE COMPLEX, SELF-ASSOCIATION, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF SER-434. RX PubMed=21282530; DOI=10.1074/mcp.M110.002642; RA Vandamme J., Volkel P., Rosnoblet C., Le Faou P., Angrand P.O.; RT "Interaction proteomics analysis of polycomb proteins defines distinct RT PRC1 Complexes in mammalian cells."; RL Mol. Cell. Proteomics 0:0-0(2011). RN [17] RP FUNCTION IN ZNF131 SUMOYLATION, SUBCELLULAR LOCATION, AND MUTAGENESIS RP OF LYS-494 AND THR-497. RX PubMed=22467880; DOI=10.1074/jbc.M111.336354; RA Oh Y., Chung K.C.; RT "Small ubiquitin-like modifier (SUMO) modification of zinc finger RT protein 131 potentiates its negative effect on estrogen signaling."; RL J. Biol. Chem. 287:17517-17529(2012). RN [18] RP FUNCTION. RX PubMed=22825850; DOI=10.1074/jbc.M112.390120; RA Pelisch F., Pozzi B., Risso G., Munoz M.J., Srebrow A.; RT "DNA damage-induced heterogeneous nuclear ribonucleoprotein K RT SUMOylation regulates p53 transcriptional activation."; RL J. Biol. Chem. 287:30789-30799(2012). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-467, 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 [20] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-106; LYS-114; LYS-149; RP LYS-205; LYS-212 AND LYS-280, AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [21] RP STRUCTURE BY NMR OF 8-65. RG Structural genomics consortium (SGC); RT "Solution NMR structure of the chromo domain of the chromobox protein RT homolog 4."; RL Submitted (FEB-2009) to the PDB data bank. RN [22] RP X-RAY CRYSTALLOGRAPHY (1.51 ANGSTROMS) OF 8-62. RG Structural genomics consortium (SGC); RT "Crystal structure of human chromobox homolog 4 (cbx4)."; RL Submitted (SEP-2009) to the PDB data bank. CC -!- FUNCTION: E3 SUMO-protein ligase which facilitates SUMO1 CC conjugation by UBE2I. Involved in the sumoylation of HNRNPK, a CC p53/TP53 transcriptional coactivator, hence indirectly regulates CC p53/TP53 transcriptional activation resulting in p21/CDKN1A CC expression. Monosumoylates ZNF131. CC -!- FUNCTION: Component of a Polycomb group (PcG) multiprotein PRC1- CC like complex, a complex class required to maintain the CC transcriptionally repressive state of many genes, including Hox CC genes, throughout development. PcG PRC1 complex acts via chromatin CC remodeling and modification of histones; it mediates CC monoubiquitination of histone H2A 'Lys-119', rendering chromatin CC heritably changed in its expressibility. CC -!- PATHWAY: Protein modification; protein sumoylation. CC -!- SUBUNIT: Interacts with histone H3-K9Me3. Interacts with CHTOP (By CC similarity). Component of a PRC1-like complex. Self-associates. CC Interacts with SUV39H1 and HIPK2. Interacts with CSNK2B. CC {ECO:0000250, ECO:0000269|PubMed:12101246, CC ECO:0000269|PubMed:12167701, ECO:0000269|PubMed:17018294, CC ECO:0000269|PubMed:19636380, ECO:0000269|PubMed:21282530}. CC -!- INTERACTION: CC P35226:BMI1; NbExp=4; IntAct=EBI-722425, EBI-2341576; CC P68400:CSNK2A1; NbExp=2; IntAct=EBI-4392727, EBI-347804; CC P67870:CSNK2B; NbExp=2; IntAct=EBI-4392727, EBI-348169; CC Q16665:HIF1A; NbExp=15; IntAct=EBI-722425, EBI-447269; CC Q9BYE7:PCGF6; NbExp=2; IntAct=EBI-4392727, EBI-1048026; CC Q99496:RNF2; NbExp=2; IntAct=EBI-4392727, EBI-722416; CC P31946:YWHAB; NbExp=2; IntAct=EBI-722425, EBI-359815; CC P62258:YWHAE; NbExp=2; IntAct=EBI-4392727, EBI-356498; CC P63104:YWHAZ; NbExp=2; IntAct=EBI-4392727, EBI-347088; CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus speckle. Note=Localization CC to nuclear polycomb bodies is required for ZNF131 sumoylation. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O00257-1; Sequence=Displayed; CC Name=2; CC IsoId=O00257-3; Sequence=VSP_041599; CC -!- TISSUE SPECIFICITY: Ubiquitous. CC -!- DOMAIN: The polyhistidine repeat may act as a targeting signal to CC nuclear speckles. {ECO:0000269|PubMed:19266028}. CC -!- PTM: Phosphorylated on Thr-497 by HIPK2 upon DNA damage. This CC phosphorylation stimulates E3 SUMO-protein ligase activity and CC promotes sumoylation on Lys-494, as well as sumoylation of other CC target proteins, such as HNRNPK. {ECO:0000269|PubMed:12679040, CC ECO:0000269|PubMed:15592428, ECO:0000269|PubMed:17018294}. CC -!- MISCELLANEOUS: The human orthologs of the Drosophila Polycomb CC group protein Pc are CBX2, CBX4, CBX6, CBX7 and CBX8. These show CC distinct nuclear localizations, contribute differently to CC transcriptional repression, and appear to be part of distinct CC PRC1-like protein complexes. The hPRC-H complex purified in CC PubMed:12167701 probably presents a mixture of different complexes CC containing different Polycomb group proteins. CC -!- SIMILARITY: Contains 1 chromo domain. {ECO:0000255|PROSITE- CC ProRule:PRU00053}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH14967.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; 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; AF013956; AAB80718.1; -; mRNA. DR EMBL; EU439707; ACA49234.1; -; mRNA. DR EMBL; AY390430; AAQ97596.1; -; mRNA. DR EMBL; AC100791; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC014967; AAH14967.1; ALT_SEQ; mRNA. DR EMBL; U94344; AAB62734.1; -; mRNA. DR CCDS; CCDS32758.1; -. [O00257-1] DR RefSeq; NP_003646.2; NM_003655.2. [O00257-1] DR UniGene; Hs.405046; -. DR PDB; 2K28; NMR; -; A=8-65. DR PDB; 3I8Z; X-ray; 1.51 A; A=8-62. DR PDBsum; 2K28; -. DR PDBsum; 3I8Z; -. DR ProteinModelPortal; O00257; -. DR SMR; O00257; 11-60. DR BioGrid; 114105; 75. DR DIP; DIP-42042N; -. DR IntAct; O00257; 47. DR MINT; MINT-1196265; -. DR STRING; 9606.ENSP00000269397; -. DR BindingDB; O00257; -. DR ChEMBL; CHEMBL3232685; -. DR PhosphoSite; O00257; -. DR BioMuta; CBX4; -. DR MaxQB; O00257; -. DR PaxDb; O00257; -. DR PRIDE; O00257; -. DR Ensembl; ENST00000269397; ENSP00000269397; ENSG00000141582. [O00257-1] DR GeneID; 8535; -. DR KEGG; hsa:8535; -. DR UCSC; uc002jxe.3; human. [O00257-1] DR CTD; 8535; -. DR GeneCards; CBX4; -. DR H-InvDB; HIX0014237; -. DR HGNC; HGNC:1554; CBX4. DR HPA; HPA008228; -. DR MIM; 603079; gene. DR neXtProt; NX_O00257; -. DR PharmGKB; PA26129; -. DR eggNOG; ENOG410IPQ6; Eukaryota. DR eggNOG; ENOG410ZQCR; LUCA. DR GeneTree; ENSGT00530000063056; -. DR HOGENOM; HOG000206923; -. DR HOVERGEN; HBG005257; -. DR InParanoid; O00257; -. DR KO; K11452; -. DR OMA; HHHHAVD; -. DR OrthoDB; EOG7PCJGP; -. DR PhylomeDB; O00257; -. DR TreeFam; TF106456; -. DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence. DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins. DR UniPathway; UPA00886; -. DR ChiTaRS; CBX4; human. DR EvolutionaryTrace; O00257; -. DR GenomeRNAi; 8535; -. DR NextBio; 31968; -. DR PRO; PR:O00257; -. DR Proteomes; UP000005640; Chromosome 17. DR Bgee; O00257; -. DR CleanEx; HS_CBX4; -. DR ExpressionAtlas; O00257; baseline and differential. DR Genevisible; O00257; HS. DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0031519; C:PcG protein complex; IDA:UniProtKB. DR GO; GO:0035102; C:PRC1 complex; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW. DR GO; GO:0003727; F:single-stranded RNA binding; IEA:Ensembl. DR GO; GO:0032183; F:SUMO binding; IDA:MGI. DR GO; GO:0019789; F:SUMO transferase activity; EXP:Reactome. DR GO; GO:0003714; F:transcription corepressor activity; TAS:ProtInc. DR GO; GO:0044212; F:transcription regulatory region DNA binding; IEA:Ensembl. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0016568; P:chromatin modification; IEA:UniProtKB-KW. DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0043687; P:post-translational protein modification; TAS:Reactome. DR GO; GO:0016925; P:protein sumoylation; TAS:Reactome. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR InterPro; IPR000953; Chromo/shadow_dom. DR InterPro; IPR017984; Chromo_dom_subgr. DR InterPro; IPR023780; Chromo_domain. DR InterPro; IPR016197; Chromodomain-like. DR InterPro; IPR023779; Chromodomain_CS. DR Pfam; PF00385; Chromo; 1. DR PRINTS; PR00504; CHROMODOMAIN. DR SMART; SM00298; CHROMO; 1. DR SUPFAM; SSF54160; SSF54160; 1. DR PROSITE; PS00598; CHROMO_1; 1. DR PROSITE; PS50013; CHROMO_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Chromatin regulator; KW Complete proteome; Isopeptide bond; Ligase; Nucleus; Phosphoprotein; KW Reference proteome; Repressor; Transcription; KW Transcription regulation; Ubl conjugation; Ubl conjugation pathway. FT CHAIN 1 560 E3 SUMO-protein ligase CBX4. FT /FTId=PRO_0000080206. FT DOMAIN 11 69 Chromo. {ECO:0000255|PROSITE- FT ProRule:PRU00053}. FT REGION 1 539 Interaction with BMI1. FT REGION 540 560 Interaction with RNF2. FT COMPBIAS 378 400 His-rich. FT COMPBIAS 389 400 Poly-His. FT COMPBIAS 499 510 Poly-Ala. FT MOD_RES 149 149 N6-acetyllysine; alternate. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 467 467 Phosphoserine. FT {ECO:0000244|PubMed:24275569}. FT MOD_RES 497 497 Phosphothreonine; by HIPK2. FT {ECO:0000269|PubMed:17018294}. FT CROSSLNK 106 106 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 114 114 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 149 149 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2); FT alternate. {ECO:0000244|PubMed:25218447}. FT CROSSLNK 205 205 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 212 212 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 280 280 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT CROSSLNK 494 494 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO). FT VAR_SEQ 127 396 Missing (in isoform 2). FT {ECO:0000303|Ref.3}. FT /FTId=VSP_041599. FT MUTAGEN 434 434 S->A: Abolishes interaction with YWHAZ FT and YWHAE; impairs interaction with PCGF6 FT and BMI1; no effect on interaction with FT RNF2. {ECO:0000269|PubMed:21282530}. FT MUTAGEN 494 494 K->R: No effect on ZNF131 sumoylation. FT {ECO:0000269|PubMed:22467880}. FT MUTAGEN 497 497 T->A: Small decrease in ZNF131 FT sumoylation. FT {ECO:0000269|PubMed:22467880}. FT CONFLICT 137 138 Missing (in Ref. 1; AAB80718). FT {ECO:0000305}. FT CONFLICT 142 142 P -> R (in Ref. 1; AAB80718). FT {ECO:0000305}. FT CONFLICT 458 458 P -> R (in Ref. 1; AAB80718 and 5; FT AAB62734). {ECO:0000305}. FT CONFLICT 477 477 C -> S (in Ref. 1; AAB80718 and 5; FT AAB62734). {ECO:0000305}. FT CONFLICT 480 480 T -> S (in Ref. 1; AAB80718 and 5; FT AAB62734). {ECO:0000305}. FT CONFLICT 505 505 V -> VAA (in Ref. 3; ACA49234). FT {ECO:0000305}. FT STRAND 13 22 {ECO:0000244|PDB:3I8Z}. FT STRAND 25 32 {ECO:0000244|PDB:3I8Z}. FT HELIX 37 39 {ECO:0000244|PDB:3I8Z}. FT STRAND 41 44 {ECO:0000244|PDB:3I8Z}. FT HELIX 45 48 {ECO:0000244|PDB:3I8Z}. FT HELIX 51 53 {ECO:0000244|PDB:3I8Z}. SQ SEQUENCE 560 AA; 61368 MW; DF5C8C4C0CCB1F31 CRC64; MELPAVGEHV FAVESIEKKR IRKGRVEYLV KWRGWSPKYN TWEPEENILD PRLLIAFQNR ERQEQLMGYR KRGPKPKPLV VQVPTFARRS NVLTGLQDSS TDNRAKLDLG AQGKGQGHQY ELNSKKHHQY QPHSKERAGK PPPPGKSGKY YYQLNSKKHH PYQPDPKMYD LQYQGGHKEA PSPTCPDLGA KSHPPDKWAQ GAGAKGYLGA VKPLAGAAGA PGKGSEKGPP NGMMPAPKEA VTGNGIGGKM KIVKNKNKNG RIVIVMSKYM ENGMQAVKIK SGEVAEGEAR SPSHKKRAAD ERHPPADRTF KKAAGAEEKK VEAPPKRREE EVSGVSDPQP QDAGSRKLSP TKEAFGEQPL QLTTKPDLLA WDPARNTHPP SHHPHPHPHH HHHHHHHHHH AVGLNLSHVR KRCLSETHGE REPCKKRLTA RSISTPTCLG GSPAAERPAD LPPAAALPQP EVILLDSDLD EPIDLRCVKT RSEAGEPPSS LQVKPETPAS AAVAVAAAAA PTTTAEKPPA EAQDEPAESL SEFKPFFGNI IITDVTANCL TVTFKEYVTV // 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 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 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 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 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 HDAC2_HUMAN Reviewed; 488 AA. AC Q92769; B3KRS5; B4DL58; E1P561; Q5SRI8; Q5SZ86; Q8NEH4; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 21-JUN-2005, sequence version 2. DT 11-NOV-2015, entry version 177. DE RecName: Full=Histone deacetylase 2; DE Short=HD2; DE EC=3.5.1.98; GN Name=HDAC2; 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 CYS-230. RC TISSUE=Mammary gland; RX PubMed=8917507; DOI=10.1073/pnas.93.23.12845; RA Yang W.-M., Inouye C.J., Zeng Y., Bearss D., Seto E.; RT "Transcriptional repression by YY1 is mediated by interaction with a RT mammalian homolog of the yeast global regulator RPD3."; RL Proc. Natl. Acad. Sci. U.S.A. 93:12845-12850(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). 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 [3] 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 [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 1), AND VARIANT RP HIS-315. 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 [6] RP INTERACTION WITH ATR, AND IDENTIFICATION IN A COMPLEX CONTAINING ATR RP AND CHD4. RX PubMed=10545197; DOI=10.1021/bi991614n; RA Schmidt D.R., Schreiber S.L.; RT "Molecular association between ATR and two components of the RT nucleosome remodeling and deacetylating complex, HDAC2 and CHD4."; RL Biochemistry 38:14711-14717(1999). RN [7] RP INTERACTION WITH SNW1. RX PubMed=10644367; DOI=10.1128/JVI.74.4.1939-1947.2000; RA Zhou S., Fujimuro M., Hsieh J.J., Chen L., Hayward S.D.; RT "A role for SKIP in EBNA2 activation of CBF1-repressed promoters."; RL J. Virol. 74:1939-1947(2000). RN [8] RP INTERACTION WITH DNMT1 AND DMAP1. RX PubMed=10888872; DOI=10.1038/77023; RA Rountree M.R., Bachman K.E., Baylin S.B.; RT "DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at RT replication foci."; RL Nat. Genet. 25:269-277(2000). RN [9] 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 [10] 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 [11] 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 [12] RP INTERACTION WITH HDAC10. RX PubMed=11739383; DOI=10.1074/jbc.M108055200; RA Fischer D.D., Cai R., Bhatia U., Asselbergs F.A.M., Song C., Terry R., RA Trogani N., Widmer R., Atadja P., Cohen D.; RT "Isolation and characterization of a novel class II histone RT deacetylase, HDAC10."; RL J. Biol. Chem. 277:6656-6666(2002). RN [13] RP INTERACTION WITH SP3. RX PubMed=12176973; DOI=10.1074/jbc.C200378200; RA Sun J.M., Chen H.Y., Moniwa M., Litchfield D.W., Seto E., Davie J.R.; RT "The transcriptional repressor Sp3 is associated with CK2- RT phosphorylated histone deacetylase 2."; RL J. Biol. Chem. 277:35783-35786(2002). RN [14] RP INTERACTION WITH DAXX AND DEK. RX PubMed=12140263; RA Hollenbach A.D., McPherson C.J., Mientjes E.J., Iyengar R., RA Grosveld G.; RT "Daxx and histone deacetylase II associate with chromatin through an RT interaction with core histones and the chromatin-associated protein RT Dek."; RL J. Cell Sci. 115:3319-3330(2002). RN [15] RP INTERACTION WITH BCL6. RX PubMed=12402037; DOI=10.1038/ng1018; RA Bereshchenko O.R., Gu W., Dalla-Favera R.; RT "Acetylation inactivates the transcriptional repressor BCL6."; RL Nat. Genet. 32:606-613(2002). RN [16] 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 [17] 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 [18] RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE BHC RP COMPLEX WITH PHF21A; HDAC1; 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 [19] 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 [20] RP INTERACTION WITH PELP1. RX PubMed=15456770; DOI=10.1074/jbc.M406831200; RA Choi Y.B., Ko J.K., Shin J.; RT "The transcriptional corepressor, PELP1, recruits HDAC2 and masks RT histones using two separate domains."; RL J. Biol. Chem. 279:50930-50941(2004). RN [21] 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 [22] RP INTERACTION WITH JMJD2A. 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 [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-422 AND RP SER-424, 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 [24] 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 [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394, 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 [26] RP IDENTIFICATION IN A COMPLEX WITH CDYL; MIER1; MIER2 AND HDAC1. 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 [27] RP INTERACTION WITH BCL6. 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 [28] 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 [29] RP INTERACTION WITH FAM64A. RX PubMed=18757745; DOI=10.1073/pnas.0709227105; RA Zhao W.M., Coppinger J.A., Seki A., Cheng X.L., Yates J.R. III, RA Fang G.; RT "RCS1, a substrate of APC/C, controls the metaphase to anaphase RT transition."; RL Proc. Natl. Acad. Sci. U.S.A. 105:13415-13420(2008). RN [30] 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 [31] RP FUNCTION, AND INTERACTION WITH 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 [32] RP INTERACTION WITH CHFR. 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 [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394 AND SER-422, 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 [34] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-422 AND RP SER-424, 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 [35] 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 [36] RP FUNCTION, AND 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 [37] RP INTERACTION WITH BEND3. RX PubMed=21914818; DOI=10.1242/jcs.086603; RA Sathyan K.M., Shen Z., Tripathi V., Prasanth K.V., Prasanth S.G.; RT "A BEN-domain-containing protein associates with heterochromatin and RT represses transcription."; RL J. Cell Sci. 124:3149-3163(2011). RN [38] 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 [39] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-422 AND RP SER-424, 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 [40] RP INTERACTION WITH NACC2. RX PubMed=22926524; DOI=10.1038/onc.2012.386; RA Xuan C., Wang Q., Han X., Duan Y., Li L., Shi L., Wang Y., Shan L., RA Yao Z., Shang Y.; RT "RBB, a novel transcription repressor, represses the transcription of RT HDM2 oncogene."; RL Oncogene 32:3711-3721(2013). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394; SER-422 AND RP SER-424, 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 [42] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-462, 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 [43] RP SUBCELLULAR LOCATION, AND INTERACTION WITH MTA1. RX PubMed=24970816; RA Liu J., Xu D., Wang H., Zhang Y., Chang Y., Zhang J., Wang J., Li C., RA Liu H., Zhao M., Lin C., Zhan Q., Huang C., Qian H.; RT "The subcellular distribution and function of MTA1 in cancer RT differentiation."; RL Oncotarget 5:5153-5164(2014). RN [44] RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 9-374 IN COMPLEX WITH RP SUBSTITUTED N-(2-AMINOPHENYL)BENZAMIDE INHIBITORS. RX PubMed=20392638; DOI=10.1016/j.bmcl.2010.03.091; RA Bressi J.C., Jennings A.J., Skene R., Wu Y., Melkus R., De Jong R., RA O'Connell S., Grimshaw C.E., Navre M., Gangloff A.R.; RT "Exploration of the HDAC2 foot pocket: Synthesis and SAR of RT substituted N-(2-aminophenyl)benzamides."; RL Bioorg. Med. Chem. Lett. 20:3142-3145(2010). 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. Forms CC transcriptional repressor complexes by associating with MAD, SIN3, CC YY1 and N-COR. Interacts in the late S-phase of DNA-replication CC with DNMT1 in the other transcriptional repressor complex composed CC of DNMT1, DMAP1, PCNA, CAF1. Deacetylates TSHZ3 and regulates its CC transcriptional repressor 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. May be involved in the CC transcriptional repression of circadian target genes, such as CC PER1, mediated by CRY1 through histone deacetylation. Involved in CC MTA1-mediated transcriptional corepression of TFF1 and CDKN1A. CC {ECO:0000269|PubMed:19343227, ECO:0000269|PubMed:21965678}. 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, MBD3, MTA1L1, CHD3 and CHD4 to form the CC nucleosome remodeling and histone deacetylation (NuRD) complex, or CC with SIN3, SAP18 and SAP30 to form the SIN3 HDAC complex. CC Component of a RCOR/GFI/KDM1A/HDAC complex. Interacts directly CC with GFI1 and GFI1B. Interacts with SNW1, HDAC7, PRDM6, SAP30, CC SETDB1 and SUV39H1. Interacts with the H2AFY (via the non-histone CC region). Component of a BHC histone deacetylase complex that CC contains HDAC1, HDAC2, HMG20B, KDM1A, RCOR1 and PHF21A. The BHC CC complex may also contain ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. CC Part of a complex containing the core histones H2A, H2B, H3 and CC H4, DEK and unphosphorylated DAXX. Part of a complex containing CC ATR and CHD4. Forms a heterologous complex at least with YY1. CC Interacts with ATR, CBFA2T3, DNMT1, MINT, HDAC10, HCFC1, NRIP1, CC KDM4A and PELP1. Component of a mSin3A corepressor complex that CC contains SIN3A, SAP130, SUDS3, ARID4B, HDAC1 and HDAC2. Interacts CC with CHFR and SAP30L. Interacts (CK2 phosphorylated form) with CC SP3. Interacts with TSHZ3 (via its N-terminus). Interacts with CC APEX1; the interaction is not dependent on the acetylated status CC of APEX1. Part of a complex composed of TRIM28, HDAC1, HDAC2 and CC EHMT2. Interacts with FAM64A. Interacts with BCL6 (non-acetylated CC form). Part of a complex containing at least CDYL, MIER1, MIER2, CC HDAC1 and HDAC2. Interacts with CRY1, INSM1 and ZNF431. Interacts CC with NACC2. Interacts with MTA1, with a preference for sumoylated CC MTA1. Interacts with SIX3 (By similarity). Interacts with BEND3. CC {ECO:0000250|UniProtKB:P70288, ECO:0000269|PubMed:10545197, CC ECO:0000269|PubMed:10644367, ECO:0000269|PubMed:10888872, CC ECO:0000269|PubMed:11331609, ECO:0000269|PubMed:11533236, CC ECO:0000269|PubMed:11739383, ECO:0000269|PubMed:12140263, CC ECO:0000269|PubMed:12176973, ECO:0000269|PubMed:12402037, CC ECO:0000269|PubMed:12493763, ECO:0000269|PubMed:12670868, CC ECO:0000269|PubMed:12724404, ECO:0000269|PubMed:14633989, CC ECO:0000269|PubMed:15060175, ECO:0000269|PubMed:15456770, CC ECO:0000269|PubMed:15927959, ECO:0000269|PubMed:16820529, CC ECO:0000269|PubMed:18212045, ECO:0000269|PubMed:18757745, CC ECO:0000269|PubMed:19061646, ECO:0000269|PubMed:19182791, CC ECO:0000269|PubMed:19343227, ECO:0000269|PubMed:20392638, CC ECO:0000269|PubMed:21549307, ECO:0000269|PubMed:21914818, CC ECO:0000269|PubMed:21965678, ECO:0000269|PubMed:22926524, CC ECO:0000269|PubMed:24970816}. CC -!- INTERACTION: CC Q9C0K0:BCL11B; NbExp=3; IntAct=EBI-301821, EBI-6597578; CC Q9HCU9:BRMS1; NbExp=4; IntAct=EBI-301821, EBI-714781; CC Q9UER7:DAXX; NbExp=2; IntAct=EBI-301821, EBI-77321; CC P51610:HCFC1; NbExp=2; IntAct=EBI-301821, EBI-396176; CC Q13547:HDAC1; NbExp=10; IntAct=EBI-301821, EBI-301834; CC Q2HR82:K8 (xeno); NbExp=7; IntAct=EBI-301821, EBI-9006943; CC Q9UIS9:MBD1; NbExp=2; IntAct=EBI-301821, EBI-867196; CC Q13330:MTA1; NbExp=4; IntAct=EBI-301821, EBI-714236; CC P01106:MYC; NbExp=2; IntAct=EBI-301821, EBI-447544; CC P06748:NPM1; NbExp=2; IntAct=EBI-301821, EBI-78579; CC P48382:RFX5; NbExp=4; IntAct=EBI-301821, EBI-923266; CC Q96ST3:SIN3A; NbExp=5; IntAct=EBI-301821, EBI-347218; CC O95863:SNAI1; NbExp=2; IntAct=EBI-301821, EBI-1045459; CC Q9HD15:SRA1; NbExp=2; IntAct=EBI-301821, EBI-727136; CC O43463:SUV39H1; NbExp=3; IntAct=EBI-301821, EBI-349968; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:24970816}. CC Cytoplasm {ECO:0000269|PubMed:24970816}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q92769-1; Sequence=Displayed; CC Name=2; CC IsoId=Q92769-3; Sequence=VSP_056175; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Widely expressed; lower levels in brain and CC lung. CC -!- PTM: S-nitrosylated by GAPDH. In neurons, S-Nitrosylation at Cys- CC 262 and Cys-274 does not affect the enzyme activity but abolishes CC chromatin-binding, leading to increases acetylation of histones CC and activate genes that are associated with neuronal development. CC In embryonic cortical neurons, S-Nitrosylation regulates dendritic CC growth and branching. S-Nitrosylation interferes with its CC interaction with MTA1 (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 1 CC subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH31055.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=BAG59420.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/HDAC2ID40803ch6q22.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; U31814; AAC50814.1; -; mRNA. DR EMBL; AK092156; BAG52487.1; -; mRNA. DR EMBL; AK296856; BAG59420.1; ALT_INIT; mRNA. DR EMBL; AL590398; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL671967; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; FO393415; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW48252.1; -; Genomic_DNA. DR EMBL; CH471051; EAW48253.1; -; Genomic_DNA. DR EMBL; CH471051; EAW48254.1; -; Genomic_DNA. DR EMBL; CH471051; EAW48255.1; -; Genomic_DNA. DR EMBL; BC031055; AAH31055.2; ALT_INIT; mRNA. DR CCDS; CCDS43493.2; -. [Q92769-1] DR RefSeq; NP_001518.3; NM_001527.3. [Q92769-1] DR RefSeq; XP_011534090.1; XM_011535788.1. [Q92769-3] DR UniGene; Hs.3352; -. DR PDB; 3MAX; X-ray; 2.05 A; A/B/C=9-374. DR PDB; 4LXZ; X-ray; 1.85 A; A/B/C=8-376. DR PDB; 4LY1; X-ray; 1.57 A; A/B/C=8-376. DR PDBsum; 3MAX; -. DR PDBsum; 4LXZ; -. DR PDBsum; 4LY1; -. DR ProteinModelPortal; Q92769; -. DR SMR; Q92769; 9-376. DR BioGrid; 109316; 293. DR DIP; DIP-24220N; -. DR IntAct; Q92769; 112. DR MINT; MINT-90593; -. DR STRING; 9606.ENSP00000430432; -. DR BindingDB; Q92769; -. DR ChEMBL; CHEMBL2093865; -. DR DrugBank; DB01223; Aminophylline. DR DrugBank; DB00227; Lovastatin. DR DrugBank; DB01303; Oxtriphylline. DR DrugBank; DB00277; Theophylline. DR DrugBank; DB00313; Valproic Acid. DR DrugBank; DB02546; Vorinostat. DR GuidetoPHARMACOLOGY; 2616; -. DR PhosphoSite; Q92769; -. DR BioMuta; HDAC2; -. DR DMDM; 68068066; -. DR MaxQB; Q92769; -. DR PaxDb; Q92769; -. DR PRIDE; Q92769; -. DR DNASU; 3066; -. DR Ensembl; ENST00000368632; ENSP00000357621; ENSG00000196591. [Q92769-3] DR Ensembl; ENST00000519065; ENSP00000430432; ENSG00000196591. [Q92769-1] DR Ensembl; ENST00000519108; ENSP00000430008; ENSG00000196591. [Q92769-3] DR GeneID; 3066; -. DR KEGG; hsa:3066; -. DR UCSC; uc003pwc.2; human. [Q92769-1] DR CTD; 3066; -. DR GeneCards; HDAC2; -. DR HGNC; HGNC:4853; HDAC2. DR HPA; CAB005054; -. DR HPA; HPA011727; -. DR MIM; 605164; gene. DR neXtProt; NX_Q92769; -. DR PharmGKB; PA29227; -. DR eggNOG; KOG1342; Eukaryota. DR eggNOG; COG0123; LUCA. DR GeneTree; ENSGT00530000062889; -. DR HOGENOM; HOG000225180; -. DR HOVERGEN; HBG057112; -. DR InParanoid; Q92769; -. DR KO; K06067; -. DR OMA; ACPSPRD; -. DR PhylomeDB; Q92769; -. DR TreeFam; TF106171; -. DR BRENDA; 3.5.1.98; 2681. DR Reactome; R-HSA-193670; p75NTR negatively regulates cell cycle via SC1. DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain 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-427413; NoRC negatively regulates rRNA expression. 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; Q92769; -. DR ChiTaRS; HDAC2; human. DR EvolutionaryTrace; Q92769; -. DR GeneWiki; Histone_deacetylase_2; -. DR GenomeRNAi; 3066; -. DR NextBio; 12129; -. DR PRO; PR:Q92769; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; Q92769; -. DR CleanEx; HS_HDAC2; -. DR ExpressionAtlas; Q92769; baseline and differential. DR Genevisible; Q92769; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0035098; C:ESC/E(Z) complex; IDA:UniProtKB. DR GO; GO:0000790; C:nuclear chromatin; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. 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:UniProtKB. DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0001047; F:core promoter binding; IEA:Ensembl. 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; IDA: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:0044822; F:poly(A) RNA binding; IDA:UniProtKB. DR GO; GO:0033558; F:protein deacetylase activity; IMP:BHF-UCL. DR GO; GO:0001103; F:RNA polymerase II repressing transcription factor binding; IPI:BHF-UCL. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL. DR GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL. DR GO; GO:0043044; P:ATP-dependent chromatin remodeling; IDA:UniProtKB. DR GO; GO:0048149; P:behavioral response to ethanol; IEA:Ensembl. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0003300; P:cardiac muscle hypertrophy; IEA:Ensembl. DR GO; GO:1903351; P:cellular response to dopamine; IEA:Ensembl. DR GO; GO:0034605; P:cellular response to heat; IEA:Ensembl. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0071300; P:cellular response to retinoic acid; IEA:Ensembl. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. 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:0016358; P:dendrite development; 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:BHF-UCL. DR GO; GO:0070932; P:histone H3 deacetylation; ISS:UniProtKB. DR GO; GO:0070933; P:histone H4 deacetylation; ISS:UniProtKB. DR GO; GO:0006344; P:maintenance of chromatin silencing; IMP: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:0061000; P:negative regulation of dendritic spine development; IEA:Ensembl. DR GO; GO:0043392; P:negative regulation of DNA binding; IEA:Ensembl. DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; TAS:Reactome. DR GO; GO:0045347; P:negative regulation of MHC class II biosynthetic process; IC:BHF-UCL. DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:BHF-UCL. DR GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; IEA:Ensembl. DR GO; GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IMP:BHF-UCL. 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; IMP:BHF-UCL. DR GO; GO:0048011; P:neurotrophin TRK receptor 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:0032967; P:positive regulation of collagen biosynthetic process; IC:BHF-UCL. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IEA:Ensembl. DR GO; GO:0032732; P:positive regulation of interleukin-1 production; IEA:Ensembl. DR GO; GO:0048714; P:positive regulation of oligodendrocyte differentiation; IEA:Ensembl. DR GO; GO:0045862; P:positive regulation of proteolysis; 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; IMP:BHF-UCL. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IC:BHF-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl. DR GO; GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; IEA:Ensembl. DR GO; GO:0040029; P:regulation of gene expression, epigenetic; TAS:Reactome. DR GO; GO:0001975; P:response to amphetamine; IEA:Ensembl. DR GO; GO:0031000; P:response to caffeine; IEA:Ensembl. DR GO; GO:0042220; P:response to cocaine; IEA:Ensembl. DR GO; GO:0042493; P:response to drug; IEA:Ensembl. DR GO; GO:0055093; P:response to hyperoxia; IEA:Ensembl. DR GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0035094; P:response to nicotine; IEA:Ensembl. DR GO; GO:0006351; P:transcription, DNA-templated; 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; Alternative splicing; Biological rhythms; KW Chromatin regulator; Complete proteome; Cytoplasm; Hydrolase; KW Isopeptide bond; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Repressor; S-nitrosylation; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1 488 Histone deacetylase 2. FT /FTId=PRO_0000114693. FT REGION 9 322 Histone deacetylase. FT COMPBIAS 300 303 Poly-Gly. FT ACT_SITE 142 142 {ECO:0000250}. FT MOD_RES 262 262 S-nitrosocysteine. FT {ECO:0000250|UniProtKB:P70288}. FT MOD_RES 274 274 S-nitrosocysteine. FT {ECO:0000250|UniProtKB:P70288}. FT MOD_RES 394 394 Phosphoserine. FT {ECO:0000244|PubMed:17081983, 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 422 422 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:24275569}. FT MOD_RES 424 424 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000244|PubMed:24275569}. FT CROSSLNK 462 462 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT VAR_SEQ 1 30 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_056175. FT VARIANT 230 230 R -> C (in dbSNP:rs1042903). FT {ECO:0000269|PubMed:8917507}. FT /FTId=VAR_025311. FT VARIANT 315 315 Y -> H (in dbSNP:rs17852888). FT {ECO:0000269|PubMed:15489334}. FT /FTId=VAR_025312. FT CONFLICT 93 94 QR -> HI (in Ref. 1; AAC50814). FT {ECO:0000305}. FT CONFLICT 103 103 V -> A (in Ref. 1; AAC50814). FT {ECO:0000305}. FT CONFLICT 146 146 S -> Y (in Ref. 1; AAC50814). FT {ECO:0000305}. FT CONFLICT 248 248 K -> M (in Ref. 2; BAG59420). FT {ECO:0000305}. FT CONFLICT 281 281 G -> D (in Ref. 2; BAG59420). FT {ECO:0000305}. FT STRAND 12 15 {ECO:0000244|PDB:4LY1}. FT HELIX 20 22 {ECO:0000244|PDB:4LY1}. FT HELIX 34 45 {ECO:0000244|PDB:4LY1}. FT HELIX 48 51 {ECO:0000244|PDB:4LY1}. FT STRAND 52 55 {ECO:0000244|PDB:4LY1}. FT HELIX 62 65 {ECO:0000244|PDB:4LY1}. FT TURN 66 68 {ECO:0000244|PDB:4LY1}. FT HELIX 71 79 {ECO:0000244|PDB:4LY1}. FT TURN 82 84 {ECO:0000244|PDB:4LY1}. FT HELIX 85 88 {ECO:0000244|PDB:4LY1}. FT HELIX 89 95 {ECO:0000244|PDB:4LY1}. FT STRAND 98 101 {ECO:0000244|PDB:4LY1}. FT HELIX 107 126 {ECO:0000244|PDB:4LY1}. FT STRAND 131 135 {ECO:0000244|PDB:4LY1}. FT HELIX 156 164 {ECO:0000244|PDB:4LY1}. FT TURN 165 167 {ECO:0000244|PDB:4LY1}. FT STRAND 171 175 {ECO:0000244|PDB:4LY1}. FT STRAND 177 179 {ECO:0000244|PDB:4LY1}. FT HELIX 182 187 {ECO:0000244|PDB:4LY1}. FT TURN 188 190 {ECO:0000244|PDB:4LY1}. FT STRAND 192 201 {ECO:0000244|PDB:4LY1}. FT HELIX 218 220 {ECO:0000244|PDB:4LY1}. FT STRAND 224 229 {ECO:0000244|PDB:4LY1}. FT HELIX 235 253 {ECO:0000244|PDB:4LY1}. FT STRAND 256 261 {ECO:0000244|PDB:4LY1}. FT HELIX 264 266 {ECO:0000244|PDB:4LY1}. FT HELIX 279 291 {ECO:0000244|PDB:4LY1}. FT STRAND 296 299 {ECO:0000244|PDB:4LY1}. FT HELIX 306 320 {ECO:0000244|PDB:4LY1}. FT HELIX 335 338 {ECO:0000244|PDB:4LY1}. FT TURN 339 341 {ECO:0000244|PDB:4LY1}. FT STRAND 343 345 {ECO:0000244|PDB:4LY1}. FT HELIX 357 371 {ECO:0000244|PDB:4LY1}. SQ SEQUENCE 488 AA; 55364 MW; 775419CCCDAE07FA CRC64; MAYSQGGGKK KVCYYYDGDI GNYYYGQGHP MKPHRIRMTH NLLLNYGLYR KMEIYRPHKA TAEEMTKYHS DEYIKFLRSI RPDNMSEYSK QMQRFNVGED CPVFDGLFEF CQLSTGGSVA GAVKLNRQQT DMAVNWAGGL HHAKKSEASG FCYVNDIVLA ILELLKYHQR VLYIDIDIHH GDGVEEAFYT TDRVMTVSFH KYGEYFPGTG DLRDIGAGKG KYYAVNFPMR DGIDDESYGQ IFKPIISKVM EMYQPSAVVL QCGADSLSGD RLGCFNLTVK GHAKCVEVVK TFNLPLLMLG GGGYTIRNVA RCWTYETAVA LDCEIPNELP YNDYFEYFGP DFKLHISPSN MTNQNTPEYM EKIKQRLFEN LRMLPHAPGV QMQAIPEDAV HEDSGDEDGE DPDKRISIRA SDKRIACDEE FSDSEDEGEG GRRNVADHKK GAKKARIEED KKETEDKKTD VKEEDKSKDN SGEKTDTKGT KSEQLSNP // 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 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 ITF2_HUMAN Reviewed; 667 AA. AC P15884; B3KT62; B3KUC0; B4DT37; B4DUG3; B7Z5M6; B7Z6Y1; G0LNT9; AC G0LNU0; G0LNU1; G0LNU2; G0LNU4; G0LNU5; G0LNU8; G0LNU9; G0LNV0; AC G0LNV1; G0LNV2; H3BPQ1; Q08AP2; Q08AP3; Q15439; Q15440; Q15441; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 15-DEC-1998, sequence version 3. DT 11-NOV-2015, entry version 171. DE RecName: Full=Transcription factor 4; DE Short=TCF-4; DE AltName: Full=Class B basic helix-loop-helix protein 19; DE Short=bHLHb19; DE AltName: Full=Immunoglobulin transcription factor 2; DE Short=ITF-2; DE AltName: Full=SL3-3 enhancer factor 2; DE Short=SEF-2; GN Name=TCF4; Synonyms=BHLHB19, ITF2, SEF2; 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 SEF2-1A; SEF2-1B AND SEF2-1D), RP AND ALTERNATIVE SPLICING (ISOFORM SEF2-1C). RC TISSUE=Thymocyte, and Thymus; RX PubMed=1681116; RA Corneliussen B., Thornell A., Hallberg B., Grundstroem T.; RT "Helix-loop-helix transcriptional activators bind to a sequence in RT glucocorticoid response elements of retrovirus enhancers."; RL J. Virol. 65:6084-6093(1991). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A-; B-DELTA; B+DELTA; C-; RP C-DELTA; D-; E-; F-; G-; H-; I-; SEF2-1A; SEF2-1B AND SEF2-1D), AND RP ALTERNATIVE SPLICING. RX PubMed=21789225; DOI=10.1371/journal.pone.0022138; RA Sepp M., Kannike K., Eesmaa A., Urb M., Timmusk T.; RT "Functional diversity of human basic helix-loop-helix transcription RT factor TCF4 isoforms generated by alternative 5' exon usage and RT splicing."; RL PLoS ONE 6:E22138-E22138(2011). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS SEF2-1A; C-; D-; F-; RP 11 AND 13). RC TISSUE=Brain, Hippocampus, Spleen, and Teratocarcinoma; 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=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 [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] (ISOFORMS SEF2-1B AND SEF2-1D). 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 1-278 (ISOFORM SEF2-1A). RA Gu J., Zhao M., Huang Q., Xu X., Li Y., Peng Y., Song H., Xiao H., RA Gu Y., Li N., Qian B., Liu F., Qu J., Gao X., Cheng Z., Xu Z., RA Zeng L., Xu S., Gu W., Tu Y., Jia J., Fu G., Ren S., Zhong M., Lu G., RA Yang Y., Gao G., Zhang Q., Chen S., Han Z., Chen Z.; RT "MDSDCE06_MDS Homo sapiens cDNA clone MDSDCE06 5',mRNA sequence."; RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 25-48. RC TISSUE=Skin fibroblast; RX PubMed=9302263; DOI=10.1093/hmg/6.11.1855; RA Breschel T.S., McInnis M.G., Margolis R.L., Sirugo G., RA Corneliussen B., Simpson S.G., McMahon F.J., Mackinnon D.F., Xu J.F., RA Pleasant N., Huo Y., Ashworth R.G., Grundstrom C., Grundstrom T., RA Kidd K.K., Depaulo J.R., Ross C.A.; RT "A novel, heritable, expanding CTG repeat in an intron of the SEF2-1 RT gene on chromosome 18q21.1."; RL Hum. Mol. Genet. 6:1855-1863(1997). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 46-667 (ISOFORM SEF2-1B). RX PubMed=2308860; DOI=10.1093/nar/18.3.678; RA Henthorn P., McCarrick-Walmsley R., Kadesch T.; RT "Sequence of the cDNA encoding ITF-2, a positive-acting transcription RT factor."; RL Nucleic Acids Res. 18:678-678(1990). RN [10] RP DISCUSSION OF SEQUENCE. RX PubMed=2105528; DOI=10.1126/science.2105528; RA Henthorn P., Kiledjian M., Kadesch T.; RT "Two distinct transcription factors that bind the immunoglobulin RT enhancer microE5/kappa 2 motif."; RL Science 247:467-470(1990). RN [11] 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-515, 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 [13] RP SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANTS PTHS VAL-358; RP GLY-535; PRO-574; TRP-576 AND VAL-610. RX PubMed=22777675; DOI=10.1002/humu.22160; RA Forrest M., Chapman R.M., Doyle A.M., Tinsley C.L., Waite A., RA Blake D.J.; RT "Functional analysis of TCF4 missense mutations that cause Pitt- RT Hopkins syndrome."; RL Hum. Mutat. 33:1676-1686(2012). RN [14] RP INTERACTION WITH AGBL1. RX PubMed=24094747; DOI=10.1016/j.ajhg.2013.08.010; RA Riazuddin S.A., Vasanth S., Katsanis N., Gottsch J.D.; RT "Mutations in AGBL1 cause dominant late-onset Fuchs corneal dystrophy RT and alter protein-protein interaction with TCF4."; RL Am. J. Hum. Genet. 93:758-764(2013). RN [15] RP INTERACTION WITH BHLHA9. RX PubMed=25466284; DOI=10.1016/j.ajhg.2014.10.012; RA Malik S., Percin F.E., Bornholdt D., Albrecht B., Percesepe A., RA Koch M.C., Landi A., Fritz B., Khan R., Mumtaz S., Akarsu N.A., RA Grzeschik K.H.; RT "Mutations affecting the BHLHA9 DNA-binding domain cause MSSD, RT mesoaxial synostotic syndactyly with phalangeal reduction, Malik- RT Percin type."; RL Am. J. Hum. Genet. 95:649-659(2014). RN [16] RP VARIANTS PTHS TRP-576 AND GLN-576. RX PubMed=17436254; DOI=10.1086/515582; RA Amiel J., Rio M., de Pontual L., Redon R., Malan V., Boddaert N., RA Plouin P., Carter N.P., Lyonnet S., Munnich A., Colleaux L.; RT "Mutations in TCF4, encoding a class I basic helix-loop-helix RT transcription factor, are responsible for Pitt-Hopkins syndrome, a RT severe epileptic encephalopathy associated with autonomic RT dysfunction."; RL Am. J. Hum. Genet. 80:988-993(2007). RN [17] RP VARIANT PTHS TRP-576. RX PubMed=17436255; DOI=10.1086/515583; RA Zweier C., Peippo M.M., Hoyer J., Sousa S., Bottani A., RA Clayton-Smith J., Reardon W., Saraiva J., Cabral A., Goehring I., RA Devriendt K., de Ravel T., Bijlsma E.K., Hennekam R.C.M., Orrico A., RA Cohen M., Dreweke A., Reis A., Nuernberg P., Rauch A.; RT "Haploinsufficiency of TCF4 causes syndromal mental retardation with RT intermittent hyperventilation (Pitt-Hopkins syndrome)."; RL Am. J. Hum. Genet. 80:994-1001(2007). RN [18] RP VARIANTS PTHS VAL-358; PRO-574 AND HIS-578. RX PubMed=18728071; DOI=10.1136/jmg.2008.060129; RA Zweier C., Sticht H., Bijlsma E.K., Clayton-Smith J., Boonen S.E., RA Fryer A., Greally M.T., Hoffmann L., den Hollander N.S., Jongmans M., RA Kant S.G., King M.D., Lynch S.A., McKee S., Midro A.T., Park S.M., RA Ricotti V., Tarantino E., Wessels M., Peippo M., Rauch A.; RT "Further delineation of Pitt-Hopkins syndrome: phenotypic and RT genotypic description of 16 novel patients."; RL J. Med. Genet. 45:738-744(2008). RN [19] RP VARIANTS PTHS GLY-535; GLY-572; GLN-576 AND VAL-610, AND RP CHARACTERIZATION OF VARIANTS PTHS GLY-535; GLY-572; GLN-576 AND RP VAL-610. RX PubMed=19235238; DOI=10.1002/humu.20935; RA de Pontual L., Mathieu Y., Golzio C., Rio M., Malan V., Boddaert N., RA Soufflet C., Picard C., Durandy A., Dobbie A., Heron D., Isidor B., RA Motte J., Newburry-Ecob R., Pasquier L., Tardieu M., Viot G., RA Jaubert F., Munnich A., Colleaux L., Vekemans M., Etchevers H., RA Lyonnet S., Amiel J.; RT "Mutational, functional, and expression studies of the TCF4 gene in RT Pitt-Hopkins syndrome."; RL Hum. Mutat. 30:669-676(2009). RN [20] RP VARIANT PTHS PRO-578. RX PubMed=20184619; DOI=10.1111/j.1399-0004.2010.01380.x; RA Takano K., Lyons M., Moyes C., Jones J., Schwartz C.E.; RT "Two percent of patients suspected of having Angelman syndrome have RT TCF4 mutations."; RL Clin. Genet. 78:282-288(2010). RN [21] RP VARIANTS PTHS TRP-565; GLY-572; GLN-572; HIS-574; PRO-574; TRP-576; RP GLN-576; PRO-578; PRO-583 AND VAL-610. RX PubMed=22045651; DOI=10.1002/humu.21639; RA Whalen S., Heron D., Gaillon T., Moldovan O., Rossi M., Devillard F., RA Giuliano F., Soares G., Mathieu-Dramard M., Afenjar A., Charles P., RA Mignot C., Burglen L., Van Maldergem L., Piard J., Aftimos S., RA Mancini G., Dias P., Philip N., Goldenberg A., Le Merrer M., Rio M., RA Josifova D., Van Hagen J.M., Lacombe D., Edery P., Dupuis-Girod S., RA Putoux A., Sanlaville D., Fischer R., Drevillon L., Briand-Suleau A., RA Metay C., Goossens M., Amiel J., Jacquette A., Giurgea I.; RT "Novel comprehensive diagnostic strategy in Pitt-Hopkins syndrome: RT clinical score and further delineation of the TCF4 mutational RT spectrum."; RL Hum. Mutat. 33:64-72(2012). CC -!- FUNCTION: Transcription factor that binds to the immunoglobulin CC enchancer Mu-E5/KE5-motif. Involved in the initiation of neuronal CC differentiation. Activates transcription by binding to the E box CC (5'-CANNTG-3'). Binds to the E-box present in the somatostatin CC receptor 2 initiator element (SSTR2-INR) to activate transcription CC (By similarity). Preferentially binds to either 5'-ACANNTGT-3' or CC 5'-CCANNTGG-3'. {ECO:0000250}. CC -!- SUBUNIT: Efficient DNA binding requires dimerization with another CC bHLH protein. Forms homo- or heterooligomers with myogenin. CC Interacts with HIVEP2. Interacts with NEUROD2 (By similarity). CC Interacts with AGBL1. Interacts with BHLHA9. {ECO:0000250, CC ECO:0000269|PubMed:24094747, ECO:0000269|PubMed:25466284}. CC -!- INTERACTION: CC Q53FW8:-; NbExp=3; IntAct=EBI-533224, EBI-10242473; CC Q08117:AES; NbExp=3; IntAct=EBI-533224, EBI-717810; CC P29972:AQP1; NbExp=3; IntAct=EBI-533224, EBI-745213; CC Q92888:ARHGEF1; NbExp=3; IntAct=EBI-533224, EBI-465400; CC Q9H6L4:ARMC7; NbExp=3; IntAct=EBI-533224, EBI-742909; CC P50553:ASCL1; NbExp=7; IntAct=EBI-533224, EBI-957042; CC Q6XD76:ASCL4; NbExp=3; IntAct=EBI-533224, EBI-10254793; CC Q9BZE9:ASPSCR1; NbExp=3; IntAct=EBI-533224, EBI-1993677; CC P21281:ATP6V1B2; NbExp=3; IntAct=EBI-533224, EBI-4290814; CC O75934:BCAS2; NbExp=3; IntAct=EBI-533224, EBI-1050106; CC Q92843:BCL2L2; NbExp=3; IntAct=EBI-533224, EBI-707714; CC Q9NUL5:C19orf66; NbExp=3; IntAct=EBI-533224, EBI-10313866; CC Q9NX04:C1orf109; NbExp=3; IntAct=EBI-533224, EBI-8643161; CC Q6ZQR2:C9orf171; NbExp=3; IntAct=EBI-533224, EBI-10255140; CC Q9NP86:CABP5; NbExp=3; IntAct=EBI-533224, EBI-10311131; CC Q96ES7:CCDC101; NbExp=3; IntAct=EBI-533224, EBI-743117; CC P38936:CDKN1A; NbExp=3; IntAct=EBI-533224, EBI-375077; CC P42773:CDKN2C; NbExp=3; IntAct=EBI-533224, EBI-711290; CC Q13111:CHAF1A; NbExp=3; IntAct=EBI-533224, EBI-1020839; CC Q9Y6H1:CHCHD2; NbExp=3; IntAct=EBI-533224, EBI-2321769; CC Q9UKJ5:CHIC2; NbExp=3; IntAct=EBI-533224, EBI-741528; CC P61024:CKS1B; NbExp=3; IntAct=EBI-533224, EBI-456371; CC P35222:CTNNB1; NbExp=19; IntAct=EBI-533224, EBI-491549; CC P26233:ctnnb1 (xeno); NbExp=2; IntAct=EBI-533224, EBI-7373758; CC P26196:DDX6; NbExp=3; IntAct=EBI-533224, EBI-351257; CC Q9H4E7:DEF6; NbExp=3; IntAct=EBI-533224, EBI-745369; CC Q9NQL9:DMRT3; NbExp=3; IntAct=EBI-533224, EBI-9679045; CC Q5JVL4:EFHC1; NbExp=6; IntAct=EBI-533224, EBI-743105; CC O60573:EIF4E2; NbExp=3; IntAct=EBI-533224, EBI-398610; CC Q13541:EIF4EBP1; NbExp=3; IntAct=EBI-533224, EBI-74090; CC Q9Y2J2-3:EPB41L3; NbExp=3; IntAct=EBI-533224, EBI-10326138; CC O15197-2:EPHB6; NbExp=3; IntAct=EBI-533224, EBI-10182490; CC Q9Y3B2:EXOSC1; NbExp=3; IntAct=EBI-533224, EBI-371892; CC P16930:FAH; NbExp=3; IntAct=EBI-533224, EBI-4397076; CC Q9H5Z6:FAM124B; NbExp=3; IntAct=EBI-533224, EBI-741626; CC Q5TZK3:FAM74A6; NbExp=3; IntAct=EBI-533224, EBI-10247271; CC Q96RJ6:FERD3L; NbExp=3; IntAct=EBI-533224, EBI-10183007; CC Q96AC1:FERMT2; NbExp=6; IntAct=EBI-533224, EBI-4399465; CC Q8NFF5:FLAD1; NbExp=3; IntAct=EBI-533224, EBI-742815; CC P21333-2:FLNA; NbExp=3; IntAct=EBI-533224, EBI-9641086; CC O43559:FRS3; NbExp=3; IntAct=EBI-533224, EBI-725515; CC P55040:GEM; NbExp=3; IntAct=EBI-533224, EBI-744104; CC O76003:GLRX3; NbExp=3; IntAct=EBI-533224, EBI-374781; CC P50151:GNG10; NbExp=3; IntAct=EBI-533224, EBI-10211741; CC Q0D2H9:GOLGA8DP; NbExp=3; IntAct=EBI-533224, EBI-10181276; CC Q08AF8:GOLGA8G; NbExp=3; IntAct=EBI-533224, EBI-10181260; CC Q9H8Y8:GORASP2; NbExp=3; IntAct=EBI-533224, EBI-739467; CC Q96NT3:GUCD1; NbExp=3; IntAct=EBI-533224, EBI-8293751; CC P61296:HAND2; NbExp=3; IntAct=EBI-533224, EBI-10218584; CC O14929:HAT1; NbExp=3; IntAct=EBI-533224, EBI-2339359; CC V9HWF5:HEL-S-69p; NbExp=3; IntAct=EBI-533224, EBI-10330249; CC Q9UBY9:HSPB7; NbExp=3; IntAct=EBI-533224, EBI-739361; CC Q02535:ID3; NbExp=3; IntAct=EBI-533224, EBI-1387094; CC I3WAC9:INS; NbExp=3; IntAct=EBI-533224, EBI-10178524; CC Q9BQ13:KCTD14; NbExp=3; IntAct=EBI-533224, EBI-10189448; CC Q6P597:KLC3; NbExp=3; IntAct=EBI-533224, EBI-1643885; CC Q5THT1:KLHL32; NbExp=3; IntAct=EBI-533224, EBI-10247181; CC Q14847:LASP1; NbExp=3; IntAct=EBI-533224, EBI-742828; CC Q96BZ8:LENG1; NbExp=3; IntAct=EBI-533224, EBI-726510; CC Q8TCE9:LGALS14; NbExp=3; IntAct=EBI-533224, EBI-10274069; CC P25800:LMO1; NbExp=3; IntAct=EBI-533224, EBI-8639312; CC P61968:LMO4; NbExp=3; IntAct=EBI-533224, EBI-2798728; CC Q9UIQ6:LNPEP; NbExp=3; IntAct=EBI-533224, EBI-2805360; CC Q9UI95:MAD2L2; NbExp=3; IntAct=EBI-533224, EBI-77889; CC Q96A72:MAGOHB; NbExp=3; IntAct=EBI-533224, EBI-746778; CC O60336:MAPKBP1; NbExp=3; IntAct=EBI-533224, EBI-947402; CC O15232:MATN3; NbExp=3; IntAct=EBI-533224, EBI-6262458; CC Q9Y316:MEMO1; NbExp=3; IntAct=EBI-533224, EBI-1104564; CC Q6P2C6:MLLT6; NbExp=3; IntAct=EBI-533224, EBI-5773143; CC Q8NDC4:MORN4; NbExp=3; IntAct=EBI-533224, EBI-10269566; CC Q96HT8:MRFAP1L1; NbExp=3; IntAct=EBI-533224, EBI-748896; CC Q7Z7H8:MRPL10; NbExp=3; IntAct=EBI-533224, EBI-723524; CC Q8IXL7:MSRB3; NbExp=3; IntAct=EBI-533224, EBI-8634060; CC Q9ULV0:MYO5B; NbExp=3; IntAct=EBI-533224, EBI-311356; CC O43639:NCK2; NbExp=3; IntAct=EBI-533224, EBI-713635; CC Q9UHB4:NDOR1; NbExp=3; IntAct=EBI-533224, EBI-10249760; CC Q9HC98:NEK6; NbExp=3; IntAct=EBI-533224, EBI-740364; CC Q86SG6:NEK8; NbExp=3; IntAct=EBI-533224, EBI-1752987; CC Q8WWR8-2:NEU4; NbExp=3; IntAct=EBI-533224, EBI-10277551; CC Q92886:NEUROG1; NbExp=3; IntAct=EBI-533224, EBI-10279647; CC Q9Y5B8:NME7; NbExp=3; IntAct=EBI-533224, EBI-744782; CC Q9GZQ4:NMUR2; NbExp=3; IntAct=EBI-533224, EBI-10303844; CC Q5SY16:NOL9; NbExp=3; IntAct=EBI-533224, EBI-1055462; CC Q86WQ0:NR2C2AP; NbExp=3; IntAct=EBI-533224, EBI-10260040; CC Q8NFP7:NUDT10; NbExp=3; IntAct=EBI-533224, EBI-726826; CC O43929:ORC4; NbExp=3; IntAct=EBI-533224, EBI-374889; CC Q9UJX0:OSGIN1; NbExp=3; IntAct=EBI-533224, EBI-9057006; CC Q01804:OTUD4; NbExp=3; IntAct=EBI-533224, EBI-1054396; CC Q8WXA2:PATE1; NbExp=3; IntAct=EBI-533224, EBI-10277790; CC P30039:PBLD; NbExp=3; IntAct=EBI-533224, EBI-750589; CC Q13526:PIN1; NbExp=3; IntAct=EBI-533224, EBI-714158; CC Q494U1:PLEKHN1; NbExp=3; IntAct=EBI-533224, EBI-10241513; CC O95602:POLR1A; NbExp=3; IntAct=EBI-533224, EBI-359472; CC O15160:POLR1C; NbExp=3; IntAct=EBI-533224, EBI-1055079; CC Q9Y3C6:PPIL1; NbExp=3; IntAct=EBI-533224, EBI-2557649; CC Q6NYC8:PPP1R18; NbExp=3; IntAct=EBI-533224, EBI-2557469; CC P54646:PRKAA2; NbExp=3; IntAct=EBI-533224, EBI-1383852; CC P25786:PSMA1; NbExp=3; IntAct=EBI-533224, EBI-359352; CC Q969U7:PSMG2; NbExp=3; IntAct=EBI-533224, EBI-723276; CC Q147X8:PTGER3; NbExp=3; IntAct=EBI-533224, EBI-10234038; CC Q5JT25:RAB41; NbExp=3; IntAct=EBI-533224, EBI-10244509; CC P47224:RABIF; NbExp=3; IntAct=EBI-533224, EBI-713992; CC Q6P9E2:RECK; NbExp=3; IntAct=EBI-533224, EBI-10253121; CC Q04206-3:RELA; NbExp=3; IntAct=EBI-533224, EBI-10223388; CC Q8IX06:REXO1L1P; NbExp=3; IntAct=EBI-533224, EBI-10262361; CC Q9UHP6:RSPH14; NbExp=3; IntAct=EBI-533224, EBI-748350; CC Q9UIL1:SCOC; NbExp=3; IntAct=EBI-533224, EBI-2686537; CC Q9UDX3:SEC14L4; NbExp=3; IntAct=EBI-533224, EBI-10320311; CC Q6NXQ0:SFRS2; NbExp=3; IntAct=EBI-533224, EBI-10251550; CC O43699:SIGLEC6; NbExp=3; IntAct=EBI-533224, EBI-2814604; CC Q96H72:SLC39A13; NbExp=3; IntAct=EBI-533224, EBI-10287091; CC Q9BWU0:SLC4A1AP; NbExp=3; IntAct=EBI-533224, EBI-1999704; CC P49901:SMCP; NbExp=3; IntAct=EBI-533224, EBI-750494; CC Q9H4F8:SMOC1; NbExp=3; IntAct=EBI-533224, EBI-2801103; CC Q61473:Sox17 (xeno); NbExp=5; IntAct=EBI-533224, EBI-9106822; CC Q06831:Sox4 (xeno); NbExp=2; IntAct=EBI-533224, EBI-6262177; CC Q9H0A9:SPATC1L; NbExp=3; IntAct=EBI-533224, EBI-372911; CC Q9NZD8:SPG21; NbExp=3; IntAct=EBI-533224, EBI-742688; CC Q96FJ0:STAMBPL1; NbExp=3; IntAct=EBI-533224, EBI-745021; CC O75716:STK16; NbExp=3; IntAct=EBI-533224, EBI-749295; CC O75558:STX11; NbExp=3; IntAct=EBI-533224, EBI-714135; CC Q5T011-5:SZT2; NbExp=3; IntAct=EBI-533224, EBI-10245139; CC Q16559:TAL2; NbExp=3; IntAct=EBI-533224, EBI-10237959; CC Q15560:TCEA2; NbExp=3; IntAct=EBI-533224, EBI-710310; CC P56279:TCL1A; NbExp=3; IntAct=EBI-533224, EBI-749995; CC Q9UL33:TRAPPC2L; NbExp=3; IntAct=EBI-533224, EBI-747601; CC Q96PN8:TSSK3; NbExp=3; IntAct=EBI-533224, EBI-3918381; CC Q8WVJ9:TWIST2; NbExp=3; IntAct=EBI-533224, EBI-1797313; CC Q9NX01:TXNL4B; NbExp=3; IntAct=EBI-533224, EBI-10309345; CC Q9BRU9:UTP23; NbExp=3; IntAct=EBI-533224, EBI-5457544; CC Q548N1:VPS28; NbExp=3; IntAct=EBI-533224, EBI-10243107; CC Q6UX98:ZDHHC24; NbExp=3; IntAct=EBI-533224, EBI-10254561; CC Q15973:ZNF124; NbExp=3; IntAct=EBI-533224, EBI-2555767; CC Q8TAU3:ZNF417; NbExp=3; IntAct=EBI-533224, EBI-740727; CC Q96SQ5:ZNF587; NbExp=3; IntAct=EBI-533224, EBI-6427977; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE- CC ProRule:PRU00981, ECO:0000269|PubMed:22777675}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=16; CC Comment=Additional isoforms seem to exist.; CC Name=SEF2-1B; Synonyms=B-; CC IsoId=P15884-1; Sequence=Displayed; CC Name=SEF2-1A; Synonyms=A+; CC IsoId=P15884-2; Sequence=VSP_030819, VSP_002111, VSP_002112; CC Name=SEF2-1D; Synonyms=B+; CC IsoId=P15884-3; Sequence=VSP_002112; CC Name=B+delta; CC IsoId=P15884-4; Sequence=VSP_044340, VSP_002112; CC Name=B-delta; CC IsoId=P15884-5; Sequence=VSP_044340; CC Name=A-; CC IsoId=P15884-6; Sequence=VSP_044336, VSP_044337, VSP_044340; CC Name=G-; CC IsoId=P15884-7; Sequence=VSP_044334, VSP_044338, VSP_044339; CC Name=H-; CC IsoId=P15884-8; Sequence=VSP_044335, VSP_057364; CC Name=D-; CC IsoId=P15884-9; Sequence=VSP_045149; CC Name=F-; CC IsoId=P15884-10; Sequence=VSP_045151; CC Name=11; CC IsoId=P15884-11; Sequence=VSP_045150, VSP_044339, VSP_002112; CC Name=E-; CC IsoId=P15884-12; Sequence=VSP_047082, VSP_047083; CC Name=13; CC IsoId=P15884-13; Sequence=VSP_047081, VSP_002112; CC Name=C-; CC IsoId=P15884-14; Sequence=VSP_047081; CC Name=C-delta; CC IsoId=P15884-15; Sequence=VSP_047081, VSP_044340; CC Name=I-; CC IsoId=P15884-16; Sequence=VSP_054279; CC -!- TISSUE SPECIFICITY: Expressed in adult heart, brain, placenta, CC skeletal muscle and to a lesser extent in the lung. In developing CC embryonic tissues, expression mostly occurs in the brain. 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 -!- DISEASE: Pitt-Hopkins syndrome (PTHS) [MIM:610954]: A syndrome CC characterized by mental retardation, wide mouth and distinctive CC facial features, and intermittent hyperventilation followed by CC apnea. Features include intellectual disability with severe speech CC impairment, normal growth parameters at birth, postnatal CC microcephaly, breathing anomalies, severe motor developmental CC delay, motor incoordination, ocular anomalies, constipation, CC seizures, typical behavior and subtle brain abnormalities. CC {ECO:0000269|PubMed:17436254, ECO:0000269|PubMed:17436255, CC ECO:0000269|PubMed:18728071, ECO:0000269|PubMed:19235238, CC ECO:0000269|PubMed:20184619, ECO:0000269|PubMed:22045651}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Contains 1 bHLH (basic helix-loop-helix) domain. CC {ECO:0000255|PROSITE-ProRule:PRU00981}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA60310.1; Type=Miscellaneous discrepancy; Note=Incomplete and probable erroneous sequence.; Evidence={ECO:0000305}; CC Sequence=AAA60312.1; Type=Miscellaneous discrepancy; Note=Incomplete and probable erroneous sequence.; 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; M74718; AAA60310.1; ALT_SEQ; mRNA. DR EMBL; M74719; AAA60311.1; -; mRNA. DR EMBL; M74720; AAA60312.1; ALT_SEQ; mRNA. DR EMBL; FR748210; CBY80189.1; -; mRNA. DR EMBL; FR748211; CBY80190.1; -; mRNA. DR EMBL; FR748212; CBY80191.1; -; mRNA. DR EMBL; FR748213; CBY80192.1; -; mRNA. DR EMBL; FR748214; CBY80193.1; -; mRNA. DR EMBL; FR748215; CBY80194.1; -; mRNA. DR EMBL; FR748216; CBY80195.1; -; mRNA. DR EMBL; FR748217; CBY80196.1; -; mRNA. DR EMBL; FR748218; CBY80197.1; -; mRNA. DR EMBL; FR748219; CBY80198.1; -; mRNA. DR EMBL; FR748220; CBY80199.1; -; mRNA. DR EMBL; FR748221; CBY80200.1; -; mRNA. DR EMBL; FR748222; CBY80201.1; -; mRNA. DR EMBL; FR748223; CBY80202.1; -; mRNA. DR EMBL; AK095041; BAG52974.1; -; mRNA. DR EMBL; AK096862; BAG53382.1; -; mRNA. DR EMBL; AK299169; BAH12962.1; -; mRNA. DR EMBL; AK300636; BAG62325.1; -; mRNA. DR EMBL; AK300038; BAG61849.1; -; mRNA. DR EMBL; AK301144; BAH13417.1; -; mRNA. DR EMBL; AK300612; BAH13314.1; -; mRNA. DR EMBL; AK316165; BAH14536.1; -; mRNA. DR EMBL; AC013587; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC018994; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC090383; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC090684; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC091103; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471096; EAW63017.1; -; Genomic_DNA. DR EMBL; CH471096; EAW63018.1; -; Genomic_DNA. DR EMBL; BC125084; AAI25085.1; -; mRNA. DR EMBL; BC125085; AAI25086.1; -; mRNA. DR EMBL; AV761952; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; U75701; AAC51824.1; -; Genomic_DNA. DR EMBL; X52079; CAA36298.1; -; mRNA. DR CCDS; CCDS11960.1; -. [P15884-1] DR CCDS; CCDS42438.1; -. [P15884-3] DR CCDS; CCDS58623.1; -. [P15884-8] DR CCDS; CCDS58624.1; -. [P15884-2] DR CCDS; CCDS58625.1; -. [P15884-6] DR CCDS; CCDS58626.1; -. [P15884-9] DR CCDS; CCDS58627.1; -. [P15884-11] DR CCDS; CCDS58628.1; -. [P15884-10] DR CCDS; CCDS58629.1; -. [P15884-13] DR CCDS; CCDS59321.1; -. [P15884-12] DR CCDS; CCDS77191.1; -. [P15884-7] DR CCDS; CCDS77192.1; -. [P15884-14] DR PIR; A41311; A41311. DR RefSeq; NP_001077431.1; NM_001083962.1. [P15884-3] DR RefSeq; NP_001230155.2; NM_001243226.2. DR RefSeq; NP_001230156.1; NM_001243227.1. [P15884-13] DR RefSeq; NP_001230157.1; NM_001243228.1. DR RefSeq; NP_001230159.1; NM_001243230.1. [P15884-12] DR RefSeq; NP_001230160.1; NM_001243231.1. [P15884-10] DR RefSeq; NP_001230161.1; NM_001243232.1. [P15884-11] DR RefSeq; NP_001230162.1; NM_001243233.1. [P15884-9] DR RefSeq; NP_001230163.1; NM_001243234.1. [P15884-2] DR RefSeq; NP_001230164.1; NM_001243235.1. [P15884-6] DR RefSeq; NP_001230165.1; NM_001243236.1. [P15884-8] DR RefSeq; NP_001293136.1; NM_001306207.1. [P15884-14] DR RefSeq; NP_001293137.1; NM_001306208.1. [P15884-7] DR RefSeq; NP_003190.1; NM_003199.2. [P15884-1] DR RefSeq; XP_005266796.2; XM_005266739.3. [P15884-13] DR RefSeq; XP_005266800.1; XM_005266743.3. [P15884-13] DR RefSeq; XP_005266801.1; XM_005266744.3. [P15884-13] DR RefSeq; XP_006722599.1; XM_006722536.2. [P15884-3] DR RefSeq; XP_006722600.1; XM_006722537.2. [P15884-3] DR RefSeq; XP_006722603.1; XM_006722540.2. [P15884-9] DR RefSeq; XP_011524466.1; XM_011526164.1. [P15884-9] DR UniGene; Hs.605153; -. DR UniGene; Hs.742885; -. DR PDB; 2KWF; NMR; -; B=11-27. DR PDBsum; 2KWF; -. DR DisProt; DP00224; -. DR ProteinModelPortal; P15884; -. DR SMR; P15884; 565-624. DR BioGrid; 112787; 193. DR DIP; DIP-163N; -. DR IntAct; P15884; 151. DR MINT; MINT-4508073; -. DR STRING; 9606.ENSP00000346440; -. DR PhosphoSite; P15884; -. DR BioMuta; TCF4; -. DR MaxQB; P15884; -. DR PaxDb; P15884; -. DR PRIDE; P15884; -. DR Ensembl; ENST00000354452; ENSP00000346440; ENSG00000196628. [P15884-3] DR Ensembl; ENST00000356073; ENSP00000348374; ENSG00000196628. [P15884-1] DR Ensembl; ENST00000457482; ENSP00000409447; ENSG00000196628. [P15884-2] DR Ensembl; ENST00000537578; ENSP00000440731; ENSG00000196628. [P15884-13] DR Ensembl; ENST00000537856; ENSP00000439827; ENSG00000196628. [P15884-9] DR Ensembl; ENST00000540999; ENSP00000445202; ENSG00000196628. [P15884-14] DR Ensembl; ENST00000543082; ENSP00000439656; ENSG00000196628. [P15884-10] DR Ensembl; ENST00000544241; ENSP00000441562; ENSG00000196628. [P15884-11] DR Ensembl; ENST00000561831; ENSP00000457765; ENSG00000196628. [P15884-8] DR Ensembl; ENST00000561992; ENSP00000455179; ENSG00000196628. [P15884-9] DR Ensembl; ENST00000564228; ENSP00000455261; ENSG00000196628. [P15884-7] DR Ensembl; ENST00000564999; ENSP00000457649; ENSG00000196628. [P15884-1] DR Ensembl; ENST00000565018; ENSP00000455984; ENSG00000196628. [P15884-15] DR Ensembl; ENST00000566279; ENSP00000456125; ENSG00000196628. [P15884-4] DR Ensembl; ENST00000566286; ENSP00000455418; ENSG00000196628. [P15884-12] DR Ensembl; ENST00000567880; ENSP00000454366; ENSG00000196628. [P15884-5] DR Ensembl; ENST00000568673; ENSP00000455135; ENSG00000196628. [P15884-13] DR Ensembl; ENST00000570177; ENSP00000454647; ENSG00000196628. [P15884-9] DR Ensembl; ENST00000570287; ENSP00000455763; ENSG00000196628. [P15884-6] DR Ensembl; ENST00000616053; ENSP00000478549; ENSG00000196628. [P15884-15] DR Ensembl; ENST00000626584; ENSP00000486072; ENSG00000196628. [P15884-16] DR Ensembl; ENST00000629387; ENSP00000486670; ENSG00000196628. [P15884-3] DR GeneID; 6925; -. DR KEGG; hsa:6925; -. DR UCSC; uc002lfw.4; human. [P15884-2] DR UCSC; uc002lfx.2; human. DR UCSC; uc002lfy.2; human. DR UCSC; uc002lfz.2; human. [P15884-1] DR UCSC; uc010dph.1; human. [P15884-3] DR UCSC; uc010xdy.1; human. DR UCSC; uc021ukh.1; human. [P15884-6] DR UCSC; uc021uki.1; human. [P15884-7] DR UCSC; uc021ukj.1; human. [P15884-5] DR UCSC; uc021ukk.1; human. [P15884-4] DR CTD; 6925; -. DR GeneCards; TCF4; -. DR GeneReviews; TCF4; -. DR HGNC; HGNC:11634; TCF4. DR HPA; CAB020722; -. DR HPA; HPA025958; -. DR MIM; 602272; gene. DR MIM; 610954; phenotype. DR neXtProt; NX_P15884; -. DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability. DR Orphanet; 98974; Fuchs endothelial corneal dystrophy. DR Orphanet; 2896; Pitt-Hopkins syndrome. DR Orphanet; 171; Primary sclerosing cholangitis. DR Orphanet; 3140; Schizophrenia. DR PharmGKB; PA164742621; -. DR eggNOG; KOG3910; Eukaryota. DR eggNOG; ENOG410XYUA; LUCA. DR GeneTree; ENSGT00510000046438; -. DR HOGENOM; HOG000234180; -. DR HOVERGEN; HBG003854; -. DR InParanoid; P15884; -. DR KO; K15603; -. DR OrthoDB; EOG72G16Q; -. DR PhylomeDB; P15884; -. DR TreeFam; TF321672; -. DR Reactome; R-HSA-375170; CDO in myogenesis. DR SignaLink; P15884; -. DR ChiTaRS; TCF4; human. DR EvolutionaryTrace; P15884; -. DR GeneWiki; TCF4; -. DR GenomeRNAi; 6925; -. DR NextBio; 27093; -. DR PRO; PR:P15884; -. DR Proteomes; UP000005640; Chromosome 18. DR Bgee; P15884; -. DR CleanEx; HS_TCF4; -. DR ExpressionAtlas; P15884; baseline and differential. DR Genevisible; P15884; HS. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005667; C:transcription factor complex; ISS:BHF-UCL. DR GO; GO:0043425; F:bHLH transcription factor binding; IBA:GO_Central. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0070888; F:E-box binding; ISS:UniProtKB. DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB. DR GO; GO:0046982; F:protein heterodimerization activity; ISS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; ISS:BHF-UCL. DR GO; GO:0001093; F:TFIIB-class transcription factor binding; ISS:BHF-UCL. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB. DR GO; GO:0001011; F:transcription factor activity, sequence-specific DNA binding, RNA polymerase recruiting; ISS:BHF-UCL. DR GO; GO:0001087; F:transcription factor activity, TFIIB-class binding; ISS:BHF-UCL. DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; ISS:BHF-UCL. DR GO; GO:0006352; P:DNA-templated transcription, initiation; ISS:BHF-UCL. 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; ISS:BHF-UCL. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0065004; P:protein-DNA complex assembly; ISS:BHF-UCL. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; ISS:BHF-UCL. DR Gene3D; 4.10.280.10; -; 1. DR InterPro; IPR011598; bHLH_dom. DR Pfam; PF00010; HLH; 1. DR SMART; SM00353; HLH; 1. DR SUPFAM; SSF47459; SSF47459; 1. DR PROSITE; PS50888; BHLH; 1. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Complete proteome; KW Differentiation; Disease mutation; DNA-binding; Epilepsy; KW Mental retardation; Neurogenesis; Nucleus; Phosphoprotein; KW Polymorphism; Primary microcephaly; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1 667 Transcription factor 4. FT /FTId=PRO_0000127256. FT DOMAIN 564 617 bHLH. {ECO:0000255|PROSITE- FT ProRule:PRU00981}. FT REGION 1 83 Essential for MYOD1 inhibition. FT {ECO:0000250}. FT REGION 379 400 Leucine-zipper. FT REGION 619 642 Class A specific domain. FT MOTIF 18 26 9aaTAD. FT COMPBIAS 228 231 Poly-Ser. FT MOD_RES 372 372 Phosphoserine. FT {ECO:0000250|UniProtKB:Q62655}. FT MOD_RES 515 515 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT VAR_SEQ 1 216 Missing (in isoform I-). FT {ECO:0000303|PubMed:21789225}. FT /FTId=VSP_054279. FT VAR_SEQ 1 160 Missing (in isoform SEF2-1A). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:1681116, FT ECO:0000303|PubMed:21789225, FT ECO:0000303|Ref.7}. FT /FTId=VSP_030819. FT VAR_SEQ 1 130 Missing (in isoform D-). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:21789225}. FT /FTId=VSP_045149. FT VAR_SEQ 1 102 MHHQQRMAALGTDKELSDLLDFSAMFSPPVSSGKNGPTSLA FT SGHFTGSNVEDRSSSGSWGNGGHPSPSRNYGDGTPYDHMTS FT RDLGSHDNLSPPFVNSRIQS -> MKDIFFQFIIARVRKCY FT SLSCLHTLPVVPTLR (in isoform 11). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_045150. FT VAR_SEQ 1 49 MHHQQRMAALGTDKELSDLLDFSAMFSPPVSSGKNGPTSLA FT SGHFTGSN -> MEEDSRD (in isoform F-). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:21789225}. FT /FTId=VSP_045151. FT VAR_SEQ 1 32 MHHQQRMAALGTDKELSDLLDFSAMFSPPVSS -> MKDIF FT FQFIIARVRKCYSLSCLHTLPVVPTLR (in isoform FT G-). {ECO:0000303|PubMed:21789225}. FT /FTId=VSP_044334. FT VAR_SEQ 1 24 Missing (in isoform 13, isoform C- and FT isoform C-delta). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:21789225}. FT /FTId=VSP_047081. FT VAR_SEQ 1 24 MHHQQRMAALGTDKELSDLLDFSA -> MQRAKTELFRLQI FT VTDDLRKNE (in isoform E-). FT {ECO:0000303|PubMed:21789225}. FT /FTId=VSP_047082. FT VAR_SEQ 1 23 MHHQQRMAALGTDKELSDLLDFS -> MYCAYTIPGMGGNS FT LMYYYNGKA (in isoform A-). FT {ECO:0000303|PubMed:21789225}. FT /FTId=VSP_044336. FT VAR_SEQ 1 23 MHHQQRMAALGTDKELSDLLDFS -> MKFKQCRCSDTGLC FT CLDHEGKAE (in isoform H-). FT {ECO:0000303|PubMed:21789225}. FT /FTId=VSP_044335. FT VAR_SEQ 24 183 Missing (in isoform H-). FT {ECO:0000303|PubMed:21789225}. FT /FTId=VSP_057364. FT VAR_SEQ 24 123 Missing (in isoform A-). FT {ECO:0000303|PubMed:21789225}. FT /FTId=VSP_044337. FT VAR_SEQ 33 102 Missing (in isoform G-). FT {ECO:0000303|PubMed:21789225}. FT /FTId=VSP_044338. FT VAR_SEQ 123 123 Missing (in isoform G- and isoform 11). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:21789225}. FT /FTId=VSP_044339. FT VAR_SEQ 124 183 Missing (in isoform A-, isoform B-delta, FT isoform B+delta and isoform C-delta). FT {ECO:0000303|PubMed:21789225}. FT /FTId=VSP_044340. FT VAR_SEQ 161 183 LHSSAMEVQTKKVRKVPPGLPSS -> MYCAYTIPGMGGNS FT LMYYYNGKA (in isoform SEF2-1A). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:1681116, FT ECO:0000303|PubMed:21789225, FT ECO:0000303|Ref.7}. FT /FTId=VSP_002111. FT VAR_SEQ 357 357 Missing (in isoform E-). FT {ECO:0000303|PubMed:21789225}. FT /FTId=VSP_047083. FT VAR_SEQ 545 545 T -> TRSRS (in isoform B+delta, isoform FT SEF2-1A, isoform SEF2-1D, isoform 11 and FT isoform 13). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:1681116, FT ECO:0000303|PubMed:21789225, FT ECO:0000303|Ref.7}. FT /FTId=VSP_002112. FT VARIANT 358 358 G -> V (in PTHS; also expressed in the FT nucleus with a pattern indistinguishable FT from the wild-type; does not have a major FT impact on homodimer formation; affects FT transcriptional activity in a context- FT dependent manner). FT {ECO:0000269|PubMed:18728071, FT ECO:0000269|PubMed:22777675}. FT /FTId=VAR_066839. FT VARIANT 450 450 M -> I (in dbSNP:rs11660217). FT /FTId=VAR_049545. FT VARIANT 535 535 D -> G (in PTHS; loss of function; also FT expressed in the nucleus with a pattern FT indistinguishable from the wild-type; FT does not have a major impact on homodimer FT formation; affects transcriptional FT activity in a context-dependent manner). FT {ECO:0000269|PubMed:19235238, FT ECO:0000269|PubMed:22777675}. FT /FTId=VAR_058632. FT VARIANT 565 565 R -> W (in PTHS). FT {ECO:0000269|PubMed:22045651}. FT /FTId=VAR_066970. FT VARIANT 572 572 R -> G (in PTHS; loss of function). FT {ECO:0000269|PubMed:19235238, FT ECO:0000269|PubMed:22045651}. FT /FTId=VAR_058633. FT VARIANT 572 572 R -> Q (in PTHS). FT {ECO:0000269|PubMed:22045651}. FT /FTId=VAR_066971. FT VARIANT 574 574 R -> H (in PTHS). FT {ECO:0000269|PubMed:22045651}. FT /FTId=VAR_066972. FT VARIANT 574 574 R -> P (in PTHS; mislocalized to small FT spherical punctae that are dispersed FT throughout the nucleus; can attenuate FT homo- and heterodimer formation; affects FT transcriptional activity in a context- FT dependent manner). FT {ECO:0000269|PubMed:18728071, FT ECO:0000269|PubMed:22045651, FT ECO:0000269|PubMed:22777675}. FT /FTId=VAR_066840. FT VARIANT 576 576 R -> Q (in PTHS; loss of function). FT {ECO:0000269|PubMed:17436254, FT ECO:0000269|PubMed:19235238, FT ECO:0000269|PubMed:22045651}. FT /FTId=VAR_034704. FT VARIANT 576 576 R -> W (in PTHS; mislocalized to small FT spherical punctae that are dispersed FT throughout the nucleus; can attenuate FT homo- and heterodimer formation; affects FT transcriptional activity in a context- FT dependent manner). FT {ECO:0000269|PubMed:17436254, FT ECO:0000269|PubMed:17436255, FT ECO:0000269|PubMed:22045651, FT ECO:0000269|PubMed:22777675}. FT /FTId=VAR_034705. FT VARIANT 578 578 R -> H (in PTHS). FT {ECO:0000269|PubMed:18728071}. FT /FTId=VAR_066841. FT VARIANT 578 578 R -> P (in PTHS). FT {ECO:0000269|PubMed:20184619, FT ECO:0000269|PubMed:22045651}. FT /FTId=VAR_066973. FT VARIANT 583 583 A -> P (in PTHS). FT {ECO:0000269|PubMed:22045651}. FT /FTId=VAR_066974. FT VARIANT 610 610 A -> V (in PTHS; loss of function; FT mislocalized to small spherical punctae FT that are dispersed throughout the FT nucleus; can attenuate homo- and FT heterodimer formation; affects FT transcriptional activity in a context- FT dependent manner). FT {ECO:0000269|PubMed:19235238, FT ECO:0000269|PubMed:22045651, FT ECO:0000269|PubMed:22777675}. FT /FTId=VAR_058634. FT CONFLICT 46 49 TGSN -> EFGG (in Ref. 9; CAA36298). FT {ECO:0000305}. FT CONFLICT 205 205 Missing (in Ref. 7; AV761952). FT {ECO:0000305}. FT CONFLICT 334 334 P -> S (in Ref. 9; CAA36298). FT {ECO:0000305}. FT HELIX 15 25 {ECO:0000244|PDB:2KWF}. SQ SEQUENCE 667 AA; 71308 MW; 53459FC7989D9487 CRC64; MHHQQRMAAL GTDKELSDLL DFSAMFSPPV SSGKNGPTSL ASGHFTGSNV EDRSSSGSWG NGGHPSPSRN YGDGTPYDHM TSRDLGSHDN LSPPFVNSRI QSKTERGSYS SYGRESNLQG CHQQSLLGGD MDMGNPGTLS PTKPGSQYYQ YSSNNPRRRP LHSSAMEVQT KKVRKVPPGL PSSVYAPSAS TADYNRDSPG YPSSKPATST FPSSFFMQDG HHSSDPWSSS SGMNQPGYAG MLGNSSHIPQ SSSYCSLHPH ERLSYPSHSS ADINSSLPPM STFHRSGTNH YSTSSCTPPA NGTDSIMANR GSGAAGSSQT GDALGKALAS IYSPDHTNNS FSSNPSTPVG SPPSLSAGTA VWSRNGGQAS SSPNYEGPLH SLQSRIEDRL ERLDDAIHVL RNHAVGPSTA MPGGHGDMHG IIGPSHNGAM GGLGSGYGTG LLSANRHSLM VGTHREDGVA LRGSHSLLPN QVPVPQLPVQ SATSPDLNPP QDPYRGMPPG LQGQSVSSGS SEIKSDDEGD ENLQDTKSSE DKKLDDDKKD IKSITSNNDD EDLTPEQKAE REKERRMANN ARERLRVRDI NEAFKELGRM VQLHLKSDKP QTKLLILHQA VAVILSLEQQ VRERNLNPKA ACLKRREEEK VSSEPPPLSL AGPHPGMGDA SNHMGQM // ID KAT2B_HUMAN Reviewed; 832 AA. AC Q92831; Q6NSK1; DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot. DT 10-MAY-2005, sequence version 3. DT 11-NOV-2015, entry version 171. DE RecName: Full=Histone acetyltransferase KAT2B; DE EC=2.3.1.48; DE AltName: Full=Histone acetyltransferase PCAF; DE Short=Histone acetylase PCAF; DE AltName: Full=Lysine acetyltransferase 2B; DE AltName: Full=P300/CBP-associated factor; DE Short=P/CAF; GN Name=KAT2B; Synonyms=PCAF; 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 {ECO:0000312|EMBL:AAC50890.2}; RN [1] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, TISSUE SPECIFICITY, AND RP INTERACTION WITH EP300 AND CREBBP. RC TISSUE=Liver; RX PubMed=8684459; DOI=10.1038/382319a0; RA Yang X.-J., Ogryzko V.V., Nishikawa J., Howard B.H., Nakatani Y.; RT "A p300/CBP-associated factor that competes with the adenoviral RT oncoprotein E1A."; RL Nature 382:319-324(1996). RN [2] {ECO:0000305} RP SEQUENCE REVISION. RC TISSUE=Liver; RA Nakatani Y.; RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases. 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 ENZYME ACTIVITY. RX PubMed=8945521; DOI=10.1016/S0092-8674(00)82001-2; RA Ogryzko V.V., Schiltz R.L., Russanova V., Howard B.H., Nakatani Y.; RT "The transcriptional coactivators p300 and CBP are histone RT acetyltransferases."; RL Cell 87:953-959(1996). RN [5] RP INTERACTION WITH NCOA3. RX PubMed=9346901; DOI=10.1074/jbc.272.44.27629; RA Takeshita A., Cardona G.R., Koibuchi N., Suen C.-S., Chin W.W.; RT "TRAM-1, a novel 160-kDa thyroid hormone receptor activator molecule, RT exhibits distinct properties from steroid receptor coactivator-1."; RL J. Biol. Chem. 272:27629-27634(1997). RN [6] RP INTERACTION WITH NCOA1. RX PubMed=9296499; DOI=10.1038/38304; RA Spencer T.E., Jenster G., Burcin M.M., Allis C.D., Zhou J., RA Mizzen C.A., McKenna N.J., Onate S.A., Tsai S.Y., Tsai M.-J., RA O'Malley B.W.; RT "Steroid receptor coactivator-1 is a histone acetyltransferase."; RL Nature 389:194-198(1997). RN [7] RP INTERACTION WITH KLF1, AND FUNCTION. RX PubMed=9707565; DOI=10.1073/pnas.95.17.9855; RA Zhang W., Bieker J.J.; RT "Acetylation and modulation of erythroid Krueppel-like factor (EKLF) RT activity by interaction with histone acetyltransferases."; RL Proc. Natl. Acad. Sci. U.S.A. 95:9855-9860(1998). RN [8] RP INTERACTION WITH E2F1, AND FUNCTION. RX PubMed=10675335; DOI=10.1093/emboj/19.4.662; RA Martinez-Balbas M.A., Bauer U.M., Nielsen S.J., Brehm A., RA Kouzarides T.; RT "Regulation of E2F1 activity by acetylation."; RL EMBO J. 19:662-671(2000). RN [9] RP INTERACTION WITH HTLV-1 TAX. RX PubMed=10766811; DOI=10.1074/jbc.275.16.11852; RA Harrod R., Kuo Y.-L., Tang Y., Yao Y., Vassilev A., Nakatani Y., RA Giam C.-Z.; RT "p300 and p300/cAMP-responsive element-binding protein associated RT factor interact with human T-cell lymphotropic virus type-1 Tax in a RT multi-histone acetyltransferase/activator-enhancer complex."; RL J. Biol. Chem. 275:11852-11857(2000). RN [10] 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 [11] RP INTERACTION WITH HIV-1 TAT. RX PubMed=12486002; DOI=10.1093/emboj/cdf669; RA Bres V., Tagami H., Peloponese J.-M., Loret E., Jeang K.-T., RA Nakatani Y., Emiliani S., Benkirane M., Kiernan R.E.; RT "Differential acetylation of Tat coordinates its interaction with the RT co-activators cyclin T1 and PCAF."; RL EMBO J. 21:6811-6819(2002). RN [12] RP FUNCTION, AND INTERACTION WITH NPAS2; ARNTL/BMAL1 AND CLOCK. RX PubMed=14645221; DOI=10.1074/jbc.M311973200; RA Curtis A.M., Seo S.B., Westgate E.J., Rudic R.D., Smyth E.M., RA Chakravarti D., FitzGerald G.A., McNamara P.; RT "Histone acetyltransferase-dependent chromatin remodeling and the RT vascular clock."; RL J. Biol. Chem. 279:7091-7097(2004). RN [13] 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 [14] RP INTERACTION WITH TACC1; TACC2 AND TACC3. RX PubMed=14767476; DOI=10.1038/sj.onc.1207424; RA Gangisetty O., Lauffart B., Sondarva G.V., Chelsea D.M., Still I.H.; RT "The transforming acidic coiled coil proteins interact with nuclear RT histone acetyltransferases."; RL Oncogene 23:2559-2563(2004). RN [15] 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 [16] RP INTERACTION WITH DDX17. RX PubMed=17226766; DOI=10.1002/jcb.21250; RA Shin S., Janknecht R.; RT "Concerted activation of the Mdm2 promoter by p72 RNA helicase and the RT coactivators p300 and P/CAF."; RL J. Cell. Biochem. 101:1252-1265(2007). RN [17] RP INTERACTION WITH CEBPB. RX PubMed=17301242; DOI=10.1073/pnas.0607378104; RA Wiper-Bergeron N., Salem H.A., Tomlinson J.J., Wu D., Hache R.J.; RT "Glucocorticoid-stimulated preadipocyte differentiation is mediated RT through acetylation of C/EBPbeta by GCN5."; RL Proc. Natl. Acad. Sci. U.S.A. 104:2703-2708(2007). RN [18] RP IDENTIFICATION IN A LARGE CHROMATIN REMODELING COMPLEX. RX PubMed=17707232; DOI=10.1016/j.molcel.2007.07.024; RA Zhu P., Zhou W., Wang J., Puc J., Ohgi K.A., Erdjument-Bromage H., RA Tempst P., Glass C.K., Rosenfeld M.G.; RT "A histone H2A deubiquitinase complex coordinating histone acetylation RT and H1 dissociation in transcriptional regulation."; RL Mol. Cell 27:609-621(2007). RN [19] RP INTERACTION WITH BCAS3. 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 [20] RP FUNCTION. RX PubMed=23932781; DOI=10.1016/j.molcel.2013.07.002; RA Lin R., Tao R., Gao X., Li T., Zhou X., Guan K.L., Xiong Y., Lei Q.Y.; RT "Acetylation stabilizes ATP-citrate lyase to promote lipid RT biosynthesis and tumor growth."; RL Mol. Cell 51:506-518(2013). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 493-658 IN COMPLEX WITH RP COENZYME A, AND ACTIVE SITE. RX PubMed=10393169; DOI=10.1093/emboj/18.13.3521; RA Clements A., Rojas J.R., Trievel R.C., Wang L., Berger S.L., RA Marmorstein R.; RT "Crystal structure of the histone acetyltransferase domain of the RT human PCAF transcriptional regulator bound to coenzyme A."; RL EMBO J. 18:3521-3532(1999). RN [22] RP STRUCTURE BY NMR OF 715-832, AND MUTAGENESIS OF VAL-752; TYR-760; RP TYR-802 AND TYR-809. RC TISSUE=Liver; RX PubMed=10365964; DOI=10.1038/20974; RA Dhalluin C., Carlson J.E., Zeng L., He C., Aggarwal A.K., Zhou M.-M.; RT "Structure and ligand of a histone acetyltransferase bromodomain."; RL Nature 399:491-496(1999). RN [23] RP STRUCTURE BY NMR OF 719-832 IN COMPLEX WITH HIV-1 TAT. RX PubMed=11931765; DOI=10.1016/S1097-2765(02)00483-5; RA Mujtaba S., He Y., Zeng L., Farooq A., Carlson J.E., Ott M., RA Verdin E., Zhou M.-M.; RT "Structural basis of lysine-acetylated HIV-1 Tat recognition by PCAF RT bromodomain."; RL Mol. Cell 9:575-586(2002). RN [24] RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 715-831. 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: Functions as a histone acetyltransferase (HAT) to CC promote transcriptional activation. Has significant histone CC acetyltransferase activity with core histones (H3 and H4), and CC also with nucleosome core particles. Also acetylates non-histone CC proteins, such as ACLY. Inhibits cell-cycle progression and CC counteracts the mitogenic activity of the adenoviral oncoprotein CC E1A. In case of HIV-1 infection, it is recruited by the viral CC protein Tat. Regulates Tat's transactivating activity and may help CC inducing chromatin remodeling of proviral genes. Acts as a CC circadian transcriptional coactivator which enhances the activity CC of the circadian transcriptional activators: NPAS2-ARNTL/BMAL1 and CC CLOCK-ARNTL/BMAL1 heterodimers. {ECO:0000269|PubMed:10675335, CC ECO:0000269|PubMed:14645221, ECO:0000269|PubMed:23932781, CC ECO:0000269|PubMed:8684459, ECO:0000269|PubMed:9707565}. CC -!- CATALYTIC ACTIVITY: Acetyl-CoA + [histone] = CoA + acetyl- CC [histone]. {ECO:0000269|PubMed:8945521}. CC -!- SUBUNIT: Interacts with SIRT1. Interacts (unsumoylated form) with CC NR2C1; the interaction promotes transactivation activity (By CC similarity). Interacts with EP300, CREBBP and DDX17. Interacts CC with NCOA1 and NCOA3. Component of a large chromatin remodeling CC complex, at least composed of MYSM1, KAT2B/PCAF, RBM10 and CC KIF11/TRIP5. Interacts with NR2C2 (hypophosphorylated and CC unsumoylated form); the interaction promotes the transactivation CC activity of NR2C2. Binds to HTLV-1 Tax. Interacts with and CC acetylates HIV-1 Tat. Interacts with KLF1; the interaction does CC not acetylate KLF1 and there is no enhancement of its CC transactivational activity. Interacts with NFE4. Interacts with CC MECOM. Interacts with E2F1; the interaction acetylates E2F1 CC augmenting its DNA-binding and transcriptional activity. Interacts CC with NPAS2, ARNTL/BMAL1 and CLOCK. Interacts with BCAS3. Interacts CC with CEBPB (PubMed:17301242). Interacts with NR4A3 (By CC similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q9JHD1, CC ECO:0000269|PubMed:10675335, ECO:0000269|PubMed:10766811, CC ECO:0000269|PubMed:11568182, ECO:0000269|PubMed:11931765, CC ECO:0000269|PubMed:12486002, ECO:0000269|PubMed:14645221, CC ECO:0000269|PubMed:14767476, ECO:0000269|PubMed:15273251, CC ECO:0000269|PubMed:16887930, ECO:0000269|PubMed:17226766, CC ECO:0000269|PubMed:17301242, ECO:0000269|PubMed:17505058, CC ECO:0000269|PubMed:17707232, ECO:0000269|PubMed:8684459, CC ECO:0000269|PubMed:9296499, ECO:0000269|PubMed:9346901, CC ECO:0000269|PubMed:9707565}. CC -!- INTERACTION: CC P03255:- (xeno); NbExp=3; IntAct=EBI-477430, EBI-2603114; CC P03255-2:- (xeno); NbExp=3; IntAct=EBI-477430, EBI-6859460; CC O60566:BUB1B; NbExp=14; IntAct=EBI-477430, EBI-1001438; CC Q92793:CREBBP; NbExp=4; IntAct=EBI-477430, EBI-81215; CC P03129:E7 (xeno); NbExp=3; IntAct=EBI-477430, EBI-866453; CC Q96KQ7:EHMT2; NbExp=3; IntAct=EBI-477430, EBI-744366; CC Q09472:EP300; NbExp=2; IntAct=EBI-477430, EBI-447295; CC Q16665:HIF1A; NbExp=2; IntAct=EBI-477430, EBI-447269; CC P02299:His3:CG33854 (xeno); NbExp=2; IntAct=EBI-477430, EBI-522090; CC P84040:His4:CG33909 (xeno); NbExp=2; IntAct=EBI-477430, EBI-185028; CC Q96EB6:SIRT1; NbExp=3; IntAct=EBI-477430, EBI-1802965; CC Q8IXJ6:SIRT2; NbExp=4; IntAct=EBI-477430, EBI-477232; CC Q16594:TAF9; NbExp=3; IntAct=EBI-477430, EBI-712521; CC O88898-2:Tp63 (xeno); NbExp=3; IntAct=EBI-477430, EBI-2338228; CC Q15672:TWIST1; NbExp=2; IntAct=EBI-477430, EBI-1797287; CC P22415:USF1; NbExp=5; IntAct=EBI-477430, EBI-1054489; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed but most abundant in CC heart and skeletal muscle. {ECO:0000269|PubMed:8684459}. CC -!- DOMAIN: The bromodomain mediates binding to HIV-1 Tat. CC -!- SIMILARITY: Belongs to the acetyltransferase family. GCN5 CC subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 bromo domain. {ECO:0000255|PROSITE- CC ProRule:PRU00035}. CC -!- SIMILARITY: Contains 1 N-acetyltransferase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00532}. 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; U57317; AAC50890.2; -; mRNA. DR EMBL; BC060823; AAH60823.1; -; mRNA. DR EMBL; BC070075; AAH70075.1; -; mRNA. DR CCDS; CCDS2634.1; -. DR PIR; S71788; S71788. DR RefSeq; NP_003875.3; NM_003884.4. DR UniGene; Hs.533055; -. DR PDB; 1CM0; X-ray; 2.30 A; A/B=493-658. DR PDB; 1JM4; NMR; -; B=719-832. DR PDB; 1N72; NMR; -; A=719-832. DR PDB; 1WUG; NMR; -; A=719-832. DR PDB; 1WUM; NMR; -; A=719-832. DR PDB; 1ZS5; NMR; -; A=719-832. DR PDB; 2RNW; NMR; -; A=719-832. DR PDB; 2RNX; NMR; -; A=719-832. DR PDB; 3GG3; X-ray; 2.25 A; A/B=715-831. DR PDB; 4NSQ; X-ray; 2.31 A; A/B/C/D=493-658. DR PDBsum; 1CM0; -. DR PDBsum; 1JM4; -. DR PDBsum; 1N72; -. DR PDBsum; 1WUG; -. DR PDBsum; 1WUM; -. DR PDBsum; 1ZS5; -. DR PDBsum; 2RNW; -. DR PDBsum; 2RNX; -. DR PDBsum; 3GG3; -. DR PDBsum; 4NSQ; -. DR ProteinModelPortal; Q92831; -. DR SMR; Q92831; 493-653, 719-832. DR BioGrid; 114375; 175. DR DIP; DIP-29778N; -. DR IntAct; Q92831; 36. DR MINT; MINT-150079; -. DR STRING; 9606.ENSP00000263754; -. DR BindingDB; Q92831; -. DR ChEMBL; CHEMBL5500; -. DR GuidetoPHARMACOLOGY; 2737; -. DR PhosphoSite; Q92831; -. DR BioMuta; KAT2B; -. DR DMDM; 83287776; -. DR REPRODUCTION-2DPAGE; Q92831; -. DR MaxQB; Q92831; -. DR PaxDb; Q92831; -. DR PRIDE; Q92831; -. DR Ensembl; ENST00000263754; ENSP00000263754; ENSG00000114166. DR GeneID; 8850; -. DR KEGG; hsa:8850; -. DR UCSC; uc003cbq.3; human. DR CTD; 8850; -. DR GeneCards; KAT2B; -. DR HGNC; HGNC:8638; KAT2B. DR HPA; CAB004526; -. DR HPA; HPA055839; -. DR MIM; 602303; gene. DR neXtProt; NX_Q92831; -. DR PharmGKB; PA162392705; -. DR eggNOG; KOG1472; Eukaryota. DR eggNOG; COG5076; LUCA. DR GeneTree; ENSGT00760000119099; -. DR HOGENOM; HOG000007151; -. DR InParanoid; Q92831; -. DR KO; K06062; -. DR OMA; HEDASNY; -. DR OrthoDB; EOG7ZKS9B; -. DR PhylomeDB; Q92831; -. DR TreeFam; TF105399; -. DR BRENDA; 2.3.1.48; 2681. DR Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation. DR Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression. DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain 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-3214847; HATs acetylate histones. DR Reactome; R-HSA-350054; Notch-HLH transcription pathway. DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation. DR ChiTaRS; KAT2B; human. DR EvolutionaryTrace; Q92831; -. DR GeneWiki; PCAF; -. DR GenomeRNAi; 8850; -. DR NextBio; 33221; -. DR PRO; PR:Q92831; -. DR Proteomes; UP000005640; Chromosome 3. DR Bgee; Q92831; -. DR CleanEx; HS_KAT2B; -. DR Genevisible; Q92831; HS. DR GO; GO:0031672; C:A band; IEA:Ensembl. DR GO; GO:0042641; C:actomyosin; IEA:Ensembl. DR GO; GO:0005671; C:Ada2/Gcn5/Ada3 transcription activator complex; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0031674; C:I band; IEA:Ensembl. DR GO; GO:0000776; C:kinetochore; IEA:Ensembl. DR GO; GO:0000790; C:nuclear chromatin; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0000125; C:PCAF complex; NAS:UniProtKB. DR GO; GO:0016407; F:acetyltransferase activity; IDA:UniProtKB. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; ISS:UniProtKB. DR GO; GO:0004402; F:histone acetyltransferase activity; IDA:UniProtKB. DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB. DR GO; GO:0004468; F:lysine N-acetyltransferase activity, acting on acetyl phosphate as donor; IDA:UniProtKB. DR GO; GO:0032403; F:protein complex binding; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB. DR GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0003712; F:transcription cofactor activity; IPI:UniProtKB. DR GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB. DR GO; GO:0007050; P:cell cycle arrest; TAS:ProtInc. DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:BHF-UCL. DR GO; GO:0034599; P:cellular response to oxidative stress; IEA:Ensembl. DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEA:Ensembl. DR GO; GO:0006325; P:chromatin organization; TAS:Reactome. DR GO; GO:0006338; P:chromatin remodeling; IDA:UniProtKB. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0043966; P:histone H3 acetylation; IDA:BHF-UCL. DR GO; GO:0043970; P:histone H3-K9 acetylation; IEA:Ensembl. DR GO; GO:0018393; P:internal peptidyl-lysine acetylation; IDA:UniProtKB. DR GO; GO:0007613; P:memory; IEA:Ensembl. DR GO; GO:0018076; P:N-terminal peptidyl-lysine acetylation; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell proliferation; IDA:UniProtKB. DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IEA:Ensembl. DR GO; GO:0007219; P:Notch signaling pathway; TAS:Reactome. DR GO; GO:0018394; P:peptidyl-lysine acetylation; IDA:BHF-UCL. DR GO; GO:0035563; P:positive regulation of chromatin binding; IEA:Ensembl. DR GO; GO:0035948; P:positive regulation of gluconeogenesis by positive regulation of transcription from RNA polymerase II promoter; IEA:Ensembl. DR GO; GO:0071442; P:positive regulation of histone H3-K14 acetylation; IEA:Ensembl. DR GO; GO:2000617; P:positive regulation of histone H3-K9 acetylation; IEA:Ensembl. DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL. DR GO; GO:0045909; P:positive regulation of vasodilation; IEA:Ensembl. DR GO; GO:0006473; P:protein acetylation; TAS:ProtInc. DR GO; GO:0010835; P:regulation of protein ADP-ribosylation; IDA:BHF-UCL. DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW. DR GO; GO:0006360; P:transcription from RNA polymerase I promoter; TAS:Reactome. 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:0016032; P:viral process; IEA:UniProtKB-KW. DR Gene3D; 1.20.920.10; -; 1. DR Gene3D; 3.40.630.30; -; 1. DR InterPro; IPR016181; Acyl_CoA_acyltransferase. DR InterPro; IPR001487; Bromodomain. DR InterPro; IPR018359; Bromodomain_CS. DR InterPro; IPR000182; GNAT_dom. DR InterPro; IPR016376; Hist_acetylase_PCAF. DR InterPro; IPR009464; PCAF_N. DR Pfam; PF13508; Acetyltransf_7; 1. DR Pfam; PF00439; Bromodomain; 1. DR Pfam; PF06466; PCAF_N; 1. DR PIRSF; PIRSF003048; Histone_acetylase_PCAF; 1. DR PRINTS; PR00503; BROMODOMAIN. DR SMART; SM00297; BROMO; 1. DR SUPFAM; SSF47370; SSF47370; 1. DR SUPFAM; SSF55729; SSF55729; 1. DR PROSITE; PS00633; BROMODOMAIN_1; 1. DR PROSITE; PS50014; BROMODOMAIN_2; 1. DR PROSITE; PS51186; GNAT; 1. PE 1: Evidence at protein level; KW 3D-structure; Activator; Acyltransferase; Biological rhythms; KW Bromodomain; Cell cycle; Complete proteome; Host-virus interaction; KW Nucleus; Polymorphism; Reference proteome; Transcription; KW Transcription regulation; Transferase. FT CHAIN 1 832 Histone acetyltransferase KAT2B. FT /FTId=PRO_0000211208. FT DOMAIN 503 651 N-acetyltransferase. FT {ECO:0000250|UniProtKB:Q92830, FT ECO:0000255|PROSITE-ProRule:PRU00532}. FT DOMAIN 740 810 Bromo. {ECO:0000255|PROSITE- FT ProRule:PRU00035, ECO:0000305}. FT REGION 574 576 Acetyl-CoA binding. FT {ECO:0000269|PubMed:10393169}. FT REGION 581 587 Acetyl-CoA binding. FT {ECO:0000269|PubMed:10393169}. FT REGION 612 615 Acetyl-CoA binding. FT {ECO:0000269|PubMed:10393169}. FT ACT_SITE 570 570 Proton donor/acceptor. FT {ECO:0000303|PubMed:10393169}. FT VARIANT 386 386 N -> S (in dbSNP:rs17006625). FT /FTId=VAR_034372. FT MUTAGEN 752 752 V->A: Reduced acetyl-lysine binding. FT {ECO:0000269|PubMed:10365964}. FT MUTAGEN 760 760 Y->A: Reduced acetyl-lysine binding. FT {ECO:0000269|PubMed:10365964}. FT MUTAGEN 802 802 Y->A: Reduced acetyl-lysine binding. FT {ECO:0000269|PubMed:10365964}. FT MUTAGEN 809 809 Y->A: Complete loss of acetyl-lysine FT binding. {ECO:0000269|PubMed:10365964}. FT CONFLICT 804 805 PP -> AA (in Ref. 1; AAC50890). FT {ECO:0000305}. FT STRAND 494 499 {ECO:0000244|PDB:1CM0}. FT STRAND 503 505 {ECO:0000244|PDB:1CM0}. FT HELIX 509 525 {ECO:0000244|PDB:1CM0}. FT HELIX 531 538 {ECO:0000244|PDB:1CM0}. FT STRAND 543 550 {ECO:0000244|PDB:1CM0}. FT STRAND 553 563 {ECO:0000244|PDB:1CM0}. FT TURN 564 567 {ECO:0000244|PDB:1CM0}. FT STRAND 568 576 {ECO:0000244|PDB:1CM0}. FT HELIX 578 580 {ECO:0000244|PDB:1CM0}. FT STRAND 582 584 {ECO:0000244|PDB:1CM0}. FT HELIX 585 599 {ECO:0000244|PDB:1CM0}. FT STRAND 604 609 {ECO:0000244|PDB:1CM0}. FT TURN 611 613 {ECO:0000244|PDB:1CM0}. FT HELIX 614 618 {ECO:0000244|PDB:1CM0}. FT TURN 619 621 {ECO:0000244|PDB:1CM0}. FT STRAND 623 625 {ECO:0000244|PDB:1CM0}. FT HELIX 630 633 {ECO:0000244|PDB:1CM0}. FT STRAND 644 649 {ECO:0000244|PDB:1CM0}. FT HELIX 727 741 {ECO:0000244|PDB:3GG3}. FT STRAND 742 744 {ECO:0000244|PDB:1WUM}. FT HELIX 746 748 {ECO:0000244|PDB:3GG3}. FT HELIX 754 756 {ECO:0000244|PDB:3GG3}. FT STRAND 757 759 {ECO:0000244|PDB:1ZS5}. FT HELIX 760 763 {ECO:0000244|PDB:3GG3}. FT STRAND 764 766 {ECO:0000244|PDB:1JM4}. FT HELIX 770 778 {ECO:0000244|PDB:3GG3}. FT HELIX 785 802 {ECO:0000244|PDB:3GG3}. FT STRAND 805 807 {ECO:0000244|PDB:1WUG}. FT HELIX 808 826 {ECO:0000244|PDB:3GG3}. FT STRAND 828 830 {ECO:0000244|PDB:1N72}. SQ SEQUENCE 832 AA; 93013 MW; 72F516E8BC00CC0C CRC64; MSEAGGAGPG GCGAGAGAGA GPGALPPQPA ALPPAPPQGS PCAAAAGGSG ACGPATAVAA AGTAEGPGGG GSARIAVKKA QLRSAPRAKK LEKLGVYSAC KAEESCKCNG WKNPNPSPTP PRADLQQIIV SLTESCRSCS HALAAHVSHL ENVSEEEMNR LLGIVLDVEY LFTCVHKEED ADTKQVYFYL FKLLRKSILQ RGKPVVEGSL EKKPPFEKPS IEQGVNNFVQ YKFSHLPAKE RQTIVELAKM FLNRINYWHL EAPSQRRLRS PNDDISGYKE NYTRWLCYCN VPQFCDSLPR YETTQVFGRT LLRSVFTVMR RQLLEQARQE KDKLPLEKRT LILTHFPKFL SMLEEEVYSQ NSPIWDQDFL SASSRTSQLG IQTVINPPPV AGTISYNSTS SSLEQPNAGS SSPACKASSG LEANPGEKRK MTDSHVLEEA KKPRVMGDIP MELINEVMST ITDPAAMLGP ETNFLSAHSA RDEAARLEER RGVIEFHVVG NSLNQKPNKK ILMWLVGLQN VFSHQLPRMP KEYITRLVFD PKHKTLALIK DGRVIGGICF RMFPSQGFTE IVFCAVTSNE QVKGYGTHLM NHLKEYHIKH DILNFLTYAD EYAIGYFKKQ GFSKEIKIPK TKYVGYIKDY EGATLMGCEL NPRIPYTEFS VIIKKQKEII KKLIERKQAQ IRKVYPGLSC FKDGVRQIPI ESIPGIRETG WKPSGKEKSK EPRDPDQLYS TLKSILQQVK SHQSAWPFME PVKRTEAPGY YEVIRFPMDL KTMSERLKNR YYVSKKLFMA DLQRVFTNCK EYNPPESEYY KCANILEKFF FSKIKEAGLI DK // 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 MDS1_HUMAN Reviewed; 169 AA. AC Q13465; Q13466; Q6FH90; DT 19-OCT-2002, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 11-NOV-2015, entry version 110. DE RecName: Full=MDS1 and EVI1 complex locus protein MDS1; DE AltName: Full=Myelodysplasia syndrome 1 protein; DE AltName: Full=Myelodysplasia syndrome-associated protein 1; GN Name=MECOM; Synonyms=MDS1; 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, and Pancreas; RX PubMed=8643684; DOI=10.1073/pnas.93.4.1642; RA Fears S., Mathieu C., Zeleznik-Le N., Huang S., Rowley J.D., RA Nucifora G.; RT "Intergenic splicing of MDS1 and EVI1 occurs in normal tissues as well RT as in myeloid leukemia and produces a new member of the PR domain RT family."; RL Proc. Natl. Acad. Sci. U.S.A. 93:1642-1647(1996). RN [2] 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 [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]. 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 Q5R372-2:RABGAP1L; NbExp=3; IntAct=EBI-8475192, EBI-10692254; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=6; CC Name=3; Synonyms=Mds1; CC IsoId=Q13465-1; Sequence=Displayed; CC Note=Produced by alternative promoter usage.; CC Name=1; Synonyms=Long, Evi-1a; CC IsoId=Q03112-1; Sequence=External; CC Name=2; Synonyms=Evi-1c, Mds1/Evi1; CC IsoId=Q03112-3; Sequence=External; CC Note=Produced by alternative promoter usage. Contains an CC additional SET domain at positions 79-194. Unable to form CC homooligomers, to interact with CTBP1 and SMAD3 and to repress CC TGF-beta signaling. Contains a glycyl lysine isopeptide CC (Lys-Gly) (interchain with G-Cter in SUMO2) at position 190.; CC Name=4; CC IsoId=Q03112-4; Sequence=External; CC Note=Contains a glycyl lysine isopeptide (Lys-Gly) (interchain CC with G-Cter in SUMO2) at position 66.; CC Name=5; CC IsoId=Q03112-5; Sequence=External; CC Name=6; CC IsoId=Q03112-6; Sequence=External; CC -!- DISEASE: Note=A chromosomal aberration involving MDS1 is found in CC a form of acute myeloid leukemia (AML). Translocation t(3;21) with CC AML1. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/EVI103q26ID19.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; U43292; AAB05839.1; -; mRNA. DR EMBL; U43293; AAB05840.1; ALT_SEQ; mRNA. DR EMBL; CR541866; CAG46664.1; -; mRNA. DR EMBL; CR541886; CAG46684.1; -; mRNA. DR EMBL; CH471052; EAW78549.1; -; Genomic_DNA. DR EMBL; BC069498; AAH69498.1; -; mRNA. DR RefSeq; NP_004982.2; NM_004991.3. DR UniGene; Hs.744090; -. DR ProteinModelPortal; Q13465; -. DR SMR; Q13465; 47-130. DR BioGrid; 108423; 21. DR IntAct; Q13465; 3. DR MINT; MINT-8417693; -. DR PhosphoSite; Q13465; -. DR MaxQB; Q13465; -. DR PRIDE; Q13465; -. DR DNASU; 2122; -. DR GeneID; 2122; -. DR UCSC; uc011bpl.1; human. [Q13465-1] DR CTD; 2122; -. DR GeneCards; MECOM; -. DR HGNC; HGNC:3498; MECOM. DR MIM; 600049; gene. DR neXtProt; NX_Q13465; -. DR PharmGKB; PA27912; -. DR PharmGKB; PA30722; -. DR HOVERGEN; HBG031707; -. DR PhylomeDB; Q13465; -. DR ChiTaRS; MECOM; human. DR GenomeRNAi; 2122; -. DR NextBio; 8579; -. DR Proteomes; UP000005640; Unplaced. DR CleanEx; HS_MDS1; -. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; TAS:ProtInc. DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:GOC. DR InterPro; IPR026710; MDS1. DR PANTHER; PTHR21652; PTHR21652; 1. PE 1: Evidence at protein level; KW Alternative promoter usage; Alternative splicing; KW Chromosomal rearrangement; Complete proteome; Polymorphism; KW Reference proteome; Ubl conjugation. FT CHAIN 1 169 MDS1 and EVI1 complex locus protein MDS1. FT /FTId=PRO_0000096338. FT VARIANT 120 120 P -> S (in dbSNP:rs7622799). FT /FTId=VAR_051183. SQ SEQUENCE 169 AA; 18696 MW; 3EE36C8ACB62EFFE CRC64; MRSKGRARKL ATNNECVYGN YPEIPLEEMP DADGVASTPS LNIQEPCSPA TSSEAFTPKE GSPYKAPIYI PDDIPIPAEF ELRESNMPGA GLGIWTKRKI EVGEKFGPYV GEQRSNLKDP SYGWEVHLPR SRRVSVHSWL YLGKRSSDVG IAFSQADVYM PGLQCAFLS // 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 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 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 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 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 //