{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q15910","secondaryAccessions":["B2RAQ1","B3KS30","B7Z1D6","B7Z7L6","Q15755","Q75MG3","Q92857","Q96FI6"],"uniProtkbId":"EZH2_HUMAN","entryAudit":{"firstPublicDate":"1998-07-15","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1998-07-15","entryVersion":229,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Histone-lysine N-methyltransferase EZH2"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22323599"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26581166"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30923826"}],"value":"2.1.1.356"}]},"alternativeNames":[{"fullName":{"value":"ENX-1"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"28229514"}],"value":"Enhancer of zeste homolog 2"}},{"fullName":{"value":"Lysine N-methyltransferase 6"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:3527"}],"value":"EZH2"},"synonyms":[{"value":"KMT6"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61188"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14532106"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15225548"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15231737"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15385962"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16179254"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16357870"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16618801"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16717091"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16936726"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17200670"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17210787"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17344414"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18086877"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18285464"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19026781"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20935635"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22323599"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23063525"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24474760"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26581166"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30026490"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30923826"}],"value":"Catalytic subunit of the PRC2/EED-EZH2 complex, a Polycomb group (PcG) complex that methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene (PubMed:14532106, PubMed:15225548, PubMed:15385962, PubMed:16618801, PubMed:16936726, PubMed:17344414, PubMed:22323599, PubMed:24474760, PubMed:26581166, PubMed:30026490, PubMed:30923826). Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively (PubMed:15231737, PubMed:17210787, PubMed:18285464, PubMed:22323599, PubMed:30923826). Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2 (PubMed:22323599, PubMed:30923826). Compared to EZH1-containing complexes, it is more abundant in embryonic stem cells and plays a major role in forming H3K27me3, which is required for embryonic stem cell identity and proper differentiation (PubMed:19026781). The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems (PubMed:16357870, PubMed:17200670). Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes (PubMed:16179254, PubMed:18086877, PubMed:20935635). EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA (PubMed:23063525). Regulates the circadian clock via histone methylation at the promoter of the circadian genes (PubMed:16717091). Essential for the CRY1/2-mediated repression of the transcriptional activation of PER1/2 by the CLOCK-BMAL1 heterodimer; involved in the di and trimethylation of 'Lys-27' of histone H3 on PER1/2 promoters which is necessary for the CRY1/2 proteins to inhibit transcription (By similarity)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"L-lysyl(27)-[histone H3] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(27)-[histone H3] + 3 S-adenosyl-L-homocysteine + 3 H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:60292"},{"database":"Rhea","id":"RHEA-COMP:15535"},{"database":"Rhea","id":"RHEA-COMP:15548"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:29969"},{"database":"ChEBI","id":"CHEBI:57856"},{"database":"ChEBI","id":"CHEBI:59789"},{"database":"ChEBI","id":"CHEBI:61961"}],"ecNumber":"2.1.1.356","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22323599"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26581166"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30923826"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61188"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10581039"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11158321"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12351676"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12435631"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15385962"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16179254"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16224021"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16357870"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18086877"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18285464"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19026781"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22009739"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30026490"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30923826"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31086175"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31451685"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"32051553"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33323928"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36064715"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9499421"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9584199"},{"evidenceCode":"ECO:0000305"}],"value":"Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2. The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12. The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit. Interacts with HDAC1 and HDAC2. Binds ATRX via the SET domain (Probable). Interacts with PRAME. Interacts with CDYL. Interacts with CLOCK, BMAL1 and CRY1 (By similarity). Interacts with DNMT3L; the interaction is direct (By similarity). Interacts with EZHIP; the interaction blocks EZH2 methyltransferase activity (PubMed:30923826, PubMed:31086175, PubMed:31451685). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (PubMed:32051553). Interacts with ARMC12 (PubMed:30026490). Interacts with ZMYND8; the interaction is dependent on the presence of chromatin (PubMed:33323928, PubMed:36064715). Interacts with DDX18; this interaction inhibits the PRC2 complex (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"P31749","geneName":"AKT1","intActId":"EBI-296087"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"Q8IXJ9","geneName":"ASXL1","intActId":"EBI-1646500"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"P46100","geneName":"ATRX","intActId":"EBI-396461"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"Q96MT8","geneName":"CEP63","intActId":"EBI-741977"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"P26358","geneName":"DNMT1","intActId":"EBI-719459"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"Q9Y6K1","geneName":"DNMT3A","intActId":"EBI-923653"},"numberOfExperiments":6,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"Q9UBC3","geneName":"DNMT3B","intActId":"EBI-80125"},"numberOfExperiments":14,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"O75530","geneName":"EED","intActId":"EBI-923794"},"numberOfExperiments":18,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"Q9BZS1","geneName":"FOXP3","intActId":"EBI-983719"},"numberOfExperiments":9,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"Q92833-1","geneName":"JARID2","intActId":"EBI-15825247"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"O43189","geneName":"PHF1","intActId":"EBI-530034"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"Q15156","geneName":"PML-RAR","intActId":"EBI-867256"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"P10276","geneName":"RARA","intActId":"EBI-413374"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"P40763","geneName":"STAT3","intActId":"EBI-518675"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"O43463","geneName":"SUV39H1","intActId":"EBI-349968"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"Q15022","geneName":"SUZ12","intActId":"EBI-1264675"},"numberOfExperiments":32,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910","intActId":"EBI-530054"},"interactantTwo":{"uniProtKBAccession":"Q9CWR8","geneName":"Dnmt3l","intActId":"EBI-3043871"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"Q15910-2","intActId":"EBI-10699473"},"interactantTwo":{"uniProtKBAccession":"P07550","geneName":"ADRB2","intActId":"EBI-491169"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910-2","intActId":"EBI-10699473"},"interactantTwo":{"uniProtKBAccession":"P28329-3","geneName":"CHAT","intActId":"EBI-25837549"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910-2","intActId":"EBI-10699473"},"interactantTwo":{"uniProtKBAccession":"O75530-2","geneName":"EED","intActId":"EBI-11132357"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910-2","intActId":"EBI-10699473"},"interactantTwo":{"uniProtKBAccession":"P22607","geneName":"FGFR3","intActId":"EBI-348399"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910-2","intActId":"EBI-10699473"},"interactantTwo":{"uniProtKBAccession":"P60411","geneName":"KRTAP10-9","intActId":"EBI-10172052"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15910-2","intActId":"EBI-10699473"},"interactantTwo":{"uniProtKBAccession":"Q7Z699","geneName":"SPRED1","intActId":"EBI-523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LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q61188"}],"value":"Localizes to the inactive X chromosome in trophoblast stem cells"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12101246"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14532106"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15231737"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9584199"}],"value":"Nucleus","id":"SL-0191"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q15910-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q15910-2"],"sequenceIds":["VSP_038815"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q15910-3"],"sequenceIds":["VSP_038814"],"isoformSequenceStatus":"Described"},{"name":{"value":"4"},"isoformIds":["Q15910-4"],"sequenceIds":["VSP_038813"],"isoformSequenceStatus":"Described"},{"name":{"value":"5"},"isoformIds":["Q15910-5"],"sequenceIds":["VSP_038813","VSP_038816"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14532106"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31451685"}],"value":"In the ovary, expressed in primordial follicles and oocytes and also in external follicle cells (at protein level) (PubMed:31451685). Expressed in many tissues (PubMed:14532106). Overexpressed in numerous tumor types including carcinomas of the breast, colon, larynx, lymphoma and testis (PubMed:14532106)"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14532106"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15208672"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17344414"}],"value":"Expression decreases during senescence of embryonic fibroblasts (HEFs). Expression peaks at the G1/S phase boundary"}],"commentType":"DEVELOPMENTAL STAGE"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14532106"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15208672"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17344414"}],"value":"Expression is induced by E2F1, E2F2 and E2F3. Expression is reduced in cells subject to numerous types of stress including UV-, IR- and bleomycin-induced DNA damage and by activation of p53/TP53"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16224021"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20935635"}],"value":"Phosphorylated by AKT1. Phosphorylation by AKT1 reduces methyltransferase activity. Phosphorylation at Thr-345 by CDK1 and CDK2 promotes maintenance of H3K27me3 levels at EZH2-target loci, thus leading to epigenetic gene silencing"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18628979"}],"value":"Sumoylated"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24474760"}],"value":"Glycosylated: O-GlcNAcylation at Ser-75 by OGT increases stability of EZH2 and facilitates the formation of H3K27me3 by the PRC2/EED-EZH2 complex"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Weaver syndrome","diseaseAccession":"DI-01141","acronym":"WVS","description":"A syndrome of accelerated growth and osseous maturation, unusual craniofacial appearance, hoarse and low-pitched cry, and hypertonia with camptodactyly. Distinguishing features of Weaver syndrome include broad forehead and face, ocular hypertelorism, prominent wide philtrum, micrognathia, deep horizontal chin groove, and deep-set nails. In addition, carpal bone development is advanced over the rest of the hand.","diseaseCrossReference":{"database":"MIM","id":"277590"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22177091"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22190405"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23239504"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26694085"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28229514"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00190"}],"value":"Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. 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