| Post Translational Modifications | 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. Sumoylated. Glycosylated: O-GlcNAcylation at Ser-75 by OGT increases stability of EZH2 and facilitates the formation of H3K27me3 by the PRC2/EED-EZH2 complex. |
| Function | Polycomb group (PcG) protein. Catalytic subunit of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene. Able to mono-, di- and trimethylate 'Lys-27' of histone H3 to form H3K27me1, H3K27me2 and H3K27me3, respectively. Displays a preference for substrates with less methylation, loses activity when progressively more methyl groups are incorporated into H3K27, H3K27me0 > H3K27me1 > H3K27me2. 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. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1, CDKN2A and retinoic acid target genes. EZH2 can also methylate non-histone proteins such as the transcription factor GATA4 and the nuclear receptor RORA. Regulates the circadian clock via histone methylation at the promoter of the circadian genes. 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. |
| Protein Name | Histone-Lysine N-Methyltransferase Ezh2Enx-1Enhancer Of Zeste Homolog 2Lysine N-Methyltransferase 6 |
| Database Links | Reactome: R-HSA-212300Reactome: R-HSA-2559580Reactome: R-HSA-3214841Reactome: R-HSA-5617472Reactome: R-HSA-8943724Reactome: R-HSA-8953750Reactome: R-HSA-9609690Reactome: R-HSA-9710421 |
| Cellular Localisation | NucleusLocalizes To The Inactive X Chromosome In Trophoblast Stem Cells |
| Alternative Protein Names | Histone-Lysine N-Methyltransferase Ezh2 proteinEnx-1 proteinEnhancer Of Zeste Homolog 2 proteinLysine N-Methyltransferase 6 proteinEZH2 proteinKMT6 protein |
Information sourced from Uniprot.org
