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Details on Person UniProt:A0A8I6GM68 Hdac6
| Class:Id | ReferenceGeneProduct:9948495 |
|---|---|
| _chainChangeLog | chain:1-1183 for 9948495 added on Wed May 21 2025 |
| _displayName | UniProt:A0A8I6GM68 Hdac6 |
| _timestamp | 2026-02-20 23:06:09 |
| chain | chain:1-1183 |
| checksum | CF96A7D4E06A5C84 |
| comment | FUNCTION Deacetylates a wide range of non-histone substrates (By similarity). Plays a central role in microtubule-dependent cell motility by mediating deacetylation of tubulin (By similarity). Required for cilia disassembly via deacetylation of alpha-tubulin (By similarity). Alpha-tubulin deacetylation results in destabilization of dynamic microtubules (By similarity). Promotes deacetylation of CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy (By similarity). Deacetylates SQSTM1. Deacetylates peroxiredoxins PRDX1 and PRDX2, decreasing their reducing activity (By similarity). Deacetylates antiviral protein RIGI in the presence of viral mRNAs which is required for viral RNA detection by RIGI (By similarity). Sequentially deacetylates and polyubiquitinates DNA mismatch repair protein MSH2 which leads to MSH2 degradation, reducing cellular sensitivity to DNA-damaging agents and decreasing cellular DNA mismatch repair activities (By similarity). Deacetylates DNA mismatch repair protein MLH1 which prevents recruitment of the MutL alpha complex (formed by the MLH1-PMS2 heterodimer) to the MutS alpha complex (formed by the MSH2-MSH6 heterodimer), leading to tolerance of DNA damage (By similarity). Deacetylates RHOT1/MIRO1 which blocks mitochondrial transport and mediates axon growth inhibition (PubMed:31068376). Deacetylates transcription factor SP1 which leads to increased expression of ENG, positively regulating angiogenesis (By similarity). Deacetylates KHDRBS1/SAM68 which regulates alternative splicing by inhibiting the inclusion of CD44 alternate exons (By similarity). Deacetylates PRDM16 (By similarity). Promotes odontoblast differentiation following IPO7-mediated nuclear import and subsequent repression of RUNX2 expression (By similarity). 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 (By similarity). Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and targets them to the aggresome, facilitating their clearance by autophagy (By similarity).CATALYTIC ACTIVITY N(6)-acetyl-L-lysyl-[protein] + H2O = L-lysyl-[protein] + acetateCATALYTIC ACTIVITY N(6)-acetyl-L-lysyl-[alpha-tubulin] + H2O = L-lysyl-[alpha-tubulin] + acetateCOFACTOR Binds 3 Zn(2+) ions per subunit.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Forms a trimeric complex in the nucleus consisting of BANP, HDAC6 and KHDRBS1/SAM68; HDAC6 keeps KHDRBS1 in a deacetylated state which inhibits the inclusion of CD44 alternate exons (By similarity). The complex is disrupted by MAPK1/MAPK3-mediated phosphorylation of BANP which results in BANP export to the cytoplasm (By similarity). This facilitates acetylation of KHDRBS1 and CD44 variant exon inclusion (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 BBIP1, CBFA2T3, CYLD, DDIT3/CHOP, ZMYND15, F-actin and HDAC11. Interacts with RIPOR2; this interaction occurs during early myogenic differentiation and prevents HDAC6 to deacetylate tubulin. Interacts with AURKA; AURKA-mediated phosphorylation of HDAC6 promotes deacetylation of alpha-tubulin. Interacts with DYSF; this interaction occurs during early myogenic differentiation. Interacts with TPPP; inhibiting the tubulin deacetylase activity of HDAC6. Interacts with DYNLL1. Interacts with ATP13A2; the interaction results in recruitment of HDAC6 to lysosomes to promote CTTN deacetylation. Interacts with CCDC141 (via the N-terminal region); inhibiting the deacetylase activity of HDAC6. Interacts with IPO7; the interaction facilitates HDAC6 nuclear translocation in dental papilla cells.SUBCELLULAR LOCATION Mainly cytoplasmic where it is associated with microtubules (By similarity). Can shuttle between the cytoplasm and the nucleus. Found exclusively in the cytoplasm in proliferative cells with a fraction found in the nucleus during differentiation (By similarity). May translocate to the nucleus following DNA damage (By similarity).DOMAIN Histone deacetylase domain 1 mediates the E3 ubiquitin-protein ligase activity.PTM Phosphorylated by AURKA; phosphorylation increases HDAC6-mediated deacetylation of alpha-tubulin and subsequent disassembly of cilia.PTM Ubiquitinated. Its polyubiquitination however does not lead to its degradation.PTM Sumoylated in vitro.SIMILARITY Belongs to the histone deacetylase family. HD type 2 subfamily.CAUTION Was originally thought to be a histone deacetylase. However, subsequent work has shown that it is predominantly cytoplasmic and deacetylates a range of non-histone substrates. |
| created | [InstanceEdit:9948485] Weiser, Joel, 2025-05-21 |
| description | recommendedName: fullName evidence="6"Protein deacetylase HDAC6 ecNumber evidence="1"3.5.1.- alternativeName: fullName evidence="6"E3 ubiquitin-protein ligase HDAC6 ecNumber evidence="1"2.3.2.- alternativeName: fullName evidence="6"Tubulin-lysine deacetylase HDAC6 ecNumber evidence="1"3.5.1.- |
| geneName | Hdac6 |
| identifier | A0A8I6GM68 |
| isSequenceChanged | FALSE |
| keyword | Actin-binding Autophagy Cell projection Chromatin regulator Cytoplasm Cytoskeleton Hydrolase Metal-binding Methylation Nucleus Phosphoprotein Reference proteome Repeat Repressor Transcription Transcription regulation Transferase Ubl conjugation Ubl conjugation pathway Zinc Zinc-finger |
| modified | [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | Hdac6 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | HDAC6_RAT |
| sequenceLength | 1183 |
| species | [Species:48895] Rattus norvegicus |
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No pathways have been reviewed or authored by UniProt:A0A8I6GM68 Hdac6 (9948495)
