InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: EZH2

Summary

InnateDB Protein

IDBP-47021.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

EZH2

Protein Name

enhancer of zeste homolog 2 (Drosophila)

Synonyms

ENX-1; ENX1; EZH1; EZH2b; KMT6; KMT6A; WVS; WVS2;

Species

Homo sapiens

Ensembl Protein

ENSP00000320147

InnateDB Gene

IDBG-47019 (EZH2)

Protein Structure

UniProt Annotation

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 and the nuclear receptor RORA. {ECO:0000269PubMed:14532106, ECO:0000269PubMed:15225548, ECO:0000269PubMed:15231737, ECO:0000269PubMed:15385962, ECO:0000269PubMed:16179254, ECO:0000269PubMed:16357870, ECO:0000269PubMed:16618801, ECO:0000269PubMed:16936726, ECO:0000269PubMed:17210787, ECO:0000269PubMed:17344414, ECO:0000269PubMed:18285464, ECO:0000269PubMed:19026781, ECO:0000269PubMed:20935635, ECO:0000269PubMed:23063525, ECO:0000269PubMed:24474760}.

Subcellular Localization

Nucleus {ECO:0000269PubMed:12101246, ECO:0000269PubMed:14532106, ECO:0000269PubMed:15231737, ECO:0000269PubMed:9584199}.

Disease Associations

Weaver syndrome (WVS) [MIM:277590]: 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. {ECO:0000269PubMed:22177091}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Expressed in many tissues. Overexpressed in numerous tumor types including carcinomas of the breast, colon, larynx, lymphoma and testis. {ECO:0000269PubMed:14532106}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 328 experimentally validated interaction(s) in this database.
They are also associated with 41 interaction(s) predicted by orthology.

Experimentally validated
Total	328 [view]
Protein-Protein	308 [view]
Protein-DNA	20 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	41 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000975	regulatory region DNA binding
GO:0001047	core promoter binding
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003723	RNA binding
GO:0005515	protein binding
GO:0018024	histone-lysine N-methyltransferase activity
GO:0031490	chromatin DNA binding
GO:0042054	histone methyltransferase activity
GO:0043565	sequence-specific DNA binding
GO:0046976	histone methyltransferase activity (H3-K27 specific)

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: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:0016571	histone methylation
GO:0021695	cerebellar cortex development
GO:0032320	positive regulation of Ras GTPase activity
GO:0034244	negative regulation of transcription elongation from RNA polymerase II promoter
GO:0042127	regulation of cell proliferation
GO:0043406	positive regulation of MAP kinase 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: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:0070734	histone H3-K27 methylation
GO:0071168	protein localization to chromatin
GO:0071902	positive regulation of protein serine/threonine kinase activity
GO:2000134	negative regulation of G1/S transition of mitotic cell cycle

Cellular Component

GO:0000790	nuclear chromatin
GO:0005634	nucleus
GO:0005654	nucleoplasm
GO:0005737	cytoplasm
GO:0035098	ESC/E(Z) complex
GO:0045120	pronucleus

Protein Structure and Domains

PDB ID

InterPro

IPR001005 SANT/Myb domain
IPR001214 SET domain
IPR009057 Homeodomain-like
IPR021654 WD repeat binding protein EZH2
IPR029048 Heat shock protein 70kD, C-terminal domain

PFAM

PF00249
PF00856
PF11616

PRINTS

PIRSF

SMART

SM00717
SM00317

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q15910