Protein: Protein deacetylase HDAC6 (EC 3.5.1.-) (E3 ubiquitin-protein ligase HDAC6) (EC 2.3.2.-) (Tubulin-lysine deacetylase HDAC6) (EC 3.5.1.-) (Q9UBN7)
Organism: Homo sapiens (Human)
Function: 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. In addition to histones, deacetylates other proteins: plays a central role in microtubule-dependent cell motility by mediating deacetylation of tubulin. Required for cilia disassembly; via deacetylation of alpha-tubulin. Promotes deacetylation of CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy. 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.
Subcellular location: Cytoplasm {ECO:0000269|PubMed:12024216, ECO:0000269|PubMed:24687993, ECO:0000269|PubMed:26246421, ECO:0000269|PubMed:30770470, ECO:0000269|PubMed:39567688}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:12024216}. Nucleus {ECO:0000269|PubMed:24882211, ECO:0000269|PubMed:26080397, ECO:0000269|PubMed:30770470, ECO:0000269|PubMed:39567688}. Perikaryon {ECO:0000250|UniProtKB:Q9Z2V5}. Cell projection, dendrite {ECO:0000250|UniProtKB:Q9Z2V5}. Cell projection, axon {ECO:0000250|UniProtKB:Q9Z2V5}. Cell projection, cilium {ECO:0000269|PubMed:17604723}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:26246421}. Cytoplasm, cytoskeleton, cilium basal body {ECO:0000269|PubMed:26246421}. Note=Mainly cytoplasmic where it is associated with microtubules (PubMed:12024216). Can shuttle between the cytoplasm and the nucleus (PubMed:39567688). Retained in the cytoplasm by binding to valine via the primate-specific SE14 repeat region while valine deprivation induces nuclear localization (PubMed:39567688). 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 (PubMed:30770470). {ECO:0000250|UniProtKB:Q9Z2V5, ECO:0000269|PubMed:12024216, ECO:0000269|PubMed:30770470, ECO:0000269|PubMed:39567688}.
Interaction partners:
- Heat shock protein HSP 90-alpha
- Heat shock protein HSP 90-beta
- Src substrate cortactin
- Polyubiquitin-C
- Transitional endoplasmic reticulum ATPase
- Histone acetyltransferase p300
- Hematopoietic lineage cell-specific protein
- TAR DNA-binding protein 43
- Sequestosome-1
- Runt-related transcription factor 2
Sequence:
MTSTGQDSTTTRQRRSRQNPQSPPQDSSVTSKRNIKKGAVPRSIPNLAEVKKKGKMKKLGQAMEEDLIVGLQGMDLNLEAEALAGTGLVLDEQLNEFHCLWDDSFPEGPERLHAIKEQLIQEGLLDRCVSFQARFAEKEELMLVHSLEYIDLMETTQYMNEGELRVLADTYDSVYLHPNSYSCACLASGSVLRLVDAVLGAEIRNGMAIIRPPGHHAQHSLMDGYCMFNHVAVAARYAQQKHRIRRVLIVDWDVHHGQGTQFTFDQDPSVLYFSIHRYEQGRFWPHLKASNWSTTGFGQGQGYTINVPWNQVGMRDADYIAAFLHVLLPVALEFQPQLVLVAAGFDALQGDPKGEMAATPAGFAQLTHLLMGLAGGKLILSLEGGYNLRALAEGVSASLHTLLGDPCPMLESPGAPCRSAQASVSCALEALEPFWEVLVRSTETVERDNMEEDNVEESEEEGPWEPPVLPILTWPVLQSRTGLVYDQNMMNHCNLWDSHHPEVPQRILRIMCRLEELGLAGRCLTLTPRPATEAELLTCHSAEYVGHLRATEKMKTRELHRESSNFDSIYICPSTFACAQLATGAACRLVEAVLSGEVLNGAAVVRPPGHHAEQDAACGFCFFNSVAVAARHAQTISGHALRILIVDWDVHHGNGTQHMFEDDPSVLYVSLHRYDHGTFFPMGDEGASSQIGRAAGTGFTVNVAWNGPRMGDADYLAAWHRLVLPIAYEFNPELVLVSAGFDAARGDPLGGCQVSPEGYAHLTHLLMGLASGRIILILEGGYNLTSISESMAACTRSLLGDPPPLLTLPRPPLSGALASITETIQVHRRYWRSLRVMKVEDREGPSSSKLVTKKAPQPAKPRLAERMTTREKKVLEAGMGKVTSASFGEESTPGQTNSETAVVALTQDQPSEAATGGATLAQTISEAAIGGAMLGQTTSEEAVGGATPDQTTSEETVGGAILDQTTSEDAVGGATLGQTTSEEAVGGATLAQTTSEAAMEGATLDQTTSEEAPGGTELIQTPLASSTDHQTPPTSPVQGTTPQISPSTLIGSLRTLELGSESQGASESQAPGEENLLGEAAGGQDMADSMLMQGSRGLTDQAIFYAVTPLPWCPHLVAVCPIPAAGLDVTQPCGDCGTIQENWVCLSCYQVYCGRYINGHMLQHHGNSGHPLVLSYIDLSAWCYYCQAYVHHQALLDVKNIAHQNKFGEDMPHPH