Histone deacetylase 6 - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot Q9UBN7 (HDAC6_HUMAN)

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

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

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Names and origin

Protein names

Recommended name:
    Histone deacetylase 6
      Short name=HD6
    EC=3.5.1.98

Gene names

Name:	HDAC6
Synonyms:	KIAA0901
ORF Names:	JM21

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	1215 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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.

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Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Domain	Repeat Zinc-finger
Ligand	Actin-binding Metal-binding Zinc
Molecular function	Chromatin regulator Hydrolase Repressor
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	cell 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 component	cytoplasm 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 function	actin 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...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
BRMS1	Q9HCU9	2	EBI-301697,EBI-714781
Cdc20	Q62623	2	EBI-301697,EBI-2256532	From a different organism.
FYN	P06241	1	EBI-301697,EBI-515315
HDAC11	Q96DB2	1	EBI-301697,EBI-301713
HIST1H4A	P62805	1	EBI-301697,EBI-302023
SIRT2	Q8IXJ6	1	EBI-301697,EBI-477232

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1215

1215

Histone deacetylase 6

PRO_0000114703

Regions

Zinc finger

1131 – 1192

UBP-type

Region

87 – 404

318

Histone deacetylase 1

Region

482 – 800

319

Histone deacetylase 2

Sites

Active site

216

Active site

611

Amino acid modifications

Modified residue

Phosphoserine Ref.9 Ref.12

Modified residue

Phosphothreonine Ref.13

Natural variations

Natural variant

994

T → I: dbSNP rs1127346. Ref.1 Ref.4

VAR_046300

Experimental info

Mutagenesis

216

H → A: Reduces histone deacetylase activity. Ref.8

Mutagenesis

611

H → A: Reduces histone deacetylase activity. Ref.8

Secondary structure

1215

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

Q9UBN7-1 [UniParc].

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

1,215

131,419

        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

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References

	« Hide 'large scale' referencesShow '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.

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Cross-references

Sequence databases

AF132609 mRNA. Translation: AAD29048.1.
AB020708 mRNA. Translation: BAA74924.2. Different initiation.
AJ011972 mRNA. Translation: CAA09893.1.

IPI

IPI00005711.

RefSeq

NP_006035.2.

UniGene

Hs.6764

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3C5K	X-ray	1.55	A	1109-1215	[»]
3GV4	X-ray	1.72	A	1109-1215	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:27544N.

IntAct

Q9UBN7. 10 interactions.

PTM databases

PhosphoSite

Q9UBN7.

Proteomic databases

PRIDE

Q9UBN7.

Genome annotation databases

Ensembl

ENSG00000094631. Homo sapiens. [Contig view]

GeneID

10013.

KEGG

hsa:10013.

Organism-specific databases

GeneCards

GC0XP048545.

H-InvDB

HIX0016783.

HGNC

HGNC:14064. HDAC6.

HPA

CAB004236.

MIM

300272. gene.

PharmGKB

PA29231.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q9UBN7.

OMA

Q9UBN7. QGQGYTI.

Enzyme and pathway databases

Pathway_Interaction_DB

hdac_classi_pathway. Signaling events mediated by HDAC Class I.
hdac_classii_pathway. Signaling events mediated by HDAC Class II.

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q9UBN7.

Bgee

Q9UBN7.

CleanEx

HS_HDAC6.

GermOnline

ENSG00000094631. Homo sapiens.

Family and domain databases

InterPro

IPR000286. His_deacetylse.
IPR001607. Znf_UBP.
[Graphical view]

Gene3D

G3DSA:3.40.800.20. His_deacetylse. 2 hits.

PANTHER

PTHR10625. His_deacetylse. 1 hit.

Pfam

PF00850. Hist_deacetyl. 2 hits.
PF02148. zf-UBP. 1 hit.
[Graphical view]

PRINTS

PR01270. HDASUPER.

SMART

SM00290. ZnF_UBP. 1 hit.
[Graphical view]

PROSITE

PS50271. ZF_UBP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB02546. Vorinostat.

NextBio

37827.

SOURCE

Search...

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Entry information

Entry name

HDAC6_HUMAN

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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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

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents