Tclin EZH2 Histone-lysine N-methyltransferase EZH2

Protein Summary

Description

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 (PubMed:22323599). 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-ARNTL/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. This gene encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein associates with the embryonic ectoderm development protein, the VAV1 oncoprotein, and the X-linked nuclear protein. This protein may play a role in the hematopoietic and central nervous systems. Multiple alternatively splcied transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Feb 2011]

Uniprot Accession IDs

• Q15910
• B2RAQ1
• B3KS30
• B7Z1D6
• B7Z7L6
• Q15755
• Q75MG3
• Q92857
• Q96FI6

Gene Name

• EZH2

Ensembl ID

• ENST00000320356
• ENSP00000320147
• ENSG00000106462
• ENST00000350995
• ENSP00000223193
• ENST00000460911
• ENSP00000419711
• ENST00000476773
• ENSP00000419050
• ENST00000478654
• ENSP00000417062
• ENST00000483967
• ENSP00000419856

Symbol

• KMT6
• WVS
• ENX1
• KMT6
• WVS2
• ENX-1
• EZH2b
• KMT6A

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
molecular function	0.91
transcription factor binding site profile	0.87
histone modification site profile	0.83
transcription factor	0.83

Protein Classes

DTO Classes

Protein / Epigenetic Regulator / Writer / Protein Methyltransferase / Histone-lysine N-methyltransferase Ezh2

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2867.71   (req: < 5)

Gene RIFs: 1320   (req: <= 3)

Antibodies: 763   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 2867.71   (req: >= 5)

Gene RIFs: 1320   (req: > 3)

Antibodies: 763   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 51

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 445

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1