Browse EZH2

Summary
SymbolEZH2
Nameenhancer of zeste 2 polycomb repressive complex 2 subunit
Aliases ENX-1; KMT6; KMT6A; enhancer of zeste (Drosophila) homolog 2; enhancer of zeste homolog 2 (Drosophila); ENX1 ......
Chromosomal Location7q35-q36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Nucleus
Domain PF11616 WD repeat binding protein EZH2
PF00856 SET domain
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 (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.

> Gene Ontology
 
Biological Process GO:0000082 G1/S transition of mitotic cell cycle
GO:0000302 response to reactive oxygen species
GO:0001837 epithelial to mesenchymal transition
GO:0001889 liver development
GO:0003012 muscle system process
GO:0003299 muscle hypertrophy in response to stress
GO:0003300 cardiac muscle hypertrophy
GO:0006304 DNA modification
GO:0006305 DNA alkylation
GO:0006306 DNA methylation
GO:0006354 DNA-templated transcription, elongation
GO:0006368 transcription elongation from RNA polymerase II promoter
GO:0006479 protein methylation
GO:0006979 response to oxidative stress
GO:0007346 regulation of mitotic cell cycle
GO:0007623 circadian rhythm
GO:0008213 protein alkylation
GO:0008544 epidermis development
GO:0009913 epidermal cell differentiation
GO:0010035 response to inorganic substance
GO:0010717 regulation of epithelial to mesenchymal transition
GO:0010718 positive regulation of epithelial to mesenchymal transition
GO:0010720 positive regulation of cell development
GO:0010948 negative regulation of cell cycle process
GO:0010975 regulation of neuron projection development
GO:0010976 positive regulation of neuron projection development
GO:0014013 regulation of gliogenesis
GO:0014834 skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration
GO:0014887 cardiac muscle adaptation
GO:0014888 striated muscle adaptation
GO:0014896 muscle hypertrophy
GO:0014897 striated muscle hypertrophy
GO:0014898 cardiac muscle hypertrophy in response to stress
GO:0016358 dendrite development
GO:0016570 histone modification
GO:0016571 histone methylation
GO:0018022 peptidyl-lysine methylation
GO:0018205 peptidyl-lysine modification
GO:0021537 telencephalon development
GO:0021543 pallium development
GO:0021549 cerebellum development
GO:0021695 cerebellar cortex development
GO:0021761 limbic system development
GO:0021766 hippocampus development
GO:0022037 metencephalon development
GO:0030522 intracellular receptor signaling pathway
GO:0030856 regulation of epithelial cell differentiation
GO:0030857 negative regulation of epithelial cell differentiation
GO:0030900 forebrain development
GO:0030902 hindbrain development
GO:0031099 regeneration
GO:0031100 animal organ regeneration
GO:0031346 positive regulation of cell projection organization
GO:0032259 methylation
GO:0032355 response to estradiol
GO:0032784 regulation of DNA-templated transcription, elongation
GO:0032785 negative regulation of DNA-templated transcription, elongation
GO:0033674 positive regulation of kinase activity
GO:0034243 regulation of transcription elongation from RNA polymerase II promoter
GO:0034244 negative regulation of transcription elongation from RNA polymerase II promoter
GO:0034502 protein localization to chromosome
GO:0034599 cellular response to oxidative stress
GO:0034614 cellular response to reactive oxygen species
GO:0034968 histone lysine methylation
GO:0035983 response to trichostatin A
GO:0035984 cellular response to trichostatin A
GO:0036333 hepatocyte homeostasis
GO:0040029 regulation of gene expression, epigenetic
GO:0042063 gliogenesis
GO:0042246 tissue regeneration
GO:0042542 response to hydrogen peroxide
GO:0042692 muscle cell differentiation
GO:0042752 regulation of circadian rhythm
GO:0043403 skeletal muscle tissue regeneration
GO:0043405 regulation of MAP kinase activity
GO:0043406 positive regulation of MAP kinase activity
GO:0043410 positive regulation of MAPK cascade
GO:0043414 macromolecule methylation
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0043500 muscle adaptation
GO:0044728 DNA methylation or demethylation
GO:0044770 cell cycle phase transition
GO:0044772 mitotic cell cycle phase transition
GO:0044843 cell cycle G1/S phase transition
GO:0045604 regulation of epidermal cell differentiation
GO:0045605 negative regulation of epidermal cell differentiation
GO:0045666 positive regulation of neuron differentiation
GO:0045682 regulation of epidermis development
GO:0045683 negative regulation of epidermis development
GO:0045786 negative regulation of cell cycle
GO:0045814 negative regulation of gene expression, epigenetic
GO:0045860 positive regulation of protein kinase activity
GO:0045930 negative regulation of mitotic cell cycle
GO:0046677 response to antibiotic
GO:0048384 retinoic acid receptor signaling pathway
GO:0048385 regulation of retinoic acid receptor signaling pathway
GO:0048387 negative regulation of retinoic acid receptor signaling pathway
GO:0048511 rhythmic process
GO:0048732 gland development
GO:0048762 mesenchymal cell differentiation
GO:0048872 homeostasis of number of cells
GO:0050769 positive regulation of neurogenesis
GO:0050773 regulation of dendrite development
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0051146 striated muscle cell differentiation
GO:0051147 regulation of muscle cell differentiation
GO:0051148 negative regulation of muscle cell differentiation
GO:0051153 regulation of striated muscle cell differentiation
GO:0051154 negative regulation of striated muscle cell differentiation
GO:0051962 positive regulation of nervous system development
GO:0060485 mesenchyme development
GO:0061008 hepaticobiliary system development
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:0071236 cellular response to antibiotic
GO:0071407 cellular response to organic cyclic compound
GO:0071417 cellular response to organonitrogen compound
GO:0071900 regulation of protein serine/threonine kinase activity
GO:0071902 positive regulation of protein serine/threonine kinase activity
GO:0097421 liver regeneration
GO:0098532 histone H3-K27 trimethylation
GO:0098727 maintenance of cell number
GO:1900006 positive regulation of dendrite development
GO:1901987 regulation of cell cycle phase transition
GO:1901988 negative regulation of cell cycle phase transition
GO:1901990 regulation of mitotic cell cycle phase transition
GO:1901991 negative regulation of mitotic cell cycle phase transition
GO:1902806 regulation of cell cycle G1/S phase transition
GO:1902807 negative regulation of cell cycle G1/S phase transition
GO:1904772 response to tetrachloromethane
GO:2000045 regulation of G1/S transition of mitotic cell cycle
GO:2000134 negative regulation of G1/S transition of mitotic cell cycle
Molecular Function GO:0000979 RNA polymerase II core promoter sequence-specific DNA binding
GO:0001046 core promoter sequence-specific DNA binding
GO:0001047 core promoter binding
GO:0003682 chromatin binding
GO:0008168 methyltransferase activity
GO:0008170 N-methyltransferase activity
GO:0008276 protein methyltransferase activity
GO:0008757 S-adenosylmethionine-dependent methyltransferase activity
GO:0016278 lysine N-methyltransferase activity
GO:0016279 protein-lysine N-methyltransferase activity
GO:0016741 transferase activity, transferring one-carbon groups
GO:0018024 histone-lysine N-methyltransferase activity
GO:0031490 chromatin DNA binding
GO:0042054 histone methyltransferase activity
GO:0043021 ribonucleoprotein complex binding
GO:0043566 structure-specific DNA binding
GO:0046976 histone methyltransferase activity (H3-K27 specific)
GO:0070878 primary miRNA binding
GO:1990841 promoter-specific chromatin binding
Cellular Component GO:0000785 chromatin
GO:0000790 nuclear chromatin
GO:0031519 PcG protein complex
GO:0034708 methyltransferase complex
GO:0035097 histone methyltransferase complex
GO:0035098 ESC/E(Z) complex
GO:0044454 nuclear chromosome part
GO:0045120 pronucleus
> KEGG and Reactome Pathway
 
KEGG hsa00310 Lysine degradation
Reactome R-HSA-5619507: Activation of HOX genes during differentiation
R-HSA-5617472: Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-2559583: Cellular Senescence
R-HSA-2262752: Cellular responses to stress
R-HSA-3247509: Chromatin modifying enzymes
R-HSA-4839726: Chromatin organization
R-HSA-1266738: Developmental Biology
R-HSA-212165: Epigenetic regulation of gene expression
R-HSA-74160: Gene Expression
R-HSA-2559580: Oxidative Stress Induced Senescence
R-HSA-3214841: PKMTs methylate histone lysines
R-HSA-212300: PRC2 methylates histones and DNA
Summary
SymbolEZH2
Nameenhancer of zeste 2 polycomb repressive complex 2 subunit
Aliases ENX-1; KMT6; KMT6A; enhancer of zeste (Drosophila) homolog 2; enhancer of zeste homolog 2 (Drosophila); ENX1 ......
Chromosomal Location7q35-q36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between EZH2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between EZH2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26567139Colon CarcinomaInhibit immunity (infiltration)We found that PRC2 components and demethylase JMJD3-mediated histone H3 lysine 27 trimethylation (H3K27me3) repress the expression and subsequent production of Th1-type chemokines CXCL9 and CXCL10, mediators of effector T-cell trafficking. Moreover, the expression levels of PRC2 components, including EZH2, SUZ12, and EED, were inversely associated with those of CD4, CD8, and Th1-type chemokines in human colon cancer tissue, and this expression pattern was significantly associated with patient survival.
26523864Ovarian CarcinomaPromote immunity (T cell function)EZH2 activated the Notch pathway by suppressing Notch repressors Numb and Fbxw7 via trimethylation of histone H3 at Lys27 and, consequently, stimulated T cell polyfunctional cytokine expression and promoted their survival via Bcl-2 signaling.
26503055Ovarian CarcinomaInhibit immunity (infiltration)Using human ovarian cancers as our model, here we show that enhancer of zeste homologue 2 (EZH2)-mediated histone H3 lysine 27 trimethylation (H3K27me3) and DNA methyltransferase 1 (DNMT1)-mediated DNA methylation repress the tumour production of T helper 1 (TH1)-type chemokines CXCL9 and CXCL10, and subsequently determine effector T-cell trafficking to the tumour microenvironment.
27505670Diffuse Large B Cell LymphomaInhibit immunity; immunotherapy targetHerein we show that the actions of EZH2 in driving GC formation and lymphoma precursor lesions require site-specific binding by the BCL6 transcriptional repressor and the presence of a non-canonical PRC1-BCOR-CBX8 complex. The chromodomain protein CBX8 is induced in GC B cells, binds to H3K27me3 at bivalent promoters, and is required for stable association of the complex and the resulting histone modifications. Moreover, oncogenic BCL6 and EZH2 cooperate to accelerate diffuse large B cell lymphoma (DLBCL) development and combinatorial targeting of these repressors results in enhanced anti-lymphoma activity in DLBCLs.
29581297hepatocellular carcinomaInhibit immunity (NK cell function); resistant to immunotherapyThe inhibition of EZH2 by small-molecule inhibitors or genetic means enhanced HCC cell eradication by NK cells in a NKG2D ligand-dependent manner.
Summary
SymbolEZH2
Nameenhancer of zeste 2 polycomb repressive complex 2 subunit
Aliases ENX-1; KMT6; KMT6A; enhancer of zeste (Drosophila) homolog 2; enhancer of zeste homolog 2 (Drosophila); ENX1 ......
Chromosomal Location7q35-q36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of EZH2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolEZH2
Nameenhancer of zeste 2 polycomb repressive complex 2 subunit
Aliases ENX-1; KMT6; KMT6A; enhancer of zeste (Drosophila) homolog 2; enhancer of zeste homolog 2 (Drosophila); ENX1 ......
Chromosomal Location7q35-q36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of EZH2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.3030.291
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)65-0.0340.982
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.5050.672
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.4750.167
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.3980.827
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.5780.813
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0520.889
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.3110.831
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.3880.785
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 480.3980.651
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.4730.706
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.4450.000136
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of EZH2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 27737.45.51.90.66
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 01407.1-7.11
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 27597.45.12.30.647
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21179.55.93.61
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13117.79.1-1.41
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160001
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470001
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22134.504.51
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16140001
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolEZH2
Nameenhancer of zeste 2 polycomb repressive complex 2 subunit
Aliases ENX-1; KMT6; KMT6A; enhancer of zeste (Drosophila) homolog 2; enhancer of zeste homolog 2 (Drosophila); ENX1 ......
Chromosomal Location7q35-q36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of EZH2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolEZH2
Nameenhancer of zeste 2 polycomb repressive complex 2 subunit
Aliases ENX-1; KMT6; KMT6A; enhancer of zeste (Drosophila) homolog 2; enhancer of zeste homolog 2 (Drosophila); ENX1 ......
Chromosomal Location7q35-q36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of EZH2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by EZH2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolEZH2
Nameenhancer of zeste 2 polycomb repressive complex 2 subunit
Aliases ENX-1; KMT6; KMT6A; enhancer of zeste (Drosophila) homolog 2; enhancer of zeste homolog 2 (Drosophila); ENX1 ......
Chromosomal Location7q35-q36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of EZH2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolEZH2
Nameenhancer of zeste 2 polycomb repressive complex 2 subunit
Aliases ENX-1; KMT6; KMT6A; enhancer of zeste (Drosophila) homolog 2; enhancer of zeste homolog 2 (Drosophila); ENX1 ......
Chromosomal Location7q35-q36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of EZH2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolEZH2
Nameenhancer of zeste 2 polycomb repressive complex 2 subunit
Aliases ENX-1; KMT6; KMT6A; enhancer of zeste (Drosophila) homolog 2; enhancer of zeste homolog 2 (Drosophila); ENX1 ......
Chromosomal Location7q35-q36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between EZH2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolEZH2
Nameenhancer of zeste 2 polycomb repressive complex 2 subunit
Aliases ENX-1; KMT6; KMT6A; enhancer of zeste (Drosophila) homolog 2; enhancer of zeste homolog 2 (Drosophila); ENX1 ......
Chromosomal Location7q35-q36
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting EZH2 collected from DrugBank database.
> Drugs from DrugBank database
 

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