Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0000999
UniProt IDQ15910
Primary gene name(s)EZH2
Synonym gene name(s)KMT6
Protein nameHistone-lysine N-methyltransferase EZH2
Protein functionPolycomb 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. 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. {ECO:0000269|PubMed:14532106, ECO:0000269|PubMed:15225548, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:15385962, ECO:0000269|PubMed:16179254, ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:16618801, ECO:0000269|PubMed:16717091, ECO:0000269|PubMed:16936726, ECO:0000269|PubMed:17210787, ECO:0000269|PubMed:17344414, ECO:0000269|PubMed:18285464, ECO:0000269|PubMed:19026781, ECO:0000269|PubMed:20935635, ECO:0000269|PubMed:23063525, ECO:0000269|PubMed:24474760}.
Subcellular locationNucleus {ECO:0000269|PubMed:12101246, ECO:0000269|PubMed:14532106, ECO:0000269|PubMed:15231737, ECO:0000269|PubMed:9584199}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q15910
Gene Ontology
(Biological Process)
Complete annatation
cardiac muscle hypertrophy in response to stress [GO:0014898];
cellular response to hydrogen peroxide [GO:0070301];
cellular response to trichostatin A [GO:0035984];
cerebellar cortex development [GO:0021695];
chromatin organization [GO:0006325];
DNA methylation [GO:0006306];
G1 to G0 transition [GO:0070314];
hepatocyte homeostasis [GO:0036333];
hippocampus development [GO:0021766];
histone H3-K27 methylation [GO:0070734];
histone H3-K27 trimethylation [GO:0098532];
liver regeneration [GO:0097421];
negative regulation of epidermal cell differentiation [GO:0045605];
negative regulation of G1/S transition of mitotic cell cycle [GO:2000134];
negative regulation of gene expression, epigenetic [GO:0045814];
negative regulation of retinoic acid receptor signaling pathway [GO:0048387];
negative regulation of sequence-specific DNA binding transcription factor activity [GO:0043433];
negative regulation of striated muscle cell differentiation [GO:0051154];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of transcription elongation from RNA polymerase II promoter [GO:0034244];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
positive regulation of dendrite development [GO:1900006];
positive regulation of epithelial to mesenchymal transition [GO:0010718];
positive regulation of GTPase activity [GO:0043547];
positive regulation of MAP kinase activity [GO:0043406];
positive regulation of protein serine/threonine kinase activity [GO:0071902];
protein localization to chromatin [GO:0071168];
regulation of cell proliferation [GO:0042127];
regulation of circadian rhythm [GO:0042752];
regulation of gliogenesis [GO:0014013];
regulation of transcription, DNA-templated [GO:0006355];
response to estradiol [GO:0032355];
response to tetrachloromethane [GO:1904772];
rhythmic process [GO:0048511];
skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration [GO:0014834];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
chromatin binding [GO:0003682];
chromatin DNA binding [GO:0031490];
core promoter binding [GO:0001047];
DNA binding [GO:0003677];
histone-lysine N-methyltransferase activity [GO:0018024];
histone methyltransferase activity [GO:0042054];
histone methyltransferase activity, H3-K27 specific [GO:0046976];
promoter-specific chromatin binding [GO:1990841];
protein-lysine N-methyltransferase activity [GO:0016279];
ribonucleoprotein complex binding [GO:0043021];
RNA binding [GO:0003723];
sequence-specific DNA binding [GO:0043565]
Gene Ontology
(Cellular Component)
Complete annatation
cytoplasm [GO:0005737];
ESC/E(Z complex [GO:0035098];
nuclear chromatin [GO:0000790];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
pronucleus [GO:0045120]
Protein-protein interaction108446
Phylogenetic treeQ15910
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD32.357329620459831.73895062960394e-061.2791344016296e-05
AZA vs. DISU0.2328725383664780.3607545619205780.893849883358823
AZA vs. IL70.1697726462396850.3835671506324660.999311006273513
AZA vs. SAHA0.450537479803690.06971687060897950.325359785622216
DISU vs. CD3-2.137483465058131.53317689178811e-050.000108809361896488
DISU vs. IL7-0.07229255389492850.7751250677626390.948193076312414
DISU vs. SAHA0.2195562145641550.4610009675227420.799761228181291
DMSO vs. AZA0.05415142614872180.7506907498087051
DMSO vs. CD3-2.316174793232952.62982542831303e-061.72478537560016e-05
DMSO vs. DISU-0.1810026599651730.4616653729049420.892965804867364
DMSO vs. IL70.1229457436460460.5002944437488660.885914818891506
DMSO vs. SAHA0.3907063766873450.1025403097423770.378399855075259
HIV vs. Mock in Activation-0.04750862411671670.9643371412511150.999983755607037
HIV vs. Mock in Latency0.1297101531370820.5021116744634040.999834320637052
IL7 vs. CD3-2.180317970523061.46507467336798e-050.000108091387918138
SAHA vs. CD3-1.931194323597160.0005159499234865810.00201069701239792
SAHA vs. IL70.2779130893976930.2726715412077780.520153228570747
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.349781 0.0100693
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
0.033 0.009

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.922 0.991 1.012 1.058 1.017
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
203358_s_at 1.34 Yes upregulated in CD4+ cells

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2C6V Model - A=508-734.
4MI0 X-ray 2.0Å A=520-746.
4MI5 X-ray 2.0Å A=521-746.
5HYN X-ray 2.9Å A/F/K/Q=1-746.
5IJ7 X-ray 2.6Å A/B=429-487# A/B=511-746.
5IJ8 X-ray 2.9Å A/B=429-487# A/B=511-531# A/B=533-746.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
HIV-1 virus replication enhanced by expression of human gene 20174665

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00310 Lysine degradation - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)