GenomeNet

Database: UniProt
Entry: Q61188
LinkDB: Q61188
Original site: Q61188 
ID   EZH2_MOUSE              Reviewed;         746 AA.
AC   Q61188; Q99L74; Q9R090;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   27-JUL-2011, sequence version 2.
DT   13-FEB-2019, entry version 178.
DE   RecName: Full=Histone-lysine N-methyltransferase EZH2 {ECO:0000305};
DE            EC=2.1.1.43;
DE   AltName: Full=ENX-1;
DE   AltName: Full=Enhancer of zeste homolog 2;
GN   Name=Ezh2 {ECO:0000312|MGI:MGI:107940}; Synonyms=Enx1h;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Placenta;
RX   PubMed=8861097; DOI=10.1016/0925-4773(96)00499-6;
RA   Hobert O., Sures I., Ciossek T., Fuchs M., Ullrich A.;
RT   "Isolation and developmental expression analysis of Enx-1, a novel
RT   mouse Polycomb group gene.";
RL   Mech. Dev. 55:171-184(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Czech II; TISSUE=Mammary tumor;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 134-497.
RC   STRAIN=129/Sv;
RX   PubMed=10051331; DOI=10.1007/s003359900993;
RA   Laible G., Haynes A.R., Lebersorger A., O'Carroll D., Mattei M.-G.,
RA   Denny P., Brown S.D.M., Jenuwein T.;
RT   "The murine polycomb-group genes ezh1 and ezh2 map close to hox gene
RT   clusters on mouse chromosomes 11 and 6.";
RL   Mamm. Genome 10:311-314(1999).
RN   [5]
RP   INTERACTION WITH EED.
RX   PubMed=9742080; DOI=10.1128/MCB.18.10.5634;
RA   Denisenko O.N., Shnyreva M., Suzuki H., Bomsztyk K.;
RT   "Point mutations in the WD40 domain of Eed block its interaction with
RT   Ezh2.";
RL   Mol. Cell. Biol. 18:5634-5642(1998).
RN   [6]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=11390661; DOI=10.1128/MCB.21.13.4330-4336.2001;
RA   O'Carroll D., Erhardt S., Pagani M., Barton S.C., Surani M.A.,
RA   Jenuwein T.;
RT   "The polycomb-group gene Ezh2 is required for early mouse
RT   development.";
RL   Mol. Cell. Biol. 21:4330-4336(2001).
RN   [7]
RP   SUBCELLULAR LOCATION.
RX   PubMed=12123576; DOI=10.1016/S0960-9822(02)00892-8;
RA   Mak W., Baxter J., Silva J., Newall A.E., Otte A.P., Brockdorff N.;
RT   "Mitotically stable association of polycomb group proteins Eed and
RT   Enx1 with the inactive X chromosome in trophoblast stem cells.";
RL   Curr. Biol. 12:1016-1020(2002).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX   PubMed=12689588; DOI=10.1016/S1534-5807(03)00068-6;
RA   Silva J., Mak W., Zvetkova I., Appanah R., Nesterova T.B., Webster Z.,
RA   Peters A.H.F.M., Jenuwein T., Otte A.P., Brockdorff N.;
RT   "Establishment of histone H3 methylation on the inactive X chromosome
RT   requires transient recruitment of Eed-Enx1 polycomb group complexes.";
RL   Dev. Cell 4:481-495(2003).
RN   [9]
RP   SUBCELLULAR LOCATION.
RX   PubMed=12649488; DOI=10.1126/science.1084274;
RA   Plath K., Fang J., Mlynarczyk-Evans S.K., Cao R., Worringer K.A.,
RA   Wang H., de la Cruz C.C., Otte A.P., Panning B., Zhang Y.;
RT   "Role of histone H3 lysine 27 methylation in X inactivation.";
RL   Science 300:131-135(2003).
RN   [10]
RP   FUNCTION.
RX   PubMed=15520282; DOI=10.1101/gad.1241904;
RA   Caretti G., Di Padova M., Micales B., Lyons G.E., Sartorelli V.;
RT   "The Polycomb Ezh2 methyltransferase regulates muscle gene expression
RT   and skeletal muscle differentiation.";
RL   Genes Dev. 18:2627-2638(2004).
RN   [11]
RP   ERRATUM.
RA   Caretti G., Di Padova M., Micales B., Lyons G.E., Sartorelli V.;
RL   Genes Dev. 19:768-768(2005).
RN   [12]
RP   FUNCTION.
RX   PubMed=15516932; DOI=10.1038/ng1467;
RA   Umlauf D., Goto Y., Cao R., Cerqueira F., Wagschal A., Zhang Y.,
RA   Feil R.;
RT   "Imprinting along the Kcnq1 domain on mouse chromosome 7 involves
RT   repressive histone methylation and recruitment of Polycomb group
RT   complexes.";
RL   Nat. Genet. 36:1296-1300(2004).
RN   [13]
RP   SUBCELLULAR LOCATION.
RX   PubMed=14752160; DOI=10.1126/science.1092674;
RA   Mak W., Nesterova T.B., de Napoles M., Appanah R., Yamanaka S.,
RA   Otte A.P., Brockdorff N.;
RT   "Reactivation of the paternal X chromosome in early mouse embryos.";
RL   Science 303:666-669(2004).
RN   [14]
RP   DEVELOPMENTAL STAGE.
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
RT   complexes change during cellular differentiation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:1859-1864(2005).
RN   [15]
RP   FUNCTION, AND INTERACTION WITH CLOCK; ARNTL AND CRY1.
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
RT   clock function.";
RL   J. Biol. Chem. 281:21209-21215(2006).
RN   [16]
RP   SUBCELLULAR LOCATION.
RX   PubMed=16415857; DOI=10.1038/ncb1351;
RA   Kalantry S., Mills K.C., Yee D., Otte A.P., Panning B., Magnuson T.;
RT   "The Polycomb group protein Eed protects the inactive X-chromosome
RT   from differentiation-induced reactivation.";
RL   Nat. Cell Biol. 8:195-202(2006).
RN   [17]
RP   DEVELOPMENTAL STAGE.
RX   PubMed=17344414; DOI=10.1101/gad.415507;
RA   Bracken A.P., Kleine-Kohlbrecher D., Dietrich N., Pasini D.,
RA   Gargiulo G., Beekman C., Theilgaard-Moench K., Minucci S., Porse B.T.,
RA   Marine J.-C., Hansen K.H., Helin K.;
RT   "The Polycomb group proteins bind throughout the INK4A-ARF locus and
RT   are disassociated in senescent cells.";
RL   Genes Dev. 21:525-530(2007).
RN   [18]
RP   INTERACTION WITH EED.
RX   PubMed=17259173; DOI=10.1074/jbc.M608722200;
RA   Kim S.Y., Levenson J.M., Korsmeyer S., Sweatt J.D., Schumacher A.;
RT   "Developmental regulation of Eed complex composition governs a switch
RT   in global histone modification in brain.";
RL   J. Biol. Chem. 282:9962-9972(2007).
RN   [19]
RP   SUBCELLULAR LOCATION, AND INDUCTION.
RX   PubMed=18281287; DOI=10.1074/jbc.M709614200;
RA   Wong C.F., Tellam R.L.;
RT   "MicroRNA-26a targets the histone methyltransferase Enhancer of Zeste
RT   homolog 2 during myogenesis.";
RL   J. Biol. Chem. 283:9836-9843(2008).
RN   [20]
RP   FUNCTION, AND IDENTIFICATION IN THE PRC2/EED-EZH1 COMPLEX.
RX   PubMed=19026780; DOI=10.1016/j.molcel.2008.10.016;
RA   Shen X., Liu Y., Hsu Y.-J., Fujiwara Y., Kim J., Mao X., Yuan G.-C.,
RA   Orkin S.H.;
RT   "EZH1 mediates methylation on histone H3 lysine 27 and complements
RT   EZH2 in maintaining stem cell identity and executing pluripotency.";
RL   Mol. Cell 32:491-502(2008).
RN   [21]
RP   TISSUE SPECIFICITY.
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   [22]
RP   FUNCTION.
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   [23]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-363; SER-366; THR-367
RP   AND THR-487, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RC   TISSUE=Kidney, Lung, and Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and
RT   expression.";
RL   Cell 143:1174-1189(2010).
RN   [24]
RP   IDENTIFICATION IN THE PRC2 COMPLEX.
RX   PubMed=20144788; DOI=10.1016/j.stem.2009.12.014;
RA   Walker E., Chang W.Y., Hunkapiller J., Cagney G., Garcha K.,
RA   Torchia J., Krogan N.J., Reiter J.F., Stanford W.L.;
RT   "Polycomb-like 2 associates with PRC2 and regulates transcriptional
RT   networks during mouse embryonic stem cell self-renewal and
RT   differentiation.";
RL   Cell Stem Cell 6:153-166(2010).
RN   [25]
RP   INTERACTION WITH DNMT3L.
RX   PubMed=24074865; DOI=10.1016/j.cell.2013.08.056;
RA   Neri F., Krepelova A., Incarnato D., Maldotti M., Parlato C.,
RA   Galvagni F., Matarese F., Stunnenberg H.G., Oliviero S.;
RT   "Dnmt3L antagonizes DNA methylation at bivalent promoters and favors
RT   DNA methylation at gene bodies in ESCs.";
RL   Cell 155:121-134(2013).
RN   [26]
RP   INTERACTION WITH ARNTL/BMAL1.
RX   PubMed=23970558; DOI=10.1126/science.1240636;
RA   Nguyen K.D., Fentress S.J., Qiu Y., Yun K., Cox J.S., Chawla A.;
RT   "Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi)
RT   inflammatory monocytes.";
RL   Science 341:1483-1488(2013).
RN   [27]
RP   X-RAY CRYSTALLOGRAPHY (1.82 ANGSTROMS) OF 39-68 IN COMPLEX WITH EED,
RP   INTERACTION WITH EED, AND MUTAGENESIS OF PHE-42; ASN-45; ILE-49;
RP   LEU-56; PRO-67 AND VAL-68.
RX   PubMed=17937919; DOI=10.1016/j.str.2007.08.007;
RA   Han Z., Xing X., Hu M., Zhang Y., Liu P., Chai J.;
RT   "Structural basis of EZH2 recognition by EED.";
RL   Structure 15:1306-1315(2007).
CC   -!- FUNCTION: Polycomb group (PcG) protein. Catalytic subunit of the
CC       PRC2/EED-EZH2 complex, which methylates (H3K9me) and 'Lys-27'
CC       (H3K27me) of histone H3, leading to transcriptional repression of
CC       the affected target gene. Able to mono-, di- and trimethylate
CC       'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3,
CC       respectively. Displays a preference for substrates with less
CC       methylation, loses activity when progressively more methyl groups
CC       are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2.
CC       Compared to EZH1-containing complexes, it is more abundant in
CC       embryonic stem cells and plays a major role in forming H3K27me3,
CC       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
CC       two epigenetic repression systems. Genes repressed by the
CC       PRC2/EED-EZH2 complex include HOXA7, HOXB6 and HOXC8. EZH2 can
CC       also methylate non-histone proteins such as the transcription
CC       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
CC       the 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:0000250|UniProtKB:Q15910,
CC       ECO:0000269|PubMed:12689588, ECO:0000269|PubMed:15516932,
CC       ECO:0000269|PubMed:15520282, ECO:0000269|PubMed:16717091,
CC       ECO:0000269|PubMed:18086877, ECO:0000269|PubMed:19026780}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.43;
CC   -!- SUBUNIT: Component of the PRC2/EED-EZH2 complex, which includes
CC       EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2 (By
CC       similarity). The minimum components required for methyltransferase
CC       activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12 (By
CC       similarity). The PRC2 complex may also interact with DNMT1,
CC       DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via
CC       the SUZ12 subunit (By similarity). Interacts with HDAC1 and HDAC2
CC       (By similarity). Binds ATRX via the SET domain (By similarity).
CC       Interacts with PRAME (By similarity). Interacts with CDYL (By
CC       similarity). Interacts with EED. Interacts with ARNTL/BMAL1.
CC       Interacts with CLOCK and CRY1. Interacts with DNMT3L; the
CC       interaction is direct (PubMed:24074865).
CC       {ECO:0000250|UniProtKB:Q15910, ECO:0000269|PubMed:16717091,
CC       ECO:0000269|PubMed:17259173, ECO:0000269|PubMed:17937919,
CC       ECO:0000269|PubMed:19026780, ECO:0000269|PubMed:20144788,
CC       ECO:0000269|PubMed:23970558, ECO:0000269|PubMed:24074865,
CC       ECO:0000269|PubMed:9742080}.
CC   -!- INTERACTION:
CC       P38398:BRCA1 (xeno); NbExp=5; IntAct=EBI-904311, EBI-349905;
CC       Q9CWR8:Dnmt3l; NbExp=10; IntAct=EBI-904311, EBI-3043871;
CC       Q921E6:Eed; NbExp=9; IntAct=EBI-904311, EBI-904301;
CC       Q62315:Jarid2; NbExp=15; IntAct=EBI-904311, EBI-493592;
CC       Q02395:Mtf2; NbExp=4; IntAct=EBI-904311, EBI-2531578;
CC       Q80U70:Suz12; NbExp=10; IntAct=EBI-904311, EBI-2526494;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Localizes to the
CC       inactive X chromosome in trophoblast stem cells.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=ENX-1A;
CC         IsoId=Q61188-1; Sequence=Displayed;
CC       Name=ENX-1B;
CC         IsoId=Q61188-2; Sequence=VSP_001501;
CC   -!- TISSUE SPECIFICITY: Present in actively dividing cells. Widely
CC       expressed in early embryos. In later embryogenesis, expression
CC       restricted to central and peripheral nervous system, liver and
CC       thymus. In adult, highest expression in spleen, testis and
CC       placenta. Lower levels in intestine and muscle and very low levels
CC       in brain and liver. No expression in heart, thyroid gland, lung
CC       and kidney. {ECO:0000269|PubMed:19026781}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in both adult and embryo with
CC       highest levels in early embryogenesis. Expressed in the fertilized
CC       oocyte. Expression decreases during differentiation of ES cells
CC       and during senescence of MEFs. Expression increases in prostate
CC       during prostate tumor development. {ECO:0000269|PubMed:12689588,
CC       ECO:0000269|PubMed:15684044, ECO:0000269|PubMed:17344414}.
CC   -!- INDUCTION: Repressed by the microRNA (miRNA) miR-26a.
CC       {ECO:0000269|PubMed:18281287}.
CC   -!- PTM: Phosphorylated by AKT1 (By similarity). Phosphorylation by
CC       AKT1 reduces methyltransferase activity. Phosphorylation at Thr-
CC       345 by CDK1 and CDK2 promotes maintenance of H3K27me3 levels at
CC       EZH2-target loci, thus leading to epigenetic gene silencing (By
CC       similarity). {ECO:0000250}.
CC   -!- PTM: Sumoylated. {ECO:0000250}.
CC   -!- PTM: Glycosylated: O-GlcNAcylation at Ser-75 by OGT increases
CC       stability of EZH2 and facilitates the formation of H3K27me3 by the
CC       PRC2/EED-EZH2 complex. {ECO:0000250}.
CC   -!- DISRUPTION PHENOTYPE: Death early in development. Embryos cease
CC       development following implantation or initiate but fail to
CC       complete gastrulation. {ECO:0000269|PubMed:11390661}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding
CC       methyltransferase superfamily. Histone-lysine methyltransferase
CC       family. EZ subfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAD54020.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
DR   EMBL; U52951; AAC52655.1; -; mRNA.
DR   EMBL; CH466533; EDL13435.1; -; Genomic_DNA.
DR   EMBL; BC003772; AAH03772.1; -; mRNA.
DR   EMBL; BC016391; AAH16391.1; -; mRNA.
DR   EMBL; AF104359; AAD54020.1; ALT_SEQ; Genomic_DNA.
DR   CCDS; CCDS20096.1; -. [Q61188-1]
DR   RefSeq; NP_031997.2; NM_007971.2. [Q61188-1]
DR   UniGene; Mm.246688; -.
DR   PDB; 2QXV; X-ray; 1.82 A; B=39-68.
DR   PDBsum; 2QXV; -.
DR   ProteinModelPortal; Q61188; -.
DR   SMR; Q61188; -.
DR   BioGrid; 199564; 61.
DR   CORUM; Q61188; -.
DR   DIP; DIP-29524N; -.
DR   IntAct; Q61188; 29.
DR   MINT; Q61188; -.
DR   STRING; 10090.ENSMUSP00000080419; -.
DR   iPTMnet; Q61188; -.
DR   PhosphoSitePlus; Q61188; -.
DR   EPD; Q61188; -.
DR   jPOST; Q61188; -.
DR   PaxDb; Q61188; -.
DR   PeptideAtlas; Q61188; -.
DR   PRIDE; Q61188; -.
DR   Ensembl; ENSMUST00000081721; ENSMUSP00000080419; ENSMUSG00000029687. [Q61188-1]
DR   Ensembl; ENSMUST00000092648; ENSMUSP00000090318; ENSMUSG00000029687. [Q61188-2]
DR   GeneID; 14056; -.
DR   KEGG; mmu:14056; -.
DR   UCSC; uc009btb.2; mouse. [Q61188-1]
DR   CTD; 2146; -.
DR   MGI; MGI:107940; Ezh2.
DR   eggNOG; KOG1079; Eukaryota.
DR   eggNOG; COG2940; LUCA.
DR   GeneTree; ENSGT00940000155013; -.
DR   HOGENOM; HOG000008176; -.
DR   HOVERGEN; HBG002453; -.
DR   InParanoid; Q61188; -.
DR   KO; K11430; -.
DR   OrthoDB; 875190at2759; -.
DR   TreeFam; TF314509; -.
DR   Reactome; R-MMU-212300; PRC2 methylates histones and DNA.
DR   Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence.
DR   Reactome; R-MMU-3214841; PKMTs methylate histone lysines.
DR   Reactome; R-MMU-8943724; Regulation of PTEN gene transcription.
DR   Reactome; R-MMU-8953750; Transcriptional Regulation by E2F6.
DR   ChiTaRS; Ezh2; mouse.
DR   EvolutionaryTrace; Q61188; -.
DR   PRO; PR:Q61188; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   Bgee; ENSMUSG00000029687; Expressed in 278 organ(s), highest expression level in secondary oocyte.
DR   ExpressionAtlas; Q61188; baseline and differential.
DR   Genevisible; Q61188; MM.
DR   GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0035098; C:ESC/E(Z) complex; IDA:UniProtKB.
DR   GO; GO:0000790; C:nuclear chromatin; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0045120; C:pronucleus; IDA:MGI.
DR   GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR   GO; GO:0031490; F:chromatin DNA binding; IDA:MGI.
DR   GO; GO:0042054; F:histone methyltransferase activity; IDA:MGI.
DR   GO; GO:0046976; F:histone methyltransferase activity (H3-K27 specific); ISO:MGI.
DR   GO; GO:0018024; F:histone-lysine N-methyltransferase activity; ISO:MGI.
DR   GO; GO:0070878; F:primary miRNA binding; IDA:MGI.
DR   GO; GO:1990841; F:promoter-specific chromatin binding; ISS:UniProtKB.
DR   GO; GO:0016279; F:protein-lysine N-methyltransferase activity; IDA:MGI.
DR   GO; GO:0043021; F:ribonucleoprotein complex binding; IDA:MGI.
DR   GO; GO:0003723; F:RNA binding; IDA:MGI.
DR   GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:0003714; F:transcription corepressor activity; IDA:ARUK-UCL.
DR   GO; GO:0044212; F:transcription regulatory region DNA binding; ISO:MGI.
DR   GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IDA:MGI.
DR   GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:MGI.
DR   GO; GO:0035984; P:cellular response to trichostatin A; IMP:MGI.
DR   GO; GO:0021695; P:cerebellar cortex development; IMP:MGI.
DR   GO; GO:0006348; P:chromatin silencing at telomere; ISO:MGI.
DR   GO; GO:0006306; P:DNA methylation; IMP:MGI.
DR   GO; GO:0070314; P:G1 to G0 transition; IMP:MGI.
DR   GO; GO:0036333; P:hepatocyte homeostasis; IGI:MGI.
DR   GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR   GO; GO:0070734; P:histone H3-K27 methylation; IMP:UniProtKB.
DR   GO; GO:0098532; P:histone H3-K27 trimethylation; IGI:MGI.
DR   GO; GO:0016571; P:histone methylation; IDA:MGI.
DR   GO; GO:0097421; P:liver regeneration; IGI:MGI.
DR   GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IGI:MGI.
DR   GO; GO:0045605; P:negative regulation of epidermal cell differentiation; IMP:MGI.
DR   GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IMP:MGI.
DR   GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR   GO; GO:0045814; P:negative regulation of gene expression, epigenetic; ISS:UniProtKB.
DR   GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:0051154; P:negative regulation of striated muscle cell differentiation; IDA:MGI.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR   GO; GO:0034244; P:negative regulation of transcription elongation from RNA polymerase II promoter; IMP:MGI.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR   GO; GO:1902808; P:positive regulation of cell cycle G1/S phase transition; ISO:MGI.
DR   GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR   GO; GO:1900006; P:positive regulation of dendrite development; ISO:MGI.
DR   GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR   GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR   GO; GO:0043406; P:positive regulation of MAP kinase activity; ISS:UniProtKB.
DR   GO; GO:0071902; P:positive regulation of protein serine/threonine kinase activity; ISS:UniProtKB.
DR   GO; GO:0071168; P:protein localization to chromatin; IMP:MGI.
DR   GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR   GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR   GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR   GO; GO:0014013; P:regulation of gliogenesis; IMP:MGI.
DR   GO; GO:0050767; P:regulation of neurogenesis; IMP:MGI.
DR   GO; GO:0001932; P:regulation of protein phosphorylation; IMP:MGI.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:MGI.
DR   GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR   GO; GO:1904772; P:response to tetrachloromethane; IGI:MGI.
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; IMP:MGI.
DR   CDD; cd00167; SANT; 1.
DR   InterPro; IPR026489; CXC_dom.
DR   InterPro; IPR021654; EZH1/EZH2.
DR   InterPro; IPR001005; SANT/Myb.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR033467; Tesmin/TSO1-like_CXC.
DR   Pfam; PF11616; EZH2_WD-Binding; 1.
DR   Pfam; PF00856; SET; 1.
DR   SMART; SM01114; CXC; 1.
DR   SMART; SM00717; SANT; 2.
DR   SMART; SM00317; SET; 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; Chromosome; Complete proteome; Glycoprotein;
KW   Isopeptide bond; Methyltransferase; Nucleus; Phosphoprotein;
KW   Reference proteome; Repressor; S-adenosyl-L-methionine; Transcription;
KW   Transcription regulation; Transferase; Ubl conjugation.
FT   CHAIN         1    746       Histone-lysine N-methyltransferase EZH2.
FT                                /FTId=PRO_0000213993.
FT   DOMAIN      503    605       CXC. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00970}.
FT   DOMAIN      612    727       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   REGION        1    340       Interaction with DNMT1, DNMT3A and
FT                                DNMT3B. {ECO:0000250}.
FT   REGION       39     68       Interaction with EED.
FT   REGION      329    522       Interaction with CDYL. {ECO:0000250}.
FT   COMPBIAS    523    605       Cys-rich.
FT   MOD_RES      21     21       Phosphoserine; by PKB/AKT1.
FT                                {ECO:0000250|UniProtKB:Q15910}.
FT   MOD_RES      76     76       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q15910}.
FT   MOD_RES     339    339       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:Q15910}.
FT   MOD_RES     345    345       Phosphothreonine; by CDK1 and CDK2.
FT                                {ECO:0000250|UniProtKB:Q15910}.
FT   MOD_RES     363    363       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES     366    366       Phosphoserine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES     367    367       Phosphothreonine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   MOD_RES     487    487       Phosphothreonine.
FT                                {ECO:0000244|PubMed:21183079}.
FT   CARBOHYD     75     75       O-linked (GlcNAc) serine. {ECO:0000250}.
FT   CROSSLNK    634    634       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000250|UniProtKB:Q15910}.
FT   VAR_SEQ     511    553       DGSSNHVYNYQPCDHPRQPCDSSCPCVIAQNFCEKFCQCSS
FT                                EC -> G (in isoform ENX-1B).
FT                                {ECO:0000305}.
FT                                /FTId=VSP_001501.
FT   MUTAGEN      42     42       F->D: Abrogates interaction with EED.
FT                                {ECO:0000269|PubMed:17937919}.
FT   MUTAGEN      45     45       N->A: Abrogates interaction with EED.
FT                                {ECO:0000269|PubMed:17937919}.
FT   MUTAGEN      49     49       I->E: Abrogates interaction with EED.
FT                                {ECO:0000269|PubMed:17937919}.
FT   MUTAGEN      56     56       L->E: Abrogates interaction with EED.
FT                                {ECO:0000269|PubMed:17937919}.
FT   MUTAGEN      67     67       P->D: Abrogates interaction with EED.
FT                                {ECO:0000269|PubMed:17937919}.
FT   MUTAGEN      68     68       V->E: Abrogates interaction with EED.
FT                                {ECO:0000269|PubMed:17937919}.
FT   CONFLICT    159    161       Missing (in Ref. 4; AAD54020).
FT                                {ECO:0000305}.
FT   CONFLICT    651    651       A -> D (in Ref. 1; AAC52655).
FT                                {ECO:0000305}.
FT   HELIX        41     62       {ECO:0000244|PDB:2QXV}.
SQ   SEQUENCE   746 AA;  85292 MW;  7442C751E13EA24B CRC64;
     MGQTGKKSEK GPVCWRKRVK SEYMRLRQLK RFRRADEVKT MFSSNRQKIL ERTETLNQEW
     KQRRIQPVHI MTSVSSLRGT RECSVTSDLD FPAQVIPLKT LNAVASVPIM YSWSPLQQNF
     MVEDETVLHN IPYMGDEVLD QDGTFIEELI KNYDGKVHGD RECGFINDEI FVELVNALGQ
     YNDDDDDDDG DDPDEREEKQ KDLEDNRDDK ETCPPRKFPA DKIFEAISSM FPDKGTAEEL
     KEKYKELTEQ QLPGALPPEC TPNIDGPNAK SVQREQSLHS FHTLFCRRCF KYDCFLHPFH
     ATPNTYKRKN TETALDNKPC GPQCYQHLEG AKEFAAALTA ERIKTPPKRP GGRRRGRLPN
     NSSRPSTPTI SVLESKDTDS DREAGTETGG ENNDKEEEEK KDETSSSSEA NSRCQTPIKM
     KPNIEPPENV EWSGAEASMF RVLIGTYYDN FCAIARLIGT KTCRQVYEFR VKESSIIAPV
     PTEDVDTPPR KKKRKHRLWA AHCRKIQLKK DGSSNHVYNY QPCDHPRQPC DSSCPCVIAQ
     NFCEKFCQCS SECQNRFPGC RCKAQCNTKQ CPCYLAVREC DPDLCLTCGA ADHWDSKNVS
     CKNCSIQRGS KKHLLLAPSD VAGWGIFIKD PVQKNEFISE YCGEIISQDE ADRRGKVYDK
     YMCSFLFNLN NDFVVDATRK GNKIRFANHS VNPNCYAKVM MVNGDHRIGI FAKRAIQTGE
     ELFFDYRYSQ ADALKYVGIE REMEIP
//
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