ID:EZH2_HUMAN DESCRIPTION: RecName: Full=Histone-lysine N-methyltransferase EZH2; EC=2.1.1.43; AltName: Full=ENX-1; AltName: Full=Enhancer of zeste homolog 2; AltName: Full=Lysine N-methyltransferase 6; 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. Compared to EZH2-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. CATALYTIC ACTIVITY: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. SUBUNIT: Binds ATRX via the SET domain (Probable). 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. Interacts with PRAME. INTERACTION: P26358:DNMT1; NbExp=8; IntAct=EBI-530054, EBI-719459; Q9Y6K1:DNMT3A; NbExp=4; IntAct=EBI-530054, EBI-923653; Q9UBC3:DNMT3B; NbExp=6; IntAct=EBI-530054, EBI-80125; Q15156:PML-RAR; NbExp=8; IntAct=EBI-530054, EBI-867256; P10276:RARA; NbExp=2; IntAct=EBI-530054, EBI-413374; SUBCELLULAR LOCATION: Nucleus. TISSUE SPECIFICITY: Expressed in many tissues. Overexpressed in numerous tumor types including carcinomas of the breast, colon, larynx, lymphoma and testis. DEVELOPMENTAL STAGE: Expression decreases during senescence of embryonic fibroblasts (HEFs). Expression peaks at the G1/S phase boundary. INDUCTION: 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. PTM: 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. PTM: Sumoylated. DISEASE: Defects in EZH2 are the cause of Weaver syndrome type 2 (WVS2) [MIM:614421]. WVS2 is 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. SIMILARITY: Belongs to the histone-lysine methyltransferase family. EZ subfamily. SIMILARITY: Contains 1 CXC domain. SIMILARITY: Contains 1 SET domain. CAUTION: Two variants of the PRC2 complex have been described, termed PRC3 and PRC4. Each of the three complexes may include a different complement of EED isoforms, although the precise sequences of the isoforms in each complex have not been determined. The PRC2 and PRC4 complexes may also methylate 'Lys- 26' of histone H1 in addition to 'Lys-27' of histone H3 (PubMed:15099518 and PubMed:15684044), although other studies have demonstrated no methylation of 'Lys-26' of histone H1 by PRC2 (PubMed:16431907). SEQUENCE CAUTION: Sequence=AAS07448.1; Type=Erroneous gene model prediction;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q15910
Front
Top
Side
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.
Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding GO:0001047 core promoter binding GO:0003677 DNA binding GO:0003682 chromatin binding GO:0003723 RNA binding GO:0005515 protein binding GO:0008168 methyltransferase activity GO:0016279 protein-lysine N-methyltransferase activity GO:0016740 transferase activity GO:0018024 histone-lysine N-methyltransferase activity GO:0031490 chromatin DNA binding GO:0042054 histone methyltransferase activity GO:0043021 ribonucleoprotein complex binding GO:0043565 sequence-specific DNA binding GO:0044212 transcription regulatory region DNA binding GO:0046976 histone methyltransferase activity (H3-K27 specific) GO:0070878 primary miRNA binding GO:1990841 promoter-specific chromatin binding
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0001932 regulation of protein phosphorylation GO:0006306 DNA methylation GO:0006325 chromatin organization GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0010468 regulation of gene expression GO:0010629 negative regulation of gene expression GO:0010718 positive regulation of epithelial to mesenchymal transition GO:0014013 regulation of gliogenesis GO:0014834 skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration GO:0014898 cardiac muscle hypertrophy in response to stress GO:0016571 histone methylation GO:0021695 cerebellar cortex development GO:0021766 hippocampus development GO:0032259 methylation GO:0032355 response to estradiol GO:0034244 negative regulation of transcription elongation from RNA polymerase II promoter GO:0035984 cellular response to trichostatin A GO:0036333 hepatocyte homeostasis GO:0042127 regulation of cell proliferation GO:0042752 regulation of circadian rhythm GO:0043406 positive regulation of MAP kinase activity GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity GO:0043547 positive regulation of GTPase activity GO:0045605 negative regulation of epidermal cell differentiation GO:0045814 negative regulation of gene expression, epigenetic GO:0045892 negative regulation of transcription, DNA-templated GO:0048387 negative regulation of retinoic acid receptor signaling pathway GO:0048511 rhythmic process GO:0050767 regulation of neurogenesis GO:0051154 negative regulation of striated muscle cell differentiation GO:0070301 cellular response to hydrogen peroxide GO:0070314 G1 to G0 transition GO:0070317 negative regulation of G0 to G1 transition GO:0070734 histone H3-K27 methylation GO:0071168 protein localization to chromatin GO:0071902 positive regulation of protein serine/threonine kinase activity GO:0097421 liver regeneration GO:0098532 histone H3-K27 trimethylation GO:1900006 positive regulation of dendrite development GO:1904772 response to tetrachloromethane GO:2000134 negative regulation of G1/S transition of mitotic cell cycle
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
