EZH2_MOUSE
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 03-AUG-2022, entry version 195.
DE RecName: Full=Histone-lysine N-methyltransferase EZH2 {ECO:0000305};
DE EC=2.1.1.356 {ECO:0000250|UniProtKB:Q15910};
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; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC 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 mouse
RT 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 project:
RT 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., Jenuwein T.;
RT "The polycomb-group gene Ezh2 is required for early mouse 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 Enx1
RT 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., Wang H.,
RA 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 and
RT skeletal muscle differentiation.";
RL Genes Dev. 18:2627-2638(2004).
RN [11]
RP ERRATUM OF PUBMED:15520282.
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., 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., Otte A.P.,
RA 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 complexes
RT 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 clock
RT 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 from
RT 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., 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 [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 in
RT 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 EZH2 in
RT 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 AND
RP THR-487, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 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., Torchia J.,
RA 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., Galvagni F.,
RA Matarese F., Stunnenberg H.G., Oliviero S.;
RT "Dnmt3L antagonizes DNA methylation at bivalent promoters and favors DNA
RT 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 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 [28]
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; LEU-56;
RP 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' (H3K27me)
CC of histone H3, leading to transcriptional repression of the affected
CC target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3
CC to form H3K27me1, H3K27me2 and H3K27me3, respectively. Displays a
CC preference for substrates with less methylation, loses activity when
CC progressively more methyl groups are incorporated into H3K27, H3K27me0
CC > H3K27me1 > H3K27me2. Compared to EZH1-containing complexes, it is
CC more 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 HOXA7, HOXB6 and HOXC8. EZH2 can also methylate non-
CC histone proteins such as the transcription factor GATA4 and the nuclear
CC receptor RORA. Regulates the circadian clock via histone methylation at
CC the promoter of the circadian genes. Essential for the CRY1/2-mediated
CC repression of the transcriptional activation of PER1/2 by the CLOCK-
CC ARNTL/BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-
CC 27' of 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(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:0000250|UniProtKB:Q15910};
CC -!- SUBUNIT: Component of the PRC2/EED-EZH2 complex, which includes EED,
CC EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2 (By similarity). The
CC minimum components required for methyltransferase activity of the
CC PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12 (By similarity). The PRC2
CC complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the
CC EZH2 subunit and with SIRT1 via the SUZ12 subunit (By similarity).
CC Interacts with HDAC1 and HDAC2 (By similarity). Binds ATRX via the SET
CC domain (By similarity). Interacts with PRAME (By similarity). Interacts
CC with CDYL (By similarity). Interacts with EED. Interacts with
CC ARNTL/BMAL1. Interacts with CLOCK and CRY1. Interacts with DNMT3L; the
CC interaction is direct (PubMed:24074865). Interacts with EZHIP; the
CC interaction blocks EZH2 methyltransferase activity (PubMed:31451685).
CC Interacts with ZNF263; recruited to the SIX3 promoter along with other
CC proteins involved in chromatin modification and transcriptional
CC corepression where it contributes to transcriptional repression (By
CC similarity). Interacts with ARMC12 (By similarity).
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:31451685, ECO:0000269|PubMed:9742080}.
CC -!- INTERACTION:
CC Q61188; Q9CWR8: Dnmt3l; NbExp=10; IntAct=EBI-904311, EBI-3043871;
CC Q61188; Q921E6: Eed; NbExp=9; IntAct=EBI-904311, EBI-904301;
CC Q61188; Q62315: Jarid2; NbExp=15; IntAct=EBI-904311, EBI-493592;
CC Q61188; Q02395: Mtf2; NbExp=4; IntAct=EBI-904311, EBI-2531578;
CC Q61188; Q80U70: Suz12; NbExp=10; IntAct=EBI-904311, EBI-2526494;
CC Q61188; P38398: BRCA1; Xeno; NbExp=5; IntAct=EBI-904311, EBI-349905;
CC Q61188-1; Q921E6: Eed; NbExp=5; IntAct=EBI-15665134, EBI-904301;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12123576}.
CC Chromosome. Note=Localizes to the inactive X chromosome in trophoblast
CC stem cells. {ECO:0000269|PubMed:12123576}.
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
CC (PubMed:19026781). Widely expressed in early embryos (PubMed:19026781).
CC In later embryogenesis, expression restricted to central and peripheral
CC nervous system, liver and thymus (PubMed:19026781). In adult, highest
CC expression in spleen, testis and placenta (PubMed:19026781,
CC PubMed:31451685). Lower levels in intestine, muscle and ovary and very
CC low levels in brain and liver (PubMed:19026781, PubMed:31451685). No
CC expression in heart, thyroid gland, lung and kidney (PubMed:19026781).
CC {ECO:0000269|PubMed:19026781, ECO:0000269|PubMed:31451685}.
CC -!- DEVELOPMENTAL STAGE: Expressed in both adult and embryo with highest
CC levels in early embryogenesis. Expressed in the fertilized oocyte.
CC Expression decreases during differentiation of ES cells and during
CC senescence of MEFs. Expression increases in prostate during prostate
CC 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 AKT1
CC reduces methyltransferase activity. Phosphorylation at Thr-345 by CDK1
CC and CDK2 promotes maintenance of H3K27me3 levels at EZH2-target loci,
CC thus leading to epigenetic gene silencing (By similarity).
CC {ECO:0000250|UniProtKB:Q15910}.
CC -!- PTM: Sumoylated. {ECO:0000250|UniProtKB:Q15910}.
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:0000250|UniProtKB:Q15910}.
CC -!- DISRUPTION PHENOTYPE: Death early in development. Embryos cease
CC development following implantation or initiate but fail to complete
CC gastrulation. {ECO:0000269|PubMed:11390661}.
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 -!- SEQUENCE CAUTION:
CC Sequence=AAD54020.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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; 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 PDB; 2QXV; X-ray; 1.82 A; B=39-68.
DR PDBsum; 2QXV; -.
DR AlphaFoldDB; Q61188; -.
DR SMR; Q61188; -.
DR BioGRID; 199564; 65.
DR CORUM; Q61188; -.
DR DIP; DIP-29524N; -.
DR IntAct; Q61188; 29.
DR MINT; Q61188; -.
DR STRING; 10090.ENSMUSP00000080419; -.
DR GlyGen; Q61188; 1 site.
DR iPTMnet; Q61188; -.
DR PhosphoSitePlus; Q61188; -.
DR EPD; Q61188; -.
DR jPOST; Q61188; -.
DR MaxQB; Q61188; -.
DR PaxDb; Q61188; -.
DR PeptideAtlas; Q61188; -.
DR PRIDE; Q61188; -.
DR ProteomicsDB; 275811; -. [Q61188-1]
DR ProteomicsDB; 275812; -. [Q61188-2]
DR Antibodypedia; 32761; 882 antibodies from 45 providers.
DR DNASU; 14056; -.
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 VEuPathDB; HostDB:ENSMUSG00000029687; -.
DR eggNOG; KOG1079; Eukaryota.
DR GeneTree; ENSGT00940000155013; -.
DR InParanoid; Q61188; -.
DR OMA; CYMHLEG; -.
DR OrthoDB; 875190at2759; -.
DR PhylomeDB; Q61188; -.
DR TreeFam; TF314509; -.
DR BRENDA; 2.1.1.356; 3474.
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 BioGRID-ORCS; 14056; 6 hits in 81 CRISPR screens.
DR ChiTaRS; Ezh2; mouse.
DR EvolutionaryTrace; Q61188; -.
DR PRO; PR:Q61188; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q61188; protein.
DR Bgee; ENSMUSG00000029687; Expressed in embryonic post-anal tail and 242 other tissues.
DR ExpressionAtlas; Q61188; baseline and differential.
DR Genevisible; Q61188; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005677; C:chromatin silencing complex; IDA:MGI.
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:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005721; C:pericentric heterochromatin; IDA:MGI.
DR GO; GO:0045120; C:pronucleus; IDA:MGI.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:MGI.
DR GO; GO:0003677; F: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; ISS:UniProtKB.
DR GO; GO:0106222; F:lncRNA binding; IDA: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:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:ARUK-UCL.
DR GO; GO:0001222; F:transcription corepressor binding; ISO:MGI.
DR GO; GO:0030183; P:B cell differentiation; IMP:MGI.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; IDA:MGI.
DR GO; GO:0048468; P:cell development; IMP: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:0006338; P:chromatin remodeling; IEA:InterPro.
DR GO; GO:0006306; P:DNA methylation; IMP:MGI.
DR GO; GO:0009913; P:epidermal cell differentiation; IMP:MGI.
DR GO; GO:0070314; P:G1 to G0 transition; IMP:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:0036333; P:hepatocyte homeostasis; IGI:MGI.
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; IMP:UniProtKB.
DR GO; GO:0098532; P:histone H3-K27 trimethylation; IDA:MGI.
DR GO; GO:0016571; P:histone methylation; IDA:MGI.
DR GO; GO:0071707; P:immunoglobulin heavy chain V-D-J recombination; TAS:MGI.
DR GO; GO:0030216; P:keratinocyte differentiation; IMP:MGI.
DR GO; GO:0097421; P:liver regeneration; IGI:MGI.
DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; ISO: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:0045617; P:negative regulation of keratinocyte differentiation; IMP:MGI.
DR GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IMP:MGI.
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 GO; GO:0048863; P:stem cell differentiation; IMP:MGI.
DR GO; GO:0031509; P:subtelomeric heterochromatin assembly; ISO:MGI.
DR GO; GO:0051932; P:synaptic transmission, GABAergic; ISO:MGI.
DR CDD; cd00167; SANT; 1.
DR CDD; cd19218; SET_EZH2; 1.
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; Chromosome; 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_0000213993"
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 /evidence="ECO:0000250"
FT REGION 39..68
FT /note="Interaction with EED"
FT REGION 180..217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 329..522
FT /note="Interaction with CDYL"
FT /evidence="ECO:0000250"
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..217
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:0000250|UniProtKB:Q15910"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q15910"
FT MOD_RES 339
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q15910"
FT MOD_RES 345
FT /note="Phosphothreonine; by CDK1 and CDK2"
FT /evidence="ECO:0000250|UniProtKB:Q15910"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 367
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 487
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CARBOHYD 75
FT /note="O-linked (GlcNAc) serine"
FT /evidence="ECO:0000250"
FT CROSSLNK 634
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q15910"
FT VAR_SEQ 511..553
FT /note="DGSSNHVYNYQPCDHPRQPCDSSCPCVIAQNFCEKFCQCSSEC -> G (in
FT isoform ENX-1B)"
FT /evidence="ECO:0000305"
FT /id="VSP_001501"
FT MUTAGEN 42
FT /note="F->D: Abrogates interaction with EED."
FT /evidence="ECO:0000269|PubMed:17937919"
FT MUTAGEN 45
FT /note="N->A: Abrogates interaction with EED."
FT /evidence="ECO:0000269|PubMed:17937919"
FT MUTAGEN 49
FT /note="I->E: Abrogates interaction with EED."
FT /evidence="ECO:0000269|PubMed:17937919"
FT MUTAGEN 56
FT /note="L->E: Abrogates interaction with EED."
FT /evidence="ECO:0000269|PubMed:17937919"
FT MUTAGEN 67
FT /note="P->D: Abrogates interaction with EED."
FT /evidence="ECO:0000269|PubMed:17937919"
FT MUTAGEN 68
FT /note="V->E: Abrogates interaction with EED."
FT /evidence="ECO:0000269|PubMed:17937919"
FT CONFLICT 159..161
FT /note="Missing (in Ref. 4; AAD54020)"
FT /evidence="ECO:0000305"
FT CONFLICT 651
FT /note="A -> D (in Ref. 1; AAC52655)"
FT /evidence="ECO:0000305"
FT HELIX 41..62
FT /evidence="ECO:0007829|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
