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HDAC6
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	3C5K, 3GV4, 3PHD, 5EDU, 5KH7
Identifiers
Aliases	HDAC6, CPBHM, HD6, PPP1R90, JM21, histone deacetylase 6
External IDs	OMIM: 300272; MGI: 1333752; HomoloGene: 31353; GeneCards: HDAC6; OMA:HDAC6 - orthologs
Gene location (Human)
Chr.	X chromosome (human)
End	48,824,982 bp
Gene location (Mouse)
Chr.	X chromosome (mouse)
End	7,814,128 bp
RNA expression pattern
	Top expressed in
	right hemisphere of cerebellum; ; anterior pituitary; ; right lobe of liver; ; right testis; ; left testis; ; body of uterus; ; right ovary; ; left ovary; ; ventricular zone; ; ganglionic eminence;
	Top expressed in
	entorhinal cortex; ; perirhinal cortex; ; islet of Langerhans; ; yolk sac; ; central gray substance of midbrain; ; CA3 field; ; epiblast; ; medullary collecting duct; ; dorsomedial hypothalamic nucleus; ; choroid plexus of fourth ventricle;
	More reference expression data
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	histone deacetylase binding; misfolded protein binding; metal ion binding; enzyme binding; NAD-dependent histone deacetylase activity (H3-K14 specific); beta-catenin binding; zinc ion binding; polyubiquitin modification-dependent protein binding; protein binding; tau protein binding; dynein complex binding; Hsp90 protein binding; histone deacetylase activity; microtubule binding; alpha-tubulin binding; ubiquitin binding; beta-tubulin binding; actin binding; hydrolase activity; ubiquitin protein ligase binding; tubulin deacetylase activity; RNA polymerase II cis-regulatory region sequence-specific DNA binding; protein deacetylase activity; acetylspermidine deacetylase activity;
Cellular component	cytosol; perinuclear region of cytoplasm; caveola; microtubule; nucleus; multivesicular body; cell projection; microtubule associated complex; aggresome; dynein complex; histone deacetylase complex; perikaryon; axon; inclusion body; dendrite; cell leading edge; cytoplasmic microtubule; cell body; neuron projection; nucleoplasm; cytoplasm; protein-containing complex;
Biological process	Hsp90 deacetylation; protein quality control for misfolded or incompletely synthesized proteins; response to organic substance; cellular response to topologically incorrect protein; tubulin deacetylation; regulation of establishment of protein localization; ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; response to growth factor; intracellular protein transport; aggresome assembly; negative regulation of proteolysis; histone H3 deacetylation; positive regulation of signal transduction; peptidyl-lysine deacetylation; response to misfolded protein; regulation of transcription, DNA-templated; regulation of protein stability; ubiquitin-dependent protein catabolic process; mitochondrion localization; positive regulation of epithelial cell migration; regulation of fat cell differentiation; transcription, DNA-templated; regulation of autophagy of mitochondrion; polyubiquitinated misfolded protein transport; response to toxic substance; positive regulation of hydrogen peroxide-mediated programmed cell death; regulation of microtubule-based movement; regulation of signaling receptor activity; protein polyubiquitination; protein deacetylation; negative regulation of hydrogen peroxide metabolic process; regulation of autophagy; negative regulation of oxidoreductase activity; regulation of androgen receptor signaling pathway; negative regulation of transcription, DNA-templated; cellular response to misfolded protein; positive regulation of chaperone-mediated protein complex assembly; regulation of gene expression, epigenetic; negative regulation of protein-containing complex disassembly; autophagy; negative regulation of microtubule depolymerization; lysosome localization; histone deacetylation; cellular response to hydrogen peroxide; collateral sprouting; dendritic spine morphogenesis; cilium assembly; regulation of macroautophagy; parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; positive regulation of mitophagy in response to mitochondrial depolarization; chromatin organization; positive regulation of protein oligomerization; protein-containing complex disassembly; positive regulation of peptidyl-serine phosphorylation; polyamine deacetylation; spermidine deacetylation;
	Sources:Amigo / QuickGO
Orthologs
	10013
	15185
	ENSG00000094631
	ENSMUSG00000031161
	Q9UBN7
	Q9Z2V5
NM_006044; NM_001321225; NM_001321226; NM_001321227; NM_001321228;
	NM_001321229; NM_001321230; NM_001321231
	NM_001130416; NM_010413
NP_001308154; NP_001308155; NP_001308156; NP_001308157; NP_001308158;
	NP_001308159; NP_001308160; NP_006035
	NP_001123888; NP_034543
	Wikidata
View/Edit Human	View/Edit Mouse

Histone deacetylase 6 is an enzyme that in humans is encoded by the HDAC6 gene.^[5]^[6] HDAC6 has emerged as a highly promising candidate to selectively inhibit as a therapeutic strategy to combat several types of cancer and neurodegenerative disorders.^[7]

Function

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromatin structure and affects transcription. The protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It contains an internal duplication of two catalytic domains that appear to function independently of each other. This protein possesses histone deacetylase activity and represses transcription.^[8]

It retracts the cilium of the cell, which is necessary prior to mitosis. ^[9]

HDAC encourages cell motility and catalyzes α-tubulin deacetylation.^[10] As a result the enzyme encourages cancer cell metastasis.^[11]

HDAC6 affects transcription and translation by regulating heat-shock protein 90 (Hsp90).

HDAC6 is required in the formation of stress granule (SG) proteins and is instrumental in SG formation; pharmacological inhibition or genetic removal of HDAC6 abolished SG formation.^[11]

HDAC6 bonds with high affinity to ubiquitinated proteins.^[12]

HDAC6 is involved in leptin sensitivity.^[13]

HDAC6 deacetylates tyrosine residue T178 on TAK1.^[14]

Clinical relevance

Mutations in this gene have been associated to Alzheimer's disease.^[15]

Over expression of this protein correlates with tumorigenesis and cell survival. HDAC6 also encourages metastasis of cancer cells.^[11]

Since HDAC6 is dysregulated and/or implicated in several cancers and neurodegenerative disorders, pharmacological inhibition of this specific enzyme holds great therapeutic potential and could also limit side effects associated with pan-inhibitors of multiple HDAC enzymes.^[7] Selective inhibition of HDAC6 as a strategy to treat cancers is however also subject of debate, since some HDAC6 inhibitors exhibited anti-tumor activity in vitro and in vivo only when administered in high concentrations, which also produced off-target effects. The findings suggest that further study is needed to clarify data on anti-cancer effects of selective HDAC6 inhibitors.^[16]