Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001259
UniProt IDP56524
Primary gene name(s)HDAC4
Synonym gene name(s)KIAA0288
Protein nameHistone deacetylase 4
Protein functionResponsible for the deacetylation of lysine residues on the N-terminal part of the core histones, H2A, H2B, H3 and H4. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. {ECO:0000269|PubMed:10523670, ECO:0000269|PubMed:24413532}.
Subcellular locationNucleus. Cytoplasm. Note=Shuttles between the nucleus and the cytoplasm. Upon muscle cells differentiation, it accumulates in the nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in muscle differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-246, Ser-467 and Ser-632 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P56524
Gene Ontology
(Biological Process)
Complete annatation
B cell activation [GO:0042113];
B cell differentiation [GO:0030183];
cardiac muscle hypertrophy in response to stress [GO:0014898];
cellular response to mechanical stimulus [GO:0071260];
cellular response to parathyroid hormone stimulus [GO:0071374];
cellular response to tumor necrosis factor [GO:0071356];
chromatin remodeling [GO:0006338];
histone deacetylation [GO:0016575];
histone H3 deacetylation [GO:0070932];
histone H4 deacetylation [GO:0070933];
inflammatory response [GO:0006954];
negative regulation of cell proliferation [GO:0008285];
negative regulation of glycolytic process [GO:0045820];
negative regulation of myotube differentiation [GO:0010832];
negative regulation of osteoblast differentiation [GO:0045668];
negative regulation of sequence-specific DNA binding transcription factor activity [GO:0043433];
negative regulation of transcription, DNA-templated [GO:0045892];
negative regulation of transcription from RNA polymerase II promoter [GO:0000122];
nervous system development [GO:0007399];
osteoblast development [GO:0002076];
peptidyl-lysine deacetylation [GO:0034983];
positive regulation of cell proliferation [GO:0008284];
positive regulation of lamellipodium assembly [GO:0010592];
positive regulation of neuron apoptotic process [GO:0043525];
positive regulation of protein sumoylation [GO:0033235];
positive regulation of reactive oxygen species biosynthetic process [GO:1903428];
positive regulation of sequence-specific DNA binding transcription factor activity [GO:0051091];
positive regulation of smooth muscle cell migration [GO:0014911];
positive regulation of smooth muscle cell proliferation [GO:0048661];
positive regulation of transcription, DNA-templated [GO:0045893];
positive regulation of transcription from RNA polymerase II promoter [GO:0045944];
regulation of cardiac muscle contraction by calcium ion signaling [GO:0010882];
regulation of gene expression, epigenetic [GO:0040029];
regulation of protein binding [GO:0043393];
regulation of skeletal muscle fiber development [GO:0048742];
response to denervation involved in regulation of muscle adaptation [GO:0014894];
response to drug [GO:0042493];
response to interleukin-1 [GO:0070555];
skeletal system development [GO:0001501];
transcription, DNA-templated [GO:0006351]
Gene Ontology
(Molecular Function)
Complete annatation
activating transcription factor binding [GO:0033613];
chromatin binding [GO:0003682];
core promoter binding [GO:0001047];
histone deacetylase activity [GO:0004407];
histone deacetylase binding [GO:0042826];
NAD-dependent histone deacetylase activity, H3-K14 specific [GO:0032041];
potassium ion binding [GO:0030955];
protein deacetylase activity [GO:0033558];
repressing transcription factor binding [GO:0070491];
RNA polymerase III transcription factor binding [GO:0001025];
transcription corepressor activity [GO:0003714];
transcription factor binding [GO:0008134];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
A band [GO:0031672];
actomyosin [GO:0042641];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
histone deacetylase complex [GO:0000118];
neuromuscular junction [GO:0031594];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
transcriptional repressor complex [GO:0017053];
Z disc [GO:0030018]
Protein-protein interaction115106
Phylogenetic treeP56524
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. CD3-0.6333567868726960.05805008282566450.11299636424492
AZA vs. DISU-0.2246858248567850.3765398538382090.89822839898246
AZA vs. IL7-0.1569871404438030.4182013530530650.999311006273513
AZA vs. SAHA-0.1278203267751830.6020893233106810.868743947405718
DISU vs. CD30.3970281114622620.2829428222111010.412882875315599
DISU vs. IL70.05796266910448630.8187321471188670.961243368243154
DISU vs. SAHA0.09911472281617230.7345129171055210.92268543851593
DMSO vs. AZA0.07482958742887540.6585231801576741
DMSO vs. CD30.6955103990967570.03395771205605020.0695071918647279
DMSO vs. DISU0.2971877108637230.2253203920378380.737960121390356
DMSO vs. IL7-0.224197686249920.2163955897058530.724804783238115
DMSO vs. SAHA-0.2076820753211990.3808741100339790.728544842512093
HIV vs. Mock in Activation0.09635655051688430.892793716545850.999983755607037
HIV vs. Mock in Latency0.08012630124197450.6294490037846980.999834320637052
IL7 vs. CD30.4819602988365180.1428991534858340.249515643576896
SAHA vs. CD30.4824861062875630.1791773877095560.277541703441567
SAHA vs. IL70.02659961943129720.9134759101028540.967061098621067
(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
0.2983 0.04852

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 -0.253024 0.0846085
(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
unknown unknown

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
unknown unknown unknown unknown unknown
(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
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB07879 N-hydroxy-5-[(3-phenyl-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl)carbonyl]thiophene-2-carboxamide experimental unknown unknown
DB08613 2,2,2-TRIFLUORO-1-{5-[(3-PHENYL-5,6-DIHYDROIMIDAZO[1,2-A]PYRAZIN-7(8H)-YL)CARBONYL]THIOPHEN-2-YL}ETHANE-1,1-DIOL experimental unknown unknown
DB06176 Romidepsin approved, investigational unknown inhibitor
DB05015 Belinostat approved, investigational yes inhibitor
DB06603 Panobinostat approved, investigational yes inhibitor

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2H8N X-ray 2.6Å A/B/C/D=62-153.
2O94 X-ray 3.0Å A/B/C/D=62-153.
2VQJ X-ray 2.1Å A=648-1057.
2VQM X-ray 1.8Å A=648-1057.
2VQO X-ray 2.1Å A/B=648-1057.
2VQQ X-ray 1.9Å A/B=648-1057.
2VQV X-ray 3.3Å A/B=648-1057.
2VQW X-ray 3.0Å G=648-1057.
3UXG X-ray 1.8Å B=343-359.
3UZD X-ray 1.8Å B=343-359.
3V31 X-ray 1.5Å B=343-359.
4CBT X-ray 3.0Å A/B/C=648-1033.
4CBY X-ray 2.7Å A/B/C/D=648-1033.
5A2S X-ray 2.6Å A/B=648-1033.

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

HIV Partner Interaction Type PubMed
reverse transcriptase regulated by 22826225

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa05034 Alcoholism - Homo sapiens (human)
hsa05169 Epstein-Barr virus infection - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)
hsa05206 MicroRNAs in cancer - Homo sapiens (human)