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EZH2 a histone H3 Lys 27 (H3K27) methyltransferase and Polycomb group protein with oncogenic activity. A master regulatory protein that plays a critical role in development. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates K9 and K27 of histone H3, leading to transcriptional repression of the affected target genes. PRC2 includes the Ezh2, EED, SUZ12, RBBP4 and RBBP7 and possibly AEBP2. The recruitment of PRC2 to a promoter leads to increased levels of di- and trimethylation of H3K27 (H3K27me2/3), regulating the balance between self-renewal and differentiation of embryonic stem cells (ESCs). The recruitment of PRC2 to promoters in ES cells is interdependent on Jarid 2. ESCs lacking the PRC2 component EED are deficient in Jarid2 promoter activity, while the knockdown of Jarid 2 reduces PRC2 at its target promoters. Able to mono-, di- and trimethylate K27 of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, p14ARF and retinoic acid target genes. Binds ATRX via the SET domain. 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. Interacts with PRAME. Overexpressed in numerous tumor types including carcinomas of the breast, colon, larynx, lymphoma and testis. Expression decreases during senescence of embryonic fibroblasts. Expression peaks at the G1/S phase boundary. 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. It has been reported that phosphorylation by AKT1 on S21 reduces methyltransferase activity. Note: This description may include information from UniProtKB.
Protein type: EC; Methyltransferase; Methyltransferase, protein lysine
Chromosomal Location of Human Ortholog: 7q36.1
Cellular Component: ESC/E(Z) complex; nuclear chromatin; nucleoplasm; nucleus
Molecular Function: chromatin binding; chromatin DNA binding; DNA binding; histone lysine N-methyltransferase activity (H3-K27 specific); histone methyltransferase activity; histone-lysine N-methyltransferase activity; protein binding; protein-lysine N-methyltransferase activity
Biological Process: establishment and/or maintenance of chromatin architecture; histone methylation; negative regulation of gene expression, epigenetic; negative regulation of retinoic acid receptor signaling pathway; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; positive regulation of GTPase activity; positive regulation of MAP kinase activity; regulation of circadian rhythm; regulation of transcription, DNA-dependent
Disease: Weaver Syndrome
Reference #:  Q15910 (UniProtKB)
Alt. Names/Synonyms: enhancer of zeste 2; Enhancer of zeste homolog 2; enhancer of zeste homolog 2 (Drosophila); ENX-1; ENX1; EZH1; EZH2; Histone-lysine N-methyltransferase EZH2; KMT6; KMT6A; Lysine N-methyltransferase 6; MGC9169
Gene Symbols: EZH2
Molecular weight: 85,363 Da
Basal Isoelectric point: 6.65  Predict pI for various phosphorylation states
CST Pathways:  Histone Methylation
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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