Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

HDAC6 (Q9UBN7) - Overview - Molecular Target Synopsis

Protein


HDAC6, Histone deacetylase 6
Enzyme Classification 3.5.1.98
UniProt Q9UBN7

Also Known as HDAC6_HUMAN, HDAC6, KIAA0901

Responsible 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., 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. Interacts with ZMYND15 (By similarity). Interacts with SIRT2 (via both phosphorylated, unphosphorylated, active or inactive forms); the interaction is necessary for the complex to interact with alpha-tubulin. Under proteasome impairment conditions, interacts with UBD via its histone deacetylase 1 and UBP-type zinc-finger regions. Interacts with BBIP10, CBFA2T3, CYLD, DDIT3/CHOP, F-actin and HDAC11. Interacts with RIPOR2; this interaction occurs during early myogenic differentiation and prevents HDAC6 to deacetylate tubulin (PubMed:24687993). Interacts with DYSF; this interaction occurs during early myogenic differentiation (PubMed:24687993).

6CEA
CRYSTAL STRUCTURE OF FRAGMENT 3-(QUINOLIN-2-YL)PROPANOIC ACID BOUND IN THE UBIQUITIN BINDING POCKET OF THE HDAC6 ZINC-FINGER DOMAIN
RCSB/PDB
Inspect Structure
See all 3D Structures for HDAC6

Isoforms / Transcripts (Protein Coding)


Drugs


HDAC6 is targeted by Approved Drugs Belinostat, Vorinostat. (see details)
Belinostat
Vorinostat

Sub-cellular localization


UniProt: HDAC6 is active in the following subcellular-locations: axon, cell projection, cytoplasm, dendrite, nucleus, perikaryon.
GO terms: HDAC6 is active in the following subcellular-locations: aggresome, axon, caveola, cell leading edge, cytoplasm, cytoplasmic microtubule, cytosol, dendrite, histone deacetylase complex, inclusion body, microtubule, microtubule associated complex, multivesicular body, nucleoplasm, nucleus, perikaryon, perinuclear region of cytoplasm.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project HDAC6 has gain in 1 cell-lines, loss in 61 cell-lines and no signal in 943 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MDA_MB_231, HOP_92, MCF7

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H1882, OCI-M2, NCI-H345

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, K562, HUVEC

(see details)

3D Structures


For HDAC6 there are:
17 structures (21 chains) solved
14 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


HDAC6 has been screened with 4406 compounds (7638 bioactivities), 1893 compounds have bioactivities that show binding affinity of <= 500nM (2609 bioactivities). (see details)