DNMT1_HUMAN
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 03-AUG-2022, entry version 234.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., 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 project:
RT 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 somatic
RT 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 OF ARG-163; GLN-164; THR-166;
RP ILE-167; SER-169; HIS-170; PHE-171; ALA-172 AND LYS-173.
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 transcription
RT 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 mRNA
RT 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 novo
RT 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., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT 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 OF PUBMED:16357870.
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 for
RT 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; CYS-667
RP AND CYS-670.
RX PubMed=18754681; DOI=10.1021/bi8011725;
RA Pradhan M., Esteve P.-O., Chin H.G., Samaranayke M., Kim G.-D., 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., Gius D.;
RT "DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment
RT of CTCFL/BORIS and modulation of promoter histone methylation.";
RL Cancer Res. 68:2726-2735(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-732, AND IDENTIFICATION BY
RP 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., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT 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., Jurkowska R.,
RA 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 SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [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., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT 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 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 [27]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-173; LYS-1111; LYS-1113 AND
RP LYS-1115, AND 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., Walther T.C.,
RA 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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT 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., Buerckstuemmer T.,
RA 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 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 alters
RT 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 and
RT 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., Dobner T.,
RA Kremmer E., Kappler R., Langst G.;
RT "The USP7/Dnmt1 complex stimulates the DNA methylation activity of Dnmt1
RT 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 SER-714, 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., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-127; THR-137; SER-143;
RP SER-154; THR-166; SER-312; SER-394; SER-398; SER-549; SER-714 AND SER-878,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [36]
RP FUNCTION, POSSIBLE IDENTIFICATION IN A COREPRESSOR COMPLEX, AND
RP CHROMATIN-BINDING.
RX PubMed=24623306; DOI=10.7554/elife.02313;
RA Serra R.W., Fang M., Park S.M., Hutchinson L., Green M.R.;
RT "A KRAS-directed transcriptional silencing pathway that mediates the CpG
RT island methylator phenotype.";
RL Elife 3:E02313-E02313(2014).
RN [37]
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., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [38]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1609, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA Vertegaal A.C.;
RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL Cell Rep. 10:1778-1791(2015).
RN [39]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-259 AND LYS-1609, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [40]
RP INTERACTION WITH ZNF263.
RX PubMed=32051553; DOI=10.1038/s41388-020-1206-7;
RA Yu Z., Feng J., Wang W., Deng Z., Zhang Y., Xiao L., Wang Z., Liu C.,
RA Liu Q., Chen S., Wu M.;
RT "The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma
RT epigenetically.";
RL Oncogene 39:3163-3178(2020).
RN [41]
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 [42]
RP X-RAY CRYSTALLOGRAPHY (3.6 ANGSTROMS) OF 646-1600 IN COMPLEX WITH
RP S-ADENOSYL-L-HOMOCYSTEINE 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 [43]
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., Hammans S.,
RA Hojo K., Yamanishi H., Karpf A.R., Wallace D.C., Simon M., Lander C.,
RA Boardman L.A., Cunningham J.M., Smith G.E., Litchy W.J., Boes B.,
RA Atkinson E.J., Middha S., Dyck P.J.B., Parisi J.E., Mer G., Smith D.I.,
RA Dyck P.J.;
RT "Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and
RT hearing loss.";
RL Nat. Genet. 43:595-600(2011).
RN [44]
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., Plazzi G.,
RA Melberg A., Cornelio F., Urban A.E., Pizza F., Poli F., Grubert F.,
RA Wieland T., Graf E., Hallmayer J., Strom T.M., Mignot E.;
RT "Mutations in DNMT1 cause autosomal dominant cerebellar ataxia, deafness
RT 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 phase
CC maintaining the methylation pattern in the newly synthesized strand,
CC that is essential for epigenetic inheritance. Associates with chromatin
CC during G2 and M phases to maintain DNA methylation independently of
CC replication. It is responsible for maintaining methylation patterns
CC established in development. DNA methylation is coordinated with
CC methylation of histones. Mediates transcriptional repression by direct
CC binding to HDAC2. In association with DNMT3B and via the recruitment of
CC CTCFL/BORIS, involved in activation of BAG1 gene expression by
CC modulating dimethylation of promoter histone H3 at H3K4 and H3K9.
CC Probably forms a corepressor complex required for activated KRAS-
CC mediated promoter hypermethylation and transcriptional silencing of
CC tumor suppressor genes (TSGs) or other tumor-related genes in
CC colorectal cancer (CRC) cells (PubMed:24623306). Also required to
CC maintain a transcriptionally repressive state of genes in
CC undifferentiated embryonic stem cells (ESCs) (PubMed:24623306).
CC Associates at promoter regions of tumor suppressor genes (TSGs) leading
CC to their gene silencing (PubMed:24623306). Promotes tumor growth
CC (PubMed:24623306). {ECO:0000269|PubMed:16357870,
CC ECO:0000269|PubMed:18413740, ECO:0000269|PubMed:18754681,
CC ECO:0000269|PubMed:24623306}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-
CC methyl-2'-deoxycytidine in DNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:13681, Rhea:RHEA-COMP:11369, Rhea:RHEA-COMP:11370,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:85452, ChEBI:CHEBI:85454; EC=2.1.1.37;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10018};
CC -!- SUBUNIT: Homodimer (PubMed:19173286). Forms a stable complex with E2F1,
CC BB1 and HDAC1 (PubMed:10888886). Forms a complex with DMAP1 and HDAC2,
CC with direct interaction (PubMed:10888872). Interacts with the PRC2/EED-
CC EZH2 complex (PubMed:16357870). Probably part of a corepressor complex
CC containing ZNF304, TRIM28, SETDB1 and DNMT1 (PubMed:24623306).
CC Interacts with UHRF1; promoting its recruitment to hemimethylated DNA
CC (PubMed:21745816). Interacts with USP7, promoting its deubiquitination
CC (PubMed:21745816). Interacts with PCNA (PubMed:9302295). Interacts with
CC MBD2 and MBD3 (PubMed:10947852). Interacts with DNMT3A and DNMT3B
CC (PubMed:12145218). Interacts with UBC9 (PubMed:19450230). Interacts
CC with CSNK1D (By similarity). Interacts with HDAC1 (By similarity).
CC Interacts with BAZ2A/TIP5 (By similarity). Interacts with SIRT7 (By
CC similarity). Interacts with ZNF263; recruited to the SIX3 promoter
CC along with other proteins involved in chromatin modification and
CC transcriptional corepression where it contributes to transcriptional
CC repression (PubMed:32051553). {ECO:0000250|UniProtKB:P13864,
CC ECO:0000269|PubMed:10888872, ECO:0000269|PubMed:10888886,
CC ECO:0000269|PubMed:10947852, ECO:0000269|PubMed:12145218,
CC ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:19173286,
CC ECO:0000269|PubMed:19450230, ECO:0000269|PubMed:21745816,
CC ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:32051553,
CC ECO:0000269|PubMed:9302295}.
CC -!- INTERACTION:
CC P26358; P31749: AKT1; NbExp=6; IntAct=EBI-719459, EBI-296087;
CC P26358; P35222: CTNNB1; NbExp=8; IntAct=EBI-719459, EBI-491549;
CC P26358; O75530: EED; NbExp=3; IntAct=EBI-719459, EBI-923794;
CC P26358; Q15910: EZH2; NbExp=8; IntAct=EBI-719459, EBI-530054;
CC P26358; P48552: NRIP1; NbExp=3; IntAct=EBI-719459, EBI-746484;
CC P26358; P09874: PARP1; NbExp=6; IntAct=EBI-719459, EBI-355676;
CC P26358; Q9NRD5: PICK1; NbExp=2; IntAct=EBI-719459, EBI-79165;
CC P26358; Q8WTS6: SETD7; NbExp=9; IntAct=EBI-719459, EBI-1268586;
CC P26358; Q96EB6: SIRT1; NbExp=11; IntAct=EBI-719459, EBI-1802965;
CC P26358; Q96T88: UHRF1; NbExp=12; IntAct=EBI-719459, EBI-1548946;
CC P26358; Q77UV9: KIE-2; Xeno; NbExp=2; IntAct=EBI-719459, EBI-2608731;
CC P26358; Q9QR71: LANA1; Xeno; NbExp=2; IntAct=EBI-719459, EBI-15602554;
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 than
CC isoform 1. {ECO:0000269|PubMed:10325416}.
CC -!- INDUCTION: Its abundance is reduced to non detectable levels at the G0
CC phase of the cell cycle and is dramatically induced upon entrance into
CC the S-phase of the cell cycle.
CC -!- DOMAIN: The N-terminal part is required for homodimerization and acts
CC as a regulatory domain.
CC -!- DOMAIN: The CXXC-type zinc finger specifically binds to unmethylated
CC CpG dinucleotides, positioning the autoinhibitory linker between the
CC DNA and the active site, thus providing a mechanism to ensure that only
CC hemimethylated CpG dinucleotides undergo methylation.
CC {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, regulates
CC cell cycle G(2)/M transition. Deacetylation of Lys-1349 and Lys-1415 by
CC 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 preventing
CC degradation by the proteasome. {ECO:0000250|UniProtKB:P13864}.
CC -!- DISEASE: Neuropathy, hereditary sensory, 1E (HSN1E) [MIM:614116]: A
CC neurodegenerative disorder characterized by adult onset of progressive
CC peripheral sensory loss associated with progressive hearing impairment
CC and early-onset dementia. {ECO:0000269|PubMed:21532572}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC 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 ataxia,
CC narcolepsy, cataplexy, sensorineural deafness, and dementia. More
CC variable features include optic atrophy, sensory neuropathy, psychosis,
CC and depression. {ECO:0000269|PubMed:22328086}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. C5-methyltransferase family. {ECO:0000255|PROSITE-
CC 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 and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/DNMT1ID40347ch19p13.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) 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_001130823.2. [P26358-2]
DR RefSeq; NP_001305659.1; NM_001318730.1.
DR RefSeq; NP_001305660.1; NM_001318731.1.
DR RefSeq; NP_001370.1; NM_001379.3. [P26358-1]
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 PDB; 4Z96; X-ray; 2.85 A; C=1098-1129.
DR PDB; 4Z97; X-ray; 3.00 A; C=1098-1129.
DR PDB; 5WVO; X-ray; 2.00 A; C=351-600.
DR PDB; 5YDR; X-ray; 2.00 A; B=351-599.
DR PDB; 6K3A; X-ray; 2.30 A; B/D/F=161-180.
DR PDB; 6L1F; X-ray; 1.90 A; A=140-145.
DR PDB; 6X9I; X-ray; 2.20 A; A=729-1600.
DR PDB; 6X9J; X-ray; 1.79 A; A=729-1600.
DR PDB; 6X9K; X-ray; 2.65 A; A=729-1600.
DR PDB; 7SFC; X-ray; 1.97 A; A=729-1600.
DR PDB; 7SFD; X-ray; 2.09 A; A=729-1600.
DR PDB; 7SFE; X-ray; 2.55 A; A=729-1600.
DR PDB; 7SFF; X-ray; 2.05 A; A=729-1600.
DR PDB; 7SFG; X-ray; 2.43 A; A=729-1600.
DR PDBsum; 3EPZ; -.
DR PDBsum; 3PTA; -.
DR PDBsum; 3SWR; -.
DR PDBsum; 4WXX; -.
DR PDBsum; 4YOC; -.
DR PDBsum; 4Z96; -.
DR PDBsum; 4Z97; -.
DR PDBsum; 5WVO; -.
DR PDBsum; 5YDR; -.
DR PDBsum; 6K3A; -.
DR PDBsum; 6L1F; -.
DR PDBsum; 6X9I; -.
DR PDBsum; 6X9J; -.
DR PDBsum; 6X9K; -.
DR PDBsum; 7SFC; -.
DR PDBsum; 7SFD; -.
DR PDBsum; 7SFE; -.
DR PDBsum; 7SFF; -.
DR PDBsum; 7SFG; -.
DR AlphaFoldDB; P26358; -.
DR SMR; P26358; -.
DR BioGRID; 108123; 196.
DR CORUM; P26358; -.
DR DIP; DIP-39693N; -.
DR ELM; P26358; -.
DR IntAct; P26358; 55.
DR MINT; P26358; -.
DR STRING; 9606.ENSP00000352516; -.
DR BindingDB; P26358; -.
DR ChEMBL; CHEMBL1993; -.
DR DrugBank; DB00928; Azacitidine.
DR DrugBank; DB01262; Decitabine.
DR DrugBank; DB12116; Epigallocatechin gallate.
DR DrugBank; DB01099; Flucytosine.
DR DrugBank; DB05668; Palifosfamide.
DR DrugBank; DB01035; Procainamide.
DR DrugBank; DB00721; Procaine.
DR DrugCentral; P26358; -.
DR GuidetoPHARMACOLOGY; 2605; -.
DR REBASE; 1161; M.HsaDnmt1A.
DR REBASE; 4240; M.HsaDnmt1B.
DR GlyGen; P26358; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P26358; -.
DR PhosphoSitePlus; P26358; -.
DR SwissPalm; P26358; -.
DR BioMuta; DNMT1; -.
DR DMDM; 12231019; -.
DR EPD; P26358; -.
DR jPOST; P26358; -.
DR MassIVE; P26358; -.
DR MaxQB; P26358; -.
DR PaxDb; P26358; -.
DR PeptideAtlas; P26358; -.
DR PRIDE; P26358; -.
DR ProteomicsDB; 54320; -. [P26358-1]
DR ProteomicsDB; 54321; -. [P26358-2]
DR ProteomicsDB; 54322; -. [P26358-3]
DR ABCD; P26358; 1 sequenced antibody.
DR Antibodypedia; 1052; 1617 antibodies from 51 providers.
DR DNASU; 1786; -.
DR Ensembl; ENST00000340748.8; ENSP00000345739.3; ENSG00000130816.17. [P26358-1]
DR Ensembl; ENST00000359526.9; ENSP00000352516.3; ENSG00000130816.17. [P26358-2]
DR GeneID; 1786; -.
DR KEGG; hsa:1786; -.
DR MANE-Select; ENST00000359526.9; ENSP00000352516.3; NM_001130823.3; NP_001124295.1. [P26358-2]
DR UCSC; uc002mng.4; human. [P26358-1]
DR CTD; 1786; -.
DR DisGeNET; 1786; -.
DR GeneCards; DNMT1; -.
DR GeneReviews; DNMT1; -.
DR HGNC; HGNC:2976; DNMT1.
DR HPA; ENSG00000130816; Low tissue specificity.
DR MalaCards; DNMT1; -.
DR MIM; 126375; gene.
DR MIM; 604121; phenotype.
DR MIM; 614116; phenotype.
DR neXtProt; NX_P26358; -.
DR OpenTargets; ENSG00000130816; -.
DR Orphanet; 314404; Autosomal dominant cerebellar ataxia-deafness-narcolepsy syndrome.
DR Orphanet; 456318; Hereditary sensory neuropathy-deafness-dementia syndrome.
DR PharmGKB; PA27443; -.
DR VEuPathDB; HostDB:ENSG00000130816; -.
DR eggNOG; ENOG502QPKK; Eukaryota.
DR GeneTree; ENSGT00390000005100; -.
DR HOGENOM; CLU_003040_0_0_1; -.
DR InParanoid; P26358; -.
DR OMA; CPEPFRI; -.
DR PhylomeDB; P26358; -.
DR TreeFam; TF328926; -.
DR BRENDA; 2.1.1.37; 2681.
DR PathwayCommons; P26358; -.
DR Reactome; R-HSA-212300; PRC2 methylates histones and DNA.
DR Reactome; R-HSA-427413; NoRC negatively regulates rRNA expression.
DR Reactome; R-HSA-4655427; SUMOylation of DNA methylation proteins.
DR Reactome; R-HSA-5334118; DNA methylation.
DR Reactome; R-HSA-9710421; Defective pyroptosis.
DR SignaLink; P26358; -.
DR SIGNOR; P26358; -.
DR BioGRID-ORCS; 1786; 342 hits in 1102 CRISPR screens.
DR ChiTaRS; DNMT1; human.
DR EvolutionaryTrace; P26358; -.
DR GeneWiki; DNMT1; -.
DR GenomeRNAi; 1786; -.
DR Pharos; P26358; Tclin.
DR PRO; PR:P26358; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P26358; protein.
DR Bgee; ENSG00000130816; Expressed in oocyte and 183 other tissues.
DR ExpressionAtlas; P26358; baseline and differential.
DR Genevisible; P26358; HS.
DR GO; GO:0001674; C:female germ cell nucleus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; HDA:UniProtKB.
DR GO; GO:0005721; C:pericentric heterochromatin; IEA:Ensembl.
DR GO; GO:0005657; C:replication fork; 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:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB.
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:1903926; P:cellular response to bisphenol A; IEA:Ensembl.
DR GO; GO:0006306; P:DNA methylation; TAS:ProtInc.
DR GO; GO:0043045; P:DNA methylation involved in embryo development; IEA:Ensembl.
DR GO; GO:0006346; P:DNA methylation-dependent heterochromatin assembly; IEA:Ensembl.
DR GO; GO:0010216; P:maintenance of DNA methylation; IDA:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL.
DR GO; GO:0051573; P:negative regulation of histone H3-K9 methylation; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; TAS:ProtInc.
DR GO; GO:1905460; P:negative regulation of vascular associated smooth muscle cell apoptotic process; IMP:BHF-UCL.
DR GO; GO:1905931; P:negative regulation of vascular associated smooth muscle cell differentiation involved in phenotypic switching; IMP:BHF-UCL.
DR GO; GO:0090309; P:positive regulation of DNA methylation-dependent heterochromatin assembly; IMP:UniProtKB.
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:1904707; P:positive regulation of vascular associated smooth muscle cell proliferation; IMP:BHF-UCL.
DR GO; GO:0007265; P:Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:Ensembl.
DR Gene3D; 2.30.30.490; -; 2.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR001025; BAH_dom.
DR InterPro; IPR043151; BAH_sf.
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-like.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR002857; Znf_CXXC.
DR Pfam; PF01426; BAH; 2.
DR Pfam; PF06464; DMAP_binding; 1.
DR Pfam; PF00145; DNA_methylase; 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 SMART; SM01137; DMAP_binding; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51038; BAH; 2.
DR PROSITE; PS00094; C5_MTASE_1; 1.
DR PROSITE; PS00095; C5_MTASE_2; 1.
DR PROSITE; PS51912; DMAP1_BIND; 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; Deafness; Disease variant; DNA-binding;
KW Isopeptide bond; Metal-binding; Methylation; Methyltransferase; Neuropathy;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor;
KW S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1616
FT /note="DNA (cytosine-5)-methyltransferase 1"
FT /id="PRO_0000088034"
FT DOMAIN 16..109
FT /note="DMAP1-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01260"
FT DOMAIN 755..880
FT /note="BAH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00370"
FT DOMAIN 972..1100
FT /note="BAH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00370"
FT REPEAT 1109..1110
FT /note="1"
FT REPEAT 1111..1112
FT /note="2"
FT REPEAT 1113..1114
FT /note="3"
FT REPEAT 1115..1116
FT /note="4"
FT REPEAT 1117..1118
FT /note="5"
FT REPEAT 1119..1120
FT /note="6; approximate"
FT DOMAIN 1139..1599
FT /note="SAM-dependent MTase C5-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01016"
FT ZN_FING 646..692
FT /note="CXXC-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT REGION 1..336
FT /note="Interaction with the PRC2/EED-EZH2 complex"
FT /evidence="ECO:0000250"
FT REGION 1..148
FT /note="Interaction with DNMT3A"
FT /evidence="ECO:0000269|PubMed:12145218"
FT REGION 1..120
FT /note="Interaction with DMAP1"
FT /evidence="ECO:0000269|PubMed:10888872"
FT REGION 103..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 149..217
FT /note="Interaction with DNMT3B"
FT /evidence="ECO:0000269|PubMed:12145218"
FT REGION 163..174
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000269|PubMed:9302295"
FT REGION 308..606
FT /note="Interaction with the PRC2/EED-EZH2 complex"
FT /evidence="ECO:0000250"
FT REGION 310..502
FT /note="Homodimerization"
FT REGION 331..550
FT /note="DNA replication foci-targeting sequence"
FT /evidence="ECO:0000250"
FT REGION 651..697
FT /note="Required for activity"
FT REGION 693..754
FT /note="Autoinhibitory linker"
FT REGION 699..729
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1095..1130
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1109..1120
FT /note="6 X 2 AA tandem repeats of K-G"
FT REGION 1121..1616
FT /note="Interaction with the PRC2/EED-EZH2 complex"
FT /evidence="ECO:0000250"
FT REGION 1139..1616
FT /note="Catalytic"
FT MOTIF 177..205
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 155..171
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 175..271
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 279..341
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1226
FT BINDING 353
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 356
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 414
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 418
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 653
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 656
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 659
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 664
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 667
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 670
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 686
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 691
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00509"
FT BINDING 1146
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13864"
FT BINDING 1150..1151
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13864"
FT BINDING 1168..1169
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21163962,
FT ECO:0007744|PDB:3PTA"
FT BINDING 1190..1191
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13864"
FT BINDING 1191
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21163962,
FT ECO:0007744|PDB:3PTA"
FT BINDING 1578
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000269|PubMed:21163962,
FT ECO:0007744|PDB:3PTA"
FT BINDING 1580
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:P13864"
FT SITE 509
FT /note="Important for activity"
FT /evidence="ECO:0000250"
FT MOD_RES 70
FT /note="N6,N6-dimethyllysine"
FT /evidence="ECO:0000269|PubMed:18438403"
FT MOD_RES 127
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 133
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 137
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 141
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13864"
FT MOD_RES 142
FT /note="N6-methyllysine; by SETD7"
FT /evidence="ECO:0000269|PubMed:21151116"
FT MOD_RES 143
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:21151116,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 152
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21565170,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:23186163"
FT MOD_RES 160
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282"
FT MOD_RES 166
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 173
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 188
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282"
FT MOD_RES 259
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000269|PubMed:21947282"
FT MOD_RES 312
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 366
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 398
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 509
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13864"
FT MOD_RES 549
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 714
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 732
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18220336"
FT MOD_RES 749
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282"
FT MOD_RES 878
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 891
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282"
FT MOD_RES 957
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282"
FT MOD_RES 961
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282"
FT MOD_RES 975
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282"
FT MOD_RES 1054
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282"
FT MOD_RES 1111
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282,
FT ECO:0007744|PubMed:19608861"
FT MOD_RES 1113
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282,
FT ECO:0007744|PubMed:19608861"
FT MOD_RES 1115
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282,
FT ECO:0007744|PubMed:19608861"
FT MOD_RES 1117
FT /note="N6-acetyllysine; by EHMT2"
FT /evidence="ECO:0000269|PubMed:21947282"
FT MOD_RES 1119
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P13864"
FT MOD_RES 1121
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P13864"
FT MOD_RES 1349
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282"
FT MOD_RES 1415
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:21947282"
FT CROSSLNK 259
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 1609
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25772364,
FT ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1..336
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_005617"
FT VAR_SEQ 149
FT /note="P -> RSRDPPASASQVTGIRA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_005618"
FT VARIANT 97
FT /note="H -> R (in dbSNP:rs16999593)"
FT /id="VAR_024605"
FT VARIANT 311
FT /note="I -> V (in dbSNP:rs2228612)"
FT /id="VAR_051960"
FT VARIANT 490..491
FT /note="DP -> EY (in HSN1E; unstable protein with decreased
FT enzymatic activity and impaired heterochromatin binding
FT ability after the S phase; dbSNP:rs199473691)"
FT /id="VAR_065965"
FT VARIANT 495
FT /note="Y -> C (in HSN1E; unstable protein with decreased
FT enzymatic activity and impaired heterochromatin binding
FT ability after the S phase; dbSNP:rs199473690)"
FT /evidence="ECO:0000269|PubMed:21532572"
FT /id="VAR_065966"
FT VARIANT 554
FT /note="A -> V (in ADCADN; dbSNP:rs397509392)"
FT /evidence="ECO:0000269|PubMed:22328086"
FT /id="VAR_070055"
FT VARIANT 589
FT /note="G -> A (in ADCADN; dbSNP:rs397509393)"
FT /evidence="ECO:0000269|PubMed:22328086"
FT /id="VAR_070056"
FT VARIANT 590
FT /note="V -> F (in ADCADN; dbSNP:rs397509391)"
FT /evidence="ECO:0000269|PubMed:22328086"
FT /id="VAR_070057"
FT MUTAGEN 163
FT /note="R->A: Abolishes interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:9302295"
FT MUTAGEN 164
FT /note="Q->A: Abolishes interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:9302295"
FT MUTAGEN 166
FT /note="T->A: Abolishes interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:9302295"
FT MUTAGEN 167
FT /note="I->A: Abolishes interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:9302295"
FT MUTAGEN 169
FT /note="S->A: No loss of interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:9302295"
FT MUTAGEN 170
FT /note="H->V: Abolishes interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:9302295"
FT MUTAGEN 171
FT /note="F->V: Abolishes interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:9302295"
FT MUTAGEN 172
FT /note="A->S: No loss of interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:9302295"
FT MUTAGEN 173
FT /note="K->A: No loss of interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:9302295"
FT MUTAGEN 653
FT /note="C->G: Reduces activity about 10-fold; when
FT associated with G-656; G-659; G-664; G-667 and G-670."
FT /evidence="ECO:0000269|PubMed:18754681"
FT MUTAGEN 656
FT /note="C->G: Reduces activity about 10-fold; when
FT associated with G-653; G-659; G-664; G-667 and G-670."
FT /evidence="ECO:0000269|PubMed:18754681"
FT MUTAGEN 659
FT /note="C->G: Reduces activity about 10-fold; when
FT associated with G-653; G-656; G-664; G-667 and G-670."
FT /evidence="ECO:0000269|PubMed:18754681"
FT MUTAGEN 664
FT /note="C->F: Reduces activity about 10-fold; when
FT associated with G-653; G-656; G-659; G-667 and G-670."
FT /evidence="ECO:0000269|PubMed:18754681"
FT MUTAGEN 667
FT /note="C->G: Reduces activity about 10-fold; when
FT associated with G-653; G-656; G-659; G-664 and G-670."
FT /evidence="ECO:0000269|PubMed:18754681"
FT MUTAGEN 670
FT /note="C->G: Reduces activity about 10-fold; when
FT associated with G-653; G-656; G-659; G-664 and G-667."
FT /evidence="ECO:0000269|PubMed:18754681"
FT MUTAGEN 1226
FT /note="C->A: Loss of activity."
FT /evidence="ECO:0000269|PubMed:19450230"
FT HELIX 167..169
FT /evidence="ECO:0007829|PDB:6K3A"
FT TURN 354..356
FT /evidence="ECO:0007829|PDB:5YDR"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:5YDR"
FT HELIX 363..365
FT /evidence="ECO:0007829|PDB:5YDR"
FT HELIX 377..381
FT /evidence="ECO:0007829|PDB:5WVO"
FT HELIX 384..386
FT /evidence="ECO:0007829|PDB:5WVO"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:5WVO"
FT STRAND 404..414
FT /evidence="ECO:0007829|PDB:5WVO"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:5WVO"
FT STRAND 422..425
FT /evidence="ECO:0007829|PDB:5WVO"
FT TURN 426..430
FT /evidence="ECO:0007829|PDB:5WVO"
FT STRAND 433..440
FT /evidence="ECO:0007829|PDB:5WVO"
FT STRAND 453..458
FT /evidence="ECO:0007829|PDB:5WVO"
FT STRAND 463..467
FT /evidence="ECO:0007829|PDB:5WVO"
FT STRAND 470..473
FT /evidence="ECO:0007829|PDB:5WVO"
FT STRAND 476..480
FT /evidence="ECO:0007829|PDB:5WVO"
FT STRAND 485..488
FT /evidence="ECO:0007829|PDB:5WVO"
FT TURN 493..495
FT /evidence="ECO:0007829|PDB:5WVO"
FT HELIX 496..518
FT /evidence="ECO:0007829|PDB:5WVO"
FT HELIX 524..533
FT /evidence="ECO:0007829|PDB:5WVO"
FT HELIX 538..540
FT /evidence="ECO:0007829|PDB:3EPZ"
FT HELIX 547..551
FT /evidence="ECO:0007829|PDB:5WVO"
FT HELIX 554..566
FT /evidence="ECO:0007829|PDB:5WVO"
FT STRAND 575..578
FT /evidence="ECO:0007829|PDB:5WVO"
FT HELIX 579..588
FT /evidence="ECO:0007829|PDB:5WVO"
FT HELIX 592..597
FT /evidence="ECO:0007829|PDB:5YDR"
FT HELIX 622..629
FT /evidence="ECO:0007829|PDB:3SWR"
FT TURN 657..659
FT /evidence="ECO:0007829|PDB:3SWR"
FT HELIX 670..672
FT /evidence="ECO:0007829|PDB:3SWR"
FT TURN 674..677
FT /evidence="ECO:0007829|PDB:4WXX"
FT HELIX 687..689
FT /evidence="ECO:0007829|PDB:3SWR"
FT HELIX 692..703
FT /evidence="ECO:0007829|PDB:4WXX"
FT STRAND 731..735
FT /evidence="ECO:0007829|PDB:6X9I"
FT STRAND 738..741
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 744..746
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 748..752
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 755..758
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 762..765
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 767..769
FT /evidence="ECO:0007829|PDB:3SWR"
FT STRAND 775..785
FT /evidence="ECO:0007829|PDB:6X9J"
FT TURN 786..788
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 789..799
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 800..802
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 803..805
FT /evidence="ECO:0007829|PDB:4YOC"
FT HELIX 806..808
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 813..824
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 825..827
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 828..832
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 834..836
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 843..845
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 851..856
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 860..870
FT /evidence="ECO:0007829|PDB:6X9J"
FT TURN 871..874
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 875..877
FT /evidence="ECO:0007829|PDB:6X9J"
FT TURN 886..891
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 894..906
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 909..916
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 918..928
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 931..934
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 938..941
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 943..945
FT /evidence="ECO:0007829|PDB:6X9J"
FT TURN 966..968
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 972..975
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 976..980
FT /evidence="ECO:0007829|PDB:3SWR"
FT STRAND 992..1003
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1005..1009
FT /evidence="ECO:0007829|PDB:6X9I"
FT STRAND 1015..1022
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1024..1026
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1027..1029
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1031..1034
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1035..1037
FT /evidence="ECO:0007829|PDB:3SWR"
FT STRAND 1041..1052
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1053..1055
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1058..1064
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1065..1067
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1072..1077
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1078..1090
FT /evidence="ECO:0007829|PDB:6X9J"
FT TURN 1091..1094
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1095..1097
FT /evidence="ECO:0007829|PDB:6X9I"
FT HELIX 1101..1103
FT /evidence="ECO:0007829|PDB:6X9I"
FT STRAND 1139..1145
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1150..1158
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1160..1167
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1171..1180
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1185..1187
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1191..1199
FT /evidence="ECO:0007829|PDB:6X9J"
FT TURN 1214..1216
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1219..1222
FT /evidence="ECO:0007829|PDB:6X9J"
FT TURN 1227..1229
FT /evidence="ECO:0007829|PDB:6X9I"
FT STRAND 1231..1233
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1237..1244
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1247..1258
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1261..1268
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1269..1272
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1274..1290
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1293..1300
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1301..1304
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1311..1318
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1336..1338
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1343..1345
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1348..1350
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1367..1371
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1384..1386
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1395..1401
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1419..1426
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1436..1438
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1447..1449
FT /evidence="ECO:0007829|PDB:6X9I"
FT STRAND 1451..1453
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1459..1461
FT /evidence="ECO:0007829|PDB:6X9I"
FT TURN 1462..1464
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1474..1476
FT /evidence="ECO:0007829|PDB:6X9K"
FT HELIX 1477..1480
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1481..1483
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1487..1489
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1493..1496
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1499..1503
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1504..1506
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1508..1510
FT /evidence="ECO:0007829|PDB:6X9J"
FT TURN 1511..1514
FT /evidence="ECO:0007829|PDB:6X9J"
FT STRAND 1523..1525
FT /evidence="ECO:0007829|PDB:3SWR"
FT STRAND 1534..1536
FT /evidence="ECO:0007829|PDB:4WXX"
FT STRAND 1542..1547
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1550..1556
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1569..1577
FT /evidence="ECO:0007829|PDB:6X9J"
FT HELIX 1582..1598
FT /evidence="ECO:0007829|PDB:6X9J"
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
