HDAC6_HUMAN
ID HDAC6_HUMAN Reviewed; 1215 AA.
AC Q9UBN7; O94975; Q6NT75; Q7L3E5; Q96CY0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Histone deacetylase 6;
DE Short=HD6;
DE EC=3.5.1.98 {ECO:0000269|PubMed:10220385};
DE AltName: Full=Tubulin-lysine deacetylase HDAC6 {ECO:0000305};
DE EC=3.5.1.- {ECO:0000269|PubMed:12024216, ECO:0000269|PubMed:20308065};
GN Name=HDAC6 {ECO:0000303|PubMed:10220385, ECO:0000312|HGNC:HGNC:14064};
GN Synonyms=KIAA0901 {ECO:0000303|PubMed:10048485}; ORFNames=JM21;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, AND
RP VARIANT ILE-994.
RX PubMed=10220385; DOI=10.1073/pnas.96.9.4868;
RA Grozinger C.M., Hassig C.A., Schreiber S.L.;
RT "Three proteins define a class of human histone deacetylases related to
RT yeast Hda1p.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:4868-4873(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [3]
RP SEQUENCE REVISION.
RA Ohara O., Suyama M., Kikuno R., Nagase T., Ishikawa K.;
RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-994.
RC TISSUE=Brain;
RA Strom T.M., Gutwillinger N., Nyakatura G., Hellebrand H., Drescher B.,
RA Rosenthal A., Meindl A.;
RT "Transcription map in Xp11.23.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15772651; DOI=10.1038/nature03440;
RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D.,
RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S.,
RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D.,
RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H.,
RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K.,
RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D.,
RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R.,
RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F.,
RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP ASP-1200.
RC TISSUE=Ovary, and Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH CBFA2T3.
RX PubMed=11533236; DOI=10.1128/mcb.21.19.6470-6483.2001;
RA Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N.,
RA Downing J.R., Meyers S., Hiebert S.W.;
RT "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with
RT multiple histone deacetylases and binds mSin3A through its oligomerization
RT domain.";
RL Mol. Cell. Biol. 21:6470-6483(2001).
RN [9]
RP INTERACTION WITH HDAC11.
RX PubMed=11948178; DOI=10.1074/jbc.m111871200;
RA Gao L., Cueto M.A., Asselbergs F., Atadja P.;
RT "Cloning and functional characterization of HDAC11, a novel member of the
RT human histone deacetylase family.";
RL J. Biol. Chem. 277:25748-25755(2002).
RN [10]
RP SUMOYLATION.
RX PubMed=12032081; DOI=10.1093/emboj/21.11.2682;
RA Kirsh O., Seeler J.-S., Pichler A., Gast A., Mueller S., Miska E.,
RA Mathieu M., Harel-Bellan A., Kouzarides T., Melchior F., Dejean A.;
RT "The SUMO E3 ligase RanBP2 promotes modification of the HDAC4
RT deacetylase.";
RL EMBO J. 21:2682-2691(2002).
RN [11]
RP UBIQUITINATION, AND MUTAGENESIS OF HIS-216 AND HIS-611.
RX PubMed=12354939; DOI=10.1073/pnas.172511699;
RA Hook S.S., Orian A., Cowley S.M., Eisenman R.N.;
RT "Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ
RT domain) and copurifies with deubiquitinating enzymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13425-13430(2002).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=12024216; DOI=10.1038/417455a;
RA Hubbert C., Guardiola A., Shao R., Kawaguchi Y., Ito A., Nixon A.,
RA Yoshida M., Wang X.-F., Yao T.-P.;
RT "HDAC6 is a microtubule-associated deacetylase.";
RL Nature 417:455-458(2002).
RN [13]
RP INTERACTION WITH SIRT2.
RX PubMed=12620231; DOI=10.1016/s1097-2765(03)00038-8;
RA North B.J., Marshall B.L., Borra M.T., Denu J.M., Verdin E.;
RT "The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin
RT deacetylase.";
RL Mol. Cell 11:437-444(2003).
RN [14]
RP PHOSPHORYLATION BY AURKA.
RX PubMed=17604723; DOI=10.1016/j.cell.2007.04.035;
RA Pugacheva E.N., Jablonski S.A., Hartman T.R., Henske E.P., Golemis E.A.;
RT "HEF1-dependent Aurora A activation induces disassembly of the primary
RT cilium.";
RL Cell 129:1351-1363(2007).
RN [15]
RP INTERACTION WITH DDIT3.
RX PubMed=17872950; DOI=10.1074/jbc.m703735200;
RA Ohoka N., Hattori T., Kitagawa M., Onozaki K., Hayashi H.;
RT "Critical and functional regulation of CHOP (C/EBP homologous protein)
RT through the N-terminal portion.";
RL J. Biol. Chem. 282:35687-35694(2007).
RN [16]
RP FUNCTION.
RX PubMed=17846173; DOI=10.1083/jcb.200611128;
RA Olzmann J.A., Li L., Chudaev M.V., Chen J., Perez F.A., Palmiter R.D.,
RA Chin L.S.;
RT "Parkin-mediated K63-linked polyubiquitination targets misfolded DJ-1 to
RT aggresomes via binding to HDAC6.";
RL J. Cell Biol. 178:1025-1038(2007).
RN [17]
RP INTERACTION WITH SIRT2.
RX PubMed=17516032; DOI=10.1007/s11010-007-9478-6;
RA Nahhas F., Dryden S.C., Abrams J., Tainsky M.A.;
RT "Mutations in SIRT2 deacetylase which regulate enzymatic activity but not
RT its interaction with HDAC6 and tubulin.";
RL Mol. Cell. Biochem. 303:221-230(2007).
RN [18]
RP INTERACTION WITH BBIP1.
RX PubMed=19081074; DOI=10.1016/j.devcel.2008.11.001;
RA Loktev A.V., Zhang Q., Beck J.S., Searby C.C., Scheetz T.E., Bazan F.,
RA Slusarski D.C., Sheffield V.C., Jackson P.K., Nachury M.V.;
RT "A BBSome subunit links ciliogenesis, microtubule stability and
RT acetylation.";
RL Dev. Cell 15:854-865(2008).
RN [19]
RP INTERACTION WITH UBD.
RX PubMed=19033385; DOI=10.1242/jcs.035006;
RA Kalveram B., Schmidtke G., Groettrup M.;
RT "The ubiquitin-like modifier FAT10 interacts with HDAC6 and localizes to
RT aggresomes under proteasome inhibition.";
RL J. Cell Sci. 121:4079-4088(2008).
RN [20]
RP ALTERNATIVE SPLICING (ISOFORM 2).
RX PubMed=20102703; DOI=10.1016/j.bbrc.2010.01.091;
RA Zhuang Y., Nguyen H.T., Lasky J.A., Cao S., Li C., Hu J., Guo X.,
RA Burow M.E., Shan B.;
RT "Requirement of a novel splicing variant of human histone deacetylase 6 for
RT TGF-beta1-mediated gene activation.";
RL Biochem. Biophys. Res. Commun. 392:608-613(2010).
RN [21]
RP INTERACTION WITH CYLD.
RX PubMed=19893491; DOI=10.1038/emboj.2009.317;
RA Wickstrom S.A., Masoumi K.C., Khochbin S., Fassler R., Massoumi R.;
RT "CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and
RT increasing the levels of acetylated tubulin.";
RL EMBO J. 29:131-144(2010).
RN [22]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH TPPP.
RX PubMed=20308065; DOI=10.1074/jbc.m109.096578;
RA Tokesi N., Lehotzky A., Horvath I., Szabo B., Olah J., Lau P., Ovadi J.;
RT "TPPP/p25 promotes tubulin acetylation by inhibiting histone deacetylase
RT 6.";
RL J. Biol. Chem. 285:17896-17906(2010).
RN [23]
RP INTERACTION WITH TPPP.
RX PubMed=23093407; DOI=10.1074/jbc.m112.394965;
RA Schofield A.V., Steel R., Bernard O.;
RT "Rho-associated coiled-coil kinase (ROCK) protein controls microtubule
RT dynamics in a novel signaling pathway that regulates cell migration.";
RL J. Biol. Chem. 287:43620-43629(2012).
RN [24]
RP INVOLVEMENT IN CDP-PBHM.
RX PubMed=20181727; DOI=10.1093/hmg/ddq083;
RA Simon D., Laloo B., Barillot M., Barnetche T., Blanchard C., Rooryck C.,
RA Marche M., Burgelin I., Coupry I., Chassaing N., Gilbert-Dussardier B.,
RA Lacombe D., Grosset C., Arveiler B.;
RT "A mutation in the 3'-UTR of the HDAC6 gene abolishing the post-
RT transcriptional regulation mediated by hsa-miR-433 is linked to a new form
RT of dominant X-linked chondrodysplasia.";
RL Hum. Mol. Genet. 19:2015-2027(2010).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [27]
RP FUNCTION.
RX PubMed=24413532; DOI=10.1158/0008-5472.can-13-2020;
RA Kang H.J., Lee M.H., Kang H.L., Kim S.H., Ahn J.R., Na H., Na T.Y.,
RA Kim Y.N., Seong J.K., Lee M.O.;
RT "Differential regulation of estrogen receptor alpha expression in breast
RT cancer cells by metastasis-associated protein 1.";
RL Cancer Res. 74:1484-1494(2014).
RN [28]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH DYSF AND RIPOR2.
RX PubMed=24687993; DOI=10.1096/fj.13-246470;
RA Balasubramanian A., Kawahara G., Gupta V.A., Rozkalne A., Beauvais A.,
RA Kunkel L.M., Gussoni E.;
RT "Fam65b is important for formation of the HDAC6-dysferlin protein complex
RT during myogenic cell differentiation.";
RL FASEB J. 28:2955-2969(2014).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1016; THR-1021; THR-1027;
RP THR-1031; THR-1034; SER-1035 AND THR-1040, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [30]
RP INTERACTION WITH UBD.
RX PubMed=25422469; DOI=10.1073/pnas.1403383111;
RA Theng S.S., Wang W., Mah W.C., Chan C., Zhuo J., Gao Y., Qin H., Lim L.,
RA Chong S.S., Song J., Lee C.G.;
RT "Disruption of FAT10-MAD2 binding inhibits tumor progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E5282-E5291(2014).
RN [31]
RP INTERACTION WITH DYNLL1.
RX PubMed=31505170; DOI=10.1016/j.bbamcr.2019.118556;
RA Olah J., Szunyogh S., Szenasi T., Szaniszlo T., Szabo A., Lehotzky A.,
RA Berki T., Nyitray L., Ovadi J.;
RT "Interactions between two regulatory proteins of microtubule dynamics,
RT HDAC6, TPPP/p25, and the hub protein, DYNLL/LC8.";
RL Biochim. Biophys. Acta 2019:118556-118556(2019).
RN [32]
RP FUNCTION, AND INTERACTION WITH ATP13A2.
RX PubMed=30538141; DOI=10.1083/jcb.201804165;
RA Wang R., Tan J., Chen T., Han H., Tian R., Tan Y., Wu Y., Cui J., Chen F.,
RA Li J., Lv L., Guan X., Shang S., Lu J., Zhang Z.;
RT "ATP13A2 facilitates HDAC6 recruitment to lysosome to promote
RT autophagosome-lysosome fusion.";
RL J. Cell Biol. 218:267-284(2019).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 1109-1215 IN COMPLEX WITH ZINC
RP IONS.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human HDAC6 zinc finger domain.";
RL Submitted (FEB-2008) to the PDB data bank.
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 1109-1215 IN COMPLEX WITH ZINC
RP IONS AND UBIQUITIN C-TERMINAL PEPTIDE RLRGG.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human HDAC6 zinc finger domain and ubiquitin C-
RT terminal peptide RLRGG.";
RL Submitted (APR-2009) to the PDB data bank.
CC -!- FUNCTION: Responsible for the deacetylation of lysine residues on the
CC N-terminal part of the core histones (H2A, H2B, H3 and H4)
CC (PubMed:10220385). Histone deacetylation gives a tag for epigenetic
CC repression and plays an important role in transcriptional regulation,
CC cell cycle progression and developmental events (PubMed:10220385).
CC Histone deacetylases act via the formation of large multiprotein
CC complexes (PubMed:10220385). In addition to histones, deacetylates
CC other proteins: plays a central role in microtubule-dependent cell
CC motility by mediating deacetylation of tubulin (PubMed:12024216,
CC PubMed:20308065). Promotes deacetylation of CTTN, leading to actin
CC polymerization, promotion of autophagosome-lysosome fusion and
CC completion of autophagy (PubMed:30538141). Involved in the MTA1-
CC mediated epigenetic regulation of ESR1 expression in breast cancer
CC (PubMed:24413532). In addition to its protein deacetylase activity,
CC plays a key role in the degradation of misfolded proteins: when
CC misfolded proteins are too abundant to be degraded by the chaperone
CC refolding system and the ubiquitin-proteasome, mediates the transport
CC of misfolded proteins to a cytoplasmic juxtanuclear structure called
CC aggresome (PubMed:17846173). Probably acts as an adapter that
CC recognizes polyubiquitinated misfolded proteins and target them to the
CC aggresome, facilitating their clearance by autophagy (PubMed:17846173).
CC {ECO:0000269|PubMed:10220385, ECO:0000269|PubMed:12024216,
CC ECO:0000269|PubMed:17846173, ECO:0000269|PubMed:20308065,
CC ECO:0000269|PubMed:24413532, ECO:0000269|PubMed:30538141}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[histone] = acetate + L-lysyl-
CC [histone]; Xref=Rhea:RHEA:58196, Rhea:RHEA-COMP:9845, Rhea:RHEA-
CC COMP:11338, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:61930; EC=3.5.1.98;
CC Evidence={ECO:0000269|PubMed:10220385};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58197;
CC Evidence={ECO:0000269|PubMed:10220385};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[alpha-tubulin] = acetate + L-lysyl-
CC [alpha-tubulin]; Xref=Rhea:RHEA:21548, Rhea:RHEA-COMP:11278,
CC Rhea:RHEA-COMP:11279, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:30089, ChEBI:CHEBI:61930;
CC Evidence={ECO:0000269|PubMed:12024216, ECO:0000269|PubMed:20308065};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21549;
CC Evidence={ECO:0000269|PubMed:12024216, ECO:0000269|PubMed:20308065};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|Ref.33, ECO:0000269|Ref.34};
CC Note=Binds 3 Zn(2+) ions per subunit. {ECO:0000269|Ref.33,
CC ECO:0000269|Ref.34};
CC -!- SUBUNIT: Interacts with SIRT2 (via both phosphorylated,
CC unphosphorylated, active or inactive forms); the interaction is
CC necessary for the complex to interact with alpha-tubulin
CC (PubMed:12620231, PubMed:17516032). Under proteasome impairment
CC conditions, interacts with UBD via its histone deacetylase 1 and UBP-
CC type zinc-finger regions (PubMed:19033385, PubMed:25422469). Interacts
CC with BBIP1, CBFA2T3, CYLD, DDIT3/CHOP, ZMYND15, F-actin and HDAC11
CC (PubMed:19893491, PubMed:11533236, PubMed:11948178, PubMed:19081074,
CC PubMed:17872950). Interacts with RIPOR2; this interaction occurs during
CC early myogenic differentiation and prevents HDAC6 to deacetylate
CC tubulin (PubMed:24687993). Interacts with DYSF; this interaction occurs
CC during early myogenic differentiation (PubMed:24687993). Interacts with
CC TPPP; inhibiting the tubulin deacetylase activity of HDAC6
CC (PubMed:20308065, PubMed:23093407). Interacts with DYNLL1
CC (PubMed:31505170). Interacts with ATP13A2; the interaction results in
CC recruitment of HDAC6 to lysosomes to promote CTTN deacetylation
CC (PubMed:30538141). {ECO:0000269|PubMed:11533236,
CC ECO:0000269|PubMed:11948178, ECO:0000269|PubMed:12620231,
CC ECO:0000269|PubMed:17516032, ECO:0000269|PubMed:17872950,
CC ECO:0000269|PubMed:19033385, ECO:0000269|PubMed:19081074,
CC ECO:0000269|PubMed:19893491, ECO:0000269|PubMed:20308065,
CC ECO:0000269|PubMed:23093407, ECO:0000269|PubMed:24687993,
CC ECO:0000269|PubMed:25422469, ECO:0000269|PubMed:30538141,
CC ECO:0000269|PubMed:31505170}.
CC -!- INTERACTION:
CC Q9UBN7; Q9NQ11: ATP13A2; NbExp=2; IntAct=EBI-301697, EBI-6308763;
CC Q9UBN7; Q9HCU9: BRMS1; NbExp=2; IntAct=EBI-301697, EBI-714781;
CC Q9UBN7; P35222: CTNNB1; NbExp=4; IntAct=EBI-301697, EBI-491549;
CC Q9UBN7; Q14247: CTTN; NbExp=4; IntAct=EBI-301697, EBI-351886;
CC Q9UBN7; Q9NQC7: CYLD; NbExp=4; IntAct=EBI-301697, EBI-2117940;
CC Q9UBN7; Q14203-5: DCTN1; NbExp=6; IntAct=EBI-301697, EBI-25840379;
CC Q9UBN7; P00533: EGFR; NbExp=12; IntAct=EBI-301697, EBI-297353;
CC Q9UBN7; P42858: HTT; NbExp=9; IntAct=EBI-301697, EBI-466029;
CC Q9UBN7; Q99836: MYD88; NbExp=6; IntAct=EBI-301697, EBI-447677;
CC Q9UBN7; P17252: PRKCA; NbExp=2; IntAct=EBI-301697, EBI-1383528;
CC Q9UBN7; O60260: PRKN; NbExp=6; IntAct=EBI-301697, EBI-716346;
CC Q9UBN7; O43490: PROM1; NbExp=4; IntAct=EBI-301697, EBI-3447549;
CC Q9UBN7; O43490-2: PROM1; NbExp=2; IntAct=EBI-301697, EBI-21452032;
CC Q9UBN7; Q13148: TARDBP; NbExp=3; IntAct=EBI-301697, EBI-372899;
CC Q9UBN7; Q62623: Cdc20; Xeno; NbExp=2; IntAct=EBI-301697, EBI-2256532;
CC Q9UBN7; Q60598: Cttn; Xeno; NbExp=3; IntAct=EBI-301697, EBI-397955;
CC Q9UBN7; P21146: GRK2; Xeno; NbExp=3; IntAct=EBI-301697, EBI-1036401;
CC Q9UBN7; P04610: tat; Xeno; NbExp=10; IntAct=EBI-301697, EBI-7845069;
CC Q9UBN7; P03409: Tax; Xeno; NbExp=4; IntAct=EBI-301697, EBI-5236464;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12024216,
CC ECO:0000269|PubMed:24687993}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:12024216}. Nucleus {ECO:0000250|UniProtKB:Q9Z2V5}.
CC Perikaryon {ECO:0000250|UniProtKB:Q9Z2V5}. Cell projection, dendrite
CC {ECO:0000250|UniProtKB:Q9Z2V5}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q9Z2V5}. Note=It is mainly cytoplasmic, where it
CC is associated with microtubules. {ECO:0000269|PubMed:12024216}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=HDAC6p131;
CC IsoId=Q9UBN7-1; Sequence=Displayed;
CC Name=2; Synonyms=HDAC6p114;
CC IsoId=Q9UBN7-2; Sequence=VSP_044576;
CC -!- PTM: Phosphorylated by AURKA. {ECO:0000269|PubMed:17604723}.
CC -!- PTM: Ubiquitinated. Its polyubiquitination however does not lead to its
CC degradation. {ECO:0000269|PubMed:12354939}.
CC -!- PTM: Sumoylated in vitro. {ECO:0000269|PubMed:12032081}.
CC -!- DISEASE: Chondrodysplasia with platyspondyly, distinctive
CC brachydactyly, hydrocephaly, and microphthalmia (CDP-PBHM)
CC [MIM:300863]: A disease characterized by chondrodysplasia, severe
CC platyspondyly, hydrocephaly, and facial features with microphthalmia.
CC Bone abnormalities include a distinctive metaphyseal cupping of the
CC metacarpals, metatarsals, and phalanges. Affected females show a milder
CC phenotype with small stature, sometimes associated with body asymmetry
CC and mild intellectual disability. {ECO:0000269|PubMed:20181727}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Required for TGF-beta1-activated gene
CC expression associated with epithelial-mesenchymal transition (EMT) in
CC A549 cells. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74924.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AF132609; AAD29048.1; -; mRNA.
DR EMBL; AB020708; BAA74924.2; ALT_INIT; mRNA.
DR EMBL; AJ011972; CAA09893.1; -; mRNA.
DR EMBL; AF196971; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471224; EAW50748.1; -; Genomic_DNA.
DR EMBL; BC013737; AAH13737.1; -; mRNA.
DR EMBL; BC069243; AAH69243.1; -; mRNA.
DR CCDS; CCDS14306.1; -. [Q9UBN7-1]
DR RefSeq; NP_001308155.1; NM_001321226.1. [Q9UBN7-1]
DR RefSeq; NP_001308156.1; NM_001321227.1. [Q9UBN7-1]
DR RefSeq; NP_001308157.1; NM_001321228.1. [Q9UBN7-1]
DR RefSeq; NP_001308158.1; NM_001321229.1. [Q9UBN7-1]
DR RefSeq; NP_006035.2; NM_006044.3. [Q9UBN7-1]
DR PDB; 3C5K; X-ray; 1.55 A; A=1109-1215.
DR PDB; 3GV4; X-ray; 1.72 A; A=1109-1215.
DR PDB; 3PHD; X-ray; 3.00 A; A/B/C/D=1109-1215.
DR PDB; 5B8D; X-ray; 1.05 A; A=1109-1213.
DR PDB; 5EDU; X-ray; 2.79 A; A/B=479-835.
DR PDB; 5KH3; X-ray; 1.60 A; A=1109-1213.
DR PDB; 5KH7; X-ray; 1.70 A; A=1109-1213.
DR PDB; 5KH9; X-ray; 1.07 A; A=1109-1213.
DR PDB; 5WBN; X-ray; 1.64 A; A=1108-1213.
DR PDB; 5WPB; X-ray; 1.55 A; A=1109-1208.
DR PDB; 6CE6; X-ray; 1.60 A; A=1109-1213.
DR PDB; 6CE8; X-ray; 1.55 A; A=1109-1213.
DR PDB; 6CEA; X-ray; 1.60 A; A=1109-1213.
DR PDB; 6CEC; X-ray; 1.55 A; A=1109-1213.
DR PDB; 6CED; X-ray; 1.70 A; A=1109-1213.
DR PDB; 6CEE; X-ray; 1.55 A; A=1109-1213.
DR PDB; 6CEF; X-ray; 1.80 A; A=1109-1213.
DR PDBsum; 3C5K; -.
DR PDBsum; 3GV4; -.
DR PDBsum; 3PHD; -.
DR PDBsum; 5B8D; -.
DR PDBsum; 5EDU; -.
DR PDBsum; 5KH3; -.
DR PDBsum; 5KH7; -.
DR PDBsum; 5KH9; -.
DR PDBsum; 5WBN; -.
DR PDBsum; 5WPB; -.
DR PDBsum; 6CE6; -.
DR PDBsum; 6CE8; -.
DR PDBsum; 6CEA; -.
DR PDBsum; 6CEC; -.
DR PDBsum; 6CED; -.
DR PDBsum; 6CEE; -.
DR PDBsum; 6CEF; -.
DR AlphaFoldDB; Q9UBN7; -.
DR SMR; Q9UBN7; -.
DR BioGRID; 115330; 416.
DR CORUM; Q9UBN7; -.
DR DIP; DIP-27544N; -.
DR IntAct; Q9UBN7; 144.
DR MINT; Q9UBN7; -.
DR STRING; 9606.ENSP00000334061; -.
DR BindingDB; Q9UBN7; -.
DR ChEMBL; CHEMBL1865; -.
DR DrugBank; DB05015; Belinostat.
DR DrugBank; DB13346; Bufexamac.
DR DrugBank; DB06603; Panobinostat.
DR DrugBank; DB05223; Pracinostat.
DR DrugBank; DB06176; Romidepsin.
DR DrugBank; DB02546; Vorinostat.
DR DrugCentral; Q9UBN7; -.
DR GuidetoPHARMACOLOGY; 2618; -.
DR GlyGen; Q9UBN7; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UBN7; -.
DR PhosphoSitePlus; Q9UBN7; -.
DR BioMuta; HDAC6; -.
DR DMDM; 205371758; -.
DR EPD; Q9UBN7; -.
DR jPOST; Q9UBN7; -.
DR MassIVE; Q9UBN7; -.
DR MaxQB; Q9UBN7; -.
DR PaxDb; Q9UBN7; -.
DR PeptideAtlas; Q9UBN7; -.
DR PRIDE; Q9UBN7; -.
DR ProteomicsDB; 84019; -. [Q9UBN7-1]
DR Antibodypedia; 3788; 1139 antibodies from 48 providers.
DR DNASU; 10013; -.
DR Ensembl; ENST00000334136.11; ENSP00000334061.5; ENSG00000094631.21. [Q9UBN7-1]
DR Ensembl; ENST00000376619.6; ENSP00000365804.2; ENSG00000094631.21. [Q9UBN7-1]
DR Ensembl; ENST00000643374.1; ENSP00000496046.1; ENSG00000094631.21. [Q9UBN7-1]
DR Ensembl; ENST00000644068.1; ENSP00000496013.1; ENSG00000094631.21. [Q9UBN7-1]
DR GeneID; 10013; -.
DR KEGG; hsa:10013; -.
DR MANE-Select; ENST00000334136.11; ENSP00000334061.5; NM_006044.4; NP_006035.2.
DR UCSC; uc004dks.2; human. [Q9UBN7-1]
DR CTD; 10013; -.
DR DisGeNET; 10013; -.
DR GeneCards; HDAC6; -.
DR HGNC; HGNC:14064; HDAC6.
DR HPA; ENSG00000094631; Low tissue specificity.
DR MalaCards; HDAC6; -.
DR MIM; 300272; gene.
DR MIM; 300863; phenotype.
DR neXtProt; NX_Q9UBN7; -.
DR OpenTargets; ENSG00000094631; -.
DR Orphanet; 163966; X-linked dominant chondrodysplasia, Chassaing-Lacombe type.
DR PharmGKB; PA29231; -.
DR VEuPathDB; HostDB:ENSG00000094631; -.
DR eggNOG; KOG1343; Eukaryota.
DR GeneTree; ENSGT00940000159563; -.
DR HOGENOM; CLU_007727_2_1_1; -.
DR InParanoid; Q9UBN7; -.
DR OMA; HEASGHP; -.
DR OrthoDB; 662615at2759; -.
DR PhylomeDB; Q9UBN7; -.
DR TreeFam; TF106173; -.
DR BioCyc; MetaCyc:HS01799-MON; -.
DR BRENDA; 3.5.1.98; 2681.
DR PathwayCommons; Q9UBN7; -.
DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-3371511; HSF1 activation.
DR Reactome; R-HSA-350054; Notch-HLH transcription pathway.
DR Reactome; R-HSA-5617833; Cilium Assembly.
DR Reactome; R-HSA-8878166; Transcriptional regulation by RUNX2.
DR Reactome; R-HSA-8940973; RUNX2 regulates osteoblast differentiation.
DR Reactome; R-HSA-9613829; Chaperone Mediated Autophagy.
DR Reactome; R-HSA-9615710; Late endosomal microautophagy.
DR Reactome; R-HSA-9646399; Aggrephagy.
DR SABIO-RK; Q9UBN7; -.
DR SignaLink; Q9UBN7; -.
DR SIGNOR; Q9UBN7; -.
DR BioGRID-ORCS; 10013; 18 hits in 728 CRISPR screens.
DR ChiTaRS; HDAC6; human.
DR EvolutionaryTrace; Q9UBN7; -.
DR GeneWiki; HDAC6; -.
DR GenomeRNAi; 10013; -.
DR Pharos; Q9UBN7; Tclin.
DR PRO; PR:Q9UBN7; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; Q9UBN7; protein.
DR Bgee; ENSG00000094631; Expressed in right hemisphere of cerebellum and 202 other tissues.
DR ExpressionAtlas; Q9UBN7; baseline and differential.
DR Genevisible; Q9UBN7; HS.
DR GO; GO:0016235; C:aggresome; IDA:BHF-UCL.
DR GO; GO:0030424; C:axon; ISS:UniProtKB.
DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC.
DR GO; GO:0005901; C:caveola; IDA:BHF-UCL.
DR GO; GO:0031252; C:cell leading edge; IDA:BHF-UCL.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0000118; C:histone deacetylase complex; IDA:UniProtKB.
DR GO; GO:0016234; C:inclusion body; IDA:BHF-UCL.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0005875; C:microtubule associated complex; IDA:BHF-UCL.
DR GO; GO:0005771; C:multivesicular body; TAS:ParkinsonsUK-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0043204; C:perikaryon; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:BHF-UCL.
DR GO; GO:0008013; F:beta-catenin binding; IPI:BHF-UCL.
DR GO; GO:0048487; F:beta-tubulin binding; IEA:Ensembl.
DR GO; GO:0070840; F:dynein complex binding; IDA:BHF-UCL.
DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB.
DR GO; GO:0004407; F:histone deacetylase activity; IDA:BHF-UCL.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0051879; F:Hsp90 protein binding; IDA:BHF-UCL.
DR GO; GO:0008017; F:microtubule binding; IDA:BHF-UCL.
DR GO; GO:0051787; F:misfolded protein binding; EXP:Reactome.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:BHF-UCL.
DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0048156; F:tau protein binding; IDA:BHF-UCL.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:ARUK-UCL.
DR GO; GO:0042903; F:tubulin deacetylase activity; IDA:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IEA:Ensembl.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0070842; P:aggresome assembly; IMP:BHF-UCL.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0019896; P:axonal transport of mitochondrion; IGI:ARUK-UCL.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IMP:BHF-UCL.
DR GO; GO:0071218; P:cellular response to misfolded protein; IEA:Ensembl.
DR GO; GO:0035967; P:cellular response to topologically incorrect protein; IMP:BHF-UCL.
DR GO; GO:0060271; P:cilium assembly; TAS:Reactome.
DR GO; GO:0061523; P:cilium disassembly; IMP:UniProtKB.
DR GO; GO:0048668; P:collateral sprouting; IEA:Ensembl.
DR GO; GO:0060997; P:dendritic spine morphogenesis; IEA:Ensembl.
DR GO; GO:0016575; P:histone deacetylation; IDA:BHF-UCL.
DR GO; GO:0070846; P:Hsp90 deacetylation; IEA:Ensembl.
DR GO; GO:0006886; P:intracellular protein transport; IMP:BHF-UCL.
DR GO; GO:0032418; P:lysosome localization; IMP:BHF-UCL.
DR GO; GO:0010727; P:negative regulation of hydrogen peroxide metabolic process; IC:BHF-UCL.
DR GO; GO:0007026; P:negative regulation of microtubule depolymerization; IEA:Ensembl.
DR GO; GO:0051354; P:negative regulation of oxidoreductase activity; IC:BHF-UCL.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IMP:ARUK-UCL.
DR GO; GO:0043242; P:negative regulation of protein-containing complex disassembly; IMP:BHF-UCL.
DR GO; GO:0045861; P:negative regulation of proteolysis; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0061734; P:parkin-mediated stimulation of mitophagy in response to mitochondrial depolarization; IGI:ParkinsonsUK-UCL.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; IMP:BHF-UCL.
DR GO; GO:0070845; P:polyubiquitinated misfolded protein transport; IMP:BHF-UCL.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; IMP:BHF-UCL.
DR GO; GO:1901300; P:positive regulation of hydrogen peroxide-mediated programmed cell death; IDA:BHF-UCL.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:ARUK-UCL.
DR GO; GO:2000273; P:positive regulation of signaling receptor activity; IMP:BHF-UCL.
DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; IEA:Ensembl.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IMP:BHF-UCL.
DR GO; GO:0032984; P:protein-containing complex disassembly; IEA:Ensembl.
DR GO; GO:0060765; P:regulation of androgen receptor signaling pathway; TAS:BHF-UCL.
DR GO; GO:0010506; P:regulation of autophagy; TAS:ParkinsonsUK-UCL.
DR GO; GO:1903146; P:regulation of autophagy of mitochondrion; TAS:ParkinsonsUK-UCL.
DR GO; GO:0070201; P:regulation of establishment of protein localization; IEA:Ensembl.
DR GO; GO:0045598; P:regulation of fat cell differentiation; IEA:Ensembl.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IMP:UniProtKB.
DR GO; GO:0016241; P:regulation of macroautophagy; IMP:BHF-UCL.
DR GO; GO:0060632; P:regulation of microtubule-based movement; IC:BHF-UCL.
DR GO; GO:0031647; P:regulation of protein stability; IMP:ParkinsonsUK-UCL.
DR GO; GO:0070848; P:response to growth factor; IMP:BHF-UCL.
DR GO; GO:0051788; P:response to misfolded protein; IMP:BHF-UCL.
DR GO; GO:0090042; P:tubulin deacetylation; IDA:UniProtKB.
DR GO; GO:0043162; P:ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; IEA:Ensembl.
DR Gene3D; 3.30.40.10; -; 1.
DR Gene3D; 3.40.800.20; -; 2.
DR InterPro; IPR000286; His_deacetylse.
DR InterPro; IPR023801; His_deacetylse_dom.
DR InterPro; IPR037138; His_deacetylse_dom_sf.
DR InterPro; IPR023696; Ureohydrolase_dom_sf.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR Pfam; PF00850; Hist_deacetyl; 2.
DR Pfam; PF02148; zf-UBP; 1.
DR PRINTS; PR01270; HDASUPER.
DR SMART; SM00290; ZnF_UBP; 1.
DR SUPFAM; SSF52768; SSF52768; 2.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Autophagy;
KW Cell projection; Chromatin regulator; Cytoplasm; Cytoskeleton; Hydrolase;
KW Metal-binding; Methylation; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1215
FT /note="Histone deacetylase 6"
FT /id="PRO_0000114703"
FT ZN_FING 1111..1209
FT /note="UBP-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502"
FT REGION 1..44
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 87..404
FT /note="Histone deacetylase 1"
FT REGION 445..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 482..800
FT /note="Histone deacetylase 2"
FT REGION 842..863
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 994..1047
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1154..1156
FT /note="Ubiquitin binding"
FT /evidence="ECO:0000269|Ref.34"
FT REGION 1182..1189
FT /note="Ubiquitin binding"
FT /evidence="ECO:0000269|Ref.34"
FT COMPBIAS 1..34
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 449..463
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 216
FT /note="1"
FT /evidence="ECO:0000269|PubMed:12354939"
FT ACT_SITE 611
FT /note="2"
FT /evidence="ECO:0000269|PubMed:12354939"
FT BINDING 1113
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502,
FT ECO:0000269|Ref.33, ECO:0000269|Ref.34"
FT BINDING 1115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502,
FT ECO:0000269|Ref.33, ECO:0000269|Ref.34"
FT BINDING 1133
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502,
FT ECO:0000269|Ref.33, ECO:0000269|Ref.34"
FT BINDING 1136
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502,
FT ECO:0000269|Ref.33, ECO:0000269|Ref.34"
FT BINDING 1145
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502,
FT ECO:0000269|Ref.33, ECO:0000269|Ref.34"
FT BINDING 1148
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502,
FT ECO:0000269|Ref.33, ECO:0000269|Ref.34"
FT BINDING 1153
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502,
FT ECO:0000269|Ref.33, ECO:0000269|Ref.34"
FT BINDING 1160
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502,
FT ECO:0000269|Ref.33, ECO:0000269|Ref.34"
FT BINDING 1164
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502,
FT ECO:0000269|Ref.33, ECO:0000269|Ref.34"
FT BINDING 1170
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502,
FT ECO:0000269|Ref.33, ECO:0000269|Ref.34"
FT BINDING 1183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502,
FT ECO:0000269|Ref.33, ECO:0000269|Ref.34"
FT BINDING 1186
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00502,
FT ECO:0000269|Ref.33, ECO:0000269|Ref.34"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 33
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2V5"
FT MOD_RES 1016
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1021
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1027
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1031
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1034
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1035
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1040
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..152
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044576"
FT VARIANT 994
FT /note="T -> I (in dbSNP:rs1127346)"
FT /evidence="ECO:0000269|PubMed:10220385, ECO:0000269|Ref.4"
FT /id="VAR_046300"
FT VARIANT 1200
FT /note="N -> D (in dbSNP:rs151130423)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_068962"
FT MUTAGEN 216
FT /note="H->A: Reduces histone deacetylase activity."
FT /evidence="ECO:0000269|PubMed:12354939"
FT MUTAGEN 611
FT /note="H->A: Reduces histone deacetylase activity."
FT /evidence="ECO:0000269|PubMed:12354939"
FT STRAND 481..484
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 487..490
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 505..516
FT /evidence="ECO:0007829|PDB:5EDU"
FT TURN 517..522
FT /evidence="ECO:0007829|PDB:5EDU"
FT STRAND 523..526
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 533..536
FT /evidence="ECO:0007829|PDB:5EDU"
FT TURN 537..539
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 542..550
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 551..553
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 556..563
FT /evidence="ECO:0007829|PDB:5EDU"
FT STRAND 566..568
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 575..593
FT /evidence="ECO:0007829|PDB:5EDU"
FT TURN 594..596
FT /evidence="ECO:0007829|PDB:5EDU"
FT STRAND 599..603
FT /evidence="ECO:0007829|PDB:5EDU"
FT STRAND 621..623
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 625..637
FT /evidence="ECO:0007829|PDB:5EDU"
FT STRAND 643..647
FT /evidence="ECO:0007829|PDB:5EDU"
FT STRAND 649..651
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 654..659
FT /evidence="ECO:0007829|PDB:5EDU"
FT TURN 660..662
FT /evidence="ECO:0007829|PDB:5EDU"
FT STRAND 666..673
FT /evidence="ECO:0007829|PDB:5EDU"
FT TURN 675..678
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 694..696
FT /evidence="ECO:0007829|PDB:5EDU"
FT STRAND 699..705
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 712..721
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 723..730
FT /evidence="ECO:0007829|PDB:5EDU"
FT STRAND 733..739
FT /evidence="ECO:0007829|PDB:5EDU"
FT STRAND 742..744
FT /evidence="ECO:0007829|PDB:5EDU"
FT TURN 748..750
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 756..766
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 770..772
FT /evidence="ECO:0007829|PDB:5EDU"
FT STRAND 774..778
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 784..798
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 814..827
FT /evidence="ECO:0007829|PDB:5EDU"
FT TURN 828..830
FT /evidence="ECO:0007829|PDB:5EDU"
FT HELIX 1116..1118
FT /evidence="ECO:0007829|PDB:5B8D"
FT TURN 1134..1136
FT /evidence="ECO:0007829|PDB:5B8D"
FT STRAND 1140..1145
FT /evidence="ECO:0007829|PDB:5B8D"
FT TURN 1146..1148
FT /evidence="ECO:0007829|PDB:5B8D"
FT STRAND 1151..1153
FT /evidence="ECO:0007829|PDB:5B8D"
FT TURN 1155..1158
FT /evidence="ECO:0007829|PDB:5B8D"
FT HELIX 1160..1168
FT /evidence="ECO:0007829|PDB:5B8D"
FT STRAND 1172..1175
FT /evidence="ECO:0007829|PDB:5B8D"
FT TURN 1176..1178
FT /evidence="ECO:0007829|PDB:5B8D"
FT STRAND 1181..1183
FT /evidence="ECO:0007829|PDB:5B8D"
FT TURN 1184..1187
FT /evidence="ECO:0007829|PDB:5B8D"
FT STRAND 1188..1190
FT /evidence="ECO:0007829|PDB:5B8D"
FT HELIX 1193..1195
FT /evidence="ECO:0007829|PDB:5B8D"
FT HELIX 1196..1206
FT /evidence="ECO:0007829|PDB:5B8D"
SQ SEQUENCE 1215 AA; 131419 MW; 6F17731268A33114 CRC64;
MTSTGQDSTT TRQRRSRQNP QSPPQDSSVT SKRNIKKGAV PRSIPNLAEV KKKGKMKKLG
QAMEEDLIVG LQGMDLNLEA EALAGTGLVL DEQLNEFHCL WDDSFPEGPE RLHAIKEQLI
QEGLLDRCVS FQARFAEKEE LMLVHSLEYI DLMETTQYMN EGELRVLADT YDSVYLHPNS
YSCACLASGS VLRLVDAVLG AEIRNGMAII RPPGHHAQHS LMDGYCMFNH VAVAARYAQQ
KHRIRRVLIV DWDVHHGQGT QFTFDQDPSV LYFSIHRYEQ GRFWPHLKAS NWSTTGFGQG
QGYTINVPWN QVGMRDADYI AAFLHVLLPV ALEFQPQLVL VAAGFDALQG DPKGEMAATP
AGFAQLTHLL MGLAGGKLIL SLEGGYNLRA LAEGVSASLH TLLGDPCPML ESPGAPCRSA
QASVSCALEA LEPFWEVLVR STETVERDNM EEDNVEESEE EGPWEPPVLP ILTWPVLQSR
TGLVYDQNMM NHCNLWDSHH PEVPQRILRI MCRLEELGLA GRCLTLTPRP ATEAELLTCH
SAEYVGHLRA TEKMKTRELH RESSNFDSIY ICPSTFACAQ LATGAACRLV EAVLSGEVLN
GAAVVRPPGH HAEQDAACGF CFFNSVAVAA RHAQTISGHA LRILIVDWDV HHGNGTQHMF
EDDPSVLYVS LHRYDHGTFF PMGDEGASSQ IGRAAGTGFT VNVAWNGPRM GDADYLAAWH
RLVLPIAYEF NPELVLVSAG FDAARGDPLG GCQVSPEGYA HLTHLLMGLA SGRIILILEG
GYNLTSISES MAACTRSLLG DPPPLLTLPR PPLSGALASI TETIQVHRRY WRSLRVMKVE
DREGPSSSKL VTKKAPQPAK PRLAERMTTR EKKVLEAGMG KVTSASFGEE STPGQTNSET
AVVALTQDQP SEAATGGATL AQTISEAAIG GAMLGQTTSE EAVGGATPDQ TTSEETVGGA
ILDQTTSEDA VGGATLGQTT SEEAVGGATL AQTTSEAAME GATLDQTTSE EAPGGTELIQ
TPLASSTDHQ TPPTSPVQGT TPQISPSTLI GSLRTLELGS ESQGASESQA PGEENLLGEA
AGGQDMADSM LMQGSRGLTD QAIFYAVTPL PWCPHLVAVC PIPAAGLDVT QPCGDCGTIQ
ENWVCLSCYQ VYCGRYINGH MLQHHGNSGH PLVLSYIDLS AWCYYCQAYV HHQALLDVKN
IAHQNKFGED MPHPH
