Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0001261
UniProt IDQ9UBN7
Primary gene name(s)HDAC6
Synonym gene name(s)KIAA0901
Protein nameHistone deacetylase 6
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, By similarity. Plays a central role in microtubule-dependent cell motility via deacetylation of tubulin. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. {ECO:0000250, ECO:0000269|PubMed:12024216, ECO:0000269|PubMed:17846173, ECO:0000269|PubMed:24413532}.; FUNCTION: In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome. Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and target them to the aggresome, facilitating their clearance by autophagy.
Subcellular locationNucleus. Cytoplasm. Perikaryon {ECO:0000250}. Cell projection, dendrite {ECO:0000250}. Cell projection, axon {ECO:0000250}. Note=It is mainly cytoplasmic, where it is associated with microtubules.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9UBN7
Gene Ontology
(Biological Process)
Complete annatation
aggresome assembly [GO:0070842];
cellular response to hydrogen peroxide [GO:0070301];
cellular response to misfolded protein [GO:0071218];
cellular response to topologically incorrect protein [GO:0035967];
collateral sprouting [GO:0048668];
dendritic spine morphogenesis [GO:0060997];
histone deacetylation [GO:0016575];
Hsp90 deacetylation [GO:0070846];
intracellular protein transport [GO:0006886];
lysosome localization [GO:0032418];
macroautophagy [GO:0016236];
misfolded or incompletely synthesized protein catabolic process [GO:0006515];
mitochondrion localization [GO:0051646];
mitophagy in response to mitochondrial depolarization [GO:0098779];
negative regulation of hydrogen peroxide metabolic process [GO:0010727];
negative regulation of microtubule depolymerization [GO:0007026];
negative regulation of oxidoreductase activity [GO:0051354];
negative regulation of protein complex disassembly [GO:0043242];
negative regulation of proteolysis [GO:0045861];
negative regulation of transcription, DNA-templated [GO:0045892];
organelle organization [GO:0006996];
peptidyl-lysine deacetylation [GO:0034983];
polyubiquitinated misfolded protein transport [GO:0070845];
positive regulation of chaperone-mediated protein complex assembly [GO:0090035];
positive regulation of epithelial cell migration [GO:0010634];
positive regulation of hydrogen peroxide-mediated programmed cell death [GO:1901300];
positive regulation of receptor biosynthetic process [GO:0010870];
positive regulation of signal transduction [GO:0009967];
protein complex disassembly [GO:0043241];
protein deacetylation [GO:0006476];
protein polyubiquitination [GO:0000209];
regulation of androgen receptor signaling pathway [GO:0060765];
regulation of autophagy [GO:0010506];
regulation of establishment of protein localization [GO:0070201];
regulation of fat cell differentiation [GO:0045598];
regulation of gene expression, epigenetic [GO:0040029];
regulation of microtubule-based movement [GO:0060632];
regulation of mitophagy [GO:1903146];
regulation of protein stability [GO:0031647];
regulation of receptor activity [GO:0010469];
response to growth factor [GO:0070848];
response to misfolded protein [GO:0051788];
response to organic substance [GO:0010033];
response to toxic substance [GO:0009636];
transcription, DNA-templated [GO:0006351];
tubulin deacetylation [GO:0090042];
ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway [GO:0043162]
Gene Ontology
(Molecular Function)
Complete annatation
alpha-tubulin binding [GO:0043014];
beta-catenin binding [GO:0008013];
core promoter binding [GO:0001047];
dynein complex binding [GO:0070840];
enzyme binding [GO:0019899];
histone deacetylase activity [GO:0004407];
histone deacetylase binding [GO:0042826];
Hsp90 protein binding [GO:0051879];
microtubule binding [GO:0008017];
misfolded protein binding [GO:0051787];
NAD-dependent histone deacetylase activity, H3-K14 specific [GO:0032041];
polyubiquitin binding [GO:0031593];
tau protein binding [GO:0048156];
tubulin deacetylase activity [GO:0042903];
ubiquitin protein ligase binding [GO:0031625];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
aggresome [GO:0016235];
axon [GO:0030424];
caveola [GO:0005901];
cell leading edge [GO:0031252];
cytoplasm [GO:0005737];
cytoplasmic microtubule [GO:0005881];
cytosol [GO:0005829];
dendrite [GO:0030425];
histone deacetylase complex [GO:0000118];
inclusion body [GO:0016234];
microtubule [GO:0005874];
microtubule associated complex [GO:0005875];
multivesicular body [GO:0005771];
nucleus [GO:0005634];
perikaryon [GO:0043204];
perinuclear region of cytoplasm [GO:0048471]
Protein-protein interaction115330
Phylogenetic treeQ9UBN7
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. CD3-1.340358543445495.90288098596403e-050.000301791798576831
AZA vs. DISU0.1225765299729020.6283669113254350.960057478314726
AZA vs. IL7-0.2086687245529380.3183299923612420.999311006273513
AZA vs. SAHA-0.310413827850020.3244193339856040.695632580440824
DISU vs. CD31.449624607431529.2107946306319e-050.000526920372911367
DISU vs. IL7-0.3409579159478260.1767136873526780.54477685824982
DISU vs. SAHA-0.4298288487936790.1444627563196170.488599237094467
DMSO vs. AZA0.1230461395930770.4933119222084961
DMSO vs. CD31.451557055411938.9182038462976e-065.19739810230071e-05
DMSO vs. DISU-0.001363903913471720.9955425381644140.998965101680981
DMSO vs. IL7-0.3243174593290080.07233029982946530.511810804782874
DMSO vs. SAHA-0.4382558890882590.1326831955065550.436558999194789
HIV vs. Mock in Activation0.3520257877188870.5727879954511380.999983755607037
HIV vs. Mock in Latency0.1856116379252850.2620897291434790.999834320637052
IL7 vs. CD31.136457238375170.0004908316312521870.00230836355003563
SAHA vs. CD31.007300667378280.004848985847771490.0139242028822249
SAHA vs. IL7-0.1039903139751570.7380673913307840.881056555732713
(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) TRUE
(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 0.011792 0.961335
(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
1.013 0.95 1.028 1.092 1.04
(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
DB02546 Vorinostat approved, investigational yes inhibitor
DB05223 SB939 investigational 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
3C5K X-ray 1.5Å A=1109-1215.
3GV4 X-ray 1.7Å A=1109-1215.
3PHD X-ray 3.0Å A/B/C/D=1109-1215.
5B8D X-ray 1.0Å A=1109-1213.
5EDU X-ray 2.7Å A/B=479-835.
5KH3 X-ray 1.6Å A=1109-1213.
5KH7 X-ray 1.7Å A=1109-1213.
5KH9 X-ray 1.0Å A=1109-1213.

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

HIV Partner Interaction Type PubMed
Vif binds 26105074
Tat increases 26031809
Tat enhanced by 26031809
Vif interacts with 26105074
Envelope surface glycoprotein gp120 inhibited by 16148047
Vif inhibited by 26105074
Vif complexes with 26105074
Vif degradation is mediated by 26105074
Vif decreased by 26105074
HIV-1 virus replication inhibited by expression of human gene 26105074
Envelope transmembrane glycoprotein gp41 inhibited by 16148047
Tat interacts with 21220424

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa05034 Alcoholism - Homo sapiens (human)
hsa05203 Viral carcinogenesis - Homo sapiens (human)