Full text data of HDAC6
HDAC6
(KIAA0901)
[Confidence: low (only semi-automatic identification from reviews)]
Histone deacetylase 6; HD6; 3.5.1.98
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Histone deacetylase 6; HD6; 3.5.1.98
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9UBN7
ID HDAC6_HUMAN Reviewed; 1215 AA.
AC Q9UBN7; O94975; Q6NT75; Q7L3E5; Q96CY0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-SEP-2008, sequence version 2.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Histone deacetylase 6;
DE Short=HD6;
DE EC=3.5.1.98;
GN Name=HDAC6; Synonyms=KIAA0901; ORFNames=JM21;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND 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
RT to 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.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large 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
RP 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.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA 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.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA 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.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA 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.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA 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.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT with multiple histone deacetylases and binds mSin3A through its
RT oligomerization 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
RT the 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
RT (PAZ domain) and copurifies with deubiquitinating enzymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13425-13430(2002).
RN [12]
RP FUNCTION.
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.,
RA 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
RT to aggresomes via binding to HDAC6.";
RL J. Cell Biol. 178:1025-1038(2007).
RN [17]
RP INTERACTION WITH BBIP10.
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 [18]
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
RT to aggresomes under proteasome inhibition.";
RL J. Cell Sci. 121:4079-4088(2008).
RN [19]
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
RT 6 for TGF-beta1-mediated gene activation.";
RL Biochem. Biophys. Res. Commun. 392:608-613(2010).
RN [20]
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
RT HDAC6 and increasing the levels of acetylated tubulin.";
RL EMBO J. 29:131-144(2010).
RN [21]
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.,
RA Buerckstuemmer T., 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 [22]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 1109-1215 IN COMPLEX WITH
RP ZINC 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 [23]
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 1109-1215 IN COMPLEX WITH
RP ZINC 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
CC the N-terminal part of the core histones (H2A, H2B, H3 and H4).
CC Histone deacetylation gives a tag for epigenetic repression and
CC plays an important role in transcriptional regulation, cell cycle
CC progression and developmental events. Histone deacetylases act via
CC the formation of large multiprotein complexes (By similarity).
CC Plays a central role in microtubule-dependent cell motility via
CC deacetylation of tubulin.
CC -!- FUNCTION: In addition to its protein deacetylase activity, plays a
CC key role in the degradation of misfolded proteins: when misfolded
CC proteins are too abundant to be degraded by the chaperone
CC refolding system and the ubiquitin-proteasome, mediates the
CC transport of misfolded proteins to a cytoplasmic juxtanuclear
CC structure called aggresome. Probably acts as an adapter that
CC recognizes polyubiquitinated misfolded proteins and target them to
CC the aggresome, facilitating their clearance by autophagy.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of an N(6)-acetyl-lysine residue of
CC a histone to yield a deacetylated histone.
CC -!- COFACTOR: Binds 3 zinc ions per subunit.
CC -!- SUBUNIT: Interacts with CBFA2T3, HDAC11 and SIRT2. Interacts with
CC F-actin. Interacts with BBIP10. Under proteasome impairment
CC conditions, interacts with UBD via its histone deacetylase 1 and
CC UBP-type zinc-finger regions. Interacts with CYLD. Interacts with
CC ZMYND15 (By similarity). Interacts with DDIT3/CHOP.
CC -!- INTERACTION:
CC P21146:ADRBK1 (xeno); NbExp=3; IntAct=EBI-301697, EBI-1036401;
CC Q9NQ11:ATP13A2; NbExp=2; IntAct=EBI-301697, EBI-6308763;
CC Q9HCU9:BRMS1; NbExp=2; IntAct=EBI-301697, EBI-714781;
CC Q62623:Cdc20 (xeno); NbExp=2; IntAct=EBI-301697, EBI-2256532;
CC Q14247:CTTN; NbExp=3; IntAct=EBI-301697, EBI-351886;
CC Q60598:Cttn (xeno); NbExp=3; IntAct=EBI-301697, EBI-397955;
CC Q9NQC7:CYLD; NbExp=4; IntAct=EBI-301697, EBI-2117940;
CC P00533:EGFR; NbExp=8; IntAct=EBI-301697, EBI-297353;
CC P17252:PRKCA; NbExp=2; IntAct=EBI-301697, EBI-1383528;
CC P03409:tax (xeno); NbExp=4; IntAct=EBI-301697, EBI-5236464;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=It is mainly
CC cytoplasmic, where it is associated with microtubules.
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 Note=Required for TGF-beta1-activated gene expression associated
CC with epithelial-mesenchymal transition (EMT) in A549 cells;
CC -!- PTM: Phosphorylated by AURKA.
CC -!- PTM: Ubiquitinated. Its polyubiquitination however does not lead
CC to its degradation.
CC -!- PTM: Sumoylated in vitro.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2
CC subfamily.
CC -!- SIMILARITY: Contains 1 UBP-type zinc finger.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74924.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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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 RefSeq; NP_006035.2; NM_006044.2.
DR RefSeq; XP_005272622.1; XM_005272565.1.
DR RefSeq; XP_005272623.1; XM_005272566.1.
DR RefSeq; XP_005272624.1; XM_005272567.1.
DR RefSeq; XP_005272625.1; XM_005272568.1.
DR RefSeq; XP_005278068.1; XM_005278011.1.
DR RefSeq; XP_005278069.1; XM_005278012.1.
DR RefSeq; XP_005278070.1; XM_005278013.1.
DR RefSeq; XP_005278071.1; XM_005278014.1.
DR UniGene; Hs.6764; -.
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 PDBsum; 3C5K; -.
DR PDBsum; 3GV4; -.
DR PDBsum; 3PHD; -.
DR ProteinModelPortal; Q9UBN7; -.
DR SMR; Q9UBN7; 86-435, 481-831, 1109-1210.
DR DIP; DIP-27544N; -.
DR IntAct; Q9UBN7; 69.
DR MINT; MINT-4905696; -.
DR STRING; 9606.ENSP00000334061; -.
DR BindingDB; Q9UBN7; -.
DR ChEMBL; CHEMBL1865; -.
DR DrugBank; DB02546; Vorinostat.
DR PhosphoSite; Q9UBN7; -.
DR DMDM; 205371758; -.
DR PaxDb; Q9UBN7; -.
DR PRIDE; Q9UBN7; -.
DR DNASU; 10013; -.
DR Ensembl; ENST00000334136; ENSP00000334061; ENSG00000094631.
DR Ensembl; ENST00000376619; ENSP00000365804; ENSG00000094631.
DR Ensembl; ENST00000595349; ENSP00000470544; ENSG00000269101.
DR Ensembl; ENST00000597097; ENSP00000471818; ENSG00000269101.
DR GeneID; 10013; -.
DR KEGG; hsa:10013; -.
DR UCSC; uc004dks.1; human.
DR CTD; 10013; -.
DR GeneCards; GC0XP048659; -.
DR H-InvDB; HIX0016783; -.
DR HGNC; HGNC:14064; HDAC6.
DR HPA; CAB004236; -.
DR HPA; HPA003714; -.
DR HPA; HPA026321; -.
DR MIM; 300272; gene.
DR neXtProt; NX_Q9UBN7; -.
DR Orphanet; 163966; X-linked dominant chondrodysplasia, Chassaing-Lacombe type.
DR PharmGKB; PA29231; -.
DR eggNOG; COG0123; -.
DR HOGENOM; HOG000004769; -.
DR HOVERGEN; HBG051894; -.
DR InParanoid; Q9UBN7; -.
DR KO; K11407; -.
DR PhylomeDB; Q9UBN7; -.
DR BRENDA; 3.5.1.98; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR SABIO-RK; Q9UBN7; -.
DR SignaLink; Q9UBN7; -.
DR ChiTaRS; HDAC6; human.
DR EvolutionaryTrace; Q9UBN7; -.
DR GeneWiki; HDAC6; -.
DR GenomeRNAi; 10013; -.
DR NextBio; 37827; -.
DR PRO; PR:Q9UBN7; -.
DR ArrayExpress; Q9UBN7; -.
DR Bgee; Q9UBN7; -.
DR CleanEx; HS_HDAC6; -.
DR Genevestigator; Q9UBN7; -.
DR GO; GO:0016235; C:aggresome; IDA:BHF-UCL.
DR GO; GO:0005901; C:caveola; IDA:BHF-UCL.
DR GO; GO:0031252; C:cell leading edge; IDA:BHF-UCL.
DR GO; GO:0005881; C:cytoplasmic microtubule; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0000118; C:histone deacetylase complex; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0005875; C:microtubule associated complex; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:BHF-UCL.
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:0051879; F:Hsp90 protein binding; IDA:BHF-UCL.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0032041; F:NAD-dependent histone deacetylase activity (H3-K14 specific); IEA:UniProtKB-EC.
DR GO; GO:0097372; F:NAD-dependent histone deacetylase activity (H3-K18 specific); IEA:UniProtKB-EC.
DR GO; GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); IEA:UniProtKB-EC.
DR GO; GO:0046970; F:NAD-dependent histone deacetylase activity (H4-K16 specific); IEA:UniProtKB-EC.
DR GO; GO:0031593; F:polyubiquitin binding; IDA:BHF-UCL.
DR GO; GO:0048156; F:tau protein binding; IDA:BHF-UCL.
DR GO; GO:0042903; F:tubulin deacetylase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0070842; P:aggresome assembly; IMP:BHF-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:0070932; P:histone H3 deacetylation; IEA:GOC.
DR GO; GO:0070933; P:histone H4 deacetylation; IEA:GOC.
DR GO; GO:0070846; P:Hsp90 deacetylation; IMP:BHF-UCL.
DR GO; GO:0032418; P:lysosome localization; IMP:BHF-UCL.
DR GO; GO:0016236; P:macroautophagy; IMP:BHF-UCL.
DR GO; GO:0006515; P:misfolded or incompletely synthesized protein catabolic process; 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:0043242; P:negative regulation of protein complex disassembly; IMP:BHF-UCL.
DR GO; GO:0045861; P:negative regulation of proteolysis; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; ISS:UniProtKB.
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:0090035; P:positive regulation of chaperone-mediated protein complex assembly; 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:0010870; P:positive regulation of receptor biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0009967; P:positive regulation of signal transduction; IMP:BHF-UCL.
DR GO; GO:0043241; P:protein complex disassembly; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; IEA:Ensembl.
DR GO; GO:0060765; P:regulation of androgen receptor signaling pathway; TAS:BHF-UCL.
DR GO; GO:0070201; P:regulation of establishment of protein localization; IEA:Ensembl.
DR GO; GO:0060632; P:regulation of microtubule-based movement; IC:BHF-UCL.
DR GO; GO:0010469; P:regulation of receptor activity; IMP:BHF-UCL.
DR GO; GO:0070848; P:response to growth factor stimulus; IMP:BHF-UCL.
DR GO; GO:0051788; P:response to misfolded protein; IMP:BHF-UCL.
DR GO; GO:0009636; P:response to toxic substance; IMP:BHF-UCL.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
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; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR PANTHER; PTHR10625; PTHR10625; 1.
DR Pfam; PF00850; Hist_deacetyl; 2.
DR Pfam; PF02148; zf-UBP; 1.
DR PRINTS; PR01270; HDASUPER.
DR SMART; SM00290; ZnF_UBP; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Autophagy;
KW Chromatin regulator; Complete proteome; Cytoplasm; Hydrolase;
KW Metal-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1 1215 Histone deacetylase 6.
FT /FTId=PRO_0000114703.
FT ZN_FING 1131 1192 UBP-type.
FT REGION 87 404 Histone deacetylase 1.
FT REGION 482 800 Histone deacetylase 2.
FT REGION 1154 1156 Ubiquitin binding.
FT REGION 1182 1189 Ubiquitin binding.
FT ACT_SITE 216 216 1.
FT ACT_SITE 611 611 2.
FT METAL 1113 1113 Zinc 1.
FT METAL 1115 1115 Zinc 1.
FT METAL 1133 1133 Zinc 3.
FT METAL 1136 1136 Zinc 3.
FT METAL 1145 1145 Zinc 2.
FT METAL 1148 1148 Zinc 2.
FT METAL 1153 1153 Zinc 3.
FT METAL 1160 1160 Zinc 3.
FT METAL 1164 1164 Zinc 2.
FT METAL 1170 1170 Zinc 2.
FT METAL 1183 1183 Zinc 1.
FT METAL 1186 1186 Zinc 1.
FT VAR_SEQ 1 152 Missing (in isoform 2).
FT /FTId=VSP_044576.
FT VARIANT 994 994 T -> I (in dbSNP:rs1127346).
FT /FTId=VAR_046300.
FT VARIANT 1200 1200 N -> D (in dbSNP:rs151130423).
FT /FTId=VAR_068962.
FT MUTAGEN 216 216 H->A: Reduces histone deacetylase
FT activity.
FT MUTAGEN 611 611 H->A: Reduces histone deacetylase
FT activity.
FT HELIX 1116 1118
FT TURN 1134 1136
FT STRAND 1140 1145
FT TURN 1146 1148
FT STRAND 1151 1153
FT TURN 1155 1158
FT HELIX 1160 1168
FT STRAND 1172 1175
FT TURN 1176 1178
FT STRAND 1181 1183
FT TURN 1184 1187
FT STRAND 1188 1190
FT HELIX 1193 1195
FT HELIX 1196 1207
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
//
ID HDAC6_HUMAN Reviewed; 1215 AA.
AC Q9UBN7; O94975; Q6NT75; Q7L3E5; Q96CY0;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
read moreDT 02-SEP-2008, sequence version 2.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Histone deacetylase 6;
DE Short=HD6;
DE EC=3.5.1.98;
GN Name=HDAC6; Synonyms=KIAA0901; ORFNames=JM21;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND 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
RT to 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.,
RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII.
RT The complete sequences of 100 new cDNA clones from brain which code
RT for large 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
RP 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.,
RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G.,
RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S.,
RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R.,
RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L.,
RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A.,
RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S.,
RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R.,
RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M.,
RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N.,
RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D.,
RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W.,
RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C.,
RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C.,
RA 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.,
RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S.,
RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I.,
RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L.,
RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P.,
RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S.,
RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A.,
RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J.,
RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J.,
RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S.,
RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z.,
RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C.,
RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W.,
RA 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.,
RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I.,
RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N.,
RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J.,
RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E.,
RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S.,
RA 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.,
RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S.,
RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L.,
RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A.,
RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L.,
RA Williams G., Williams L., Williamson A., Williamson H., Wilming L.,
RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H.,
RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A.,
RA 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.,
RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T.,
RA Gibbs R.A., Beck S., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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
RT with multiple histone deacetylases and binds mSin3A through its
RT oligomerization 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
RT the 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
RT (PAZ domain) and copurifies with deubiquitinating enzymes.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:13425-13430(2002).
RN [12]
RP FUNCTION.
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.,
RA 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
RT to aggresomes via binding to HDAC6.";
RL J. Cell Biol. 178:1025-1038(2007).
RN [17]
RP INTERACTION WITH BBIP10.
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 [18]
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
RT to aggresomes under proteasome inhibition.";
RL J. Cell Sci. 121:4079-4088(2008).
RN [19]
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
RT 6 for TGF-beta1-mediated gene activation.";
RL Biochem. Biophys. Res. Commun. 392:608-613(2010).
RN [20]
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
RT HDAC6 and increasing the levels of acetylated tubulin.";
RL EMBO J. 29:131-144(2010).
RN [21]
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.,
RA Buerckstuemmer T., 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 [22]
RP X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 1109-1215 IN COMPLEX WITH
RP ZINC 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 [23]
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 1109-1215 IN COMPLEX WITH
RP ZINC 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
CC the N-terminal part of the core histones (H2A, H2B, H3 and H4).
CC Histone deacetylation gives a tag for epigenetic repression and
CC plays an important role in transcriptional regulation, cell cycle
CC progression and developmental events. Histone deacetylases act via
CC the formation of large multiprotein complexes (By similarity).
CC Plays a central role in microtubule-dependent cell motility via
CC deacetylation of tubulin.
CC -!- FUNCTION: In addition to its protein deacetylase activity, plays a
CC key role in the degradation of misfolded proteins: when misfolded
CC proteins are too abundant to be degraded by the chaperone
CC refolding system and the ubiquitin-proteasome, mediates the
CC transport of misfolded proteins to a cytoplasmic juxtanuclear
CC structure called aggresome. Probably acts as an adapter that
CC recognizes polyubiquitinated misfolded proteins and target them to
CC the aggresome, facilitating their clearance by autophagy.
CC -!- CATALYTIC ACTIVITY: Hydrolysis of an N(6)-acetyl-lysine residue of
CC a histone to yield a deacetylated histone.
CC -!- COFACTOR: Binds 3 zinc ions per subunit.
CC -!- SUBUNIT: Interacts with CBFA2T3, HDAC11 and SIRT2. Interacts with
CC F-actin. Interacts with BBIP10. Under proteasome impairment
CC conditions, interacts with UBD via its histone deacetylase 1 and
CC UBP-type zinc-finger regions. Interacts with CYLD. Interacts with
CC ZMYND15 (By similarity). Interacts with DDIT3/CHOP.
CC -!- INTERACTION:
CC P21146:ADRBK1 (xeno); NbExp=3; IntAct=EBI-301697, EBI-1036401;
CC Q9NQ11:ATP13A2; NbExp=2; IntAct=EBI-301697, EBI-6308763;
CC Q9HCU9:BRMS1; NbExp=2; IntAct=EBI-301697, EBI-714781;
CC Q62623:Cdc20 (xeno); NbExp=2; IntAct=EBI-301697, EBI-2256532;
CC Q14247:CTTN; NbExp=3; IntAct=EBI-301697, EBI-351886;
CC Q60598:Cttn (xeno); NbExp=3; IntAct=EBI-301697, EBI-397955;
CC Q9NQC7:CYLD; NbExp=4; IntAct=EBI-301697, EBI-2117940;
CC P00533:EGFR; NbExp=8; IntAct=EBI-301697, EBI-297353;
CC P17252:PRKCA; NbExp=2; IntAct=EBI-301697, EBI-1383528;
CC P03409:tax (xeno); NbExp=4; IntAct=EBI-301697, EBI-5236464;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=It is mainly
CC cytoplasmic, where it is associated with microtubules.
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 Note=Required for TGF-beta1-activated gene expression associated
CC with epithelial-mesenchymal transition (EMT) in A549 cells;
CC -!- PTM: Phosphorylated by AURKA.
CC -!- PTM: Ubiquitinated. Its polyubiquitination however does not lead
CC to its degradation.
CC -!- PTM: Sumoylated in vitro.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2
CC subfamily.
CC -!- SIMILARITY: Contains 1 UBP-type zinc finger.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74924.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
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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 RefSeq; NP_006035.2; NM_006044.2.
DR RefSeq; XP_005272622.1; XM_005272565.1.
DR RefSeq; XP_005272623.1; XM_005272566.1.
DR RefSeq; XP_005272624.1; XM_005272567.1.
DR RefSeq; XP_005272625.1; XM_005272568.1.
DR RefSeq; XP_005278068.1; XM_005278011.1.
DR RefSeq; XP_005278069.1; XM_005278012.1.
DR RefSeq; XP_005278070.1; XM_005278013.1.
DR RefSeq; XP_005278071.1; XM_005278014.1.
DR UniGene; Hs.6764; -.
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 PDBsum; 3C5K; -.
DR PDBsum; 3GV4; -.
DR PDBsum; 3PHD; -.
DR ProteinModelPortal; Q9UBN7; -.
DR SMR; Q9UBN7; 86-435, 481-831, 1109-1210.
DR DIP; DIP-27544N; -.
DR IntAct; Q9UBN7; 69.
DR MINT; MINT-4905696; -.
DR STRING; 9606.ENSP00000334061; -.
DR BindingDB; Q9UBN7; -.
DR ChEMBL; CHEMBL1865; -.
DR DrugBank; DB02546; Vorinostat.
DR PhosphoSite; Q9UBN7; -.
DR DMDM; 205371758; -.
DR PaxDb; Q9UBN7; -.
DR PRIDE; Q9UBN7; -.
DR DNASU; 10013; -.
DR Ensembl; ENST00000334136; ENSP00000334061; ENSG00000094631.
DR Ensembl; ENST00000376619; ENSP00000365804; ENSG00000094631.
DR Ensembl; ENST00000595349; ENSP00000470544; ENSG00000269101.
DR Ensembl; ENST00000597097; ENSP00000471818; ENSG00000269101.
DR GeneID; 10013; -.
DR KEGG; hsa:10013; -.
DR UCSC; uc004dks.1; human.
DR CTD; 10013; -.
DR GeneCards; GC0XP048659; -.
DR H-InvDB; HIX0016783; -.
DR HGNC; HGNC:14064; HDAC6.
DR HPA; CAB004236; -.
DR HPA; HPA003714; -.
DR HPA; HPA026321; -.
DR MIM; 300272; gene.
DR neXtProt; NX_Q9UBN7; -.
DR Orphanet; 163966; X-linked dominant chondrodysplasia, Chassaing-Lacombe type.
DR PharmGKB; PA29231; -.
DR eggNOG; COG0123; -.
DR HOGENOM; HOG000004769; -.
DR HOVERGEN; HBG051894; -.
DR InParanoid; Q9UBN7; -.
DR KO; K11407; -.
DR PhylomeDB; Q9UBN7; -.
DR BRENDA; 3.5.1.98; 2681.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_116125; Disease.
DR SABIO-RK; Q9UBN7; -.
DR SignaLink; Q9UBN7; -.
DR ChiTaRS; HDAC6; human.
DR EvolutionaryTrace; Q9UBN7; -.
DR GeneWiki; HDAC6; -.
DR GenomeRNAi; 10013; -.
DR NextBio; 37827; -.
DR PRO; PR:Q9UBN7; -.
DR ArrayExpress; Q9UBN7; -.
DR Bgee; Q9UBN7; -.
DR CleanEx; HS_HDAC6; -.
DR Genevestigator; Q9UBN7; -.
DR GO; GO:0016235; C:aggresome; IDA:BHF-UCL.
DR GO; GO:0005901; C:caveola; IDA:BHF-UCL.
DR GO; GO:0031252; C:cell leading edge; IDA:BHF-UCL.
DR GO; GO:0005881; C:cytoplasmic microtubule; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0000118; C:histone deacetylase complex; IDA:UniProtKB.
DR GO; GO:0005874; C:microtubule; IDA:UniProtKB.
DR GO; GO:0005875; C:microtubule associated complex; IDA:BHF-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0043014; F:alpha-tubulin binding; IDA:BHF-UCL.
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:0051879; F:Hsp90 protein binding; IDA:BHF-UCL.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0032041; F:NAD-dependent histone deacetylase activity (H3-K14 specific); IEA:UniProtKB-EC.
DR GO; GO:0097372; F:NAD-dependent histone deacetylase activity (H3-K18 specific); IEA:UniProtKB-EC.
DR GO; GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); IEA:UniProtKB-EC.
DR GO; GO:0046970; F:NAD-dependent histone deacetylase activity (H4-K16 specific); IEA:UniProtKB-EC.
DR GO; GO:0031593; F:polyubiquitin binding; IDA:BHF-UCL.
DR GO; GO:0048156; F:tau protein binding; IDA:BHF-UCL.
DR GO; GO:0042903; F:tubulin deacetylase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0070842; P:aggresome assembly; IMP:BHF-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:0070932; P:histone H3 deacetylation; IEA:GOC.
DR GO; GO:0070933; P:histone H4 deacetylation; IEA:GOC.
DR GO; GO:0070846; P:Hsp90 deacetylation; IMP:BHF-UCL.
DR GO; GO:0032418; P:lysosome localization; IMP:BHF-UCL.
DR GO; GO:0016236; P:macroautophagy; IMP:BHF-UCL.
DR GO; GO:0006515; P:misfolded or incompletely synthesized protein catabolic process; 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:0043242; P:negative regulation of protein complex disassembly; IMP:BHF-UCL.
DR GO; GO:0045861; P:negative regulation of proteolysis; IMP:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-dependent; ISS:UniProtKB.
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:0090035; P:positive regulation of chaperone-mediated protein complex assembly; 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:0010870; P:positive regulation of receptor biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0009967; P:positive regulation of signal transduction; IMP:BHF-UCL.
DR GO; GO:0043241; P:protein complex disassembly; IEA:Ensembl.
DR GO; GO:0000209; P:protein polyubiquitination; IEA:Ensembl.
DR GO; GO:0060765; P:regulation of androgen receptor signaling pathway; TAS:BHF-UCL.
DR GO; GO:0070201; P:regulation of establishment of protein localization; IEA:Ensembl.
DR GO; GO:0060632; P:regulation of microtubule-based movement; IC:BHF-UCL.
DR GO; GO:0010469; P:regulation of receptor activity; IMP:BHF-UCL.
DR GO; GO:0070848; P:response to growth factor stimulus; IMP:BHF-UCL.
DR GO; GO:0051788; P:response to misfolded protein; IMP:BHF-UCL.
DR GO; GO:0009636; P:response to toxic substance; IMP:BHF-UCL.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
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; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR001607; Znf_UBP.
DR PANTHER; PTHR10625; PTHR10625; 1.
DR Pfam; PF00850; Hist_deacetyl; 2.
DR Pfam; PF02148; zf-UBP; 1.
DR PRINTS; PR01270; HDASUPER.
DR SMART; SM00290; ZnF_UBP; 1.
DR PROSITE; PS50271; ZF_UBP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Autophagy;
KW Chromatin regulator; Complete proteome; Cytoplasm; Hydrolase;
KW Metal-binding; Nucleus; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1 1215 Histone deacetylase 6.
FT /FTId=PRO_0000114703.
FT ZN_FING 1131 1192 UBP-type.
FT REGION 87 404 Histone deacetylase 1.
FT REGION 482 800 Histone deacetylase 2.
FT REGION 1154 1156 Ubiquitin binding.
FT REGION 1182 1189 Ubiquitin binding.
FT ACT_SITE 216 216 1.
FT ACT_SITE 611 611 2.
FT METAL 1113 1113 Zinc 1.
FT METAL 1115 1115 Zinc 1.
FT METAL 1133 1133 Zinc 3.
FT METAL 1136 1136 Zinc 3.
FT METAL 1145 1145 Zinc 2.
FT METAL 1148 1148 Zinc 2.
FT METAL 1153 1153 Zinc 3.
FT METAL 1160 1160 Zinc 3.
FT METAL 1164 1164 Zinc 2.
FT METAL 1170 1170 Zinc 2.
FT METAL 1183 1183 Zinc 1.
FT METAL 1186 1186 Zinc 1.
FT VAR_SEQ 1 152 Missing (in isoform 2).
FT /FTId=VSP_044576.
FT VARIANT 994 994 T -> I (in dbSNP:rs1127346).
FT /FTId=VAR_046300.
FT VARIANT 1200 1200 N -> D (in dbSNP:rs151130423).
FT /FTId=VAR_068962.
FT MUTAGEN 216 216 H->A: Reduces histone deacetylase
FT activity.
FT MUTAGEN 611 611 H->A: Reduces histone deacetylase
FT activity.
FT HELIX 1116 1118
FT TURN 1134 1136
FT STRAND 1140 1145
FT TURN 1146 1148
FT STRAND 1151 1153
FT TURN 1155 1158
FT HELIX 1160 1168
FT STRAND 1172 1175
FT TURN 1176 1178
FT STRAND 1181 1183
FT TURN 1184 1187
FT STRAND 1188 1190
FT HELIX 1193 1195
FT HELIX 1196 1207
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
//
MIM
300272
*RECORD*
*FIELD* NO
300272
*FIELD* TI
*300272 HISTONE DEACETYLASE 6; HDAC6
;;KIAA0901
*FIELD* TX
DESCRIPTION
Histone acetylation (see HAT1; 603053) and deacetylation (see HDAC1;
read more601241) alternately exposes and occludes DNA to transcription factors.
There are at least 2 classes of HDACs, class I consisting of proteins
homologous to yeast Rpd3 (e.g., HDAC1, HDAC2 (605164), and HDAC3
(605166)) and class II consisting of proteins homologous to yeast Hda1
(e.g., HDAC4; 605314). HDAC6 belongs to class II.
CLONING
Nagase et al. (1998) isolated a cDNA encoding HDAC6, which they called
KIAA0901, from a brain cDNA library. RT-PCR analysis detected HDAC6
expression in all tissues tested, with highest expression in brain and
lowest expression in heart, spleen, and pancreas.
By searching an EST database for sequences similar to yeast Hda1,
followed by screening a cDNA library and PCR, Grozinger et al. (1999)
identified cDNAs encoding the class II HDACs HDAC4, HDAC5 (605315), and
HDAC6. Sequence analysis predicted that the 1,216-amino acid HDAC6
protein consists of an apparent internal dimer containing 2 highly
homologous catalytic domains, the first beginning at residue 215 and the
second at residue 610. Northern blot analysis detected expression of a
5.0-kb HDAC6 transcript that was highest in heart, liver, kidney, and
pancreas. Functional analysis confirmed that HDAC6 possesses
deacetylation activity against all 4 core histones and that the 2
catalytic domains function independently. Western blot analysis showed
that HDAC6 is expressed as a 131-kD protein that does not
coimmunoprecipitate with other HDACs or transcription factors. Grozinger
et al. (1999) speculated that HDAC6 may not interact with histones in
vivo but may deacetylate other substrates.
Bertos et al. (2004) determined that the human HDAC6 protein contains 8
consecutive serine- and glutamic acid-containing tetradecapeptide (SE14)
repeats between the second deacetylase domain and the C-terminal
ubiquitin-binding zinc finger. The SE14 domain is not present in
orthologs from C. elegans, Drosophila, and mouse. HDAC6 also contains 2
nuclear export signals and a nuclear localization signal.
GENE FUNCTION
Hubbert et al. (2002) demonstrated that HDAC6 functions as a tubulin
deacetylase. HDAC6 is localized exclusively in the cytoplasm, where it
associates with microtubules and localizes with the microtubule motor
complex (see 601143). In vivo the overexpression of HDAC6 led to a
global deacetylation of alpha-tubulin (see 602529), whereas a decrease
in HDAC6 increased alpha-tubulin acetylation. In vitro, purified HDAC6
potently deacetylated alpha-tubulin in assembled microtubules.
Furthermore, overexpression of HDAC6 promoted chemotactic cell movement,
supporting the idea that HDAC6-mediated deacetylation regulates
microtubule-dependent cell motility. Hubbert et al. (2002) concluded
that HDAC6 is the tubulin deacetylase, and provided evidence that
reversible acetylation regulates important biologic processes beyond
histone metabolism and gene transcription.
Aggregates of misfolded proteins are transported and removed from the
cytoplasm by dynein motors via the microtubule network to an organelle
termed the aggresome, where they are processed. Kawaguchi et al. (2003)
identified HDAC6 as a component of the aggresome in human cells. HDAC6
could bind both polyubiquitinated misfolded proteins and dynein motors,
thereby recruiting misfolded protein cargo to dynein motors for
transport to aggresomes. Cells deficient in HDAC6 failed to clear
misfolded protein aggregates from the cytoplasm, could not form
aggresomes properly, and were hypersensitive to accumulation of
misfolded proteins.
Bertos et al. (2004) determined that the SE14 domain of HDAC6 was
dispensable for the deacetylase and ubiquitin-binding activities of
HDAC6, but it conferred acetyl-microtubule targeting. They further found
that HDAC6 maintained a cytoplasmic distribution in the presence of
leptomycin B, an inhibitor of nuclear export signals, and that the SE14
domain conferred leptomycin B resistance. The SE14 domain formed a
unique structure that caused monomeric HDAC6 to migrate at a molecular
mass of about 500 kD by gel filtration, rather than the predicted mass
of about 150 kD. Bertos et al. (2004) concluded that the cytoplasmic
distribution of HDAC6 is differentially regulated in mice and humans,
and that the SE14 domain serves to stably retain human HDAC6 in the
cytoplasm.
Kovacs et al. (2005) found that inactivation of HDAC6 in human embryonic
kidney cells led to HSP90 (see 140571) hyperacetylation, dissociation of
HSP90 from an essential cochaperone, p23 (607061), and loss of chaperone
activity. In HDAC6-deficient cells, HSP90-dependent maturation of the
glucocorticoid receptor (GCCR; 138040) was compromised, resulting in a
receptor defective in ligand binding, nuclear translocation, and
transcriptional activation. Kovacs et al. (2005) concluded that HSP90 is
a target of HDAC6 and that reversible acetylation is a mechanism that
regulates HSP90 chaperone complex activity.
Pandey et al. (2007) demonstrated in Drosophila that autophagy acts as a
compensatory degradation system when the ubiquitin proteasome system
(UPS) is impaired, and that HDAC6, a microtubule-associated deacetylase
that interacts with polyubiquitinated proteins, is an essential
mechanistic link in this compensatory interaction. The authors found
that compensatory autophagy was induced in response to mutations
affecting the proteasome and in response to UPS impairment in a fly
model of the neurodegenerative disease spinobulbar muscular atrophy.
Autophagy compensated for impaired UPS function in an HDAC6-dependent
manner. Furthermore, expression of HDAC6 was sufficient to rescue
degeneration associated with UPS dysfunction in vivo in an
autophagy-dependent manner. Pandey et al. (2007) concluded that
impairment of autophagy (i.e., associated with aging or genetic
variation) might predispose to neurodegeneration. Moreover, their
findings suggested that it may be possible to intervene in
neurodegeneration by augmenting HDAC6 to enhance autophagy.
Pugacheva et al. (2007) found that AURKA (603072) and its activator HEF1
(NEDD9; 602265) localized to the basal body and the second centriole in
quiescent ciliated human retinal pigment epithelial cells. Association
of AURKA with HEF1 in response to extracellular cues was required for
ciliary disassembly. Activation of AURKA was independently sufficient to
induce rapid ciliary resorption, and AURKA acted in this process through
phosphorylation of HDAC6, leading to HDAC6-dependent tubulin
deacetylation and destabilization of the ciliary axoneme. Small molecule
inhibitors of AURKA and HDAC6 reduced regulated disassembly of cilia.
An immediate response to cell stress is reversible blockade of mRNA
translation. Stalled mRNAs are sequestered into cytoplasmic stress
granules (SGs), which are complex assemblies of initiation factors and
proteins involved in translational control and RNA remodeling or
degradation, as well as 40S ribosome subunits and polyadenylated mRNAs
whose translation has been arrested. Kwon et al. (2007) showed that the
SG protein G3BP (608431) interacted with HDAC6 in vivo and in vitro and
that HDAC6 was recruited to SGs. Inhibition of HDAC led to impaired SG
assembly, and Hdac6-deficient mouse embryo fibroblasts failed to form
SGs, although they exhibited normal phosphorylation of Eif2a (609234) in
response to stress. Inactivating mutations in the catalytic domains or
the C-terminal zinc finger domain of HDAC6 impaired SG assembly. Kwon et
al. (2007) also found that HDAC6 was required for cells to recover from
oxidative stress. They proposed that HDAC6 is a central component of the
stress response that regulates SG formation and potentially contributes
to control of RNA metabolism and translation.
MAPPING
By in situ hybridization, Mahlknecht et al. (2001) mapped the HDAC6 gene
to chromosome Xp11.23.
MOLECULAR GENETICS
Chassaing et al. (2005) reported a 4-generation family segregating an
apparent X-linked dominant chondrodysplasia (300863) with features
including intrauterine growth retardation, hydrocephaly, rhizomelic
shortening, facial dysmorphism, and microphthalmia. Using X-linked
polymorphic microsatellite markers, Simon et al. (2010) performed
linkage analysis in the family described by Chassaing et al. (2005) and
mapped the disease locus to a 24-Mb interval on chromosome Xp11.3-q13.1
(lod = 3.30). By exon sequencing, Simon et al. (2010) identified a
variant in exon 29 of HDAC6, 281 bp after the translation termination
codon (c.*281A>T; 300272.0001) that completely segregated with the
disorder. The variant was located in the sequence corresponding to the
seed sequence of miR433 (611711). Transduction experiments with an HDAC6
3-prime UTR-bearing transgene showed that the mutation abrogated the
posttranscriptional regulation normally exerted by this microRNA.
*FIELD* AV
.0001
CHONDRODYSPLASIA WITH PLATYSPONDYLY, DISTINCTIVE BRACHYDACTYLY, HYDROCEPHALY,
AND MICROPHTHALMIA (1 family)
HDAC6, 4023A-T
In the 4-generation family with X-linked dominant chondrodysplasia
described by Chassaing et al. (2005), Simon et al. (2010) detected an
A-to-T transversion in exon 29 of the HDAC6 gene, in the 3-prime
untranslated region 281 basepairs after the TAA translation termination
codon (c.*281A-T). The mutation completely cosegregated with the
disorder and was not found in SNP databases or in 100 control
individuals. The variant was located in the sequence corresponding to
the seed sequence of miR433 (611711). In MG63 osteosarcoma cells, miR433
downregulated both the expression of endogenous HDAC6 and that of an
enhanced green fluorescent protein-reporter mRNA bearing the wildtype
3-prime UTR of HDAC6. This effect was totally abrogated when the
reporter mRNA bore the mutated HDAC6 3-prime UTR. The HDAC6 protein was
overexpressed in thymus from an affected male fetus. Concomitantly, the
level of total alpha-tubulin (see 602529), a target of HDAC6, was
increased in the affected fetal thymus, whereas the level of acetylated
alpha-tubulin was profoundly decreased. Skin biopsies from a female
patient with striking body asymmetry expressed a mutated HDAC6 allele in
31% of affected arm-derived fibroblasts, whereas it was not expressed in
the contralateral arm. Overexpression of HDAC6 was also observed in
affected arm-derived fibroblasts. The authors concluded that the HDAC6
3-prime UTR variant suppressed miR433-mediated posttranscriptional
regulation, causing overexpression of HDAC6 and resulting in this form
of X-linked chondrodysplasia.
*FIELD* RF
1. Bertos, N. R.; Gilquin, B.; Chan, G. K. T.; Yen, T. J.; Khochbin,
S.; Yang, X.-J.: Role of the tetradecapeptide repeat domain of human
histone deacetylase 6 in cytoplasmic retention. J. Biol. Chem. 279:
48246-48254, 2004.
2. Chassaing, N.; Siani, V.; Carles, D.; Delezoide, A. L.; Alberti,
E. M.; Battin, J.; Chateil, J. F.; Gilbert-Dussardier, B.; Coupry,
I.; Arveiler, B.; Saura, R.; Lacombe, D.: X-linked dominant chondrodysplasia
with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia
. Am. J. Med. Genet. 136A: 307-312, 2005.
3. Grozinger, C. M.; Hassig, C. A.; Schreiber, S. L.: Three proteins
define a class of human histone deacetylases related to yeast Hda1p. Proc.
Nat. Acad. Sci. 96: 4868-4873, 1999.
4. Hubbert, C.; Guardiola, A.; Shao, R.; Kawaguchi, Y.; Ito, A.; Nixon,
A.; Yoshida, M.; Wang, X.-F.; Yao, T.-P.: HDAC6 is a microtubule-associated
deacetylase. Nature 417: 455-458, 2002.
5. Kawaguchi, Y.; Kovacs, J. J.; McLaurin, A.; Vance, J. M.; Ito,
A.; Yao, T.-P.: The deacetylase HDAC6 regulates aggresome formation
and cell viability in response to misfolded protein stress. Cell 115:
727-738, 2003.
6. Kovacs, J. J.; Murphy, P. J. M.; Gaillard, S.; Zhao, X.; Wu, J.-T.;
Nicchitta, C. V.; Yoshida, M.; Toft, D. O.; Pratt, W. B.; Yao, T.-P.
: HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation
of glucocorticoid receptor. Molec. Cell 18: 601-607, 2005.
7. Kwon, S.; Zhang, Y.; Matthias, P.: The deacetylase HDAC6 is a
novel critical component of stress granules involved in the stress
response. Genes Dev. 21: 3381-3394, 2007.
8. Mahlknecht, U.; Schnittger, S.; Landgraf, F.; Schoch, C.; Ottmann,
O. G.; Hiddemann, W.; Hoelzer, D.: Assignment of the human histone
deacetylase 6 gene (HDAC6) to X chromosome p11.23 by in situ hybridization. Cytogenet.
Cell Genet. 93: 135-136, 2001.
9. Nagase, T.; Isikawa, K.; Suyama, M.; Kikuno, R.; Hirosawa, M.;
Miyajima, N.; Tanaka, A.; Kotani, H.; Nomura, N.; Ohara, O.: Prediction
of the coding sequences of unidentified human genes. XII. The complete
sequences of 100 new cDNA clones from brain which code for large proteins
in vitro. DNA Res. 5: 355-364, 1998.
10. Pandey, U. B.; Nie, Z.; Batlevi, Y.; McCray, B. A.; Ritson, G.
P.; Nedelsky, N. B.; Schwartz, S. L.; DiProspero, N. A.; Knight, M.
A.; Schuldiner, O.; Padmanabhan, R.; Hild, M.; Berry, D. L.; Garza,
D.; Hubbert, C. C.; Yao, T.-P.; Baehrecke, E. H.; Taylor, J. P.:
HDAC6 rescues neurodegeneration and provides an essential link between
autophagy and the UPS. Nature 447: 859-863, 2007.
11. Pugacheva, E. N.; Jablonski, S. A.; Hartman, T. R.; Henske, E.
P.; Golemis, E. A.: HEF1-dependent Aurora A activation induces disassembly
of the primary cilium. Cell 129: 1351-1363, 2007.
12. Simon, D.; Laloo, B.; Barillot, M.; Barnetche, T.; Blanchard,
C.; Rooryck, C.; Marche, M.; Burgelin, I.; Coupry, I.; Chassaing,
N.; Gilbert-Dussardier, B.; Lacombe, D.; Grosset, C.; Arveiler, B.
: A mutation in the 3-prime-UTR of the HDAC6 gene abolishing the post-transcriptional
regulation mediated by hsa-miR-433 is linked to a new form of dominant
X-linked chondrodysplasia. Hum. Molec. Genet. 19: 2015-2027, 2010.
*FIELD* CN
George E. Tiller - updated: 09/16/2013
Patricia A. Hartz - updated: 1/14/2008
Patricia A. Hartz - updated: 8/23/2007
Ada Hamosh - updated: 6/29/2007
Patricia A. Hartz - updated: 6/2/2006
Patricia A. Hartz - updated: 6/13/2005
Ada Hamosh - updated: 5/28/2002
Carol A. Bocchini - updated: 8/28/2001
*FIELD* CD
Paul J. Converse: 10/4/2000
*FIELD* ED
alopez: 09/16/2013
mgross: 1/15/2008
terry: 1/14/2008
mgross: 8/30/2007
terry: 8/23/2007
alopez: 7/3/2007
terry: 6/29/2007
mgross: 6/8/2006
terry: 6/2/2006
wwang: 7/7/2005
wwang: 6/28/2005
terry: 6/13/2005
alopez: 5/31/2002
terry: 5/28/2002
mcapotos: 8/28/2001
mgross: 11/29/2000
mgross: 10/4/2000
*RECORD*
*FIELD* NO
300272
*FIELD* TI
*300272 HISTONE DEACETYLASE 6; HDAC6
;;KIAA0901
*FIELD* TX
DESCRIPTION
Histone acetylation (see HAT1; 603053) and deacetylation (see HDAC1;
read more601241) alternately exposes and occludes DNA to transcription factors.
There are at least 2 classes of HDACs, class I consisting of proteins
homologous to yeast Rpd3 (e.g., HDAC1, HDAC2 (605164), and HDAC3
(605166)) and class II consisting of proteins homologous to yeast Hda1
(e.g., HDAC4; 605314). HDAC6 belongs to class II.
CLONING
Nagase et al. (1998) isolated a cDNA encoding HDAC6, which they called
KIAA0901, from a brain cDNA library. RT-PCR analysis detected HDAC6
expression in all tissues tested, with highest expression in brain and
lowest expression in heart, spleen, and pancreas.
By searching an EST database for sequences similar to yeast Hda1,
followed by screening a cDNA library and PCR, Grozinger et al. (1999)
identified cDNAs encoding the class II HDACs HDAC4, HDAC5 (605315), and
HDAC6. Sequence analysis predicted that the 1,216-amino acid HDAC6
protein consists of an apparent internal dimer containing 2 highly
homologous catalytic domains, the first beginning at residue 215 and the
second at residue 610. Northern blot analysis detected expression of a
5.0-kb HDAC6 transcript that was highest in heart, liver, kidney, and
pancreas. Functional analysis confirmed that HDAC6 possesses
deacetylation activity against all 4 core histones and that the 2
catalytic domains function independently. Western blot analysis showed
that HDAC6 is expressed as a 131-kD protein that does not
coimmunoprecipitate with other HDACs or transcription factors. Grozinger
et al. (1999) speculated that HDAC6 may not interact with histones in
vivo but may deacetylate other substrates.
Bertos et al. (2004) determined that the human HDAC6 protein contains 8
consecutive serine- and glutamic acid-containing tetradecapeptide (SE14)
repeats between the second deacetylase domain and the C-terminal
ubiquitin-binding zinc finger. The SE14 domain is not present in
orthologs from C. elegans, Drosophila, and mouse. HDAC6 also contains 2
nuclear export signals and a nuclear localization signal.
GENE FUNCTION
Hubbert et al. (2002) demonstrated that HDAC6 functions as a tubulin
deacetylase. HDAC6 is localized exclusively in the cytoplasm, where it
associates with microtubules and localizes with the microtubule motor
complex (see 601143). In vivo the overexpression of HDAC6 led to a
global deacetylation of alpha-tubulin (see 602529), whereas a decrease
in HDAC6 increased alpha-tubulin acetylation. In vitro, purified HDAC6
potently deacetylated alpha-tubulin in assembled microtubules.
Furthermore, overexpression of HDAC6 promoted chemotactic cell movement,
supporting the idea that HDAC6-mediated deacetylation regulates
microtubule-dependent cell motility. Hubbert et al. (2002) concluded
that HDAC6 is the tubulin deacetylase, and provided evidence that
reversible acetylation regulates important biologic processes beyond
histone metabolism and gene transcription.
Aggregates of misfolded proteins are transported and removed from the
cytoplasm by dynein motors via the microtubule network to an organelle
termed the aggresome, where they are processed. Kawaguchi et al. (2003)
identified HDAC6 as a component of the aggresome in human cells. HDAC6
could bind both polyubiquitinated misfolded proteins and dynein motors,
thereby recruiting misfolded protein cargo to dynein motors for
transport to aggresomes. Cells deficient in HDAC6 failed to clear
misfolded protein aggregates from the cytoplasm, could not form
aggresomes properly, and were hypersensitive to accumulation of
misfolded proteins.
Bertos et al. (2004) determined that the SE14 domain of HDAC6 was
dispensable for the deacetylase and ubiquitin-binding activities of
HDAC6, but it conferred acetyl-microtubule targeting. They further found
that HDAC6 maintained a cytoplasmic distribution in the presence of
leptomycin B, an inhibitor of nuclear export signals, and that the SE14
domain conferred leptomycin B resistance. The SE14 domain formed a
unique structure that caused monomeric HDAC6 to migrate at a molecular
mass of about 500 kD by gel filtration, rather than the predicted mass
of about 150 kD. Bertos et al. (2004) concluded that the cytoplasmic
distribution of HDAC6 is differentially regulated in mice and humans,
and that the SE14 domain serves to stably retain human HDAC6 in the
cytoplasm.
Kovacs et al. (2005) found that inactivation of HDAC6 in human embryonic
kidney cells led to HSP90 (see 140571) hyperacetylation, dissociation of
HSP90 from an essential cochaperone, p23 (607061), and loss of chaperone
activity. In HDAC6-deficient cells, HSP90-dependent maturation of the
glucocorticoid receptor (GCCR; 138040) was compromised, resulting in a
receptor defective in ligand binding, nuclear translocation, and
transcriptional activation. Kovacs et al. (2005) concluded that HSP90 is
a target of HDAC6 and that reversible acetylation is a mechanism that
regulates HSP90 chaperone complex activity.
Pandey et al. (2007) demonstrated in Drosophila that autophagy acts as a
compensatory degradation system when the ubiquitin proteasome system
(UPS) is impaired, and that HDAC6, a microtubule-associated deacetylase
that interacts with polyubiquitinated proteins, is an essential
mechanistic link in this compensatory interaction. The authors found
that compensatory autophagy was induced in response to mutations
affecting the proteasome and in response to UPS impairment in a fly
model of the neurodegenerative disease spinobulbar muscular atrophy.
Autophagy compensated for impaired UPS function in an HDAC6-dependent
manner. Furthermore, expression of HDAC6 was sufficient to rescue
degeneration associated with UPS dysfunction in vivo in an
autophagy-dependent manner. Pandey et al. (2007) concluded that
impairment of autophagy (i.e., associated with aging or genetic
variation) might predispose to neurodegeneration. Moreover, their
findings suggested that it may be possible to intervene in
neurodegeneration by augmenting HDAC6 to enhance autophagy.
Pugacheva et al. (2007) found that AURKA (603072) and its activator HEF1
(NEDD9; 602265) localized to the basal body and the second centriole in
quiescent ciliated human retinal pigment epithelial cells. Association
of AURKA with HEF1 in response to extracellular cues was required for
ciliary disassembly. Activation of AURKA was independently sufficient to
induce rapid ciliary resorption, and AURKA acted in this process through
phosphorylation of HDAC6, leading to HDAC6-dependent tubulin
deacetylation and destabilization of the ciliary axoneme. Small molecule
inhibitors of AURKA and HDAC6 reduced regulated disassembly of cilia.
An immediate response to cell stress is reversible blockade of mRNA
translation. Stalled mRNAs are sequestered into cytoplasmic stress
granules (SGs), which are complex assemblies of initiation factors and
proteins involved in translational control and RNA remodeling or
degradation, as well as 40S ribosome subunits and polyadenylated mRNAs
whose translation has been arrested. Kwon et al. (2007) showed that the
SG protein G3BP (608431) interacted with HDAC6 in vivo and in vitro and
that HDAC6 was recruited to SGs. Inhibition of HDAC led to impaired SG
assembly, and Hdac6-deficient mouse embryo fibroblasts failed to form
SGs, although they exhibited normal phosphorylation of Eif2a (609234) in
response to stress. Inactivating mutations in the catalytic domains or
the C-terminal zinc finger domain of HDAC6 impaired SG assembly. Kwon et
al. (2007) also found that HDAC6 was required for cells to recover from
oxidative stress. They proposed that HDAC6 is a central component of the
stress response that regulates SG formation and potentially contributes
to control of RNA metabolism and translation.
MAPPING
By in situ hybridization, Mahlknecht et al. (2001) mapped the HDAC6 gene
to chromosome Xp11.23.
MOLECULAR GENETICS
Chassaing et al. (2005) reported a 4-generation family segregating an
apparent X-linked dominant chondrodysplasia (300863) with features
including intrauterine growth retardation, hydrocephaly, rhizomelic
shortening, facial dysmorphism, and microphthalmia. Using X-linked
polymorphic microsatellite markers, Simon et al. (2010) performed
linkage analysis in the family described by Chassaing et al. (2005) and
mapped the disease locus to a 24-Mb interval on chromosome Xp11.3-q13.1
(lod = 3.30). By exon sequencing, Simon et al. (2010) identified a
variant in exon 29 of HDAC6, 281 bp after the translation termination
codon (c.*281A>T; 300272.0001) that completely segregated with the
disorder. The variant was located in the sequence corresponding to the
seed sequence of miR433 (611711). Transduction experiments with an HDAC6
3-prime UTR-bearing transgene showed that the mutation abrogated the
posttranscriptional regulation normally exerted by this microRNA.
*FIELD* AV
.0001
CHONDRODYSPLASIA WITH PLATYSPONDYLY, DISTINCTIVE BRACHYDACTYLY, HYDROCEPHALY,
AND MICROPHTHALMIA (1 family)
HDAC6, 4023A-T
In the 4-generation family with X-linked dominant chondrodysplasia
described by Chassaing et al. (2005), Simon et al. (2010) detected an
A-to-T transversion in exon 29 of the HDAC6 gene, in the 3-prime
untranslated region 281 basepairs after the TAA translation termination
codon (c.*281A-T). The mutation completely cosegregated with the
disorder and was not found in SNP databases or in 100 control
individuals. The variant was located in the sequence corresponding to
the seed sequence of miR433 (611711). In MG63 osteosarcoma cells, miR433
downregulated both the expression of endogenous HDAC6 and that of an
enhanced green fluorescent protein-reporter mRNA bearing the wildtype
3-prime UTR of HDAC6. This effect was totally abrogated when the
reporter mRNA bore the mutated HDAC6 3-prime UTR. The HDAC6 protein was
overexpressed in thymus from an affected male fetus. Concomitantly, the
level of total alpha-tubulin (see 602529), a target of HDAC6, was
increased in the affected fetal thymus, whereas the level of acetylated
alpha-tubulin was profoundly decreased. Skin biopsies from a female
patient with striking body asymmetry expressed a mutated HDAC6 allele in
31% of affected arm-derived fibroblasts, whereas it was not expressed in
the contralateral arm. Overexpression of HDAC6 was also observed in
affected arm-derived fibroblasts. The authors concluded that the HDAC6
3-prime UTR variant suppressed miR433-mediated posttranscriptional
regulation, causing overexpression of HDAC6 and resulting in this form
of X-linked chondrodysplasia.
*FIELD* RF
1. Bertos, N. R.; Gilquin, B.; Chan, G. K. T.; Yen, T. J.; Khochbin,
S.; Yang, X.-J.: Role of the tetradecapeptide repeat domain of human
histone deacetylase 6 in cytoplasmic retention. J. Biol. Chem. 279:
48246-48254, 2004.
2. Chassaing, N.; Siani, V.; Carles, D.; Delezoide, A. L.; Alberti,
E. M.; Battin, J.; Chateil, J. F.; Gilbert-Dussardier, B.; Coupry,
I.; Arveiler, B.; Saura, R.; Lacombe, D.: X-linked dominant chondrodysplasia
with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia
. Am. J. Med. Genet. 136A: 307-312, 2005.
3. Grozinger, C. M.; Hassig, C. A.; Schreiber, S. L.: Three proteins
define a class of human histone deacetylases related to yeast Hda1p. Proc.
Nat. Acad. Sci. 96: 4868-4873, 1999.
4. Hubbert, C.; Guardiola, A.; Shao, R.; Kawaguchi, Y.; Ito, A.; Nixon,
A.; Yoshida, M.; Wang, X.-F.; Yao, T.-P.: HDAC6 is a microtubule-associated
deacetylase. Nature 417: 455-458, 2002.
5. Kawaguchi, Y.; Kovacs, J. J.; McLaurin, A.; Vance, J. M.; Ito,
A.; Yao, T.-P.: The deacetylase HDAC6 regulates aggresome formation
and cell viability in response to misfolded protein stress. Cell 115:
727-738, 2003.
6. Kovacs, J. J.; Murphy, P. J. M.; Gaillard, S.; Zhao, X.; Wu, J.-T.;
Nicchitta, C. V.; Yoshida, M.; Toft, D. O.; Pratt, W. B.; Yao, T.-P.
: HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation
of glucocorticoid receptor. Molec. Cell 18: 601-607, 2005.
7. Kwon, S.; Zhang, Y.; Matthias, P.: The deacetylase HDAC6 is a
novel critical component of stress granules involved in the stress
response. Genes Dev. 21: 3381-3394, 2007.
8. Mahlknecht, U.; Schnittger, S.; Landgraf, F.; Schoch, C.; Ottmann,
O. G.; Hiddemann, W.; Hoelzer, D.: Assignment of the human histone
deacetylase 6 gene (HDAC6) to X chromosome p11.23 by in situ hybridization. Cytogenet.
Cell Genet. 93: 135-136, 2001.
9. Nagase, T.; Isikawa, K.; Suyama, M.; Kikuno, R.; Hirosawa, M.;
Miyajima, N.; Tanaka, A.; Kotani, H.; Nomura, N.; Ohara, O.: Prediction
of the coding sequences of unidentified human genes. XII. The complete
sequences of 100 new cDNA clones from brain which code for large proteins
in vitro. DNA Res. 5: 355-364, 1998.
10. Pandey, U. B.; Nie, Z.; Batlevi, Y.; McCray, B. A.; Ritson, G.
P.; Nedelsky, N. B.; Schwartz, S. L.; DiProspero, N. A.; Knight, M.
A.; Schuldiner, O.; Padmanabhan, R.; Hild, M.; Berry, D. L.; Garza,
D.; Hubbert, C. C.; Yao, T.-P.; Baehrecke, E. H.; Taylor, J. P.:
HDAC6 rescues neurodegeneration and provides an essential link between
autophagy and the UPS. Nature 447: 859-863, 2007.
11. Pugacheva, E. N.; Jablonski, S. A.; Hartman, T. R.; Henske, E.
P.; Golemis, E. A.: HEF1-dependent Aurora A activation induces disassembly
of the primary cilium. Cell 129: 1351-1363, 2007.
12. Simon, D.; Laloo, B.; Barillot, M.; Barnetche, T.; Blanchard,
C.; Rooryck, C.; Marche, M.; Burgelin, I.; Coupry, I.; Chassaing,
N.; Gilbert-Dussardier, B.; Lacombe, D.; Grosset, C.; Arveiler, B.
: A mutation in the 3-prime-UTR of the HDAC6 gene abolishing the post-transcriptional
regulation mediated by hsa-miR-433 is linked to a new form of dominant
X-linked chondrodysplasia. Hum. Molec. Genet. 19: 2015-2027, 2010.
*FIELD* CN
George E. Tiller - updated: 09/16/2013
Patricia A. Hartz - updated: 1/14/2008
Patricia A. Hartz - updated: 8/23/2007
Ada Hamosh - updated: 6/29/2007
Patricia A. Hartz - updated: 6/2/2006
Patricia A. Hartz - updated: 6/13/2005
Ada Hamosh - updated: 5/28/2002
Carol A. Bocchini - updated: 8/28/2001
*FIELD* CD
Paul J. Converse: 10/4/2000
*FIELD* ED
alopez: 09/16/2013
mgross: 1/15/2008
terry: 1/14/2008
mgross: 8/30/2007
terry: 8/23/2007
alopez: 7/3/2007
terry: 6/29/2007
mgross: 6/8/2006
terry: 6/2/2006
wwang: 7/7/2005
wwang: 6/28/2005
terry: 6/13/2005
alopez: 5/31/2002
terry: 5/28/2002
mcapotos: 8/28/2001
mgross: 11/29/2000
mgross: 10/4/2000