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histone-lysine N-methyltransferase EZH2; ENX-1; enhancer of zeste homolog 2; lysine N-methyltransferase 6 (EZH2, KMT6)
Function:
- polycomb group (PcG) protein
- catalytic subunit of the PRC2/EED-EZH2 complex, which methylates Lys-9 & Lys-27 of histone H3
- phosphorylated by AKT1
- phosphorylation by AKT1 reduces methyltransferase activity
- binds ATRX (X-linked helicase 2) via the SET domain (probable)
- interacts with HDAC1 & HDAC2
- interacts with PRAME
Structure:
- belongs to the histone-lysine methyltransferase family, EZ subfamily
- contains 1 SET domain
Compartment: nucleus
Alternative splicing: named isoforms=5
Expression:
- expressed in many tissues
- expression decreases during senescence of embryonic fibroblasts
- expression peaks at the G1/S phase boundary
- expression is induced by E2F1, E2F2 & E2F3
- expression is reduced in cells subject to numerous types of stress including UV-, IR- & bleomycin-induced DNA damage & by activation of TP53/p53
Pathology:
- increased expression in BPH & prostate cancer
- overexpressed in numerous tumor types including carcinomas of the breast, colon, larynx, lymphoma & testis
Interactions
molecular events
Related
EZ2H gene
General
methyltransferase
phosphoprotein
transcriptional silencer (transcriptional repressor)
Properties
SIZE: entity length = 746 aa
MW = 85 kD
COMPARTMENT: cell nucleus
MOTIF: DNMT1, DNMT3A and DNMT3B interaction {1-340}
MOTIF: Ser phosphorylation site {S21}
EED interaction {39-68}
Thr phosphorylation site {T339}
Ser phosphorylation site {S363}
Ser phosphorylation site {S366}
Thr phosphorylation site {T367}
Ser phosphorylation site {S380}
Thr phosphorylation site {T487}
cysteine-rich region {523-605}
SET domain {611-731}
Database Correlations
OMIM 601573
UniProt Q15910
PFAM correlations
Entrez Gene 2146
Kegg hsa:2146
ENZYME 2.1.1.43
References
- UniProt :accession Q15910
- Journal Watch 22(23):174, 2002
Varambally S et al
The polycomb group protein EZH2 is involved in progression
of prostate cancer.
Nature 419:624, 2002
PMID: 12374981
Zetter BR & Banyard J
Cancer. The silence of the genes.
Nature 419:572, 2002
PMID: 12374961
Component-of
molecular complex