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Q9Z2V5 (HDAC6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histone deacetylase 6

Short name=HD6
EC=3.5.1.98
Alternative name(s):
Histone deacetylase mHDA2
Gene names
Name:Hdac6
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1149 AA.
Sequence statusComplete.
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. Ref.4

In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome. Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and target them to the aggresome, facilitating their clearance by autophagy By similarity. Ref.4

Catalytic activity

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

Cofactor

Binds 3 zinc ions per subunit By similarity.

Subunit structure

Interacts with HDAC11 and SIRT2. Interacts with F-actin F-actin. Interacts with BBIP10. Under proteasome impairment conditions, interacts with UBD via its histone deacetylase 1 and UBP-type zinc-finger regions. Interacts with CYLD. Interacts with CBFA2T3. Interacts with ZMYND15. Interacts with DDIT3/CHOP By similarity. Ref.3 Ref.4 Ref.5

Subcellular location

Nucleus. Cytoplasm. Note: It is mainly cytoplasmic, where it is associated with microtubules. Ref.4

Tissue specificity

Detected in keratinocytes (at protein level). Ref.4

Post-translational modification

Phosphorylated by AURKA By similarity.

Ubiquitinated. Its polyubiquitination however does not lead to its degradation By similarity.

Sumoylated in vitro By similarity.

Sequence similarities

Belongs to the histone deacetylase family. HD type 2 subfamily.

Contains 1 UBP-type zinc finger.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DomainRepeat
Zinc-finger
   LigandActin-binding
Metal-binding
Zinc
   Molecular functionChromatin regulator
Hydrolase
Repressor
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processHsp90 deacetylation

Inferred from mutant phenotype PubMed 17785525. Source: MGI

aggresome assembly

Inferred from genetic interaction PubMed 16810319. Source: MGI

cellular response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

cellular response to misfolded protein

Inferred from mutant phenotype PubMed 17785525. Source: MGI

lysosome localization

Inferred from electronic annotation. Source: Ensembl

macroautophagy

Inferred from electronic annotation. Source: Ensembl

misfolded or incompletely synthesized protein catabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of microtubule depolymerization

Inferred from direct assay PubMed 12486003. Source: MGI

negative regulation of proteolysis

Inferred from electronic annotation. Source: Ensembl

peptidyl-lysine deacetylation

Inferred from electronic annotation. Source: Ensembl

polyubiquitinated misfolded protein transport

Inferred from electronic annotation. Source: Ensembl

positive regulation of chaperone-mediated protein complex assembly

Inferred from electronic annotation. Source: Ensembl

positive regulation of epithelial cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of hydrogen peroxide-mediated programmed cell death

Inferred from electronic annotation. Source: Ensembl

positive regulation of receptor biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of signal transduction

Inferred from electronic annotation. Source: Ensembl

protein complex disassembly

Inferred from genetic interaction PubMed 17785525. Source: MGI

protein deacetylation

Inferred from direct assay PubMed 12486003. Source: MGI

protein polyubiquitination

Inferred from direct assay PubMed 11689694. Source: MGI

regulation of establishment of protein localization

Inferred from mutant phenotype PubMed 22792322. Source: MGI

regulation of receptor activity

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

response to growth factor

Inferred from electronic annotation. Source: Ensembl

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

tubulin deacetylation

Inferred from direct assay Ref.4. Source: UniProtKB

ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype PubMed 16810319. Source: MGI

ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway

Inferred from mutant phenotype PubMed 17785525. Source: MGI

   Cellular_componentaggresome

Inferred from electronic annotation. Source: Ensembl

axon

Inferred from direct assay PubMed 16933150. Source: UniProtKB

caveola

Inferred from electronic annotation. Source: Ensembl

cell leading edge

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 11689694. Source: MGI

cytosol

Inferred from direct assay Ref.4. Source: UniProtKB

dendrite

Inferred from direct assay PubMed 16933150. Source: UniProtKB

dynein complex

Inferred from electronic annotation. Source: Ensembl

histone deacetylase complex

Inferred from electronic annotation. Source: Ensembl

microtubule

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay Ref.4. Source: UniProtKB

perikaryon

Inferred from direct assay PubMed 16933150. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

protein complex

Inferred from physical interaction PubMed 17785525. Source: MGI

   Molecular_functionNAD-dependent histone deacetylase activity (H3-K14 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H3-K18 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H3-K9 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

NAD-dependent histone deacetylase activity (H4-K16 specific)

Inferred from electronic annotation. Source: UniProtKB-EC

beta-tubulin binding

Inferred from direct assay PubMed 12606581. Source: MGI

histone deacetylase activity

Inferred from direct assay PubMed 11689694Ref.1. Source: MGI

microtubule binding

Inferred from direct assay Ref.4. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.4. Source: UniProtKB

tubulin deacetylase activity

Inferred from direct assay Ref.4. Source: UniProtKB

ubiquitin binding

Inferred from direct assay PubMed 16810319. Source: MGI

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

ADRBK1P211462EBI-1009256,EBI-1036401From a different organism.
CyldQ80TQ23EBI-1009256,EBI-943859

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11491149Histone deacetylase 6
PRO_0000114704

Regions

Zinc finger1065 – 112662UBP-type
Region87 – 403317Histone deacetylase 1
Region481 – 799319Histone deacetylase 2
Region1088 – 10903Ubiquitin binding By similarity
Region1116 – 11238Ubiquitin binding By similarity
Compositional bias455 – 4606Poly-Glu

Sites

Active site21511 By similarity
Active site61012 By similarity
Metal binding10471Zinc 1 By similarity
Metal binding10491Zinc 1 By similarity
Metal binding10671Zinc 3 By similarity
Metal binding10701Zinc 3 By similarity
Metal binding10791Zinc 2 By similarity
Metal binding10821Zinc 2 By similarity
Metal binding10871Zinc 3 By similarity
Metal binding10941Zinc 3 By similarity
Metal binding10981Zinc 2 By similarity
Metal binding11041Zinc 2 By similarity
Metal binding11171Zinc 1 By similarity
Metal binding11201Zinc 1 By similarity

Experimental info

Sequence conflict1331R → W in AAD09835. Ref.1
Sequence conflict3941V → I in AAD09835. Ref.1
Sequence conflict4211T → I in AAD09835. Ref.1
Sequence conflict5321D → G in AAD09835. Ref.1
Sequence conflict8361M → S in AAD09835. Ref.1
Sequence conflict8511I → V in AAD09835. Ref.1
Sequence conflict1126 – 11272HE → QD in AAD09835. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9Z2V5 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: D5F73BA3F79AF520

FASTA1,149125,787
        10         20         30         40         50         60 
MTSTGQDSST RQRKSRHNPQ SPLQESSATL KRGGKKCAVP HSSPNLAEVK KKGKMKKLSQ 

        70         80         90        100        110        120 
PAEEDLVVGL QGLDLNPETR VPVGTGLVFD EQLNDFHCLW DDSFPESPER LHAIREQLIL 

       130        140        150        160        170        180 
EGLLGRCVSF QARFAEKEEL MLVHSLEYID LMETTQYMNE GELRVLAETY DSVYLHPNSY 

       190        200        210        220        230        240 
SCACLATGSV LRLVDALMGA EIRNGMAVIR PPGHHAQHNL MDGYCMFNHL AVAARYAQKK 

       250        260        270        280        290        300 
HRIQRVLIVD WDVHHGQGTQ FIFDQDPSVL YFSIHRYEHG RFWPHLKASN WSTIGFGQGQ 

       310        320        330        340        350        360 
GYTINVPWNQ TGMRDADYIA AFLHILLPVA SEFQPQLVLV AAGFDALHGD PKGEMAATPA 

       370        380        390        400        410        420 
GFAHLTHLLM GLAGGKLILS LEGGYNLRAL AKGVSASLHT LLGDPCPMLE SCVVPCASAQ 

       430        440        450        460        470        480 
TSIYCTLEAL EPFWEVLERS VETQEEDEVE EAVLEEEEEE GGWEATALPM DTWPLLQNRT 

       490        500        510        520        530        540 
GLVYDEKMMS HCNLWDNHHP ETPQRILRIM CHLEEVGLAA RCLILPARPA LDSELLTCHS 

       550        560        570        580        590        600 
AEYVEHLRTT EKMKTRDLHR EGANFDSIYI CPSTFACAKL ATGAACRLVE AVLSGEVLNG 

       610        620        630        640        650        660 
IAVVRPPGHH AEPNAACGFC FFNSVAVAAR HAQIIAGRAL RILIVDWDVH HGNGTQHIFE 

       670        680        690        700        710        720 
DDPSVLYVSL HRYDRGTFFP MGDEGASSQV GRDAGIGFTV NVPWNGPRMG DADYLAAWHR 

       730        740        750        760        770        780 
LVLPIAYEFN PELVLISAGF DAAQGDPLGG CQVTPEGYAH LTHLLMGLAG GRIILILEGG 

       790        800        810        820        830        840 
YNLASISESM AACTHSLLGD PPPQLTLLRP PQSGALVSIS EVIQVHRKYW RSLRLMKMED 

       850        860        870        880        890        900 
KEECSSSRLV IKKLPPTASP VSAKEMTTPK GKVPEESVRK TIAALPGKES TLGQAKSKMA 

       910        920        930        940        950        960 
KAVLAQGQSS EQAAKGTTLD LATSKETVGG ATTDLWASAA APENFPNQTT SVEALGETEP 

       970        980        990       1000       1010       1020 
TPPASHTNKQ TTGASPLQGV TAQQSLQLGV LSTLELSREA EEAHDSEEGL LGEAAGGQDM 

      1030       1040       1050       1060       1070       1080 
NSLMLTQGFG DFNTQDVFYA VTPLSWCPHL MAVCPIPAAG LDVSQPCKTC GTVQENWVCL 

      1090       1100       1110       1120       1130       1140 
TCYQVYCSRY VNAHMVCHHE ASEHPLVLSC VDLSTWCYVC QAYVHHEDLQ DVKNAAHQNK 


FGEDMPHSH 

« Hide

References

« Hide 'large scale' references
[1]"Identification of a new family of higher eukaryotic histone deacetylases. Coordinate expression of differentiation-dependent chromatin modifiers."
Verdel A., Khochbin S.
J. Biol. Chem. 274:2440-2445(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: C57BL/6J.
Tissue: Fetus.
[2]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[3]"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] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CBFA2T3.
[4]"CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin."
Wickstrom S.A., Masoumi K.C., Khochbin S., Fassler R., Massoumi R.
EMBO J. 29:131-144(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CYLD AND MICROTUBULES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[5]"Zmynd15 encodes a histone deacetylase-dependent transcriptional repressor essential for spermiogenesis and male fertility."
Yan W., Si Y., Slaymaker S., Li J., Zheng H., Young D.L., Aslanian A., Saunders L., Verdin E., Charo I.F.
J. Biol. Chem. 285:31418-31426(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ZMYND15.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF006603 mRNA. Translation: AAD09835.2.
AL670169 Genomic DNA. Translation: CAM17240.1.
CCDSCCDS40845.1.
PIRT13964.
RefSeqNP_001123888.1. NM_001130416.1.
NP_034543.3. NM_010413.3.
XP_006527630.1. XM_006527567.1.
UniGeneMm.29854.

3D structure databases

ProteinModelPortalQ9Z2V5.
SMRQ9Z2V5. Positions 1043-1144.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200263. 16 interactions.
IntActQ9Z2V5. 8 interactions.
MINTMINT-220628.

Chemistry

BindingDBQ9Z2V5.
ChEMBLCHEMBL2878.

PTM databases

PhosphoSiteQ9Z2V5.

Proteomic databases

MaxQBQ9Z2V5.
PaxDbQ9Z2V5.
PRIDEQ9Z2V5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000033501; ENSMUSP00000033501; ENSMUSG00000031161.
ENSMUST00000115642; ENSMUSP00000111306; ENSMUSG00000031161.
GeneID15185.
KEGGmmu:15185.
UCSCuc009snh.2. mouse.

Organism-specific databases

CTD10013.
MGIMGI:1333752. Hdac6.

Phylogenomic databases

eggNOGCOG0123.
GeneTreeENSGT00530000062809.
HOGENOMHOG000004769.
HOVERGENHBG051894.
KOK11407.
OMALQENWVC.
OrthoDBEOG7992PT.
TreeFamTF106173.

Gene expression databases

ArrayExpressQ9Z2V5.
BgeeQ9Z2V5.
CleanExMM_HDAC6.
GenevestigatorQ9Z2V5.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
3.40.800.20. 2 hits.
InterProIPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR013083. Znf_RING/FYVE/PHD.
IPR001607. Znf_UBP.
[Graphical view]
PANTHERPTHR10625. PTHR10625. 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

NextBio287707.
PROQ9Z2V5.
SOURCESearch...

Entry information

Entry nameHDAC6_MOUSE
AccessionPrimary (citable) accession number: Q9Z2V5
Secondary accession number(s): B1AUA6
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 120 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot