EZH2_HUMAN
ID EZH2_HUMAN Reviewed; 746 AA.
AC Q15910; B2RAQ1; B3KS30; B7Z1D6; B7Z7L6; Q15755; Q75MG3; Q92857; Q96FI6;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Histone-lysine N-methyltransferase EZH2 {ECO:0000305};
DE EC=2.1.1.356 {ECO:0000269|PubMed:22323599};
DE AltName: Full=ENX-1;
DE AltName: Full=Enhancer of zeste homolog 2 {ECO:0000303|PubMed:28229514};
DE AltName: Full=Lysine N-methyltransferase 6;
GN Name=EZH2 {ECO:0000312|HGNC:HGNC:3527}; Synonyms=KMT6;
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).
RC TISSUE=Brain;
RX PubMed=8954776; DOI=10.1006/geno.1996.0588;
RA Chen H., Rossier C., Antonarakis S.E.;
RT "Cloning of a human homolog of the Drosophila enhancer of zeste gene (EZH2)
RT that maps to chromosome 21q22.2.";
RL Genomics 38:30-37(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9214638; DOI=10.1093/emboj/16.11.3219;
RA Laible G., Wolf A., Dorn R., Reuter G., Nislow C., Lebersorger A.,
RA Popkin D., Pillus L., Jenuwein T.;
RT "Mammalian homologues of the Polycomb-group gene Enhancer of zeste mediate
RT gene silencing in Drosophila heterochromatin and at S. cerevisiae
RT telomeres.";
RL EMBO J. 16:3219-3232(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4 AND 5).
RC TISSUE=Brain, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 134-746.
RX PubMed=8649418; DOI=10.1128/mcb.16.6.3066;
RA Hobert O., Jallal B., Ullrich A.;
RT "Interaction of Vav with ENX-1, a putative transcriptional regulator of
RT homeobox gene expression.";
RL Mol. Cell. Biol. 16:3066-3073(1996).
RN [8]
RP INTERACTION WITH ATRX.
RX PubMed=9499421; DOI=10.1093/hmg/7.4.679;
RA Cardoso C., Timsit S., Villard L., Khrestchatisky M., Fontes M.,
RA Colleaux L.;
RT "Specific interaction between the XNP/ATR-X gene product and the SET domain
RT of the human EZH2 protein.";
RL Hum. Mol. Genet. 7:679-684(1998).
RN [9]
RP INTERACTION WITH EED, AND SUBCELLULAR LOCATION.
RX PubMed=9584199; DOI=10.1128/mcb.18.6.3586;
RA Sewalt R.G.A.B., van der Vlag J., Gunster M.J., Hamer K.M.,
RA den Blaauwen J.L., Satijn D.P.E., Hendrix T., van Driel R., Otte A.P.;
RT "Characterization of interactions between the mammalian polycomb-group
RT proteins Enx1/EZH2 and EED suggests the existence of different mammalian
RT polycomb-group protein complexes.";
RL Mol. Cell. Biol. 18:3586-3595(1998).
RN [10]
RP INTERACTION WITH EED; HDAC1 AND HDAC2.
RX PubMed=10581039; DOI=10.1038/70602;
RA van der Vlag J., Otte A.P.;
RT "Transcriptional repression mediated by the human polycomb-group protein
RT EED involves histone deacetylation.";
RL Nat. Genet. 23:474-478(1999).
RN [11]
RP INTERACTION WITH EED.
RX PubMed=11158321; DOI=10.1128/mcb.21.4.1360-1369.2001;
RA Satijn D.P.E., Hamer K.M., den Blaauwen J., Otte A.P.;
RT "The polycomb group protein EED interacts with YY1, and both proteins
RT induce neural tissue in Xenopus embryos.";
RL Mol. Cell. Biol. 21:1360-1369(2001).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE PRC2 COMPLEX
RP WITH EED; RBBP4; RBBP7 AND SUZ12, METHYLTRANSFERASE ACTIVITY OF THE PRC2
RP COMPLEX, AND MUTAGENESIS OF CYS-588 AND HIS-689.
RX PubMed=12435631; DOI=10.1101/gad.1035902;
RA Kuzmichev A., Nishioka K., Erdjument-Bromage H., Tempst P., Reinberg D.;
RT "Histone methyltransferase activity associated with a human multiprotein
RT complex containing the Enhancer of Zeste protein.";
RL Genes Dev. 16:2893-2905(2002).
RN [13]
RP SUBCELLULAR LOCATION.
RX PubMed=12101246; DOI=10.1128/mcb.22.15.5539-5553.2002;
RA Sewalt R.G.A.B., Lachner M., Vargas M., Hamer K.M., den Blaauwen J.L.,
RA Hendrix T., Melcher M., Schweizer D., Jenuwein T., Otte A.P.;
RT "Selective interactions between vertebrate polycomb homologs and the
RT SUV39H1 histone lysine methyltransferase suggest that histone H3-K9
RT methylation contributes to chromosomal targeting of Polycomb group
RT proteins.";
RL Mol. Cell. Biol. 22:5539-5553(2002).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE PRC2 COMPLEX
RP WITH EED; RBBP4; RBBP7 AND SUZ12, AND METHYLTRANSFERASE ACTIVITY OF THE
RP PRC2 COMPLEX.
RX PubMed=12351676; DOI=10.1126/science.1076997;
RA Cao R., Wang L., Wang H., Xia L., Erdjument-Bromage H., Tempst P.,
RA Jones R.S., Zhang Y.;
RT "Role of histone H3 lysine 27 methylation in Polycomb-group silencing.";
RL Science 298:1039-1043(2002).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, INDUCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=14532106; DOI=10.1093/emboj/cdg542;
RA Bracken A.P., Pasini D., Capra M., Prosperini E., Colli E., Helin K.;
RT "EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and
RT amplified in cancer.";
RL EMBO J. 22:5323-5335(2003).
RN [16]
RP FUNCTION, INTERACTION WITH EED AND SUZ12, AND METHYLTRANSFERASE ACTIVITY OF
RP THE PRC2 COMPLEX.
RX PubMed=15385962; DOI=10.1038/sj.emboj.7600402;
RA Pasini D., Bracken A.P., Jensen M.R., Lazzerini Denchi E., Helin K.;
RT "Suz12 is essential for mouse development and for EZH2 histone
RT methyltransferase activity.";
RL EMBO J. 23:4061-4071(2004).
RN [17]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15231737; DOI=10.1101/gad.1200204;
RA Kirmizis A., Bartley S.M., Kuzmichev A., Margueron R., Reinberg D.,
RA Green R., Farnham P.J.;
RT "Silencing of human polycomb target genes is associated with methylation of
RT histone H3 Lys 27.";
RL Genes Dev. 18:1592-1605(2004).
RN [18]
RP CHARACTERIZATION OF THE PRC2 AND PRC3 COMPLEXES INCLUDING EED; EZH2; RBBP4;
RP RBBP7 AND SUZ12, AND METHYLTRANSFERASE ACTIVITY OF THE PRC2 AND PRC3
RP COMPLEXES.
RX PubMed=15099518; DOI=10.1016/s1097-2765(04)00185-6;
RA Kuzmichev A., Jenuwein T., Tempst P., Reinberg D.;
RT "Different EZH2-containing complexes target methylation of histone H1 or
RT nucleosomal histone H3.";
RL Mol. Cell 14:183-193(2004).
RN [19]
RP FUNCTION, CHARACTERIZATION OF THE PRC2 COMPLEX INCLUDING AEBP2; EED; EZH2;
RP RBBP4 AND SUZ12, AND METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
RX PubMed=15225548; DOI=10.1016/j.molcel.2004.06.020;
RA Cao R., Zhang Y.;
RT "SUZ12 is required for both the histone methyltransferase activity and the
RT silencing function of the EED-EZH2 complex.";
RL Mol. Cell 15:57-67(2004).
RN [20]
RP DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=15208672; DOI=10.1038/sj.onc.1207706;
RA Tang X., Milyavsky M., Shats I., Erez N., Goldfinger N., Rotter V.;
RT "Activated p53 suppresses the histone methyltransferase EZH2 gene.";
RL Oncogene 23:5759-5769(2004).
RN [21]
RP FUNCTION IN RETINOIC ACID SIGNALING, AND INTERACTION WITH PRAME.
RX PubMed=16179254; DOI=10.1016/j.cell.2005.07.003;
RA Epping M.T., Wang L., Edel M.J., Carlee L., Hernandez M., Bernards R.;
RT "The human tumor antigen PRAME is a dominant repressor of retinoic acid
RT receptor signaling.";
RL Cell 122:835-847(2005).
RN [22]
RP CHARACTERIZATION OF THE PRC4 COMPLEX INCLUDING EED; EZH2; RBBP4; RBBP7;
RP SUZ12 AND SIRT1, AND METHYLTRANSFERASE ACTIVITY OF THE PRC4 COMPLEX.
RX PubMed=15684044; DOI=10.1073/pnas.0409875102;
RA Kuzmichev A., Margueron R., Vaquero A., Preissner T.S., Scher M.,
RA Kirmizis A., Ouyang X., Brockdorff N., Abate-Shen C., Farnham P.J.,
RA Reinberg D.;
RT "Composition and histone substrates of polycomb repressive group complexes
RT change during cellular differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1859-1864(2005).
RN [23]
RP INTERACTION WITH EED AND SUZ12, PHOSPHORYLATION AT SER-21 BY AKT1, AND
RP MUTAGENESIS OF SER-21.
RX PubMed=16224021; DOI=10.1126/science.1118947;
RA Cha T.-L., Zhou B.P., Xia W., Wu Y., Yang C.-C., Chen C.-T., Ping B.,
RA Otte A.P., Hung M.-C.;
RT "Akt-mediated phosphorylation of EZH2 suppresses methylation of lysine 27
RT in histone H3.";
RL Science 310:306-310(2005).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, AND IDENTIFICATION BY
RP 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 [25]
RP FUNCTION.
RX PubMed=16618801; DOI=10.1101/gad.381706;
RA Bracken A.P., Dietrich N., Pasini D., Hansen K.H., Helin K.;
RT "Genome-wide mapping of Polycomb target genes unravels their roles in cell
RT fate transitions.";
RL Genes Dev. 20:1123-1136(2006).
RN [26]
RP METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
RX PubMed=16431907; DOI=10.1074/jbc.m513425200;
RA Martin C., Cao R., Zhang Y.;
RT "Substrate preferences of the EZH2 histone methyltransferase complex.";
RL J. Biol. Chem. 281:8365-8370(2006).
RN [27]
RP FUNCTION.
RX PubMed=16717091; DOI=10.1074/jbc.m603722200;
RA Etchegaray J.P., Yang X., DeBruyne J.P., Peters A.H., Weaver D.R.,
RA Jenuwein T., Reppert S.M.;
RT "The polycomb group protein EZH2 is required for mammalian circadian clock
RT function.";
RL J. Biol. Chem. 281:21209-21215(2006).
RN [28]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, AND IDENTIFICATION BY
RP 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 phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [29]
RP FUNCTION, AND INTERACTION OF THE PRC2 COMPLEX WITH DNMT1; DNMT3A AND
RP DNMT3B.
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 [30]
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 [31]
RP FUNCTION.
RX PubMed=16936726; DOI=10.1038/nsmb1142;
RA Kim D.H., Villeneuve L.M., Morris K.V., Rossi J.J.;
RT "Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human
RT cells.";
RL Nat. Struct. Mol. Biol. 13:793-797(2006).
RN [32]
RP FUNCTION.
RX PubMed=17210787; DOI=10.1101/gad.1499407;
RA Kotake Y., Cao R., Viatour P., Sage J., Zhang Y., Xiong Y.;
RT "pRB family proteins are required for H3K27 trimethylation and Polycomb
RT repression complexes binding to and silencing p16INK4alpha tumor suppressor
RT gene.";
RL Genes Dev. 21:49-54(2007).
RN [33]
RP FUNCTION, DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=17344414; DOI=10.1101/gad.415507;
RA Bracken A.P., Kleine-Kohlbrecher D., Dietrich N., Pasini D., Gargiulo G.,
RA Beekman C., Theilgaard-Moench K., Minucci S., Porse B.T., Marine J.-C.,
RA Hansen K.H., Helin K.;
RT "The Polycomb group proteins bind throughout the INK4A-ARF locus and are
RT disassociated in senescent cells.";
RL Genes Dev. 21:525-530(2007).
RN [34]
RP DE NOVO DNA METHYLATION OF PRC2 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 [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, 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 [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, AND IDENTIFICATION BY
RP 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 the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [37]
RP FUNCTION, AND IDENTIFICATION IN THE PRC2/EED-EZH1 COMPLEX.
RX PubMed=19026781; DOI=10.1016/j.molcel.2008.11.004;
RA Margueron R., Li G., Sarma K., Blais A., Zavadil J., Woodcock C.L.,
RA Dynlacht B.D., Reinberg D.;
RT "Ezh1 and Ezh2 maintain repressive chromatin through different
RT mechanisms.";
RL Mol. Cell 32:503-518(2008).
RN [38]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE PRC2 COMPLEX,
RP AND METHYLTRANSFERASE ACTIVITY OF THE PRC2 COMPLEX.
RX PubMed=18086877; DOI=10.1128/mcb.01589-07;
RA Cao R., Wang H., He J., Erdjument-Bromage H., Tempst P., Zhang Y.;
RT "Role of hPHF1 in H3K27 methylation and Hox gene silencing.";
RL Mol. Cell. Biol. 28:1862-1872(2008).
RN [39]
RP FUNCTION, INTERACTION WITH EED; SUZ12 AND PHF1, METHYLTRANSFERASE ACTIVITY
RP OF THE PRC2 COMPLEX, AND MUTAGENESIS OF HIS-689.
RX PubMed=18285464; DOI=10.1128/mcb.02017-07;
RA Sarma K., Margueron R., Ivanov A., Pirrotta V., Reinberg D.;
RT "Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in
RT vivo.";
RL Mol. Cell. Biol. 28:2718-2731(2008).
RN [40]
RP SUMOYLATION.
RX PubMed=18628979; DOI=10.1371/journal.pone.0002704;
RA Riising E.M., Boggio R., Chiocca S., Helin K., Pasini D.;
RT "The polycomb repressive complex 2 is a potential target of SUMO
RT modifications.";
RL PLoS ONE 3:E2704-E2704(2008).
RN [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-366; THR-367 AND THR-487, 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 [42]
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 [43]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, 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 [44]
RP FUNCTION, PHOSPHORYLATION AT THR-345 BY CDK1 AND CDK2, AND MUTAGENESIS OF
RP THR-345.
RX PubMed=20935635; DOI=10.1038/ncb2116;
RA Chen S., Bohrer L.R., Rai A.N., Pan Y., Gan L., Zhou X., Bagchi A.,
RA Simon J.A., Huang H.;
RT "Cyclin-dependent kinases regulate epigenetic gene silencing through
RT phosphorylation of EZH2.";
RL Nat. Cell Biol. 12:1108-1114(2010).
RN [45]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, AND IDENTIFICATION BY
RP 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 [46]
RP INTERACTION WITH CDYL.
RX PubMed=22009739; DOI=10.1074/jbc.m111.271064;
RA Zhang Y., Yang X., Gui B., Xie G., Zhang D., Shang Y., Liang J.;
RT "Corepressor protein CDYL functions as a molecular bridge between polycomb
RT repressor complex 2 and repressive chromatin mark trimethylated histone
RT lysine 27.";
RL J. Biol. Chem. 286:42414-42425(2011).
RN [47]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-487, AND IDENTIFICATION BY
RP 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 [48]
RP FUNCTION.
RX PubMed=23063525; DOI=10.1016/j.molcel.2012.09.004;
RA Lee J.M., Lee J.S., Kim H., Kim K., Park H., Kim J.Y., Lee S.H., Kim I.S.,
RA Kim J., Lee M., Chung C.H., Seo S.B., Yoon J.B., Ko E., Noh D.Y., Kim K.I.,
RA Kim K.K., Baek S.H.;
RT "EZH2 generates a methyl degron that is recognized by the DCAF1/DDB1/CUL4
RT E3 ubiquitin ligase complex.";
RL Mol. Cell 48:572-586(2012).
RN [49]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-76; THR-339; SER-363; THR-367
RP AND THR-487, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [50]
RP GLYCOSYLATION AT SER-75, MUTAGENESIS OF SER-75, AND FUNCTION.
RX PubMed=24474760; DOI=10.1073/pnas.1323226111;
RA Chu C.S., Lo P.W., Yeh Y.H., Hsu P.H., Peng S.H., Teng Y.C., Kang M.L.,
RA Wong C.H., Juan L.J.;
RT "O-GlcNAcylation regulates EZH2 protein stability and function.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:1355-1360(2014).
RN [51]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-634, AND IDENTIFICATION BY MASS
RP 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 [52]
RP FUNCTION, AND INTERACTION WITH ARMC12.
RX PubMed=30026490; DOI=10.1038/s41467-018-05286-2;
RA Li D., Song H., Mei H., Fang E., Wang X., Yang F., Li H., Chen Y.,
RA Huang K., Zheng L., Tong Q.;
RT "Armadillo repeat containing 12 promotes neuroblastoma progression through
RT interaction with retinoblastoma binding protein 4.";
RL Nat. Commun. 9:2829-2829(2018).
RN [53]
RP INTERACTION WITH EZHIP.
RX PubMed=31086175; DOI=10.1038/s41467-019-09981-6;
RA Jain S.U., Do T.J., Lund P.J., Rashoff A.Q., Diehl K.L., Cieslik M.,
RA Bajic A., Juretic N., Deshmukh S., Venneti S., Muir T.W., Garcia B.A.,
RA Jabado N., Lewis P.W.;
RT "PFA ependymoma-associated protein EZHIP inhibits PRC2 activity through a
RT H3 K27M-like mechanism.";
RL Nat. Commun. 10:2146-2146(2019).
RN [54]
RP INTERACTION WITH EZHIP, AND TISSUE SPECIFICITY.
RX PubMed=31451685; DOI=10.1038/s41467-019-11800-x;
RA Ragazzini R., Perez-Palacios R., Baymaz I.H., Diop S., Ancelin K.,
RA Zielinski D., Michaud A., Givelet M., Borsos M., Aflaki S., Legoix P.,
RA Jansen P.W.T.C., Servant N., Torres-Padilla M.E., Bourc'his D., Fouchet P.,
RA Vermeulen M., Margueron R.;
RT "EZHIP constrains Polycomb Repressive Complex 2 activity in germ cells.";
RL Nat. Commun. 10:3858-3858(2019).
RN [55]
RP FUNCTION, AND INTERACTION WITH EZHIP.
RX PubMed=30923826; DOI=10.1093/neuonc/noz058;
RA Huebner J.M., Mueller T., Papageorgiou D.N., Mauermann M., Krijgsveld J.,
RA Russell R.B., Ellison D.W., Pfister S.M., Pajtler K.W., Kool M.;
RT "EZHIP / CXorf67 mimics K27M mutated oncohistones and functions as an
RT intrinsic inhibitor of PRC2 function in aggressive posterior fossa
RT ependymoma.";
RL Neuro-oncol. 21:878-889(2019).
RN [56]
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 [57]
RP VARIANTS PHE-641; SER-641; ASN-641; HIS-641 AND CYS-641.
RX PubMed=20081860; DOI=10.1038/ng.518;
RA Morin R.D., Johnson N.A., Severson T.M., Mungall A.J., An J., Goya R.,
RA Paul J.E., Boyle M., Woolcock B.W., Kuchenbauer F., Yap D., Humphries R.K.,
RA Griffith O.L., Shah S., Zhu H., Kimbara M., Shashkin P., Charlot J.F.,
RA Tcherpakov M., Corbett R., Tam A., Varhol R., Smailus D., Moksa M.,
RA Zhao Y., Delaney A., Qian H., Birol I., Schein J., Moore R., Holt R.,
RA Horsman D.E., Connors J.M., Jones S., Aparicio S., Hirst M., Gascoyne R.D.,
RA Marra M.A.;
RT "Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large
RT B-cell lymphomas of germinal-center origin.";
RL Nat. Genet. 42:181-185(2010).
RN [58]
RP VARIANTS TRP-571; CYS-641; CYS-685 AND ASP-726, AND CHARACTERIZATION OF
RP VARIANTS TRP-571; CYS-641; CYS-685 AND ASP-726.
RX PubMed=20601953; DOI=10.1038/ng.621;
RA Ernst T., Chase A.J., Score J., Hidalgo-Curtis C.E., Bryant C., Jones A.V.,
RA Waghorn K., Zoi K., Ross F.M., Reiter A., Hochhaus A., Drexler H.G.,
RA Duncombe A., Cervantes F., Oscier D., Boultwood J., Grand F.H., Cross N.C.;
RT "Inactivating mutations of the histone methyltransferase gene EZH2 in
RT myeloid disorders.";
RL Nat. Genet. 42:722-726(2010).
RN [59]
RP CHARACTERIZATION OF VARIANTS PHE-641 AND ASN-641.
RX PubMed=21190999; DOI=10.1182/blood-2010-11-321208;
RA Yap D.B., Chu J., Berg T., Schapira M., Cheng S.W., Moradian A.,
RA Morin R.D., Mungall A.J., Meissner B., Boyle M., Marquez V.E., Marra M.A.,
RA Gascoyne R.D., Humphries R.K., Arrowsmith C.H., Morin G.B., Aparicio S.A.;
RT "Somatic mutations at EZH2 Y641 act dominantly through a mechanism of
RT selectively altered PRC2 catalytic activity, to increase H3K27
RT trimethylation.";
RL Blood 117:2451-2459(2011).
RN [60]
RP VARIANT HIS-685.
RX PubMed=21828135; DOI=10.1182/blood-2010-10-311019;
RA Jankowska A.M., Makishima H., Tiu R.V., Szpurka H., Huang Y., Traina F.,
RA Visconte V., Sugimoto Y., Prince C., O'Keefe C., Hsi E.D., List A.,
RA Sekeres M.A., Rao A., McDevitt M.A., Maciejewski J.P.;
RT "Mutational spectrum analysis of chronic myelomonocytic leukemia includes
RT genes associated with epigenetic regulation: UTX, EZH2, and DNMT3A.";
RL Blood 118:3932-3941(2011).
RN [61]
RP VARIANTS WVS THR-134; GLU-156; ARG-279; MET-621; ASN-658; THR-677; CYS-679;
RP LEU-690; 728-TYR--PRO-746 DEL AND CYS-736.
RX PubMed=22190405; DOI=10.18632/oncotarget.385;
RG Childhood Overgrowth Collaboration;
RA Tatton-Brown K., Hanks S., Ruark E., Zachariou A., Duarte S.V., Ramsay E.,
RA Snape K., Murray A., Perdeaux E.R., Seal S., Loveday C., Banka S.,
RA Clericuzio C., Flinter F., Magee A., McConnell V., Patton M., Raith W.,
RA Rankin J., Splitt M., Strenger V., Taylor C., Wheeler P., Temple K.I.,
RA Cole T., Douglas J., Rahman N.;
RT "Germline mutations in the oncogene EZH2 cause Weaver syndrome and
RT increased human height.";
RL Oncotarget 2:1127-1133(2011).
RN [62]
RP VARIANTS WVS SER-132; TYR-153 DEL AND TYR-689.
RX PubMed=22177091; DOI=10.1016/j.ajhg.2011.11.018;
RA Gibson W.T., Hood R.L., Zhan S.H., Bulman D.E., Fejes A.P., Moore R.,
RA Mungall A.J., Eydoux P., Babul-Hirji R., An J., Marra M.A., Chitayat D.,
RA Boycott K.M., Weaver D.D., Jones S.J.;
RT "Mutations in EZH2 cause Weaver syndrome.";
RL Am. J. Hum. Genet. 90:110-118(2012).
RN [63]
RP VARIANT GLY-677, CHARACTERIZATION OF VARIANTS ASN-641; CYS-641; HIS-641;
RP PHE-641 AND GLY-677, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22323599; DOI=10.1073/pnas.1116418109;
RA McCabe M.T., Graves A.P., Ganji G., Diaz E., Halsey W.S., Jiang Y.,
RA Smitheman K.N., Ott H.M., Pappalardi M.B., Allen K.E., Chen S.B.,
RA Della Pietra A. III, Dul E., Hughes A.M., Gilbert S.A., Thrall S.H.,
RA Tummino P.J., Kruger R.G., Brandt M., Schwartz B., Creasy C.L.;
RT "Mutation of A677 in histone methyltransferase EZH2 in human B-cell
RT lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27).";
RL Proc. Natl. Acad. Sci. U.S.A. 109:2989-2994(2012).
RN [64]
RP VARIANT WVS LYS-740.
RX PubMed=23239504; DOI=10.1002/ajmg.a.35660;
RA Al-Salem A., Alshammari M.J., Hassan H., Alazami A.M., Alkuraya F.S.;
RT "Weaver syndrome and defective cortical development: a rare association.";
RL Am. J. Med. Genet. A 161A:225-227(2013).
RN [65]
RP VARIANTS WVS CYS-133 AND CYS-679, CHARACTERIZATION OF VARIANTS WVS SER-132;
RP CYS-133; TYR-153 DEL; CYS-679 AND TYR-689, VARIANT HIS-185,
RP CHARACTERIZATION OF VARIANT HIS-185, AND MUTAGENESIS OF PHE-667.
RX PubMed=26694085; DOI=10.1002/humu.22946;
RA Cohen A.S., Yap D.B., Lewis M.E., Chijiwa C., Ramos-Arroyo M.A.,
RA Tkachenko N., Milano V., Fradin M., McKinnon M.L., Townsend K.N., Xu J.,
RA Van Allen M.I., Ross C.J., Dobyns W.B., Weaver D.D., Gibson W.T.;
RT "Weaver Syndrome-Associated EZH2 Protein Variants Show Impaired Histone
RT Methyltransferase Function In Vitro.";
RL Hum. Mutat. 37:301-307(2016).
RN [66]
RP INVOLVEMENT IN WVS.
RX PubMed=28229514; DOI=10.1002/humu.23200;
RA Imagawa E., Higashimoto K., Sakai Y., Numakura C., Okamoto N.,
RA Matsunaga S., Ryo A., Sato Y., Sanefuji M., Ihara K., Takada Y.,
RA Nishimura G., Saitsu H., Mizuguchi T., Miyatake S., Nakashima M.,
RA Miyake N., Soejima H., Matsumoto N.;
RT "Mutations in genes encoding polycomb repressive complex 2 subunits cause
RT Weaver syndrome.";
RL Hum. Mutat. 38:637-648(2017).
CC -!- FUNCTION: Polycomb group (PcG) protein. Catalytic subunit of the
CC PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27'
CC (H3K27me) of histone H3, leading to transcriptional repression of the
CC affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of
CC histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively.
CC Displays a preference for substrates with less methylation, loses
CC activity when progressively more methyl groups are incorporated into
CC H3K27, H3K27me0 > H3K27me1 > H3K27me2 (PubMed:22323599,
CC PubMed:30923826). Compared to EZH1-containing complexes, it is more
CC abundant in embryonic stem cells and plays a major role in forming
CC H3K27me3, which is required for embryonic stem cell identity and proper
CC differentiation. The PRC2/EED-EZH2 complex may also serve as a
CC recruiting platform for DNA methyltransferases, thereby linking two
CC epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2
CC complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target
CC genes. EZH2 can also methylate non-histone proteins such as the
CC transcription factor GATA4 and the nuclear receptor RORA. Regulates the
CC circadian clock via histone methylation at the promoter of the
CC circadian genes. Essential for the CRY1/2-mediated repression of the
CC transcriptional activation of PER1/2 by the CLOCK-ARNTL/BMAL1
CC heterodimer; involved in the di and trimethylation of 'Lys-27' of
CC histone H3 on PER1/2 promoters which is necessary for the CRY1/2
CC proteins to inhibit transcription. {ECO:0000269|PubMed:14532106,
CC ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737,
CC ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16179254,
CC ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:16618801,
CC ECO:0000269|PubMed:16717091, ECO:0000269|PubMed:16936726,
CC ECO:0000269|PubMed:17210787, ECO:0000269|PubMed:17344414,
CC ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:19026781,
CC ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:22323599,
CC ECO:0000269|PubMed:23063525, ECO:0000269|PubMed:24474760,
CC ECO:0000269|PubMed:30026490, ECO:0000269|PubMed:30923826}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(27)-[histone H3] + 3 S-adenosyl-L-methionine = 3 H(+)
CC + N(6),N(6),N(6)-trimethyl-L-lysyl(27)-[histone H3] + 3 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60292, Rhea:RHEA-COMP:15535, Rhea:RHEA-
CC COMP:15548, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61961; EC=2.1.1.356;
CC Evidence={ECO:0000269|PubMed:22323599};
CC -!- SUBUNIT: Component of the PRC2/EED-EZH2 complex, which includes EED,
CC EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2. The minimum components
CC required for methyltransferase activity of the PRC2/EED-EZH2 complex
CC are EED, EZH2 and SUZ12. The PRC2 complex may also interact with DNMT1,
CC DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the
CC SUZ12 subunit. Interacts with HDAC1 and HDAC2. Binds ATRX via the SET
CC domain (Probable). Interacts with PRAME. Interacts with CDYL. Interacts
CC with CLOCK, ARNTL/BMAL1 and CRY1 (By similarity). Interacts with
CC DNMT3L; the interaction is direct (By similarity). Interacts with
CC EZHIP; the interaction blocks EZH2 methyltransferase activity
CC (PubMed:30923826, PubMed:31086175, PubMed:31451685). Interacts with
CC ZNF263; recruited to the SIX3 promoter along with other proteins
CC involved in chromatin modification and transcriptional corepression
CC where it contributes to transcriptional repression (PubMed:32051553).
CC Interacts with ARMC12 (PubMed:30026490). {ECO:0000250|UniProtKB:Q61188,
CC ECO:0000269|PubMed:10581039, ECO:0000269|PubMed:11158321,
CC ECO:0000269|PubMed:12351676, ECO:0000269|PubMed:12435631,
CC ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16179254,
CC ECO:0000269|PubMed:16224021, ECO:0000269|PubMed:16357870,
CC ECO:0000269|PubMed:18086877, ECO:0000269|PubMed:18285464,
CC ECO:0000269|PubMed:19026781, ECO:0000269|PubMed:22009739,
CC ECO:0000269|PubMed:30026490, ECO:0000269|PubMed:30923826,
CC ECO:0000269|PubMed:31086175, ECO:0000269|PubMed:31451685,
CC ECO:0000269|PubMed:32051553, ECO:0000269|PubMed:9499421,
CC ECO:0000269|PubMed:9584199, ECO:0000305}.
CC -!- INTERACTION:
CC Q15910; Q8IXJ9: ASXL1; NbExp=6; IntAct=EBI-530054, EBI-1646500;
CC Q15910; P46100: ATRX; NbExp=2; IntAct=EBI-530054, EBI-396461;
CC Q15910; Q96MT8: CEP63; NbExp=4; IntAct=EBI-530054, EBI-741977;
CC Q15910; P26358: DNMT1; NbExp=8; IntAct=EBI-530054, EBI-719459;
CC Q15910; Q9Y6K1: DNMT3A; NbExp=6; IntAct=EBI-530054, EBI-923653;
CC Q15910; Q9UBC3: DNMT3B; NbExp=14; IntAct=EBI-530054, EBI-80125;
CC Q15910; O75530: EED; NbExp=12; IntAct=EBI-530054, EBI-923794;
CC Q15910; Q92833-1: JARID2; NbExp=7; IntAct=EBI-530054, EBI-15825247;
CC Q15910; O43189: PHF1; NbExp=6; IntAct=EBI-530054, EBI-530034;
CC Q15910; Q15156: PML-RAR; NbExp=8; IntAct=EBI-530054, EBI-867256;
CC Q15910; P10276: RARA; NbExp=2; IntAct=EBI-530054, EBI-413374;
CC Q15910; P40763: STAT3; NbExp=5; IntAct=EBI-530054, EBI-518675;
CC Q15910; O43463: SUV39H1; NbExp=2; IntAct=EBI-530054, EBI-349968;
CC Q15910; Q15022: SUZ12; NbExp=25; IntAct=EBI-530054, EBI-1264675;
CC Q15910; Q9CWR8: Dnmt3l; Xeno; NbExp=2; IntAct=EBI-530054, EBI-3043871;
CC Q15910-2; P07550: ADRB2; NbExp=3; IntAct=EBI-10699473, EBI-491169;
CC Q15910-2; P28329-3: CHAT; NbExp=3; IntAct=EBI-10699473, EBI-25837549;
CC Q15910-2; O75530-2: EED; NbExp=3; IntAct=EBI-10699473, EBI-11132357;
CC Q15910-2; P22607: FGFR3; NbExp=3; IntAct=EBI-10699473, EBI-348399;
CC Q15910-2; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-10699473, EBI-10172052;
CC Q15910-2; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-10699473, EBI-5235340;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12101246,
CC ECO:0000269|PubMed:14532106, ECO:0000269|PubMed:15231737,
CC ECO:0000269|PubMed:9584199}. Note=Localizes to the inactive X
CC chromosome in trophoblast stem cells. {ECO:0000250|UniProtKB:Q61188}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q15910-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15910-2; Sequence=VSP_038815;
CC Name=3;
CC IsoId=Q15910-3; Sequence=VSP_038814;
CC Name=4;
CC IsoId=Q15910-4; Sequence=VSP_038813;
CC Name=5;
CC IsoId=Q15910-5; Sequence=VSP_038813, VSP_038816;
CC -!- TISSUE SPECIFICITY: In the ovary, expressed in primordial follicles and
CC oocytes and also in external follicle cells (at protein level)
CC (PubMed:31451685). Expressed in many tissues (PubMed:14532106).
CC Overexpressed in numerous tumor types including carcinomas of the
CC breast, colon, larynx, lymphoma and testis (PubMed:14532106).
CC {ECO:0000269|PubMed:14532106, ECO:0000269|PubMed:31451685}.
CC -!- DEVELOPMENTAL STAGE: Expression decreases during senescence of
CC embryonic fibroblasts (HEFs). Expression peaks at the G1/S phase
CC boundary. {ECO:0000269|PubMed:14532106, ECO:0000269|PubMed:15208672,
CC ECO:0000269|PubMed:17344414}.
CC -!- INDUCTION: Expression is induced by E2F1, E2F2 and E2F3. Expression is
CC reduced in cells subject to numerous types of stress including UV-,
CC IR- and bleomycin-induced DNA damage and by activation of p53/TP53.
CC {ECO:0000269|PubMed:14532106, ECO:0000269|PubMed:15208672,
CC ECO:0000269|PubMed:17344414}.
CC -!- PTM: Phosphorylated by AKT1. Phosphorylation by AKT1 reduces
CC methyltransferase activity. Phosphorylation at Thr-345 by CDK1 and CDK2
CC promotes maintenance of H3K27me3 levels at EZH2-target loci, thus
CC leading to epigenetic gene silencing. {ECO:0000269|PubMed:16224021,
CC ECO:0000269|PubMed:20935635}.
CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:18628979}.
CC -!- PTM: Glycosylated: O-GlcNAcylation at Ser-75 by OGT increases stability
CC of EZH2 and facilitates the formation of H3K27me3 by the PRC2/EED-EZH2
CC complex. {ECO:0000269|PubMed:24474760}.
CC -!- DISEASE: Weaver syndrome (WVS) [MIM:277590]: A syndrome of accelerated
CC growth and osseous maturation, unusual craniofacial appearance, hoarse
CC and low-pitched cry, and hypertonia with camptodactyly. Distinguishing
CC features of Weaver syndrome include broad forehead and face, ocular
CC hypertelorism, prominent wide philtrum, micrognathia, deep horizontal
CC chin groove, and deep-set nails. In addition, carpal bone development
CC is advanced over the rest of the hand. {ECO:0000269|PubMed:22177091,
CC ECO:0000269|PubMed:22190405, ECO:0000269|PubMed:23239504,
CC ECO:0000269|PubMed:26694085, ECO:0000269|PubMed:28229514}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. EZ subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC -!- CAUTION: Two variants of the PRC2 complex have been described, termed
CC PRC3 and PRC4. Each of the three complexes may include a different
CC complement of EED isoforms, although the precise sequences of the
CC isoforms in each complex have not been determined. The PRC2 and PRC4
CC complexes may also methylate 'Lys-26' of histone H1 in addition to
CC 'Lys-27' of histone H3 (PubMed:15099518 and PubMed:15684044), although
CC other studies have demonstrated no methylation of 'Lys-26' of histone
CC H1 by PRC2 (PubMed:16431907). {ECO:0000305|PubMed:16431907}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAS07448.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; X95653; CAA64955.1; -; mRNA.
DR EMBL; U61145; AAC51520.1; -; mRNA.
DR EMBL; AK302216; BAH13652.1; -; mRNA.
DR EMBL; AK092676; BAG52592.1; -; mRNA.
DR EMBL; AK293239; BAH11472.1; -; mRNA.
DR EMBL; AK314291; BAG36948.1; -; mRNA.
DR EMBL; AC006323; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC073140; AAS07448.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CH471146; EAW80067.1; -; Genomic_DNA.
DR EMBL; CH471146; EAW80070.1; -; Genomic_DNA.
DR EMBL; BC010858; AAH10858.1; -; mRNA.
DR EMBL; U52965; AAC50591.1; -; Genomic_DNA.
DR CCDS; CCDS56516.1; -. [Q15910-1]
DR CCDS; CCDS56517.1; -. [Q15910-5]
DR CCDS; CCDS56518.1; -. [Q15910-4]
DR CCDS; CCDS5891.1; -. [Q15910-2]
DR CCDS; CCDS5892.1; -. [Q15910-3]
DR PIR; G02838; G02838.
DR RefSeq; NP_001190176.1; NM_001203247.1. [Q15910-1]
DR RefSeq; NP_001190177.1; NM_001203248.1. [Q15910-4]
DR RefSeq; NP_001190178.1; NM_001203249.1. [Q15910-5]
DR RefSeq; NP_004447.2; NM_004456.4. [Q15910-2]
DR RefSeq; NP_694543.1; NM_152998.2. [Q15910-3]
DR RefSeq; XP_011514186.1; XM_011515884.2. [Q15910-2]
DR PDB; 4MI0; X-ray; 2.00 A; A=520-746.
DR PDB; 4MI5; X-ray; 2.00 A; A=521-746.
DR PDB; 5GSA; X-ray; 2.49 A; C/D=40-68.
DR PDB; 5H14; X-ray; 1.90 A; C/D=40-68.
DR PDB; 5H15; X-ray; 2.27 A; C/D=40-68.
DR PDB; 5H17; X-ray; 2.30 A; B=40-68.
DR PDB; 5H19; X-ray; 1.90 A; B=40-68.
DR PDB; 5H24; X-ray; 2.50 A; C/D=40-68.
DR PDB; 5H25; X-ray; 2.88 A; C/D=40-68.
DR PDB; 5HYN; X-ray; 2.95 A; A/F/K/Q=1-746.
DR PDB; 5IJ7; X-ray; 2.62 A; A/B=429-487, A/B=511-746.
DR PDB; 5IJ8; X-ray; 2.99 A; A/B=429-487, A/B=511-531, A/B=533-746.
DR PDB; 5LS6; X-ray; 3.47 A; A/D/G/J=1-385, A/D/G/J=421-746.
DR PDB; 5U5T; X-ray; 1.60 A; C/D=39-68.
DR PDB; 5U62; X-ray; 1.90 A; C/D=39-68.
DR PDB; 5WG6; X-ray; 3.90 A; A/C=2-746.
DR PDB; 5WUK; X-ray; 2.03 A; B=41-68.
DR PDB; 6C23; EM; 3.90 A; C/K=1-746.
DR PDB; 6C24; EM; 3.50 A; C/K=1-746.
DR PDB; 6LO2; X-ray; 2.21 A; C/D=40-68.
DR PDB; 6P5L; X-ray; 3.30 A; D=489-496.
DR PDB; 6U4Y; X-ray; 2.91 A; A/B/C=2-182, A/B/C=220-257.
DR PDB; 6WKR; EM; 3.50 A; C=1-746.
DR PDB; 7AT8; EM; 4.40 A; A=1-746.
DR PDB; 7QJG; X-ray; 1.80 A; C/D=40-68.
DR PDB; 7QJU; X-ray; 1.80 A; C/D=40-68.
DR PDB; 7QK4; X-ray; 1.60 A; B=40-68.
DR PDBsum; 4MI0; -.
DR PDBsum; 4MI5; -.
DR PDBsum; 5GSA; -.
DR PDBsum; 5H14; -.
DR PDBsum; 5H15; -.
DR PDBsum; 5H17; -.
DR PDBsum; 5H19; -.
DR PDBsum; 5H24; -.
DR PDBsum; 5H25; -.
DR PDBsum; 5HYN; -.
DR PDBsum; 5IJ7; -.
DR PDBsum; 5IJ8; -.
DR PDBsum; 5LS6; -.
DR PDBsum; 5U5T; -.
DR PDBsum; 5U62; -.
DR PDBsum; 5WG6; -.
DR PDBsum; 5WUK; -.
DR PDBsum; 6C23; -.
DR PDBsum; 6C24; -.
DR PDBsum; 6LO2; -.
DR PDBsum; 6P5L; -.
DR PDBsum; 6U4Y; -.
DR PDBsum; 6WKR; -.
DR PDBsum; 7AT8; -.
DR PDBsum; 7QJG; -.
DR PDBsum; 7QJU; -.
DR PDBsum; 7QK4; -.
DR AlphaFoldDB; Q15910; -.
DR SMR; Q15910; -.
DR BioGRID; 108446; 786.
DR CORUM; Q15910; -.
DR DIP; DIP-34002N; -.
DR IntAct; Q15910; 128.
DR MINT; Q15910; -.
DR STRING; 9606.ENSP00000320147; -.
DR BindingDB; Q15910; -.
DR ChEMBL; CHEMBL2189110; -.
DR DrugBank; DB14581; CPI-1205.
DR DrugBank; DB12887; Tazemetostat.
DR DrugCentral; Q15910; -.
DR GuidetoPHARMACOLOGY; 2654; -.
DR GlyGen; Q15910; 6 sites, 1 O-linked glycan (5 sites).
DR iPTMnet; Q15910; -.
DR PhosphoSitePlus; Q15910; -.
DR SwissPalm; Q15910; -.
DR BioMuta; EZH2; -.
DR DMDM; 3334180; -.
DR EPD; Q15910; -.
DR jPOST; Q15910; -.
DR MassIVE; Q15910; -.
DR MaxQB; Q15910; -.
DR PaxDb; Q15910; -.
DR PeptideAtlas; Q15910; -.
DR PRIDE; Q15910; -.
DR ProteomicsDB; 60809; -. [Q15910-1]
DR ProteomicsDB; 60810; -. [Q15910-2]
DR ProteomicsDB; 60811; -. [Q15910-3]
DR ProteomicsDB; 60812; -. [Q15910-4]
DR ProteomicsDB; 60813; -. [Q15910-5]
DR Antibodypedia; 32761; 882 antibodies from 45 providers.
DR DNASU; 2146; -.
DR Ensembl; ENST00000320356.7; ENSP00000320147.2; ENSG00000106462.12. [Q15910-2]
DR Ensembl; ENST00000350995.6; ENSP00000223193.2; ENSG00000106462.12. [Q15910-3]
DR Ensembl; ENST00000460911.5; ENSP00000419711.1; ENSG00000106462.12. [Q15910-1]
DR Ensembl; ENST00000476773.5; ENSP00000419050.1; ENSG00000106462.12. [Q15910-5]
DR Ensembl; ENST00000478654.5; ENSP00000417062.1; ENSG00000106462.12. [Q15910-5]
DR Ensembl; ENST00000483967.5; ENSP00000419856.1; ENSG00000106462.12. [Q15910-4]
DR GeneID; 2146; -.
DR KEGG; hsa:2146; -.
DR MANE-Select; ENST00000320356.7; ENSP00000320147.2; NM_004456.5; NP_004447.2. [Q15910-2]
DR UCSC; uc003wfb.3; human. [Q15910-1]
DR CTD; 2146; -.
DR DisGeNET; 2146; -.
DR GeneCards; EZH2; -.
DR GeneReviews; EZH2; -.
DR HGNC; HGNC:3527; EZH2.
DR HPA; ENSG00000106462; Tissue enhanced (bone marrow, lymphoid tissue, testis).
DR MalaCards; EZH2; -.
DR MIM; 277590; phenotype.
DR MIM; 601573; gene.
DR neXtProt; NX_Q15910; -.
DR OpenTargets; ENSG00000106462; -.
DR Orphanet; 3447; Weaver syndrome.
DR PharmGKB; PA27939; -.
DR VEuPathDB; HostDB:ENSG00000106462; -.
DR eggNOG; KOG1079; Eukaryota.
DR GeneTree; ENSGT00940000155013; -.
DR HOGENOM; CLU_011342_0_0_1; -.
DR InParanoid; Q15910; -.
DR OMA; CYMHLEG; -.
DR OrthoDB; 875190at2759; -.
DR PhylomeDB; Q15910; -.
DR TreeFam; TF314509; -.
DR BioCyc; MetaCyc:HS02911-MON; -.
DR BRENDA; 2.1.1.356; 2681.
DR PathwayCommons; Q15910; -.
DR Reactome; R-HSA-212300; PRC2 methylates histones and DNA.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-HSA-8953750; Transcriptional Regulation by E2F6.
DR Reactome; R-HSA-9609690; HCMV Early Events.
DR Reactome; R-HSA-9710421; Defective pyroptosis.
DR SignaLink; Q15910; -.
DR SIGNOR; Q15910; -.
DR BioGRID-ORCS; 2146; 69 hits in 1109 CRISPR screens.
DR ChiTaRS; EZH2; human.
DR GeneWiki; EZH2; -.
DR GenomeRNAi; 2146; -.
DR Pharos; Q15910; Tclin.
DR PRO; PR:Q15910; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q15910; protein.
DR Bgee; ENSG00000106462; Expressed in ganglionic eminence and 133 other tissues.
DR ExpressionAtlas; Q15910; baseline and differential.
DR Genevisible; Q15910; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005677; C:chromatin silencing complex; IEA:Ensembl.
DR GO; GO:0000781; C:chromosome, telomeric region; IGI:ARUK-UCL.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0035098; C:ESC/E(Z) complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005721; C:pericentric heterochromatin; IEA:Ensembl.
DR GO; GO:0045120; C:pronucleus; IEA:Ensembl.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:UniProtKB.
DR GO; GO:0042054; F:histone methyltransferase activity; IDA:MGI.
DR GO; GO:0046976; F:histone methyltransferase activity (H3-K27 specific); IDA:UniProtKB.
DR GO; GO:0018024; F:histone-lysine N-methyltransferase activity; IDA:MGI.
DR GO; GO:0106222; F:lncRNA binding; IEA:Ensembl.
DR GO; GO:0070878; F:primary miRNA binding; IEA:Ensembl.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:UniProtKB.
DR GO; GO:0016279; F:protein-lysine N-methyltransferase activity; TAS:Reactome.
DR GO; GO:0043021; F:ribonucleoprotein complex binding; IEA:Ensembl.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0003714; F:transcription corepressor activity; ISS:ARUK-UCL.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:ARUK-UCL.
DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IEA:Ensembl.
DR GO; GO:0048468; P:cell development; IEA:Ensembl.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0035984; P:cellular response to trichostatin A; IEA:Ensembl.
DR GO; GO:0021695; P:cerebellar cortex development; IEA:Ensembl.
DR GO; GO:0006325; P:chromatin organization; TAS:ProtInc.
DR GO; GO:0006338; P:chromatin remodeling; IEA:InterPro.
DR GO; GO:0006306; P:DNA methylation; IEA:Ensembl.
DR GO; GO:0070314; P:G1 to G0 transition; IEA:Ensembl.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0036333; P:hepatocyte homeostasis; IEA:Ensembl.
DR GO; GO:0031507; P:heterochromatin assembly; IBA:GO_Central.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0070734; P:histone H3-K27 methylation; IDA:UniProtKB.
DR GO; GO:0098532; P:histone H3-K27 trimethylation; IMP:UniProtKB.
DR GO; GO:0016571; P:histone methylation; IMP:UniProtKB.
DR GO; GO:0030216; P:keratinocyte differentiation; IEA:Ensembl.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; IEA:Ensembl.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; IDA:UniProtKB.
DR GO; GO:0045617; P:negative regulation of keratinocyte differentiation; IEA:Ensembl.
DR GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IEA:Ensembl.
DR GO; GO:0051154; P:negative regulation of striated muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; IMP:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:1900006; P:positive regulation of dendrite development; IEA:Ensembl.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0043406; P:positive regulation of MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0071168; P:protein localization to chromatin; IEA:Ensembl.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0014013; P:regulation of gliogenesis; IEA:Ensembl.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:ProtInc.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:1904772; P:response to tetrachloromethane; IEA:Ensembl.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0014834; P:skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration; IEA:Ensembl.
DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl.
DR GO; GO:0031509; P:subtelomeric heterochromatin assembly; IGI:ARUK-UCL.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; IEA:Ensembl.
DR CDD; cd00167; SANT; 1.
DR CDD; cd19218; SET_EZH2; 1.
DR DisProt; DP01817; -.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR026489; CXC_dom.
DR InterPro; IPR045318; EZH1/2-like.
DR InterPro; IPR021654; EZH1/EZH2.
DR InterPro; IPR044439; EZH2_SET.
DR InterPro; IPR041343; PRC2_HTH_1.
DR InterPro; IPR041355; Pre-SET_CXC.
DR InterPro; IPR001005; SANT/Myb.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR033467; Tesmin/TSO1-like_CXC.
DR PANTHER; PTHR45747; PTHR45747; 1.
DR Pfam; PF11616; EZH2_WD-Binding; 1.
DR Pfam; PF18118; PRC2_HTH_1; 1.
DR Pfam; PF18264; preSET_CXC; 1.
DR Pfam; PF00856; SET; 1.
DR SMART; SM01114; CXC; 1.
DR SMART; SM00717; SANT; 2.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS51633; CXC; 1.
DR PROSITE; PS50280; SET; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Biological rhythms;
KW Chromatin regulator; Disease variant; Glycoprotein; Isopeptide bond;
KW Methyltransferase; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW S-adenosyl-L-methionine; Transcription; Transcription regulation;
KW Transferase; Ubl conjugation.
FT CHAIN 1..746
FT /note="Histone-lysine N-methyltransferase EZH2"
FT /id="PRO_0000213992"
FT DOMAIN 503..605
FT /note="CXC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00970"
FT DOMAIN 612..727
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 1..340
FT /note="Interaction with DNMT1, DNMT3A and DNMT3B"
FT REGION 39..68
FT /note="Interaction with EED"
FT /evidence="ECO:0000250"
FT REGION 180..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 329..522
FT /note="Interaction with CDYL"
FT /evidence="ECO:0000269|PubMed:22009739"
FT REGION 340..426
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 180..195
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 196..220
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 359..374
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 375..407
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 21
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:16224021"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 339
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 345
FT /note="Phosphothreonine; by CDK1 and CDK2"
FT /evidence="ECO:0000269|PubMed:20935635"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 367
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 487
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18220336,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT CARBOHYD 75
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000269|PubMed:24474760"
FT CROSSLNK 634
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 74..82
FT /note="Missing (in isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038813"
FT VAR_SEQ 83..121
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038814"
FT VAR_SEQ 297..298
FT /note="HP -> HRKCNYS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_038815"
FT VAR_SEQ 511..553
FT /note="DGSSNHVYNYQPCDHPRQPCDSSCPCVIAQNFCEKFCQCSSEC -> G (in
FT isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038816"
FT VARIANT 132
FT /note="P -> S (in WVS; decreased histone methyltransferase
FT activity; dbSNP:rs193921148)"
FT /evidence="ECO:0000269|PubMed:22177091,
FT ECO:0000269|PubMed:26694085"
FT /id="VAR_067595"
FT VARIANT 133
FT /note="Y -> C (in WVS; decreased histone methyltransferase
FT activity)"
FT /evidence="ECO:0000269|PubMed:26694085"
FT /id="VAR_078320"
FT VARIANT 134
FT /note="M -> T (in WVS)"
FT /evidence="ECO:0000269|PubMed:22190405"
FT /id="VAR_078321"
FT VARIANT 153
FT /note="Missing (in WVS; decreased histone methyltransferase
FT activity; dbSNP:rs193921146)"
FT /evidence="ECO:0000269|PubMed:22177091,
FT ECO:0000269|PubMed:26694085"
FT /id="VAR_067596"
FT VARIANT 156
FT /note="K -> E (in WVS)"
FT /evidence="ECO:0000269|PubMed:22190405"
FT /id="VAR_078322"
FT VARIANT 185
FT /note="D -> H (decreased histone methyltransferase
FT activity; dbSNP:rs2302427)"
FT /evidence="ECO:0000269|PubMed:26694085"
FT /id="VAR_055795"
FT VARIANT 279
FT /note="H -> R (in WVS)"
FT /evidence="ECO:0000269|PubMed:22190405"
FT /id="VAR_078323"
FT VARIANT 571
FT /note="C -> W (found in a patient with myelodysplastic
FT syndrome and myelodysplastic-myeloproliferative neoplasms;
FT somatic mutation; loss of histone methyltransferase
FT activity)"
FT /evidence="ECO:0000269|PubMed:20601953"
FT /id="VAR_078324"
FT VARIANT 621
FT /note="V -> M (in WVS; unknown pathological significance;
FT dbSNP:rs587783625)"
FT /evidence="ECO:0000269|PubMed:22190405"
FT /id="VAR_078325"
FT VARIANT 641
FT /note="Y -> C (in a patient with diffuse large B-cell
FT lymphoma; somatic mutation; changed substrate preferences;
FT prefers substrates with greater methylation
FT H3K27me0
