ID CDN1A_HUMAN Reviewed; 164 AA. AC P38936; Q14010; Q6FI05; Q9BUT4; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 11-NOV-2015, entry version 181. DE RecName: Full=Cyclin-dependent kinase inhibitor 1; DE AltName: Full=CDK-interacting protein 1; DE AltName: Full=Melanoma differentiation-associated protein 6; DE Short=MDA-6; DE AltName: Full=p21; GN Name=CDKN1A; Synonyms=CAP20, CDKN1, CIP1, MDA6, PIC1, SDI1, WAF1; 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, AND INDUCTION. RX PubMed=8242751; DOI=10.1016/0092-8674(93)90499-G; RA Harper J.W., Adami G.R., Wei N., Keyomarsi K., Elledge S.J.; RT "The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 RT cyclin-dependent kinases."; RL Cell 75:805-816(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND INDUCTION. RX PubMed=8242752; DOI=10.1016/0092-8674(93)90500-P; RA El-Deiry W.S., Tokino T., Velculescu V.E., Levy D.B., Parsons R., RA Trent J.M., Lin D., Mercer W.E., Kinzler K.W., Vogelstein B.; RT "WAF1, a potential mediator of p53 tumor suppression."; RL Cell 75:817-825(1993). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8259214; DOI=10.1038/366701a0; RA Xiong Y., Hannon G.J., Zhang H., Casso D., Kobayashi R., Beach D.; RT "p21 is a universal inhibitor of cyclin kinases."; RL Nature 366:701-704(1993). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Jiang H., Fisher P.B.; RT "Use of a sensitive and efficient subtraction hybridization protocol RT for the identification of genes differentially regulated during the RT induction of differentiation in human melanoma cells."; RL Mol. Cell. Differ. 1:285-299(1993). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=7753561; RA Jiang H., Lin J., Su Z.Z., Herlyn M., Kerbel R.S., Weissman B.E., RA Welch D.R., Fisher P.B.; RT "The melanoma differentiation-associated gene mda-6, which encodes the RT cyclin-dependent kinase inhibitor p21, is differentially expressed RT during growth, differentiation and progression in human melanoma RT cells."; RL Oncogene 10:1855-1864(1995). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8125163; DOI=10.1006/excr.1994.1063; RA Noda A., Ning Y., Venable S.F., Pereira-Smith O.M., Smith J.R.; RT "Cloning of senescent cell-derived inhibitors of DNA synthesis using RT an expression screen."; RL Exp. Cell Res. 211:90-98(1994). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT ARG-31. RX PubMed=7655464; DOI=10.1093/hmg/4.6.1089; RA Mousses S., Oezcelik H., Lee P.D., Malkin D., Bull S.B., RA Andrulis I.L.; RT "Two variants of the CIP1/WAF1 gene occur together and are associated RT with human cancer."; RL Hum. Mol. Genet. 4:1089-1092(1995). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-31. RG NIEHS SNPs program; RL Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [10] 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 [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=19054851; DOI=10.1038/nmeth.1273; RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R., RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y., RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B., RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., RA Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M., RA Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T., RA Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A., RA Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K., RA Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S., RA Isogai T., Imai J., Watanabe S., Nomura N.; RT "Human protein factory for converting the transcriptome into an in RT vitro-expressed proteome."; RL Nat. Methods 5:1011-1017(2008). RN [12] 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 [13] 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 [14] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-31. RC TISSUE=Eye, 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 [15] RP PROTEIN SEQUENCE OF 2-16, ACETYLATION AT SER-2, AND IDENTIFICATION BY RP MASS SPECTROMETRY. RX PubMed=15574338; DOI=10.1016/j.molcel.2004.11.011; RA Chen X., Chi Y., Bloecher A., Aebersold R., Clurman B.E., RA Roberts J.M.; RT "N-acetylation and ubiquitin-independent proteasomal degradation of RT p21(Cip1)."; RL Mol. Cell 16:839-847(2004). RN [16] RP PROTEIN SEQUENCE OF 136-148, PHOSPHORYLATION AT THR-145; SER-146 AND RP SER-160, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=10753973; DOI=10.1074/jbc.275.15.11529; RA Scott M.T., Morrice N., Ball K.L.; RT "Reversible phosphorylation at the C-terminal regulatory domain of RT p21(Waf1/Cip1) modulates proliferating cell nuclear antigen binding."; RL J. Biol. Chem. 275:11529-11537(2000). RN [17] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CDK4 AND CCND1 IN RP THE CYCLIN D-CDK4-CDKN1A COMPLEX. RX PubMed=9106657; DOI=10.1101/gad.11.7.847; RA LaBaer J., Garrett M.D., Stevenson L.F., Slingerland J.M., Sandhu C., RA Chou H.S., Fattaey A., Harlow E.; RT "New functional activities for the p21 family of CDK inhibitors."; RL Genes Dev. 11:847-862(1997). RN [18] RP INTERACTION WITH PSMA3. RX PubMed=11350925; DOI=10.1093/emboj/20.10.2367; RA Touitou R., Richardson J., Bose S., Nakanishi M., Rivett J., RA Allday M.J.; RT "A degradation signal located in the C-terminus of p21WAF1/CIP1 is a RT binding site for the C8 alpha-subunit of the 20S proteasome."; RL EMBO J. 20:2367-2375(2001). RN [19] RP PHOSPHORYLATION AT THR-145, MUTAGENESIS OF THR-145 AND SER-146, AND RP SUBCELLULAR LOCATION. RX PubMed=11463845; DOI=10.1128/MCB.21.16.5644-5657.2001; RA Roessig L., Jadidi A.S., Urbich C., Badorff C., Zeiher A.M., RA Dimmeler S.; RT "Akt-dependent phosphorylation of p21(Cip1) regulates PCNA binding and RT proliferation of endothelial cells."; RL Mol. Cell. Biol. 21:5644-5657(2001). RN [20] RP PHOSPHORYLATION AT THR-145 BY PIM1, SUBCELLULAR LOCATION, AND RP INTERACTION WITH PIM1. RX PubMed=12431783; DOI=10.1016/S0167-4889(02)00347-6; RA Wang Z., Bhattacharya N., Mixter P.F., Wei W., Sedivy J., RA Magnuson N.S.; RT "Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1 RT kinase."; RL Biochim. Biophys. Acta 1593:45-55(2002). RN [21] RP UBIQUITINATION AT SER-2. RX PubMed=15226418; DOI=10.1128/MCB.24.14.6140-6150.2004; RA Coulombe P., Rodier G., Bonneil E., Thibault P., Meloche S.; RT "N-Terminal ubiquitination of extracellular signal-regulated kinase 3 RT and p21 directs their degradation by the proteasome."; RL Mol. Cell. Biol. 24:6140-6150(2004). RN [22] RP PHOSPHORYLATION AT THR-145. RX PubMed=16982699; DOI=10.1128/MCB.00201-06; RA Heron-Milhavet L., Franckhauser C., Rana V., Berthenet C., Fisher D., RA Hemmings B.A., Fernandez A., Lamb N.J.; RT "Only Akt1 is required for proliferation, while Akt2 promotes cell RT cycle exit through p21 binding."; RL Mol. Cell. Biol. 26:8267-8280(2006). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-130, AND IDENTIFICATION RP 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 [24] RP UBIQUITINATION, DOMAIN PIP-BOX K+4 MOTIF, INTERACTION WITH PCNA, RP MUTAGENESIS OF SER-114 AND 144-GLN--PHE-150, AND PHOSPHORYLATION AT RP SER-114. RX PubMed=18794347; DOI=10.1101/gad.1676108; RA Abbas T., Sivaprasad U., Terai K., Amador V., Pagano M., Dutta A.; RT "PCNA-dependent regulation of p21 ubiquitylation and degradation via RT the CRL4Cdt2 ubiquitin ligase complex."; RL Genes Dev. 22:2496-2506(2008). RN [25] RP UBIQUITINATION. RX PubMed=18794348; DOI=10.1101/gad.1703708; RA Kim Y., Starostina N.G., Kipreos E.T.; RT "The CRL4Cdt2 ubiquitin ligase targets the degradation of p21Cip1 to RT control replication licensing."; RL Genes Dev. 22:2507-2519(2008). RN [26] RP UBIQUITINATION, DOMAIN PIP-BOX K+4 MOTIF, MUTAGENESIS OF RP 147-MET--TYR-151 AND 154-LYS--ARG-156, AND INTERACTION WITH PCNA. RX PubMed=18703516; DOI=10.1074/jbc.M806045200; RA Nishitani H., Shiomi Y., Iida H., Michishita M., Takami T., RA Tsurimoto T.; RT "CDK inhibitor p21 is degraded by a proliferating cell nuclear RT antigen-coupled Cul4-DDB1Cdt2 pathway during S phase and after UV RT irradiation."; RL J. Biol. Chem. 283:29045-29052(2008). RN [27] 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). RN [28] RP REVIEW ON DNA REPAIR, AND INTERACTION WITH CDK2. RX PubMed=19445729; DOI=10.1186/1747-1028-4-9; RA Satyanarayana A., Kaldis P.; RT "A dual role of Cdk2 in DNA damage response."; RL Cell Div. 4:9-9(2009). RN [29] RP UBIQUITINATION, AND INTERACTION WITH MKRN1. RX PubMed=19536131; DOI=10.1038/emboj.2009.164; RA Lee E.-W., Lee M.-S., Camus S., Ghim J., Yang M.-R., Oh W., Ha N.-C., RA Lane D.P., Song J.; RT "Differential regulation of p53 and p21 by MKRN1 E3 ligase controls RT cell cycle arrest and apoptosis."; RL EMBO J. 28:2100-2113(2009). RN [30] RP UBIQUITINATION. RX PubMed=19332548; DOI=10.1074/jbc.M808810200; RA Stuart S.A., Wang J.Y.; RT "Ionizing radiation induces ATM-independent degradation of p21Cip1 in RT transformed cells."; RL J. Biol. Chem. 284:15061-15070(2009). RN [31] RP PHOSPHORYLATION AT THR-145 BY PIM2. RX PubMed=20307683; DOI=10.1016/j.biocel.2010.03.012; RA Wang Z., Zhang Y., Gu J.J., Davitt C., Reeves R., Magnuson N.S.; RT "Pim-2 phosphorylation of p21(Cip1/WAF1) enhances its stability and RT inhibits cell proliferation in HCT116 cells."; RL Int. J. Biochem. Cell Biol. 42:1030-1038(2010). RN [32] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [33] RP UBIQUITINATION BY RNF114. RX PubMed=23645206; DOI=10.1038/cdd.2013.33; RA Han J., Kim Y.L., Lee K.W., Her N.G., Ha T.K., Yoon S., Jeong S.I., RA Lee J.H., Kang M.J., Lee M.G., Ryu B.K., Baik J.H., Chi S.G.; RT "ZNF313 is a novel cell cycle activator with an E3 ligase activity RT inhibiting cellular senescence by destabilizing p21(WAF1.)."; RL Cell Death Differ. 20:1055-1067(2013). RN [34] RP FUNCTION, INTERACTION WITH STK11 AND NUAK1, PHOSPHORYLATION AT THR-80 RP AND SER-146, AND MUTAGENESIS OF THR-80 AND SER-146. RX PubMed=25329316; DOI=10.1371/journal.pgen.1004721; RA Esteve-Puig R., Gil R., Gonzalez-Sanchez E., Bech-Serra J.J., RA Grueso J., Hernandez-Losa J., Moline T., Canals F., Ferrer B., RA Cortes J., Bastian B., Cajal S.R.Y., Martin-Caballero J., Flores J.M., RA Vivancos A., Garcia-Patos V., Recio J.A.; RT "A mouse model uncovers LKB1 as an UVB-induced DNA damage sensor RT mediating CDKN1A (p21WAF1/CIP1) degradation."; RL PLoS Genet. 10:E1004721-E1004721(2014). RN [35] RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 139-160 IN COMPLEX WITH PCNA. RX PubMed=8861913; DOI=10.1016/S0092-8674(00)81347-1; RA Gulbis J.M., Kelman Z., Hurwitz J., O'Donnell M., Kuriyan J.; RT "Structure of the C-terminal region of p21(WAF1/CIP1) complexed with RT human PCNA."; RL Cell 87:297-306(1996). CC -!- FUNCTION: May be the important intermediate by which p53/TP53 CC mediates its role as an inhibitor of cellular proliferation in CC response to DNA damage. Binds to and inhibits cyclin-dependent CC kinase activity, preventing phosphorylation of critical cyclin- CC dependent kinase substrates and blocking cell cycle progression. CC Functions in the nuclear localization and assembly of cyclin D- CC CDK4 complex and promotes its kinase activity towards RB1. At CC higher stoichiometric ratios, inhibits the kinase activity of the CC cyclin D-CDK4 complex. {ECO:0000269|PubMed:8242751, CC ECO:0000269|PubMed:9106657}. CC -!- SUBUNIT: Interacts with HDAC1; the interaction is prevented by CC competitive binding of C10orf90/FATS to HDAC1 facilitating CC acetylation and protein stabilization of CDKN1A/p21 (By CC similarity). Interacts with MKRN1. Interacts with PSMA3. Interacts CC with PCNA. Component of the ternary complex, cyclin D-CDK4-CDKN1A. CC Interacts (via its N-terminal domain) with CDK4; the interaction CC promotes the assembly of the cyclin D-CDK4 complex, its nuclear CC translocation and promotes the cyclin D-dependent enzyme activity CC of CDK4. Binding to CDK2 leads to CDK2/cyclin E inactivation at CC the G1-S phase DNA damage checkpoint, thereby arresting cells at CC the G1-S transition during DNA repair. Interacts with PIM1. CC Interacts with STK11 and NUAK1. {ECO:0000250|UniProtKB:P39689, CC ECO:0000269|PubMed:11350925, ECO:0000269|PubMed:12431783, CC ECO:0000269|PubMed:18703516, ECO:0000269|PubMed:18794347, CC ECO:0000269|PubMed:19445729, ECO:0000269|PubMed:19536131, CC ECO:0000269|PubMed:25329316, ECO:0000269|PubMed:8861913, CC ECO:0000269|PubMed:9106657}. CC -!- INTERACTION: CC P27958:- (xeno); NbExp=3; IntAct=EBI-375077, EBI-6377335; CC P78396:CCNA1; NbExp=3; IntAct=EBI-375077, EBI-375065; CC P20248:CCNA2; NbExp=2; IntAct=EBI-375077, EBI-457097; CC P24385:CCND1; NbExp=11; IntAct=EBI-375077, EBI-375001; CC P30279:CCND2; NbExp=6; IntAct=EBI-375077, EBI-748789; CC P30281:CCND3; NbExp=10; IntAct=EBI-375077, EBI-375013; CC P24864:CCNE1; NbExp=9; IntAct=EBI-375077, EBI-519526; CC O96020:CCNE2; NbExp=2; IntAct=EBI-375077, EBI-375033; CC O75419:CDC45; NbExp=2; IntAct=EBI-375077, EBI-374969; CC Q99741:CDC6; NbExp=2; IntAct=EBI-375077, EBI-374862; CC O94921:CDK14; NbExp=8; IntAct=EBI-375077, EBI-1043945; CC P24941:CDK2; NbExp=15; IntAct=EBI-375077, EBI-375096; CC P11802:CDK4; NbExp=5; IntAct=EBI-375077, EBI-295644; CC Q00535:CDK5; NbExp=4; IntAct=EBI-375077, EBI-1041567; CC Q9UKT9:IKZF3; NbExp=3; IntAct=EBI-375077, EBI-747204; CC Q15323:KRT31; NbExp=3; IntAct=EBI-375077, EBI-948001; CC Q9UHC7:MKRN1; NbExp=5; IntAct=EBI-375077, EBI-373524; CC Q9BQ15:NABP2; NbExp=7; IntAct=EBI-375077, EBI-2120336; CC P12004:PCNA; NbExp=15; IntAct=EBI-375077, EBI-358311; CC Q6FI35:PCNA; NbExp=2; IntAct=EBI-375077, EBI-8469539; CC Q96FS4:SIPA1; NbExp=2; IntAct=EBI-375077, EBI-1054981; CC P63208:SKP1; NbExp=3; IntAct=EBI-375077, EBI-307486; CC Q13309:SKP2; NbExp=2; IntAct=EBI-375077, EBI-456291; CC P15884:TCF4; NbExp=3; IntAct=EBI-375077, EBI-533224; CC Q8IYF3:TEX11; NbExp=4; IntAct=EBI-375077, EBI-742397; CC P04637:TP53; NbExp=3; IntAct=EBI-375077, EBI-366083; CC Q13077:TRAF1; NbExp=3; IntAct=EBI-375077, EBI-359224; CC Q9BYV2:TRIM54; NbExp=3; IntAct=EBI-375077, EBI-2130429; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. CC -!- TISSUE SPECIFICITY: Expressed in all adult tissues, with 5-fold CC lower levels observed in the brain. CC -!- INDUCTION: Activated by p53/TP53, mezerein (antileukemic compound) CC and IFNB1. Repressed by HDAC1. {ECO:0000269|PubMed:8242751, CC ECO:0000269|PubMed:8242752}. CC -!- DOMAIN: The PIP-box K+4 motif mediates both the interaction with CC PCNA and the recuitment of the DCX(DTL) complex: while the PIP-box CC interacts with PCNA, the presence of the K+4 submotif, recruits CC the DCX(DTL) complex, leading to its ubiquitination. CC -!- DOMAIN: The C-terminal is required for nuclear localization of the CC cyclin D-CDK4 complex. CC -!- PTM: Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC CC impairs binding to PCNA. Phosphorylation at Ser-114 by GSK3-beta CC enhances ubiquitination by the DCX(DTL) complex. Phosphorylation CC of Thr-145 by PIM2 enhances CDKN1A stability and inhibits cell CC proliferation. Phosphorylation of Thr-145 by PIM1 results in the CC relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein CC stability. UV radiation-induced phosphorylation at Thr-80 by LKB1 CC and at Ser-146 by NUAK1 leads to its degradation. CC {ECO:0000269|PubMed:10753973, ECO:0000269|PubMed:11463845, CC ECO:0000269|PubMed:12431783, ECO:0000269|PubMed:16982699, CC ECO:0000269|PubMed:18794347, ECO:0000269|PubMed:20307683, CC ECO:0000269|PubMed:25329316}. CC -!- PTM: Ubiquitinated by MKRN1; leading to polyubiquitination and 26S CC proteasome-dependent degradation. Ubiquitinated by the DCX(DTL) CC complex, also named CRL4(CDT2) complex, leading to its degradation CC during S phase or following UV irradiation. Ubiquitination by the CC DCX(DTL) complex is essential to control replication licensing and CC is PCNA-dependent: interacts with PCNA via its PIP-box, while the CC presence of the containing the 'K+4' motif in the PIP box, recruit CC the DCX(DTL) complex, leading to its degradation. Ubiquitination CC at Ser-2 leads to degradation by the proteasome pathway. CC Ubiquitinated by RNF114; leading to proteasomal degradation. CC {ECO:0000269|PubMed:15226418}. CC -!- PTM: Acetylation leads to protein stability. Acetylated in vitro CC on Lys-141, Lys-154, Lys-161 and Lys-163. Deacetylation by HDAC1 CC is prevented by competitive binding of C10orf90/FATS to HDAC1 (By CC similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the CDI family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB59559.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=AAB59560.1; 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/CDKN1AID139.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cdkn1a/"; 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; L25610; AAA16109.1; -; mRNA. DR EMBL; S67388; AAB29246.1; -; mRNA. DR EMBL; U09579; AAA85641.1; -; mRNA. DR EMBL; U03106; AAC04313.1; -; mRNA. DR EMBL; L26165; AAA19811.1; -; mRNA. DR EMBL; L47232; AAB59559.1; ALT_INIT; mRNA. DR EMBL; L47233; AAB59560.1; ALT_INIT; mRNA. DR EMBL; AF497972; AAM11787.1; -; Genomic_DNA. DR EMBL; BT006719; AAP35365.1; -; mRNA. DR EMBL; AB451290; BAG70104.1; -; mRNA. DR EMBL; AB451422; BAG70236.1; -; mRNA. DR EMBL; CR536533; CAG38770.1; -; mRNA. DR EMBL; Z85996; CAB06656.1; -; Genomic_DNA. DR EMBL; CH471081; EAX03904.1; -; Genomic_DNA. DR EMBL; BC000275; AAH00275.1; -; mRNA. DR EMBL; BC000312; AAH00312.1; -; mRNA. DR EMBL; BC001935; AAH01935.1; -; mRNA. DR EMBL; BC013967; AAH13967.1; -; mRNA. DR CCDS; CCDS4824.1; -. DR PIR; I54380; I54380. DR PIR; I68674; I68674. DR RefSeq; NP_000380.1; NM_000389.4. DR RefSeq; NP_001207706.1; NM_001220777.1. DR RefSeq; NP_001207707.1; NM_001220778.1. DR RefSeq; NP_001278478.1; NM_001291549.1. DR RefSeq; NP_510867.1; NM_078467.2. DR UniGene; Hs.370771; -. DR UniGene; Hs.732576; -. DR PDB; 1AXC; X-ray; 2.60 A; B/D/F=139-160. DR PDB; 2ZVV; X-ray; 2.00 A; X/Y=139-160. DR PDB; 2ZVW; X-ray; 2.50 A; I/J/K/L/M/N/O/P=139-160. DR PDB; 4RJF; X-ray; 2.01 A; B/D/F=139-160. DR PDBsum; 1AXC; -. DR PDBsum; 2ZVV; -. DR PDBsum; 2ZVW; -. DR PDBsum; 4RJF; -. DR DisProt; DP00016; -. DR ProteinModelPortal; P38936; -. DR SMR; P38936; 17-77. DR BioGrid; 107460; 260. DR DIP; DIP-246N; -. DR IntAct; P38936; 157. DR MINT; MINT-104203; -. DR STRING; 9606.ENSP00000244741; -. DR BindingDB; P38936; -. DR ChEMBL; CHEMBL5021; -. DR PhosphoSite; P38936; -. DR BioMuta; CDKN1A; -. DR DMDM; 729143; -. DR SWISS-2DPAGE; P38936; -. DR PaxDb; P38936; -. DR PRIDE; P38936; -. DR DNASU; 1026; -. DR Ensembl; ENST00000244741; ENSP00000244741; ENSG00000124762. DR Ensembl; ENST00000373711; ENSP00000362815; ENSG00000124762. DR Ensembl; ENST00000405375; ENSP00000384849; ENSG00000124762. DR Ensembl; ENST00000448526; ENSP00000409259; ENSG00000124762. DR Ensembl; ENST00000615513; ENSP00000482768; ENSG00000124762. DR GeneID; 1026; -. DR KEGG; hsa:1026; -. DR UCSC; uc003omm.4; human. DR CTD; 1026; -. DR GeneCards; CDKN1A; -. DR HGNC; HGNC:1784; CDKN1A. DR HPA; CAB000064; -. DR HPA; HPA051359; -. DR MIM; 116899; gene. DR neXtProt; NX_P38936; -. DR Orphanet; 652; Multiple endocrine neoplasia type 1. DR PharmGKB; PA104; -. DR eggNOG; KOG4743; Eukaryota. DR eggNOG; ENOG410XXN5; LUCA. DR GeneTree; ENSGT00530000063588; -. DR HOGENOM; HOG000285999; -. DR HOVERGEN; HBG050868; -. DR InParanoid; P38936; -. DR KO; K06625; -. DR OMA; FAWERVW; -. DR OrthoDB; EOG7GJ6HD; -. DR PhylomeDB; P38936; -. DR TreeFam; TF101038; -. DR Reactome; R-HSA-187577; SCF(Skp2)-mediated degradation of p27/p21. DR Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol. DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence. DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer. DR Reactome; R-HSA-68949; Orc1 removal from chromatin. DR Reactome; R-HSA-69202; Cyclin E associated events during G1/S transition. DR Reactome; R-HSA-69231; Cyclin D associated events in G1. DR Reactome; R-HSA-69563; p53-Dependent G1 DNA Damage Response. DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry. DR Reactome; R-HSA-69895; Transcriptional activation of cell cycle inhibitor p21. DR ChiTaRS; CDKN1A; human. DR EvolutionaryTrace; P38936; -. DR GeneWiki; P21; -. DR GenomeRNAi; 1026; -. DR NextBio; 4309; -. DR PRO; PR:P38936; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; P38936; -. DR CleanEx; HS_CDKN1A; -. DR ExpressionAtlas; P38936; baseline and differential. DR Genevisible; P38936; HS. DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0070557; C:PCNA-p21 complex; IDA:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0019912; F:cyclin-dependent protein kinase activating kinase activity; IDA:UniProtKB. DR GO; GO:0004861; F:cyclin-dependent protein serine/threonine kinase inhibitor activity; TAS:BHF-UCL. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0007050; P:cell cycle arrest; IDA:BHF-UCL. DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:BHF-UCL. DR GO; GO:0031668; P:cellular response to extracellular stimulus; IMP:BHF-UCL. DR GO; GO:0034605; P:cellular response to heat; IEA:Ensembl. DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:BHF-UCL. DR GO; GO:0071493; P:cellular response to UV-B; ISS:UniProtKB. DR GO; GO:0090398; P:cellular senescence; IMP:BHF-UCL. DR GO; GO:0006977; P:DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; IDA:BHF-UCL. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IDA:BHF-UCL. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:BHF-UCL. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0060574; P:intestinal epithelial cell maturation; IEA:Ensembl. DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; TAS:ProtInc. DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IEA:Ensembl. DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome. DR GO; GO:0071850; P:mitotic cell cycle arrest; IEA:Ensembl. DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0030308; P:negative regulation of cell growth; IDA:BHF-UCL. DR GO; GO:0008285; P:negative regulation of cell proliferation; IDA:BHF-UCL. DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IEA:Ensembl. DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IGI:MGI. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0042326; P:negative regulation of phosphorylation; IDA:BHF-UCL. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome. DR GO; GO:0031100; P:organ regeneration; IEA:Ensembl. DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; TAS:Reactome. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IEA:Ensembl. DR GO; GO:1904031; P:positive regulation of cyclin-dependent protein kinase activity; IDA:GOC. DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:BHF-UCL. DR GO; GO:0043068; P:positive regulation of programmed cell death; IEA:Ensembl. DR GO; GO:2000379; P:positive regulation of reactive oxygen species metabolic process; IMP:BHF-UCL. DR GO; GO:0007265; P:Ras protein signal transduction; IEP:BHF-UCL. DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; TAS:ProtInc. DR GO; GO:2000278; P:regulation of DNA biosynthetic process; IEA:Ensembl. DR GO; GO:0033158; P:regulation of protein import into nucleus, translocation; IEA:Ensembl. DR GO; GO:0046685; P:response to arsenic-containing substance; IEA:Ensembl. DR GO; GO:0051412; P:response to corticosterone; 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:0010243; P:response to organonitrogen compound; IEA:Ensembl. DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl. DR GO; GO:0090400; P:stress-induced premature senescence; TAS:BHF-UCL. DR InterPro; IPR003175; CDI. DR InterPro; IPR029841; CDKN1A_vertebrate. DR PANTHER; PTHR10265; PTHR10265; 1. DR PANTHER; PTHR10265:SF16; PTHR10265:SF16; 1. DR Pfam; PF02234; CDI; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cell cycle; Complete proteome; Cytoplasm; KW Direct protein sequencing; Metal-binding; Nucleus; Phosphoprotein; KW Polymorphism; Protein kinase inhibitor; Reference proteome; KW Ubl conjugation; Zinc; Zinc-finger. FT INIT_MET 1 1 Removed. {ECO:0000269|PubMed:15574338}. FT CHAIN 2 164 Cyclin-dependent kinase inhibitor 1. FT /FTId=PRO_0000190079. FT ZN_FING 13 41 C4-type. {ECO:0000255}. FT REGION 17 24 Required for binding cyclins. FT REGION 53 58 Required for binding CDKs. FT MOTIF 140 164 PIP-box K+4 motif. FT MOTIF 141 156 Nuclear localization signal. FT {ECO:0000255}. FT MOD_RES 2 2 N-acetylserine. FT {ECO:0000269|PubMed:15574338}. FT MOD_RES 80 80 Phosphothreonine; by LKB1. FT {ECO:0000269|PubMed:25329316}. FT MOD_RES 114 114 Phosphoserine; by GSK3-beta. FT {ECO:0000269|PubMed:18794347}. FT MOD_RES 130 130 Phosphoserine. FT {ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:18669648}. FT MOD_RES 145 145 Phosphothreonine; by PKA; PKB/AKT1, PIM1 FT and PIM2. {ECO:0000269|PubMed:10753973, FT ECO:0000269|PubMed:11463845, FT ECO:0000269|PubMed:12431783, FT ECO:0000269|PubMed:16982699, FT ECO:0000269|PubMed:20307683}. FT MOD_RES 146 146 Phosphoserine; by PKC and NUAK1. FT {ECO:0000269|PubMed:10753973, FT ECO:0000269|PubMed:25329316}. FT MOD_RES 160 160 Phosphoserine; by PKC; in vitro. FT {ECO:0000269|PubMed:10753973}. FT CROSSLNK 2 2 Glycyl serine ester (Ser-Gly) (interchain FT with G-Cter in ubiquitin). FT {ECO:0000305|PubMed:15226418}. FT VARIANT 4 4 P -> L (in dbSNP:rs4986866). FT /FTId=VAR_048686. FT VARIANT 31 31 S -> R (in dbSNP:rs1801270). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7655464, FT ECO:0000269|Ref.8}. FT /FTId=VAR_011870. FT VARIANT 63 63 F -> L (in dbSNP:rs4986867). FT /FTId=VAR_048687. FT VARIANT 149 149 D -> G (in dbSNP:rs1801724). FT /FTId=VAR_014875. FT MUTAGEN 80 80 T->A: Abolishes UV radiation-induced FT phosphorylation and subsequent FT degradation. FT {ECO:0000269|PubMed:25329316}. FT MUTAGEN 114 114 S->E: Phosphomimetic mutant, increases FT ubiquitination by the DCX(DTL) complex. FT {ECO:0000269|PubMed:18794347}. FT MUTAGEN 144 150 QTSMTDF->ATSATDA: Abolishes interaction FT with PCNA and subsequent degradation by FT the proteasome. FT {ECO:0000269|PubMed:18794347}. FT MUTAGEN 145 145 T->A: Reduces phosphorylation by Akt; no FT change in interaction with PCNA, CDK2 or FT CDK4; no change in subcellular location. FT {ECO:0000269|PubMed:11463845}. FT MUTAGEN 145 145 T->D: No interaction with PCNA; 59% FT inhibition of CDK2 binding; modest FT inhibition of CDK4 binding; no change in FT subcellular location. FT {ECO:0000269|PubMed:11463845}. FT MUTAGEN 146 146 S->A: No change in interaction with PCNA. FT Abolishes UV radiation-induced FT phosphorylation and subsequent FT degradation. FT {ECO:0000269|PubMed:11463845, FT ECO:0000269|PubMed:25329316}. FT MUTAGEN 146 146 S->D: Reduces interaction with PCNA. FT {ECO:0000269|PubMed:11463845}. FT MUTAGEN 147 151 MTDFY->ATDAAA: Abolishes interaction with FT PCNA and subsequent degradation by the FT proteasome. FT {ECO:0000269|PubMed:18703516}. FT MUTAGEN 154 156 KRR->AAA: Abolishes degradation by the FT proteasome without affecting the FT interaction with PCNA. FT {ECO:0000269|PubMed:18703516}. FT HELIX 147 149 {ECO:0000244|PDB:2ZVV}. FT STRAND 151 158 {ECO:0000244|PDB:4RJF}. SQ SEQUENCE 164 AA; 18119 MW; 98D1E7C519ADFCA9 CRC64; MSEPAGDVRQ NPCGSKACRR LFGPVDSEQL SRDCDALMAG CIQEARERWN FDFVTETPLE GDFAWERVRG LGLPKLYLPT GPRRGRDELG GGRRPGTSPA LLQGTAEEDH VDLSLSCTLV PRSGEQAEGS PGGPGDSQGR KRRQTSMTDF YHSKRRLIFS KRKP // ID DNLI1_HUMAN Reviewed; 919 AA. AC P18858; B2RAI8; B4DTU4; Q2TB12; Q32P23; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1990, sequence version 1. DT 11-NOV-2015, entry version 174. DE RecName: Full=DNA ligase 1; DE EC=6.5.1.1; DE AltName: Full=DNA ligase I; DE AltName: Full=Polydeoxyribonucleotide synthase [ATP] 1; GN Name=LIG1; 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=T lymphoblast; RX PubMed=2204063; DOI=10.1073/pnas.87.17.6679; RA Barnes D.E., Johnston L.H., Kodama K., Tomkinson A.E., Lasko D.D., RA Lindahl T.; RT "Human DNA ligase I cDNA: cloning and functional expression in RT Saccharomyces cerevisiae."; RL Proc. Natl. Acad. Sci. U.S.A. 87:6679-6683(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-24; TRP-62; RP GLU-249; SER-267; MET-349; ILE-369; VAL-480; ILE-614 AND LEU-677. RG NIEHS SNPs program; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Placenta, and Thymus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M., RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [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 1 AND 2). RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 716-753 (ISOFORM 1). RX PubMed=1881902; DOI=10.1073/pnas.88.17.7615; RA Petrini J.H.J., Huwiler K.G., Weaver D.T.; RT "A wild-type DNA ligase I gene is expressed in Bloom's syndrome RT cells."; RL Proc. Natl. Acad. Sci. U.S.A. 88:7615-7619(1991). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-66; SER-76 AND SER-141, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-66; SER-76; RP THR-195 AND THR-233, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-66 AND SER-76, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17693683; DOI=10.1074/mcp.M700120-MCP200; RA Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., RA Li S.-J., Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R.; RT "Quantitative phosphoproteome profiling of Wnt3a-mediated signaling RT network: indicating the involvement of ribonucleoside-diphosphate RT reductase M2 subunit phosphorylation at residue serine 20 in canonical RT Wnt signal transduction."; RL Mol. Cell. Proteomics 6:1952-1967(2007). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-51; SER-141; THR-195; RP SER-201; THR-233; SER-911 AND SER-913, 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 [12] RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-422. RC TISSUE=Cervix carcinoma; RX PubMed=18655026; DOI=10.1002/pmic.200700887; RA Tan F., Lu L., Cai Y., Wang J., Xie Y., Wang L., Gong Y., Xu B.-E., RA Wu J., Luo Y., Qiang B., Yuan J., Sun X., Peng X.; RT "Proteomic analysis of ubiquitinated proteins in normal hepatocyte RT cell line Chang liver cells."; RL Proteomics 8:2885-2896(2008). RN [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-49; SER-51; SER-66; RP SER-141; THR-195; SER-201; SER-911 AND SER-913, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47; SER-49; SER-51; RP SER-66; SER-76; SER-141; THR-195; SER-201 AND SER-911, 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-51; SER-66; SER-76; RP SER-141 AND THR-195, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [18] RP INTERACTION WITH PCNA. RX PubMed=24911150; DOI=10.1172/JCI74593; RA Baple E.L., Chambers H., Cross H.E., Fawcett H., Nakazawa Y., RA Chioza B.A., Harlalka G.V., Mansour S., Sreekantan-Nair A., RA Patton M.A., Muggenthaler M., Rich P., Wagner K., Coblentz R., RA Stein C.K., Last J.I., Taylor A.M., Jackson A.P., Ogi T., RA Lehmann A.R., Green C.M., Crosby A.H.; RT "Hypomorphic PCNA mutation underlies a human DNA repair disorder."; RL J. Clin. Invest. 124:3137-3146(2014). RN [19] RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 233-919 IN COMPLEX WITH RP NICKED DNA AND AMP, COFACTOR, AND ACTIVE SITE. RX PubMed=15565146; DOI=10.1038/nature03082; RA Pascal J.M., O'Brien P.J., Tomkinson A.E., Ellenberger T.; RT "Human DNA ligase I completely encircles and partially unwinds nicked RT DNA."; RL Nature 432:473-478(2004). RN [20] RP VARIANTS LYS-566 AND TRP-771. RX PubMed=1581963; DOI=10.1016/0092-8674(92)90450-Q; RA Barnes D.E., Tomkinson A.E., Lehmann A.R., Webster A.D.B., Lindahl T.; RT "Mutations in the DNA ligase I gene of an individual with RT immunodeficiencies and cellular hypersensitivity to DNA-damaging RT agents."; RL Cell 69:495-503(1992). RN [21] RP VARIANTS [LARGE SCALE ANALYSIS] GLU-152 AND LEU-612. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C., RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., RA Vogelstein B., Kinzler K.W., Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal RT cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: DNA ligase that seals nicks in double-stranded DNA CC during DNA replication, DNA recombination and DNA repair. CC -!- CATALYTIC ACTIVITY: ATP + (deoxyribonucleotide)(n) + CC (deoxyribonucleotide)(m) = AMP + diphosphate + CC (deoxyribonucleotide)(n+m). {ECO:0000255|PROSITE- CC ProRule:PRU10135}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:15565146}; CC -!- SUBUNIT: Interacts with PCNA. {ECO:0000269|PubMed:24911150}. CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P18858-1; Sequence=Displayed; CC Name=2; CC IsoId=P18858-2; Sequence=VSP_056139, VSP_056140; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=P18858-3; Sequence=VSP_057320, VSP_057321; CC Note=No experimental confirmation available.; CC -!- SIMILARITY: Belongs to the ATP-dependent DNA ligase family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=LIG1base; Note=LIG1 mutation db; CC URL="http://structure.bmc.lu.se/idbase/LIG1base/"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/lig1/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=DNA ligase entry; CC URL="https://en.wikipedia.org/wiki/DNA_ligase"; 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; M36067; AAA59518.1; -; mRNA. DR EMBL; AF527418; AAM77697.1; -; Genomic_DNA. DR EMBL; AK300370; BAG62106.1; -; mRNA. DR EMBL; AK314210; BAG36885.1; -; mRNA. DR EMBL; AC011466; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; KC877741; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471177; EAW52316.1; -; Genomic_DNA. DR EMBL; BC108318; AAI08319.1; -; mRNA. DR EMBL; BC110622; AAI10623.1; -; mRNA. DR CCDS; CCDS12711.1; -. [P18858-1] DR CCDS; CCDS74409.1; -. [P18858-3] DR PIR; A36048; A41275. DR RefSeq; NP_000225.1; NM_000234.2. [P18858-1] DR RefSeq; NP_001275992.1; NM_001289063.1. [P18858-3] DR RefSeq; NP_001275993.1; NM_001289064.1. DR RefSeq; XP_006723279.1; XM_006723216.2. [P18858-1] DR UniGene; Hs.1770; -. DR PDB; 1X9N; X-ray; 3.00 A; A=233-919. DR PDBsum; 1X9N; -. DR ProteinModelPortal; P18858; -. DR SMR; P18858; 262-901. DR BioGrid; 110166; 6. DR DIP; DIP-24215N; -. DR IntAct; P18858; 4. DR MINT; MINT-141868; -. DR STRING; 9606.ENSP00000263274; -. DR BindingDB; P18858; -. DR ChEMBL; CHEMBL5694; -. DR DrugBank; DB00290; Bleomycin. DR PhosphoSite; P18858; -. DR BioMuta; LIG1; -. DR DMDM; 118773; -. DR MaxQB; P18858; -. DR PaxDb; P18858; -. DR PeptideAtlas; P18858; -. DR PRIDE; P18858; -. DR Ensembl; ENST00000263274; ENSP00000263274; ENSG00000105486. [P18858-1] DR Ensembl; ENST00000427526; ENSP00000442841; ENSG00000105486. [P18858-3] DR Ensembl; ENST00000601091; ENSP00000471836; ENSG00000105486. [P18858-2] DR Ensembl; ENST00000613670; ENSP00000483027; ENSG00000105486. [P18858-2] DR GeneID; 3978; -. DR KEGG; hsa:3978; -. DR UCSC; uc002pia.1; human. [P18858-1] DR UCSC; uc010xzg.1; human. DR CTD; 3978; -. DR GeneCards; LIG1; -. DR HGNC; HGNC:6598; LIG1. DR HPA; CAB037015; -. DR HPA; HPA041431; -. DR HPA; HPA048071; -. DR MIM; 126391; gene. DR neXtProt; NX_P18858; -. DR PharmGKB; PA30372; -. DR eggNOG; KOG0967; Eukaryota. DR eggNOG; COG1793; LUCA. DR GeneTree; ENSGT00810000125528; -. DR HOGENOM; HOG000036006; -. DR HOVERGEN; HBG005514; -. DR InParanoid; P18858; -. DR KO; K10747; -. DR OMA; PQVVIEV; -. DR OrthoDB; EOG7RFTGN; -. DR PhylomeDB; P18858; -. DR TreeFam; TF300342; -. DR BRENDA; 6.5.1.1; 2681. DR Reactome; R-HSA-109979; Gap-filling DNA repair synthesis and ligation in TC-NER. DR Reactome; R-HSA-110362; POLB-Dependent Long Patch Base Excision Repair. DR Reactome; R-HSA-174414; Processive synthesis on the C-strand of the telomere. DR Reactome; R-HSA-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha). DR Reactome; R-HSA-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta). DR Reactome; R-HSA-5651801; PCNA-Dependent Long Patch Base Excision Repair. DR Reactome; R-HSA-69183; Processive synthesis on the lagging strand. DR Reactome; R-HSA-74969; Gap-filling DNA repair synthesis and ligation in GG-NER. DR Reactome; R-HSA-75228; Resolution of D-loop Structures through Holliday Junction Intermediates. DR ChiTaRS; LIG1; human. DR EvolutionaryTrace; P18858; -. DR GeneWiki; LIG1; -. DR GenomeRNAi; 3978; -. DR NextBio; 15592; -. DR PRO; PR:P18858; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; P18858; -. DR CleanEx; HS_LIG1; -. DR ExpressionAtlas; P18858; baseline and differential. DR Genevisible; P18858; HS. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; TAS:ProtInc. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003677; F:DNA binding; TAS:ProtInc. DR GO; GO:0003910; F:DNA ligase (ATP) activity; IBA:GO_Central. DR GO; GO:0003909; F:DNA ligase activity; IDA:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc. DR GO; GO:0006284; P:base-excision repair; IDA:BHF-UCL. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0071897; P:DNA biosynthetic process; IEA:InterPro. DR GO; GO:0006266; P:DNA ligation; IDA:GOC. DR GO; GO:0006259; P:DNA metabolic process; TAS:ProtInc. DR GO; GO:0006281; P:DNA repair; TAS:Reactome. DR GO; GO:0006271; P:DNA strand elongation involved in DNA replication; TAS:Reactome. DR GO; GO:0006302; P:double-strand break repair; TAS:Reactome. DR GO; GO:0000724; P:double-strand break repair via homologous recombination; TAS:Reactome. DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IEA:Ensembl. DR GO; GO:0006273; P:lagging strand elongation; IBA:GO_Central. DR GO; GO:0006298; P:mismatch repair; TAS:Reactome. DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome. DR GO; GO:0006289; P:nucleotide-excision repair; TAS:Reactome. DR GO; GO:0006297; P:nucleotide-excision repair, DNA gap filling; TAS:Reactome. DR GO; GO:1903461; P:Okazaki fragment processing involved in mitotic DNA replication; IBA:GO_Central. DR GO; GO:1903469; P:removal of RNA primer involved in mitotic DNA replication; IBA:GO_Central. DR GO; GO:0042542; P:response to hydrogen peroxide; IEA:Ensembl. DR GO; GO:0000723; P:telomere maintenance; TAS:Reactome. DR GO; GO:0000722; P:telomere maintenance via recombination; TAS:Reactome. DR GO; GO:0032201; P:telomere maintenance via semi-conservative replication; TAS:Reactome. DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; TAS:Reactome. DR Gene3D; 1.10.3260.10; -; 1. DR Gene3D; 2.40.50.140; -; 1. DR InterPro; IPR000977; DNA_ligase_ATP-dep. DR InterPro; IPR012309; DNA_ligase_ATP-dep_C. DR InterPro; IPR012310; DNA_ligase_ATP-dep_cent. DR InterPro; IPR016059; DNA_ligase_ATP-dep_CS. DR InterPro; IPR012308; DNA_ligase_ATP-dep_N. DR InterPro; IPR012340; NA-bd_OB-fold. DR Pfam; PF04679; DNA_ligase_A_C; 1. DR Pfam; PF01068; DNA_ligase_A_M; 1. DR Pfam; PF04675; DNA_ligase_A_N; 1. DR SUPFAM; SSF117018; SSF117018; 1. DR SUPFAM; SSF50249; SSF50249; 1. DR TIGRFAMs; TIGR00574; dnl1; 1. DR PROSITE; PS00697; DNA_LIGASE_A1; 1. DR PROSITE; PS00333; DNA_LIGASE_A2; 1. DR PROSITE; PS50160; DNA_LIGASE_A3; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Cell cycle; Cell division; Complete proteome; DNA damage; KW DNA recombination; DNA repair; DNA replication; Isopeptide bond; KW Ligase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; KW Phosphoprotein; Polymorphism; Reference proteome; Ubl conjugation. FT CHAIN 1 919 DNA ligase 1. FT /FTId=PRO_0000059570. FT REGION 449 458 Interaction with target DNA. FT REGION 642 644 Interaction with target DNA. FT ACT_SITE 568 568 N6-AMP-lysine intermediate. FT {ECO:0000255|PROSITE-ProRule:PRU10135}. FT METAL 621 621 Magnesium 1. {ECO:0000305}. FT METAL 720 720 Magnesium 2. {ECO:0000305}. FT BINDING 566 566 ATP. FT BINDING 573 573 ATP. FT BINDING 589 589 ATP. FT BINDING 725 725 ATP. FT BINDING 738 738 ATP. {ECO:0000250}. FT BINDING 744 744 ATP. FT SITE 305 305 Interaction with target DNA. FT SITE 590 590 Interaction with target DNA. FT SITE 770 770 Interaction with target DNA. FT SITE 795 795 Interaction with target DNA. FT MOD_RES 47 47 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 49 49 Phosphoserine. FT {ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231}. FT MOD_RES 51 51 Phosphoserine. FT {ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 66 66 Phosphoserine. FT {ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:17693683, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 76 76 Phosphoserine. FT {ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:17693683, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 141 141 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 195 195 Phosphothreonine. FT {ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 201 201 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231}. FT MOD_RES 226 226 N6-acetyllysine. FT {ECO:0000250|UniProtKB:P37913}. FT MOD_RES 233 233 Phosphothreonine. FT {ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:18669648}. FT MOD_RES 911 911 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231}. FT MOD_RES 913 913 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332}. FT CROSSLNK 422 422 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000269|PubMed:18655026}. FT VAR_SEQ 7 36 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_057320. FT VAR_SEQ 153 153 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_057321. FT VAR_SEQ 796 801 LGTGFS -> VLGNWG (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_056139. FT VAR_SEQ 802 919 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_056140. FT VARIANT 24 24 A -> V (in dbSNP:rs3730855). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_018802. FT VARIANT 52 52 P -> L (in dbSNP:rs4987181). FT /FTId=VAR_020194. FT VARIANT 62 62 R -> W (in dbSNP:rs3730863). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_018803. FT VARIANT 72 72 D -> G (in dbSNP:rs4987070). FT /FTId=VAR_020195. FT VARIANT 152 152 K -> E (in a colorectal cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_036511. FT VARIANT 249 249 G -> E (in dbSNP:rs3730911). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_016766. FT VARIANT 267 267 N -> S (in dbSNP:rs3730933). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_016767. FT VARIANT 349 349 V -> M (in dbSNP:rs3730947). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_018804. FT VARIANT 369 369 V -> I (in dbSNP:rs3730966). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_018805. FT VARIANT 409 409 R -> H (in dbSNP:rs4987068). FT /FTId=VAR_016768. FT VARIANT 480 480 M -> V (in dbSNP:rs3730980). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_016769. FT VARIANT 566 566 E -> K (found in a patient with a FT syndrome of immunodeficiency and FT increased cellular sensitivity to DNA- FT damaging agents due to LIG1 deficiency; FT compound heterozygote carrying W-771). FT {ECO:0000269|PubMed:1581963}. FT /FTId=VAR_002262. FT VARIANT 612 612 S -> L (in a colorectal cancer sample; FT somatic mutation). FT {ECO:0000269|PubMed:16959974}. FT /FTId=VAR_036512. FT VARIANT 614 614 T -> I (in dbSNP:rs3731003). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_016770. FT VARIANT 677 677 R -> L (in dbSNP:rs3731008). FT {ECO:0000269|Ref.2}. FT /FTId=VAR_018806. FT VARIANT 771 771 R -> W (found in a patient with a FT syndrome of immunodeficiency and FT increased cellular sensitivity to DNA- FT damaging agents due to LIG1 deficiency; FT compound heterozygote carrying K-566). FT {ECO:0000269|PubMed:1581963}. FT /FTId=VAR_002263. FT HELIX 263 265 {ECO:0000244|PDB:1X9N}. FT HELIX 275 278 {ECO:0000244|PDB:1X9N}. FT HELIX 289 300 {ECO:0000244|PDB:1X9N}. FT HELIX 305 322 {ECO:0000244|PDB:1X9N}. FT HELIX 324 326 {ECO:0000244|PDB:1X9N}. FT HELIX 327 335 {ECO:0000244|PDB:1X9N}. FT HELIX 341 343 {ECO:0000244|PDB:1X9N}. FT HELIX 351 362 {ECO:0000244|PDB:1X9N}. FT HELIX 366 376 {ECO:0000244|PDB:1X9N}. FT HELIX 379 382 {ECO:0000244|PDB:1X9N}. FT HELIX 401 413 {ECO:0000244|PDB:1X9N}. FT HELIX 419 433 {ECO:0000244|PDB:1X9N}. FT HELIX 438 446 {ECO:0000244|PDB:1X9N}. FT HELIX 456 469 {ECO:0000244|PDB:1X9N}. FT TURN 483 486 {ECO:0000244|PDB:1X9N}. FT HELIX 489 509 {ECO:0000244|PDB:1X9N}. FT HELIX 513 527 {ECO:0000244|PDB:1X9N}. FT HELIX 529 531 {ECO:0000244|PDB:1X9N}. FT STRAND 544 550 {ECO:0000244|PDB:1X9N}. FT HELIX 551 557 {ECO:0000244|PDB:1X9N}. FT TURN 558 560 {ECO:0000244|PDB:1X9N}. FT STRAND 563 578 {ECO:0000244|PDB:1X9N}. FT STRAND 584 587 {ECO:0000244|PDB:1X9N}. FT TURN 595 597 {ECO:0000244|PDB:1X9N}. FT HELIX 599 603 {ECO:0000244|PDB:1X9N}. FT HELIX 606 608 {ECO:0000244|PDB:1X9N}. FT STRAND 616 625 {ECO:0000244|PDB:1X9N}. FT TURN 627 629 {ECO:0000244|PDB:1X9N}. FT HELIX 635 638 {ECO:0000244|PDB:1X9N}. FT HELIX 648 650 {ECO:0000244|PDB:1X9N}. FT STRAND 653 665 {ECO:0000244|PDB:1X9N}. FT HELIX 675 685 {ECO:0000244|PDB:1X9N}. FT TURN 690 692 {ECO:0000244|PDB:1X9N}. FT STRAND 693 695 {ECO:0000244|PDB:1X9N}. FT HELIX 704 716 {ECO:0000244|PDB:1X9N}. FT STRAND 718 730 {ECO:0000244|PDB:1X9N}. FT TURN 735 737 {ECO:0000244|PDB:1X9N}. FT STRAND 739 746 {ECO:0000244|PDB:1X9N}. FT HELIX 747 751 {ECO:0000244|PDB:1X9N}. FT STRAND 755 767 {ECO:0000244|PDB:1X9N}. FT STRAND 774 784 {ECO:0000244|PDB:1X9N}. FT TURN 785 788 {ECO:0000244|PDB:1X9N}. FT STRAND 789 796 {ECO:0000244|PDB:1X9N}. FT HELIX 802 814 {ECO:0000244|PDB:1X9N}. FT STRAND 816 819 {ECO:0000244|PDB:1X9N}. FT STRAND 827 829 {ECO:0000244|PDB:1X9N}. FT STRAND 833 836 {ECO:0000244|PDB:1X9N}. FT STRAND 841 854 {ECO:0000244|PDB:1X9N}. FT TURN 857 861 {ECO:0000244|PDB:1X9N}. FT STRAND 867 872 {ECO:0000244|PDB:1X9N}. FT STRAND 874 878 {ECO:0000244|PDB:1X9N}. FT HELIX 884 886 {ECO:0000244|PDB:1X9N}. FT HELIX 890 900 {ECO:0000244|PDB:1X9N}. SQ SEQUENCE 919 AA; 101736 MW; B2854DAE38A8D4AD CRC64; MQRSIMSFFH PKKEGKAKKP EKEASNSSRE TEPPPKAALK EWNGVVSESD SPVKRPGRKA ARVLGSEGEE EDEALSPAKG QKPALDCSQV SPPRPATSPE NNASLSDTSP MDSSPSGIPK RRTARKQLPK RTIQEVLEEQ SEDEDREAKR KKEEEEEETP KESLTEAEVA TEKEGEDGDQ PTTPPKPLKT SKAETPTESV SEPEVATKQE LQEEEEQTKP PRRAPKTLSS FFTPRKPAVK KEVKEEEPGA PGKEGAAEGP LDPSGYNPAK NNYHPVEDAC WKPGQKVPYL AVARTFEKIE EVSARLRMVE TLSNLLRSVV ALSPPDLLPV LYLSLNHLGP PQQGLELGVG DGVLLKAVAQ ATGRQLESVR AEAAEKGDVG LVAENSRSTQ RLMLPPPPLT ASGVFSKFRD IARLTGSAST AKKIDIIKGL FVACRHSEAR FIARSLSGRL RLGLAEQSVL AALSQAVSLT PPGQEFPPAM VDAGKGKTAE ARKTWLEEQG MILKQTFCEV PDLDRIIPVL LEHGLERLPE HCKLSPGIPL KPMLAHPTRG ISEVLKRFEE AAFTCEYKYD GQRAQIHALE GGEVKIFSRN QEDNTGKYPD IISRIPKIKL PSVTSFILDT EAVAWDREKK QIQPFQVLTT RKRKEVDASE IQVQVCLYAF DLIYLNGESL VREPLSRRRQ LLRENFVETE GEFVFATSLD TKDIEQIAEF LEQSVKDSCE GLMVKTLDVD ATYEIAKRSH NWLKLKKDYL DGVGDTLDLV VIGAYLGRGK RAGRYGGFLL ASYDEDSEEL QAICKLGTGF SDEELEEHHQ SLKALVLPSP RPYVRIDGAV IPDHWLDPSA VWEVKCADLS LSPIYPAARG LVDSDKGISL RFPRFIRVRE DKQPEQATTS AQVACLYRKQ SQIQNQQGED SGSDPEDTY // ID DNLI1_YEAST Reviewed; 755 AA. AC P04819; D6VRI7; Q12736; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 11-NOV-2015, entry version 170. DE RecName: Full=DNA ligase 1; DE EC=6.5.1.1; DE AltName: Full=DNA ligase I; DE AltName: Full=Polydeoxyribonucleotide synthase [ATP] 1; DE Flags: Precursor; GN Name=CDC9; OrderedLocusNames=YDL164C; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3909103; DOI=10.1093/nar/13.23.8323; RA Barker D.G., White J.H.M., Johnston L.H.; RT "The nucleotide sequence of the DNA ligase gene (CDC9) from RT Saccharomyces cerevisiae: a gene which is cell-cycle regulated and RT induced in response to DNA damage."; RL Nucleic Acids Res. 13:8323-8337(1985). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169867; RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G., RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C., RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F., RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M., RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T., RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C., RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S., RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., RA Paulin L., Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., RA Prydz H., Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., RA Rieger M., Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., RA Scharfe M., Schmidt E.R., Schneider C., Scholler P., Schwarz S., RA Soler-Mira A., Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., RA Volckaert G., Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., RA Harris D.E., Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., RA Gentles S., Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., RA Niblett D., Odell C., Oliver K., Rajandream M.A., Richards C., RA Shore L., Walsh S.V., Barrell B.G., Dietrich F.S., Mulligan J.T., RA Allen E., Araujo R., Aviles E., Berno A., Carpenter J., Chen E., RA Cherry J.M., Chung E., Duncan M., Hunicke-Smith S., Hyman R.W., RA Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., RA Namath A., Oefner P., Oh C., Petel F.X., Roberts D., Schramm S., RA Schroeder M., Shogren T., Shroff N., Winant A., Yelton M.A., RA Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R., RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., RA Greco T., Hallsworth K., Hawkins J., Hillier L.W., Jier M., RA Johnson D., Johnston L., Kirsten J., Kucaba T., Langston Y., RA Latreille P., Le T., Mardis E., Menezes S., Miller N., Nhan M., RA Pauley A., Peluso D., Rifkin L., Riles L., Taich A., Trevaskis E., RA Vignati D., Wilcox L., Wohldman P., Vaudin M., Wilson R., RA Waterston R., Albermann K., Hani J., Heumann K., Kleine K., RA Mewes H.-W., Zollner A., Zaccaria P.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV."; RL Nature 387:75-78(1997). RN [3] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., RA Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and RT now."; RL G3 (Bethesda) 4:389-398(2014). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., RA Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., RA Williamson J., Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., RA Kolodner R.D., LaBaer J.; RT "Approaching a complete repository of sequence-verified protein- RT encoding clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 610-755. RC STRAIN=ATCC 38626 / AH22 / NRRL Y-12843; RX PubMed=8483449; RA Wehner E.P., Rao E., Brendel M.; RT "Molecular structure and genetic regulation of SFA, a gene responsible RT for resistance to formaldehyde in Saccharomyces cerevisiae, and RT characterization of its protein product."; RL Mol. Gen. Genet. 237:351-358(1993). RN [6] RP ALTERNATIVE INITIATION. RX PubMed=10531002; DOI=10.1016/S0960-9822(99)80477-1; RA Willer M., Rainey M., Pullen T., Stirling C.J.; RT "The yeast CDC9 gene encodes both a nuclear and a mitochondrial form RT of DNA ligase I."; RL Curr. Biol. 9:1085-1094(1999). RN [7] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., RA Dephoure N., O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58 AND SER-75, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=17287358; DOI=10.1073/pnas.0607084104; RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L., RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.; RT "Analysis of phosphorylation sites on proteins from Saccharomyces RT cerevisiae by electron transfer dissociation (ETD) mass RT spectrometry."; RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58 AND SER-75, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=18407956; DOI=10.1074/mcp.M700468-MCP200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth RT phosphoproteome analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-75; SER-119 AND SER-123, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19779198; DOI=10.1126/science.1172867; RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.; RT "Global analysis of Cdk1 substrate phosphorylation sites provides RT insights into evolution."; RL Science 325:1682-1686(2009). RN [11] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2 (ISOFORM NUCLEAR), RP CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS] (ISOFORM RP NUCLEAR), AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). CC -!- FUNCTION: DNA ligase that seals nicks in double-stranded DNA CC during DNA replication, DNA recombination and DNA repair. The CC mitochondrial form is required for mitochondrial DNA maintenance CC but is non-essential while the nuclear form is essential for cell CC viability. CC -!- CATALYTIC ACTIVITY: ATP + (deoxyribonucleotide)(n) + CC (deoxyribonucleotide)(m) = AMP + diphosphate + CC (deoxyribonucleotide)(n+m). {ECO:0000255|PROSITE- CC ProRule:PRU10135}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- SUBCELLULAR LOCATION: Isoform Mitochondrial: Mitochondrion. CC -!- SUBCELLULAR LOCATION: Isoform Nuclear: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=Mitochondrial; CC IsoId=P04819-1; Sequence=Displayed; CC Name=Nuclear; CC IsoId=P04819-2; Sequence=VSP_018719; CC Note=Produced by alternative initiation at Met-24 of isoform CC Mitochondrial. Initiator Met-1 is removed. Contains a CC N-acetylserine at position 2. {ECO:0000244|PubMed:22814378}; CC -!- MISCELLANEOUS: Cdc9 is included within the category of so-called CC 'start genes', encoding proteins which are required in early G1, CC when the cell is faced with the option of initiating a further CC cell cycle. CC -!- MISCELLANEOUS: Present with 149 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the ATP-dependent DNA ligase family. CC {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X03246; CAA27005.1; -; Genomic_DNA. DR EMBL; Z67750; CAA91582.1; -; Genomic_DNA. DR EMBL; Z74212; CAA98737.1; -; Genomic_DNA. DR EMBL; AY723764; AAU09681.1; -; Genomic_DNA. DR EMBL; X68020; CAA48158.1; -; Genomic_DNA. DR EMBL; BK006938; DAA11697.1; -; Genomic_DNA. DR PIR; S61049; LQBYPX. DR RefSeq; NP_010117.1; NM_001180224.1. [P04819-1] DR PDB; 2OD8; X-ray; 2.80 A; B=32-53. DR PDBsum; 2OD8; -. DR ProteinModelPortal; P04819; -. DR SMR; P04819; 146-751. DR BioGrid; 31901; 50. DR DIP; DIP-5630N; -. DR IntAct; P04819; 19. DR MINT; MINT-499551; -. DR MaxQB; P04819; -. DR PeptideAtlas; P04819; -. DR EnsemblFungi; YDL164C; YDL164C; YDL164C. [P04819-1] DR GeneID; 851391; -. DR KEGG; sce:YDL164C; -. DR EuPathDB; FungiDB:YDL164C; -. DR SGD; S000002323; CDC9. DR GeneTree; ENSGT00810000125528; -. DR HOGENOM; HOG000036006; -. DR InParanoid; P04819; -. DR KO; K10747; -. DR OMA; SQCPNYD; -. DR OrthoDB; EOG7TXKRG; -. DR BioCyc; YEAST:G3O-29556-MONOMER; -. DR Reactome; R-SCE-109979; Gap-filling DNA repair synthesis and ligation in TC-NER. DR Reactome; R-SCE-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha). DR Reactome; R-SCE-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta). DR Reactome; R-SCE-75228; Resolution of D-loop Structures through Holliday Junction Intermediates. DR EvolutionaryTrace; P04819; -. DR NextBio; 968546; -. DR PRO; PR:P04819; -. DR Proteomes; UP000002311; Chromosome IV. DR GO; GO:0005739; C:mitochondrion; IDA:SGD. DR GO; GO:0005634; C:nucleus; IDA:SGD. DR GO; GO:0005657; C:replication fork; NAS:SGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. DR GO; GO:0003910; F:DNA ligase (ATP) activity; IDA:SGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006284; P:base-excision repair; IMP:SGD. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0071897; P:DNA biosynthetic process; IEA:InterPro. DR GO; GO:0006266; P:DNA ligation; IDA:SGD. DR GO; GO:0051103; P:DNA ligation involved in DNA repair; IEA:InterPro. DR GO; GO:0006310; P:DNA recombination; IMP:SGD. DR GO; GO:0006273; P:lagging strand elongation; IDA:SGD. DR GO; GO:0035753; P:maintenance of DNA trinucleotide repeats; IMP:SGD. DR GO; GO:0000278; P:mitotic cell cycle; IMP:SGD. DR GO; GO:0006289; P:nucleotide-excision repair; IMP:SGD. DR Gene3D; 1.10.3260.10; -; 1. DR Gene3D; 2.40.50.140; -; 1. DR InterPro; IPR000977; DNA_ligase_ATP-dep. DR InterPro; IPR012309; DNA_ligase_ATP-dep_C. DR InterPro; IPR012310; DNA_ligase_ATP-dep_cent. DR InterPro; IPR016059; DNA_ligase_ATP-dep_CS. DR InterPro; IPR012308; DNA_ligase_ATP-dep_N. DR InterPro; IPR012340; NA-bd_OB-fold. DR Pfam; PF04679; DNA_ligase_A_C; 1. DR Pfam; PF01068; DNA_ligase_A_M; 1. DR Pfam; PF04675; DNA_ligase_A_N; 1. DR SUPFAM; SSF117018; SSF117018; 1. DR SUPFAM; SSF50249; SSF50249; 1. DR TIGRFAMs; TIGR00574; dnl1; 1. DR PROSITE; PS00697; DNA_LIGASE_A1; 1. DR PROSITE; PS00333; DNA_LIGASE_A2; 1. DR PROSITE; PS50160; DNA_LIGASE_A3; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative initiation; ATP-binding; KW Cell cycle; Cell division; Complete proteome; DNA damage; KW DNA recombination; DNA repair; DNA replication; Ligase; Magnesium; KW Metal-binding; Mitochondrion; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Transit peptide. FT TRANSIT 1 44 Mitochondrion. {ECO:0000255}. FT CHAIN 45 755 DNA ligase 1. FT /FTId=PRO_0000007274. FT REGION 309 318 Interaction with target DNA. FT {ECO:0000250}. FT REGION 493 495 Interaction with target DNA. FT {ECO:0000250}. FT ACT_SITE 419 419 N6-AMP-lysine intermediate. FT {ECO:0000255|PROSITE-ProRule:PRU10135}. FT METAL 472 472 Magnesium 1. {ECO:0000250}. FT METAL 571 571 Magnesium 2. {ECO:0000250}. FT BINDING 417 417 ATP. {ECO:0000250}. FT BINDING 424 424 ATP. {ECO:0000250}. FT BINDING 440 440 ATP. {ECO:0000250}. FT BINDING 576 576 ATP. {ECO:0000250}. FT BINDING 590 590 ATP. {ECO:0000250}. FT BINDING 596 596 ATP. {ECO:0000250}. FT SITE 164 164 Interaction with target DNA. FT {ECO:0000250}. FT SITE 441 441 Interaction with target DNA. FT {ECO:0000250}. FT SITE 622 622 Interaction with target DNA. FT {ECO:0000250}. FT SITE 647 647 Interaction with target DNA. FT {ECO:0000250}. FT MOD_RES 58 58 Phosphoserine. FT {ECO:0000244|PubMed:17287358, FT ECO:0000244|PubMed:18407956}. FT MOD_RES 75 75 Phosphoserine. FT {ECO:0000244|PubMed:17287358, FT ECO:0000244|PubMed:18407956, FT ECO:0000244|PubMed:19779198}. FT MOD_RES 119 119 Phosphoserine. FT {ECO:0000244|PubMed:19779198}. FT MOD_RES 123 123 Phosphoserine. FT {ECO:0000244|PubMed:19779198}. FT VAR_SEQ 1 23 Missing (in isoform Nuclear). FT {ECO:0000305}. FT /FTId=VSP_018719. FT CONFLICT 69 69 D -> E (in Ref. 1; CAA27005). FT {ECO:0000305}. FT CONFLICT 186 186 L -> V (in Ref. 1; CAA27005). FT {ECO:0000305}. FT CONFLICT 671 671 G -> E (in Ref. 5; CAA48158). FT {ECO:0000305}. FT CONFLICT 724 724 R -> I (in Ref. 5; CAA48158). FT {ECO:0000305}. FT HELIX 41 44 {ECO:0000244|PDB:2OD8}. SQ SEQUENCE 755 AA; 84828 MW; B7C2ECAF5C61CAE7 CRC64; MRRLLTGCLL SSARPLKSRL PLLMSSSLPS SAGKKPKQAT LARFFTSMKN KPTEGTPSPK KSSKHMLEDR MDNVSGEEEY ATKKLKQTAV THTVAAPSSM GSNFSSIPSS APSSGVADSP QQSQRLVGEV EDALSSNNND HYSSNIPYSE VCEVFNKIEA ISSRLEIIRI CSDFFIKIMK QSSKNLIPTT YLFINRLGPD YEAGLELGLG ENLLMKTISE TCGKSMSQIK LKYKDIGDLG EIAMGARNVQ PTMFKPKPLT VGEVFKNLRA IAKTQGKDSQ LKKMKLIKRM LTACKGIEAK FLIRSLESKL RIGLAEKTVL ISLSKALLLH DENREDSPDK DVPMDVLESA QQKIRDAFCQ VPNYEIVINS CLEHGIMNLD KYCTLRPGIP LKPMLAKPTK AINEVLDRFQ GETFTSEYKY DGERAQVHLL NDGTMRIYSR NGENMTERYP EINITDFIQD LDTTKNLILD CEAVAWDKDQ GKILPFQVLS TRKRKDVELN DVKVKVCLFA FDILCYNDER LINKSLKERR EYLTKVTKVV PGEFQYATQI TTNNLDELQK FLDESVNHSC EGLMVKMLEG PESHYEPSKR SRNWLKLKKD YLEGVGDSLD LCVLGAYYGR GKRTGTYGGF LLGCYNQDTG EFETCCKIGT GFSDEMLQLL HDRLTPTIID GPKATFVFDS SAEPDVWFEP TTLFEVLTAD LSLSPIYKAG SATFDKGVSL RFPRFLRIRE DKGVEDATSS DQIVELYENQ SHMQN // ID DNMT1_HUMAN Reviewed; 1616 AA. AC P26358; A0AV63; B7ZLW6; Q9UHG5; Q9ULA2; Q9UMZ6; DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2001, sequence version 2. DT 11-NOV-2015, entry version 180. DE RecName: Full=DNA (cytosine-5)-methyltransferase 1; DE Short=Dnmt1; DE EC=2.1.1.37; DE AltName: Full=CXXC-type zinc finger protein 9; DE AltName: Full=DNA methyltransferase HsaI; DE Short=DNA MTase HsaI; DE Short=M.HsaI; DE AltName: Full=MCMT; GN Name=DNMT1; Synonyms=AIM, CXXC9, DNMT; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1594447; DOI=10.1093/nar/20.9.2287; RA Yen R.-W.C., Vertino P.M., Nelkin B.D., Yu J.J., Deiry W.E., RA Cumaraswamy A., Lennon G.G., Trask B.J., Celano P., Baylin S.B.; RT "Isolation and characterization of the cDNA encoding human DNA RT methyltransferase."; RL Nucleic Acids Res. 20:2287-2291(1992). RN [2] RP SEQUENCE REVISION TO N-TERMINUS. RX PubMed=8940105; DOI=10.1074/jbc.271.49.31092; RA Yoder J.A., Yen R.-W.C., Vertino P.M., Bestor T.H., Baylin S.B.; RT "New 5' regions of the murine and human genes for DNA (cytosine-5)- RT methyltransferase."; RL J. Biol. Chem. 271:31092-31097(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RC TISSUE=Prostatic carcinoma; RA Li L.C., Au H., Chui R., Dahiya R.; RT "Human DNA methyltransferase (DNMT1) is alternatively spliced."; RL Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M., RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2). RX PubMed=10449766; DOI=10.1073/pnas.96.17.9751; RA Hsu D.-W., Lin M.-J., Lee T.-L., Wen S.-C., Chen X., Shen C.-K.J.; RT "Two major forms of DNA (cytosine-5) methyltransferase in human RT somatic tissues."; RL Proc. Natl. Acad. Sci. U.S.A. 96:9751-9756(1999). RN [7] RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2). RX PubMed=10753866; DOI=10.1074/jbc.275.15.10754; RA Bonfils C., Beaulieu N., Chan E., Cotton-Montpetit J., MacLeod A.R.; RT "Characterization of the human DNA methyltransferase splice variant RT Dnmt1b."; RL J. Biol. Chem. 275:10754-10760(2000). RN [8] RP INTERACTION WITH PCNA, AND MUTAGENESIS. RX PubMed=9302295; DOI=10.1126/science.277.5334.1996; RA Chuang L.S.-H., Ian H.-I., Koh T.-W., Ng H.-H., Xu G., Li B.F.L.; RT "Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for RT p21WAF1."; RL Science 277:1996-2000(1997). RN [9] RP INTERACTION WITH MBD2 AND MBD3. RX PubMed=10947852; DOI=10.1046/j.1365-2443.2000.00359.x; RA Tatematsu K., Yamazaki T., Ishikawa F.; RT "MBD2-MBD3 complex binds to hemi-methylated DNA and forms a complex RT containing DNMT1 at the replication foci in late S phase."; RL Genes Cells 5:677-688(2000). RN [10] RP INTERACTION WITH HDAC2 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 [11] RP INTERACTION WITH RB1; E2F1 AND HDAC1. RX PubMed=10888886; DOI=10.1038/77124; RA Robertson K.D., Ait-Si-Ali S., Yokochi T., Wade P.A., Jones P.L., RA Wolffe A.P.; RT "DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses RT transcription from E2F-responsive promoters."; RL Nat. Genet. 25:338-342(2000). RN [12] RP TISSUE SPECIFICITY. RX PubMed=10325416; DOI=10.1093/nar/27.11.2291; RA Robertson K.D., Uzvolgyi E., Liang G., Talmadge C., Sumegi J., RA Gonzales F.A., Jones P.A.; RT "The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate RT mRNA expression in normal tissues and overexpression in tumors."; RL Nucleic Acids Res. 27:2291-2298(1999). RN [13] RP INTERACTION WITH DNMT3A AND DNMT3B, AND SUBCELLULAR LOCATION. RX PubMed=12145218; DOI=10.1093/emboj/cdf401; RA Kim G.-D., Ni J., Kelesoglu N., Roberts R.J., Pradhan S.; RT "Co-operation and communication between the human maintenance and de RT novo DNA (cytosine-5) methyltransferases."; RL EMBO J. 21:4183-4195(2002). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127 AND SER-714, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [15] RP FUNCTION, AND INTERACTION WITH EED AND EZH2. RX PubMed=16357870; DOI=10.1038/nature04431; RA Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C., RA Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M., RA Esteller M., Di Croce L., de Launoit Y., Fuks F.; RT "The Polycomb group protein EZH2 directly controls DNA methylation."; RL Nature 439:871-874(2006). RN [16] RP ERRATUM. RA Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C., RA Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M., RA Esteller M., Di Croce L., de Launoit Y., Fuks F.; RL Nature 446:824-824(2006). RN [17] RP DE NOVO DNA METHYLATION OF TARGET GENES. RX PubMed=17200670; DOI=10.1038/ng1950; RA Schlesinger Y., Straussman R., Keshet I., Farkash S., Hecht M., RA Zimmerman J., Eden E., Yakhini Z., Ben-Shushan E., Reubinoff B.E., RA Bergman Y., Simon I., Cedar H.; RT "Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes RT for de novo methylation in cancer."; RL Nat. Genet. 39:232-236(2007). RN [18] RP FUNCTION, AND MUTAGENESIS OF CYS-653; CYS-656; CYS-659; CYS-664; RP CYS-667 AND CYS-670. RX PubMed=18754681; DOI=10.1021/bi8011725; RA Pradhan M., Esteve P.-O., Chin H.G., Samaranayke M., Kim G.-D., RA Pradhan S.; RT "CXXC domain of human DNMT1 is essential for enzymatic activity."; RL Biochemistry 47:10000-10009(2008). RN [19] RP FUNCTION. RX PubMed=18413740; DOI=10.1158/0008-5472.CAN-07-6654; RA Sun L., Huang L., Nguyen P., Bisht K.S., Bar-Sela G., Ho A.S., RA Bradbury C.M., Yu W., Cui H., Lee S., Trepel J.B., Feinberg A.P., RA Gius D.; RT "DNA methyltransferase 1 and 3B activate BAG-1 expression via RT recruitment of CTCFL/BORIS and modulation of promoter histone RT methylation."; RL Cancer Res. 68:2726-2735(2008). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-732, 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 [21] RP METHYLATION AT LYS-70, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=18438403; DOI=10.1038/nchembio.88; RA Rathert P., Dhayalan A., Murakami M., Zhang X., Tamas R., RA Jurkowska R., Komatsu Y., Shinkai Y., Cheng X., Jeltsch A.; RT "Protein lysine methyltransferase G9a acts on non-histone targets."; RL Nat. Chem. Biol. 4:344-346(2008). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127; SER-143; SER-152; RP SER-154 AND SER-394, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP 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 [23] 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 [24] RP SUMOYLATION, INTERACTION WITH UBC9, AND MUTAGENESIS OF CYS-1226. RX PubMed=19450230; DOI=10.1042/BJ20090142; RA Lee B., Muller M.T.; RT "SUMOylation enhances DNA methyltransferase 1 activity."; RL Biochem. J. 421:449-461(2009). RN [25] RP HOMODIMERIZATION. RX PubMed=19173286; DOI=10.1002/jcb.22071; RA Fellinger K., Rothbauer U., Felle M., Laengst G., Leonhardt H.; RT "Dimerization of DNA methyltransferase 1 is mediated by its regulatory RT domain."; RL J. Cell. Biochem. 106:521-528(2009). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [27] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-173; LYS-1111; LYS-1113 AND RP LYS-1115, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-394 AND SER-714, 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 [29] 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 [30] RP PHOSPHORYLATION AT SER-154. RX PubMed=21565170; DOI=10.1016/j.bbrc.2011.04.115; RA Lavoie G., St-Pierre Y.; RT "Phosphorylation of human DNMT1: implication of cyclin-dependent RT kinases."; RL Biochem. Biophys. Res. Commun. 409:187-192(2011). RN [31] RP ACETYLATION AT LYS-160; LYS-188; LYS-259; LYS-366; LYS-749; LYS-891; RP LYS-957; LYS-961; LYS-975; LYS-1054; LYS-1111; LYS-1113; LYS-1115; RP LYS-1117; LYS-1349 AND LYS-1415, AND DEACETYLATION BY SIRT1. RX PubMed=21947282; DOI=10.1128/MCB.06147-11; RA Peng L., Yuan Z., Ling H., Fukasawa K., Robertson K., Olashaw N., RA Koomen J., Chen J., Lane W.S., Seto E.; RT "SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and RT alters its activities."; RL Mol. Cell. Biol. 31:4720-4734(2011). RN [32] RP METHYLATION AT LYS-142, AND PHOSPHORYLATION AT SER-143. RX PubMed=21151116; DOI=10.1038/nsmb.1939; RA Esteve P.O., Chang Y., Samaranayake M., Upadhyay A.K., Horton J.R., RA Feehery G.R., Cheng X., Pradhan S.; RT "A methylation and phosphorylation switch between an adjacent lysine RT and serine determines human DNMT1 stability."; RL Nat. Struct. Mol. Biol. 18:42-48(2011). RN [33] RP INTERACTION WITH USP7 AND UHRF1. RX PubMed=21745816; DOI=10.1093/nar/gkr528; RA Felle M., Joppien S., Nemeth A., Diermeier S., Thalhammer V., RA Dobner T., Kremmer E., Kappler R., Langst G.; RT "The USP7/Dnmt1 complex stimulates the DNA methylation activity of RT Dnmt1 and regulates the stability of UHRF1."; RL Nucleic Acids Res. 39:8355-8365(2011). RN [34] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127; SER-133 AND RP SER-714, 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 [35] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [36] RP X-RAY CRYSTALLOGRAPHY (2.31 ANGSTROMS) OF 351-600 IN COMPLEX WITH ZINC RP IONS. RX PubMed=21389349; DOI=10.1074/jbc.M110.209882; RA Syeda F., Fagan R.L., Wean M., Avvakumov G.V., Walker J.R., Xue S., RA Dhe-Paganon S., Brenner C.; RT "The replication focus targeting sequence (RFTS) domain is a DNA- RT competitive inhibitor of Dnmt1."; RL J. Biol. Chem. 286:15344-15351(2011). RN [37] RP X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 646-1600 IN COMPLEX WITH SAH RP AND DNA, AND AUTOINHIBITORY LINKER. RX PubMed=21163962; DOI=10.1126/science.1195380; RA Song J., Rechkoblit O., Bestor T.H., Patel D.J.; RT "Structure of DNMT1-DNA complex reveals a role for autoinhibition in RT maintenance DNA methylation."; RL Science 331:1036-1040(2011). RN [38] RP VARIANTS HSN1E 490-GLU-TYR-491 AND CYS-495, AND CHARACTERIZATION OF RP VARIANTS HSN1E 490-GLU-TYR-491 AND CYS-495. RX PubMed=21532572; DOI=10.1038/ng.830; RA Klein C.J., Botuyan M.V., Wu Y., Ward C.J., Nicholson G.A., RA Hammans S., Hojo K., Yamanishi H., Karpf A.R., Wallace D.C., Simon M., RA Lander C., Boardman L.A., Cunningham J.M., Smith G.E., Litchy W.J., RA Boes B., Atkinson E.J., Middha S., Dyck P.J.B., Parisi J.E., Mer G., RA Smith D.I., Dyck P.J.; RT "Mutations in DNMT1 cause hereditary sensory neuropathy with dementia RT and hearing loss."; RL Nat. Genet. 43:595-600(2011). RN [39] RP VARIANTS ADCADN VAL-554; ALA-589 AND PHE-590. RX PubMed=22328086; DOI=10.1093/hmg/dds035; RA Winkelmann J., Lin L., Schormair B., Kornum B.R., Faraco J., RA Plazzi G., Melberg A., Cornelio F., Urban A.E., Pizza F., Poli F., RA Grubert F., Wieland T., Graf E., Hallmayer J., Strom T.M., Mignot E.; RT "Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, RT deafness and narcolepsy."; RL Hum. Mol. Genet. 21:2205-2210(2012). CC -!- FUNCTION: Methylates CpG residues. Preferentially methylates CC hemimethylated DNA. Associates with DNA replication sites in S CC phase maintaining the methylation pattern in the newly synthesized CC strand, that is essential for epigenetic inheritance. Associates CC with chromatin during G2 and M phases to maintain DNA methylation CC independently of replication. It is responsible for maintaining CC methylation patterns established in development. DNA methylation CC is coordinated with methylation of histones. Mediates CC transcriptional repression by direct binding to HDAC2. In CC association with DNMT3B and via the recruitment of CTCFL/BORIS, CC involved in activation of BAG1 gene expression by modulating CC dimethylation of promoter histone H3 at H3K4 and H3K9. CC {ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:18413740, CC ECO:0000269|PubMed:18754681}. CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + DNA = S-adenosyl-L- CC homocysteine + DNA containing 5-methylcytosine. CC {ECO:0000255|PROSITE-ProRule:PRU10018}. CC -!- SUBUNIT: Binds to CSNK1D (By similarity). Homodimer. Interacts CC with HDAC1 and with PCNA. Forms a complex with DMAP1 and HDAC2, CC with direct interaction. Forms also a stable complex with E2F1, CC BB1 and HDAC1. Binds MBD2 and MBD3. Component of complexes CC containing SUV39H1. Interacts with DNMT3A and DNMT3B. Interacts CC with the PRC2/EED-EZH2 complex. Interacts with UBC9 and CC BAZ2A/TIP5. Interacts with UHRF1; promoting its recruitment to CC hemimethylated DNA. Interacts with USP7, promoting its CC deubiquitination. {ECO:0000250, ECO:0000269|PubMed:10888872, CC ECO:0000269|PubMed:10888886, ECO:0000269|PubMed:10947852, CC ECO:0000269|PubMed:12145218, ECO:0000269|PubMed:16357870, CC ECO:0000269|PubMed:19450230, ECO:0000269|PubMed:21163962, CC ECO:0000269|PubMed:21389349, ECO:0000269|PubMed:21745816, CC ECO:0000269|PubMed:9302295}. CC -!- INTERACTION: CC O75530:EED; NbExp=3; IntAct=EBI-719459, EBI-923794; CC Q15910:EZH2; NbExp=8; IntAct=EBI-719459, EBI-530054; CC P48552:NRIP1; NbExp=3; IntAct=EBI-719459, EBI-746484; CC Q96EB6:SIRT1; NbExp=11; IntAct=EBI-719459, EBI-1802965; CC Q96T88:UHRF1; NbExp=12; IntAct=EBI-719459, EBI-1548946; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12145218}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P26358-1; Sequence=Displayed; CC Name=2; Synonyms=Dnmt1b; CC IsoId=P26358-2; Sequence=VSP_005618; CC Name=3; CC IsoId=P26358-3; Sequence=VSP_005617; CC -!- TISSUE SPECIFICITY: Ubiquitous; highly expressed in fetal tissues, CC heart, kidney, placenta, peripheral blood mononuclear cells, and CC expressed at lower levels in spleen, lung, brain, small intestine, CC colon, liver, and skeletal muscle. Isoform 2 is less expressed CC than isoform 1. {ECO:0000269|PubMed:10325416}. CC -!- INDUCTION: Its abundance is reduced to non detectable levels at CC the G0 phase of the cell cycle and is dramatically induced upon CC entrance into the S-phase of the cell cycle. CC -!- DOMAIN: The N-terminal part is required for homodimerization and CC acts as a regulatory domain. CC -!- DOMAIN: The CXXC-type zinc finger specifically binds to CC unmethylated CpG dinucleotides, positioning the autoinhibitory CC linker between the DNA and the active site, thus providing a CC mechanism to ensure that only hemimethylated CpG dinucleotides CC undergo methylation. {ECO:0000269|PubMed:21163962}. CC -!- PTM: Sumoylated; sumoylation increases activity. CC {ECO:0000269|PubMed:19450230}. CC -!- PTM: Acetylation on multiple lysines, mainly by KAT2B/PCAF, CC regulates cell cycle G(2)/M transition. Deacetylation of Lys-1349 CC and Lys-1415 by SIRT1 increases methyltransferase activity. CC {ECO:0000269|PubMed:21947282}. CC -!- PTM: Phosphorylation of Ser-154 by CDKs is important for enzymatic CC activity and protein stability. Phosphorylation of Ser-143 by AKT1 CC prevents methylation by SETD7 therebye increasing DNMT1 stability. CC {ECO:0000269|PubMed:21151116, ECO:0000269|PubMed:21565170}. CC -!- PTM: Methylation at Lys-142 by SETD7 promotes DNMT1 proteasomal CC degradation. {ECO:0000269|PubMed:18438403, CC ECO:0000269|PubMed:21151116}. CC -!- PTM: Ubiquitinated by UHRF1; interaction with USP7 counteracts CC ubiquitination by UHRF1 by promoting deubiquitination and CC preventing degradation by the proteasome. {ECO:0000250}. CC -!- DISEASE: Neuropathy, hereditary sensory, 1E (HSN1E) [MIM:614116]: CC A neurodegenerative disorder characterized by adult onset of CC progressive peripheral sensory loss associated with progressive CC hearing impairment and early-onset dementia. CC {ECO:0000269|PubMed:21532572}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Cerebellar ataxia, deafness, and narcolepsy, autosomal CC dominant (ADCADN) [MIM:604121]: An autosomal dominant neurologic CC disorder characterized by adult onset of progressive cerebellar CC ataxia, narcolepsy, cataplexy, sensorineural deafness, and CC dementia. More variable features include optic atrophy, sensory CC neuropathy, psychosis, and depression. CC {ECO:0000269|PubMed:22328086}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the class I-like SAM-binding CC methyltransferase superfamily. C5-methyltransferase family. CC {ECO:0000255|PROSITE-ProRule:PRU01016}. CC -!- SIMILARITY: Contains 2 BAH domains. {ECO:0000255|PROSITE- CC ProRule:PRU00370}. CC -!- SIMILARITY: Contains 1 CXXC-type zinc finger. CC {ECO:0000255|PROSITE-ProRule:PRU00509}. CC -!- SIMILARITY: Contains 1 DMAP-interaction domain. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 SAM-dependent MTase C5-type domain. CC {ECO:0000255|PROSITE-ProRule:PRU01016}. CC -!- SEQUENCE CAUTION: CC Sequence=AAD54507.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/DNMT1ID40347ch19p13.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; X63692; CAA45219.1; -; mRNA. DR EMBL; AF180682; AAF23609.1; -; mRNA. DR EMBL; AC010077; AAD54507.1; ALT_SEQ; Genomic_DNA. DR EMBL; AC011511; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC020931; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC126227; AAI26228.1; -; mRNA. DR EMBL; BC144093; AAI44094.1; -; mRNA. DR EMBL; AH008119; AAD51619.1; -; Genomic_DNA. DR CCDS; CCDS12228.1; -. [P26358-1] DR CCDS; CCDS45958.1; -. [P26358-2] DR PIR; S22610; S22610. DR RefSeq; NP_001124295.1; NM_001130823.1. [P26358-2] DR RefSeq; NP_001370.1; NM_001379.2. [P26358-1] DR UniGene; Hs.202672; -. DR PDB; 3EPZ; X-ray; 2.31 A; A/B=351-600. DR PDB; 3PTA; X-ray; 3.60 A; A=646-1600. DR PDB; 3SWR; X-ray; 2.49 A; A=601-1600. DR PDB; 4WXX; X-ray; 2.62 A; A/B=351-1600. DR PDB; 4YOC; X-ray; 2.92 A; A=600-1600. DR PDBsum; 3EPZ; -. DR PDBsum; 3PTA; -. DR PDBsum; 3SWR; -. DR PDBsum; 4WXX; -. DR PDBsum; 4YOC; -. DR ProteinModelPortal; P26358; -. DR SMR; P26358; 351-599, 601-1600. DR BioGrid; 108123; 75. DR DIP; DIP-39693N; -. DR IntAct; P26358; 22. DR MINT; MINT-232346; -. DR STRING; 9606.ENSP00000352516; -. DR BindingDB; P26358; -. DR ChEMBL; CHEMBL1993; -. DR DrugBank; DB00928; Azacitidine. DR DrugBank; DB01262; Decitabine. DR DrugBank; DB01099; Flucytosine. DR DrugBank; DB01035; Procainamide. DR REBASE; 1161; M.HsaDnmt1A. DR PhosphoSite; P26358; -. DR BioMuta; DNMT1; -. DR DMDM; 12231019; -. DR MaxQB; P26358; -. DR PaxDb; P26358; -. DR PRIDE; P26358; -. DR Ensembl; ENST00000340748; ENSP00000345739; ENSG00000130816. [P26358-1] DR Ensembl; ENST00000359526; ENSP00000352516; ENSG00000130816. [P26358-2] DR Ensembl; ENST00000540357; ENSP00000440457; ENSG00000130816. [P26358-3] DR GeneID; 1786; -. DR KEGG; hsa:1786; -. DR UCSC; uc002mng.3; human. [P26358-1] DR UCSC; uc010xlc.2; human. [P26358-2] DR CTD; 1786; -. DR GeneCards; DNMT1; -. DR GeneReviews; DNMT1; -. DR HGNC; HGNC:2976; DNMT1. DR HPA; CAB005876; -. DR HPA; HPA002694; -. DR MIM; 126375; gene. DR MIM; 604121; phenotype. DR MIM; 614116; phenotype. DR neXtProt; NX_P26358; -. DR Orphanet; 314404; Autosomal dominant cerebellar ataxia, deafness and narcolepsy. DR PharmGKB; PA27443; -. DR eggNOG; ENOG410IF68; Eukaryota. DR eggNOG; COG0270; LUCA. DR GeneTree; ENSGT00390000005100; -. DR HOGENOM; HOG000082497; -. DR HOVERGEN; HBG051384; -. DR InParanoid; P26358; -. DR KO; K00558; -. DR OMA; DEPEMLT; -. DR OrthoDB; EOG77WWBH; -. DR PhylomeDB; P26358; -. DR TreeFam; TF328926; -. DR BRENDA; 2.1.1.37; 2681. DR Reactome; R-HSA-212300; PRC2 methylates histones and DNA. DR Reactome; R-HSA-427413; NoRC negatively regulates rRNA expression. DR Reactome; R-HSA-5334118; DNA methylation. DR ChiTaRS; DNMT1; human. DR EvolutionaryTrace; P26358; -. DR GeneWiki; DNMT1; -. DR GenomeRNAi; 1786; -. DR NextBio; 7267; -. DR PRO; PR:P26358; -. DR Proteomes; UP000005640; Chromosome 19. DR Bgee; P26358; -. DR CleanEx; HS_DNMT1; -. DR ExpressionAtlas; P26358; baseline and differential. DR Genevisible; P26358; HS. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005721; C:pericentric heterochromatin; IEA:Ensembl. DR GO; GO:0005657; C:replication fork; IEA:Ensembl. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0003886; F:DNA (cytosine-5-)-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB. DR GO; GO:0009008; F:DNA-methyltransferase activity; IDA:UniProtKB. DR GO; GO:0008327; F:methyl-CpG binding; IEA:Ensembl. DR GO; GO:0003723; F:RNA binding; IEA:Ensembl. DR GO; GO:0008270; F:zinc ion binding; IEA:Ensembl. DR GO; GO:0071230; P:cellular response to amino acid stimulus; IEA:Ensembl. DR GO; GO:0016568; P:chromatin modification; IEA:UniProtKB-KW. DR GO; GO:0006306; P:DNA methylation; TAS:ProtInc. DR GO; GO:0032776; P:DNA methylation on cytosine; TAS:Reactome. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0016458; P:gene silencing; IEA:Ensembl. DR GO; GO:0010216; P:maintenance of DNA methylation; IDA:UniProtKB. DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; TAS:Reactome. DR GO; GO:0051573; P:negative regulation of histone H3-K9 methylation; IMP:UniProtKB. DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; TAS:ProtInc. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; IMP:UniProtKB. DR GO; GO:0042127; P:regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0040029; P:regulation of gene expression, epigenetic; TAS:Reactome. DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW. DR Gene3D; 3.40.50.150; -; 1. DR InterPro; IPR001025; BAH_dom. DR InterPro; IPR018117; C5_DNA_meth_AS. DR InterPro; IPR001525; C5_MeTfrase. DR InterPro; IPR031303; C5_meth_CS. DR InterPro; IPR022702; Cytosine_MeTrfase1_RFD. DR InterPro; IPR010506; DMAP1-bd. DR InterPro; IPR017198; DNMT1_meta. DR InterPro; IPR029063; SAM-dependent_MTases. DR InterPro; IPR002857; Znf_CXXC. DR Pfam; PF01426; BAH; 2. DR Pfam; PF06464; DMAP_binding; 1. DR Pfam; PF12047; DNMT1-RFD; 1. DR Pfam; PF02008; zf-CXXC; 1. DR PIRSF; PIRSF037404; DNMT1; 1. DR PRINTS; PR00105; C5METTRFRASE. DR SMART; SM00439; BAH; 2. DR SUPFAM; SSF53335; SSF53335; 2. DR PROSITE; PS51038; BAH; 2. DR PROSITE; PS00094; C5_MTASE_1; 1. DR PROSITE; PS00095; C5_MTASE_2; 1. DR PROSITE; PS51679; SAM_MT_C5; 1. DR PROSITE; PS51058; ZF_CXXC; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Activator; Alternative splicing; KW Chromatin regulator; Complete proteome; Deafness; Disease mutation; KW DNA-binding; Metal-binding; Methylation; Methyltransferase; KW Neuropathy; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; KW Repeat; Repressor; S-adenosyl-L-methionine; Transcription; KW Transcription regulation; Transferase; Ubl conjugation; Zinc; KW Zinc-finger. FT CHAIN 1 1616 DNA (cytosine-5)-methyltransferase 1. FT /FTId=PRO_0000088034. FT DOMAIN 18 103 DMAP-interaction. FT DOMAIN 755 880 BAH 1. {ECO:0000255|PROSITE- FT ProRule:PRU00370}. FT DOMAIN 972 1100 BAH 2. {ECO:0000255|PROSITE- FT ProRule:PRU00370}. FT REPEAT 1109 1110 1. FT REPEAT 1111 1112 2. FT REPEAT 1113 1114 3. FT REPEAT 1115 1116 4. FT REPEAT 1117 1118 5. FT REPEAT 1119 1120 6; approximate. FT DOMAIN 1139 1599 SAM-dependent MTase C5-type. FT {ECO:0000255|PROSITE-ProRule:PRU01016}. FT ZN_FING 646 692 CXXC-type. {ECO:0000255|PROSITE- FT ProRule:PRU00509}. FT REGION 1 336 Interaction with the PRC2/EED-EZH2 FT complex. {ECO:0000250}. FT REGION 1 148 Interaction with DNMT3A. FT REGION 1 120 Interaction with DMAP1. FT REGION 149 217 Interaction with DNMT3B. FT REGION 163 174 Interaction with PCNA. FT REGION 308 606 Interaction with the PRC2/EED-EZH2 FT complex. {ECO:0000250}. FT REGION 310 502 Homodimerization. FT REGION 331 550 DNA replication foci-targeting sequence. FT {ECO:0000250}. FT REGION 651 697 Required for activity. FT REGION 693 754 Autoinhibitory linker. FT REGION 1109 1120 6 X 2 AA tandem repeats of K-G. FT REGION 1121 1616 Interaction with the PRC2/EED-EZH2 FT complex. {ECO:0000250}. FT REGION 1139 1616 Catalytic. FT MOTIF 177 205 Nuclear localization signal. FT {ECO:0000255}. FT ACT_SITE 1226 1226 FT METAL 353 353 Zinc. FT METAL 356 356 Zinc. FT METAL 414 414 Zinc. FT METAL 418 418 Zinc. FT SITE 509 509 Important for activity. {ECO:0000250}. FT MOD_RES 70 70 N6,N6-dimethyllysine. FT {ECO:0000269|PubMed:18438403}. FT MOD_RES 127 127 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 133 133 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT MOD_RES 141 141 Phosphoserine. FT {ECO:0000250|UniProtKB:P13864}. FT MOD_RES 142 142 N6-methyllysine; by SETD7. FT {ECO:0000269|PubMed:21151116}. FT MOD_RES 143 143 Phosphoserine; by PKB/AKT1. FT {ECO:0000244|PubMed:18669648, FT ECO:0000269|PubMed:21151116}. FT MOD_RES 152 152 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 154 154 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000269|PubMed:21565170}. FT MOD_RES 160 160 N6-acetyllysine. FT {ECO:0000269|PubMed:21947282}. FT MOD_RES 173 173 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 188 188 N6-acetyllysine. FT {ECO:0000269|PubMed:21947282}. FT MOD_RES 259 259 N6-acetyllysine. FT {ECO:0000269|PubMed:21947282}. FT MOD_RES 366 366 N6-acetyllysine. FT {ECO:0000269|PubMed:21947282}. FT MOD_RES 394 394 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:20068231}. FT MOD_RES 509 509 Phosphoserine. FT {ECO:0000250|UniProtKB:P13864}. FT MOD_RES 714 714 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 732 732 Phosphoserine. FT {ECO:0000244|PubMed:18220336}. FT MOD_RES 749 749 N6-acetyllysine. FT {ECO:0000269|PubMed:21947282}. FT MOD_RES 891 891 N6-acetyllysine. FT {ECO:0000269|PubMed:21947282}. FT MOD_RES 957 957 N6-acetyllysine. FT {ECO:0000269|PubMed:21947282}. FT MOD_RES 961 961 N6-acetyllysine. FT {ECO:0000269|PubMed:21947282}. FT MOD_RES 975 975 N6-acetyllysine. FT {ECO:0000269|PubMed:21947282}. FT MOD_RES 1054 1054 N6-acetyllysine. FT {ECO:0000269|PubMed:21947282}. FT MOD_RES 1111 1111 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861, FT ECO:0000269|PubMed:21947282}. FT MOD_RES 1113 1113 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861, FT ECO:0000269|PubMed:21947282}. FT MOD_RES 1115 1115 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861, FT ECO:0000269|PubMed:21947282}. FT MOD_RES 1117 1117 N6-acetyllysine; by EHMT2. FT {ECO:0000269|PubMed:21947282}. FT MOD_RES 1119 1119 N6-acetyllysine. FT {ECO:0000250|UniProtKB:P13864}. FT MOD_RES 1121 1121 N6-acetyllysine. FT {ECO:0000250|UniProtKB:P13864}. FT MOD_RES 1349 1349 N6-acetyllysine. FT {ECO:0000269|PubMed:21947282}. FT MOD_RES 1415 1415 N6-acetyllysine. FT {ECO:0000269|PubMed:21947282}. FT VAR_SEQ 1 336 Missing (in isoform 3). FT {ECO:0000303|Ref.3}. FT /FTId=VSP_005617. FT VAR_SEQ 149 149 P -> RSRDPPASASQVTGIRA (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_005618. FT VARIANT 97 97 H -> R (in dbSNP:rs16999593). FT /FTId=VAR_024605. FT VARIANT 311 311 I -> V (in dbSNP:rs2228612). FT /FTId=VAR_051960. FT VARIANT 490 491 DP -> EY (in HSN1E; unstable protein with FT decreased enzymatic activity and impaired FT heterochromatin binding ability after the FT S phase). FT /FTId=VAR_065965. FT VARIANT 495 495 Y -> C (in HSN1E; unstable protein with FT decreased enzymatic activity and impaired FT heterochromatin binding ability after the FT S phase). {ECO:0000269|PubMed:21532572}. FT /FTId=VAR_065966. FT VARIANT 554 554 A -> V (in ADCADN). FT {ECO:0000269|PubMed:22328086}. FT /FTId=VAR_070055. FT VARIANT 589 589 G -> A (in ADCADN). FT {ECO:0000269|PubMed:22328086}. FT /FTId=VAR_070056. FT VARIANT 590 590 V -> F (in ADCADN). FT {ECO:0000269|PubMed:22328086}. FT /FTId=VAR_070057. FT MUTAGEN 163 163 R->A: Abolishes interaction with PCNA. FT {ECO:0000269|PubMed:9302295}. FT MUTAGEN 164 164 Q->A: Abolishes interaction with PCNA. FT {ECO:0000269|PubMed:9302295}. FT MUTAGEN 166 166 T->A: Abolishes interaction with PCNA. FT {ECO:0000269|PubMed:9302295}. FT MUTAGEN 167 167 I->A: Abolishes interaction with PCNA. FT {ECO:0000269|PubMed:9302295}. FT MUTAGEN 169 169 S->A: No loss of interaction with PCNA. FT {ECO:0000269|PubMed:9302295}. FT MUTAGEN 170 170 H->V: Abolishes interaction with PCNA. FT {ECO:0000269|PubMed:9302295}. FT MUTAGEN 171 171 F->V: Abolishes interaction with PCNA. FT {ECO:0000269|PubMed:9302295}. FT MUTAGEN 172 172 A->S: No loss of interaction with PCNA. FT {ECO:0000269|PubMed:9302295}. FT MUTAGEN 173 173 K->A: No loss of interaction with PCNA. FT {ECO:0000269|PubMed:9302295}. FT MUTAGEN 653 653 C->G: Reduces activity about 10-fold; FT when associated with G-656; G-659; G-664; FT G-667 and G-670. FT {ECO:0000269|PubMed:18754681}. FT MUTAGEN 656 656 C->G: Reduces activity about 10-fold; FT when associated with G-653; G-659; G-664; FT G-667 and G-670. FT {ECO:0000269|PubMed:18754681}. FT MUTAGEN 659 659 C->G: Reduces activity about 10-fold; FT when associated with G-653; G-656; G-664; FT G-667 and G-670. FT {ECO:0000269|PubMed:18754681}. FT MUTAGEN 664 664 C->F: Reduces activity about 10-fold; FT when associated with G-653; G-656; G-659; FT G-667 and G-670. FT {ECO:0000269|PubMed:18754681}. FT MUTAGEN 667 667 C->G: Reduces activity about 10-fold; FT when associated with G-653; G-656; G-659; FT G-664 and G-670. FT {ECO:0000269|PubMed:18754681}. FT MUTAGEN 670 670 C->G: Reduces activity about 10-fold; FT when associated with G-653; G-656; G-659; FT G-664 and G-667. FT {ECO:0000269|PubMed:18754681}. FT MUTAGEN 1226 1226 C->A: Loss of activity. FT {ECO:0000269|PubMed:19450230}. FT TURN 354 356 {ECO:0000244|PDB:3EPZ}. FT STRAND 359 364 {ECO:0000244|PDB:4WXX}. FT HELIX 377 389 {ECO:0000244|PDB:3EPZ}. FT STRAND 405 413 {ECO:0000244|PDB:3EPZ}. FT STRAND 422 425 {ECO:0000244|PDB:3EPZ}. FT TURN 426 430 {ECO:0000244|PDB:3EPZ}. FT STRAND 434 441 {ECO:0000244|PDB:3EPZ}. FT STRAND 453 458 {ECO:0000244|PDB:3EPZ}. FT STRAND 462 467 {ECO:0000244|PDB:3EPZ}. FT STRAND 476 480 {ECO:0000244|PDB:3EPZ}. FT STRAND 485 488 {ECO:0000244|PDB:3EPZ}. FT TURN 493 495 {ECO:0000244|PDB:3EPZ}. FT HELIX 496 499 {ECO:0000244|PDB:3EPZ}. FT HELIX 504 518 {ECO:0000244|PDB:3EPZ}. FT HELIX 524 533 {ECO:0000244|PDB:3EPZ}. FT HELIX 538 540 {ECO:0000244|PDB:3EPZ}. FT HELIX 547 551 {ECO:0000244|PDB:3EPZ}. FT HELIX 554 567 {ECO:0000244|PDB:3EPZ}. FT HELIX 575 577 {ECO:0000244|PDB:3EPZ}. FT HELIX 579 587 {ECO:0000244|PDB:3EPZ}. FT HELIX 592 598 {ECO:0000244|PDB:3EPZ}. FT HELIX 622 629 {ECO:0000244|PDB:3SWR}. FT TURN 657 659 {ECO:0000244|PDB:3SWR}. FT HELIX 670 672 {ECO:0000244|PDB:3SWR}. FT TURN 674 677 {ECO:0000244|PDB:4WXX}. FT HELIX 687 689 {ECO:0000244|PDB:3SWR}. FT HELIX 692 703 {ECO:0000244|PDB:4WXX}. FT STRAND 731 735 {ECO:0000244|PDB:3SWR}. FT STRAND 738 740 {ECO:0000244|PDB:4WXX}. FT STRAND 744 746 {ECO:0000244|PDB:3SWR}. FT STRAND 748 752 {ECO:0000244|PDB:3SWR}. FT STRAND 755 758 {ECO:0000244|PDB:3SWR}. FT STRAND 762 765 {ECO:0000244|PDB:3SWR}. FT STRAND 767 769 {ECO:0000244|PDB:3SWR}. FT STRAND 775 785 {ECO:0000244|PDB:3SWR}. FT TURN 786 788 {ECO:0000244|PDB:3SWR}. FT STRAND 789 799 {ECO:0000244|PDB:3SWR}. FT HELIX 800 802 {ECO:0000244|PDB:3SWR}. FT STRAND 803 805 {ECO:0000244|PDB:4YOC}. FT HELIX 806 808 {ECO:0000244|PDB:3SWR}. FT STRAND 813 824 {ECO:0000244|PDB:3SWR}. FT HELIX 825 827 {ECO:0000244|PDB:3SWR}. FT STRAND 828 832 {ECO:0000244|PDB:3SWR}. FT STRAND 834 836 {ECO:0000244|PDB:3SWR}. FT HELIX 843 845 {ECO:0000244|PDB:3SWR}. FT TURN 851 853 {ECO:0000244|PDB:4WXX}. FT HELIX 856 860 {ECO:0000244|PDB:3SWR}. FT STRAND 862 870 {ECO:0000244|PDB:3SWR}. FT TURN 871 874 {ECO:0000244|PDB:3SWR}. FT STRAND 875 877 {ECO:0000244|PDB:3SWR}. FT STRAND 886 888 {ECO:0000244|PDB:4YOC}. FT TURN 889 891 {ECO:0000244|PDB:3SWR}. FT HELIX 894 905 {ECO:0000244|PDB:3SWR}. FT STRAND 912 916 {ECO:0000244|PDB:3SWR}. FT STRAND 921 928 {ECO:0000244|PDB:3SWR}. FT STRAND 931 934 {ECO:0000244|PDB:3SWR}. FT STRAND 938 941 {ECO:0000244|PDB:3SWR}. FT TURN 966 968 {ECO:0000244|PDB:3SWR}. FT HELIX 973 975 {ECO:0000244|PDB:3SWR}. FT HELIX 976 980 {ECO:0000244|PDB:3SWR}. FT STRAND 992 1001 {ECO:0000244|PDB:3SWR}. FT STRAND 1005 1008 {ECO:0000244|PDB:3SWR}. FT STRAND 1015 1020 {ECO:0000244|PDB:3SWR}. FT HELIX 1024 1026 {ECO:0000244|PDB:3SWR}. FT HELIX 1031 1034 {ECO:0000244|PDB:3SWR}. FT STRAND 1035 1037 {ECO:0000244|PDB:3SWR}. FT STRAND 1041 1044 {ECO:0000244|PDB:3SWR}. FT STRAND 1048 1052 {ECO:0000244|PDB:3SWR}. FT HELIX 1053 1055 {ECO:0000244|PDB:3SWR}. FT STRAND 1058 1064 {ECO:0000244|PDB:3SWR}. FT HELIX 1065 1067 {ECO:0000244|PDB:3SWR}. FT HELIX 1072 1077 {ECO:0000244|PDB:3SWR}. FT STRAND 1079 1090 {ECO:0000244|PDB:3SWR}. FT TURN 1091 1094 {ECO:0000244|PDB:3SWR}. FT STRAND 1095 1097 {ECO:0000244|PDB:3SWR}. FT HELIX 1101 1103 {ECO:0000244|PDB:4WXX}. FT STRAND 1139 1145 {ECO:0000244|PDB:3SWR}. FT HELIX 1150 1158 {ECO:0000244|PDB:3SWR}. FT STRAND 1160 1167 {ECO:0000244|PDB:3SWR}. FT HELIX 1171 1180 {ECO:0000244|PDB:3SWR}. FT STRAND 1184 1187 {ECO:0000244|PDB:3SWR}. FT HELIX 1191 1200 {ECO:0000244|PDB:3SWR}. FT TURN 1214 1216 {ECO:0000244|PDB:3SWR}. FT STRAND 1218 1222 {ECO:0000244|PDB:3SWR}. FT STRAND 1231 1233 {ECO:0000244|PDB:3SWR}. FT HELIX 1237 1243 {ECO:0000244|PDB:3SWR}. FT HELIX 1247 1258 {ECO:0000244|PDB:3SWR}. FT STRAND 1261 1268 {ECO:0000244|PDB:3SWR}. FT HELIX 1269 1272 {ECO:0000244|PDB:3SWR}. FT HELIX 1275 1277 {ECO:0000244|PDB:3SWR}. FT HELIX 1278 1289 {ECO:0000244|PDB:3SWR}. FT STRAND 1293 1300 {ECO:0000244|PDB:3SWR}. FT HELIX 1301 1304 {ECO:0000244|PDB:3SWR}. FT STRAND 1311 1318 {ECO:0000244|PDB:3SWR}. FT HELIX 1336 1338 {ECO:0000244|PDB:3SWR}. FT STRAND 1343 1345 {ECO:0000244|PDB:3SWR}. FT STRAND 1348 1350 {ECO:0000244|PDB:3SWR}. FT HELIX 1367 1371 {ECO:0000244|PDB:3SWR}. FT STRAND 1384 1386 {ECO:0000244|PDB:3SWR}. FT HELIX 1395 1401 {ECO:0000244|PDB:3SWR}. FT HELIX 1419 1426 {ECO:0000244|PDB:3SWR}. FT HELIX 1436 1438 {ECO:0000244|PDB:3SWR}. FT STRAND 1451 1453 {ECO:0000244|PDB:3SWR}. FT TURN 1462 1464 {ECO:0000244|PDB:3SWR}. FT STRAND 1474 1476 {ECO:0000244|PDB:4YOC}. FT HELIX 1477 1479 {ECO:0000244|PDB:3SWR}. FT STRAND 1480 1482 {ECO:0000244|PDB:3SWR}. FT HELIX 1487 1489 {ECO:0000244|PDB:3SWR}. FT STRAND 1493 1496 {ECO:0000244|PDB:3SWR}. FT HELIX 1499 1503 {ECO:0000244|PDB:3SWR}. FT HELIX 1504 1506 {ECO:0000244|PDB:3SWR}. FT HELIX 1508 1510 {ECO:0000244|PDB:3SWR}. FT TURN 1511 1514 {ECO:0000244|PDB:3SWR}. FT STRAND 1523 1525 {ECO:0000244|PDB:3SWR}. FT STRAND 1534 1536 {ECO:0000244|PDB:4WXX}. FT STRAND 1542 1547 {ECO:0000244|PDB:3SWR}. FT HELIX 1550 1556 {ECO:0000244|PDB:3SWR}. FT HELIX 1569 1578 {ECO:0000244|PDB:3SWR}. FT HELIX 1582 1598 {ECO:0000244|PDB:3SWR}. SQ SEQUENCE 1616 AA; 183165 MW; 1E833192D22AFA5B CRC64; MPARTAPARV PTLAVPAISL PDDVRRRLKD LERDSLTEKE CVKEKLNLLH EFLQTEIKNQ LCDLETKLRK EELSEEGYLA KVKSLLNKDL SLENGAHAYN REVNGRLENG NQARSEARRV GMADANSPPK PLSKPRTPRR SKSDGEAKPE PSPSPRITRK STRQTTITSH FAKGPAKRKP QEESERAKSD ESIKEEDKDQ DEKRRRVTSR ERVARPLPAE EPERAKSGTR TEKEEERDEK EEKRLRSQTK EPTPKQKLKE EPDREARAGV QADEDEDGDE KDEKKHRSQP KDLAAKRRPE EKEPEKVNPQ ISDEKDEDEK EEKRRKTTPK EPTEKKMARA KTVMNSKTHP PKCIQCGQYL DDPDLKYGQH PPDAVDEPQM LTNEKLSIFD ANESGFESYE ALPQHKLTCF SVYCKHGHLC PIDTGLIEKN IELFFSGSAK PIYDDDPSLE GGVNGKNLGP INEWWITGFD GGEKALIGFS TSFAEYILMD PSPEYAPIFG LMQEKIYISK IVVEFLQSNS DSTYEDLINK IETTVPPSGL NLNRFTEDSL LRHAQFVVEQ VESYDEAGDS DEQPIFLTPC MRDLIKLAGV TLGQRRAQAR RQTIRHSTRE KDRGPTKATT TKLVYQIFDT FFAEQIEKDD REDKENAFKR RRCGVCEVCQ QPECGKCKAC KDMVKFGGSG RSKQACQERR CPNMAMKEAD DDEEVDDNIP EMPSPKKMHQ GKKKKQNKNR ISWVGEAVKT DGKKSYYKKV CIDAETLEVG DCVSVIPDDS SKPLYLARVT ALWEDSSNGQ MFHAHWFCAG TDTVLGATSD PLELFLVDEC EDMQLSYIHS KVKVIYKAPS ENWAMEGGMD PESLLEGDDG KTYFYQLWYD QDYARFESPP KTQPTEDNKF KFCVSCARLA EMRQKEIPRV LEQLEDLDSR VLYYSATKNG ILYRVGDGVY LPPEAFTFNI KLSSPVKRPR KEPVDEDLYP EHYRKYSDYI KGSNLDAPEP YRIGRIKEIF CPKKSNGRPN ETDIKIRVNK FYRPENTHKS TPASYHADIN LLYWSDEEAV VDFKAVQGRC TVEYGEDLPE CVQVYSMGGP NRFYFLEAYN AKSKSFEDPP NHARSPGNKG KGKGKGKGKP KSQACEPSEP EIEIKLPKLR TLDVFSGCGG LSEGFHQAGI SDTLWAIEMW DPAAQAFRLN NPGSTVFTED CNILLKLVMA GETTNSRGQR LPQKGDVEML CGGPPCQGFS GMNRFNSRTY SKFKNSLVVS FLSYCDYYRP RFFLLENVRN FVSFKRSMVL KLTLRCLVRM GYQCTFGVLQ AGQYGVAQTR RRAIILAAAP GEKLPLFPEP LHVFAPRACQ LSVVVDDKKF VSNITRLSSG PFRTITVRDT MSDLPEVRNG ASALEISYNG EPQSWFQRQL RGAQYQPILR DHICKDMSAL VAARMRHIPL APGSDWRDLP NIEVRLSDGT MARKLRYTHH DRKNGRSSSG ALRGVCSCVE AGKACDPAAR QFNTLIPWCL PHTGNRHNHW AGLYGRLEWD GFFSTTVTNP EPMGKQGRVL HPEQHRVVSV RECARSQGFP DTYRLFGNIL DKHRQVGNAV PPPLAKAIGL EIKLCMLAKA RESASAKIKE EEAAKD // ID DPOD3_HUMAN Reviewed; 466 AA. AC Q15054; B7ZAI6; Q32MZ9; Q32N00; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 26-SEP-2001, sequence version 2. DT 11-NOV-2015, entry version 138. DE RecName: Full=DNA polymerase delta subunit 3; DE AltName: Full=DNA polymerase delta subunit p66; GN Name=POLD3; Synonyms=KIAA0039; 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=Bone marrow; RX PubMed=7584026; DOI=10.1093/dnares/1.1.27; RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., RA Sato S., Nagase T., Seki N., Ishikawa K., Tabata S.; RT "Prediction of the coding sequences of unidentified human genes. I. RT The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by RT analysis of randomly sampled cDNA clones from human immature myeloid RT cell line KG-1."; RL DNA Res. 1:27-35(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE 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 2 AND 3). RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PROTEIN SEQUENCE OF 2-19 AND 110-123, CLEAVAGE OF INITIATOR RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Embryonic kidney; RA Bienvenut W.V., Waridel P., Quadroni M.; RL Submitted (MAR-2009) to UniProtKB. RN [7] RP FUNCTION. RX PubMed=10219083; DOI=10.1093/nar/27.10.2108; RA Hughes P., Tratner I., Ducoux M., Piard K., Baldacci G.; RT "Isolation and identification of the third subunit of mammalian DNA RT polymerase delta by PCNA-affinity chromatography of mouse FM3A cell RT extracts."; RL Nucleic Acids Res. 27:2108-2114(1999). RN [8] RP FUNCTION. RX PubMed=10852724; DOI=10.1021/bi0000871; RA Mo J.-Y., Liu L., Leon A., Mazloum N., Lee M.Y.W.T.; RT "Evidence that DNA polymerase delta isolated by immunoaffinity RT chromatography exhibits high-molecular weight characteristics and is RT associated with the KIAA0039 protein and RPA."; RL Biochemistry 39:7245-7254(2000). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307, 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 [10] RP FUNCTION, AND INTERACTION WITH PCNA. RX PubMed=16510448; DOI=10.1074/jbc.M600322200; RA Li H., Xie B., Zhou Y., Rahmeh A., Trusa S., Zhang S., Gao Y., RA Lee E.Y., Lee M.Y.; RT "Functional roles of p12, the fourth subunit of human DNA polymerase RT delta."; RL J. Biol. Chem. 281:14748-14755(2006). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307, 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-307; SER-407; SER-409; RP THR-411; SER-413 AND SER-458, AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP 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-307, 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307, 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 [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-307, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [18] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.M111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., RA Meinnel T., Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [19] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-258, 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 [20] RP VARIANTS VAL-194 AND LEU-195. RX PubMed=21248752; DOI=10.1038/nature09639; RA Varela I., Tarpey P., Raine K., Huang D., Ong C.K., Stephens P., RA Davies H., Jones D., Lin M.L., Teague J., Bignell G., Butler A., RA Cho J., Dalgliesh G.L., Galappaththige D., Greenman C., Hardy C., RA Jia M., Latimer C., Lau K.W., Marshall J., McLaren S., Menzies A., RA Mudie L., Stebbings L., Largaespada D.A., Wessels L.F.A., Richard S., RA Kahnoski R.J., Anema J., Tuveson D.A., Perez-Mancera P.A., RA Mustonen V., Fischer A., Adams D.J., Rust A., Chan-On W., Subimerb C., RA Dykema K., Furge K., Campbell P.J., Teh B.T., Stratton M.R., RA Futreal P.A.; RT "Exome sequencing identifies frequent mutation of the SWI/SNF complex RT gene PBRM1 in renal carcinoma."; RL Nature 469:539-542(2011). CC -!- FUNCTION: Required for optimal DNA polymerase delta activity. CC {ECO:0000269|PubMed:10219083, ECO:0000269|PubMed:10852724, CC ECO:0000269|PubMed:16510448}. CC -!- SUBUNIT: Heterotetramer composed of subunits of 125 kDa, 50 kDa, CC 66 kDa and 12 kDa. Interacts with POLD2. Interacts with PCNA. CC {ECO:0000269|PubMed:16510448}. CC -!- INTERACTION: CC P12004:PCNA; NbExp=4; IntAct=EBI-864956, EBI-358311; CC P49005:POLD2; NbExp=5; IntAct=EBI-864956, EBI-372354; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q15054-1; Sequence=Displayed; CC Name=2; CC IsoId=Q15054-2; Sequence=VSP_054150; CC Note=No experimental confirmation available.; CC Name=3; CC IsoId=Q15054-3; Sequence=VSP_054149; CC Note=No experimental confirmation available.; CC -!- SEQUENCE CAUTION: CC Sequence=BAA05039.1; 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; D26018; BAA05039.1; ALT_INIT; mRNA. DR EMBL; AK316301; BAH14672.1; -; mRNA. DR EMBL; AP001104; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP001324; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP001372; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471076; EAW74942.1; -; Genomic_DNA. DR EMBL; BC108908; AAI08909.1; -; mRNA. DR EMBL; BC108909; AAI08910.1; -; mRNA. DR CCDS; CCDS8233.1; -. [Q15054-1] DR RefSeq; NP_006582.1; NM_006591.2. [Q15054-1] DR UniGene; Hs.82502; -. DR PDB; 1U76; X-ray; 2.60 A; B/D/F=452-466. DR PDB; 3E0J; X-ray; 3.00 A; B/D/F/H=1-144. DR PDBsum; 1U76; -. DR PDBsum; 3E0J; -. DR ProteinModelPortal; Q15054; -. DR SMR; Q15054; 2-144. DR BioGrid; 115940; 23. DR DIP; DIP-35772N; -. DR IntAct; Q15054; 6. DR MINT; MINT-2789689; -. DR STRING; 9606.ENSP00000263681; -. DR PhosphoSite; Q15054; -. DR BioMuta; POLD3; -. DR DMDM; 17375506; -. DR MaxQB; Q15054; -. DR PaxDb; Q15054; -. DR PeptideAtlas; Q15054; -. DR PRIDE; Q15054; -. DR Ensembl; ENST00000263681; ENSP00000263681; ENSG00000077514. [Q15054-1] DR Ensembl; ENST00000527458; ENSP00000432951; ENSG00000077514. [Q15054-2] DR Ensembl; ENST00000532497; ENSP00000436018; ENSG00000077514. [Q15054-3] DR GeneID; 10714; -. DR KEGG; hsa:10714; -. DR UCSC; uc001ovf.2; human. [Q15054-1] DR CTD; 10714; -. DR GeneCards; POLD3; -. DR HGNC; HGNC:20932; POLD3. DR HPA; HPA039627; -. DR HPA; HPA058846; -. DR MIM; 611415; gene. DR neXtProt; NX_Q15054; -. DR PharmGKB; PA134868595; -. DR eggNOG; ENOG410IGGV; Eukaryota. DR eggNOG; ENOG410XSD1; LUCA. DR GeneTree; ENSGT00390000015282; -. DR HOGENOM; HOG000008055; -. DR HOVERGEN; HBG051397; -. DR InParanoid; Q15054; -. DR KO; K03504; -. DR OMA; FSAIQCA; -. DR PhylomeDB; Q15054; -. DR TreeFam; TF103006; -. DR Reactome; R-HSA-109977; Repair synthesis for gap-filling by DNA polymerase in TC-NER. DR Reactome; R-HSA-110314; Recognition of DNA damage by PCNA-containing replication complex. DR Reactome; R-HSA-174411; Polymerase switching on the C-strand of the telomere. DR Reactome; R-HSA-174414; Processive synthesis on the C-strand of the telomere. DR Reactome; R-HSA-174417; Telomere C-strand (Lagging Strand) Synthesis. DR Reactome; R-HSA-174437; Removal of the Flap Intermediate from the C-strand. DR Reactome; R-HSA-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha). DR Reactome; R-HSA-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta). DR Reactome; R-HSA-5651801; PCNA-Dependent Long Patch Base Excision Repair. DR Reactome; R-HSA-5656169; Termination of translesion DNA synthesis. DR Reactome; R-HSA-69091; Polymerase switching. DR Reactome; R-HSA-69109; Leading Strand Synthesis. DR Reactome; R-HSA-69166; Removal of the Flap Intermediate. DR Reactome; R-HSA-69183; Processive synthesis on the lagging strand. DR Reactome; R-HSA-74967; Repair synthesis of patch ~27-30 bases long by DNA polymerase. DR EvolutionaryTrace; Q15054; -. DR GeneWiki; POLD3; -. DR GenomeRNAi; 10714; -. DR NextBio; 40675; -. DR PRO; PR:Q15054; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; Q15054; -. DR ExpressionAtlas; Q15054; baseline and differential. DR Genevisible; Q15054; HS. DR GO; GO:0043625; C:delta DNA polymerase complex; NAS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; NAS:UniProtKB. DR GO; GO:0006284; P:base-excision repair; TAS:Reactome. DR GO; GO:0042769; P:DNA damage response, detection of DNA damage; TAS:Reactome. DR GO; GO:0006281; P:DNA repair; TAS:Reactome. DR GO; GO:0006271; P:DNA strand elongation involved in DNA replication; TAS:Reactome. DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; NAS:UniProtKB. DR GO; GO:0006298; P:mismatch repair; NAS:UniProtKB. DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome. DR GO; GO:0006289; P:nucleotide-excision repair; TAS:Reactome. DR GO; GO:0006297; P:nucleotide-excision repair, DNA gap filling; IMP:UniProtKB. DR GO; GO:0000723; P:telomere maintenance; TAS:Reactome. DR GO; GO:0000722; P:telomere maintenance via recombination; TAS:Reactome. DR GO; GO:0032201; P:telomere maintenance via semi-conservative replication; TAS:Reactome. DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; TAS:Reactome. DR GO; GO:0019985; P:translesion synthesis; TAS:Reactome. DR InterPro; IPR019038; DNA_polymerase_subunit_Cdc27. DR Pfam; PF09507; CDC27; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Complete proteome; KW Direct protein sequencing; DNA replication; KW DNA-directed DNA polymerase; Isopeptide bond; Nucleotidyltransferase; KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome; KW Transferase; Ubl conjugation. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:22223895, FT ECO:0000269|Ref.6}. FT CHAIN 2 466 DNA polymerase delta subunit 3. FT /FTId=PRO_0000186047. FT MOD_RES 2 2 N-acetylalanine. FT {ECO:0000244|PubMed:22223895, FT ECO:0000269|Ref.6}. FT MOD_RES 307 307 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:19369195, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 407 407 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 409 409 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 411 411 Phosphothreonine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 413 413 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 458 458 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT CROSSLNK 258 258 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in SUMO2). FT {ECO:0000244|PubMed:25218447}. FT VAR_SEQ 1 106 Missing (in isoform 3). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_054149. FT VAR_SEQ 1 39 Missing (in isoform 2). FT {ECO:0000303|PubMed:15489334}. FT /FTId=VSP_054150. FT VARIANT 194 194 G -> V (found in a renal cell carcinoma FT sample; somatic mutation). FT {ECO:0000269|PubMed:21248752}. FT /FTId=VAR_064745. FT VARIANT 195 195 M -> L (found in a renal cell carcinoma FT sample; somatic mutation). FT {ECO:0000269|PubMed:21248752}. FT /FTId=VAR_064746. FT HELIX 3 14 {ECO:0000244|PDB:3E0J}. FT TURN 15 17 {ECO:0000244|PDB:3E0J}. FT HELIX 23 30 {ECO:0000244|PDB:3E0J}. FT HELIX 34 52 {ECO:0000244|PDB:3E0J}. FT STRAND 58 81 {ECO:0000244|PDB:3E0J}. FT TURN 82 84 {ECO:0000244|PDB:3E0J}. FT HELIX 85 91 {ECO:0000244|PDB:3E0J}. FT STRAND 93 106 {ECO:0000244|PDB:3E0J}. FT STRAND 109 111 {ECO:0000244|PDB:3E0J}. FT HELIX 113 125 {ECO:0000244|PDB:3E0J}. FT HELIX 129 131 {ECO:0000244|PDB:3E0J}. FT STRAND 134 136 {ECO:0000244|PDB:3E0J}. FT HELIX 459 461 {ECO:0000244|PDB:1U76}. SQ SEQUENCE 466 AA; 51400 MW; E9625E0188725F45 CRC64; MADQLYLENI DEFVTDQNKI VTYKWLSYTL GVHVNQAKQM LYDYVERKRK ENSGAQLHVT YLVSGSLIQN GHSCHKVAVV REDKLEAVKS KLAVTASIHV YSIQKAMLKD SGPLFNTDYD ILKSNLQNCS KFSAIQCAAA VPRAPAESSS SSKKFEQSHL HMSSETQANN ELTTNGHGPP ASKQVSQQPK GIMGMFASKA AAKTQETNKE TKTEAKEVTN ASAAGNKAPG KGNMMSNFFG KAAMNKFKVN LDSEQAVKEE KIVEQPTVSV TEPKLATPAG LKKSSKKAEP VKVLQKEKKR GKRVALSDDE TKETENMRKK RRRIKLPESD SSEDEVFPDS PGAYEAESPS PPPPPSPPLE PVPKTEPEPP SVKSSSGENK RKRKRVLKSK TYLDGEGCIV TEKVYESESC TDSEEELNMK TSSVHRPPAM TVKKEPREER KGPKKGTAAL GKANRQVSIT GFFQRK // ID DPOD3_YEAST Reviewed; 350 AA. AC P47110; D6VWL4; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 1. DT 11-NOV-2015, entry version 126. DE RecName: Full=DNA polymerase delta subunit 3; GN Name=POL32; OrderedLocusNames=YJR043C; ORFNames=J1626; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=7668047; DOI=10.1002/yea.320110809; RA Huang M.-E., Chuat J.-C., Galibert F.; RT "Analysis of a 42.5 kb DNA sequence of chromosome X reveals three tRNA RT genes and 14 new open reading frames including a gene most probably RT belonging to the family of ubiquitin-protein ligases."; RL Yeast 11:775-781(1995). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=8641269; RA Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., RA Chuat J.-C., Coster F., Cziepluch C., de Haan M., Domdey H., RA Durand P., Entian K.-D., Gatius M., Goffeau A., Grivell L.A., RA Hennemann A., Herbert C.J., Heumann K., Hilger F., Hollenberg C.P., RA Huang M.-E., Jacq C., Jauniaux J.-C., Katsoulou C., Kirchrath L., RA Kleine K., Kordes E., Koetter P., Liebl S., Louis E.J., Manus V., RA Mewes H.-W., Miosga T., Obermaier B., Perea J., Pohl T.M., RA Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rasmussen S.W., RA Rose M., Rossau R., Schaaff-Gerstenschlaeger I., Smits P.H.M., RA Scarcez T., Soriano N., To Van D., Tzermia M., Van Broekhoven A., RA Vandenbol M., Wedler H., von Wettstein D., Wambutt R., Zagulski M., RA Zollner A., Karpfinger-Hartl L.; RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome RT X."; RL EMBO J. 15:2031-2049(1996). RN [3] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., RA Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and RT now."; RL G3 (Bethesda) 4:389-398(2014). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., RA Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., RA Williamson J., Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., RA Kolodner R.D., LaBaer J.; RT "Approaching a complete repository of sequence-verified protein- RT encoding clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [5] RP CHARACTERIZATION. RX PubMed=9677405; DOI=10.1074/jbc.273.31.19747; RA Gerik K.J., Li X., Pautz A., Burgers P.M.; RT "Characterization of the two small subunits of Saccharomyces RT cerevisiae DNA polymerase delta."; RL J. Biol. Chem. 273:19747-19755(1998). RN [6] RP COMPOSITION OF THE DNA POLYMERASE DELTA COMPLEX. RX PubMed=11568188; DOI=10.1074/jbc.M108842200; RA Johansson E., Majka J., Burgers P.M.; RT "Structure of DNA polymerase delta from Saccharomyces cerevisiae."; RL J. Biol. Chem. 276:43824-43828(2001). RN [7] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., RA Dephoure N., O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=17287358; DOI=10.1073/pnas.0607084104; RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L., RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.; RT "Analysis of phosphorylation sites on proteins from Saccharomyces RT cerevisiae by electron transfer dissociation (ETD) mass RT spectrometry."; RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=18407956; DOI=10.1074/mcp.M700468-MCP200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth RT phosphoproteome analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-223 AND SER-230, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19779198; DOI=10.1126/science.1172867; RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.; RT "Global analysis of Cdk1 substrate phosphorylation sites provides RT insights into evolution."; RL Science 325:1682-1686(2009). CC -!- FUNCTION: DNA polymerase delta (DNA polymerase III) participates CC in chromosomal DNA replication. It is required during synthesis of CC the leading and lagging DNA strands at the replication fork and CC binds at/or near replication origins and moves along DNA with the CC replication fork. It has 3'-5' proofreading exonuclease activity CC that correct errors arising during DNA replication. It is also CC involved in DNA synthesis during DNA repair. CC -!- SUBUNIT: DNA polymerase delta is a heterotrimer of POL3, POL32 and CC HYS2. POL32 can form homodimers. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. CC -!- MISCELLANEOUS: Present with 2410 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. 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; L36344; AAA88745.1; -; Genomic_DNA. DR EMBL; Z49543; CAA89571.1; -; Genomic_DNA. DR EMBL; AY557918; AAS56244.1; -; Genomic_DNA. DR EMBL; BK006943; DAA08830.1; -; Genomic_DNA. DR PIR; S57062; S57062. DR RefSeq; NP_012577.1; NM_001181701.1. DR ProteinModelPortal; P47110; -. DR BioGrid; 33794; 282. DR DIP; DIP-2523N; -. DR IntAct; P47110; 9. DR MINT; MINT-477170; -. DR MaxQB; P47110; -. DR PRIDE; P47110; -. DR EnsemblFungi; YJR043C; YJR043C; YJR043C. DR GeneID; 853500; -. DR KEGG; sce:YJR043C; -. DR EuPathDB; FungiDB:YJR043C; -. DR SGD; S000003804; POL32. DR HOGENOM; HOG000112262; -. DR InParanoid; P47110; -. DR KO; K03504; -. DR OMA; DCFIYAF; -. DR OrthoDB; EOG7R5765; -. DR BioCyc; YEAST:G3O-31678-MONOMER; -. DR NextBio; 974143; -. DR PRO; PR:P47110; -. DR Proteomes; UP000002311; Chromosome X. DR GO; GO:0043625; C:delta DNA polymerase complex; TAS:SGD. DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IDA:SGD. DR GO; GO:0006284; P:base-excision repair; TAS:SGD. DR GO; GO:0006277; P:DNA amplification; IMP:SGD. DR GO; GO:0043137; P:DNA replication, removal of RNA primer; IDA:SGD. DR GO; GO:0000727; P:double-strand break repair via break-induced replication; IMP:SGD. DR GO; GO:0006273; P:lagging strand elongation; TAS:SGD. DR GO; GO:0006272; P:leading strand elongation; TAS:SGD. DR GO; GO:0006298; P:mismatch repair; NAS:SGD. DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; TAS:GOC. DR GO; GO:0006289; P:nucleotide-excision repair; TAS:SGD. DR GO; GO:0006301; P:postreplication repair; TAS:SGD. DR GO; GO:0006278; P:RNA-dependent DNA replication; IDA:SGD. PE 1: Evidence at protein level; KW Complete proteome; DNA replication; DNA-directed DNA polymerase; KW Nucleotidyltransferase; Nucleus; Phosphoprotein; Reference proteome; KW Transferase. FT CHAIN 1 350 DNA polymerase delta subunit 3. FT /FTId=PRO_0000186050. FT MOD_RES 223 223 Phosphothreonine. FT {ECO:0000244|PubMed:19779198}. FT MOD_RES 230 230 Phosphoserine. FT {ECO:0000244|PubMed:19779198}. SQ SEQUENCE 350 AA; 40310 MW; D0B9CC52F26E20B2 CRC64; MDQKASYFIN EKLFTEVKPV LFTDLIHHLK IGPSMAKKLM FDYYKQTTNA KYNCVVICCY KDQTIKIIHD LSNIPQQDSI IDCFIYAFNP MDSFIPYYDI IDQKDCLTIK NSYELKVSES SKIIERTKTL EEKSKPLVRP TARSKTTPEE TTGRKSKSKD MGLRSTALLA KMKKDRDDKE TSRQNELRKR KEENLQKINK QNPEREAQMK ELNNLFVEDD LDTEEVNGGS KPNSPKETDS NDKDKNNDDL EDLLETTAED SLMDVPKIQQ TKPSETEHSK EPKSEEEPSS FIDEDGYIVT KRPATSTPPR KPSPVVKRAL SSSKKQETPS SNKRLKKQGT LESFFKRKAK // ID DPOD3_SCHPO Reviewed; 372 AA. AC P30261; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1993, sequence version 1. DT 11-NOV-2015, entry version 102. DE RecName: Full=DNA polymerase delta subunit 3; DE AltName: Full=Cell division control protein 27; GN Name=cdc27; ORFNames=SPBC1734.02c, SPBC337.18c; OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina; OC Schizosaccharomycetes; Schizosaccharomycetales; OC Schizosaccharomycetaceae; Schizosaccharomyces. OX NCBI_TaxID=284812; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RX PubMed=1538696; DOI=10.1007/BF00292709; RA Hughes D.A., Macneill S.A., Fantes P.A.; RT "Molecular cloning and sequence analysis of cdc27+ required for the RT G2-M transition in the fission yeast Schizosaccharomyces pombe."; RL Mol. Gen. Genet. 231:401-410(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=972 / ATCC 24843; RX PubMed=11859360; DOI=10.1038/nature724; RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A., RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S., RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., RA Collins M., Connor R., Cronin A., Davis P., Feltwell T., Fraser A., RA Gentles S., Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., RA Holroyd S., Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., RA James K.D., Jones L., Jones M., Leather S., McDonald S., McLean J., RA Mooney P., Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., RA Oliver K., O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., RA Rutherford K.M., Rutter S., Saunders D., Seeger K., Sharp S., RA Skelton J., Simmonds M.N., Squares R., Squares S., Stevens K., RA Taylor K., Taylor R.G., Tivey A., Walsh S.V., Warren T., Whitehead S., RA Woodward J.R., Volckaert G., Aert R., Robben J., Grymonprez B., RA Weltjens I., Vanstreels E., Rieger M., Schaefer M., Mueller-Auer S., RA Gabel C., Fuchs M., Duesterhoeft A., Fritzc C., Holzer E., Moestl D., RA Hilbert H., Borzym K., Langer I., Beck A., Lehrach H., Reinhardt R., RA Pohl T.M., Eger P., Zimmermann W., Wedler H., Wambutt R., Purnelle B., RA Goffeau A., Cadieu E., Dreano S., Gloux S., Lelaure V., Mottier S., RA Galibert F., Aves S.J., Xiang Z., Hunt C., Moore K., Hurst S.M., RA Lucas M., Rochet M., Gaillardin C., Tallada V.A., Garzon A., Thode G., RA Daga R.R., Cruzado L., Jimenez J., Sanchez M., del Rey F., Benito J., RA Dominguez A., Revuelta J.L., Moreno S., Armstrong J., Forsburg S.L., RA Cerutti L., Lowe T., McCombie W.R., Paulsen I., Potashkin J., RA Shpakovski G.V., Ussery D., Barrell B.G., Nurse P.; RT "The genome sequence of Schizosaccharomyces pombe."; RL Nature 415:871-880(2002). RN [3] RP FUNCTION, AND SUBUNIT. RX PubMed=10671561; DOI=10.1074/jbc.275.7.5153; RA Zuo S., Bermudez V., Zhang G., Kelman Z., Hurwitz J.; RT "Structure and activity associated with multiple forms of RT Schizosaccharomyces pombe DNA polymerase delta."; RL J. Biol. Chem. 275:5153-5162(2000). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163, AND IDENTIFICATION RP BY MASS SPECTROMETRY. RX PubMed=18257517; DOI=10.1021/pr7006335; RA Wilson-Grady J.T., Villen J., Gygi S.P.; RT "Phosphoproteome analysis of fission yeast."; RL J. Proteome Res. 7:1088-1097(2008). CC -!- SUBUNIT: Heterotetramer that consist of the pol3, cdc1, cdc27 and CC cdm1 subunits. Cdc27 interacts with cdc1 and is required for CC dimerization of the tetramer. {ECO:0000269|PubMed:10671561}. CC -!- INTERACTION: CC P87324:cdc1; NbExp=3; IntAct=EBI-866919, EBI-865227; CC Q03392:pcn1; NbExp=5; IntAct=EBI-866919, EBI-768724; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. 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; M74062; AAA35295.1; -; Genomic_DNA. DR EMBL; M83307; AAA35296.1; -; mRNA. DR EMBL; CU329671; CAA21288.1; -; Genomic_DNA. DR PIR; T39649; T39649. DR RefSeq; NP_595419.1; NM_001021326.2. DR BioGrid; 276184; 20. DR IntAct; P30261; 2. DR MINT; MINT-4688159; -. DR MaxQB; P30261; -. DR EnsemblFungi; SPBC1734.02c.1; SPBC1734.02c.1:pep; SPBC1734.02c. DR GeneID; 2539627; -. DR KEGG; spo:SPBC1734.02c; -. DR EuPathDB; FungiDB:SPBC1734.02c; -. DR PomBase; SPBC1734.02c; cdc27. DR InParanoid; P30261; -. DR KO; K03504; -. DR OrthoDB; EOG7XPZFV; -. DR NextBio; 20800783; -. DR PRO; PR:P30261; -. DR Proteomes; UP000002485; Chromosome II. DR GO; GO:0005829; C:cytosol; IDA:PomBase. DR GO; GO:0043625; C:delta DNA polymerase complex; IDA:PomBase. DR GO; GO:0043596; C:nuclear replication fork; IC:PomBase. DR GO; GO:0005634; C:nucleus; IDA:PomBase. DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0006271; P:DNA strand elongation involved in DNA replication; IDA:PomBase. DR GO; GO:1904161; P:DNA synthesis involved in UV-damage excision repair; IDA:PomBase. DR GO; GO:1903459; P:mitotic DNA replication lagging strand elongation; IC:PomBase. DR GO; GO:0007067; P:mitotic nuclear division; IEA:UniProtKB-KW. DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IC:GOC. DR InterPro; IPR019038; DNA_polymerase_subunit_Cdc27. DR Pfam; PF09507; CDC27; 2. PE 1: Evidence at protein level; KW Cell cycle; Cell division; Complete proteome; DNA replication; KW DNA-directed DNA polymerase; Mitosis; Nucleotidyltransferase; Nucleus; KW Phosphoprotein; Reference proteome; Transferase. FT CHAIN 1 372 DNA polymerase delta subunit 3. FT /FTId=PRO_0000186049. FT MOD_RES 163 163 Phosphoserine. FT {ECO:0000269|PubMed:18257517}. FT MUTAGEN 57 57 G->E: Cell cycle arrest at 35 degrees FT Celsius. FT MUTAGEN 57 57 G->R: Cell cycle arrest at 35 degrees FT Celsius. SQ SEQUENCE 372 AA; 42350 MW; 6E6F9AD407B17673 CRC64; MEEWRNFLDI KVINESSLVT VDNLSLQLDI SSEKAQEYLN MFYQGNDFLY PIYLIHGQPI DDEINLEIDE ESQPISNFPV LQYILCDKSS LQEKQSRLKS GYKTVIFALS SAPLSDFDEL LPAVYEIREK DVLYKKEDAD KYGFIFNENS VPRVLKKAPS THSPQLSVPS KTSTIDKTDT RSTEKTKGKD IFSNARNQKG NSSRKNKKAP LENHKEKEPL LPKEEKLSEQ AKRERDDLKN IMQLEDESVS TTSVHDSEDD NLDSNNFQLE IGTEAKSAAP DEPQEIIKSV SGGKRRGKRK VKKYATTKDE EGFLVTKEEE VWESFSEDEN ISTGTSNVVR NKPTTVNIAT KKKNTAQSKP QQKSIMSFFG KK // ID ERCC5_HUMAN Reviewed; 1186 AA. AC P28715; A6NGT4; Q5JUS4; Q5JUS5; Q7Z2V3; Q8IZL6; Q8N1B7; Q9HD59; AC Q9HD60; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 02-SEP-2008, sequence version 3. DT 11-NOV-2015, entry version 185. DE RecName: Full=DNA repair protein complementing XP-G cells; DE EC=3.1.-.-; DE AltName: Full=DNA excision repair protein ERCC-5; DE AltName: Full=Xeroderma pigmentosum group G-complementing protein; GN Name=ERCC5; Synonyms=ERCM2, XPG, XPGC; 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 VARIANTS ARG-1053; RP ARG-1080 AND HIS-1104. RX PubMed=8483504; DOI=10.1038/363182a0; RA Scherly D., Nouspikel T., Corlet J., Ucla C., Bairoch A., RA Clarkson S.G.; RT "Complementation of the DNA repair defect in Xeroderma pigmentosum RT group G cells by a human cDNA related to yeast RAD2."; RL Nature 363:182-185(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS VAL-254; ARG-1053 RP AND ARG-1080. RX PubMed=7510366; DOI=10.1016/0921-8777(94)90080-9; RA Shiomi T., Harada Y.-N., Saito T., Shiomi N., Okuno Y., Yamaizumi M.; RT "An ERCC5 gene with homology to yeast RAD2 is involved in group G RT Xeroderma pigmentosum."; RL Mutat. Res. 314:167-175(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS VAL-254; ARG-1053 RP AND ARG-1080. RX PubMed=8413238; RA Macinnes M.A., Dickson J.A., Hernandez R.R., Learmonth D., Lin G.Y., RA Mudgett J.S., Park M.S., Schauer S., Reynolds R.J., Strniste G.F., RA Yu J.Y.; RT "Human ERCC5 cDNA-cosmid complementation for excision repair and RT bipartite amino acid domains conserved with RAD proteins of RT Saccharomyces cerevisiae and Schizosaccharomyces pombe."; RL Mol. Cell. Biol. 13:6393-6402(1993). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS RP 1 AND 3). RX PubMed=11266544; DOI=10.1093/nar/29.7.1443; RA Emmert S., Schneider T.D., Khan S.G., Kraemer K.H.; RT "The human XPG gene: gene architecture, alternative splicing and RT single nucleotide polymorphisms."; RL Nucleic Acids Res. 29:1443-1452(2001). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS RP VAL-254; ARG-1053 AND ARG-1080. RC TISSUE=Bone marrow; RA Zan Q., Guo J.H., Yu L.; RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-181; VAL-254; RP ARG-256; CYS-311; LYS-399; SER-529; ILE-590; LEU-597; SER-879; RP HIS-1009 AND ARG-1053; ARG-1080 AND GLN-1080. RG NIEHS SNPs program; RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057823; DOI=10.1038/nature02379; RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., RA Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., RA Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T., RA Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., RA Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., RA Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., RA Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., RA Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., RA Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., RA Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., RA Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., RA Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., RA Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., RA King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., RA Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., RA Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., RA Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., RA Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., RA Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., RA Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., RA Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.; RT "The DNA sequence and analysis of human chromosome 13."; RL Nature 428:522-528(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS RP ARG-1053 AND ARG-1080. RC TISSUE=Eye; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-88. RX PubMed=8088806; DOI=10.1006/geno.1994.1261; RA Samec S., Jones T.A., Corlet J., Scherly D., Sheer D., Wood R.D., RA Clarkson S.G.; RT "The human gene for Xeroderma pigmentosum complementation group G RT (XPG) maps to 13q33 by fluorescence in situ hybridization."; RL Genomics 21:283-285(1994). RN [10] RP CHARACTERIZATION. RX PubMed=8206890; RA O'Donovan A., Scherly D., Clarkson S.G., Wood R.D.; RT "Isolation of active recombinant XPG protein, a human DNA repair RT endonuclease."; RL J. Biol. Chem. 269:15965-15968(1994). RN [11] RP CHARACTERIZATION. RX PubMed=8090225; DOI=10.1038/371432a0; RA O'Donovan A., Davies A.A., Moggs J.G., West S.C., Wood R.D.; RT "XPG endonuclease makes the 3' incision in human DNA nucleotide RT excision repair."; RL Nature 371:432-435(1994). RN [12] RP CHARACTERIZATION. RX PubMed=8078765; DOI=10.1093/nar/22.16.3312; RA Habraken Y., Sung P., Prakash L., Prakash S.; RT "Human Xeroderma pigmentosum group G gene encodes a DNA RT endonuclease."; RL Nucleic Acids Res. 22:3312-3316(1994). RN [13] RP CHARACTERIZATION, AND SUBCELLULAR LOCATION. RX PubMed=7651464; DOI=10.1016/0165-7992(95)90070-5; RA Cloud K.G., Shen B., Strniste G.F., Park M.S.; RT "XPG protein has a structure-specific endonuclease activity."; RL Mutat. Res. 347:55-60(1995). RN [14] RP INTERACTION WITH PCNA. RX PubMed=9305916; DOI=10.1074/jbc.272.39.24522; RA Gary R., Ludwig D.L., Cornelius H.L., MacInnes M.A., Park M.S.; RT "The DNA repair endonuclease XPG binds to proliferating cell nuclear RT antigen (PCNA) and shares sequence elements with the PCNA-binding RT regions of FEN-1 and cyclin-dependent kinase inhibitor p21."; RL J. Biol. Chem. 272:24522-24529(1997). RN [15] RP REVIEW. RX PubMed=14726017; DOI=10.1016/j.biochi.2003.10.014; RA Clarkson S.G.; RT "The XPG story."; RL Biochimie 85:1113-1121(2003). RN [16] RP REVIEW ON VARIANTS XP-G. RX PubMed=10447254; RX DOI=10.1002/(SICI)1098-1004(1999)14:1<9::AID-HUMU2>3.0.CO;2-6; RA Cleaver J.E., Thompson L.H., Richardson A.S., States J.C.; RT "A summary of mutations in the UV-sensitive disorders: xeroderma RT pigmentosum, Cockayne syndrome, and trichothiodystrophy."; RL Hum. Mutat. 14:9-22(1999). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-8, 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 [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 VARIANT XP-G VAL-792. RX PubMed=7951246; DOI=10.1093/hmg/3.6.963; RA Nouspikel T., Clarkson S.G.; RT "Mutations that disable the DNA repair gene XPG in a Xeroderma RT pigmentosum group G patient."; RL Hum. Mol. Genet. 3:963-967(1994). RN [20] RP VARIANT XP-G VAL-792. RX PubMed=9096355; DOI=10.1073/pnas.94.7.3116; RA Nouspikel T., Lalle P., Leadon S.A., Cooper P.K., Clarkson S.G.; RT "A common mutational pattern in Cockayne syndrome patients from RT Xeroderma pigmentosum group G: implications for a second XPG RT function."; RL Proc. Natl. Acad. Sci. U.S.A. 94:3116-3121(1997). RN [21] RP VARIANT XP-G HIS-72. RX PubMed=11228268; DOI=10.1203/00006450-200103000-00016; RA Zafeiriou D.I., Thorel F., Andreou A., Kleijer W.J., Raams A., RA Garritsen V.H., Gombakis N., Jaspers N.G.J., Clarkson S.G.; RT "Xeroderma pigmentosum group G with severe neurological involvement RT and features of Cockayne syndrome in infancy."; RL Pediatr. Res. 49:407-412(2001). RN [22] RP VARIANT XP-G PRO-858. RX PubMed=11841555; DOI=10.1046/j.0022-202x.2001.01673.x; RA Lalle P., Nouspikel T., Constantinou A., Thorel F., Clarkson S.G.; RT "The founding members of xeroderma pigmentosum group G produce XPG RT protein with severely impaired endonuclease activity."; RL J. Invest. Dermatol. 118:344-351(2002). RN [23] RP VARIANT XP-G THR-874. RX PubMed=12060391; DOI=10.1046/j.1523-1747.2002.01782.x; RA Emmert S., Slor H., Busch D.B., Batko S., Albert R.B., Coleman D., RA Khan S.G., Abu-Libdeh B., DiGiovanna J.J., Cunningham B.B., Lee M.M., RA Crollick J., Inui H., Ueda T., Hedayati M., Grossman L., Shahlavi T., RA Cleaver J.E., Kraemer K.H.; RT "Relationship of neurologic degeneration to genotype in three RT xeroderma pigmentosum group G patients."; RL J. Invest. Dermatol. 118:972-982(2002). CC -!- FUNCTION: Single-stranded structure-specific DNA endonuclease CC involved in DNA excision repair. Makes the 3'incision in DNA CC nucleotide excision repair (NER). Acts as a cofactor for a DNA CC glycosylase that removes oxidized pyrimidines from DNA. May also CC be involved in transcription-coupled repair of this kind of CC damage, in transcription by RNA polymerase II, and perhaps in CC other processes too. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC Note=Binds 2 magnesium ions per subunit. They probably participate CC in the reaction catalyzed by the enzyme. May bind an additional CC third magnesium ion after substrate binding. {ECO:0000250}; CC -!- SUBUNIT: Interacts with PCNA. {ECO:0000269|PubMed:9305916}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:7651464}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P28715-1; Sequence=Displayed; CC Name=2; CC IsoId=P28715-2; Sequence=VSP_035380; CC Name=3; CC IsoId=P28715-3; Sequence=VSP_053828, VSP_053829; CC Note=No experimental confirmation available. Includes a cryptic CC exon found in intron 6.; CC -!- DISEASE: Xeroderma pigmentosum complementation group G (XP-G) CC [MIM:278780]: An autosomal recessive pigmentary skin disorder CC characterized by solar hypersensitivity of the skin, high CC predisposition for developing cancers on areas exposed to sunlight CC and, in some cases, neurological abnormalities. The skin develops CC marked freckling and other pigmentation abnormalities. Some XP-G CC patients present features of Cockayne syndrome, cachectic CC dwarfism, pigmentary retinopathy, ataxia, decreased nerve CC conduction velocities. The phenotype combining xeroderma CC pigmentosum and Cockayne syndrome traits is referred to as XP-CS CC complex. {ECO:0000269|PubMed:11228268, CC ECO:0000269|PubMed:11841555, ECO:0000269|PubMed:12060391, CC ECO:0000269|PubMed:7951246, ECO:0000269|PubMed:9096355}. Note=The CC disease is caused by mutations affecting the gene represented in CC this entry. CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. XPG CC subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Allelic variations of the XP genes; CC URL="http://www.xpmutations.org/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/XPGID300.html"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/ercc5/"; 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; X69978; CAA49598.1; -; mRNA. DR EMBL; D16305; BAA03812.1; -; mRNA. DR EMBL; L20046; AAC37533.1; -; mRNA. DR EMBL; AF255436; AAF89178.1; -; Genomic_DNA. DR EMBL; AF255431; AAF89178.1; JOINED; Genomic_DNA. DR EMBL; AF255433; AAF89178.1; JOINED; Genomic_DNA. DR EMBL; AF255434; AAF89178.1; JOINED; Genomic_DNA. DR EMBL; AF255435; AAF89178.1; JOINED; Genomic_DNA. DR EMBL; AF255442; AAF89179.1; -; Genomic_DNA. DR EMBL; AF255431; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255433; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255434; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255435; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255436; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255437; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255438; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255439; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255440; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF255441; AAF89179.1; JOINED; Genomic_DNA. DR EMBL; AF462447; AAP97715.1; -; mRNA. DR EMBL; AF550128; AAN46091.1; -; Genomic_DNA. DR EMBL; AL157769; CAI14530.1; -; Genomic_DNA. DR EMBL; AL157769; CAI14531.1; -; Genomic_DNA. DR EMBL; BC031522; AAH31522.1; -; mRNA. DR EMBL; X71341; CAA50481.1; -; Genomic_DNA. DR EMBL; X71342; CAA50481.1; JOINED; Genomic_DNA. DR CCDS; CCDS32004.1; -. [P28715-1] DR PIR; I58009; I58009. DR PIR; S35993; S35993. DR RefSeq; NP_000114.2; NM_000123.3. DR UniGene; Hs.258429; -. DR ProteinModelPortal; P28715; -. DR SMR; P28715; 2-113, 711-981. DR BioGrid; 108385; 14. DR DIP; DIP-750N; -. DR IntAct; P28715; 4. DR MINT; MINT-192239; -. DR STRING; 9606.ENSP00000347978; -. DR BindingDB; P28715; -. DR ChEMBL; CHEMBL4736; -. DR PhosphoSite; P28715; -. DR BioMuta; ERCC5; -. DR DMDM; 205371791; -. DR MaxQB; P28715; -. DR PaxDb; P28715; -. DR PRIDE; P28715; -. DR DNASU; 2073; -. DR Ensembl; ENST00000355739; ENSP00000347978; ENSG00000134899. [P28715-1] DR Ensembl; ENST00000375954; ENSP00000365121; ENSG00000134899. [P28715-2] DR Ensembl; ENST00000535557; ENSP00000442117; ENSG00000134899. [P28715-3] DR GeneID; 2073; -. DR KEGG; hsa:2073; -. DR UCSC; uc001vpw.3; human. [P28715-1] DR CTD; 2073; -. DR GeneCards; ERCC5; -. DR GeneReviews; ERCC5; -. DR HGNC; HGNC:3437; ERCC5. DR HPA; HPA045845; -. DR HPA; HPA050374; -. DR MIM; 133530; gene. DR MIM; 278780; phenotype. DR neXtProt; NX_P28715; -. DR Orphanet; 1466; COFS syndrome. DR Orphanet; 276267; Xeroderma pigmentosum complementation group G. DR PharmGKB; PA27851; -. DR eggNOG; KOG2520; Eukaryota. DR eggNOG; COG0258; LUCA. DR GeneTree; ENSGT00640000091542; -. DR HOVERGEN; HBG051501; -. DR InParanoid; P28715; -. DR KO; K10846; -. DR OMA; EAQCCEL; -. DR OrthoDB; EOG72ZCD4; -. DR PhylomeDB; P28715; -. DR TreeFam; TF101235; -. DR Reactome; R-HSA-110302; Formation of transcription-coupled NER (TC-NER) repair complex. DR Reactome; R-HSA-110304; Dual incision reaction in TC-NER. DR Reactome; R-HSA-73935; Formation of incision complex in GG-NER. DR Reactome; R-HSA-73941; Dual incision reaction in GG-NER. DR GeneWiki; ERCC5; -. DR GenomeRNAi; 2073; -. DR NextBio; 8433; -. DR PRO; PR:P28715; -. DR Proteomes; UP000005640; Chromosome 13. DR Bgee; P28715; -. DR CleanEx; HS_ERCC5; -. DR ExpressionAtlas; P28715; baseline and differential. DR Genevisible; P28715; HS. DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0000405; F:bubble DNA binding; IDA:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0004520; F:endodeoxyribonuclease activity; IDA:UniProtKB. DR GO; GO:0004519; F:endonuclease activity; TAS:Reactome. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB. DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; TAS:Reactome. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB. DR GO; GO:0006289; P:nucleotide-excision repair; TAS:Reactome. DR GO; GO:0000718; P:nucleotide-excision repair, DNA damage removal; TAS:Reactome. DR GO; GO:0006295; P:nucleotide-excision repair, DNA incision, 3'-to lesion; IDA:UniProtKB. DR GO; GO:0009411; P:response to UV; IDA:UniProtKB. DR GO; GO:0010225; P:response to UV-C; IMP:UniProtKB. DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; IMP:UniProtKB. DR GO; GO:0009650; P:UV protection; IGI:MGI. DR Gene3D; 3.40.50.1010; -; 2. DR InterPro; IPR020045; 5-3_exonuclease_C. DR InterPro; IPR008918; HhH2. DR InterPro; IPR029060; PIN_domain-like. DR InterPro; IPR006086; XPG-I_dom. DR InterPro; IPR006084; XPG/Rad2. DR InterPro; IPR001044; XPG/Rad2_eukaryotes. DR InterPro; IPR019974; XPG_CS. DR InterPro; IPR006085; XPG_DNA_repair_N. DR Pfam; PF00867; XPG_I; 1. DR Pfam; PF00752; XPG_N; 1. DR PRINTS; PR00853; XPGRADSUPER. DR PRINTS; PR00066; XRODRMPGMNTG. DR SMART; SM00279; HhH2; 1. DR SMART; SM00484; XPGI; 1. DR SMART; SM00485; XPGN; 1. DR SUPFAM; SSF47807; SSF47807; 2. DR SUPFAM; SSF88723; SSF88723; 2. DR TIGRFAMs; TIGR00600; rad2; 1. DR PROSITE; PS00841; XPG_1; 1. DR PROSITE; PS00842; XPG_2; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Cockayne syndrome; KW Complete proteome; Deafness; Disease mutation; DNA damage; DNA repair; KW DNA-binding; Dwarfism; Endonuclease; Hydrolase; Magnesium; KW Metal-binding; Nuclease; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Xeroderma pigmentosum. FT CHAIN 1 1186 DNA repair protein complementing XP-G FT cells. FT /FTId=PRO_0000154031. FT REGION 1 95 N-domain. FT REGION 753 881 I-domain. FT REGION 981 1009 Interaction with PCNA. FT MOTIF 1057 1073 Nuclear localization signal. FT {ECO:0000255}. FT METAL 30 30 Magnesium 1. {ECO:0000250}. FT METAL 77 77 Magnesium 1. {ECO:0000250}. FT METAL 789 789 Magnesium 1. {ECO:0000250}. FT METAL 791 791 Magnesium 1. {ECO:0000250}. FT METAL 810 810 Magnesium 2. {ECO:0000250}. FT METAL 812 812 Magnesium 2. {ECO:0000250}. FT METAL 861 861 Magnesium 2. {ECO:0000250}. FT MOD_RES 8 8 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 384 384 Phosphoserine. FT {ECO:0000250|UniProtKB:P35689}. FT MOD_RES 705 705 Phosphoserine. FT {ECO:0000250|UniProtKB:P35689}. FT VAR_SEQ 1 767 Missing (in isoform 2). {ECO:0000305}. FT /FTId=VSP_035380. FT VAR_SEQ 225 232 ESDDFSQY -> VYLPLLQP (in isoform 3). FT {ECO:0000305}. FT /FTId=VSP_053828. FT VAR_SEQ 233 1186 Missing (in isoform 3). {ECO:0000305}. FT /FTId=VSP_053829. FT VARIANT 72 72 P -> H (in XP-G; combined with features FT of Cockayne syndrome). FT {ECO:0000269|PubMed:11228268}. FT /FTId=VAR_015280. FT VARIANT 145 145 V -> I (in dbSNP:rs4987063). FT /FTId=VAR_020431. FT VARIANT 181 181 H -> R (in dbSNP:rs4150295). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_023120. FT VARIANT 254 254 M -> V (in dbSNP:rs1047769). FT {ECO:0000269|PubMed:7510366, FT ECO:0000269|PubMed:8413238, FT ECO:0000269|Ref.5, ECO:0000269|Ref.6}. FT /FTId=VAR_007732. FT VARIANT 256 256 Q -> R (in dbSNP:rs4150313). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_020432. FT VARIANT 311 311 S -> C (in dbSNP:rs2307491). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_014829. FT VARIANT 399 399 E -> K (in dbSNP:rs4150315). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_023121. FT VARIANT 529 529 C -> S (in dbSNP:rs2227869). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_020433. FT VARIANT 590 590 V -> I (in dbSNP:rs4150318). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_023122. FT VARIANT 597 597 V -> L (in dbSNP:rs4150319). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_023123. FT VARIANT 670 670 F -> L (in dbSNP:rs1803542). FT /FTId=VAR_046373. FT VARIANT 680 680 Q -> R (in dbSNP:rs4987168). FT /FTId=VAR_020434. FT VARIANT 792 792 A -> V (in XP-G; mild form). FT {ECO:0000269|PubMed:7951246, FT ECO:0000269|PubMed:9096355}. FT /FTId=VAR_007733. FT VARIANT 858 858 L -> P (in XP-G; reduced stability and FT greatly impaired endonuclease activity). FT {ECO:0000269|PubMed:11841555}. FT /FTId=VAR_017097. FT VARIANT 874 874 A -> T (in XP-G; mild form; residual FT activity; dbSNP:rs28929496). FT {ECO:0000269|PubMed:12060391}. FT /FTId=VAR_017096. FT VARIANT 879 879 N -> S (in dbSNP:rs4150342). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_020435. FT VARIANT 1009 1009 R -> H (in dbSNP:rs4150387). FT {ECO:0000269|Ref.6}. FT /FTId=VAR_023124. FT VARIANT 1053 1053 G -> R (in dbSNP:rs9514066). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7510366, FT ECO:0000269|PubMed:8413238, FT ECO:0000269|PubMed:8483504, FT ECO:0000269|Ref.5, ECO:0000269|Ref.6}. FT /FTId=VAR_046374. FT VARIANT 1080 1080 G -> Q (requires 2 nucleotide FT substitutions). {ECO:0000269|Ref.6}. FT /FTId=VAR_023125. FT VARIANT 1080 1080 G -> R (in dbSNP:rs9514067). FT {ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7510366, FT ECO:0000269|PubMed:8413238, FT ECO:0000269|PubMed:8483504, FT ECO:0000269|Ref.5, ECO:0000269|Ref.6}. FT /FTId=VAR_046375. FT VARIANT 1104 1104 D -> H (in dbSNP:rs17655). FT {ECO:0000269|PubMed:8483504}. FT /FTId=VAR_007734. FT VARIANT 1119 1119 A -> V (in dbSNP:rs2227871). FT /FTId=VAR_020436. FT CONFLICT 55 55 L -> P (in Ref. 2; BAA03812). FT {ECO:0000305}. FT CONFLICT 120 122 KTA -> QTS (in Ref. 2; BAA03812). FT {ECO:0000305}. FT CONFLICT 126 126 K -> Q (in Ref. 2; BAA03812). FT {ECO:0000305}. FT CONFLICT 264 266 RQY -> SSH (in Ref. 2; BAA03812). FT {ECO:0000305}. FT CONFLICT 760 760 I -> F (in Ref. 2; BAA03812). FT {ECO:0000305}. FT CONFLICT 796 796 I -> V (in Ref. 2; BAA03812). FT {ECO:0000305}. FT CONFLICT 864 872 EGIPTVGCV -> GNTNCGLC (in Ref. 2; FT BAA03812). {ECO:0000305}. FT CONFLICT 959 959 R -> S (in Ref. 2; BAA03812). FT {ECO:0000305}. SQ SEQUENCE 1186 AA; 133108 MW; B0A844D617C53F2E CRC64; MGVQGLWKLL ECSGRQVSPE ALEGKILAVD ISIWLNQALK GVRDRHGNSI ENPHLLTLFH RLCKLLFFRI RPIFVFDGDA PLLKKQTLVK RRQRKDLASS DSRKTTEKLL KTFLKRQAIK TAFRSKRDEA LPSLTQVRRE NDLYVLPPLQ EEEKHSSEEE DEKEWQERMN QKQALQEEFF HNPQAIDIES EDFSSLPPEV KHEILTDMKE FTKRRRTLFE AMPEESDDFS QYQLKGLLKK NYLNQHIEHV QKEMNQQHSG HIRRQYEDEG GFLKEVESRR VVSEDTSHYI LIKGIQAKTV AEVDSESLPS SSKMHGMSFD VKSSPCEKLK TEKEPDATPP SPRTLLAMQA ALLGSSSEEE LESENRRQAR GRNAPAAVDE GSISPRTLSA IKRALDDDED VKVCAGDDVQ TGGPGAEEMR INSSTENSDE GLKVRDGKGI PFTATLASSS VNSAEEHVAS TNEGREPTDS VPKEQMSLVH VGTEAFPISD ESMIKDRKDR LPLESAVVRH SDAPGLPNGR ELTPASPTCT NSVSKNETHA EVLEQQNELC PYESKFDSSL LSSDDETKCK PNSASEVIGP VSLQETSSIV SVPSEAVDNV ENVVSFNAKE HENFLETIQE QQTTESAGQD LISIPKAVEP MEIDSEESES DGSFIEVQSV ISDEELQAEF PETSKPPSEQ GEEELVGTRE GEAPAESESL LRDNSERDDV DGEPQEAEKD AEDSLHEWQD INLEELETLE SNLLAQQNSL KAQKQQQERI AATVTGQMFL ESQELLRLFG IPYIQAPMEA EAQCAILDLT DQTSGTITDD SDIWLFGARH VYRNFFNKNK FVEYYQYVDF HNQLGLDRNK LINLAYLLGS DYTEGIPTVG CVTAMEILNE FPGHGLEPLL KFSEWWHEAQ KNPKIRPNPH DTKVKKKLRT LQLTPGFPNP AVAEAYLKPV VDDSKGSFLW GKPDLDKIRE FCQRYFGWNR TKTDESLFPV LKQLDAQQTQ LRIDSFFRLA QQEKEDAKRI KSQRLNRAVT CMLRKEKEAA ASEIEAVSVA MEKEFELLDK AKGKTQKRGI TNTLEESSSL KRKRLSDSKG KNTCGGFLGE TCLSESSDGS SSEDAESSSL MNVQRRTAAK EPKTSASDSQ NSVKEAPVKN GGATTSSSSD SDDDGGKEKM VLVTARSVFG KKRRKLRRAR GRKRKT // ID FEN1_HUMAN Reviewed; 380 AA. AC P39748; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 1. DT 11-NOV-2015, entry version 159. DE RecName: Full=Flap endonuclease 1 {ECO:0000255|HAMAP-Rule:MF_03140}; DE Short=FEN-1 {ECO:0000255|HAMAP-Rule:MF_03140}; DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_03140}; DE AltName: Full=DNase IV; DE AltName: Full=Flap structure-specific endonuclease 1 {ECO:0000255|HAMAP-Rule:MF_03140}; DE AltName: Full=Maturation factor 1; DE Short=MF1; DE Short=hFEN-1; GN Name=FEN1 {ECO:0000255|HAMAP-Rule:MF_03140}; Synonyms=RAD2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8007985; RA Murray J.M., Tavassoli M., Al-Harithy R., Sheldrick K.S., RA Lehmann A.R., Carr A.M., Watts F.Z.; RT "Structural and functional conservation of the human homolog of the RT Schizosaccharomyces pombe rad2 gene, which is required for chromosome RT segregation and recovery from DNA damage."; RL Mol. Cell. Biol. 14:4878-4888(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Leukemic T-cell; RX PubMed=7774922; DOI=10.1016/0888-7543(95)80129-A; RA Hiraoka L.R., Harrington J.J., Gerhard D.S., Lieber M.R., Hsieh C.-L.; RT "Sequence of human FEN-1, a structure-specific endonuclease, and RT chromosomal localization of the gene (FEN1) in mouse and human."; RL Genomics 25:220-225(1995). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., RA Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., RA FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S., RA Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., RA Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., RA Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PARTIAL PROTEIN SEQUENCE, FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=7961795; RA Robins P., Pappin D.J.C., Wood R.D., Lindahl T.; RT "Structural and functional homology between mammalian DNase IV and the RT 5'-nuclease domain of Escherichia coli DNA polymerase I."; RL J. Biol. Chem. 269:28535-28538(1994). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE-BINDING SITES, AND MUTAGENESIS RP OF ASP-34; ASP-86; ARG-103; GLU-158; ASP-179; ASP-181; GLY-231 AND RP ASP-233. RX PubMed=8621570; DOI=10.1074/jbc.271.16.9173; RA Shen B., Nolan J.P., Sklar L.A., Park M.S.; RT "Essential amino acids for substrate binding and catalysis of human RT flap endonuclease 1."; RL J. Biol. Chem. 271:9173-9176(1996). RN [8] RP INTERACTION WITH PCNA. RX PubMed=9305916; DOI=10.1074/jbc.272.39.24522; RA Gary R., Ludwig D.L., Cornelius H.L., MacInnes M.A., Park M.S.; RT "The DNA repair endonuclease XPG binds to proliferating cell nuclear RT antigen (PCNA) and shares sequence elements with the PCNA-binding RT regions of FEN-1 and cyclin-dependent kinase inhibitor p21."; RL J. Biol. Chem. 272:24522-24529(1997). RN [9] RP FUNCTION. RX PubMed=10744741; DOI=10.1074/jbc.275.14.10498; RA Tom S., Henricksen L.A., Bambara R.A.; RT "Mechanism whereby proliferating cell nuclear antigen stimulates flap RT endonuclease 1."; RL J. Biol. Chem. 275:10498-10505(2000). RN [10] RP INTERACTION WITH P300, AND ACETYLATION AT LYS-354; LYS-375; LYS-377 RP AND LYS-380. RX PubMed=11430825; DOI=10.1016/S1097-2765(01)00272-6; RA Hasan S., Stucki M., Hassa P.O., Imhof R., Gehrig P., Hunziker P., RA Hubscher U., Hottiger M.O.; RT "Regulation of human flap endonuclease-1 activity by acetylation RT through the transcriptional coactivator p300."; RL Mol. Cell 7:1221-1231(2001). RN [11] RP FUNCTION, SUBSTRATE-BINDING SITES ARG-47 AND ARG-70, AND MUTAGENESIS RP OF ARG-29; ARG-47; ARG-70; ARG-73 AND LYS-80. RX PubMed=11986308; DOI=10.1074/jbc.M111941200; RA Qiu J., Bimston D.N., Partikian A., Shen B.; RT "Arginine residues 47 and 70 of human flap endonuclease-1 are involved RT in DNA substrate interactions and cleavage site determination."; RL J. Biol. Chem. 277:24659-24666(2002). RN [12] RP INTERACTION WITH DDX11. RX PubMed=18499658; DOI=10.1074/jbc.M802696200; RA Farina A., Shin J.H., Kim D.H., Bermudez V.P., Kelman Z., Seo Y.S., RA Hurwitz J.; RT "Studies with the human cohesin establishment factor, ChlR1. RT Association of ChlR1 with Ctf18-RFC and Fen1."; RL J. Biol. Chem. 283:20925-20936(2008). RN [13] RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND MUTAGENESIS OF RP SER-187. RX PubMed=18443037; DOI=10.1128/MCB.00200-08; RA Guo Z., Qian L., Liu R., Dai H., Zhou M., Zheng L., Shen B.; RT "Nucleolar localization and dynamic roles of flap endonuclease 1 in RT ribosomal DNA replication and damage repair."; RL Mol. Cell. Biol. 28:4310-4319(2008). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-80 AND LYS-375, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [15] RP FUNCTION, MUTAGENESIS OF ARG-192, METHYLATION AT ARG-19; ARG-100; RP ARG-104 AND ARG-192, AND PHOSPHORYLATION AT SER-187. RX PubMed=20729856; DOI=10.1038/nchembio.422; RA Guo Z., Zheng L., Xu H., Dai H., Zhou M., Pascua M.R., Chen Q.M., RA Shen B.; RT "Methylation of FEN1 suppresses nearby phosphorylation and facilitates RT PCNA binding."; RL Nat. Chem. Biol. 6:766-773(2010). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197 AND THR-364, 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 [17] 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 [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [19] RP ALTERNATIVE INITIATION (ISOFORM FENMIT), AND SUBCELLULAR LOCATION RP (ISOFORM FENMIT). RX PubMed=23675412; DOI=10.1371/journal.pone.0062340; RA Kazak L., Reyes A., He J., Wood S.R., Brea-Calvo G., Holen T.T., RA Holt I.J.; RT "A cryptic targeting signal creates a mitochondrial FEN1 isoform with RT tailed R-loop binding properties."; RL PLoS ONE 8:E62340-E62340(2013). RN [20] 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 [21] RP X-RAY CRYSTALLOGRAPHY (1.88 ANGSTROMS) OF 331-350. RX PubMed=15576034; DOI=10.1016/j.str.2004.09.018; RA Bruning J.B., Shamoo Y.; RT "Structural and thermodynamic analysis of human PCNA with peptides RT derived from DNA polymerase-delta p66 subunit and flap endonuclease- RT 1."; RL Structure 12:2209-2219(2004). RN [22] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 2-380 IN COMPLEX WITH PCNA. RX PubMed=15616578; DOI=10.1038/sj.emboj.7600519; RA Sakurai S., Kitano K., Yamaguchi H., Hamada K., Okada K., Fukuda K., RA Uchida M., Ohtsuka E., Morioka H., Hakoshima T.; RT "Structural basis for recruitment of human flap endonuclease 1 to RT PCNA."; RL EMBO J. 24:683-693(2005). CC -!- FUNCTION: Structure-specific nuclease with 5'-flap endonuclease CC and 5'-3' exonuclease activities involved in DNA replication and CC repair. During DNA replication, cleaves the 5'-overhanging flap CC structure that is generated by displacement synthesis when DNA CC polymerase encounters the 5'-end of a downstream Okazaki fragment. CC It enters the flap from the 5'-end and then tracks to cleave the CC flap base, leaving a nick for ligation. Also involved in the long CC patch base excision repair (LP-BER) pathway, by cleaving within CC the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a CC genome stabilization factor that prevents flaps from equilibrating CC into structurs that lead to duplications and deletions. Also CC possesses 5'-3' exonuclease activity on nicked or gapped double- CC stranded DNA, and exhibits RNase H activity. Also involved in CC replication and repair of rDNA and in repairing mitochondrial DNA. CC {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:10744741, CC ECO:0000269|PubMed:11986308, ECO:0000269|PubMed:18443037, CC ECO:0000269|PubMed:20729856, ECO:0000269|PubMed:7961795, CC ECO:0000269|PubMed:8621570}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Note=Binds 2 magnesium ions per subunit. They probably participate CC in the reaction catalyzed by the enzyme. May bind an additional CC third magnesium ion after substrate binding.; CC -!- SUBUNIT: Interacts with PCNA. Three molecules of FEN1 bind to one CC PCNA trimer with each molecule binding to one PCNA monomer. PCNA CC stimulates the nuclease activity without altering cleavage CC specificity. The C-terminal domain binds EP300. Can bind CC simultaneously to both PCNA and EP300. Interacts with DDX11. CC {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:11430825, CC ECO:0000269|PubMed:15616578, ECO:0000269|PubMed:18499658, CC ECO:0000269|PubMed:9305916}. CC -!- INTERACTION: CC P54132:BLM; NbExp=4; IntAct=EBI-707816, EBI-621372; CC Q96NY9:MUS81; NbExp=5; IntAct=EBI-707816, EBI-2370806; CC P12004:PCNA; NbExp=4; IntAct=EBI-707816, EBI-358311; CC Q14191:WRN; NbExp=9; IntAct=EBI-707816, EBI-368417; CC -!- SUBCELLULAR LOCATION: Isoform 1: Nucleus, nucleolus. Nucleus, CC nucleoplasm. Note=Resides mostly in the nucleoli and relocalizes CC to the nucleoplasm upon DNA damage. CC -!- SUBCELLULAR LOCATION: Isoform FENMIT: Mitochondrion CC {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:23675412}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=1; CC IsoId=P39748-1; Sequence=Displayed; CC Name=FENMIT; CC IsoId=P39748-2; Sequence=VSP_047520; CC Note=No nuclease activity. Binds preferentially to RNA flap CC structures and R-loops.; CC -!- PTM: Acetylated by EP300. Acetylation inhibits both endonuclease CC and exonuclease activity. Acetylation also reduces DNA-binding CC activity but does not affect interaction with PCNA or EP300. CC {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:11430825}. CC -!- PTM: Phosphorylation upon DNA damage induces relocalization to the CC nuclear plasma. Phosphorylation at Ser-187 by CDK2 occurs during CC late S-phase and results in dissociation from PCNA. CC {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:20729856}. CC -!- PTM: Methylation at Arg-192 by PRMT5 impedes Ser-187 CC phosphorylation and increases interaction with PCNA. CC {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:20729856}. CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. FEN1 CC subfamily. {ECO:0000255|HAMAP-Rule:MF_03140}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/fen1/"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/FEN1ID40543ch11q12.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; X76771; CAA54166.1; -; mRNA. DR EMBL; L37374; AAA91331.1; -; mRNA. DR EMBL; AF523117; AAM74238.1; -; Genomic_DNA. DR EMBL; AC004770; AAC23394.1; -; Genomic_DNA. DR EMBL; BC000323; AAH00323.1; -; mRNA. DR CCDS; CCDS8010.1; -. [P39748-1] DR PIR; A56531; A56531. DR RefSeq; NP_004102.1; NM_004111.5. [P39748-1] DR UniGene; Hs.409065; -. DR PDB; 1U7B; X-ray; 1.88 A; B=331-350. DR PDB; 1UL1; X-ray; 2.90 A; X/Y/Z=2-380. DR PDB; 3Q8K; X-ray; 2.20 A; A=2-336. DR PDB; 3Q8L; X-ray; 2.32 A; A=2-336. DR PDB; 3Q8M; X-ray; 2.60 A; A/B=2-336. DR PDB; 3UVU; X-ray; 2.38 A; B=352-370. DR PDBsum; 1U7B; -. DR PDBsum; 1UL1; -. DR PDBsum; 3Q8K; -. DR PDBsum; 3Q8L; -. DR PDBsum; 3Q8M; -. DR PDBsum; 3UVU; -. DR ProteinModelPortal; P39748; -. DR SMR; P39748; 2-336. DR BioGrid; 108528; 46. DR DIP; DIP-24216N; -. DR IntAct; P39748; 15. DR MINT; MINT-5004212; -. DR STRING; 9606.ENSP00000305480; -. DR BindingDB; P39748; -. DR ChEMBL; CHEMBL5027; -. DR PhosphoSite; P39748; -. DR BioMuta; FEN1; -. DR DMDM; 729475; -. DR MaxQB; P39748; -. DR PaxDb; P39748; -. DR PeptideAtlas; P39748; -. DR PRIDE; P39748; -. DR DNASU; 2237; -. DR Ensembl; ENST00000305885; ENSP00000305480; ENSG00000168496. [P39748-1] DR GeneID; 2237; -. DR KEGG; hsa:2237; -. DR UCSC; uc001nsg.3; human. [P39748-1] DR CTD; 2237; -. DR GeneCards; FEN1; -. DR HGNC; HGNC:3650; FEN1. DR HPA; CAB002262; -. DR HPA; HPA006581; -. DR HPA; HPA006748; -. DR MIM; 600393; gene. DR neXtProt; NX_P39748; -. DR PharmGKB; PA28090; -. DR eggNOG; KOG2519; Eukaryota. DR eggNOG; COG0258; LUCA. DR HOGENOM; HOG000193853; -. DR HOVERGEN; HBG000844; -. DR InParanoid; P39748; -. DR KO; K04799; -. DR OMA; GSQDYDS; -. DR OrthoDB; EOG72JWHG; -. DR PhylomeDB; P39748; -. DR TreeFam; TF105701; -. DR Reactome; R-HSA-110362; POLB-Dependent Long Patch Base Excision Repair. DR Reactome; R-HSA-174437; Removal of the Flap Intermediate from the C-strand. DR Reactome; R-HSA-5651801; PCNA-Dependent Long Patch Base Excision Repair. DR Reactome; R-HSA-69166; Removal of the Flap Intermediate. DR SignaLink; P39748; -. DR ChiTaRS; FEN1; human. DR EvolutionaryTrace; P39748; -. DR GeneWiki; Flap_structure-specific_endonuclease_1; -. DR GenomeRNAi; 2237; -. DR NextBio; 9055; -. DR PRO; PR:P39748; -. DR Proteomes; UP000005640; Chromosome 11. DR Bgee; P39748; -. DR CleanEx; HS_FEN1; -. DR ExpressionAtlas; P39748; baseline and differential. DR Genevisible; P39748; HS. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB. DR GO; GO:0000784; C:nuclear chromosome, telomeric region; IDA:BHF-UCL. 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:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0043234; C:protein complex; IDA:MGI. DR GO; GO:0008409; F:5'-3' exonuclease activity; IDA:UniProtKB. DR GO; GO:0017108; F:5'-flap endonuclease activity; IDA:UniProtKB. DR GO; GO:0003684; F:damaged DNA binding; TAS:ProtInc. DR GO; GO:0003677; F:DNA binding; IMP:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; TAS:ProtInc. DR GO; GO:0008309; F:double-stranded DNA exodeoxyribonuclease activity; TAS:ProtInc. DR GO; GO:0004519; F:endonuclease activity; TAS:ProtInc. DR GO; GO:0004527; F:exonuclease activity; TAS:ProtInc. DR GO; GO:0000287; F:magnesium ion binding; IEA:Ensembl. DR GO; GO:0030145; F:manganese ion binding; IEA:Ensembl. DR GO; GO:0004523; F:RNA-DNA hybrid ribonuclease activity; IDA:UniProtKB. DR GO; GO:0006284; P:base-excision repair; TAS:Reactome. DR GO; GO:0006281; P:DNA repair; TAS:Reactome. DR GO; GO:0006260; P:DNA replication; TAS:ProtInc. DR GO; GO:0043137; P:DNA replication, removal of RNA primer; IDA:UniProtKB. DR GO; GO:0006271; P:DNA strand elongation involved in DNA replication; TAS:Reactome. DR GO; GO:0006302; P:double-strand break repair; TAS:ProtInc. DR GO; GO:0007613; P:memory; IEA:Ensembl. DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome. DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IDA:GOC. DR GO; GO:0090502; P:RNA phosphodiester bond hydrolysis, endonucleolytic; IDA:GOC. DR GO; GO:0000723; P:telomere maintenance; TAS:Reactome. DR GO; GO:0000722; P:telomere maintenance via recombination; TAS:Reactome. DR GO; GO:0032201; P:telomere maintenance via semi-conservative replication; TAS:Reactome. DR GO; GO:0009650; P:UV protection; TAS:ProtInc. DR Gene3D; 3.40.50.1010; -; 1. DR HAMAP; MF_00614; Fen; 1. DR InterPro; IPR020045; 5-3_exonuclease_C. DR InterPro; IPR023426; Flap_endonuc. DR InterPro; IPR008918; HhH2. DR InterPro; IPR029060; PIN_domain-like. DR InterPro; IPR006086; XPG-I_dom. DR InterPro; IPR006084; XPG/Rad2. DR InterPro; IPR019974; XPG_CS. DR InterPro; IPR006085; XPG_DNA_repair_N. DR PANTHER; PTHR11081; PTHR11081; 1. DR Pfam; PF00867; XPG_I; 1. DR Pfam; PF00752; XPG_N; 1. DR PRINTS; PR00853; XPGRADSUPER. DR SMART; SM00279; HhH2; 1. DR SMART; SM00484; XPGI; 1. DR SMART; SM00485; XPGN; 1. DR SUPFAM; SSF47807; SSF47807; 1. DR SUPFAM; SSF88723; SSF88723; 1. DR PROSITE; PS00841; XPG_1; 1. DR PROSITE; PS00842; XPG_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative initiation; Complete proteome; KW Direct protein sequencing; DNA damage; DNA repair; DNA replication; KW Endonuclease; Exonuclease; Hydrolase; Magnesium; Metal-binding; KW Methylation; Mitochondrion; Nuclease; Nucleus; Phosphoprotein; KW Reference proteome. FT CHAIN 1 380 Flap endonuclease 1. FT /FTId=PRO_0000154069. FT REGION 1 104 N-domain. FT REGION 122 253 I-domain. FT REGION 336 344 Interaction with PCNA. FT METAL 34 34 Magnesium 1. FT METAL 86 86 Magnesium 1. FT METAL 158 158 Magnesium 1. FT METAL 160 160 Magnesium 1. FT METAL 179 179 Magnesium 2. FT METAL 181 181 Magnesium 2. FT METAL 233 233 Magnesium 2. FT BINDING 47 47 DNA substrate. FT BINDING 70 70 DNA substrate. FT BINDING 158 158 DNA substrate. FT BINDING 231 231 DNA substrate. FT BINDING 233 233 DNA substrate. FT MOD_RES 19 19 Symmetric dimethylarginine; by PRMT5. FT {ECO:0000255|HAMAP-Rule:MF_03140, FT ECO:0000269|PubMed:20729856}. FT MOD_RES 80 80 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 100 100 Symmetric dimethylarginine; by PRMT5. FT {ECO:0000255|HAMAP-Rule:MF_03140, FT ECO:0000269|PubMed:20729856}. FT MOD_RES 104 104 Symmetric dimethylarginine; by PRMT5. FT {ECO:0000255|HAMAP-Rule:MF_03140, FT ECO:0000269|PubMed:20729856}. FT MOD_RES 187 187 Phosphoserine; by CDK2. FT {ECO:0000255|HAMAP-Rule:MF_03140, FT ECO:0000269|PubMed:20729856}. FT MOD_RES 192 192 Symmetric dimethylarginine; by PRMT5. FT {ECO:0000255|HAMAP-Rule:MF_03140, FT ECO:0000269|PubMed:20729856}. FT MOD_RES 197 197 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 354 354 N6-acetyllysine. {ECO:0000255|HAMAP- FT Rule:MF_03140, FT ECO:0000269|PubMed:11430825}. FT MOD_RES 364 364 Phosphothreonine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 375 375 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861, FT ECO:0000255|HAMAP-Rule:MF_03140, FT ECO:0000269|PubMed:11430825}. FT MOD_RES 377 377 N6-acetyllysine. {ECO:0000255|HAMAP- FT Rule:MF_03140, FT ECO:0000269|PubMed:11430825}. FT MOD_RES 380 380 N6-acetyllysine. {ECO:0000255|HAMAP- FT Rule:MF_03140, FT ECO:0000269|PubMed:11430825}. FT VAR_SEQ 1 64 Missing (in isoform FENMIT). FT {ECO:0000305}. FT /FTId=VSP_047520. FT MUTAGEN 29 29 R->A: No significant effect on FT exonuclease activity or flap endonuclease FT activity. {ECO:0000269|PubMed:11986308}. FT MUTAGEN 34 34 D->A: Loss of flap endonuclease activity FT but substrate binding activity is FT retained. {ECO:0000269|PubMed:8621570}. FT MUTAGEN 47 47 R->A: Significantly reduced exonuclease FT activity and reduced substrate binding. FT The positions of the cleavage sites are FT also shifted. FT {ECO:0000269|PubMed:11986308}. FT MUTAGEN 70 70 R->A: Loss of exonuclease activity and FT reduced endonuclease activity. Reduced FT substrate binding. FT {ECO:0000269|PubMed:11986308}. FT MUTAGEN 73 73 R->A: No significant effect on FT exonuclease activity or flap endonuclease FT activity. {ECO:0000269|PubMed:11986308}. FT MUTAGEN 80 80 K->A: No significant effect on FT exonuclease activity or flap endonuclease FT activity. {ECO:0000269|PubMed:11986308}. FT MUTAGEN 86 86 D->A: Loss of flap endonuclease activity FT but substrate binding activity is FT retained. {ECO:0000269|PubMed:8621570}. FT MUTAGEN 103 103 R->A: No effect on flap endonuclease FT activity or substrate binding. FT {ECO:0000269|PubMed:8621570}. FT MUTAGEN 158 158 E->A: Loss of flap endonuclease activity FT and substrate binding. FT {ECO:0000269|PubMed:8621570}. FT MUTAGEN 179 179 D->A: No effect on flap endonuclease FT activity or substrate binding. FT {ECO:0000269|PubMed:8621570}. FT MUTAGEN 181 181 D->A: Loss of flap endonuclease activity FT but substrate binding activity is FT retained. {ECO:0000269|PubMed:8621570}. FT MUTAGEN 187 187 S->A: Fails to translocate from nucleoli FT to the nuclear plasma. FT {ECO:0000269|PubMed:18443037}. FT MUTAGEN 187 187 S->D: Diminishes nucleolar localization. FT {ECO:0000269|PubMed:18443037}. FT MUTAGEN 192 192 R->K: Impairs ability to localize to FT sites of DNA replication or repair. FT {ECO:0000269|PubMed:20729856}. FT MUTAGEN 231 231 G->A: Loss of flap endonuclease activity FT and substrate binding. FT {ECO:0000269|PubMed:8621570}. FT MUTAGEN 233 233 D->A: Loss of flap endonuclease activity FT and substrate binding. FT {ECO:0000269|PubMed:8621570}. FT HELIX 6 13 {ECO:0000244|PDB:3Q8K}. FT HELIX 15 17 {ECO:0000244|PDB:3Q8K}. FT STRAND 18 22 {ECO:0000244|PDB:3Q8K}. FT HELIX 23 26 {ECO:0000244|PDB:3Q8K}. FT STRAND 30 34 {ECO:0000244|PDB:3Q8K}. FT HELIX 35 45 {ECO:0000244|PDB:3Q8K}. FT STRAND 47 52 {ECO:0000244|PDB:3Q8M}. FT HELIX 62 75 {ECO:0000244|PDB:3Q8K}. FT TURN 76 78 {ECO:0000244|PDB:3Q8K}. FT STRAND 80 85 {ECO:0000244|PDB:3Q8K}. FT HELIX 91 93 {ECO:0000244|PDB:3Q8K}. FT HELIX 94 115 {ECO:0000244|PDB:3Q8K}. FT HELIX 120 129 {ECO:0000244|PDB:3Q8K}. FT HELIX 135 148 {ECO:0000244|PDB:3Q8K}. FT STRAND 152 154 {ECO:0000244|PDB:3Q8K}. FT HELIX 159 168 {ECO:0000244|PDB:3Q8K}. FT STRAND 171 176 {ECO:0000244|PDB:3Q8K}. FT HELIX 181 184 {ECO:0000244|PDB:3Q8K}. FT STRAND 188 193 {ECO:0000244|PDB:3Q8K}. FT STRAND 203 208 {ECO:0000244|PDB:3Q8K}. FT HELIX 209 216 {ECO:0000244|PDB:3Q8K}. FT HELIX 220 230 {ECO:0000244|PDB:3Q8K}. FT STRAND 233 235 {ECO:0000244|PDB:3Q8K}. FT HELIX 243 253 {ECO:0000244|PDB:3Q8K}. FT HELIX 256 262 {ECO:0000244|PDB:3Q8K}. FT TURN 265 267 {ECO:0000244|PDB:3Q8K}. FT HELIX 276 284 {ECO:0000244|PDB:3Q8K}. FT TURN 291 293 {ECO:0000244|PDB:3Q8K}. FT HELIX 303 310 {ECO:0000244|PDB:3Q8K}. FT TURN 311 314 {ECO:0000244|PDB:3Q8K}. FT HELIX 318 335 {ECO:0000244|PDB:3Q8K}. FT HELIX 340 342 {ECO:0000244|PDB:1U7B}. FT STRAND 344 351 {ECO:0000244|PDB:1UL1}. SQ SEQUENCE 380 AA; 42593 MW; 5154F2F6E57592C5 CRC64; MGIQGLAKLI ADVAPSAIRE NDIKSYFGRK VAIDASMSIY QFLIAVRQGG DVLQNEEGET TSHLMGMFYR TIRMMENGIK PVYVFDGKPP QLKSGELAKR SERRAEAEKQ LQQAQAAGAE QEVEKFTKRL VKVTKQHNDE CKHLLSLMGI PYLDAPSEAE ASCAALVKAG KVYAAATEDM DCLTFGSPVL MRHLTASEAK KLPIQEFHLS RILQELGLNQ EQFVDLCILL GSDYCESIRG IGPKRAVDLI QKHKSIEEIV RRLDPNKYPV PENWLHKEAH QLFLEPEVLD PESVELKWSE PNEEELIKFM CGEKQFSEER IRSGVKRLSK SRQGSTQGRL DDFFKVTGSL SSAKRKEPEP KGSTKKKAKT GAAGKFKRGK // ID FEN1_YEAST Reviewed; 382 AA. AC P26793; D6VXH5; DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1992, sequence version 1. DT 11-NOV-2015, entry version 145. DE RecName: Full=Flap endonuclease 1 {ECO:0000255|HAMAP-Rule:MF_03140}; DE Short=FEN-1 {ECO:0000255|HAMAP-Rule:MF_03140}; DE EC=3.1.-.- {ECO:0000255|HAMAP-Rule:MF_03140}; DE AltName: Full=Flap structure-specific endonuclease 1 {ECO:0000255|HAMAP-Rule:MF_03140}; DE AltName: Full=RAD2 homolog nuclease 1; DE Short=RTH1 nuclease; DE AltName: Full=Structure-specific endonuclease RAD27; GN Name=RAD27 {ECO:0000255|HAMAP-Rule:MF_03140}; GN Synonyms=FEN1 {ECO:0000255|HAMAP-Rule:MF_03140}, RTH1; GN OrderedLocusNames=YKL113C; ORFNames=YKL510; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1561835; DOI=10.1002/yea.320080207; RA Jacquier A., Legrain P., Dujon B.; RT "Sequence of a 10.7 kb segment of yeast chromosome XI identifies the RT APN1 and the BAF1 loci and reveals one tRNA gene and several new open RT reading frames including homologs to RAD2 and kinases."; RL Yeast 8:121-132(1992). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=8196765; DOI=10.1038/369371a0; RA Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V., RA Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., RA Bossier P., Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L., RA Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A., RA Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H., RA Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L., RA Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M., RA Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H., RA Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J., RA Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H., RA Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J., RA Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S., RA Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F., RA Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R., RA Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W., RA Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M., RA Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C., RA Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H., RA Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L., RA van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., RA Vissers S., von Wettstein D., Voss H., Wiemann S., Xu G., RA Zimmermann J., Haasemann M., Becker I., Mewes H.-W.; RT "Complete DNA sequence of yeast chromosome XI."; RL Nature 369:371-378(1994). RN [3] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., RA Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and RT now."; RL G3 (Bethesda) 4:389-398(2014). RN [4] RP PROTEIN SEQUENCE OF 284-298, FUNCTION, AND EXONUCLEASE AND RNASE H RP ACTIVITIES. RX PubMed=9166764; DOI=10.1021/bi962889v; RA Zhu F.X., Biswas E.E., Biswas S.B.; RT "Purification and characterization of the DNA polymerase alpha RT associated exonuclease: the RTH1 gene product."; RL Biochemistry 36:5947-5954(1997). RN [5] RP CHARACTERIZATION. RX PubMed=7926735; DOI=10.1101/gad.8.11.1344; RA Harrington J.J., Lieber M.R.; RT "Functional domains within FEN-1 and RAD2 define a family of RT structure-specific endonucleases: implications for nucleotide excision RT repair."; RL Genes Dev. 8:1344-1355(1994). RN [6] RP CHARACTERIZATION. RX PubMed=7814325; RA Reagan M.S., Pittenger C., Siede W., Friedberg E.C.; RT "Characterization of a mutant strain of Saccharomyces cerevisiae with RT a deletion of the RAD27 gene, a structural homolog of the RAD2 RT nucleotide excision repair gene."; RL J. Bacteriol. 177:364-371(1995). RN [7] RP INTERACTION WITH POL30, AND MUTAGENESIS OF 346-PHE-PHE-347. RX PubMed=10899134; DOI=10.1093/emboj/19.14.3811; RA Gomes X.V., Burgers P.M.; RT "Two modes of FEN1 binding to PCNA regulated by DNA."; RL EMBO J. 19:3811-3821(2000). RN [8] RP FUNCTION, ENDONUCLEASE ACTIVITY, SUBSTRATE SPECIFICITY, AND RP MUTAGENESIS OF GLY-240. RX PubMed=11825897; DOI=10.1074/jbc.M110662200; RA Kao H.I., Henricksen L.A., Liu Y., Bambara R.A.; RT "Cleavage specificity of Saccharomyces cerevisiae flap endonuclease 1 RT suggests a double-flap structure as the cellular substrate."; RL J. Biol. Chem. 277:14379-14389(2002). RN [9] RP FUNCTION. RX PubMed=12424238; DOI=10.1074/jbc.M209801200; RA Ayyagari R., Gomes X.V., Gordenin D.A., Burgers P.M.; RT "Okazaki fragment maturation in yeast. I. Distribution of functions RT between FEN1 AND DNA2."; RL J. Biol. Chem. 278:1618-1625(2003). RN [10] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=14562095; DOI=10.1038/nature02026; RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., RA Weissman J.S., O'Shea E.K.; RT "Global analysis of protein localization in budding yeast."; RL Nature 425:686-691(2003). RN [11] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., RA Dephoure N., O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [12] RP FUNCTION, AND MUTAGENESIS OF GLY-67. RX PubMed=16837458; DOI=10.1074/jbc.M604805200; RA Rossi M.L., Bambara R.A.; RT "Reconstituted Okazaki fragment processing indicates two pathways of RT primer removal."; RL J. Biol. Chem. 281:26051-26061(2006). RN [13] RP FUNCTION, ENDONUCLEASE AND EXONUCLEASE ACTIVITIES, AND MUTAGENESIS OF RP GLU-176. RX PubMed=17138563; DOI=10.1074/jbc.M606582200; RA Singh P., Zheng L., Chavez V., Qiu J., Shen B.; RT "Concerted action of exonuclease and Gap-dependent endonuclease RT activities of FEN-1 contributes to the resolution of triplet repeat RT sequences (CTG)n-and (GAA)n-derived secondary structures formed during RT maturation of Okazaki fragments."; RL J. Biol. Chem. 282:3465-3477(2007). RN [14] RP FUNCTION IN RDNA REPLICATION AND REPAIR. RX PubMed=18443037; DOI=10.1128/MCB.00200-08; RA Guo Z., Qian L., Liu R., Dai H., Zhou M., Zheng L., Shen B.; RT "Nucleolar localization and dynamic roles of flap endonuclease 1 in RT ribosomal DNA replication and damage repair."; RL Mol. Cell. Biol. 28:4310-4319(2008). RN [15] RP FUNCTION IN MITOCHONDRIAL DNA REPAIR, AND SUBCELLULAR LOCATION. RX PubMed=19699691; DOI=10.1016/j.dnarep.2009.07.008; RA Kalifa L., Beutner G., Phadnis N., Sheu S.S., Sia E.A.; RT "Evidence for a role of FEN1 in maintaining mitochondrial DNA RT integrity."; RL DNA Repair 8:1242-1249(2009). RN [16] RP FUNCTION IN DNA REPAIR. RX PubMed=19075004; DOI=10.1128/MCB.01499-08; RA Ma W., Panduri V., Sterling J.F., Van Houten B., Gordenin D.A., RA Resnick M.A.; RT "The transition of closely opposed lesions to double-strand breaks RT during long-patch base excision repair is prevented by the coordinated RT action of DNA polymerase delta and Rad27/Fen1."; RL Mol. Cell. Biol. 29:1212-1221(2009). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). CC -!- FUNCTION: Structure-specific nuclease with 5'-flap endonuclease CC and 5'-3' exonuclease activities involved in DNA replication and CC repair. During DNA replication, cleaves the 5'-overhanging flap CC structure that is generated by displacement synthesis when DNA CC polymerase encounters the 5'-end of a downstream Okazaki fragment. CC It enters the flap from the 5'-end and then tracks to cleave the CC flap base, leaving a nick for ligation. Also involved in the long CC patch base excision repair (LP-BER) pathway, by cleaving within CC the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a CC genome stabilization factor that prevents flaps from equilibrating CC into structurs that lead to duplications and deletions. Also CC possesses 5'-3' exonuclease activity on nicked or gapped double- CC stranded DNA, and exhibits RNase H activity. Also involved in CC replication and repair of rDNA and in repairing mitochondrial DNA. CC {ECO:0000255|HAMAP-Rule:MF_03140, ECO:0000269|PubMed:11825897, CC ECO:0000269|PubMed:12424238, ECO:0000269|PubMed:16837458, CC ECO:0000269|PubMed:17138563, ECO:0000269|PubMed:18443037, CC ECO:0000269|PubMed:19075004, ECO:0000269|PubMed:19699691, CC ECO:0000269|PubMed:9166764}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000255|HAMAP-Rule:MF_03140}; CC Note=Binds 2 magnesium ions per subunit. They probably participate CC in the reaction catalyzed by the enzyme. May bind an additional CC third magnesium ion after substrate binding. {ECO:0000255|HAMAP- CC Rule:MF_03140}; CC -!- SUBUNIT: Interacts with PCNA (POL30). Three molecules of RAD27 CC bind to one PCNA trimer with each molecule binding to one PCNA CC monomer. PCNA stimulates the nuclease activity without altering CC cleavage specificity. {ECO:0000269|PubMed:10899134}. CC -!- INTERACTION: CC P38859:DNA2; NbExp=3; IntAct=EBI-14693, EBI-5973; CC P15873:POL30; NbExp=3; IntAct=EBI-14693, EBI-12993; CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus. Nucleus, nucleoplasm. CC Mitochondrion. Note=Resides mostly in the nucleoli and relocalizes CC to the nucleoplasm upon DNA damage. CC -!- PTM: Phosphorylated. Phosphorylation upon DNA damage induces CC relocalization to the nuclear plasma. {ECO:0000255|HAMAP- CC Rule:MF_03140}. CC -!- MISCELLANEOUS: Present with 6120 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. FEN1 CC subfamily. {ECO:0000255|HAMAP-Rule:MF_03140}. 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; S93804; AAB21998.1; -; Genomic_DNA. DR EMBL; Z28113; CAA81953.1; -; Genomic_DNA. DR EMBL; BK006944; DAA09045.1; -; Genomic_DNA. DR PIR; S22267; S22267. DR RefSeq; NP_012809.1; NM_001179679.1. DR ProteinModelPortal; P26793; -. DR SMR; P26793; 2-333. DR BioGrid; 34021; 372. DR DIP; DIP-2325N; -. DR IntAct; P26793; 3. DR MINT; MINT-536469; -. DR MaxQB; P26793; -. DR PeptideAtlas; P26793; -. DR EnsemblFungi; YKL113C; YKL113C; YKL113C. DR GeneID; 853747; -. DR KEGG; sce:YKL113C; -. DR EuPathDB; FungiDB:YKL113C; -. DR SGD; S000001596; RAD27. DR GeneTree; ENSGT00640000091478; -. DR InParanoid; P26793; -. DR KO; K04799; -. DR OMA; GSQDYDS; -. DR OrthoDB; EOG7QK0MK; -. DR BioCyc; YEAST:G3O-31898-MONOMER; -. DR Reactome; R-SCE-69166; Removal of the Flap Intermediate. DR NextBio; 974807; -. DR PRO; PR:P26793; -. DR Proteomes; UP000002311; Chromosome XI. DR GO; GO:0005829; C:cytosol; IDA:SGD. DR GO; GO:0005739; C:mitochondrion; IDA:SGD. DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IDA:SGD. DR GO; GO:0008409; F:5'-3' exonuclease activity; IDA:SGD. DR GO; GO:0017108; F:5'-flap endonuclease activity; IDA:SGD. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006286; P:base-excision repair, base-free sugar-phosphate removal; IMP:SGD. DR GO; GO:0043137; P:DNA replication, removal of RNA primer; IDA:SGD. DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IDA:SGD. DR GO; GO:0000734; P:gene conversion at mating-type locus, DNA repair synthesis; IMP:SGD. DR GO; GO:0035753; P:maintenance of DNA trinucleotide repeats; IMP:SGD. DR GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IDA:GOC. DR GO; GO:0001302; P:replicative cell aging; IMP:SGD. DR Gene3D; 3.40.50.1010; -; 1. DR HAMAP; MF_00614; Fen; 1. DR InterPro; IPR020045; 5-3_exonuclease_C. DR InterPro; IPR023426; Flap_endonuc. DR InterPro; IPR008918; HhH2. DR InterPro; IPR029060; PIN_domain-like. DR InterPro; IPR006086; XPG-I_dom. DR InterPro; IPR006084; XPG/Rad2. DR InterPro; IPR019974; XPG_CS. DR InterPro; IPR006085; XPG_DNA_repair_N. DR PANTHER; PTHR11081; PTHR11081; 1. DR Pfam; PF00867; XPG_I; 1. DR Pfam; PF00752; XPG_N; 1. DR PRINTS; PR00853; XPGRADSUPER. DR SMART; SM00279; HhH2; 1. DR SMART; SM00484; XPGI; 1. DR SMART; SM00485; XPGN; 1. DR SUPFAM; SSF47807; SSF47807; 1. DR SUPFAM; SSF88723; SSF88723; 1. DR PROSITE; PS00841; XPG_1; 1. DR PROSITE; PS00842; XPG_2; 1. PE 1: Evidence at protein level; KW Complete proteome; Direct protein sequencing; DNA damage; DNA repair; KW DNA replication; Endonuclease; Exonuclease; Hydrolase; Magnesium; KW Metal-binding; Mitochondrion; Nuclease; Nucleus; Phosphoprotein; KW Reference proteome. FT CHAIN 1 382 Flap endonuclease 1. FT /FTId=PRO_0000154038. FT REGION 1 105 N-domain. FT REGION 120 251 I-domain. FT REGION 339 347 Interaction with PCNA. FT {ECO:0000255|HAMAP-Rule:MF_03140}. FT METAL 34 34 Magnesium 1. {ECO:0000255|HAMAP- FT Rule:MF_03140}. FT METAL 87 87 Magnesium 1. {ECO:0000255|HAMAP- FT Rule:MF_03140}. FT METAL 156 156 Magnesium 1. {ECO:0000255|HAMAP- FT Rule:MF_03140}. FT METAL 158 158 Magnesium 1. {ECO:0000255|HAMAP- FT Rule:MF_03140}. FT METAL 177 177 Magnesium 2. {ECO:0000255|HAMAP- FT Rule:MF_03140}. FT METAL 179 179 Magnesium 2. {ECO:0000255|HAMAP- FT Rule:MF_03140}. FT METAL 231 231 Magnesium 2. {ECO:0000255|HAMAP- FT Rule:MF_03140}. FT BINDING 47 47 DNA substrate. {ECO:0000255|HAMAP- FT Rule:MF_03140}. FT BINDING 71 71 DNA substrate. {ECO:0000255|HAMAP- FT Rule:MF_03140}. FT BINDING 156 156 DNA substrate. {ECO:0000255|HAMAP- FT Rule:MF_03140}. FT BINDING 229 229 DNA substrate. {ECO:0000255|HAMAP- FT Rule:MF_03140}. FT BINDING 231 231 DNA substrate. {ECO:0000255|HAMAP- FT Rule:MF_03140}. FT MUTAGEN 67 67 G->S: Deficient in double and single flap FT endonuclease cleavage and exonucleolytic FT cleavage. {ECO:0000269|PubMed:16837458}. FT MUTAGEN 176 176 E->A: Deficient in exonuclease and gap FT endonuclease activities, but retains FT almost all of its flap endonuclease FT activity. {ECO:0000269|PubMed:17138563}. FT MUTAGEN 240 240 G->D: Can only cleave double-flap FT structures with a 3' 1-nucleotide tail. FT Has no exonuclease activity. FT {ECO:0000269|PubMed:11825897}. FT MUTAGEN 346 347 FF->GA: Reduces interaction with POL30 FT more than 100 fold. FT {ECO:0000269|PubMed:10899134}. SQ SEQUENCE 382 AA; 43279 MW; 1F54B08720121C8C CRC64; MGIKGLNAII SEHVPSAIRK SDIKSFFGRK VAIDASMSLY QFLIAVRQQD GGQLTNEAGE TTSHLMGMFY RTLRMIDNGI KPCYVFDGKP PDLKSHELTK RSSRRVETEK KLAEATTELE KMKQERRLVK VSKEHNEEAQ KLLGLMGIPY IIAPTEAEAQ CAELAKKGKV YAAASEDMDT LCYRTPFLLR HLTFSEAKKE PIHEIDTELV LRGLDLTIEQ FVDLCIMLGC DYCESIRGVG PVTALKLIKT HGSIEKIVEF IESGESNNTK WKIPEDWPYK QARMLFLDPE VIDGNEINLK WSPPKEKELI EYLCDDKKFS EERVKSGISR LKKGLKSGIQ GRLDGFFQVV PKTKEQLAAA AKRAQENKKL NKNKNKVTKG RR // ID MSH3_YEAST Reviewed; 1018 AA. AC P25336; D6VR92; DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot. DT 10-JUN-2008, sequence version 2. DT 11-NOV-2015, entry version 132. DE RecName: Full=DNA mismatch repair protein MSH3; DE AltName: Full=Mismatch-binding protein; DE Short=MBP; DE AltName: Full=MutS protein homolog 3; GN Name=MSH3; OrderedLocusNames=YCR092C; ORFNames=YCR1152, YCR92C; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8510668; RA New L., Liu K., Crouse G.F.; RT "The yeast gene MSH3 defines a new class of eukaryotic MutS RT homologues."; RL Mol. Gen. Genet. 239:97-108(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=1803822; DOI=10.1002/yea.320070910; RA Valle G., Bergantino E., Lanfranchi G., Carignani G.; RT "The sequence of a 6.3 kb segment of yeast chromosome III reveals an RT open reading frame coding for a putative mismatch binding protein."; RL Yeast 7:981-988(1991). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=1574125; DOI=10.1038/357038a0; RA Oliver S.G., van der Aart Q.J.M., Agostoni-Carbone M.L., Aigle M., RA Alberghina L., Alexandraki D., Antoine G., Anwar R., Ballesta J.P.G., RA Benit P., Berben G., Bergantino E., Biteau N., Bolle P.-A., RA Bolotin-Fukuhara M., Brown A., Brown A.J.P., Buhler J.-M., Carcano C., RA Carignani G., Cederberg H., Chanet R., Contreras R., Crouzet M., RA Daignan-Fornier B., Defoor E., Delgado M.D., Demolder J., Doira C., RA Dubois E., Dujon B., Duesterhoeft A., Erdmann D., Esteban M., RA Fabre F., Fairhead C., Faye G., Feldmann H., Fiers W., RA Francingues-Gaillard M.-C., Franco L., Frontali L., Fukuhara H., RA Fuller L.J., Galland P., Gent M.E., Gigot D., Gilliquet V., RA Glansdorff N., Goffeau A., Grenson M., Grisanti P., Grivell L.A., RA de Haan M., Haasemann M., Hatat D., Hoenicka J., Hegemann J.H., RA Herbert C.J., Hilger F., Hohmann S., Hollenberg C.P., Huse K., RA Iborra F., Indge K.J., Isono K., Jacq C., Jacquet M., James C.M., RA Jauniaux J.-C., Jia Y., Jimenez A., Kelly A., Kleinhans U., Kreisl P., RA Lanfranchi G., Lewis C., van der Linden C.G., Lucchini G., RA Lutzenkirchen K., Maat M.J., Mallet L., Mannhaupt G., Martegani E., RA Mathieu A., Maurer C.T.C., McConnell D., McKee R.A., Messenguy F., RA Mewes H.-W., Molemans F., Montague M.A., Muzi Falconi M., Navas L., RA Newlon C.S., Noone D., Pallier C., Panzeri L., Pearson B.M., Perea J., RA Philippsen P., Pierard A., Planta R.J., Plevani P., Poetsch B., RA Pohl F.M., Purnelle B., Ramezani Rad M., Rasmussen S.W., Raynal A., RA Remacha M.A., Richterich P., Roberts A.B., Rodriguez F., Sanz E., RA Schaaff-Gerstenschlaeger I., Scherens B., Schweitzer B., Shu Y., RA Skala J., Slonimski P.P., Sor F., Soustelle C., Spiegelberg R., RA Stateva L.I., Steensma H.Y., Steiner S., Thierry A., Thireos G., RA Tzermia M., Urrestarazu L.A., Valle G., Vetter I., RA van Vliet-Reedijk J.C., Voet M., Volckaert G., Vreken P., Wang H., RA Warmington J.R., von Wettstein D., Wicksteed B.L., Wilson C., RA Wurst H., Xu G., Yoshikawa A., Zimmermann F.K., Sgouros J.G.; RT "The complete DNA sequence of yeast chromosome III."; RL Nature 357:38-46(1992). RN [4] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., RA Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and RT now."; RL G3 (Bethesda) 4:389-398(2014). RN [5] RP DNA-BINDING SPECIFICITY, AND INTERACTION WITH MSH2. RX PubMed=8805366; DOI=10.1016/S0960-9822(02)70686-6; RA Habraken Y., Sung P., Prakash L., Prakash S.; RT "Binding of insertion/deletion DNA mismatches by the heterodimer of RT yeast mismatch repair proteins MSH2 and MSH3."; RL Curr. Biol. 6:1185-1187(1996). RN [6] RP FUNCTION, AND INTERACTION WITH MSH2. RX PubMed=8600025; DOI=10.1101/gad.10.4.407; RA Marsischky G.T., Filosi N., Kane M.F., Kolodner R.D.; RT "Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2- RT dependent mismatch repair."; RL Genes Dev. 10:407-420(1996). RN [7] RP INTERACTION WITH POL30. RX PubMed=8910404; DOI=10.1074/jbc.271.45.27987; RA Johnson R.E., Kovvali G.K., Guzder S.N., Amin N.S., Holm C., RA Habraken Y., Sung P., Prakash L., Prakash S.; RT "Evidence for involvement of yeast proliferating cell nuclear antigen RT in DNA mismatch repair."; RL J. Biol. Chem. 271:27987-27990(1996). RN [8] RP FUNCTION, DNA-BINDING SPECIFICITY, AND COMPLEX FORMATION WITH RP MLH1-PMS1. RX PubMed=9368761; DOI=10.1016/S0960-9822(06)00337-X; RA Habraken Y., Sung P., Prakash L., Prakash S.; RT "Enhancement of MSH2-MSH3-mediated mismatch recognition by the yeast RT MLH1-PMS1 complex."; RL Curr. Biol. 7:790-793(1997). RN [9] RP FUNCTION IN MMR. RX PubMed=9111357; RA Sia E.A., Kokoska R.J., Dominska M., Greenwell P., Petes T.D.; RT "Microsatellite instability in yeast: dependence on repeat unit size RT and DNA mismatch repair genes."; RL Mol. Cell. Biol. 17:2851-2858(1997). RN [10] RP FUNCTION IN NHTR. RX PubMed=9256462; DOI=10.1073/pnas.94.17.9214; RA Sugawara N., Paques F., Colaiacovo M., Haber J.E.; RT "Role of Saccharomyces cerevisiae Msh2 and Msh3 repair proteins in RT double-strand break-induced recombination."; RL Proc. Natl. Acad. Sci. U.S.A. 94:9214-9219(1997). RN [11] RP FUNCTION. RX PubMed=9770499; DOI=10.1073/pnas.95.21.12404; RA Flores-Rozas H., Kolodner R.D.; RT "The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent RT suppression of frameshift mutations."; RL Proc. Natl. Acad. Sci. U.S.A. 95:12404-12409(1998). RN [12] RP MUTAGENESIS OF GLY-796. RX PubMed=10523644; RA Studamire B., Price G., Sugawara N., Haber J.E., Alani E.; RT "Separation-of-function mutations in Saccharomyces cerevisiae MSH2 RT that confer mismatch repair defects but do not affect nonhomologous- RT tail removal during recombination."; RL Mol. Cell. Biol. 19:7558-7567(1999). RN [13] RP MUTAGENESIS OF GLN-4 AND 10-PHE-PHE-11. RX PubMed=11005803; DOI=10.1074/jbc.C000513200; RA Clark A.B., Valle F., Drotschmann K., Gary R.K., Kunkel T.A.; RT "Functional interaction of proliferating cell nuclear antigen with RT MSH2-MSH6 and MSH2-MSH3 complexes."; RL J. Biol. Chem. 275:36498-36501(2000). RN [14] RP IDENTIFICATION OF PROBABLE INITIATION SITE. RX PubMed=12748633; DOI=10.1038/nature01644; RA Kellis M., Patterson N., Endrizzi M., Birren B.W., Lander E.S.; RT "Sequencing and comparison of yeast species to identify genes and RT regulatory elements."; RL Nature 423:241-254(2003). RN [15] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=14562095; DOI=10.1038/nature02026; RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., RA Weissman J.S., O'Shea E.K.; RT "Global analysis of protein localization in budding yeast."; RL Nature 425:686-691(2003). RN [16] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., RA Dephoure N., O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [17] RP FUNCTION. RX PubMed=16702432; DOI=10.1534/genetics.106.055616; RA Stone J.E., Petes T.D.; RT "Analysis of the proteins involved in the in vivo repair of base-base RT mismatches and four-base loops formed during meiotic recombination in RT the yeast Saccharomyces cerevisiae."; RL Genetics 173:1223-1239(2006). RN [18] RP FUNCTION IN NHTR, AND DNA-BINDING. RX PubMed=16781730; DOI=10.1016/j.jmb.2006.05.032; RA Surtees J.A., Alani E.; RT "Mismatch repair factor MSH2-MSH3 binds and alters the conformation of RT branched DNA structures predicted to form during genetic RT recombination."; RL J. Mol. Biol. 360:523-536(2006). RN [19] RP FUNCTION, DNA-BINDING, AND MUTAGENESIS OF LYS-158; LYS-160; PRO-203; RP GLN-226 AND ARG-247. RX PubMed=17157869; DOI=10.1016/j.jmb.2006.10.099; RA Lee S.D., Surtees J.A., Alani E.; RT "Saccharomyces cerevisiae MSH2-MSH3 and MSH2-MSH6 complexes display RT distinct requirements for DNA binding domain I in mismatch RT recognition."; RL J. Mol. Biol. 366:53-66(2007). RN [20] RP FUNCTION, AND IDENTIFICATION OF INITIATION SITE. RX PubMed=17636021; DOI=10.1128/MCB.00855-07; RA Harrington J.M., Kolodner R.D.; RT "Saccharomyces cerevisiae Msh2-Msh3 acts in repair of base-base RT mispairs."; RL Mol. Cell. Biol. 27:6546-6554(2007). RN [21] RP FUNCTION. RX PubMed=17573527; DOI=10.1073/pnas.0704148104; RA Shell S.S., Putnam C.D., Kolodner R.D.; RT "Chimeric Saccharomyces cerevisiae Msh6 protein with an Msh3 mispair- RT binding domain combines properties of both proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 104:10956-10961(2007). RN [22] RP INTERACTION WITH SAW1. RX PubMed=18471978; DOI=10.1016/j.molcel.2008.02.028; RA Li F., Dong J., Pan X., Oum J.-H., Boeke J.D., Lee S.E.; RT "Microarray-based genetic screen defines SAW1, a gene required for RT Rad1/Rad10-dependent processing of recombination intermediates."; RL Mol. Cell 30:325-335(2008). CC -!- FUNCTION: Component of the post-replicative DNA mismatch repair CC system (MMR). Heterodimerizes with MSH2 to form MutS beta, which CC binds to DNA mismatches thereby initiating DNA repair. MSH3 CC provides substrate-binding and substrate specificity to the CC complex. When bound, the MutS beta heterodimer bends the DNA helix CC and shields approximately 20 base pairs. Acts mainly to repair CC insertion-deletion loops (IDLs) from 2 to 13 nucleotides in size, CC but can also repair base-base and single insertion-deletion CC mismatches that occur during replication. After mismatch binding, CC forms a ternary complex with either the MutL alpha or MutL beta CC heterodimer, which is thought to be responsible for directing the CC downstream MMR events, including strand discrimination, excision, CC and resynthesis. MutS beta also has a role in regulation of CC heteroduplex formation during mitotic and meiotic recombination. CC MutS beta binds to DNA flap structures predicted to form during CC recombination, and is required for 3' non-homologous tail removal CC (NHTR). MutS beta-binding alters the DNA conformation of its CC substrate at the ds/ssDNA junction and may facilitate its CC recognition and/or cleavage by the downstream nucleotide excision CC repair (NER) RAD1-RAD10 endonuclease. ATP binding and hydrolysis CC play a pivotal role in MMR and NHTR. {ECO:0000269|PubMed:16702432, CC ECO:0000269|PubMed:16781730, ECO:0000269|PubMed:17157869, CC ECO:0000269|PubMed:17573527, ECO:0000269|PubMed:17636021, CC ECO:0000269|PubMed:8600025, ECO:0000269|PubMed:9111357, CC ECO:0000269|PubMed:9256462, ECO:0000269|PubMed:9368761, CC ECO:0000269|PubMed:9770499}. CC -!- SUBUNIT: Heterodimer consisting of MSH2-MSH3 (MutS beta). Forms a CC ternary complex with either MutL alpha (MLH1-PMS1) or MutL beta CC (MLH1-MLH3). MutS beta interacts with proliferating cell nuclear CC antigen (PCNA/POL30). Interacts with SAW1. CC {ECO:0000269|PubMed:18471978, ECO:0000269|PubMed:8600025, CC ECO:0000269|PubMed:8805366, ECO:0000269|PubMed:8910404}. CC -!- INTERACTION: CC P25847:MSH2; NbExp=3; IntAct=EBI-11362, EBI-11352; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095}. CC -!- DOMAIN: The PIP box serves as a PCNA(POL30)-recognition and CC -binding motif. CC -!- MISCELLANEOUS: Present with 736 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutS family. MSH3 CC subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA34803.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAA42247.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=CAA46116.1; 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; X64954; CAA46116.1; ALT_INIT; Genomic_DNA. DR EMBL; M96250; AAA34803.1; ALT_INIT; Genomic_DNA. DR EMBL; X59720; CAA42247.1; ALT_INIT; Genomic_DNA. DR EMBL; BK006937; DAA07561.1; -; Genomic_DNA. DR PIR; S19508; S19508. DR RefSeq; NP_010016.2; NM_001178798.1. DR ProteinModelPortal; P25336; -. DR SMR; P25336; 132-991. DR BioGrid; 31064; 35. DR DIP; DIP-2422N; -. DR IntAct; P25336; 24. DR MINT; MINT-633647; -. DR MaxQB; P25336; -. DR PeptideAtlas; P25336; -. DR PRIDE; P25336; -. DR EnsemblFungi; YCR092C; YCR092C; YCR092C. DR GeneID; 850454; -. DR KEGG; sce:YCR092C; -. DR EuPathDB; FungiDB:YCR092C; -. DR SGD; S000000688; MSH3. DR GeneTree; ENSGT00550000074949; -. DR HOGENOM; HOG000057130; -. DR InParanoid; P25336; -. DR KO; K08736; -. DR OMA; GYLLCIT; -. DR OrthoDB; EOG773XQH; -. DR BioCyc; YEAST:G3O-29386-MONOMER; -. DR Reactome; R-SCE-5358606; Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta). DR NextBio; 966078; -. DR PRO; PR:P25336; -. DR Proteomes; UP000002311; Chromosome III. DR GO; GO:0032302; C:MutSbeta complex; IPI:SGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0032135; F:DNA insertion or deletion binding; IDA:SGD. DR GO; GO:0000406; F:double-strand/single-strand DNA junction binding; IDA:SGD. DR GO; GO:0006310; P:DNA recombination; IMP:SGD. DR GO; GO:0000710; P:meiotic mismatch repair; IMP:SGD. DR GO; GO:0006298; P:mismatch repair; IMP:SGD. DR GO; GO:0006312; P:mitotic recombination; IMP:SGD. DR GO; GO:0000735; P:removal of nonhomologous ends; IMP:SGD. DR Gene3D; 3.40.1170.10; -; 1. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR007695; DNA_mismatch_repair_MutS-lik_N. DR InterPro; IPR000432; DNA_mismatch_repair_MutS_C. DR InterPro; IPR007861; DNA_mismatch_repair_MutS_clamp. DR InterPro; IPR007696; DNA_mismatch_repair_MutS_core. DR InterPro; IPR016151; DNA_mismatch_repair_MutS_N. DR InterPro; IPR007860; DNA_mmatch_repair_MutS_con_dom. DR InterPro; IPR027417; P-loop_NTPase. DR Pfam; PF01624; MutS_I; 1. DR Pfam; PF05188; MutS_II; 1. DR Pfam; PF05192; MutS_III; 1. DR Pfam; PF05190; MutS_IV; 1. DR Pfam; PF00488; MutS_V; 1. DR SMART; SM00534; MUTSac; 1. DR SMART; SM00533; MUTSd; 1. DR SUPFAM; SSF48334; SSF48334; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR SUPFAM; SSF55271; SSF55271; 1. DR PROSITE; PS00486; DNA_MISMATCH_REPAIR_2; 1. PE 1: Evidence at protein level; KW ATP-binding; Complete proteome; DNA damage; DNA repair; DNA-binding; KW Nucleotide-binding; Nucleus; Reference proteome. FT CHAIN 1 1018 DNA mismatch repair protein MSH3. FT /FTId=PRO_0000115195. FT NP_BIND 791 798 ATP. {ECO:0000255}. FT REGION 126 256 Mispair-binding domain. FT MOTIF 4 11 PIP box. FT MUTAGEN 4 4 Q->A: Partially functional in a mismatch FT repair assay; when associated with 10-AA- FT 11. {ECO:0000269|PubMed:11005803}. FT MUTAGEN 10 11 FF->AA: Partially functional in a FT mismatch repair assay; when associated FT with A-4. {ECO:0000269|PubMed:11005803}. FT MUTAGEN 158 158 K->A: Alters DNA-binding activity and FT impairs MSH2-MSH3-mediated DNA mismatch FT repair; when associated with ALA-160. FT {ECO:0000269|PubMed:17157869}. FT MUTAGEN 160 160 K->A: Alters DNA-binding activity and FT impairs MSH2-MSH3-mediated DNA mismatch FT repair; when associated with ALA-158. FT {ECO:0000269|PubMed:17157869}. FT MUTAGEN 203 203 P->A: No effect. FT {ECO:0000269|PubMed:17157869}. FT MUTAGEN 226 226 Q->A: No effect. FT {ECO:0000269|PubMed:17157869}. FT MUTAGEN 247 247 R->A: Impairs MSH2-MSH3-mediated DNA FT mismatch repair. FT {ECO:0000269|PubMed:17157869}. FT MUTAGEN 796 796 G->D: Defective in MMR and in NHTR. FT {ECO:0000269|PubMed:10523644}. SQ SEQUENCE 1018 AA; 116534 MW; 1AD91C2E2F2856EF CRC64; MAGQPTISRF FKKAVKSELT HKQEQEVAVG NGAGSESICL DTDEEDNLSS VASTTVTNDS FPLKGSVSSK NSKNSEKTSG TSTTFNDIDF AKKLDRIMKR RSDENVEAED DEEEGEEDFV KKKARKSPTA KLTPLDKQVK DLKMHHRDKV LVIRVGYKYK CFAEDAVTVS RILHIKLVPG KLTIDESNPQ DCNHRQFAYC SFPDVRLNVH LERLVHHNLK VAVVEQAETS AIKKHDPGAS KSSVFERKIS NVFTKATFGV NSTFVLRGKR ILGDTNSIWA LSRDVHQGKV AKYSLISVNL NNGEVVYDEF EEPNLADEKL QIRIKYLQPI EVLVNTDDLP LHVAKFFKDI SCPLIHKQEY DLEDHVVQAI KVMNEKIQLS PSLIRLVSKL YSHMVEYNNE QVMLIPSIYS PFASKIHMLL DPNSLQSLDI FTHDGGKGSL FWLLDHTRTS FGLRMLREWI LKPLVDVHQI EERLDAIECI TSEINNSIFF ESLNQMLNHT PDLLRTLNRI MYGTTSRKEV YFYLKQITSF VDHFKMHQSY LSEHFKSSDG RIGKQSPLLF RLFSELNELL STTQLPHFLT MINVSAVMEK NSDKQVMDFF NLNNYDCSEG IIKIQRESES VRSQLKEELA EIRKYLKRPY LNFRDEVDYL IEVKNSQIKD LPDDWIKVNN TKMVSRFTTP RTQKLTQKLE YYKDLLIRES ELQYKEFLNK ITAEYTELRK ITLNLAQYDC ILSLAATSCN VNYVRPTFVN GQQAIIAKNA RNPIIESLDV HYVPNDIMMS PENGKINIIT GPNMGGKSSY IRQVALLTIM AQIGSFVPAE EIRLSIFENV LTRIGAHDDI INGDSTFKVE MLDILHILKN CNKRSLLLLD EVGRGTGTHD GIAISYALIK YFSELSDCPL ILFTTHFPML GEIKSPLIRN YHMDYVEEQK TGEDWMSVIF LYKLKKGLTY NSYGMNVAKL ARLDKDIINR AFSISEELRK ESINEDALKL FSSLKRILKS DNITATDKLA KLLSLDIH // ID MSH6_HUMAN Reviewed; 1360 AA. AC P52701; B4DF41; B4E3I4; F5H2F9; O43706; O43917; Q8TCX4; Q9BTB5; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 21-JUN-2005, sequence version 2. DT 11-NOV-2015, entry version 188. DE RecName: Full=DNA mismatch repair protein Msh6; DE Short=hMSH6; DE AltName: Full=G/T mismatch-binding protein; DE Short=GTBP; DE Short=GTMBP; DE AltName: Full=MutS-alpha 160 kDa subunit; DE Short=p160; GN Name=MSH6; Synonyms=GTBP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], AND VARIANT GLU-39. RX PubMed=8942985; DOI=10.1073/pnas.93.24.13629; RA Acharya S., Wilson T., Gradia S., Kane M.F., Guerrette S., RA Marsischky G.T., Kolodner R.D., Fishel R.; RT "hMSH2 forms specific mispair-binding complexes with hMSH3 and RT hMSH6."; RL Proc. Natl. Acad. Sci. U.S.A. 93:13629-13634(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING. RX PubMed=9455487; DOI=10.1093/dnares/4.5.359; RA Shiwaku H.O., Wakatsuki S., Mori Y., Fukushige S., Horii A.; RT "Alternative splicing of GTBP in normal human tissues."; RL DNA Res. 4:359-362(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). RC TISSUE=Cerebellum, and Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-39; VAL-396; RP ALA-623 AND VAL-886. RG NIEHS SNPs program; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 69-1360, AND PARTIAL PROTEIN SEQUENCE. RX PubMed=7604265; DOI=10.1126/science.7604265; RA Palombo F., Gallinari P., Iaccarino I., Lettieri T., Hughes M., RA D'Arrigo A., Truong O., Hsuan J.J., Jiricny J.; RT "GTBP, a 160-kilodalton protein essential for mismatch-binding RT activity in human cells."; RL Science 268:1912-1914(1995). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-116. RX PubMed=8838326; DOI=10.1006/geno.1996.0067; RA Nicolaides N.C., Palombo F., Kinzler K.W., Vogelstein B., Jiricny J.; RT "Molecular cloning of the N-terminus of GTBP."; RL Genomics 31:395-397(1996). RN [9] RP CHARACTERIZATION, AND PARTIAL PROTEIN SEQUENCE. RX PubMed=7604264; DOI=10.1126/science.7604264; RA Drummond J.T., Li G.-M., Longley M.J., Modrich P.; RT "Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch RT repair to tumor cells."; RL Science 268:1909-1912(1995). RN [10] RP FUNCTION. RX PubMed=9822680; DOI=10.1074/jbc.273.48.32055; RA Blackwell L.J., Martik D., Bjornson K.P., Bjornson E.S., Modrich P.; RT "Nucleotide-promoted release of hMutSalpha from heteroduplex DNA is RT consistent with an ATP-dependent translocation mechanism."; RL J. Biol. Chem. 273:32055-32062(1998). RN [11] RP FUNCTION. RX PubMed=9822679; DOI=10.1074/jbc.273.48.32049; RA Blackwell L.J., Bjornson K.P., Modrich P.; RT "DNA-dependent activation of the hMutSalpha ATPase."; RL J. Biol. Chem. 273:32049-32054(1998). RN [12] RP FUNCTION, AND MUTAGENESIS OF LYS-1140. RX PubMed=9564049; DOI=10.1093/emboj/17.9.2677; RA Iaccarino I., Marra G., Palombo F., Jiricny J.; RT "hMSH2 and hMSH6 play distinct roles in mismatch binding and RT contribute differently to the ATPase activity of hMutSalpha."; RL EMBO J. 17:2677-2686(1998). RN [13] RP MISMATCH-BINDING. RX PubMed=9889267; DOI=10.1093/nar/27.3.736; RA Clark A.B., Cook M.E., Tran H.T., Gordenin D.A., Resnick M.A., RA Kunkel T.A.; RT "Functional analysis of human MutSalpha and MutSbeta complexes in RT yeast."; RL Nucleic Acids Res. 27:736-742(1999). RN [14] RP FUNCTION. RX PubMed=10078208; DOI=10.1016/S1097-2765(00)80316-0; RA Gradia S., Subramanian D., Wilson T., Acharya S., Makhov A., RA Griffith J., Fishel R.; RT "hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on RT mismatched DNA."; RL Mol. Cell 3:255-261(1999). RN [15] RP FUNCTION. RX PubMed=10660545; DOI=10.1074/jbc.275.6.3922; RA Gradia S., Acharya S., Fishel R.; RT "The role of mismatched nucleotides in activating the hMSH2-hMSH6 RT molecular switch."; RL J. Biol. Chem. 275:3922-3930(2000). RN [16] RP FUNCTION. RX PubMed=15064730; DOI=10.1038/sj.onc.1207462; RA Yang Q., Zhang R., Wang X.W., Linke S.P., Sengupta S., Hickson I.D., RA Pedrazzi G., Perrera C., Stagljar I., Littman S.J., Modrich P., RA Harris C.C.; RT "The mismatch DNA repair heterodimer, hMSH2/6, regulates BLM RT helicase."; RL Oncogene 23:3749-3756(2004). RN [17] RP PHOSPHORYLATION BY PRKCZ. RX PubMed=15808853; DOI=10.1016/j.jmb.2005.02.001; RA Hernandez-Pigeon H., Quillet-Mary A., Louat T., Schambourg A., RA Humbert O., Selves J., Salles B., Laurent G., Lautier D.; RT "hMutS alpha is protected from ubiquitin-proteasome-dependent RT degradation by atypical protein kinase C zeta phosphorylation."; RL J. Mol. Biol. 348:63-74(2005). RN [18] RP IDENTIFICATION OF MSH6 AS MEMBER OF BASC. 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 [19] RP INVOLVEMENT IN HNPCC5. RX PubMed=9354786; DOI=10.1038/ng1197-271; RA Miyaki M., Konishi M., Tanaka K., Kikuchi-Yanoshita R., Muraoka M., RA Yasuno M., Igari T., Koike M., Chiba M., Mori T.; RT "Germline mutation of MSH6 as the cause of hereditary nonpolyposis RT colorectal cancer."; RL Nat. Genet. 17:271-272(1997). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-219; SER-227 AND RP SER-261, 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 [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-41 AND SER-43, RP VARIANT [LARGE SCALE ANALYSIS] GLU-39, AND IDENTIFICATION BY MASS RP 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 [22] RP INVOLVEMENT IN MMRCS. RX PubMed=17557300; DOI=10.1002/humu.20569; RA Auclair J., Leroux D., Desseigne F., Lasset C., Saurin J.C., RA Joly M.O., Pinson S., Xu X.L., Montmain G., Ruano E., Navarro C., RA Puisieux A., Wang Q.; RT "Novel biallelic mutations in MSH6 and PMS2 genes: gene conversion as RT a likely cause of PMS2 gene inactivation."; RL Hum. Mutat. 28:1084-1090(2007). RN [23] 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 [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., RA Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for RT efficient phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-309, 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-79; SER-91; RP SER-137; SER-200; SER-227; SER-252; SER-254; SER-256 AND SER-261, 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 [27] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-70 AND LYS-504, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., RA Walther T.C., Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-137; SER-227 AND RP SER-830, 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 [29] 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 [30] RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 UL12. RX PubMed=21957315; DOI=10.1128/JVI.05487-11; RA Mohni K.N., Mastrocola A.S., Bai P., Weller S.K., Heinen C.D.; RT "DNA mismatch repair proteins are required for efficient herpes RT simplex virus 1 replication."; RL J. Virol. 85:12241-12253(2011). RN [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-137; SER-219; RP SER-227; SER-252; SER-261; THR-269; SER-274; SER-275; SER-279; SER-280 RP AND SER-309, 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 [32] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TYR-103 AND RP 105-TRP-TRP-106. RX PubMed=23622243; DOI=10.1016/j.cell.2013.03.025; RA Li F., Mao G., Tong D., Huang J., Gu L., Yang W., Li G.M.; RT "The histone mark H3K36me3 regulates human DNA mismatch repair through RT its interaction with MutSalpha."; RL Cell 153:590-600(2013). RN [33] RP X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS). RX PubMed=17531815; DOI=10.1016/j.molcel.2007.04.018; RA Warren J.J., Pohlhaus T.J., Changela A., Iyer R.R., Modrich P.L., RA Beese L.S.; RT "Structure of the human MutSalpha DNA lesion recognition complex."; RL Mol. Cell 26:579-592(2007). RN [34] RP VARIANTS VAL-1213 AND ILE-1260. RX PubMed=7604266; DOI=10.1126/science.7604266; RA Papadopoulos N., Nicolaides N.C., Liu B., Parsons R., Lengauer C., RA Palombo F., D'Arrigo A., Markowitz S., Willson J.K.V., Kinzler K.W., RA Jiricny J., Vogelstein B.; RT "Mutations of GTBP in genetically unstable cells."; RL Science 268:1915-1917(1995). RN [35] RP VARIANTS HNPCC5 ILE-144 AND CYS-850. RX PubMed=10521294; DOI=10.1086/302612; RA Wu Y., Berends M.J.W., Mensink R.G.J., Kempinga C., Sijmons R.H., RA van Der Zee A.G.J., Hollema H., Kleibeuker J.H., Buys C.H.C.M., RA Hofstra R.M.W.; RT "Association of hereditary nonpolyposis colorectal cancer-related RT tumors displaying low microsatellite instability with MSH6 germline RT mutations."; RL Am. J. Hum. Genet. 65:1291-1298(1999). RN [36] RP VARIANTS CRC ILE-285; ARG-566; GLY-803 AND THR-1087, AND VARIANTS RP GLU-39; ASP-220; VAL-396 AND LEU-800. RX PubMed=10537275; RA Kolodner R.D., Tytell J.D., Schmeits J.L., Kane M.F., Das Gupta R., RA Weger J., Wahlberg S., Fox E.A., Peel D., Ziogas A., Garber J.E., RA Syngal S., Anton-Culver H., Li F.P.; RT "Germ-line msh6 mutations in colorectal cancer families."; RL Cancer Res. 59:5068-5074(1999). RN [37] RP VARIANT HNPCC5 GLU-698. RX PubMed=10480359; DOI=10.1007/s004399900064; RA Wang Q., Lasset C., Desseigne F., Saurin J.-C., Maugard C., RA Navarro C., Ruano E., Descos L., Trillet-Lenoir V., Bosset J.-F., RA Puisieux A.; RT "Prevalence of germline mutations of hMLH1, hMSH2, hPMS1, hPMS2, and RT hMSH6 genes in 75 French kindreds with nonpolyposis colorectal RT cancer."; RL Hum. Genet. 105:79-85(1999). RN [38] RP VARIANT CRC MET-1284. RX PubMed=10413423; DOI=10.1093/jnci/91.14.1221; RA Chan T.L., Yuen S.T., Chung L.P., Ho J.W.C., Kwan K.Y.M., Chan A.S.Y., RA Ho J.C.Y., Leung S.Y., Wyllie A.H.; RT "Frequent microsatellite instability and mismatch repair gene RT mutations in young Chinese patients with colorectal cancer."; RL J. Natl. Cancer Inst. 91:1221-1226(1999). RN [39] RP VARIANTS COLORECTAL/ENDOMETRIAL CANCER VAL-20; ALA-878 AND HIS-901. RX PubMed=11153917; DOI=10.1007/s004390000417; RA Charames G.S., Millar A.L., Pal T., Narod S., Bapat B.; RT "Do MSH6 mutations contribute to double primary cancers of the RT colorectum and endometrium?"; RL Hum. Genet. 107:623-629(2000). RN [40] RP VARIANT CRC SER-340, AND VARIANT GLU-39. RX PubMed=10699937; RX DOI=10.1002/(SICI)1097-0215(20000301)85:5<606::AID-IJC2>3.0.CO;2-B; RA Plaschke J., Kruppa C., Tischler R., Bocker T., Pistorius S., RA Dralle H., Rueschoff J., Saeger H.D., Fishel R., Schackert H.K.; RT "Sequence analysis of the mismatch repair gene hMSH6 in the germline RT of patients with familial and sporadic colorectal cancer."; RL Int. J. Cancer 85:606-613(2000). RN [41] RP VARIANTS CRC ALA-685; GLN-772; ALA-800; MET-854; ALA-878; VAL-1031 AND RP ARG-1158. RX PubMed=11470537; DOI=10.1016/S0378-1119(01)00517-0; RA Ohmiya N., Matsumoto S., Yamamoto H., Baranovskaya S., RA Malkhosyan S.R., Perucho M.; RT "Germline and somatic mutations in hMSH6 and hMSH3 in gastrointestinal RT cancers of the microsatellite mutator phenotype."; RL Gene 272:301-313(2001). RN [42] RP VARIANT HNPCC5 ALA-878. RX PubMed=11586295; DOI=10.1038/ng1001-137; RA Wu Y., Berends M.J.W., Sijmons R.H., Mensink R.G.J., Verlind E., RA Kooi K.A., van der Sluis T., Kempinga C., van der Zee A.G.J., RA Hollema H., Buys C.H.C.M., Kleibeuker J.H., Hofstra R.M.W.; RT "A role for MLH3 in hereditary nonpolyposis colorectal cancer."; RL Nat. Genet. 29:137-138(2001). RN [43] RP VARIANTS CRC ILE-144; ARG-522; MET-725; CYS-850; ALA-878; ASP-1021; RP MET-1100; ILE-1219 AND ASP-1248. RX PubMed=11709755; DOI=10.1086/337944; RA Berends M.J.W., Wu Y., Sijmons R.H., Mensink R.G.J., van der Sluis T., RA Hordijk-Hos J.M., de Vries E.G.E., Hollema H., Karrenbeld A., RA Buys C.H.C.M., van der Zee A.G.J., Hofstra R.M.W., Kleibeuker J.H.; RT "Molecular and clinical characteristics of MSH6 variants: an analysis RT of 25 index carriers of a germline variant."; RL Am. J. Hum. Genet. 70:26-37(2002). RN [44] RP VARIANT CRC HIS-976. RX PubMed=11807791; DOI=10.1002/ijc.10097; RA Plaschke J., Krueger S., Pistorius S., Theissig F., Saeger H.D., RA Schackert H.K.; RT "Involvement of hMSH6 in the development of hereditary and sporadic RT colorectal cancer revealed by immunostaining is based on germline RT mutations, but rarely on somatic inactivation."; RL Int. J. Cancer 97:643-648(2002). RN [45] RP VARIANT HNPCC5 VAL-492. RX PubMed=12658575; DOI=10.1086/373963; RA Wagner A., Barrows A., Wijnen J.T., van der Klift H., Franken P.F., RA Verkuijlen P., Nakagawa H., Geugien M., Jaghmohan-Changur S., RA Breukel C., Meijers-Heijboer H., Morreau H., van Puijenbroek M., RA Burn J., Coronel S., Kinarski Y., Okimoto R., Watson P., Lynch J.F., RA de la Chapelle A., Lynch H.T., Fodde R.; RT "Molecular analysis of hereditary nonpolyposis colorectal cancer in RT the United States: high mutation detection rate among clinically RT selected families and characterization of an American founder genomic RT deletion of the MSH2 gene."; RL Am. J. Hum. Genet. 72:1088-1100(2003). RN [46] RP VARIANTS CRC HIS-1095 AND GLN-1354. RX PubMed=12522549; DOI=10.1007/s00439-002-0866-4; RA Kariola R., Otway R., Loennqvist K.E., Raevaara T.E., Macrae F., RA Vos Y.J., Kohonen-Corish M., Hofstra R.M.W., Nystroem-Lahti M.; RT "Two mismatch repair gene mutations found in a colon cancer patient - RT which one is pathogenic?"; RL Hum. Genet. 112:105-109(2003). RN [47] RP VARIANT CRC ALA-54, AND VARIANTS GLU-39; ALA-509; MET-854 AND ALA-878. RX PubMed=14520694; DOI=10.1002/ijc.11415; RA Peterlongo P., Nafa K., Lerman G.S., Glogowski E., Shia J., Ye T.Z., RA Markowitz A.J., Guillem J.G., Kolachana P., Boyd J.A., Offit K., RA Ellis N.A.; RT "MSH6 germline mutations are rare in colorectal cancer families."; RL Int. J. Cancer 107:571-579(2003). RN [48] RP VARIANTS LEU-128; LEU-623; THR-728 AND LYS-1193, AND CHARACTERIZATION RP OF VARIANTS LEU-128; LEU-623; THR-728 AND LYS-1193. RX PubMed=15354210; DOI=10.1038/sj.bjc.6602129; RA Kariola R., Hampel H., Frankel W.L., Raevaara T.E., de la Chapelle A., RA Nystroem-Lahti M.; RT "MSH6 missense mutations are often associated with no or low cancer RT susceptibility."; RL Br. J. Cancer 91:1287-1292(2004). RN [49] RP VARIANT HNPCC5 TRP-772. RX PubMed=14974087; DOI=10.1002/humu.9217; RG The German HNPCC consortium; RA Plaschke J., Krueger S., Dietmaier W., Gebert J., Sutter C., RA Mangold E., Pagenstecher C., Holinski-Feder E., Schulmann K., RA Moeslein G., Rueschoff J., Engel C., Evans G., Schackert H.K.; RT "Eight novel MSH6 germline mutations in patients with familial and RT nonfamilial colorectal cancer selected by loss of protein expression RT in tumor tissue."; RL Hum. Mutat. 23:285-285(2004). RN [50] RP VARIANT HNPCC5 VAL-1163. RX PubMed=15365995; DOI=10.1002/humu.9277; RA Shin Y.-K., Heo S.-C., Shin J.-H., Hong S.-H., Ku J.-L., Yoo B.-C., RA Kim I.-J., Park J.-G.; RT "Germline mutations in MLH1, MSH2 and MSH6 in Korean hereditary non- RT polyposis colorectal cancer families."; RL Hum. Mutat. 24:351-351(2004). RN [51] RP VARIANT COLORECTAL/ENDOMETRIAL CANCER PRO-449. RX PubMed=14961575; DOI=10.1002/ijc.11718; RA Cederquist K., Emanuelsson M., Goeransson I., Holinski-Feder E., RA Mueller-Koch Y., Golovleva I., Groenberg H.; RT "Mutation analysis of the MLH1, MSH2 and MSH6 genes in patients with RT double primary cancers of the colorectum and the endometrium: a RT population-based study in northern Sweden."; RL Int. J. Cancer 109:370-376(2004). RN [52] RP VARIANTS CRC ASN-99; ASP-619; VAL-787; ALA-878 AND CYS-1076. RX PubMed=15483016; DOI=10.1200/JCO.2004.02.033; RA Plaschke J., Engel C., Krueger S., Holinski-Feder E., Pagenstecher C., RA Mangold E., Moeslein G., Schulmann K., Gebert J., RA von Knebel Doeberitz M., Rueschoff J., Loeffler M., Schackert H.K.; RT "Lower incidence of colorectal cancer and later age of disease onset RT in 27 families with pathogenic MSH6 germline mutations compared with RT families with MLH1 or MSH2 mutations: the German hereditary RT nonpolyposis colorectal cancer consortium."; RL J. Clin. Oncol. 22:4486-4494(2004). RN [53] RP VARIANTS [LARGE SCALE ANALYSIS] ASP-221 AND VAL-492. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [54] RP VARIANTS THR-13; LEU-65; ILE-144; HIS-468; CYS-503; LEU-580; ALA-878; RP LEU-1232 AND GLY-1321. RX PubMed=18033691; DOI=10.1002/humu.20635; RA Barnetson R.A., Cartwright N., van Vliet A., Haq N., Drew K., RA Farrington S., Williams N., Warner J., Campbell H., Porteous M.E., RA Dunlop M.G.; RT "Classification of ambiguous mutations in DNA mismatch repair genes RT identified in a population-based study of colorectal cancer."; RL Hum. Mutat. 29:367-374(2008). RN [55] RP CHARACTERIZATION OF VARIANT HNPCC5 VAL-20, CHARACTERIZATION OF RP VARIANTS CRC HIS-976 AND ASP-1021, AND CHARACTERIZATION OF VARIANTS RP SER-25; VAL-326; VAL-396; VAL-492; CYS-503; ARG-522; ASN-610; CYS-850; RP ALA-878; TYR-1026; SER-1087 AND MET-1225. RX PubMed=22102614; DOI=10.1002/humu.22000; RA Drost M., Zonneveld J.B., van Hees S., Rasmussen L.J., Hofstra R.M., RA de Wind N.; RT "A rapid and cell-free assay to test the activity of lynch syndrome- RT associated MSH2 and MSH6 missense variants."; RL Hum. Mutat. 33:488-494(2012). RN [56] RP CHARACTERIZATION OF VARIANTS PRO-435; PRO-585; THR-677; ALA-878; RP HIS-1095 AND GLN-1354. RX PubMed=22581703; DOI=10.1002/humu.22119; RA Kantelinen J., Kansikas M., Candelin S., Hampel H., Smith B., Holm L., RA Kariola R., Nystrom M.; RT "Mismatch repair analysis of inherited MSH2 and/or MSH6 variation RT pairs found in cancer patients."; RL Hum. Mutat. 33:1294-1301(2012). CC -!- FUNCTION: Component of the post-replicative DNA mismatch repair CC system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which CC binds to DNA mismatches thereby initiating DNA repair. When bound, CC MutS alpha bends the DNA helix and shields approximately 20 base CC pairs, and recognizes single base mismatches and dinucleotide CC insertion-deletion loops (IDL) in the DNA. After mismatch binding, CC forms a ternary complex with the MutL alpha heterodimer, which is CC thought to be responsible for directing the downstream MMR events, CC including strand discrimination, excision, and resynthesis. ATP CC binding and hydrolysis play a pivotal role in mismatch repair CC functions. The ATPase activity associated with MutS alpha CC regulates binding similar to a molecular switch: mismatched DNA CC provokes ADP-->ATP exchange, resulting in a discernible CC conformational transition that converts MutS alpha into a sliding CC clamp capable of hydrolysis-independent diffusion along the DNA CC backbone. This transition is crucial for mismatch repair. MutS CC alpha may also play a role in DNA homologous recombination repair. CC Recruited on chromatin in G1 and early S phase via its PWWP domain CC that specifically binds trimethylated 'Lys-36' of histone H3 CC (H3K36me3): early recruitment to chromatin to be replicated CC allowing a quick identification of mismatch repair to initiate the CC DNA mismatch repair reaction. {ECO:0000269|PubMed:10078208, CC ECO:0000269|PubMed:10660545, ECO:0000269|PubMed:15064730, CC ECO:0000269|PubMed:23622243, ECO:0000269|PubMed:9564049, CC ECO:0000269|PubMed:9822679, ECO:0000269|PubMed:9822680}. CC -!- SUBUNIT: Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms a CC ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1. CC Part of the BRCA1-associated genome surveillance complex (BASC), CC which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the CC RAD50-MRE11-NBS1 protein complex. This association could be a CC dynamic process changing throughout the cell cycle and within CC subnuclear domains. Interacts with ATR. Interacts with herpes CC simplex virus 1 protein UL12 (PubMed:21957315). CC {ECO:0000269|PubMed:21957315}. CC -!- INTERACTION: CC P43246:MSH2; NbExp=5; IntAct=EBI-395529, EBI-355888; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23622243}. CC Chromosome {ECO:0000269|PubMed:23622243}. Note=Associates with CC H3K36me3 via its PWWP domain. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=GTBP-N; CC IsoId=P52701-1; Sequence=Displayed; CC Name=GTBP-alt; CC IsoId=P52701-2; Sequence=VSP_003291, VSP_003292; CC Name=3; CC IsoId=P52701-3; Sequence=VSP_054419; CC Note=No experimental confirmation available.; CC Name=4; CC IsoId=P52701-4; Sequence=VSP_055020; CC Note=No experimental confirmation available.; CC -!- DOMAIN: The PWWP domain specifically recognizes and binds CC trimethylated 'Lys-36' of histone H3 (H3K36me3). CC {ECO:0000269|PubMed:23622243}. CC -!- PTM: The N-terminus is blocked. CC -!- PTM: Phosphorylated by PRKCZ, which may prevent MutS alpha CC degradation by the ubiquitin-proteasome pathway. CC {ECO:0000269|PubMed:15808853}. CC -!- DISEASE: Hereditary non-polyposis colorectal cancer 5 (HNPCC5) CC [MIM:614350]: An autosomal dominant disease associated with marked CC increase in cancer susceptibility. It is characterized by a CC familial predisposition to early-onset colorectal carcinoma (CRC) CC and extra-colonic tumors of the gastrointestinal, urological and CC female reproductive tracts. HNPCC is reported to be the most CC common form of inherited colorectal cancer in the Western world. CC Clinically, HNPCC is often divided into two subgroups. Type I is CC characterized by hereditary predisposition to colorectal cancer, a CC young age of onset, and carcinoma observed in the proximal colon. CC Type II is characterized by increased risk for cancers in certain CC tissues such as the uterus, ovary, breast, stomach, small CC intestine, skin, and larynx in addition to the colon. Diagnosis of CC classical HNPCC is based on the Amsterdam criteria: 3 or more CC relatives affected by colorectal cancer, one a first degree CC relative of the other two; 2 or more generation affected; 1 or CC more colorectal cancers presenting before 50 years of age; CC exclusion of hereditary polyposis syndromes. The term 'suspected CC HNPCC' or 'incomplete HNPCC' can be used to describe families who CC do not or only partially fulfill the Amsterdam criteria, but in CC whom a genetic basis for colon cancer is strongly suspected. CC {ECO:0000269|PubMed:10480359, ECO:0000269|PubMed:10521294, CC ECO:0000269|PubMed:11586295, ECO:0000269|PubMed:12658575, CC ECO:0000269|PubMed:14974087, ECO:0000269|PubMed:15365995, CC ECO:0000269|PubMed:9354786}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of CC endometrium, the mucous lining of the uterus. Most endometrial CC cancers are adenocarcinomas, cancers that begin in cells that make CC and release mucus and other fluids. {ECO:0000269|PubMed:11153917, CC ECO:0000269|PubMed:14961575}. Note=Disease susceptibility is CC associated with variations affecting the gene represented in this CC entry. CC -!- DISEASE: Mismatch repair cancer syndrome (MMRCS) [MIM:276300]: An CC autosomal recessive, rare, childhood cancer predisposition CC syndrome encompassing a broad tumor spectrum. This includes CC hematological malignancies, central nervous system tumors, Lynch CC syndrome-associated malignancies such as colorectal tumors as well CC as multiple intestinal polyps, embryonic tumors and CC rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature CC reminiscent of neurofibromatosis type 1, are often found as first CC manifestation of the underlying cancer. Areas of skin CC hypopigmentation have also been reported in MMRCS patients. CC {ECO:0000269|PubMed:17557300}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutS family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 PWWP domain. {ECO:0000255|PROSITE- CC ProRule:PRU00162}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/MSH6ID344ch2p16.html"; CC -!- WEB RESOURCE: Name=Hereditary non-polyposis colorectal cancer db; CC URL="http://www.nfdht.nl/"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/msh6/"; 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; U73737; AAB47425.1; -; Genomic_DNA. DR EMBL; U73732; AAB47425.1; JOINED; Genomic_DNA. DR EMBL; U73733; AAB47425.1; JOINED; Genomic_DNA. DR EMBL; U73734; AAB47425.1; JOINED; Genomic_DNA. DR EMBL; U73736; AAB47425.1; JOINED; Genomic_DNA. DR EMBL; D89645; BAA23674.1; -; Genomic_DNA. DR EMBL; D89646; BAA23675.1; -; mRNA. DR EMBL; AK293921; BAG57302.1; -; mRNA. DR EMBL; AK304735; BAG65496.1; -; mRNA. DR EMBL; AY082894; AAL87401.1; -; Genomic_DNA. DR EMBL; AC006509; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC004246; AAH04246.1; -; mRNA. DR EMBL; U54777; AAB39212.2; -; mRNA. DR EMBL; U28946; AAC50461.1; -; mRNA. DR CCDS; CCDS1836.1; -. [P52701-1] DR CCDS; CCDS62906.1; -. [P52701-3] DR CCDS; CCDS62907.1; -. [P52701-4] DR PIR; JC5839; JC5839. DR RefSeq; NP_000170.1; NM_000179.2. [P52701-1] DR RefSeq; NP_001268421.1; NM_001281492.1. [P52701-3] DR RefSeq; NP_001268422.1; NM_001281493.1. [P52701-4] DR RefSeq; NP_001268423.1; NM_001281494.1. [P52701-4] DR UniGene; Hs.445052; -. DR PDB; 2GFU; NMR; -; A=68-201. DR PDB; 2O8B; X-ray; 2.75 A; B=341-1360. DR PDB; 2O8C; X-ray; 3.37 A; B=341-1360. DR PDB; 2O8D; X-ray; 3.00 A; B=341-1360. DR PDB; 2O8E; X-ray; 3.30 A; B=341-1360. DR PDB; 2O8F; X-ray; 3.25 A; B=341-1360. DR PDBsum; 2GFU; -. DR PDBsum; 2O8B; -. DR PDBsum; 2O8C; -. DR PDBsum; 2O8D; -. DR PDBsum; 2O8E; -. DR PDBsum; 2O8F; -. DR ProteinModelPortal; P52701; -. DR SMR; P52701; 68-201, 362-1335. DR BioGrid; 109211; 54. DR DIP; DIP-32972N; -. DR IntAct; P52701; 24. DR MINT; MINT-131993; -. DR STRING; 9606.ENSP00000234420; -. DR PhosphoSite; P52701; -. DR BioMuta; MSH6; -. DR DMDM; 68067672; -. DR MaxQB; P52701; -. DR PaxDb; P52701; -. DR PeptideAtlas; P52701; -. DR PRIDE; P52701; -. DR DNASU; 2956; -. DR Ensembl; ENST00000234420; ENSP00000234420; ENSG00000116062. [P52701-1] DR Ensembl; ENST00000538136; ENSP00000438580; ENSG00000116062. [P52701-4] DR Ensembl; ENST00000540021; ENSP00000446475; ENSG00000116062. [P52701-3] DR Ensembl; ENST00000614496; ENSP00000477844; ENSG00000116062. [P52701-4] DR GeneID; 2956; -. DR KEGG; hsa:2956; -. DR UCSC; uc002rwc.2; human. [P52701-2] DR UCSC; uc002rwd.4; human. [P52701-1] DR CTD; 2956; -. DR GeneCards; MSH6; -. DR GeneReviews; MSH6; -. DR HGNC; HGNC:7329; MSH6. DR HPA; CAB009091; -. DR HPA; HPA028376; -. DR HPA; HPA028446; -. DR MIM; 276300; phenotype. DR MIM; 600678; gene. DR MIM; 608089; phenotype. DR MIM; 614350; phenotype. DR neXtProt; NX_P52701; -. DR Orphanet; 252202; Constitutional mismatch repair deficiency syndrome. DR Orphanet; 144; Hereditary nonpolyposis colon cancer. DR Orphanet; 587; Muir-Torre syndrome. DR Orphanet; 99817; Non-polyposis Turcot syndrome. DR PharmGKB; PA184; -. DR eggNOG; KOG0217; Eukaryota. DR eggNOG; COG0249; LUCA. DR GeneTree; ENSGT00550000075024; -. DR HOGENOM; HOG000243127; -. DR HOVERGEN; HBG000101; -. DR InParanoid; P52701; -. DR KO; K08737; -. DR OMA; ALKDCMR; -. DR OrthoDB; EOG7K9K27; -. DR PhylomeDB; P52701; -. DR TreeFam; TF105842; -. DR Reactome; R-HSA-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha). DR ChiTaRS; MSH6; human. DR EvolutionaryTrace; P52701; -. DR GeneWiki; MSH6; -. DR GenomeRNAi; 2956; -. DR NextBio; 11716; -. DR PMAP-CutDB; P52701; -. DR PRO; PR:P52701; -. DR Proteomes; UP000005640; Chromosome 2. DR Bgee; P52701; -. DR CleanEx; HS_MSH6; -. DR ExpressionAtlas; P52701; baseline and differential. DR Genevisible; P52701; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0032301; C:MutSalpha complex; IDA:UniProtKB. DR GO; GO:0000790; C:nuclear chromatin; IEA:Ensembl. DR GO; GO:0000228; C:nuclear chromosome; IBA:GO_Central. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0003684; F:damaged DNA binding; IEA:Ensembl. DR GO; GO:0008094; F:DNA-dependent ATPase activity; IBA:GO_Central. DR GO; GO:0032137; F:guanine/thymine mispair binding; IEA:Ensembl. DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB. DR GO; GO:0030983; F:mismatched DNA binding; IDA:UniProtKB. DR GO; GO:0008340; P:determination of adult lifespan; ISS:BHF-UCL. DR GO; GO:0006281; P:DNA repair; IDA:BHF-UCL. DR GO; GO:0097193; P:intrinsic apoptotic signaling pathway; ISS:BHF-UCL. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISS:BHF-UCL. DR GO; GO:0045190; P:isotype switching; ISS:BHF-UCL. DR GO; GO:0000710; P:meiotic mismatch repair; ISS:BHF-UCL. DR GO; GO:0006298; P:mismatch repair; IDA:UniProtKB. DR GO; GO:0045910; P:negative regulation of DNA recombination; IDA:BHF-UCL. DR GO; GO:0051096; P:positive regulation of helicase activity; IDA:BHF-UCL. DR GO; GO:0007131; P:reciprocal meiotic recombination; IBA:GO_Central. DR GO; GO:0009411; P:response to UV; ISS:BHF-UCL. DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; ISS:BHF-UCL. DR GO; GO:0016447; P:somatic recombination of immunoglobulin gene segments; ISS:BHF-UCL. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. DR Gene3D; 3.40.1170.10; -; 1. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR007695; DNA_mismatch_repair_MutS-lik_N. DR InterPro; IPR000432; DNA_mismatch_repair_MutS_C. DR InterPro; IPR007861; DNA_mismatch_repair_MutS_clamp. DR InterPro; IPR007696; DNA_mismatch_repair_MutS_core. DR InterPro; IPR016151; DNA_mismatch_repair_MutS_N. DR InterPro; IPR007860; DNA_mmatch_repair_MutS_con_dom. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR000313; PWWP_dom. DR Pfam; PF01624; MutS_I; 1. DR Pfam; PF05188; MutS_II; 1. DR Pfam; PF05192; MutS_III; 1. DR Pfam; PF05190; MutS_IV; 1. DR Pfam; PF00488; MutS_V; 1. DR Pfam; PF00855; PWWP; 1. DR SMART; SM00534; MUTSac; 1. DR SMART; SM00533; MUTSd; 1. DR SMART; SM00293; PWWP; 1. DR SUPFAM; SSF48334; SSF48334; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR SUPFAM; SSF55271; SSF55271; 1. DR PROSITE; PS00486; DNA_MISMATCH_REPAIR_2; 1. DR PROSITE; PS50812; PWWP; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; ATP-binding; KW Chromosome; Complete proteome; Direct protein sequencing; KW Disease mutation; DNA damage; DNA repair; DNA-binding; KW Hereditary nonpolyposis colorectal cancer; Host-virus interaction; KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome. FT CHAIN 1 1360 DNA mismatch repair protein Msh6. FT /FTId=PRO_0000115207. FT DOMAIN 92 154 PWWP. {ECO:0000255|PROSITE- FT ProRule:PRU00162}. FT NP_BIND 1134 1141 ATP. {ECO:0000255}. FT COMPBIAS 34 37 Poly-Ala. FT COMPBIAS 201 209 Poly-Glu. FT COMPBIAS 1118 1123 Poly-Glu. FT MOD_RES 14 14 Phosphoserine. FT {ECO:0000244|PubMed:16964243, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 41 41 Phosphoserine. FT {ECO:0000244|PubMed:16964243}. FT MOD_RES 43 43 Phosphoserine. FT {ECO:0000244|PubMed:16964243}. FT MOD_RES 70 70 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 79 79 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 91 91 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 137 137 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 200 200 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 219 219 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 227 227 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 252 252 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 254 254 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 256 256 Phosphoserine. FT {ECO:0000244|PubMed:18669648}. FT MOD_RES 261 261 Phosphoserine. FT {ECO:0000244|PubMed:17081983, FT ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 269 269 Phosphothreonine. FT {ECO:0000244|PubMed:21406692}. FT MOD_RES 274 274 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT MOD_RES 275 275 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT MOD_RES 279 279 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT MOD_RES 280 280 Phosphoserine. FT {ECO:0000244|PubMed:21406692}. FT MOD_RES 309 309 Phosphoserine. FT {ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 504 504 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT MOD_RES 830 830 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT VAR_SEQ 1 302 Missing (in isoform 4). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_055020. FT VAR_SEQ 80 209 Missing (in isoform 3). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_054419. FT VAR_SEQ 1058 1068 DVLLCLANYSR -> GKTLNKLVLRL (in isoform FT GTBP-alt). {ECO:0000305}. FT /FTId=VSP_003291. FT VAR_SEQ 1069 1360 Missing (in isoform GTBP-alt). FT {ECO:0000305}. FT /FTId=VSP_003292. FT VARIANT 13 13 K -> T (in dbSNP:rs41294988). FT {ECO:0000269|PubMed:18033691}. FT /FTId=VAR_038032. FT VARIANT 20 20 A -> V (in colorectal/endometrial cancer FT and HNPCC5; repair proficient; FT dbSNP:rs63750664). FT {ECO:0000269|PubMed:11153917, FT ECO:0000269|PubMed:22102614}. FT /FTId=VAR_043943. FT VARIANT 25 25 A -> S (associated with HNPCC5; unknown FT pathologiacl significance; repair FT proficient). FT {ECO:0000269|PubMed:22102614}. FT /FTId=VAR_067294. FT VARIANT 25 25 A -> V (in dbSNP:rs35462442). FT /FTId=VAR_038033. FT VARIANT 39 39 G -> E (in dbSNP:rs1042821). FT {ECO:0000244|PubMed:16964243, FT ECO:0000269|PubMed:10537275, FT ECO:0000269|PubMed:10699937, FT ECO:0000269|PubMed:14520694, FT ECO:0000269|PubMed:8942985, FT ECO:0000269|Ref.4}. FT /FTId=VAR_004490. FT VARIANT 54 54 G -> A (in CRC; unknown pathological FT significance; dbSNP:rs63751098). FT {ECO:0000269|PubMed:14520694}. FT /FTId=VAR_043944. FT VARIANT 65 65 S -> L (in dbSNP:rs41294984). FT {ECO:0000269|PubMed:18033691}. FT /FTId=VAR_038034. FT VARIANT 99 99 K -> N (in CRC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15483016}. FT /FTId=VAR_043945. FT VARIANT 128 128 R -> L (no impairment of FT heterodimerization with MSH2 and of in FT vitro mismatch repair capacity). FT {ECO:0000269|PubMed:15354210}. FT /FTId=VAR_043946. FT VARIANT 144 144 S -> I (in suspected HNPCC5 and CRC; FT dbSNP:rs3211299). FT {ECO:0000269|PubMed:10521294, FT ECO:0000269|PubMed:11709755, FT ECO:0000269|PubMed:18033691}. FT /FTId=VAR_012955. FT VARIANT 220 220 E -> D (in dbSNP:rs1800938). FT {ECO:0000269|PubMed:10537275}. FT /FTId=VAR_012956. FT VARIANT 221 221 E -> D (in dbSNP:rs41557217). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_042274. FT VARIANT 285 285 S -> I (in CRC). FT {ECO:0000269|PubMed:10537275}. FT /FTId=VAR_012957. FT VARIANT 295 295 K -> R (in multiple colorectal adenoma). FT /FTId=VAR_043947. FT VARIANT 326 326 A -> V (associated with HNPCC5; unknown FT pathological significance; repair FT proficient). FT {ECO:0000269|PubMed:22102614}. FT /FTId=VAR_067295. FT VARIANT 340 340 F -> S (in CRC, breast cancer and FT leukemia). {ECO:0000269|PubMed:10699937}. FT /FTId=VAR_043948. FT VARIANT 396 396 L -> V (associated with HNPCC5; unknown FT pathological significance; repair FT proficient; dbSNP:rs2020908). FT {ECO:0000269|PubMed:10537275, FT ECO:0000269|PubMed:22102614, FT ECO:0000269|Ref.4}. FT /FTId=VAR_012958. FT VARIANT 435 435 L -> P (mismatch repair deficient). FT {ECO:0000269|PubMed:22581703}. FT /FTId=VAR_068710. FT VARIANT 449 449 L -> P (in colorectal/endometrial cancer; FT unknown pathological significance). FT {ECO:0000269|PubMed:14961575}. FT /FTId=VAR_043949. FT VARIANT 468 468 R -> H (in dbSNP:rs41295268). FT {ECO:0000269|PubMed:18033691}. FT /FTId=VAR_038035. FT VARIANT 492 492 M -> V (associated with HNPCC5; unknown FT pathological significance; repair FT proficient). FT {ECO:0000269|PubMed:12658575, FT ECO:0000269|PubMed:17344846, FT ECO:0000269|PubMed:22102614}. FT /FTId=VAR_042275. FT VARIANT 503 503 S -> C (associated with HNPCC5; unknown FT pathological significance; repair FT proficient). FT {ECO:0000269|PubMed:18033691, FT ECO:0000269|PubMed:22102614}. FT /FTId=VAR_038036. FT VARIANT 509 509 V -> A. {ECO:0000269|PubMed:14520694}. FT /FTId=VAR_043950. FT VARIANT 522 522 Q -> R (in CRC; also associated with FT HNPCC5; repair proficient). FT {ECO:0000269|PubMed:11709755, FT ECO:0000269|PubMed:22102614}. FT /FTId=VAR_043951. FT VARIANT 538 538 Y -> S (in dbSNP:rs728619). FT /FTId=VAR_038037. FT VARIANT 566 566 G -> R (in CRC; partial functional loss). FT {ECO:0000269|PubMed:10537275}. FT /FTId=VAR_012959. FT VARIANT 580 580 S -> L (in dbSNP:rs41295270). FT {ECO:0000269|PubMed:18033691}. FT /FTId=VAR_038038. FT VARIANT 585 585 L -> P (mismatch repair deficient). FT {ECO:0000269|PubMed:22581703}. FT /FTId=VAR_068711. FT VARIANT 610 610 K -> N (associated with HNPCC5; unknown FT pathological significance; repair FT proficient). FT {ECO:0000269|PubMed:22102614}. FT /FTId=VAR_067296. FT VARIANT 619 619 E -> D (in CRC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15483016}. FT /FTId=VAR_043952. FT VARIANT 623 623 P -> A (in dbSNP:rs3136334). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_029244. FT VARIANT 623 623 P -> L (no impairment of FT heterodimerization with MSH2 and of in FT vitro mismatch repair capacity). FT {ECO:0000269|PubMed:15354210}. FT /FTId=VAR_043953. FT VARIANT 677 677 S -> T (mismatch repair proficient). FT {ECO:0000269|PubMed:22581703}. FT /FTId=VAR_068712. FT VARIANT 685 685 G -> A (in CRC). FT {ECO:0000269|PubMed:11470537}. FT /FTId=VAR_043954. FT VARIANT 698 698 Q -> E (in HNPCC; unknown pathological FT significance). FT {ECO:0000269|PubMed:10480359}. FT /FTId=VAR_012960. FT VARIANT 725 725 I -> M (in CRC; unknown pathological FT significance). FT {ECO:0000269|PubMed:11709755}. FT /FTId=VAR_043955. FT VARIANT 728 728 K -> T (no impairment of FT heterodimerization with MSH2 and of in FT vitro mismatch repair capacity; FT dbSNP:rs35552856). FT {ECO:0000269|PubMed:15354210}. FT /FTId=VAR_043956. FT VARIANT 772 772 R -> Q (in CRC). FT {ECO:0000269|PubMed:11470537}. FT /FTId=VAR_043957. FT VARIANT 772 772 R -> W (in HNPCC5). FT {ECO:0000269|PubMed:14974087}. FT /FTId=VAR_043958. FT VARIANT 787 787 A -> V (in CRC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15483016}. FT /FTId=VAR_043959. FT VARIANT 800 800 V -> A (in CRC; somatic mutation). FT {ECO:0000269|PubMed:11470537}. FT /FTId=VAR_043960. FT VARIANT 800 800 V -> L (may be a rare polymorphism). FT {ECO:0000269|PubMed:10537275}. FT /FTId=VAR_012961. FT VARIANT 803 803 D -> G (in CRC). FT {ECO:0000269|PubMed:10537275}. FT /FTId=VAR_012962. FT VARIANT 850 850 Y -> C (associated with HNPCC5 and CRC; FT unknown pathological significance; repair FT proficient). FT {ECO:0000269|PubMed:10521294, FT ECO:0000269|PubMed:11709755, FT ECO:0000269|PubMed:22102614}. FT /FTId=VAR_012963. FT VARIANT 854 854 K -> M (in CRC; unknown pathological FT significance; dbSNP:rs34374438). FT {ECO:0000269|PubMed:11470537, FT ECO:0000269|PubMed:14520694}. FT /FTId=VAR_043961. FT VARIANT 878 878 V -> A (in suspected HNPCC5, colorectal/ FT endometrial cancer and CRC; repair FT proficient; dbSNP:rs2020912). FT {ECO:0000269|PubMed:11153917, FT ECO:0000269|PubMed:11470537, FT ECO:0000269|PubMed:11586295, FT ECO:0000269|PubMed:11709755, FT ECO:0000269|PubMed:14520694, FT ECO:0000269|PubMed:15483016, FT ECO:0000269|PubMed:18033691, FT ECO:0000269|PubMed:22102614, FT ECO:0000269|PubMed:22581703}. FT /FTId=VAR_012964. FT VARIANT 886 886 I -> V (in dbSNP:rs2020914). FT {ECO:0000269|Ref.4}. FT /FTId=VAR_014902. FT VARIANT 901 901 R -> H (in colorectal/endometrial FT cancer). {ECO:0000269|PubMed:11153917}. FT /FTId=VAR_043962. FT VARIANT 976 976 R -> H (in CRC; sporadic; also associated FT with HNPCC5; repair proficient). FT {ECO:0000269|PubMed:11807791, FT ECO:0000269|PubMed:22102614}. FT /FTId=VAR_012965. FT VARIANT 1021 1021 A -> D (in CRC; unknown pathological FT significance; repair proficient). FT {ECO:0000269|PubMed:11709755, FT ECO:0000269|PubMed:22102614}. FT /FTId=VAR_043963. FT VARIANT 1026 1026 D -> Y (associated with HNPCC5; unknown FT pathological significance; repair FT proficient). FT {ECO:0000269|PubMed:22102614}. FT /FTId=VAR_067297. FT VARIANT 1031 1031 D -> V (in CRC; somatic mutation). FT {ECO:0000269|PubMed:11470537}. FT /FTId=VAR_043964. FT VARIANT 1076 1076 R -> C (in CRC; unknown pathological FT significance). FT {ECO:0000269|PubMed:15483016}. FT /FTId=VAR_043965. FT VARIANT 1087 1087 P -> S (associated with HNPCC5; unknown FT pathological significance; repair FT proficient; dbSNP:rs63750998). FT {ECO:0000269|PubMed:22102614}. FT /FTId=VAR_067298. FT VARIANT 1087 1087 P -> T (in CRC; dbSNP:rs63750998). FT {ECO:0000269|PubMed:10537275}. FT /FTId=VAR_012966. FT VARIANT 1095 1095 R -> H (in CRC; unknown pathological FT significance; mismatch repair FT proficient). FT {ECO:0000269|PubMed:12522549, FT ECO:0000269|PubMed:22581703}. FT /FTId=VAR_043966. FT VARIANT 1100 1100 T -> M (in CRC; unknown pathological FT significance). FT {ECO:0000269|PubMed:11709755}. FT /FTId=VAR_043967. FT VARIANT 1158 1158 C -> R (in CRC; somatic mutation). FT {ECO:0000269|PubMed:11470537}. FT /FTId=VAR_043968. FT VARIANT 1163 1163 E -> V (in HNPCC5; dbSNP:rs63750252). FT {ECO:0000269|PubMed:15365995}. FT /FTId=VAR_043969. FT VARIANT 1193 1193 E -> K (found in an endometrial cancer FT sample; displays marked impairment of FT heterodimerization with MSH2 and of in FT vitro mismatch repair capacity). FT {ECO:0000269|PubMed:15354210}. FT /FTId=VAR_043970. FT VARIANT 1213 1213 D -> V. {ECO:0000269|PubMed:7604266}. FT /FTId=VAR_004491. FT VARIANT 1219 1219 T -> I (in CRC; unknown pathological FT significance). FT {ECO:0000269|PubMed:11709755}. FT /FTId=VAR_043971. FT VARIANT 1225 1225 T -> M (associated with HNPCC5; unknown FT pathological significance; repair FT proficient). FT {ECO:0000269|PubMed:22102614}. FT /FTId=VAR_067299. FT VARIANT 1232 1232 V -> L (in dbSNP:rs41295276). FT {ECO:0000269|PubMed:18033691}. FT /FTId=VAR_038039. FT VARIANT 1234 1234 E -> Q (in dbSNP:rs35717727). FT /FTId=VAR_038040. FT VARIANT 1248 1248 H -> D (in CRC; unknown pathological FT significance). FT {ECO:0000269|PubMed:11709755}. FT /FTId=VAR_043972. FT VARIANT 1260 1260 V -> I. {ECO:0000269|PubMed:7604266}. FT /FTId=VAR_004492. FT VARIANT 1284 1284 T -> M (in CRC). FT {ECO:0000269|PubMed:10413423}. FT /FTId=VAR_043973. FT VARIANT 1321 1321 R -> G (in dbSNP:rs41295278). FT {ECO:0000269|PubMed:18033691}. FT /FTId=VAR_038041. FT VARIANT 1354 1354 L -> Q (in CRC; unknown pathological FT significance; mismatch repair FT proficient). FT {ECO:0000269|PubMed:12522549, FT ECO:0000269|PubMed:22581703}. FT /FTId=VAR_043974. FT MUTAGEN 103 103 Y->A: Abolishes binding to H3K36me3 and FT DNA mismatch repair activity. FT {ECO:0000269|PubMed:23622243}. FT MUTAGEN 105 106 WW->AA: Abolishes binding to H3K36me3 and FT DNA mismatch repair activity. FT {ECO:0000269|PubMed:23622243}. FT MUTAGEN 1140 1140 K->R: No effect on mismatch binding, FT complete loss of DNA repair function when FT associated with MSH2 mutant R-675. FT {ECO:0000269|PubMed:9564049}. FT CONFLICT 36 57 AAPGASPSPGGDAAWSEAGPGP -> GCPRGLSFPRRGCGL FT ERGWAWA (in Ref. 2; BAA23674/BAA23675). FT {ECO:0000305}. FT CONFLICT 868 868 M -> V (in Ref. 3; BAG65496). FT {ECO:0000305}. FT CONFLICT 1358 1360 KEL -> D (in Ref. 4; AAL87401). FT {ECO:0000305}. FT STRAND 74 79 {ECO:0000244|PDB:2GFU}. FT STRAND 94 98 {ECO:0000244|PDB:2GFU}. FT STRAND 106 109 {ECO:0000244|PDB:2GFU}. FT STRAND 120 125 {ECO:0000244|PDB:2GFU}. FT STRAND 127 133 {ECO:0000244|PDB:2GFU}. FT STRAND 135 137 {ECO:0000244|PDB:2GFU}. FT STRAND 139 143 {ECO:0000244|PDB:2GFU}. FT HELIX 145 147 {ECO:0000244|PDB:2GFU}. FT STRAND 148 151 {ECO:0000244|PDB:2GFU}. FT TURN 157 159 {ECO:0000244|PDB:2GFU}. FT HELIX 170 183 {ECO:0000244|PDB:2GFU}. FT HELIX 187 191 {ECO:0000244|PDB:2GFU}. FT TURN 192 195 {ECO:0000244|PDB:2GFU}. FT STRAND 197 199 {ECO:0000244|PDB:2GFU}. FT HELIX 366 369 {ECO:0000244|PDB:2O8B}. FT HELIX 371 373 {ECO:0000244|PDB:2O8B}. FT TURN 375 377 {ECO:0000244|PDB:2O8B}. FT HELIX 400 403 {ECO:0000244|PDB:2O8B}. FT HELIX 408 419 {ECO:0000244|PDB:2O8B}. FT STRAND 423 429 {ECO:0000244|PDB:2O8B}. FT STRAND 432 436 {ECO:0000244|PDB:2O8B}. FT HELIX 437 447 {ECO:0000244|PDB:2O8B}. FT STRAND 453 456 {ECO:0000244|PDB:2O8B}. FT STRAND 458 462 {ECO:0000244|PDB:2O8B}. FT HELIX 463 465 {ECO:0000244|PDB:2O8B}. FT HELIX 466 475 {ECO:0000244|PDB:2O8B}. FT STRAND 480 485 {ECO:0000244|PDB:2O8B}. FT HELIX 489 497 {ECO:0000244|PDB:2O8B}. FT HELIX 505 507 {ECO:0000244|PDB:2O8B}. FT STRAND 511 517 {ECO:0000244|PDB:2O8B}. FT HELIX 519 521 {ECO:0000244|PDB:2O8F}. FT STRAND 526 528 {ECO:0000244|PDB:2O8D}. FT STRAND 538 546 {ECO:0000244|PDB:2O8B}. FT STRAND 554 561 {ECO:0000244|PDB:2O8B}. FT TURN 563 565 {ECO:0000244|PDB:2O8B}. FT STRAND 568 575 {ECO:0000244|PDB:2O8B}. FT HELIX 580 588 {ECO:0000244|PDB:2O8B}. FT STRAND 591 597 {ECO:0000244|PDB:2O8B}. FT TURN 598 600 {ECO:0000244|PDB:2O8B}. FT HELIX 603 609 {ECO:0000244|PDB:2O8B}. FT TURN 610 615 {ECO:0000244|PDB:2O8B}. FT STRAND 616 621 {ECO:0000244|PDB:2O8B}. FT TURN 624 626 {ECO:0000244|PDB:2O8B}. FT HELIX 630 639 {ECO:0000244|PDB:2O8B}. FT TURN 640 643 {ECO:0000244|PDB:2O8B}. FT STRAND 644 647 {ECO:0000244|PDB:2O8B}. FT HELIX 657 661 {ECO:0000244|PDB:2O8B}. FT STRAND 667 669 {ECO:0000244|PDB:2O8F}. FT STRAND 671 673 {ECO:0000244|PDB:2O8B}. FT HELIX 675 677 {ECO:0000244|PDB:2O8B}. FT HELIX 678 693 {ECO:0000244|PDB:2O8B}. FT HELIX 697 701 {ECO:0000244|PDB:2O8B}. FT STRAND 706 708 {ECO:0000244|PDB:2O8B}. FT HELIX 712 715 {ECO:0000244|PDB:2O8B}. FT HELIX 737 742 {ECO:0000244|PDB:2O8B}. FT STRAND 746 748 {ECO:0000244|PDB:2O8F}. FT STRAND 750 753 {ECO:0000244|PDB:2O8B}. FT HELIX 758 762 {ECO:0000244|PDB:2O8B}. FT HELIX 768 779 {ECO:0000244|PDB:2O8B}. FT HELIX 785 799 {ECO:0000244|PDB:2O8B}. FT HELIX 802 812 {ECO:0000244|PDB:2O8B}. FT HELIX 818 829 {ECO:0000244|PDB:2O8B}. FT HELIX 831 836 {ECO:0000244|PDB:2O8B}. FT HELIX 838 841 {ECO:0000244|PDB:2O8B}. FT HELIX 847 879 {ECO:0000244|PDB:2O8B}. FT HELIX 885 890 {ECO:0000244|PDB:2O8B}. FT TURN 894 896 {ECO:0000244|PDB:2O8B}. FT STRAND 897 900 {ECO:0000244|PDB:2O8B}. FT HELIX 906 913 {ECO:0000244|PDB:2O8B}. FT HELIX 918 923 {ECO:0000244|PDB:2O8B}. FT HELIX 936 955 {ECO:0000244|PDB:2O8B}. FT HELIX 959 961 {ECO:0000244|PDB:2O8B}. FT STRAND 968 970 {ECO:0000244|PDB:2O8B}. FT HELIX 973 975 {ECO:0000244|PDB:2O8B}. FT STRAND 978 981 {ECO:0000244|PDB:2O8B}. FT TURN 983 986 {ECO:0000244|PDB:2O8B}. FT STRAND 995 999 {ECO:0000244|PDB:2O8B}. FT STRAND 1002 1005 {ECO:0000244|PDB:2O8B}. FT TURN 1008 1010 {ECO:0000244|PDB:2O8B}. FT HELIX 1011 1041 {ECO:0000244|PDB:2O8B}. FT HELIX 1044 1066 {ECO:0000244|PDB:2O8B}. FT STRAND 1070 1072 {ECO:0000244|PDB:2O8B}. FT TURN 1082 1084 {ECO:0000244|PDB:2O8B}. FT STRAND 1089 1094 {ECO:0000244|PDB:2O8B}. FT STRAND 1111 1116 {ECO:0000244|PDB:2O8B}. FT STRAND 1120 1122 {ECO:0000244|PDB:2O8F}. FT STRAND 1129 1133 {ECO:0000244|PDB:2O8B}. FT STRAND 1136 1138 {ECO:0000244|PDB:2O8F}. FT HELIX 1140 1154 {ECO:0000244|PDB:2O8B}. FT TURN 1155 1157 {ECO:0000244|PDB:2O8B}. FT STRAND 1160 1167 {ECO:0000244|PDB:2O8B}. FT STRAND 1171 1176 {ECO:0000244|PDB:2O8B}. FT HELIX 1189 1203 {ECO:0000244|PDB:2O8B}. FT STRAND 1209 1213 {ECO:0000244|PDB:2O8B}. FT TURN 1215 1218 {ECO:0000244|PDB:2O8B}. FT HELIX 1221 1237 {ECO:0000244|PDB:2O8B}. FT STRAND 1242 1246 {ECO:0000244|PDB:2O8B}. FT HELIX 1250 1255 {ECO:0000244|PDB:2O8B}. FT TURN 1256 1258 {ECO:0000244|PDB:2O8F}. FT STRAND 1260 1269 {ECO:0000244|PDB:2O8B}. FT STRAND 1285 1292 {ECO:0000244|PDB:2O8B}. FT HELIX 1298 1305 {ECO:0000244|PDB:2O8B}. FT HELIX 1310 1322 {ECO:0000244|PDB:2O8B}. FT TURN 1323 1326 {ECO:0000244|PDB:2O8F}. FT TURN 1330 1332 {ECO:0000244|PDB:2O8B}. SQ SEQUENCE 1360 AA; 152786 MW; 4A4AA9F8ECB8FFE9 CRC64; MSRQSTLYSF FPKSPALSDA NKASARASRE GGRAAAAPGA SPSPGGDAAW SEAGPGPRPL ARSASPPKAK NLNGGLRRSV APAAPTSCDF SPGDLVWAKM EGYPWWPCLV YNHPFDGTFI REKGKSVRVH VQFFDDSPTR GWVSKRLLKP YTGSKSKEAQ KGGHFYSAKP EILRAMQRAD EALNKDKIKR LELAVCDEPS EPEEEEEMEV GTTYVTDKSE EDNEIESEEE VQPKTQGSRR SSRQIKKRRV ISDSESDIGG SDVEFKPDTK EEGSSDEISS GVGDSESEGL NSPVKVARKR KRMVTGNGSL KRKSSRKETP SATKQATSIS SETKNTLRAF SAPQNSESQA HVSGGGDDSS RPTVWYHETL EWLKEEKRRD EHRRRPDHPD FDASTLYVPE DFLNSCTPGM RKWWQIKSQN FDLVICYKVG KFYELYHMDA LIGVSELGLV FMKGNWAHSG FPEIAFGRYS DSLVQKGYKV ARVEQTETPE MMEARCRKMA HISKYDRVVR REICRIITKG TQTYSVLEGD PSENYSKYLL SLKEKEEDSS GHTRAYGVCF VDTSLGKFFI GQFSDDRHCS RFRTLVAHYP PVQVLFEKGN LSKETKTILK SSLSCSLQEG LIPGSQFWDA SKTLRTLLEE EYFREKLSDG IGVMLPQVLK GMTSESDSIG LTPGEKSELA LSALGGCVFY LKKCLIDQEL LSMANFEEYI PLDSDTVSTT RSGAIFTKAY QRMVLDAVTL NNLEIFLNGT NGSTEGTLLE RVDTCHTPFG KRLLKQWLCA PLCNHYAIND RLDAIEDLMV VPDKISEVVE LLKKLPDLER LLSKIHNVGS PLKSQNHPDS RAIMYEETTY SKKKIIDFLS ALEGFKVMCK IIGIMEEVAD GFKSKILKQV ISLQTKNPEG RFPDLTVELN RWDTAFDHEK ARKTGLITPK AGFDSDYDQA LADIRENEQS LLEYLEKQRN RIGCRTIVYW GIGRNRYQLE IPENFTTRNL PEEYELKSTK KGCKRYWTKT IEKKLANLIN AEERRDVSLK DCMRRLFYNF DKNYKDWQSA VECIAVLDVL LCLANYSRGG DGPMCRPVIL LPEDTPPFLE LKGSRHPCIT KTFFGDDFIP NDILIGCEEE EQENGKAYCV LVTGPNMGGK STLMRQAGLL AVMAQMGCYV PAEVCRLTPI DRVFTRLGAS DRIMSGESTF FVELSETASI LMHATAHSLV LVDELGRGTA TFDGTAIANA VVKELAETIK CRTLFSTHYH SLVEDYSQNV AVRLGHMACM VENECEDPSQ ETITFLYKFI KGACPKSYGF NAARLANLPE EVIQKGHRKA REFEKMNQSL RLFREVCLAS ERSTVDAEAV HKLLTLIKEL // ID MSH6_YEAST Reviewed; 1242 AA. AC Q03834; D6VS82; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 11-NOV-2015, entry version 142. DE RecName: Full=DNA mismatch repair protein MSH6; DE AltName: Full=MutS protein homolog 6; DE AltName: Full=Postmeiotic segregation protein 3; GN Name=MSH6; Synonyms=PMS3; OrderedLocusNames=YDR097C; GN ORFNames=YD8557.04C; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169867; RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G., RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C., RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F., RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M., RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T., RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C., RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S., RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., RA Paulin L., Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., RA Prydz H., Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., RA Rieger M., Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., RA Scharfe M., Schmidt E.R., Schneider C., Scholler P., Schwarz S., RA Soler-Mira A., Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., RA Volckaert G., Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., RA Harris D.E., Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., RA Gentles S., Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., RA Niblett D., Odell C., Oliver K., Rajandream M.A., Richards C., RA Shore L., Walsh S.V., Barrell B.G., Dietrich F.S., Mulligan J.T., RA Allen E., Araujo R., Aviles E., Berno A., Carpenter J., Chen E., RA Cherry J.M., Chung E., Duncan M., Hunicke-Smith S., Hyman R.W., RA Komp C., Lashkari D., Lew H., Lin D., Mosedale D., Nakahara K., RA Namath A., Oefner P., Oh C., Petel F.X., Roberts D., Schramm S., RA Schroeder M., Shogren T., Shroff N., Winant A., Yelton M.A., RA Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R., RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., RA Greco T., Hallsworth K., Hawkins J., Hillier L.W., Jier M., RA Johnson D., Johnston L., Kirsten J., Kucaba T., Langston Y., RA Latreille P., Le T., Mardis E., Menezes S., Miller N., Nhan M., RA Pauley A., Peluso D., Rifkin L., Riles L., Taich A., Trevaskis E., RA Vignati D., Wilcox L., Wohldman P., Vaudin M., Wilson R., RA Waterston R., Albermann K., Hani J., Heumann K., Kleine K., RA Mewes H.-W., Zollner A., Zaccaria P.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV."; RL Nature 387:75-78(1997). RN [2] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., RA Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and RT now."; RL G3 (Bethesda) 4:389-398(2014). RN [3] RP CHARACTERIZATION. RX PubMed=8723353; DOI=10.1016/S0960-9822(02)00516-X; RA Iaccarino I., Palombo F., Drummond J.T., Totty N.F., Hsuan J.J., RA Modrich P., Jiricny J.; RT "MSH6, a Saccharomyces cerevisiae protein that binds to mismatches as RT a heterodimer with MSH2."; RL Curr. Biol. 6:484-486(1996). RN [4] RP FUNCTION, INTERACTION WITH MSH2, AND MUTAGENESIS OF GLY-421. RX PubMed=8600025; DOI=10.1101/gad.10.4.407; RA Marsischky G.T., Filosi N., Kane M.F., Kolodner R.D.; RT "Redundancy of Saccharomyces cerevisiae MSH3 and MSH6 in MSH2- RT dependent mismatch repair."; RL Genes Dev. 10:407-420(1996). RN [5] RP CHARACTERIZATION, AND INTERACTION WITH MSH2. RX PubMed=8816473; RA Alani E.; RT "The Saccharomyces cerevisiae Msh2 and Msh6 proteins form a complex RT that specifically binds to duplex oligonucleotides containing RT mismatched DNA base pairs."; RL Mol. Cell. Biol. 16:5604-5615(1996). RN [6] RP FUNCTION IN MMR. RX PubMed=9111357; RA Sia E.A., Kokoska R.J., Dominska M., Greenwell P., Petes T.D.; RT "Microsatellite instability in yeast: dependence on repeat unit size RT and DNA mismatch repair genes."; RL Mol. Cell. Biol. 17:2851-2858(1997). RN [7] RP FUNCTION, DNA-BINDING, AND COMPLEX FORMATION WITH MLH1-PMS1. RX PubMed=9545323; DOI=10.1074/jbc.273.16.9837; RA Habraken Y., Sung P., Prakash L., Prakash S.; RT "ATP-dependent assembly of a ternary complex consisting of a DNA RT mismatch and the yeast MSH2-MSH6 and MLH1-PMS1 protein complexes."; RL J. Biol. Chem. 273:9837-9841(1998). RN [8] RP MUTAGENESIS OF GLY-987. RX PubMed=9819445; RA Studamire B., Quach T., Alani E.; RT "Saccharomyces cerevisiae Msh2p and Msh6p ATPase activities are both RT required during mismatch repair."; RL Mol. Cell. Biol. 18:7590-7601(1998). RN [9] RP FUNCTION. RX PubMed=9770499; DOI=10.1073/pnas.95.21.12404; RA Flores-Rozas H., Kolodner R.D.; RT "The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent RT suppression of frameshift mutations."; RL Proc. Natl. Acad. Sci. U.S.A. 95:12404-12409(1998). RN [10] RP MUTAGENESIS OF LEU-301 AND GLY-477. RX PubMed=10537275; RA Kolodner R.D., Tytell J.D., Schmeits J.L., Kane M.F., Das Gupta R., RA Weger J., Wahlberg S., Fox E.A., Peel D., Ziogas A., Garber J.E., RA Syngal S., Anton-Culver H., Li F.P.; RT "Germ-line msh6 mutations in colorectal cancer families."; RL Cancer Res. 59:5068-5074(1999). RN [11] RP DNA-BINDING SPECIFICITY. RX PubMed=10066781; DOI=10.1074/jbc.274.11.7200; RA Marsischky G.T., Lee S., Griffith J., Kolodner R.D.; RT "Saccharomyces cerevisiae MSH2/6 complex interacts with Holliday RT junctions and facilitates their cleavage by phage resolution RT enzymes."; RL J. Biol. Chem. 274:7200-7206(1999). RN [12] RP MUTAGENESIS OF PHE-337. RX PubMed=10347163; DOI=10.1074/jbc.274.23.16115; RA Bowers J., Sokolsky T., Quach T., Alani E.; RT "A mutation in the MSH6 subunit of the Saccharomyces cerevisiae MSH2- RT MSH6 complex disrupts mismatch recognition."; RL J. Biol. Chem. 274:16115-16125(1999). RN [13] RP DNA-BINDING SPECIFICITY. RX PubMed=10480869; DOI=10.1074/jbc.274.38.26668; RA Marsischky G.T., Kolodner R.D.; RT "Biochemical characterization of the interaction between the RT Saccharomyces cerevisiae MSH2-MSH6 complex and mispaired bases in RT DNA."; RL J. Biol. Chem. 274:26668-26682(1999). RN [14] RP FUNCTION. RX PubMed=10518225; DOI=10.1016/S1097-2765(00)80346-9; RA Ni T.T., Marsischky G.T., Kolodner R.D.; RT "MSH2 and MSH6 are required for removal of adenine misincorporated RT opposite 8-oxo-guanine in S. cerevisiae."; RL Mol. Cell 4:439-444(1999). RN [15] RP INTERACTION WITH POL30, AND MUTAGENESIS OF 26-LYS-GLN-27 AND RP 33-PHE-PHE-34. RX PubMed=11005803; DOI=10.1074/jbc.C000513200; RA Clark A.B., Valle F., Drotschmann K., Gary R.K., Kunkel T.A.; RT "Functional interaction of proliferating cell nuclear antigen with RT MSH2-MSH6 and MSH2-MSH3 complexes."; RL J. Biol. Chem. 275:36498-36501(2000). RN [16] RP FUNCTION, AND MUTAGENESIS OF PHE-337. RX PubMed=10970737; DOI=10.1006/jmbi.2000.4081; RA Bowers J., Tran P.T., Liskay R.M., Alani E.; RT "Analysis of yeast MSH2-MSH6 suggests that the initiation of mismatch RT repair can be separated into discrete steps."; RL J. Mol. Biol. 302:327-338(2000). RN [17] RP MUTAGENESIS. RX PubMed=10615127; DOI=10.1038/71684; RA Das Gupta R., Kolodner R.D.; RT "Novel dominant mutations in Saccharomyces cerevisiae MSH6."; RL Nat. Genet. 24:53-56(2000). RN [18] RP INTERACTION WITH POL30, AND MUTAGENESIS OF 33-PHE-PHE-34. RX PubMed=11062484; DOI=10.1038/81708; RA Flores-Rozas H., Clark D., Kolodner R.D.; RT "Proliferating cell nuclear antigen and Msh2p-Msh6p interact to form RT an active mispair recognition complex."; RL Nat. Genet. 26:375-378(2000). RN [19] RP DNA-BINDING, AND MUTAGENESIS OF PRO-313; PHE-337; GLU-339; GLY-368; RP PRO-370; GLN-393; ARG-412; LYS-848 AND ARG-852. RX PubMed=11641390; DOI=10.1074/jbc.C100450200; RA Drotschmann K., Yang W., Brownewell F.E., Kool E.T., Kunkel T.A.; RT "Asymmetric recognition of DNA local distortion. Structure-based RT functional studies of eukaryotic Msh2-Msh6."; RL J. Biol. Chem. 276:46225-46229(2001). RN [20] RP FUNCTION, AND COMPLEX FORMATION WITH MLH1-PMS1. RX PubMed=11237611; DOI=10.1006/jmbi.2001.4467; RA Bowers J., Tran P.T., Joshi A., Liskay R.M., Alani E.; RT "MSH-MLH complexes formed at a DNA mismatch are disrupted by the PCNA RT sliding clamp."; RL J. Mol. Biol. 306:957-968(2001). RN [21] RP FUNCTION, AND MUTAGENESIS OF GLU-1062. RX PubMed=12509278; DOI=10.1016/S1568-7864(02)00081-2; RA Drotschmann K., Yang W., Kunkel T.A.; RT "Evidence for sequential action of two ATPase active sites in yeast RT Msh2-Msh6."; RL DNA Repair 1:743-753(2002). RN [22] RP MUTAGENESIS OF SER-1036; GLY-1067; HIS-1096 AND GLY-1142. RX PubMed=11986324; DOI=10.1074/jbc.M202282200; RA Hess M.T., Das Gupta R., Kolodner R.D.; RT "Dominant Saccharomyces cerevisiae msh6 mutations cause increased RT mispair binding and decreased dissociation from mispairs by Msh2-Msh6 RT in the presence of ATP."; RL J. Biol. Chem. 277:25545-25553(2002). RN [23] RP FUNCTION. RX PubMed=12820877; DOI=10.1021/bi034602h; RA Antony E., Hingorani M.M.; RT "Mismatch recognition-coupled stabilization of Msh2-Msh6 in an ATP- RT bound state at the initiation of DNA repair."; RL Biochemistry 42:7682-7693(2003). RN [24] RP INTERACTION WITH POL30. RX PubMed=12435741; DOI=10.1074/jbc.C200627200; RA Lau P.J., Kolodner R.D.; RT "Transfer of the MSH2.MSH6 complex from proliferating cell nuclear RT antigen to mispaired bases in DNA."; RL J. Biol. Chem. 278:14-17(2003). RN [25] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=14562095; DOI=10.1038/nature02026; RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., RA Weissman J.S., O'Shea E.K.; RT "Global analysis of protein localization in budding yeast."; RL Nature 425:686-691(2003). RN [26] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., RA Dephoure N., O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [27] RP ENZYME REGULATION, AND MUTAGENESIS OF GLU-1062. RX PubMed=15513922; DOI=10.1074/jbc.C400495200; RA Clark A.B., Kunkel T.A.; RT "Cadmium inhibits the functions of eukaryotic MutS complexes."; RL J. Biol. Chem. 279:53903-53906(2004). RN [28] RP FUNCTION, AND COMPLEX FORMATION WITH MLH1-PMS1. RX PubMed=15811858; DOI=10.1074/jbc.M407545200; RA Mendillo M.L., Mazur D.J., Kolodner R.D.; RT "Analysis of the interaction between the Saccharomyces cerevisiae RT MSH2-MSH6 and MLH1-PMS1 complexes with DNA using a reversible DNA end- RT blocking system."; RL J. Biol. Chem. 280:22245-22257(2005). RN [29] RP FUNCTION. RX PubMed=16337600; DOI=10.1016/j.molcel.2005.10.014; RA Jiang J., Bai L., Surtees J.A., Gemici Z., Wang M.D., Alani E.; RT "Detection of high-affinity and sliding clamp modes for MSH2-MSH6 by RT single-molecule unzipping force analysis."; RL Mol. Cell 20:771-781(2005). RN [30] RP ENZYME REGULATION. RX PubMed=15746000; DOI=10.1093/nar/gki291; RA Banerjee S., Flores-Rozas H.; RT "Cadmium inhibits mismatch repair by blocking the ATPase activity of RT the MSH2-MSH6 complex."; RL Nucleic Acids Res. 33:1410-1419(2005). RN [31] RP FUNCTION, AND MUTAGENESIS OF LYS-988 AND GLU-1062. RX PubMed=16214425; DOI=10.1016/j.dnarep.2005.08.016; RA Antony E., Khubchandani S., Chen S., Hingorani M.M.; RT "Contribution of Msh2 and Msh6 subunits to the asymmetric ATPase and RT DNA mismatch binding activities of Saccharomyces cerevisiae Msh2-Msh6 RT mismatch repair protein."; RL DNA Repair 5:153-162(2006). RN [32] RP FUNCTION. RX PubMed=16702432; DOI=10.1534/genetics.106.055616; RA Stone J.E., Petes T.D.; RT "Analysis of the proteins involved in the in vivo repair of base-base RT mismatches and four-base loops formed during meiotic recombination in RT the yeast Saccharomyces cerevisiae."; RL Genetics 173:1223-1239(2006). RN [33] RP FUNCTION, AND MUTAGENESIS OF LYS-988. RX PubMed=16600868; DOI=10.1016/j.molcel.2006.02.010; RA Mazur D.J., Mendillo M.L., Kolodner R.D.; RT "Inhibition of Msh6 ATPase activity by mispaired DNA induces a RT Msh2(ATP)-Msh6(ATP) state capable of hydrolysis-independent movement RT along DNA."; RL Mol. Cell 22:39-49(2006). RN [34] RP FUNCTION, AND MUTAGENESIS OF SER-1036; GLY-1067 AND GLY-1142. RX PubMed=16407100; DOI=10.1073/pnas.0510078103; RA Hess M.T., Mendillo M.L., Mazur D.J., Kolodner R.D.; RT "Biochemical basis for dominant mutations in the Saccharomyces RT cerevisiae MSH6 gene."; RL Proc. Natl. Acad. Sci. U.S.A. 103:558-563(2006). RN [35] RP FUNCTION, AND MUTAGENESIS OF GLU-339. RX PubMed=17141577; DOI=10.1016/j.dnarep.2006.10.023; RA Holmes S.F., Scarpinato K.D., McCulloch S.D., Schaaper R.M., RA Kunkel T.A.; RT "Specialized mismatch repair function of Glu339 in the Phe-X-Glu motif RT of yeast Msh6."; RL DNA Repair 6:293-303(2007). RN [36] RP FUNCTION. RX PubMed=17157869; DOI=10.1016/j.jmb.2006.10.099; RA Lee S.D., Surtees J.A., Alani E.; RT "Saccharomyces cerevisiae MSH2-MSH3 and MSH2-MSH6 complexes display RT distinct requirements for DNA binding domain I in mismatch RT recognition."; RL J. Mol. Biol. 366:53-66(2007). RN [37] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145 AND SER-150, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC STRAIN=ADR376; RX PubMed=17330950; DOI=10.1021/pr060559j; RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., RA Elias J.E., Gygi S.P.; RT "Large-scale phosphorylation analysis of alpha-factor-arrested RT Saccharomyces cerevisiae."; RL J. Proteome Res. 6:1190-1197(2007). RN [38] RP FUNCTION, AND DNA-BINDING DOMAIN. RX PubMed=17567610; DOI=10.1093/nar/gkm409; RA Clark A.B., Deterding L., Tomer K.B., Kunkel T.A.; RT "Multiple functions for the N-terminal region of Msh6."; RL Nucleic Acids Res. 35:4114-4123(2007). RN [39] RP FUNCTION. RX PubMed=17573527; DOI=10.1073/pnas.0704148104; RA Shell S.S., Putnam C.D., Kolodner R.D.; RT "Chimeric Saccharomyces cerevisiae Msh6 protein with an Msh3 mispair- RT binding domain combines properties of both proteins."; RL Proc. Natl. Acad. Sci. U.S.A. 104:10956-10961(2007). RN [40] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=17287358; DOI=10.1073/pnas.0607084104; RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L., RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.; RT "Analysis of phosphorylation sites on proteins from Saccharomyces RT cerevisiae by electron transfer dissociation (ETD) mass RT spectrometry."; RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007). RN [41] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-102; SER-145; SER-150 RP AND THR-451, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=18407956; DOI=10.1074/mcp.M700468-MCP200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth RT phosphoproteome analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [42] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145; SER-150 AND RP SER-201, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=19779198; DOI=10.1126/science.1172867; RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.; RT "Global analysis of Cdk1 substrate phosphorylation sites provides RT insights into evolution."; RL Science 325:1682-1686(2009). CC -!- FUNCTION: Component of the post-replicative DNA mismatch repair CC system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which CC binds to DNA mismatches thereby initiating DNA repair. MSH6 CC provides substrate-binding and substrate specificity to the CC complex. When bound, MutS alpha bends the DNA helix and shields CC approximately 20 base pairs. Acts mainly to repair base-base and CC single insertion-deletion mismatches that occur during CC replication, but can also repair longer insertion-deletion loops CC (IDLs), although with decreasing efficiency as the size of the CC extrahelical loop increases. After mismatch binding, forms a CC ternary complex with the MutL alpha heterodimer, which is thought CC to be responsible for directing the downstream MMR events, CC including strand discrimination, excision, and resynthesis. ATP CC binding and hydrolysis by the MutS alpha complex is crucial for CC MMR. Both subunits bind ATP, but with differing affinities, and CC their ATPase kinetics are also very different. MSH6 binds and CC hydrolyzes ATP rapidly, whereas MSH2 catalyzes ATP at a CC substantially slower rate. Binding to a mismatched base pair CC suppresses MSH6-catalyzed ATP hydrolysis, but not the activity of CC MSH2. ATP binding to both subunits is necessary to trigger a CC change in MutS alpha interaction with mismatched DNA, converting CC MutS alpha into a sliding clamp capable of hydrolysis-independent CC movement along DNA, and also facilitates formation of ternary CC complexes containing MutS and MutL proteins and the mismatch. May CC also be involved in resolution of recombination intermediates. CC {ECO:0000269|PubMed:10518225, ECO:0000269|PubMed:10970737, CC ECO:0000269|PubMed:11237611, ECO:0000269|PubMed:12509278, CC ECO:0000269|PubMed:12820877, ECO:0000269|PubMed:15811858, CC ECO:0000269|PubMed:16214425, ECO:0000269|PubMed:16337600, CC ECO:0000269|PubMed:16407100, ECO:0000269|PubMed:16600868, CC ECO:0000269|PubMed:16702432, ECO:0000269|PubMed:17141577, CC ECO:0000269|PubMed:17157869, ECO:0000269|PubMed:17567610, CC ECO:0000269|PubMed:17573527, ECO:0000269|PubMed:8600025, CC ECO:0000269|PubMed:9111357, ECO:0000269|PubMed:9545323, CC ECO:0000269|PubMed:9770499}. CC -!- ENZYME REGULATION: Inhibited by Cd(2+). CC {ECO:0000269|PubMed:15513922, ECO:0000269|PubMed:15746000}. CC -!- SUBUNIT: Heterodimer consisting of MSH2-MSH6 (MutS alpha). Forms a CC ternary complex with MutL alpha (MLH1-PMS1). MutS alpha interacts CC with proliferating cell nuclear antigen (PCNA/POL30). This CC interaction is disrupted upon binding of MutS alpha to mismatch CC DNA. {ECO:0000269|PubMed:11005803, ECO:0000269|PubMed:11062484, CC ECO:0000269|PubMed:12435741, ECO:0000269|PubMed:8600025, CC ECO:0000269|PubMed:8816473}. CC -!- INTERACTION: CC P25847:MSH2; NbExp=6; IntAct=EBI-11383, EBI-11352; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095}. CC -!- DOMAIN: The PIP box serves as a PCNA(POL30)-recognition and CC -binding motif. CC -!- MISCELLANEOUS: Present with 5330 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutS family. CC {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; Z47746; CAA87671.1; -; Genomic_DNA. DR EMBL; BK006938; DAA11942.1; -; Genomic_DNA. DR PIR; S51246; S51246. DR RefSeq; NP_010382.3; NM_001180405.3. DR ProteinModelPortal; Q03834; -. DR BioGrid; 32152; 60. DR DIP; DIP-2423N; -. DR IntAct; Q03834; 32. DR MINT; MINT-618151; -. DR MaxQB; Q03834; -. DR PeptideAtlas; Q03834; -. DR EnsemblFungi; YDR097C; YDR097C; YDR097C. DR GeneID; 851671; -. DR KEGG; sce:YDR097C; -. DR EuPathDB; FungiDB:YDR097C; -. DR SGD; S000002504; MSH6. DR GeneTree; ENSGT00550000075024; -. DR HOGENOM; HOG000189303; -. DR InParanoid; Q03834; -. DR KO; K08737; -. DR OMA; ALKDCMR; -. DR OrthoDB; EOG773XQH; -. DR BioCyc; YEAST:G3O-29700-MONOMER; -. DR Reactome; R-SCE-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha). DR NextBio; 969292; -. DR PRO; PR:Q03834; -. DR Proteomes; UP000002311; Chromosome IV. DR GO; GO:0032301; C:MutSalpha complex; IPI:SGD. DR GO; GO:0005524; F:ATP binding; IDA:SGD. DR GO; GO:0016887; F:ATPase activity; IDA:SGD. DR GO; GO:0000400; F:four-way junction DNA binding; IDA:SGD. DR GO; GO:0030983; F:mismatched DNA binding; IEA:InterPro. DR GO; GO:0036297; P:interstrand cross-link repair; IGI:SGD. DR GO; GO:0000710; P:meiotic mismatch repair; IMP:SGD. DR GO; GO:0006298; P:mismatch repair; IDA:SGD. DR Gene3D; 3.30.420.110; -; 1. DR Gene3D; 3.40.1170.10; -; 1. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR007695; DNA_mismatch_repair_MutS-lik_N. DR InterPro; IPR000432; DNA_mismatch_repair_MutS_C. DR InterPro; IPR007861; DNA_mismatch_repair_MutS_clamp. DR InterPro; IPR007696; DNA_mismatch_repair_MutS_core. DR InterPro; IPR016151; DNA_mismatch_repair_MutS_N. DR InterPro; IPR007860; DNA_mmatch_repair_MutS_con_dom. DR InterPro; IPR027417; P-loop_NTPase. DR Pfam; PF01624; MutS_I; 1. DR Pfam; PF05188; MutS_II; 1. DR Pfam; PF05192; MutS_III; 1. DR Pfam; PF05190; MutS_IV; 1. DR Pfam; PF00488; MutS_V; 1. DR SMART; SM00534; MUTSac; 1. DR SMART; SM00533; MUTSd; 1. DR SUPFAM; SSF48334; SSF48334; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR SUPFAM; SSF53150; SSF53150; 1. DR SUPFAM; SSF55271; SSF55271; 1. DR PROSITE; PS00486; DNA_MISMATCH_REPAIR_2; 1. PE 1: Evidence at protein level; KW ATP-binding; Complete proteome; DNA damage; DNA repair; DNA-binding; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1 1242 DNA mismatch repair protein MSH6. FT /FTId=PRO_0000115213. FT DNA_BIND 228 299 FT NP_BIND 982 989 ATP. {ECO:0000255}. FT REGION 305 421 Mispair-binding domain. FT MOTIF 27 34 PIP box. FT MOD_RES 102 102 Phosphoserine. FT {ECO:0000244|PubMed:18407956}. FT MOD_RES 145 145 Phosphoserine. FT {ECO:0000244|PubMed:17330950, FT ECO:0000244|PubMed:18407956, FT ECO:0000244|PubMed:19779198}. FT MOD_RES 150 150 Phosphoserine. FT {ECO:0000244|PubMed:17330950, FT ECO:0000244|PubMed:18407956, FT ECO:0000244|PubMed:19779198}. FT MOD_RES 201 201 Phosphoserine. FT {ECO:0000244|PubMed:19779198}. FT MOD_RES 451 451 Phosphothreonine. FT {ECO:0000244|PubMed:18407956}. FT MUTAGEN 26 27 KQ->AA: Partially functional in a FT mismatch repair assay; when associated FT with 33-AA-34. FT {ECO:0000269|PubMed:11005803}. FT MUTAGEN 33 34 FF->AA: Abolishes interaction with PCNA FT (POL30), but only causes a moderate FT mismatch repair defect. Partially FT functional in a mismatch repair assay; FT when associated with 26-AA-27. FT {ECO:0000269|PubMed:11005803, FT ECO:0000269|PubMed:11062484}. FT MUTAGEN 301 301 L->V: Fully functional in a mismatch FT repair assay. FT {ECO:0000269|PubMed:10537275}. FT MUTAGEN 313 313 P->A: Fully functional in a mismatch FT repair assay. FT {ECO:0000269|PubMed:11641390}. FT MUTAGEN 337 337 F->A: Shows defects in both homoduplex FT and mispair DNA binding and is only FT partially functional in a mismatch repair FT assay. {ECO:0000269|PubMed:10347163, FT ECO:0000269|PubMed:10970737, FT ECO:0000269|PubMed:11641390}. FT MUTAGEN 337 337 F->H,I,Y: Partially functional in a FT mismatch repair assay. FT {ECO:0000269|PubMed:10347163, FT ECO:0000269|PubMed:10970737, FT ECO:0000269|PubMed:11641390}. FT MUTAGEN 337 337 F->K: Completely abolishes mismatch FT repair. {ECO:0000269|PubMed:10347163, FT ECO:0000269|PubMed:10970737, FT ECO:0000269|PubMed:11641390}. FT MUTAGEN 337 337 F->S: In MSH6-6; partially functional in FT a mismatch repair assay. FT {ECO:0000269|PubMed:10347163, FT ECO:0000269|PubMed:10970737, FT ECO:0000269|PubMed:11641390}. FT MUTAGEN 339 339 E->A: Defective in repairing 8-oxo-G-A FT mismatches. {ECO:0000269|PubMed:11641390, FT ECO:0000269|PubMed:17141577}. FT MUTAGEN 340 343 LYEK->CFAE: In MSH6-340; shows defects in FT mispair DNA binding, but not in FT homoduplex DNA binding. FT {ECO:0000269|PubMed:10615127}. FT MUTAGEN 368 368 G->A: Moderately reduced activity in a FT mismatch repair assay. FT {ECO:0000269|PubMed:11641390}. FT MUTAGEN 370 370 P->A: Partially functional in a mismatch FT repair assay. FT {ECO:0000269|PubMed:11641390}. FT MUTAGEN 393 393 Q->A: Moderately reduced activity in a FT mismatch repair assay. FT {ECO:0000269|PubMed:11641390}. FT MUTAGEN 393 393 Q->R: In MSH6-5; partially functional in FT a mismatch repair assay. FT {ECO:0000269|PubMed:11641390}. FT MUTAGEN 412 412 R->A: Completely abolishes mismatch FT repair. {ECO:0000269|PubMed:11641390}. FT MUTAGEN 412 412 R->G: In MSH6-7; partially functional in FT a mismatch repair assay. FT {ECO:0000269|PubMed:11641390}. FT MUTAGEN 421 421 G->D: In PMS3-1; completely abolishes FT mismatch repair. FT {ECO:0000269|PubMed:8600025}. FT MUTAGEN 477 477 G->R: Partially functional in a mismatch FT repair assay. FT {ECO:0000269|PubMed:10537275}. FT MUTAGEN 848 848 K->A: Fully functional in a mismatch FT repair assay. FT {ECO:0000269|PubMed:11641390}. FT MUTAGEN 852 852 R->A: Moderately reduced activity in a FT mismatch repair assay. FT {ECO:0000269|PubMed:11641390}. FT MUTAGEN 987 987 G->D: Has no defect in mismatch DNA FT binding, but lacks ATP-induced FT conformational change. FT {ECO:0000269|PubMed:9819445}. FT MUTAGEN 988 988 K->A: Impairs ATP binding; reduces FT catalytic activity 13-fold for ATP FT hydrolysis. {ECO:0000269|PubMed:16214425, FT ECO:0000269|PubMed:16600868}. FT MUTAGEN 1036 1036 S->P: In MSH6-4; defective for ATP- FT induced sliding clamp formation and FT assembly of ternary complexes with MutL FT alpha. {ECO:0000269|PubMed:11986324, FT ECO:0000269|PubMed:16407100}. FT MUTAGEN 1062 1062 E->A: Reduces catalytic activity 13-fold FT for ATP hydrolysis. FT {ECO:0000269|PubMed:12509278, FT ECO:0000269|PubMed:15513922, FT ECO:0000269|PubMed:16214425}. FT MUTAGEN 1067 1067 G->D: In MSH6-3; defective for ATP- FT induced sliding clamp formation and FT assembly of ternary complexes with MutL FT alpha. {ECO:0000269|PubMed:11986324, FT ECO:0000269|PubMed:16407100}. FT MUTAGEN 1096 1096 H->A: In MSH6-9; shows normal mispair FT binding and dissociation, but fails to FT show complete mispair activation of the FT ATPase. {ECO:0000269|PubMed:11986324}. FT MUTAGEN 1142 1142 G->D: In MSH6-2; defective for ATP- FT induced sliding clamp formation, but FT assembles ternary complexes with MutL FT alpha. {ECO:0000269|PubMed:11986324, FT ECO:0000269|PubMed:16407100}. SQ SEQUENCE 1242 AA; 140080 MW; 11A6883AADCFA222 CRC64; MAPATPKTSK TAHFENGSTS SQKKMKQSSL LSFFSKQVPS GTPSKKVQKP TPATLENTAT DKITKNPQGG KTGKLFVDVD EDNDLTIAEE TVSTVRSDIM HSQEPQSDTM LNSNTTEPKS TTTDEDLSSS QSRRNHKRRV NYAESDDDDS DTTFTAKRKK GKVVDSESDE DEYLPDKNDG DEDDDIADDK EDIKGELAED SGDDDDLISL AETTSKKKFS YNTSHSSSPF TRNISRDNSK KKSRPNQAPS RSYNPSHSQP SATSKSSKFN KQNEERYQWL VDERDAQRRP KSDPEYDPRT LYIPSSAWNK FTPFEKQYWE IKSKMWDCIV FFKKGKFFEL YEKDALLANA LFDLKIAGGG RANMQLAGIP EMSFEYWAAQ FIQMGYKVAK VDQRESMLAK EMREGSKGIV KRELQCILTS GTLTDGDMLH SDLATFCLAI REEPGNFYNE TQLDSSTIVQ KLNTKIFGAA FIDTATGELQ MLEFEDDSEC TKLDTLMSQV RPMEVVMERN NLSTLANKIV KFNSAPNAIF NEVKAGEEFY DCDKTYAEII SSEYFSTEED WPEVLKSYYD TGKKVGFSAF GGLLYYLKWL KLDKNLISMK NIKEYDFVKS QHSMVLDGIT LQNLEIFSNS FDGSDKGTLF KLFNRAITPM GKRMMKKWLM HPLLRKNDIE SRLDSVDSLL QDITLREQLE ITFSKLPDLE RMLARIHSRT IKVKDFEKVI TAFETIIELQ DSLKNNDLKG DVSKYISSFP EGLVEAVKSW TNAFERQKAI NENIIVPQRG FDIEFDKSMD RIQELEDELM EILMTYRKQF KCSNIQYKDS GKEIYTIEIP ISATKNVPSN WVQMAANKTY KRYYSDEVRA LARSMAEAKE IHKTLEEDLK NRLCQKFDAH YNTIWMPTIQ AISNIDCLLA ITRTSEYLGA PSCRPTIVDE VDSKTNTQLN GFLKFKSLRH PCFNLGATTA KDFIPNDIEL GKEQPRLGLL TGANAAGKST ILRMACIAVI MAQMGCYVPC ESAVLTPIDR IMTRLGANDN IMQGKSTFFV ELAETKKILD MATNRSLLVV DELGRGGSSS DGFAIAESVL HHVATHIQSL GFFATHYGTL ASSFKHHPQV RPLKMSILVD EATRNVTFLY KMLEGQSEGS FGMHVASMCG ISKEIIDNAQ IAADNLEHTS RLVKERDLAA NNLNGEVVSV PGGLQSDFVR IAYGDGLKNT KLGSGEGVLN YDWNIKRNVL KSLFSIIDDL QS // ID RAD2_YEAST Reviewed; 1031 AA. AC P07276; D6VV38; E9P8X9; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1991, sequence version 2. DT 11-NOV-2015, entry version 159. DE RecName: Full=DNA repair protein RAD2; DE EC=3.1.-.-; GN Name=RAD2; OrderedLocusNames=YGR258C; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=3000874; DOI=10.1016/0378-1119(85)90177-5; RA Nicolet C.M., Chenevert J.M., Friedberg E.C.; RT "The RAD2 gene of Saccharomyces cerevisiae: nucleotide sequence and RT transcript mapping."; RL Gene 36:225-234(1985). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND SEQUENCE REVISION. RX PubMed=3011752; RA Madura K., Prakash S.; RT "Nucleotide sequence, transcript mapping, and regulation of the RAD2 RT gene of Saccharomyces cerevisiae."; RL J. Bacteriol. 166:914-923(1986). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169869; RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., RA Arroyo J., Backes U., Barreiros T., Bertani I., Bjourson A.J., RA Brueckner M., Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., RA Clemente M.L., Coblenz A., Coglievina M., Coissac E., Defoor E., RA Del Bino S., Delius H., Delneri D., de Wergifosse P., Dujon B., RA Durand P., Entian K.-D., Eraso P., Escribano V., Fabiani L., RA Fartmann B., Feroli F., Feuermann M., Frontali L., Garcia-Gonzalez M., RA Garcia-Saez M.I., Goffeau A., Guerreiro P., Hani J., Hansen M., RA Hebling U., Hernandez K., Heumann K., Hilger F., Hofmann B., RA Indge K.J., James C.M., Klima R., Koetter P., Kramer B., Kramer W., RA Lauquin G., Leuther H., Louis E.J., Maillier E., Marconi A., RA Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., RA Nawrocki A., Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., RA Paoluzi S., Plevani P., Portetelle D., Portillo F., Potier S., RA Purnelle B., Rieger M., Riles L., Rinaldi T., Robben J., RA Rodrigues-Pousada C., Rodriguez-Belmonte E., Rodriguez-Torres A.M., RA Rose M., Ruzzi M., Saliola M., Sanchez-Perez M., Schaefer B., RA Schaefer M., Scharfe M., Schmidheini T., Schreer A., Skala J., RA Souciet J.-L., Steensma H.Y., Talla E., Thierry A., Vandenbol M., RA van der Aart Q.J.M., Van Dyck L., Vanoni M., Verhasselt P., Voet M., RA Volckaert G., Wambutt R., Watson M.D., Weber N., Wedler E., Wedler H., RA Wipfli P., Wolf K., Wright L.F., Zaccaria P., Zimmermann M., RA Zollner A., Kleine K.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII."; RL Nature 387:81-84(1997). RN [4] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., RA Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and RT now."; RL G3 (Bethesda) 4:389-398(2014). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., RA Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., RA Williamson J., Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., RA Kolodner R.D., LaBaer J.; RT "Approaching a complete repository of sequence-verified protein- RT encoding clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-51. RC STRAIN=ATCC 96604 / S288c / FY1679; RX PubMed=9090059; RX DOI=10.1002/(SICI)1097-0061(19970315)13:3<287::AID-YEA75>3.0.CO;2-5; RA Clemente M.L., Sartori G., Cardazzo B., Carignani G.; RT "Analysis of an 11.6 kb region from the right arm of chromosome VII of RT Saccharomyces cerevisiae between the RAD2 and the MES1 genes reveals RT the presence of three new genes."; RL Yeast 13:287-290(1997). RN [7] RP FUNCTION. RX PubMed=8247134; DOI=10.1038/366365a0; RA Habraken Y., Sung P., Prakash L., Prakash S.; RT "Yeast excision repair gene RAD2 encodes a single-stranded DNA RT endonuclease."; RL Nature 366:365-368(1993). RN [8] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., RA Dephoure N., O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-583, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=18407956; DOI=10.1074/mcp.M700468-MCP200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth RT phosphoproteome analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-118 AND SER-367, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19779198; DOI=10.1126/science.1172867; RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.; RT "Global analysis of Cdk1 substrate phosphorylation sites provides RT insights into evolution."; RL Science 325:1682-1686(2009). CC -!- FUNCTION: Single-stranded DNA endonuclease involved in excision CC repair of DNA damaged with UV light, bulky adducts, or cross- CC linking agents. Essential for the incision step of excision- CC repair. {ECO:0000269|PubMed:8247134}. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC Note=Binds 2 magnesium ions per subunit. They probably participate CC in the reaction catalyzed by the enzyme. May bind an additional CC third magnesium ion after substrate binding. {ECO:0000250}; CC -!- INTERACTION: CC Q00416:SEN1; NbExp=3; IntAct=EBI-14757, EBI-16945; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- MISCELLANEOUS: Present with 846 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. XPG CC subfamily. {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M10275; AAA66928.1; -; Genomic_DNA. DR EMBL; Y07777; CAA69080.1; -; Genomic_DNA. DR EMBL; Z73043; CAA97287.1; -; Genomic_DNA. DR EMBL; BK006941; DAA08349.1; -; Genomic_DNA. DR EMBL; AY692857; AAT92876.1; -; Genomic_DNA. DR PIR; A29839; A29839. DR RefSeq; NP_011774.1; NM_001181387.1. DR PDB; 2LOX; NMR; -; B=642-690. DR PDB; 4Q0R; X-ray; 2.75 A; A/B=2-986. DR PDB; 4Q0W; X-ray; 2.10 A; A/B=2-986. DR PDB; 4Q0Z; X-ray; 2.40 A; A/B/E/F=2-986. DR PDB; 4Q10; X-ray; 2.70 A; A/B=2-986. DR PDBsum; 2LOX; -. DR PDBsum; 4Q0R; -. DR PDBsum; 4Q0W; -. DR PDBsum; 4Q0Z; -. DR PDBsum; 4Q10; -. DR ProteinModelPortal; P07276; -. DR SMR; P07276; 2-104, 762-983. DR BioGrid; 33510; 44. DR DIP; DIP-5869N; -. DR IntAct; P07276; 1. DR MINT; MINT-683829; -. DR MaxQB; P07276; -. DR PeptideAtlas; P07276; -. DR PRIDE; P07276; -. DR EnsemblFungi; YGR258C; YGR258C; YGR258C. DR GeneID; 853174; -. DR KEGG; sce:YGR258C; -. DR EuPathDB; FungiDB:YGR258C; -. DR SGD; S000003490; RAD2. DR GeneTree; ENSGT00640000091542; -. DR HOGENOM; HOG000214817; -. DR InParanoid; P07276; -. DR KO; K10846; -. DR OMA; FQATMRD; -. DR OrthoDB; EOG7QK0MK; -. DR BioCyc; YEAST:G3O-30928-MONOMER; -. DR Reactome; R-SCE-110302; Formation of transcription-coupled NER (TC-NER) repair complex. DR Reactome; R-SCE-110304; Dual incision reaction in TC-NER. DR Reactome; R-SCE-73935; Formation of incision complex in GG-NER. DR Reactome; R-SCE-73941; Dual incision reaction in GG-NER. DR NextBio; 973302; -. DR PRO; PR:P07276; -. DR Proteomes; UP000002311; Chromosome VII. DR GO; GO:0000112; C:nucleotide-excision repair factor 3 complex; IDA:SGD. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0003697; F:single-stranded DNA binding; IEA:InterPro. DR GO; GO:0000014; F:single-stranded DNA endodeoxyribonuclease activity; IDA:SGD. DR GO; GO:0006295; P:nucleotide-excision repair, DNA incision, 3'-to lesion; IDA:SGD. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IGI:SGD. DR Gene3D; 3.40.50.1010; -; 2. DR InterPro; IPR020045; 5-3_exonuclease_C. DR InterPro; IPR008918; HhH2. DR InterPro; IPR029060; PIN_domain-like. DR InterPro; IPR006086; XPG-I_dom. DR InterPro; IPR006084; XPG/Rad2. DR InterPro; IPR001044; XPG/Rad2_eukaryotes. DR InterPro; IPR019974; XPG_CS. DR InterPro; IPR006085; XPG_DNA_repair_N. DR Pfam; PF00867; XPG_I; 1. DR Pfam; PF00752; XPG_N; 1. DR PRINTS; PR00853; XPGRADSUPER. DR PRINTS; PR00066; XRODRMPGMNTG. DR SMART; SM00279; HhH2; 1. DR SMART; SM00484; XPGI; 1. DR SMART; SM00485; XPGN; 1. DR SUPFAM; SSF47807; SSF47807; 2. DR SUPFAM; SSF88723; SSF88723; 2. DR TIGRFAMs; TIGR00600; rad2; 1. DR PROSITE; PS00841; XPG_1; 1. DR PROSITE; PS00842; XPG_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Complete proteome; DNA damage; DNA repair; Endonuclease; KW Hydrolase; Magnesium; Metal-binding; Nuclease; Nucleus; KW Phosphoprotein; Reference proteome. FT CHAIN 1 1031 DNA repair protein RAD2. FT /FTId=PRO_0000154035. FT REGION 1 95 N-domain. FT REGION 756 884 I-domain. FT METAL 30 30 Magnesium 1. {ECO:0000250}. FT METAL 77 77 Magnesium 1. {ECO:0000250}. FT METAL 792 792 Magnesium 1. {ECO:0000250}. FT METAL 794 794 Magnesium 1. {ECO:0000250}. FT METAL 813 813 Magnesium 2. {ECO:0000250}. FT METAL 815 815 Magnesium 2. {ECO:0000250}. FT METAL 864 864 Magnesium 2. {ECO:0000250}. FT MOD_RES 118 118 Phosphoserine. FT {ECO:0000244|PubMed:19779198}. FT MOD_RES 367 367 Phosphoserine. FT {ECO:0000244|PubMed:19779198}. FT MOD_RES 583 583 Phosphoserine. FT {ECO:0000244|PubMed:18407956}. FT CONFLICT 782 782 F -> L (in Ref. 5; AAT92876). FT {ECO:0000305}. FT HELIX 6 10 {ECO:0000244|PDB:4Q0W}. FT HELIX 11 13 {ECO:0000244|PDB:4Q0W}. FT STRAND 15 18 {ECO:0000244|PDB:4Q0W}. FT HELIX 19 22 {ECO:0000244|PDB:4Q0W}. FT STRAND 26 30 {ECO:0000244|PDB:4Q0W}. FT HELIX 34 41 {ECO:0000244|PDB:4Q0W}. FT STRAND 45 49 {ECO:0000244|PDB:4Q0Z}. FT HELIX 53 67 {ECO:0000244|PDB:4Q0W}. FT STRAND 71 76 {ECO:0000244|PDB:4Q0W}. FT HELIX 82 96 {ECO:0000244|PDB:4Q0W}. FT STRAND 667 669 {ECO:0000244|PDB:2LOX}. FT HELIX 769 781 {ECO:0000244|PDB:4Q0W}. FT STRAND 786 788 {ECO:0000244|PDB:4Q0W}. FT HELIX 793 802 {ECO:0000244|PDB:4Q0W}. FT STRAND 807 810 {ECO:0000244|PDB:4Q0W}. FT HELIX 815 818 {ECO:0000244|PDB:4Q0W}. FT STRAND 823 827 {ECO:0000244|PDB:4Q0W}. FT STRAND 830 839 {ECO:0000244|PDB:4Q0W}. FT HELIX 840 847 {ECO:0000244|PDB:4Q0W}. FT HELIX 851 861 {ECO:0000244|PDB:4Q0W}. FT HELIX 874 884 {ECO:0000244|PDB:4Q0W}. FT HELIX 887 899 {ECO:0000244|PDB:4Q0W}. FT HELIX 901 904 {ECO:0000244|PDB:4Q0W}. FT HELIX 909 920 {ECO:0000244|PDB:4Q0W}. FT HELIX 932 939 {ECO:0000244|PDB:4Q0W}. FT HELIX 957 968 {ECO:0000244|PDB:4Q0W}. FT HELIX 972 982 {ECO:0000244|PDB:4Q0W}. SQ SEQUENCE 1031 AA; 117838 MW; 682D4AECFBD7F0F3 CRC64; MGVHSFWDIA GPTARPVRLE SLEDKRMAVD ASIWIYQFLK AVRDQEGNAV KNSHITGFFR RICKLLYFGI RPVFVFDGGV PVLKRETIRQ RKERRQGKRE SAKSTARKLL ALQLQNGSND NVKNSTPSSG SSVQIFKPQD EWDLPDIPGF KYDKEDARVN SNKTFEKLMN SINGDGLEDI DLDTINPASA EFEELPKATQ YLILSSLRLK SRLRMGYSKE QLETIFPNSM DFSRFQIDMV KRRNFFTQKL INTTGFQDGG ASKLNEEVIN RISGQKSKEY KLTKTNNGWI LGLGANDGSD AQKAIVIDDK DAGALVKQLD SNAEDGDVLR WDDLEDNSLK IVRHESSNAT TAPQKRSNRS EDEGCDSDEC EWEEVELKPK NVKFVEDFSL KAARLPYMGQ SLNNAGSKSF LDKRHDQASP SKTTPTMRIS RISVEDDDED YLKQIEEIEM MEAVQLSKME KKPEADDKSK IAKPVTSKGT EARPPIVQYG LLGAQPDSKQ PYHVTNLNSK SESVIKRTSK TVLSEFRPPS QQEDKGAILT EGEQNLNFIS HKIPQFDFNN ENSLLFQKNT ESNVSQEATK EKSPIPEMPS WFSSTASQQL YNPYNTTNFV EDKNVRNEQE SGAETTNKGS SYELLTGLNA TEILERESEK ESSNDENKDD DLEVLSEELF EDVPTKSQIS KEAEDNDSRK VESINKEHRK PLIFDYDFSE DEEDNIVENM IKEQEEFDTF KNTTLSTSAE RNVAENAFVE DELFEQQMKD KRDSDEVTMD MIKEVQELLS RFGIPYITAP MEAEAQCAEL LQLNLVDGII TDDSDVFLFG GTKIYKNMFH EKNYVEFYDA ESILKLLGLD RKNMIELAQL LGSDYTNGLK GMGPVSSIEV IAEFGNLKNF KDWYNNGQFD KRKQETENKF EKDLRKKLVN NEIILDDDFP SVMVYDAYMR PEVDHDTTPF VWGVPDLDML RSFMKTQLGW PHEKSDEILI PLIRDVNKRK KKGKQKRINE FFPREYISGD KKLNTSKRIS TATGKLKKRK M // ID RFC1_YEAST Reviewed; 861 AA. AC P38630; D6W2S3; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1994, sequence version 1. DT 11-NOV-2015, entry version 147. DE RecName: Full=Replication factor C subunit 1; DE Short=Replication factor C1; DE AltName: Full=Activator 1 95 kDa subunit; DE AltName: Full=Cell division control protein 44; GN Name=RFC1; Synonyms=CDC44; OrderedLocusNames=YOR217W; GN ORFNames=YOR50-7; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE, AND MUTAGENESIS OF ASP-427; GLY-436; GLY-512 AND RP ASP-513. RC STRAIN=ATCC 204508 / S288c; RX PubMed=8264593; RA Howell E.A., McAlear M.A., Rose D., Holm C.; RT "CDC44: a putative nucleotide-binding protein required for cell cycle RT progression that has homology to subunits of replication factor C."; RL Mol. Cell. Biol. 14:255-267(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND IDENTIFICATION IN THE RFC RP COMPLEX. RC STRAIN=ATCC 204508 / S288c; RX PubMed=7651383; RA Cullmann G., Fien K., Kobayashi R., Stillman B.; RT "Characterization of the five replication factor C genes of RT Saccharomyces cerevisiae."; RL Mol. Cell. Biol. 15:4661-4671(1995). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 96604 / S288c / FY1679; RX PubMed=8840505; RX DOI=10.1002/(SICI)1097-0061(199607)12:9<877::AID-YEA969>3.0.CO;2-S; RA Galisson F., Dujon B.; RT "Sequence and analysis of a 33 kb fragment from the right arm of RT chromosome XV of the yeast Saccharomyces cerevisiae."; RL Yeast 12:877-885(1996). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169874; RA Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., RA Arino J., Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., RA Boyer J., Camasses A., Casamayor A., Casas C., Cheret G., RA Cziepluch C., Daignan-Fornier B., Dang V.-D., de Haan M., Delius H., RA Durand P., Fairhead C., Feldmann H., Gaillon L., Galisson F., RA Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E., Grivell L.A., RA Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U., RA Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B., RA Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A., RA Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., RA Maarse A.C., Madania A., Mannhaupt G., Marck C., Martin R.P., RA Mewes H.-W., Michaux G., Paces V., Parle-McDermott A.G., Pearson B.M., RA Perrin A., Pettersson B., Poch O., Pohl T.M., Poirey R., RA Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rechmann S., RA Schwager C., Schweizer M., Sor F., Sterky F., Tarassov I.A., RA Teodoru C., Tettelin H., Thierry A., Tobiasch E., Tzermia M., RA Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I., Vlcek C., RA Voet M., Volckaert G., Voss H., Wambutt R., Wedler H., Wiemann S., RA Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XV."; RL Nature 387:98-102(1997). RN [5] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., RA Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and RT now."; RL G3 (Bethesda) 4:389-398(2014). RN [6] RP INTERACTION WITH POL30. RX PubMed=14530260; DOI=10.1074/jbc.M309206200; RA Yao N., Coryell L., Zhang D., Georgescu R.E., Finkelstein J., RA Coman M.M., Hingorani M.M., O'Donnell M.; RT "Replication factor C clamp loader subunit arrangement within the RT circular pentamer and its attachment points to proliferating cell RT nuclear antigen."; RL J. Biol. Chem. 278:50744-50753(2003). RN [7] RP INTERACTION WITH ECO1. RX PubMed=12665596; DOI=10.1128/MCB.23.8.2999-3007.2003; RA Kenna M.A., Skibbens R.V.; RT "Mechanical link between cohesion establishment and DNA replication: RT Ctf7p/Eco1p, a cohesion establishment factor, associates with three RT different replication factor C complexes."; RL Mol. Cell. Biol. 23:2999-3007(2003). RN [8] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., RA Dephoure N., O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [9] RP IDENTIFICATION IN THE RFC COMPLEX. RX PubMed=15964801; DOI=10.1128/MCB.25.13.5445-5455.2005; RA Bylund G.O., Burgers P.M.; RT "Replication protein A-directed unloading of PCNA by the Ctf18 RT cohesion establishment complex."; RL Mol. Cell. Biol. 25:5445-5455(2005). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-38 AND SER-40, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC STRAIN=ADR376; RX PubMed=17330950; DOI=10.1021/pr060559j; RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J., RA Elias J.E., Gygi S.P.; RT "Large-scale phosphorylation analysis of alpha-factor-arrested RT Saccharomyces cerevisiae."; RL J. Proteome Res. 6:1190-1197(2007). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-38 AND SER-40, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=18407956; DOI=10.1074/mcp.M700468-MCP200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth RT phosphoproteome analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-38; SER-40 AND THR-63, RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19779198; DOI=10.1126/science.1172867; RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.; RT "Global analysis of Cdk1 substrate phosphorylation sites provides RT insights into evolution."; RL Science 325:1682-1686(2009). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 295-785 IN COMPLEX WITH AN RP ATP ANALOG; RCF2; RCF3; RCF4; RCF5 AND PCNA. RX PubMed=15201901; DOI=10.1038/nature02585; RA Bowman G.D., O'Donnell M., Kuriyan J.; RT "Structural analysis of a eukaryotic sliding DNA clamp-clamp loader RT complex."; RL Nature 429:724-730(2004). CC -!- FUNCTION: Component of the ATP-dependent clamp loader RFC complex CC for the POL30/PCNA homotrimer DNA clamp. During a clamp loading CC circle, the RFC:clamp complex binds to DNA and the recognition of CC the double-stranded/single-stranded junction stimulates ATP CC hydrolysis by RFC. The complex presumably provides bipartite ATP CC sites in which one subunit supplies a catalytic site for CC hydrolysis of ATP bound to the neighboring subunit. Dissociation CC of RFC from the clamp leaves the clamp encircling DNA. Replication CC factor C (RFC or activator 1) complex acts during elongation of CC primed DNA templates by DNA polymerase delta and epsilon. RFC has CC an essential but redundant activity in sister chromatid cohesion CC establishment. CC -!- SUBUNIT: Replication factor C (RFC) is a heteropentamer of CC subunits RFC1, RFC2, RFC3, RFC4 and RFC5 and forms a complex with CC POL30/PCNA in the presence of ATP. Interacts with ECO1 and CC POL30/PCNA. {ECO:0000269|PubMed:12665596, CC ECO:0000269|PubMed:14530260, ECO:0000269|PubMed:15201901, CC ECO:0000269|PubMed:15964801, ECO:0000269|PubMed:7651383}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. CC -!- MISCELLANEOUS: Present with 2360 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the activator 1 large subunit family. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 BRCT domain. {ECO:0000255|PROSITE- CC ProRule:PRU00033}. 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; U03102; AAC48916.1; -; Unassigned_DNA. DR EMBL; U26027; AAC49060.1; -; Genomic_DNA. DR EMBL; X92441; CAA63180.1; -; Genomic_DNA. DR EMBL; Z75125; CAA99434.1; -; Genomic_DNA. DR EMBL; BK006948; DAA10989.1; -; Genomic_DNA. DR PIR; S44763; S44763. DR RefSeq; NP_014860.1; NM_001183636.1. DR PDB; 1SXJ; X-ray; 2.85 A; A=295-785. DR PDBsum; 1SXJ; -. DR ProteinModelPortal; P38630; -. DR SMR; P38630; 151-243, 298-554. DR BioGrid; 34612; 61. DR DIP; DIP-2527N; -. DR IntAct; P38630; 12. DR MINT; MINT-619267; -. DR MaxQB; P38630; -. DR PeptideAtlas; P38630; -. DR EnsemblFungi; YOR217W; YOR217W; YOR217W. DR GeneID; 854392; -. DR KEGG; sce:YOR217W; -. DR EuPathDB; FungiDB:YOR217W; -. DR SGD; S000005743; RFC1. DR GeneTree; ENSGT00730000111066; -. DR HOGENOM; HOG000164552; -. DR InParanoid; P38630; -. DR KO; K10754; -. DR OMA; AHSHILA; -. DR OrthoDB; EOG7BGHVG; -. DR BioCyc; YEAST:G3O-33719-MONOMER; -. DR Reactome; R-SCE-109977; Repair synthesis for gap-filling by DNA polymerase in TC-NER. DR Reactome; R-SCE-110312; Translesion synthesis by REV1. DR Reactome; R-SCE-110320; Translesion Synthesis by POLH. DR Reactome; R-SCE-174411; Polymerase switching on the C-strand of the telomere. DR Reactome; R-SCE-5655862; Translesion synthesis by POLK. DR Reactome; R-SCE-5656121; Translesion synthesis by POLI. DR Reactome; R-SCE-5656169; Termination of translesion DNA synthesis. DR Reactome; R-SCE-69091; Polymerase switching. DR EvolutionaryTrace; P38630; -. DR NextBio; 976553; -. DR PRO; PR:P38630; -. DR Proteomes; UP000002311; Chromosome XV. DR GO; GO:0005663; C:DNA replication factor C complex; IDA:SGD. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0003689; F:DNA clamp loader activity; IEA:InterPro. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0006281; P:DNA repair; IMP:SGD. DR GO; GO:0006272; P:leading strand elongation; IDA:SGD. DR GO; GO:0006298; P:mismatch repair; IGI:SGD. DR GO; GO:0000278; P:mitotic cell cycle; IMP:SGD. DR Gene3D; 3.40.50.10190; -; 1. DR Gene3D; 3.40.50.300; -; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR003959; ATPase_AAA_core. DR InterPro; IPR001357; BRCT_dom. DR InterPro; IPR008921; DNA_pol3_clamp-load_cplx_C. DR InterPro; IPR013725; DNA_replication_fac_RFC1_C. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR012178; RFC1. DR Pfam; PF00004; AAA; 1. DR Pfam; PF00533; BRCT; 1. DR Pfam; PF08519; RFC1; 1. DR PIRSF; PIRSF036578; RFC1; 1. DR SMART; SM00382; AAA; 1. DR SMART; SM00292; BRCT; 1. DR SUPFAM; SSF48019; SSF48019; 1. DR SUPFAM; SSF52113; SSF52113; 1. DR SUPFAM; SSF52540; SSF52540; 1. DR PROSITE; PS50172; BRCT; 1. PE 1: Evidence at protein level; KW 3D-structure; ATP-binding; Cell cycle; Cell division; KW Complete proteome; DNA replication; DNA-binding; Nucleotide-binding; KW Nucleus; Phosphoprotein; Reference proteome. FT CHAIN 1 861 Replication factor C subunit 1. FT /FTId=PRO_0000121776. FT DOMAIN 153 243 BRCT. {ECO:0000255|PROSITE- FT ProRule:PRU00033}. FT NP_BIND 353 361 ATP. FT MOTIF 830 834 Nuclear localization signal. FT {ECO:0000255}. FT MOTIF 855 860 Nuclear localization signal. FT {ECO:0000255}. FT BINDING 299 299 ATP; via carbonyl oxygen. FT BINDING 311 311 ATP; via amide nitrogen and carbonyl FT oxygen. FT BINDING 456 456 ATP. FT MOD_RES 38 38 Phosphothreonine. FT {ECO:0000244|PubMed:17330950, FT ECO:0000244|PubMed:18407956, FT ECO:0000244|PubMed:19779198}. FT MOD_RES 40 40 Phosphoserine. FT {ECO:0000244|PubMed:17330950, FT ECO:0000244|PubMed:18407956, FT ECO:0000244|PubMed:19779198}. FT MOD_RES 63 63 Phosphothreonine. FT {ECO:0000244|PubMed:19779198}. FT MUTAGEN 427 427 D->H: In cs mutant CDC44-2; causes cell FT cycle arrest. FT {ECO:0000269|PubMed:8264593}. FT MUTAGEN 436 436 G->R: In cs mutant CDC44-3/4; causes cell FT cycle arrest. FT {ECO:0000269|PubMed:8264593}. FT MUTAGEN 512 512 G->A: In cs mutant CDC44-9; no effect. FT {ECO:0000269|PubMed:8264593}. FT MUTAGEN 513 513 D->N: In cs mutants CDC44-1/5/8 and FT CDC44-9; causes cell cycle arrest. FT {ECO:0000269|PubMed:8264593}. FT HELIX 298 301 {ECO:0000244|PDB:1SXJ}. FT HELIX 307 309 {ECO:0000244|PDB:1SXJ}. FT HELIX 314 325 {ECO:0000244|PDB:1SXJ}. FT HELIX 327 332 {ECO:0000244|PDB:1SXJ}. FT TURN 333 335 {ECO:0000244|PDB:1SXJ}. FT STRAND 347 352 {ECO:0000244|PDB:1SXJ}. FT HELIX 359 369 {ECO:0000244|PDB:1SXJ}. FT STRAND 373 377 {ECO:0000244|PDB:1SXJ}. FT HELIX 385 390 {ECO:0000244|PDB:1SXJ}. FT HELIX 392 395 {ECO:0000244|PDB:1SXJ}. FT TURN 402 406 {ECO:0000244|PDB:1SXJ}. FT STRAND 418 423 {ECO:0000244|PDB:1SXJ}. FT HELIX 426 428 {ECO:0000244|PDB:1SXJ}. FT HELIX 436 446 {ECO:0000244|PDB:1SXJ}. FT STRAND 451 456 {ECO:0000244|PDB:1SXJ}. FT HELIX 464 466 {ECO:0000244|PDB:1SXJ}. FT TURN 467 469 {ECO:0000244|PDB:1SXJ}. FT STRAND 470 474 {ECO:0000244|PDB:1SXJ}. FT HELIX 480 493 {ECO:0000244|PDB:1SXJ}. FT HELIX 502 509 {ECO:0000244|PDB:1SXJ}. FT TURN 510 512 {ECO:0000244|PDB:1SXJ}. FT HELIX 514 521 {ECO:0000244|PDB:1SXJ}. FT HELIX 523 527 {ECO:0000244|PDB:1SXJ}. FT HELIX 535 544 {ECO:0000244|PDB:1SXJ}. FT TURN 545 548 {ECO:0000244|PDB:1SXJ}. FT HELIX 550 558 {ECO:0000244|PDB:1SXJ}. FT HELIX 561 563 {ECO:0000244|PDB:1SXJ}. FT HELIX 568 570 {ECO:0000244|PDB:1SXJ}. FT HELIX 574 581 {ECO:0000244|PDB:1SXJ}. FT TURN 585 587 {ECO:0000244|PDB:1SXJ}. FT HELIX 588 595 {ECO:0000244|PDB:1SXJ}. FT STRAND 596 602 {ECO:0000244|PDB:1SXJ}. FT HELIX 610 631 {ECO:0000244|PDB:1SXJ}. FT HELIX 638 640 {ECO:0000244|PDB:1SXJ}. FT HELIX 641 648 {ECO:0000244|PDB:1SXJ}. FT HELIX 650 654 {ECO:0000244|PDB:1SXJ}. FT HELIX 669 687 {ECO:0000244|PDB:1SXJ}. FT TURN 688 692 {ECO:0000244|PDB:1SXJ}. FT HELIX 699 703 {ECO:0000244|PDB:1SXJ}. FT TURN 704 706 {ECO:0000244|PDB:1SXJ}. FT HELIX 707 714 {ECO:0000244|PDB:1SXJ}. FT HELIX 725 730 {ECO:0000244|PDB:1SXJ}. FT TURN 731 733 {ECO:0000244|PDB:1SXJ}. FT HELIX 737 746 {ECO:0000244|PDB:1SXJ}. SQ SEQUENCE 861 AA; 94903 MW; A7D9208D66DD9A98 CRC64; MVNISDFFGK NKKSVRSSTS RPTRQVGSSK PEVIDLDTES DQESTNKTPK KMPVSNVIDV SETPEGEKKL PLPAKRKASS PTVKPASSKK TKPSSKSSDS ASNITAQDVL DKIPSLDLSN VHVKENAKFD FKSANSNADP DEIVSEIGSF PEGKPNCLLG LTIVFTGVLP TLERGASEAL AKRYGARVTK SISSKTSVVV LGDEAGPKKL EKIKQLKIKA IDEEGFKQLI AGMPAEGGDG EAAEKARRKL EEQHNIATKE AELLVKKEEE RSKKLAATRV SGGHLERDNV VREEDKLWTV KYAPTNLQQV CGNKGSVMKL KNWLANWENS KKNSFKHAGK DGSGVFRAAM LYGPPGIGKT TAAHLVAQEL GYDILEQNAS DVRSKTLLNA GVKNALDNMS VVGYFKHNEE AQNLNGKHFV IIMDEVDGMS GGDRGGVGQL AQFCRKTSTP LILICNERNL PKMRPFDRVC LDIQFRRPDA NSIKSRLMTI AIREKFKLDP NVIDRLIQTT RGDIRQVINL LSTISTTTKT INHENINEIS KAWEKNIALK PFDIAHKMLD GQIYSDIGSR NFTLNDKIAL YFDDFDFTPL MIQENYLSTR PSVLKPGQSH LEAVAEAANC ISLGDIVEKK IRSSEQLWSL LPLHAVLSSV YPASKVAGHM AGRINFTAWL GQNSKSAKYY RLLQEIHYHT RLGTSTDKIG LRLDYLPTFR KRLLDPFLKQ GADAISSVIE VMDDYYLTKE DWDSIMEFFV GPDVTTAIIK KIPATVKSGF TRKYNSMTHP VAIYRTGSTI GGGGVGTSTS TPDFEDVVDA DDNPVPADDE ETQDSSTDLK KDKLIKQKAK PTKRKTATSK PGGSKKRKTK A // ID RRM3_YEAST Reviewed; 723 AA. AC P38766; D3DKX8; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 1. DT 11-NOV-2015, entry version 130. DE RecName: Full=ATP-dependent DNA helicase RRM3 {ECO:0000255|HAMAP-Rule:MF_03177}; DE EC=3.6.4.12 {ECO:0000255|HAMAP-Rule:MF_03177}; DE AltName: Full=Regulation of Ty1 transposition protein 104; DE AltName: Full=rDNA recombination mutation protein 3 {ECO:0000255|HAMAP-Rule:MF_03177}; GN Name=RRM3 {ECO:0000255|HAMAP-Rule:MF_03177}; Synonyms=RTT104; GN OrderedLocusNames=YHR031C; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=8091229; DOI=10.1126/science.8091229; RA Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., RA Du Z., Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., RA Kucaba T., Hillier L.W., Jier M., Johnston L., Langston Y., RA Latreille P., Louis E.J., Macri C., Mardis E., Menezes S., Mouser L., RA Nhan M., Rifkin L., Riles L., St Peter H., Trevaskis E., Vaughan K., RA Vignati D., Wilcox L., Wohldman P., Waterston R., Wilson R., RA Vaudin M.; RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome RT VIII."; RL Science 265:2077-2082(1994). RN [2] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., RA Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and RT now."; RL G3 (Bethesda) 4:389-398(2014). RN [3] RP FUNCTION. RX PubMed=8293975; RA Keil R.L., McWilliams A.D.; RT "A gene with specific and global effects on recombination of sequences RT from tandemly repeated genes in Saccharomyces cerevisiae."; RL Genetics 135:711-718(1993). RN [4] RP FUNCTION. RX PubMed=10693764; DOI=10.1016/S0092-8674(00)80683-2; RA Ivessa A.S., Zhou J.-Q., Zakian V.A.; RT "The Saccharomyces Pif1p DNA helicase and the highly related Rrm3p RT have opposite effects on replication fork progression in ribosomal RT DNA."; RL Cell 100:479-489(2000). RN [5] RP FUNCTION. RX PubMed=11779788; RA Scholes D.T., Banerjee M., Bowen B., Curcio M.J.; RT "Multiple regulators of Ty1 transposition in Saccharomyces cerevisiae RT have conserved roles in genome maintenance."; RL Genetics 159:1449-1465(2001). RN [6] RP FUNCTION, AND DNA-BINDING. RX PubMed=12050116; DOI=10.1101/gad.982902; RA Ivessa A.S., Zhou J.Q., Schulz V.P., Monson E.K., Zakian V.A.; RT "Saccharomyces Rrm3p, a 5' to 3' DNA helicase that promotes RT replication fork progression through telomeric and subtelomeric DNA."; RL Genes Dev. 16:1383-1396(2002). RN [7] RP INTERACTION WITH POL30, AND MUTAGENESIS OF PHE-41 AND PHE-42. RX PubMed=12239216; DOI=10.1074/jbc.M207263200; RA Schmidt K.H., Derry K.L., Kolodner R.D.; RT "Saccharomyces cerevisiae RRM3, a 5' to 3' DNA helicase, physically RT interacts with proliferating cell nuclear antigen."; RL J. Biol. Chem. 277:45331-45337(2002). RN [8] RP FUNCTION. RX PubMed=12686542; DOI=10.1074/jbc.M301610200; RA Weitao T., Budd M., Hoopes L.L., Campbell J.L.; RT "Dna2 helicase/nuclease causes replicative fork stalling and double- RT strand breaks in the ribosomal DNA of Saccharomyces cerevisiae."; RL J. Biol. Chem. 278:22513-22522(2003). RN [9] RP FUNCTION. RX PubMed=14690605; DOI=10.1016/S1097-2765(03)00456-8; RA Ivessa A.S., Lenzmeier B.A., Bessler J.B., Goudsouzian L.K., RA Schnakenberg S.L., Zakian V.A.; RT "The Saccharomyces cerevisiae helicase Rrm3p facilitates replication RT past nonhistone protein-DNA complexes."; RL Mol. Cell 12:1525-1536(2003). RN [10] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., RA Dephoure N., O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [11] RP FUNCTION. RX PubMed=15037547; DOI=10.1101/gad.1154704; RA Torres J.Z., Bessler J.B., Zakian V.A.; RT "Local chromatin structure at the ribosomal DNA causes replication RT fork pausing and genome instability in the absence of the S. RT cerevisiae DNA helicase Rrm3p."; RL Genes Dev. 18:498-503(2004). RN [12] RP FUNCTION, AND DOMAIN. RX PubMed=15579680; DOI=10.1534/genetics.104.028035; RA Bessler J.B., Zakian V.A.; RT "The amino terminus of the Saccharomyces cerevisiae DNA helicase Rrm3p RT modulates protein function altering replication and checkpoint RT activity."; RL Genetics 168:1205-1218(2004). RN [13] RP FUNCTION. RX PubMed=15060144; DOI=10.1128/MCB.24.8.3198-3212.2004; RA Torres J.Z., Schnakenberg S.L., Zakian V.A.; RT "Saccharomyces cerevisiae Rrm3p DNA helicase promotes genome integrity RT by preventing replication fork stalling: viability of rrm3 cells RT requires the intra-S-phase checkpoint and fork restart activities."; RL Mol. Cell. Biol. 24:3198-3212(2004). RN [14] RP FUNCTION. RX PubMed=15060145; DOI=10.1128/MCB.24.8.3213-3226.2004; RA Schmidt K.H., Kolodner R.D.; RT "Requirement of Rrm3 helicase for repair of spontaneous DNA lesions in RT cells lacking Srs2 or Sgs1 helicase."; RL Mol. Cell. Biol. 24:3213-3226(2004). RN [15] RP FUNCTION. RX PubMed=15082794; DOI=10.1128/MCB.24.9.4019-4031.2004; RA Makovets S., Herskowitz I., Blackburn E.H.; RT "Anatomy and dynamics of DNA replication fork movement in yeast RT telomeric regions."; RL Mol. Cell. Biol. 24:4019-4031(2004). RN [16] RP FUNCTION. RX PubMed=15542831; DOI=10.1128/MCB.24.23.10208-10222.2004; RA Gibson D.G., Aparicio J.G., Hu F., Aparicio O.M.; RT "Diminished S-phase cyclin-dependent kinase function elicits vital RT Rad53-dependent checkpoint responses in Saccharomyces cerevisiae."; RL Mol. Cell. Biol. 24:10208-10222(2004). RN [17] RP FUNCTION. RX PubMed=15775982; DOI=10.1038/sj.emboj.7600602; RA Prado F., Aguilera A.; RT "Impairment of replication fork progression mediates RNA polII RT transcription-associated recombination."; RL EMBO J. 24:1267-1276(2005). RN [18] RP FUNCTION. RX PubMed=15907372; DOI=10.1016/j.gene.2005.03.031; RA O'Rourke T.W., Doudican N.A., Zhang H., Eaton J.S., Doetsch P.W., RA Shadel G.S.; RT "Differential involvement of the related DNA helicases Pif1p and Rrm3p RT in mtDNA point mutagenesis and stability."; RL Gene 354:86-92(2005). RN [19] RP RECRUITMENT TO PAUSED REPLISOME. RX PubMed=16103218; DOI=10.1101/gad.337205; RA Calzada A., Hodgson B., Kanemaki M., Bueno A., Labib K.; RT "Molecular anatomy and regulation of a stable replisome at a paused RT eukaryotic DNA replication fork."; RL Genes Dev. 19:1905-1919(2005). RN [20] RP INTERACTION WITH DEF1. RX PubMed=15863512; DOI=10.1074/jbc.M413562200; RA Chen Y.B., Yang C.P., Li R.X., Zeng R., Zhou J.Q.; RT "Def1p is involved in telomere maintenance in budding yeast."; RL J. Biol. Chem. 280:24784-24791(2005). RN [21] RP FUNCTION. RX PubMed=15829566; DOI=10.1091/mbc.E05-01-0053; RA Taylor S.D., Zhang H., Eaton J.S., Rodeheffer M.S., Lebedeva M.A., RA O'rourke T.W., Siede W., Shadel G.S.; RT "The conserved Mec1/Rad53 nuclear checkpoint pathway regulates RT mitochondrial DNA copy number in Saccharomyces cerevisiae."; RL Mol. Biol. Cell 16:3010-3018(2005). RN [22] RP FUNCTION. RX PubMed=16137624; DOI=10.1016/j.molcel.2005.06.037; RA Szyjka S.J., Viggiani C.J., Aparicio O.M.; RT "Mrc1 is required for normal progression of replication forks RT throughout chromatin in S. cerevisiae."; RL Mol. Cell 19:691-697(2005). RN [23] RP FUNCTION. RX PubMed=16327883; DOI=10.1371/journal.pgen.0010061; RA Budd M.E., Tong A.H., Polaczek P., Peng X., Boone C., Campbell J.L.; RT "A network of multi-tasking proteins at the DNA replication fork RT preserves genome stability."; RL PLoS Genet. 1:E61-E61(2005). RN [24] RP FUNCTION. RX PubMed=16631586; DOI=10.1016/j.cub.2006.02.071; RA Luke B., Versini G., Jaquenoud M., Zaidi I.W., Kurz T., Pintard L., RA Pasero P., Peter M.; RT "The cullin Rtt101p promotes replication fork progression through RT damaged DNA and natural pause sites."; RL Curr. Biol. 16:786-792(2006). RN [25] RP FUNCTION, AND DNA-BINDING. RX PubMed=17114583; DOI=10.1101/gad.1478906; RA Azvolinsky A., Dunaway S., Torres J.Z., Bessler J.B., Zakian V.A.; RT "The S. cerevisiae Rrm3p DNA helicase moves with the replication fork RT and affects replication of all yeast chromosomes."; RL Genes Dev. 20:3104-3116(2006). RN [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-64, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=18407956; DOI=10.1074/mcp.M700468-MCP200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth RT phosphoproteome analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [27] RP FUNCTION. RX PubMed=19168400; DOI=10.1016/j.dnarep.2008.12.010; RA de la Loza M.C., Wellinger R.E., Aguilera A.; RT "Stimulation of direct-repeat recombination by RNA polymerase III RT transcription."; RL DNA Repair 8:620-626(2009). RN [28] RP FUNCTION. RX PubMed=19414561; DOI=10.1534/genetics.109.104208; RA Stamenova R., Maxwell P.H., Kenny A.E., Curcio M.J.; RT "Rrm3 protects the Saccharomyces cerevisiae genome from instability at RT nascent sites of retrotransposition."; RL Genetics 182:711-723(2009). RN [29] RP FUNCTION. RX PubMed=21087929; DOI=10.1074/jbc.M110.189456; RA Bairwa N.K., Mohanty B.K., Stamenova R., Curcio M.J., Bastia D.; RT "The intra-S phase checkpoint protein Tof1 collaborates with the RT helicase Rrm3 and the F-box protein Dia2 to maintain genome stability RT in Saccharomyces cerevisiae."; RL J. Biol. Chem. 286:2445-2454(2011). RN [30] RP FUNCTION. RX PubMed=21172804; DOI=10.1242/jcs.077313; RA Hashash N., Johnson A.L., Cha R.S.; RT "Regulation of fragile sites expression in budding yeast by MEC1, RRM3 RT and hydroxyurea."; RL J. Cell Sci. 124:181-185(2011). RN [31] RP FUNCTION IN G4-UNWINDING. RX PubMed=23657261; DOI=10.1038/nature12149; RA Paeschke K., Bochman M.L., Garcia P.D., Cejka P., Friedman K.L., RA Kowalczykowski S.C., Zakian V.A.; RT "Pif1 family helicases suppress genome instability at G-quadruplex RT motifs."; RL Nature 497:458-462(2013). CC -!- FUNCTION: 5' to 3' DNA replicative helicase recruited to paused CC replisomes to promote fork progression throughout nonhistone CC protein-DNA complexes, naturally occurring impediments that are CC encountered in each S phase where replication forks pauses. Needed CC for normal fork progression through over 1000 discrete sites CC scattered throughout the genome, like rDNA, tRNA genes, CC centromeres, active replication origins, or transcriptional CC silencers. Required for timely replication of the telomere and CC subtelomeric DNA and for wild-type levels of telomeric silencing. CC Involved in regulation of Ty1 transposition and protects the CC genome from instability at nascent sites of retrotransposition. CC Involved in DNA repair during stalled replication fork, regulation CC of fragile sites expression and essential for genome stability. CC Plays also a role in mtDNA replication. Has G-quadruplex (G4) CC unwinding activity and can suppress G4-induced genome instability CC when PIF1 levels are low. {ECO:0000269|PubMed:10693764, CC ECO:0000269|PubMed:11779788, ECO:0000269|PubMed:12050116, CC ECO:0000269|PubMed:12686542, ECO:0000269|PubMed:14690605, CC ECO:0000269|PubMed:15037547, ECO:0000269|PubMed:15060144, CC ECO:0000269|PubMed:15060145, ECO:0000269|PubMed:15082794, CC ECO:0000269|PubMed:15542831, ECO:0000269|PubMed:15579680, CC ECO:0000269|PubMed:15775982, ECO:0000269|PubMed:15829566, CC ECO:0000269|PubMed:15907372, ECO:0000269|PubMed:16137624, CC ECO:0000269|PubMed:16327883, ECO:0000269|PubMed:16631586, CC ECO:0000269|PubMed:17114583, ECO:0000269|PubMed:19168400, CC ECO:0000269|PubMed:19414561, ECO:0000269|PubMed:21087929, CC ECO:0000269|PubMed:21172804, ECO:0000269|PubMed:23657261, CC ECO:0000269|PubMed:8293975}. CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. CC {ECO:0000255|HAMAP-Rule:MF_03177}. CC -!- SUBUNIT: Interacts with DEF1 and POL30. CC {ECO:0000269|PubMed:12239216, ECO:0000269|PubMed:15863512}. CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome, telomere. CC -!- DOMAIN: The N-terminal part (residues 1 to 249) is essential for CC function and confers locus specificity. CC {ECO:0000269|PubMed:15579680}. CC -!- MISCELLANEOUS: Present with 656 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the helicase 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; U00062; AAB68913.1; -; Genomic_DNA. DR EMBL; BK006934; DAA06722.1; -; Genomic_DNA. DR PIR; S46744; S46744. DR RefSeq; NP_011896.1; NM_001179161.1. DR ProteinModelPortal; P38766; -. DR BioGrid; 36462; 156. DR DIP; DIP-2858N; -. DR IntAct; P38766; 4. DR MINT; MINT-1556551; -. DR MaxQB; P38766; -. DR PRIDE; P38766; -. DR EnsemblFungi; YHR031C; YHR031C; YHR031C. DR GeneID; 856426; -. DR KEGG; sce:YHR031C; -. DR EuPathDB; FungiDB:YHR031C; -. DR SGD; S000001073; RRM3. DR GeneTree; ENSGT00530000063561; -. DR HOGENOM; HOG000132960; -. DR InParanoid; P38766; -. DR KO; K15255; -. DR OMA; TESEWAD; -. DR OrthoDB; EOG76MKKK; -. DR BioCyc; YEAST:G3O-31091-MONOMER; -. DR NextBio; 982006; -. DR PRO; PR:P38766; -. DR Proteomes; UP000002311; Chromosome VIII. DR GO; GO:0005724; C:nuclear telomeric heterochromatin; IPI:SGD. DR GO; GO:0005657; C:replication fork; IDA:SGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004003; F:ATP-dependent DNA helicase activity; IDA:SGD. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0003678; F:DNA helicase activity; IMP:SGD. DR GO; GO:0032508; P:DNA duplex unwinding; IDA:GOC. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:0006260; P:DNA replication; IMP:SGD. DR GO; GO:0044806; P:G-quadruplex DNA unwinding; IMP:SGD. DR GO; GO:0000002; P:mitochondrial genome maintenance; IGI:SGD. DR GO; GO:0097046; P:replication fork progression beyond termination site; IMP:SGD. DR GO; GO:0000723; P:telomere maintenance; IEA:InterPro. DR Gene3D; 3.40.50.300; -; 3. DR HAMAP; MF_03176; PIF1; 1. DR HAMAP; MF_03177; RRM3; 1. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR003840; DNA_helicase. DR InterPro; IPR010285; DNA_helicase_pif1-like. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR028880; Rrm3. DR PANTHER; PTHR23274; PTHR23274; 2. DR Pfam; PF05970; PIF1; 1. DR SMART; SM00382; AAA; 1. DR SUPFAM; SSF52540; SSF52540; 3. PE 1: Evidence at protein level; KW ATP-binding; Chromosome; Complete proteome; DNA damage; DNA repair; KW DNA-binding; Helicase; Hydrolase; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Telomere. FT CHAIN 1 723 ATP-dependent DNA helicase RRM3. FT /FTId=PRO_0000101986. FT NP_BIND 254 261 ATP. {ECO:0000255|HAMAP-Rule:MF_03177}. FT DNA_BIND 682 701 {ECO:0000255|HAMAP-Rule:MF_03177}. FT MOD_RES 64 64 Phosphoserine. FT {ECO:0000244|PubMed:18407956}. FT MUTAGEN 41 41 F->A,D: Reduces the interaction with FT POL30; when associated with A-42 or D-42. FT {ECO:0000269|PubMed:12239216}. FT MUTAGEN 42 42 F->A,D: Reduces the interaction with FT POL30; when associated with A-42 or D-42. FT {ECO:0000269|PubMed:12239216}. SQ SEQUENCE 723 AA; 81581 MW; 8E0010ABB870CAB6 CRC64; MFRSHASGNK KQWSKRSSNG STPAASASGS HAYRQQTLSS FFMGCGKKSA AASKNSTTII DLESGDEGNR NITAPPRPRL IRNNSSSLFS QSQGSFGDDD PDAEFKKLVD VPRLNSYKKS SRSLSMTSSL HKTASASTTQ KTYHFDEDET LREVTSVKSN SRQLSFTSTI NIEDSSMKLS TDSERPAKRS KPSMEFQGLK LTVPKKIKPL LRKTVSNMDS MNHRSASSPV VLTMEQERVV NLIVKKRTNV FYTGSAGTGK SVILQTIIRQ LSSLYGKESI AITASTGLAA VTIGGSTLHK WSGIGIGNKT IDQLVKKIQS QKDLLAAWRY TKVLIIDEIS MVDGNLLDKL EQIARRIRKN DDPFGGIQLV LTGDFFQLPP VAKKDEHNVV KFCFESEMWK RCIQKTILLT KVFRQQDNKL IDILNAIRYG ELTVDIAKTI RNLNRDIDYA DGIAPTELYA TRREVELSNV KKLQSLPGDL YEFKAVDNAP ERYQAILDSS LMVEKVVALK EDAQVMMLKN KPDVELVNGS LGKVLFFVTE SLVVKMKEIY KIVDDEVVMD MRLVSRVIGN PLLKESKEFR QDLNARPLAR LERLKILINY AVKISPHKEK FPYVRWTVGK NKYIHELMVP ERFPIDIPRE NVGLERTQIP LMLCWALSIH KAQGQTIQRL KVDLRRIFEA GQVYVALSRA VTMDTLQVLN FDPGKIRTNE RVKDFYKRLE TLK // ID UNG_HUMAN Reviewed; 313 AA. AC P13051; A8K5M6; B2R8Y1; O00637; O00719; Q93028; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 10-OCT-2003, sequence version 2. DT 11-NOV-2015, entry version 179. DE RecName: Full=Uracil-DNA glycosylase {ECO:0000255|HAMAP-Rule:MF_03166}; DE Short=UDG {ECO:0000255|HAMAP-Rule:MF_03166}; DE EC=3.2.2.27 {ECO:0000255|HAMAP-Rule:MF_03166}; GN Name=UNG {ECO:0000255|HAMAP-Rule:MF_03166}; GN Synonyms=DGU, UNG1 {ECO:0000255|HAMAP-Rule:MF_03166}, GN UNG15 {ECO:0000255|HAMAP-Rule:MF_03166}; 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 PROTEIN SEQUENCE OF RP 87-113. RC TISSUE=Placenta; RX PubMed=2555154; RA Olsen L.C., Aasland R., Wittwer C.U., Krokan H.E., Helland D.E.; RT "Molecular cloning of human uracil-DNA glycosylase, a highly conserved RT DNA repair enzyme."; RL EMBO J. 8:3121-3125(1989). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=7926048; DOI=10.1016/0014-5793(94)01042-0; RA Haug T., Skorpen F., Lund H., Krokan H.E.; RT "Structure of the gene for human uracil-DNA glycosylase and analysis RT of the promoter function."; RL FEBS Lett. 353:180-184(1994). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), AND ALTERNATIVE RP SPLICING. RX PubMed=9016624; DOI=10.1093/nar/25.4.750; RA Nilsen H., Solum K., Haug T., Krokan H.E.; RT "Nuclear and mitochondrial uracil-DNA glycosylases are generated by RT alternative splicing and transcription from different positions in the RT UNG gene."; RL Nucleic Acids Res. 25:750-755(1997). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [5] 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Uterus; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP SUBCELLULAR LOCATION. RX PubMed=8332455; DOI=10.1093/nar/21.11.2579; RA Slupphaug G., Markussen F.-H., Olsen L.C., Aasland R., Aarsaether N., RA Bakke O., Krokan H.E., Helland D.E.; RT "Nuclear and mitochondrial forms of human uracil-DNA glycosylase are RT encoded by the same gene."; RL Nucleic Acids Res. 21:2579-2584(1993). RN [9] RP MUTAGENESIS. RX PubMed=8670846; RA Kavli B., Slupphaug G., Mol C.D., Arvai A.S., Petersen S.B., RA Tainer J.A., Krohan H.E.; RT "Excision of cytosine and thymine from DNA by mutants of human uracil- RT DNA glycosylase."; RL EMBO J. 15:3442-3447(1996). RN [10] RP INTERACTION WITH HIV-1 VPR. RX PubMed=8551605; RA Bouhamdan M., Benichou S., Rey F., Navarro J.-M., Agostini I., RA Spire B., Camonis J., Slupphaug G., Vigne R., Benarous R., Sire J.; RT "Human immunodeficiency virus type 1 Vpr protein binds to the uracil RT DNA glycosylase DNA repair enzyme."; RL J. Virol. 70:697-704(1996). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=9753728; DOI=10.1093/nar/26.20.4611; RA Otterlei M., Haug T., Nagelhus T.A., Slupphaug G., Lindmo T., RA Krokan H.E.; RT "Nuclear and mitochondrial splice forms of human uracil-DNA RT glycosylase contain a complex nuclear localisation signal and a strong RT classical mitochondrial localisation signal, respectively."; RL Nucleic Acids Res. 26:4611-4617(1998). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [13] RP INTERACTION WITH FAM72A. RX PubMed=18676834; DOI=10.1158/0008-5472.CAN-08-1259; RA Guo C., Zhang X., Fink S.P., Platzer P., Wilson K., Willson J.K., RA Wang Z., Markowitz S.D.; RT "Ugene, a newly identified protein that is commonly overexpressed in RT cancer and binds uracil DNA glycosylase."; RL Cancer Res. 68:6118-6126(2008). RN [14] RP IDENTIFICATION 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; SER-14; SER-23; RP THR-60 AND SER-64, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE RP 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 [16] 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 [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-23; THR-60 AND RP SER-64, 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 ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-295, 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 [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; SER-14; SER-23 AND RP THR-60, 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 [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23 AND THR-60, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [21] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS). RX PubMed=7697717; DOI=10.1016/0092-8674(95)90290-2; RA Mol C.D., Arvai A.S., Slupphaug G., Kavli B., Alseth I., Krohan H.E., RA Tainer J.A.; RT "Crystal structure and mutational analysis of human uracil-DNA RT glycosylase: structural basis for specificity and catalysis."; RL Cell 80:869-878(1995). RN [22] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS). RX PubMed=7671300; DOI=10.1016/0092-8674(95)90467-0; RA Mol C.D., Arvai A.S., Sanderson R.J., Slupphaug G., Kavli B., RA Krokan H.E., Mosbaugh D.W., Tainer J.A.; RT "Crystal structure of human uracil-DNA glycosylase in complex with a RT protein inhibitor: protein mimicry of DNA."; RL Cell 82:701-708(1995). RN [23] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS). RX PubMed=8900285; DOI=10.1038/384087a0; RA Slupphaug G., Mol C.D., Kavli B., Arvai A.S., Krohan H.E., RA Tainer J.A.; RT "A nucleotide-flipping mechanism from the structure of human uracil- RT DNA glycosylase bound to DNA."; RL Nature 384:87-92(1996). RN [24] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 94-313. RX PubMed=9724657; DOI=10.1093/emboj/17.17.5214; RA Parikh S.S., Mol C.D., Slupphaug G., Bharati S., Krokan H.E., RA Tainer J.A.; RT "Base excision repair initiation revealed by crystal structures and RT binding kinetics of human uracil-DNA glycosylase with DNA."; RL EMBO J. 17:5214-5226(1998). RN [25] RP VARIANT HIGM5 SER-251. RX PubMed=12958596; DOI=10.1038/ni974; RA Imai K., Slupphaug G., Lee W.-I., Revy P., Nonoyama S., Catalan N., RA Yel L., Forveille M., Kavli B., Krokan H.E., Ochs H.D., Fischer A., RA Durandy A.; RT "Human uracil-DNA glycosylase deficiency associated with profoundly RT impaired immunoglobulin class-switch recombination."; RL Nat. Immunol. 4:1023-1028(2003). RN [26] RP CHARACTERIZATION OF VARIANT HIGM5 SER-251. RX PubMed=15967827; DOI=10.1084/jem.20050042; RA Kavli B., Andersen S., Otterlei M., Liabakk N.B., Imai K., Fischer A., RA Durandy A., Krokan H.E., Slupphaug G.; RT "B cells from hyper-IgM patients carrying UNG mutations lack ability RT to remove uracil from ssDNA and have elevated genomic uracil."; RL J. Exp. Med. 201:2011-2021(2005). CC -!- FUNCTION: Excises uracil residues from the DNA which can arise as CC a result of misincorporation of dUMP residues by DNA polymerase or CC due to deamination of cytosine. CC -!- CATALYTIC ACTIVITY: Hydrolyzes single-stranded DNA or mismatched CC double-stranded DNA and polynucleotides, releasing free uracil. CC {ECO:0000255|HAMAP-Rule:MF_03166}. CC -!- SUBUNIT: Monomer. Interacts with FAM72A. Interacts with HIV-1 Vpr. CC {ECO:0000255|HAMAP-Rule:MF_03166, ECO:0000269|PubMed:18676834, CC ECO:0000269|PubMed:8551605}. CC -!- INTERACTION: CC P15927:RPA2; NbExp=6; IntAct=EBI-1025947, EBI-621404; CC -!- SUBCELLULAR LOCATION: Isoform 1: Mitochondrion. CC -!- SUBCELLULAR LOCATION: Isoform 2: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=2; Synonyms=UNG2; CC IsoId=P13051-1; Sequence=Displayed; CC Name=1; Synonyms=UNG1; CC IsoId=P13051-2; Sequence=VSP_008513; CC -!- TISSUE SPECIFICITY: Isoform 1 is widely expressed with the highest CC expression in skeletal muscle, heart and testicles. Isoform 2 has CC the highest expression levels in tissues containing proliferating CC cells. CC -!- PTM: Isoform 1 is processed by cleavage of a transit peptide. CC -!- DISEASE: Immunodeficiency with hyper-IgM 5 (HIGM5) [MIM:608106]: A CC rare immunodeficiency syndrome characterized by normal or elevated CC serum IgM levels with absence of IgG, IgA, and IgE. It results in CC a profound susceptibility to bacterial infections. CC {ECO:0000269|PubMed:12958596}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the uracil-DNA glycosylase family. CC {ECO:0000255|HAMAP-Rule:MF_03166}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/ung/"; CC -!- WEB RESOURCE: Name=UNGbase; Note=UNG mutation db; CC URL="http://structure.bmc.lu.se/idbase/UNGbase/"; 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; X15653; CAA33679.1; -; mRNA. DR EMBL; X89398; CAA61578.1; -; Genomic_DNA. DR EMBL; X89398; CAA61579.1; -; Genomic_DNA. DR EMBL; Y09008; CAA70211.1; -; mRNA. DR EMBL; AF526277; AAM77695.1; -; Genomic_DNA. DR EMBL; AK291341; BAF84030.1; -; mRNA. DR EMBL; AK313552; BAG36328.1; -; mRNA. DR EMBL; CH471054; EAW97846.1; -; Genomic_DNA. DR EMBL; CH471054; EAW97847.1; -; Genomic_DNA. DR EMBL; BC015205; AAH15205.1; -; mRNA. DR EMBL; BC050634; AAH50634.1; -; mRNA. DR CCDS; CCDS9124.1; -. [P13051-1] DR CCDS; CCDS9125.1; -. [P13051-2] DR PIR; S05964; A60472. DR RefSeq; NP_003353.1; NM_003362.3. [P13051-2] DR RefSeq; NP_550433.1; NM_080911.2. [P13051-1] DR UniGene; Hs.191334; -. DR PDB; 1AKZ; X-ray; 1.57 A; A=94-313. DR PDB; 1DPU; NMR; -; B=73-88. DR PDB; 1EMH; X-ray; 1.80 A; A=94-313. DR PDB; 1EMJ; X-ray; 2.00 A; A=94-313. DR PDB; 1Q3F; X-ray; 1.90 A; A=94-313. DR PDB; 1SSP; X-ray; 1.90 A; E=94-313. DR PDB; 1UGH; X-ray; 1.90 A; E=94-313. DR PDB; 1YUO; X-ray; 1.95 A; A=91-313. DR PDB; 2HXM; X-ray; 1.30 A; A=94-313. DR PDB; 2OXM; X-ray; 2.50 A; A=94-313. DR PDB; 2OYT; X-ray; 2.00 A; A=94-313. DR PDB; 2SSP; X-ray; 2.25 A; E=94-313. DR PDB; 3FCF; X-ray; 1.84 A; A=94-313. DR PDB; 3FCI; X-ray; 1.27 A; A=94-313. DR PDB; 3FCK; X-ray; 1.64 A; B=94-313. DR PDB; 3FCL; X-ray; 1.70 A; A/B=94-313. DR PDB; 3TKB; X-ray; 1.50 A; A=94-313. DR PDB; 4SKN; X-ray; 2.90 A; E=94-313. DR PDBsum; 1AKZ; -. DR PDBsum; 1DPU; -. DR PDBsum; 1EMH; -. DR PDBsum; 1EMJ; -. DR PDBsum; 1Q3F; -. DR PDBsum; 1SSP; -. DR PDBsum; 1UGH; -. DR PDBsum; 1YUO; -. DR PDBsum; 2HXM; -. DR PDBsum; 2OXM; -. DR PDBsum; 2OYT; -. DR PDBsum; 2SSP; -. DR PDBsum; 3FCF; -. DR PDBsum; 3FCI; -. DR PDBsum; 3FCK; -. DR PDBsum; 3FCL; -. DR PDBsum; 3TKB; -. DR PDBsum; 4SKN; -. DR ProteinModelPortal; P13051; -. DR SMR; P13051; 94-313. DR BioGrid; 113220; 15. DR DIP; DIP-24194N; -. DR IntAct; P13051; 9. DR MINT; MINT-1507980; -. DR STRING; 9606.ENSP00000242576; -. DR BindingDB; P13051; -. DR ChEMBL; CHEMBL3277; -. DR PhosphoSite; P13051; -. DR BioMuta; UNG; -. DR DMDM; 37999897; -. DR MaxQB; P13051; -. DR PaxDb; P13051; -. DR PRIDE; P13051; -. DR DNASU; 7374; -. DR Ensembl; ENST00000242576; ENSP00000242576; ENSG00000076248. [P13051-1] DR Ensembl; ENST00000336865; ENSP00000337398; ENSG00000076248. [P13051-2] DR GeneID; 7374; -. DR KEGG; hsa:7374; -. DR UCSC; uc001tnz.2; human. [P13051-1] DR CTD; 7374; -. DR GeneCards; UNG; -. DR HGNC; HGNC:12572; UNG. DR HPA; CAB011605; -. DR MIM; 191525; gene. DR MIM; 608106; phenotype. DR neXtProt; NX_P13051; -. DR Orphanet; 101092; Hyper-IgM syndrome type 5. DR PharmGKB; PA364; -. DR eggNOG; KOG2994; Eukaryota. DR eggNOG; COG0692; LUCA. DR GeneTree; ENSGT00390000003405; -. DR HOGENOM; HOG000229528; -. DR HOVERGEN; HBG000396; -. DR InParanoid; P13051; -. DR KO; K03648; -. DR OMA; YPAPKNI; -. DR OrthoDB; EOG786H4X; -. DR PhylomeDB; P13051; -. DR TreeFam; TF315028; -. DR BRENDA; 3.2.2.27; 2681. DR Reactome; R-HSA-110328; Recognition and association of DNA glycosylase with site containing an affected pyrimidine. DR Reactome; R-HSA-110329; Cleavage of the damaged pyrimidine. DR Reactome; R-HSA-110357; Displacement of DNA glycosylase by APEX1. DR SABIO-RK; P13051; -. DR ChiTaRS; UNG; human. DR EvolutionaryTrace; P13051; -. DR GeneWiki; Uracil-DNA_glycosylase; -. DR GenomeRNAi; 7374; -. DR NextBio; 28874; -. DR PRO; PR:P13051; -. DR Proteomes; UP000005640; Chromosome 12. DR Bgee; P13051; -. DR CleanEx; HS_UNG; -. DR ExpressionAtlas; P13051; baseline and differential. DR Genevisible; P13051; HS. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome. DR GO; GO:0005634; C:nucleus; NAS:UniProtKB. DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB. DR GO; GO:0004844; F:uracil DNA N-glycosylase activity; NAS:UniProtKB. DR GO; GO:0006284; P:base-excision repair; TAS:Reactome. DR GO; GO:0006285; P:base-excision repair, AP site formation; IDA:UniProtKB. DR GO; GO:0045008; P:depyrimidination; TAS:Reactome. DR GO; GO:0006281; P:DNA repair; TAS:Reactome. DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; IEA:Ensembl. DR GO; GO:0016447; P:somatic recombination of immunoglobulin gene segments; IEA:Ensembl. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. DR Gene3D; 3.40.470.10; -; 1. DR HAMAP; MF_00148; UDG; 1. DR InterPro; IPR018085; Ura-DNA_Glyclase_AS. DR InterPro; IPR002043; Ura_DNA_glycsylse. DR InterPro; IPR005122; Uracil-DNA_glycosylase-like. DR PANTHER; PTHR11264; PTHR11264; 1. DR Pfam; PF03167; UDG; 1. DR SMART; SM00986; UDG; 1. DR SUPFAM; SSF52141; SSF52141; 1. DR TIGRFAMs; TIGR00628; ung; 1. DR PROSITE; PS00130; U_DNA_GLYCOSYLASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Complete proteome; KW Direct protein sequencing; Disease mutation; DNA damage; DNA repair; KW Glycosidase; Host-virus interaction; Hydrolase; Mitochondrion; KW Nucleus; Phosphoprotein; Polymorphism; Reference proteome. FT CHAIN 1 313 Uracil-DNA glycosylase. FT /FTId=PRO_0000176173. FT REGION 1 25 FAM72A-binding. FT ACT_SITE 154 154 Proton acceptor. {ECO:0000255|HAMAP- FT Rule:MF_03166}. FT MOD_RES 12 12 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:20068231}. FT MOD_RES 14 14 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231}. FT MOD_RES 23 23 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 60 60 Phosphothreonine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 64 64 Phosphoserine. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332}. FT MOD_RES 295 295 N6-acetyllysine. FT {ECO:0000244|PubMed:19608861}. FT VAR_SEQ 1 44 MIGQKTLYSFFSPSPARKRHAPSPEPAVQGTGVAGVPEESG FT DAA -> MGVFCLGPWGLGRKLRTPGKGPLQLLSRLCGDHL FT Q (in isoform 1). FT {ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:2555154}. FT /FTId=VSP_008513. FT VARIANT 4 4 Q -> R (in dbSNP:rs7488798). FT /FTId=VAR_052697. FT VARIANT 251 251 F -> S (in HIGM5; fully active and stable FT when expressed in E.coli; mistargeted to FT mitochondria rather than the nucleus). FT {ECO:0000269|PubMed:12958596, FT ECO:0000269|PubMed:15967827}. FT /FTId=VAR_017094. FT MUTAGEN 154 154 D->E,N: Loss of activity. FT {ECO:0000269|PubMed:8670846}. FT MUTAGEN 156 156 Y->A,C,S: Thymine-DNA glycosylase FT activity. {ECO:0000269|PubMed:8670846}. FT MUTAGEN 213 213 N->D: Cytosine-DNA glycosylase activity. FT {ECO:0000269|PubMed:8670846}. FT HELIX 77 86 {ECO:0000244|PDB:1DPU}. FT HELIX 96 102 {ECO:0000244|PDB:3FCI}. FT HELIX 103 105 {ECO:0000244|PDB:3FCI}. FT HELIX 109 124 {ECO:0000244|PDB:3FCI}. FT STRAND 127 129 {ECO:0000244|PDB:3FCI}. FT HELIX 131 133 {ECO:0000244|PDB:3FCI}. FT HELIX 136 138 {ECO:0000244|PDB:3FCI}. FT STRAND 139 141 {ECO:0000244|PDB:1EMH}. FT HELIX 143 145 {ECO:0000244|PDB:3FCI}. FT STRAND 148 152 {ECO:0000244|PDB:3FCI}. FT TURN 159 161 {ECO:0000244|PDB:3FCI}. FT STRAND 163 165 {ECO:0000244|PDB:3FCK}. FT HELIX 177 189 {ECO:0000244|PDB:3FCI}. FT TURN 190 192 {ECO:0000244|PDB:3TKB}. FT HELIX 202 205 {ECO:0000244|PDB:3FCI}. FT TURN 206 208 {ECO:0000244|PDB:3FCI}. FT STRAND 209 215 {ECO:0000244|PDB:3FCI}. FT TURN 223 228 {ECO:0000244|PDB:3FCI}. FT HELIX 231 245 {ECO:0000244|PDB:3FCI}. FT STRAND 250 255 {ECO:0000244|PDB:3FCI}. FT HELIX 256 261 {ECO:0000244|PDB:3FCI}. FT TURN 262 264 {ECO:0000244|PDB:3FCI}. FT TURN 267 269 {ECO:0000244|PDB:3FCI}. FT STRAND 270 275 {ECO:0000244|PDB:3FCI}. FT TURN 280 282 {ECO:0000244|PDB:3FCI}. FT HELIX 283 285 {ECO:0000244|PDB:3FCI}. FT TURN 286 289 {ECO:0000244|PDB:3FCI}. FT HELIX 292 302 {ECO:0000244|PDB:3FCI}. SQ SEQUENCE 313 AA; 34645 MW; A4B27E6198AFE9C0 CRC64; MIGQKTLYSF FSPSPARKRH APSPEPAVQG TGVAGVPEES GDAAAIPAKK APAGQEEPGT PPSSPLSAEQ LDRIQRNKAA ALLRLAARNV PVGFGESWKK HLSGEFGKPY FIKLMGFVAE ERKHYTVYPP PHQVFTWTQM CDIKDVKVVI LGQDPYHGPN QAHGLCFSVQ RPVPPPPSLE NIYKELSTDI EDFVHPGHGD LSGWAKQGVL LLNAVLTVRA HQANSHKERG WEQFTDAVVS WLNQNSNGLV FLLWGSYAQK KGSAIDRKRH HVLQTAHPSP LSVYRGFFGC RHFSKTNELL QKSGKKPIDW KEL // ID UNG_YEAST Reviewed; 359 AA. AC P12887; D6VZF3; E9P912; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1989, sequence version 1. DT 11-NOV-2015, entry version 135. DE RecName: Full=Uracil-DNA glycosylase {ECO:0000255|HAMAP-Rule:MF_03166}; DE Short=UDG {ECO:0000255|HAMAP-Rule:MF_03166}; DE EC=3.2.2.27 {ECO:0000255|HAMAP-Rule:MF_03166}; DE Flags: Precursor; GN Name=UNG1 {ECO:0000255|HAMAP-Rule:MF_03166}; GN OrderedLocusNames=YML021C; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; OC Saccharomycetes; Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION. RX PubMed=2644266; RA Percival K.J., Klein M.B., Burgers P.M.J.; RT "Molecular cloning and primary structure of the uracil-DNA glycosylase RT gene from Saccharomyces cerevisiae."; RL J. Biol. Chem. 264:2593-2598(1989). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169872; RA Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T., RA Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., RA Jagels K., Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., RA Rice P., Skelton J., Walsh S.V., Whitehead S., Barrell B.G.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome RT XIII."; RL Nature 387:90-93(1997). RN [3] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., RA Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and RT now."; RL G3 (Bethesda) 4:389-398(2014). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=17322287; DOI=10.1101/gr.6037607; RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F., RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., RA Raphael J., Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., RA Williamson J., Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., RA Kolodner R.D., LaBaer J.; RT "Approaching a complete repository of sequence-verified protein- RT encoding clones for Saccharomyces cerevisiae."; RL Genome Res. 17:536-543(2007). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RC STRAIN=ATCC 204626 / S288c / A364A; RX PubMed=7031606; DOI=10.1093/nar/9.21.5797; RA Crosby B., Prakash L., Davis H., Hinkle D.C.; RT "Purification and characterization of a uracil-DNA glycosylase from RT the yeast, Saccharomyces cerevisiae."; RL Nucleic Acids Res. 9:5797-5809(1981). RN [6] RP FUNCTION, AND INDUCTION. RX PubMed=1938887; RA Impellizzeri K.J., Anderson B., Burgers P.M.; RT "The spectrum of spontaneous mutations in a Saccharomyces cerevisiae RT uracil-DNA-glycosylase mutant limits the function of this enzyme to RT cytosine deamination repair."; RL J. Bacteriol. 173:6807-6810(1991). RN [7] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=11812822; DOI=10.1093/nar/29.24.4935; RA Chatterjee A., Singh K.K.; RT "Uracil-DNA glycosylase-deficient yeast exhibit a mitochondrial RT mutator phenotype."; RL Nucleic Acids Res. 29:4935-4940(2001). RN [8] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., RA Dephoure N., O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [9] RP INDUCTION. RX PubMed=17934734; DOI=10.1007/s00294-007-0159-5; RA Lucaccioni A., Pavlov Y.I., Achilli A., Babudri N.; RT "High rate of starvation-associated mutagenesis in Ung(-) yeast caused RT by the overproduction of human activation-induced deaminase."; RL Curr. Genet. 52:239-245(2007). CC -!- FUNCTION: Excises uracil residues from the DNA which can arise as CC a result of misincorporation of dUMP residues by DNA polymerase or CC due to deamination of cytosine. Not involved in strand-directed CC mismatch repair. {ECO:0000255|HAMAP-Rule:MF_03166, CC ECO:0000269|PubMed:11812822, ECO:0000269|PubMed:1938887, CC ECO:0000269|PubMed:2644266, ECO:0000269|PubMed:7031606}. CC -!- CATALYTIC ACTIVITY: Hydrolyzes single-stranded DNA or mismatched CC double-stranded DNA and polynucleotides, releasing free uracil. CC {ECO:0000255|HAMAP-Rule:MF_03166, ECO:0000269|PubMed:7031606}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 7.5-8. {ECO:0000269|PubMed:7031606}; CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000255|HAMAP- CC Rule:MF_03166, ECO:0000269|PubMed:11812822}. Nucleus CC {ECO:0000255|HAMAP-Rule:MF_03166, ECO:0000269|PubMed:11812822}. CC -!- INDUCTION: Induced in late G1 and early S phase of the cell cycle. CC {ECO:0000269|PubMed:17934734, ECO:0000269|PubMed:1938887}. CC -!- MISCELLANEOUS: Present with 4820 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the uracil-DNA glycosylase family. CC {ECO:0000255|HAMAP-Rule:MF_03166}. 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; J04470; AAA35195.1; -; Genomic_DNA. DR EMBL; Z46659; CAA86634.1; -; Genomic_DNA. DR EMBL; AY693020; AAT93039.1; -; Genomic_DNA. DR EMBL; BK006946; DAA09877.1; -; Genomic_DNA. DR PIR; A31425; A31425. DR RefSeq; NP_013691.1; NM_001182379.1. DR ProteinModelPortal; P12887; -. DR SMR; P12887; 99-334. DR BioGrid; 35148; 37. DR DIP; DIP-8264N; -. DR MINT; MINT-4496681; -. DR MaxQB; P12887; -. DR EnsemblFungi; YML021C; YML021C; YML021C. DR GeneID; 854987; -. DR KEGG; sce:YML021C; -. DR EuPathDB; FungiDB:YML021C; -. DR SGD; S000004483; UNG1. DR GeneTree; ENSGT00390000003405; -. DR HOGENOM; HOG000229528; -. DR InParanoid; P12887; -. DR KO; K03648; -. DR OMA; KCLILGQ; -. DR OrthoDB; EOG71ZPC8; -. DR BioCyc; YEAST:G3O-32624-MONOMER; -. DR Reactome; R-SCE-110329; Cleavage of the damaged pyrimidine. DR NextBio; 978118; -. DR PRO; PR:P12887; -. DR Proteomes; UP000002311; Chromosome XIII. DR GO; GO:0005739; C:mitochondrion; IDA:SGD. DR GO; GO:0005634; C:nucleus; IDA:SGD. DR GO; GO:0004844; F:uracil DNA N-glycosylase activity; IDA:SGD. DR GO; GO:0006284; P:base-excision repair; IEA:UniProtKB-HAMAP. DR GO; GO:0006281; P:DNA repair; IMP:SGD. DR Gene3D; 3.40.470.10; -; 1. DR HAMAP; MF_00148; UDG; 1. DR InterPro; IPR018085; Ura-DNA_Glyclase_AS. DR InterPro; IPR002043; Ura_DNA_glycsylse. DR InterPro; IPR005122; Uracil-DNA_glycosylase-like. DR PANTHER; PTHR11264; PTHR11264; 1. DR Pfam; PF03167; UDG; 1. DR SMART; SM00986; UDG; 1. DR SUPFAM; SSF52141; SSF52141; 1. DR TIGRFAMs; TIGR00628; ung; 1. DR PROSITE; PS00130; U_DNA_GLYCOSYLASE; 1. PE 1: Evidence at protein level; KW Complete proteome; DNA damage; DNA repair; Glycosidase; Hydrolase; KW Mitochondrion; Nucleus; Reference proteome; Transit peptide. FT TRANSIT 1 21 Mitochondrion. {ECO:0000255}. FT CHAIN 22 359 Uracil-DNA glycosylase. FT /FTId=PRO_0000036085. FT ACT_SITE 162 162 Proton acceptor. {ECO:0000255|HAMAP- FT Rule:MF_03166}. FT CONFLICT 173 173 L -> S (in Ref. 4; AAT93039). FT {ECO:0000305}. SQ SEQUENCE 359 AA; 40471 MW; CC06971E05FE7751 CRC64; MWCMRRLPTN SVMTVARKRK QTTIEDFFGT KKSTNEAPNK KGKSGATFMT ITNGAAIKTE TKAVAKEANT DKYPANSNAK DVYSKNLSSN LRTLLSLELE TIDDSWFPHL MDEFKKPYFV KLKQFVTKEQ ADHTVFPPAK DIYSWTRLTP FNKVKVVIIG QDPYHNFNQA HGLAFSVKPP TPAPPSLKNI YKELKQEYPD FVEDNKVGDL THWASQGVLL LNTSLTVRAH NANSHSKHGW ETFTKRVVQL LIQDREADGK SLVFLLWGNN AIKLVESLLG STSVGSGSKY PNIMVMKSVH PSPLSASRGF FGTNHFKMIN DWLYNTRGEK MIDWSVVPGT SLREVQEANA RLESESKDP //