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Q9Z2V6 (HDAC5_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Histone deacetylase 5

Short name=HD5
EC=3.5.1.98
Alternative name(s):
Histone deacetylase mHDA1
Gene names
Name:Hdac5
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1113 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. Involved in muscle maturation by repressing transcription of myocyte enhancer MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors By similarity.

Catalytic activity

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

Subunit structure

Interacts with AHRR, BAHD1, BCOR, HDAC7, HDAC9, CTBP1, MEF2C, NCOR2, NRIP1, PHB2 and a 14-3-3 chaperone protein. Interacts with BCL6, DDIT3/CHOP, GRK5, KDM5B and MYOCD. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7 Ref.9 Ref.10

Subcellular location

Nucleus. Cytoplasm. Note: Shuttles between the nucleus and the cytoplasm. In muscle cells, it shuttles into the cytoplasm during myocyte differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-250 and Ser-488 by AMPK, CaMK1 and SIK1. Ref.8 Ref.11

Domain

The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.

Post-translational modification

Phosphorylated by AMPK, CaMK1, SIK1 and PRKD1 at Ser-250 and Ser-488. The phosphorylation is required for the export to the cytoplasm and inhibition. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import By similarity. Phosphorylated by GRK5, leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription. Ref.8 Ref.10 Ref.11

Ubiquitinated. Polyubiquitination however does not lead to its degradation By similarity.

Sequence similarities

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

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   LigandMetal-binding
Zinc
   Molecular functionChromatin regulator
Hydrolase
Repressor
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell activation

Traceable author statement PubMed 12711221. Source: UniProtKB

B cell differentiation

Traceable author statement PubMed 12711221. Source: UniProtKB

cellular response to fluid shear stress

Inferred from direct assay PubMed 20181743. Source: UniProtKB

chromatin modification

Traceable author statement PubMed 12711221. Source: UniProtKB

heart development

Inferred from genetic interaction PubMed 15367668. Source: MGI

histone deacetylation

Traceable author statement PubMed 12711221. Source: GOC

inflammatory response

Traceable author statement PubMed 12711221. Source: UniProtKB

multicellular organismal response to stress

Inferred from mutant phenotype PubMed 17988634. Source: MGI

negative regulation of osteoblast differentiation

Inferred from mutant phenotype PubMed 15990875. Source: MGI

negative regulation of striated muscle tissue development

Traceable author statement PubMed 12711221. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.2. Source: MGI

negative regulation of transcription, DNA-templated

Traceable author statement PubMed 12711221. Source: UniProtKB

nervous system development

Traceable author statement PubMed 12711221. Source: UniProtKB

osteoblast development

Inferred from mutant phenotype PubMed 15990875. Source: MGI

positive regulation of neural precursor cell proliferation

Inferred from mutant phenotype PubMed 20123967. Source: BHF-UCL

positive regulation of stem cell proliferation

Inferred from mutant phenotype PubMed 20123967. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 20181743. Source: UniProtKB

regulation of myotube differentiation

Inferred from direct assay Ref.8. Source: UniProtKB

regulation of skeletal muscle fiber development

Inferred from genetic interaction PubMed 17786239. Source: MGI

regulation of striated muscle cell differentiation

Inferred from genetic interaction PubMed 17786239. Source: MGI

renal tubule morphogenesis

Inferred from mutant phenotype PubMed 20181743. Source: UniProtKB

response to cocaine

Inferred from direct assay PubMed 17988634. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay Ref.8. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 18198354PubMed 18332106. Source: MGI

histone deacetylase complex

Traceable author statement PubMed 12711221. Source: UniProtKB

nuclear body

Inferred from direct assay PubMed 11641275. Source: MGI

nucleus

Inferred from direct assay Ref.8PubMed 20181743. Source: UniProtKB

   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

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from mutant phenotype PubMed 20181743. Source: UniProtKB

RNA polymerase II transcription factor binding

Inferred from physical interaction PubMed 20123967. Source: BHF-UCL

core promoter sequence-specific DNA binding

Inferred from direct assay PubMed 20181743. Source: UniProtKB

histone deacetylase activity

Traceable author statement PubMed 12711221. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.5Ref.7. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.8. Source: UniProtKB

transcription corepressor activity

Inferred from direct assay Ref.2. Source: MGI

transcription factor binding

Inferred from physical interaction PubMed 10748098. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11131113Histone deacetylase 5
PRO_0000114702

Regions

Region675 – 1019345Histone deacetylase
Motif1072 – 111342Nuclear export signal By similarity
Compositional bias47 – 526Poly-Gly
Compositional bias85 – 928Poly-Gln
Compositional bias577 – 58812Poly-Glu

Sites

Active site8241 By similarity
Metal binding6871Zinc By similarity
Metal binding6891Zinc By similarity
Metal binding6951Zinc By similarity
Metal binding7721Zinc By similarity

Amino acid modifications

Modified residue2501Phosphoserine; by AMPK, CaMK1, SIK1 and PKD/PRKD1 Ref.8 Ref.11
Modified residue2831Phosphothreonine; by PKC By similarity
Modified residue4881Phosphoserine; by AMPK, CaMK1, SIK1 and PKD/PRKD1 Ref.8 Ref.11
Modified residue5231N6-acetyllysine By similarity
Modified residue6501Phosphoserine By similarity

Experimental info

Mutagenesis2501S → A: Abolishes phosphorylation by SIK1 and fails to promote beta-catenin expression; when associated with A-488. Ref.8 Ref.11
Mutagenesis4881S → A: Abolishes phosphorylation by SIK1 and fails to promote beta-catenin expression; when associated with A-250. Ref.8 Ref.11
Mutagenesis8241H → A: Abolishes deacetylase activity. Ref.3
Mutagenesis8841H → F: Disrupts the dot-like nuclear pattern. Ref.3
Sequence conflict71S → SA in AAF31418. Ref.2
Sequence conflict181G → E in AAF31418. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9Z2V6 [UniParc].

Last modified May 1, 2000. Version 2.
Checksum: 63071AF45B87815A

FASTA1,113120,942
        10         20         30         40         50         60 
MNSPNESDGM SGREPSLGIL PRTPLHSIPV AVEVKPVLPG AMPSSMGGGG GGSPSPVELR 

        70         80         90        100        110        120 
GALAGPMDPA LREQQLQQEL LVLKQQQQLQ KQLLFAEFQK QHDHLTRQHE VQLQKHLKQQ 

       130        140        150        160        170        180 
QEMLAAKRQQ ELEQQRQREQ QRQEELEKQR LEQQLLILRN KEKSKESAIA STEVKLRLQE 

       190        200        210        220        230        240 
FLLSKSKEPT PGGLNHSLPQ HPKCWGAHHA SLDQSSPPQS GPPGTPPSYK LPLLGPYDSR 

       250        260        270        280        290        300 
DDFPLRKTAS EPNLKVRSRL KQKVAERRSS PLLRRKDGTV ISTFKKRAVE ITGTGPGVSS 

       310        320        330        340        350        360 
VCNSAPGSGP SSPNSSHSTI AENGFTGSVP NIPTEMIPQH RALPLDSSPN QFSLYTSPSL 

       370        380        390        400        410        420 
PNISLGLQAT VTVTNSHLTA SPKLSTQQEA ERQALQSLRQ GGTLTGKFMS TSSIPGCLLG 

       430        440        450        460        470        480 
VALEGDTSPH GHASLLQHVC SWTGRQQSTL IAVPLHGQSP LVTGERVATS MRTVGKLPRH 

       490        500        510        520        530        540 
RPLSRTQSSP LPQSPQALQQ LVMQQQHQQF LEKQKQQQMQ LGKILTKTGE LSRQPTTHPE 

       550        560        570        580        590        600 
ETEEELTEQQ EALLGEGALT IPREGSTESE STQEDLEEEE EEEEEEEEDC IQVKDEDGES 

       610        620        630        640        650        660 
GPDEGPDLEE SSAGYKKLFA DAQQLQPLQV YQAPLSLATV PHQALGRTQS SPAAPGSMKS 

       670        680        690        700        710        720 
PTDQPTVVKH LFTTGVVYDT FMLKHQCMCG NTHVHPEHAG RIQSIWSRLQ ETGLLGKCER 

       730        740        750        760        770        780 
IRGRKATLDE IQTVHSEYHT LLYGTSPLNR QKLDSKKLLG PISQKMYAML PCGGIGVDSD 

       790        800        810        820        830        840 
TVWNEMHSSS AVRMAVGCLV ELAFKVAAGE LKNGFAIIRP PGHHAEESTA MGFCFFNSVA 

       850        860        870        880        890        900 
ITAKLLQQKL SVGKVLIVDW DIHHGNGTQQ AFYNDPSVLY ISLHRYDNGN FFPGSGAPEE 

       910        920        930        940        950        960 
VGGGPGVGYN VNVAWTGGVD PPIGDVEYLT AFRTVVMPIA QEFSPDVVLV SAGFDAVEGH 

       970        980        990       1000       1010       1020 
LSPLGGYSVT ARCFGHLTRQ LMTLAGGRVV LALEGGHDLT AICDASEACV SALLSVELQP 

      1030       1040       1050       1060       1070       1080 
LDEAVLQQKP SVNAVATLEK VIEIQSKHWS CVQRFAAGLG CSLREAQTGE KEEAETVSAM 

      1090       1100       1110 
ALLSVGAEQA QAVATQEHSP RPAEEPMEQE PAL 

« Hide

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]"Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression."
Kao H.-Y., Downes M., Ordentlich P., Evans R.M.
Genes Dev. 14:55-66(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH NCOR2.
Strain: C57BL/6.
[3]"Identification of a nuclear domain with deacetylase activity."
Downes M., Ordentlich P., Kao H.-Y., Alvarez J.G.A., Evans R.M.
Proc. Natl. Acad. Sci. U.S.A. 97:10330-10335(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HDAC7, NUCLEAR EXPORT, MUTAGENESIS OF HIS-824 AND HIS-884.
[4]"Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor."
Zhang C.L., McKinsey T.A., Lu J.R., Olson E.N.
J. Biol. Chem. 276:35-39(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CTBP1 AND HDAC9.
[5]"Transcriptional regulation by the repressor of estrogen receptor activity via recruitment of histone deacetylases."
Kurtev V., Margueron R., Kroboth K., Ogris E., Cavailles V., Seiser C.
J. Biol. Chem. 279:24834-24843(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PHB2.
[6]"Multiple domains of the receptor-interacting protein 140 contribute to transcription inhibition."
Castet A., Boulahtouf A., Versini G., Bonnet S., Augereau P., Vignon F., Khochbin S., Jalaguier S., Cavailles V.
Nucleic Acids Res. 32:1957-1966(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NRIP1.
[7]"Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin."
Cao D., Wang Z., Zhang C.L., Oh J., Xing W., Li S., Richardson J.A., Wang D.Z., Olson E.N.
Mol. Cell. Biol. 25:364-376(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MYOCD.
[8]"SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes."
Berdeaux R., Goebel N., Banaszynski L., Takemori H., Wandless T., Shelton G.D., Montminy M.
Nat. Med. 13:597-603(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-250 AND SER-488, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-250 AND SER-488.
[9]"Molecular mechanism of transcriptional repression of AhR repressor involving ANKRA2, HDAC4, and HDAC5."
Oshima M., Mimura J., Yamamoto M., Fujii-Kuriyama Y.
Biochem. Biophys. Res. Commun. 364:276-282(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AHRR.
[10]"Uncovering G protein-coupled receptor kinase-5 as a histone deacetylase kinase in the nucleus of cardiomyocytes."
Martini J.S., Raake P., Vinge L.E., DeGeorge B.R. Jr., Chuprun J.K., Harris D.M., Gao E., Eckhart A.D., Pitcher J.A., Koch W.J.
Proc. Natl. Acad. Sci. U.S.A. 105:12457-12462(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRK5, PHOSPHORYLATION.
[11]"AMP-activated protein kinase regulates beta-catenin transcription via histone deacetylase 5."
Zhao J.X., Yue W.F., Zhu M.J., Du M.
J. Biol. Chem. 286:16426-16434(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-250 AND SER-488, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-250 AND SER-488.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF006602 mRNA. Translation: AAD09834.2.
AF207748 mRNA. Translation: AAF31418.1.
UniGeneMm.22665.

3D structure databases

ProteinModelPortalQ9Z2V6.
SMRQ9Z2V6. Positions 68-132, 672-1052.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-40855N.
IntActQ9Z2V6. 4 interactions.
MINTMINT-125422.

Chemistry

BindingDBQ9Z2V6.
ChEMBLCHEMBL2768.

PTM databases

PhosphoSiteQ9Z2V6.

Proteomic databases

PaxDbQ9Z2V6.
PRIDEQ9Z2V6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

MGIMGI:1333784. Hdac5.

Phylogenomic databases

eggNOGCOG0123.
HOVERGENHBG057100.

Gene expression databases

CleanExMM_HDAC5.
GenevestigatorQ9Z2V6.

Family and domain databases

Gene3D3.40.800.20. 1 hit.
InterProIPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR024643. Hist_deacetylase_Gln_rich_N.
IPR017320. Histone_deAcase_II_euk.
[Graphical view]
PANTHERPTHR10625. PTHR10625. 1 hit.
PfamPF12203. HDAC4_Gln. 1 hit.
PF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFPIRSF037911. HDAC_II_euk. 1 hit.
PRINTSPR01270. HDASUPER.
ProtoNetSearch...

Other

ChiTaRSHDAC5. mouse.
PROQ9Z2V6.
SOURCESearch...

Entry information

Entry nameHDAC5_MOUSE
AccessionPrimary (citable) accession number: Q9Z2V6
Secondary accession number(s): Q9JL73
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 2000
Last modified: June 11, 2014
This is version 120 of the entry and version 2 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