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Reviewed, UniProtKB/Swiss-Prot Q9UBN7 (HDAC6_HUMAN)

Last modified June 16, 2009. Version 85. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Histone deacetylase 6
      Short name=HD6
    EC=3.5.1.98
Gene names
Name: HDAC6
Synonyms: KIAA0901
ORF Names: JM21
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1215 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes By similarity. Plays a central role in microtubule-dependent cell motility via deacetylation of tubulin.

Catalytic activity

Hydrolysis of an N(6)-acetyl-lysine residue of a histone to yield a deacetylated histone.

Subunit structure

Interacts with CBFA2T3, HDAC11 and SIRT2. Interacts with F-actin. Interacts with BBIP10. Ref.5 Ref.6 Ref.11 Ref.14

Subcellular location

Nucleus. Cytoplasm. Note: It is mainly cytoplasmic, where it is associated with microtubules.

Post-translational modification

Ubiquitinated. Its polyubiquitination however does not lead to its degradation. Ref.8

Sumoylated in vitro. Ref.7

Sequence similarities

Belongs to the histone deacetylase family. Type 2 subfamily.

Contains 1 UBP-type zinc finger.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainRepeat
Zinc-finger
   LigandActin-binding
Metal-binding
Zinc
   Molecular functionChromatin regulator
Hydrolase
Repressor
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Gene Ontology (GO)
   Biological processcell cycle

Non-traceable author statement. Source: UniProtKB

histone deacetylation

Inferred from sequence or structural similarity. Source: UniProtKB

multicellular organismal development

Non-traceable author statement. Source: UniProtKB

regulation of transcription, DNA-dependent

Inferred from electronic annotation. Source: UniProtKB-KW

transcription

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

histone deacetylase complex Ref.6

Inferred from direct assay. Source: UniProtKB

microtubule Ref.11

Inferred from direct assay. Source: UniProtKB

   Molecular functionactin binding

Inferred from electronic annotation. Source: UniProtKB-KW

histone deacetylase binding Ref.11

Inferred from physical interaction. Source: UniProtKB

specific transcriptional repressor activity

Inferred from sequence or structural similarity. Source: UniProtKB

tubulin deacetylase activity Ref.11

Inferred from direct assay. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12151215Histone deacetylase 6
PRO_0000114703

Regions

Zinc finger1131 – 119262UBP-type
Region87 – 404318Histone deacetylase 1
Region482 – 800319Histone deacetylase 2

Sites

Active site21611
Active site61112

Amino acid modifications

Modified residue221Phosphoserine Ref.9 Ref.12
Modified residue301Phosphothreonine Ref.13

Natural variations

Natural variant9941T → I: dbSNP rs1127346. Ref.1 Ref.4
VAR_046300

Experimental info

Mutagenesis2161H → A: Reduces histone deacetylase activity. Ref.8
Mutagenesis6111H → A: Reduces histone deacetylase activity. Ref.8

Secondary structure

........................ 1215
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UBN7-1 [UniParc].

Last modified September 2, 2008. Version 2.
Checksum: 6F17731268A33114

FASTA1,215131,419
        10         20         30         40         50         60 
MTSTGQDSTT TRQRRSRQNP QSPPQDSSVT SKRNIKKGAV PRSIPNLAEV KKKGKMKKLG 

        70         80         90        100        110        120 
QAMEEDLIVG LQGMDLNLEA EALAGTGLVL DEQLNEFHCL WDDSFPEGPE RLHAIKEQLI 

       130        140        150        160        170        180 
QEGLLDRCVS FQARFAEKEE LMLVHSLEYI DLMETTQYMN EGELRVLADT YDSVYLHPNS 

       190        200        210        220        230        240 
YSCACLASGS VLRLVDAVLG AEIRNGMAII RPPGHHAQHS LMDGYCMFNH VAVAARYAQQ 

       250        260        270        280        290        300 
KHRIRRVLIV DWDVHHGQGT QFTFDQDPSV LYFSIHRYEQ GRFWPHLKAS NWSTTGFGQG 

       310        320        330        340        350        360 
QGYTINVPWN QVGMRDADYI AAFLHVLLPV ALEFQPQLVL VAAGFDALQG DPKGEMAATP 

       370        380        390        400        410        420 
AGFAQLTHLL MGLAGGKLIL SLEGGYNLRA LAEGVSASLH TLLGDPCPML ESPGAPCRSA 

       430        440        450        460        470        480 
QASVSCALEA LEPFWEVLVR STETVERDNM EEDNVEESEE EGPWEPPVLP ILTWPVLQSR 

       490        500        510        520        530        540 
TGLVYDQNMM NHCNLWDSHH PEVPQRILRI MCRLEELGLA GRCLTLTPRP ATEAELLTCH 

       550        560        570        580        590        600 
SAEYVGHLRA TEKMKTRELH RESSNFDSIY ICPSTFACAQ LATGAACRLV EAVLSGEVLN 

       610        620        630        640        650        660 
GAAVVRPPGH HAEQDAACGF CFFNSVAVAA RHAQTISGHA LRILIVDWDV HHGNGTQHMF 

       670        680        690        700        710        720 
EDDPSVLYVS LHRYDHGTFF PMGDEGASSQ IGRAAGTGFT VNVAWNGPRM GDADYLAAWH 

       730        740        750        760        770        780 
RLVLPIAYEF NPELVLVSAG FDAARGDPLG GCQVSPEGYA HLTHLLMGLA SGRIILILEG 

       790        800        810        820        830        840 
GYNLTSISES MAACTRSLLG DPPPLLTLPR PPLSGALASI TETIQVHRRY WRSLRVMKVE 

       850        860        870        880        890        900 
DREGPSSSKL VTKKAPQPAK PRLAERMTTR EKKVLEAGMG KVTSASFGEE STPGQTNSET 

       910        920        930        940        950        960 
AVVALTQDQP SEAATGGATL AQTISEAAIG GAMLGQTTSE EAVGGATPDQ TTSEETVGGA 

       970        980        990       1000       1010       1020 
ILDQTTSEDA VGGATLGQTT SEEAVGGATL AQTTSEAAME GATLDQTTSE EAPGGTELIQ 

      1030       1040       1050       1060       1070       1080 
TPLASSTDHQ TPPTSPVQGT TPQISPSTLI GSLRTLELGS ESQGASESQA PGEENLLGEA 

      1090       1100       1110       1120       1130       1140 
AGGQDMADSM LMQGSRGLTD QAIFYAVTPL PWCPHLVAVC PIPAAGLDVT QPCGDCGTIQ 

      1150       1160       1170       1180       1190       1200 
ENWVCLSCYQ VYCGRYINGH MLQHHGNSGH PLVLSYIDLS AWCYYCQAYV HHQALLDVKN 

      1210 
IAHQNKFGED MPHPH 

« Hide

References

« Hide 'large scale' references
[1]"Three proteins define a class of human histone deacetylases related to yeast Hda1p."
Grozinger C.M., Hassig C.A., Schreiber S.L.
Proc. Natl. Acad. Sci. U.S.A. 96:4868-4873(1999) [PubMed: 10220385] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-994.
[2]"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."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:355-364(1998) [PubMed: 10048485] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]Ohara O., Suyama M., Kikuno R., Nagase T., Ishikawa K.
Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[4]"Transcription map in Xp11.23."
Strom T.M., Gutwillinger N., Nyakatura G., Hellebrand H., Drescher B., Rosenthal A., Meindl A.
Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ILE-994.
Tissue: Brain.
[5]"ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with multiple histone deacetylases and binds mSin3A through its oligomerization domain."
Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N., Downing J.R., Meyers S., Hiebert S.W.
Mol. Cell. Biol. 21:6470-6483(2001) [PubMed: 11533236] [Abstract]
Cited for: INTERACTION WITH CBFA2T3.
[6]"Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family."
Gao L., Cueto M.A., Asselbergs F., Atadja P.
J. Biol. Chem. 277:25748-25755(2002) [PubMed: 11948178] [Abstract]
Cited for: INTERACTION WITH HDAC11.
[7]"The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase."
Kirsh O., Seeler J.-S., Pichler A., Gast A., Mueller S., Miska E., Mathieu M., Harel-Bellan A., Kouzarides T., Melchior F., Dejean A.
EMBO J. 21:2682-2691(2002) [PubMed: 12032081] [Abstract]
Cited for: SUMOYLATION.
[8]"Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes."
Hook S.S., Orian A., Cowley S.M., Eisenman R.N.
Proc. Natl. Acad. Sci. U.S.A. 99:13425-13430(2002) [PubMed: 12354939] [Abstract]
Cited for: UBIQUITINATION, MUTAGENESIS OF HIS-216 AND HIS-611.
[9]"Large-scale characterization of HeLa cell nuclear phosphoproteins."
Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, MASS SPECTROMETRY.
Tissue: Epithelium.
[10]"HDAC6 is a microtubule-associated deacetylase."
Hubbert C., Guardiola A., Shao R., Kawaguchi Y., Ito A., Nixon A., Yoshida M., Wang X.-F., Yao T.-P.
Nature 417:455-458(2002) [PubMed: 12024216] [Abstract]
Cited for: FUNCTION.
[11]"The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase."
North B.J., Marshall B.L., Borra M.T., Denu J.M., Verdin E.
Mol. Cell 11:437-444(2003) [PubMed: 12620231] [Abstract]
Cited for: INTERACTION WITH SIRT2.
[12]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22, MASS SPECTROMETRY.
Tissue: Epithelium.
[13]"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry."
Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.
Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-30, MASS SPECTROMETRY.
[14]"A BBSome subunit links ciliogenesis, microtubule stability and acetylation."
Loktev A.V., Zhang Q., Beck J.S., Searby C.C., Scheetz T.E., Bazan F., Slusarski D.C., Sheffield V.C., Jackson P.K., Nachury M.V.
Dev. Cell 15:854-865(2008)
Cited for: INTERACTION WITH BBIP10.
[15]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]"Crystal structure of human HDAC6 zinc finger domain."
Structural genomics consortium (SGC)
Submitted (FEB-2008) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 1108-1215 IN COMPLEX WITH ZINC IONS.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF132609 mRNA. Translation: AAD29048.1.
AB020708 mRNA. Translation: BAA74924.2. Different initiation.
AJ011972 mRNA. Translation: CAA09893.1.
IPIIPI00005711.
RefSeqNP_006035.2.
UniGeneHs.6764

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
3C5KX-ray1.55A1109-1215[»]
3GV4X-ray1.72A1109-1215[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP:27544N.
IntActQ9UBN7. 10 interactions.

PTM databases

PhosphoSiteQ9UBN7.

Proteomic databases

PRIDEQ9UBN7.

Genome annotation databases

EnsemblENSG00000094631. Homo sapiens. [Contig view]
GeneID10013.
KEGGhsa:10013.

Organism-specific databases

GeneCardsGC0XP048545.
H-InvDBHIX0016783.
HGNCHGNC:14064. HDAC6.
HPACAB004236.
MIM300272. gene.
PharmGKBPA29231.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ9UBN7.
OMAQ9UBN7. QGQGYTI.

Enzyme and pathway databases

Pathway_Interaction_DBhdac_classi_pathway. Signaling events mediated by HDAC Class I.
hdac_classii_pathway. Signaling events mediated by HDAC Class II.
ReactomeREACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ9UBN7.
BgeeQ9UBN7.
CleanExHS_HDAC6.
GermOnlineENSG00000094631. Homo sapiens.

Family and domain databases

InterProIPR000286. His_deacetylse.
IPR001607. Znf_UBP.
[Graphical view]
Gene3DG3DSA:3.40.800.20. His_deacetylse. 2 hits.
PANTHERPTHR10625. His_deacetylse. 1 hit.
PfamPF00850. Hist_deacetyl. 2 hits.
PF02148. zf-UBP. 1 hit.
[Graphical view]
PRINTSPR01270. HDASUPER.
SMARTSM00290. ZnF_UBP. 1 hit.
[Graphical view]
PROSITEPS50271. ZF_UBP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB02546. Vorinostat.
NextBio37827.
SOURCESearch...

Entry information

Entry nameHDAC6_HUMAN
AccessionPrimary (citable) accession number: Q9UBN7
Secondary accession number(s): O94975, Q96CY0
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: September 2, 2008
Last modified: June 16, 2009
This is version 85 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome X

Human chromosome X: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents