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Q99P99 (HDAC4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 76. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | 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 4

Short name=HD4
EC=3.5.1.98
Gene names
Name:Hdac4
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1077 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 via its interaction with the myocyte enhancer factors such as MEF2A, MEF2C and MEF2D By similarity.

Catalytic activity

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

Subunit structure

Interacts with HDAC7. Homodimer By similarity. Homodimerization via its N-terminal domain. Interacts with MEF2C and NR2C1. Interacts with a 14-3-3 chaperone protein in a phosphorylation dependent manner. Interacts with KDM5B and AHRR By similarity. Interacts with BTBD14B. Interacts with MYOCD. Interacts with ANKRA2 By similarity. Ref.3

Subcellular location

Nucleus. Cytoplasm. Note: Shuttles between the nucleus and the cytoplasm. Upon muscle cells differentiation, it accumulates in the nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in muscle differentiation. The export to cytoplasm depends on the interaction with a 14-3-3 chaperone protein and is due to its phosphorylation at Ser-245, Ser-466 and Ser-630 by CaMK4 and SIK1. The nuclear localization probably depends on sumoylation By similarity.

Domain

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

Post-translational modification

Phosphorylated by CaMK4 at Ser-245, Ser-466 and Ser-630. Phosphorylation at other residues by CaMK2D is required for the interaction with 14-3-3. Phosphorylation at Ser-349 impairs the binding of ANKRA2 but generates a high-affinity docking site for 14-3-3 By similarity.

Sumoylation on Lys-557 is promoted by the E3 SUMO-protein ligase RANBP2, and prevented by phosphorylation by CaMK4.

Sequence similarities

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

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DomainCoiled coil
   LigandMetal-binding
Zinc
   Molecular functionChromatin regulator
Hydrolase
Repressor
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchromatin remodeling

Inferred from electronic annotation. Source: Ensembl

histone deacetylation

Inferred from mutant phenotype PubMed 21586557. Source: RGD

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of glycolytic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of myotube differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of osteoblast differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

osteoblast development

Inferred from electronic annotation. Source: Ensembl

peptidyl-lysine deacetylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein sumoylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

regulation of cardiac muscle contraction by calcium ion signaling

Inferred from electronic annotation. Source: Ensembl

regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

regulation of skeletal muscle fiber development

Inferred from electronic annotation. Source: Ensembl

response to denervation involved in regulation of muscle adaptation

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from direct assay PubMed 16767219. Source: RGD

response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

skeletal system development

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentA band

Inferred from direct assay PubMed 18250163. Source: MGI

Z disc

Inferred from direct assay PubMed 18250163. Source: MGI

actomyosin

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 16767219. Source: RGD

cytosol

Inferred from direct assay PubMed 22360269. Source: RGD

histone deacetylase complex

Inferred from electronic annotation. Source: Ensembl

neuromuscular junction

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 16767219PubMed 22360269. Source: RGD

protein complex

Inferred from direct assay PubMed 22360269. Source: RGD

sarcomere

Inferred from direct assay PubMed 18250163. Source: MGI

transcriptional repressor complex

Inferred from electronic annotation. Source: Ensembl

   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

core promoter binding

Inferred from direct assay PubMed 21586557. Source: RGD

histone deacetylase activity

Inferred from mutant phenotype PubMed 21586557. Source: RGD

potassium ion binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 21464227. Source: RGD

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

transcription corepressor activity

Inferred from electronic annotation. Source: Ensembl

zinc ion binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10771077Histone deacetylase 4
PRO_0000281034

Regions

Region117 – 312196Interaction with MEF2A By similarity
Region653 – 1077425Histone deacetylase By similarity
Coiled coil66 – 169104 Potential
Motif1044 – 107734Nuclear export signal By similarity
Compositional bias465 – 50036Gln-rich
Compositional bias562 – 5698Poly-Glu

Sites

Active site7961 By similarity
Metal binding6651Zinc By similarity
Metal binding6671Zinc By similarity
Metal binding6731Zinc By similarity
Metal binding7441Zinc By similarity

Amino acid modifications

Modified residue2451Phosphoserine; by CaMK4 and SIK1 By similarity
Modified residue3491Phosphoserine By similarity
Modified residue4661Phosphoserine; by CaMK4 and SIK1 By similarity
Modified residue5631Phosphoserine By similarity
Modified residue6301Phosphoserine; by CaMK4 By similarity
Modified residue6311Phosphoserine By similarity
Cross-link557Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) By similarity

Sequences

Sequence LengthMass (Da)Tools
Q99P99 [UniParc].

Last modified March 20, 2007. Version 2.
Checksum: 88127299D9962DBA

FASTA1,077118,652
        10         20         30         40         50         60 
MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPAAVPMD LRLDHQFSLP 

        70         80         90        100        110        120 
LEPALREQQL QQELLALKQK QQIQRQILIA EFQRQHEQLS RQHEAQLHEH IKQQQEMLAM 

       130        140        150        160        170        180 
KHQQELLEHQ RKLERHRQEQ ELEKQHREQK LQQLKNKEKG KESAVASTEV KMKLQEFVLN 

       190        200        210        220        230        240 
KKKALAHRNL NHCMSSDPRY WYGKTQHSSL DQSSPPQSGV SASYNHPVLG MYDAKDDFPL 

       250        260        270        280        290        300 
RKTASEPNLK LRSRLKQKVA ERRSSPLLRR KDGPVATALK KRPLDVTDSA CSSAPGSGPS 

       310        320        330        340        350        360 
SPNSSSGNVS TENGIAPTVP STPAETSLAH RLVTREGSVA PLPLYTSPSL PNITLGLPAT 

       370        380        390        400        410        420 
GPAAGAAGQQ DAERLALPAL QQRISLFPGT HLTPYLSTSP LERDGGAAHN PLLQHMVLLE 

       430        440        450        460        470        480 
QPPTQTPLVT GLGALPLHTQ SLVGADRVSP SIHKLRQHRP LGRTQSAPLP QNAQALQHLV 

       490        500        510        520        530        540 
IQQQHQQFLE KHKQQFQQQQ LHLSKMISKP SEPPRQPESH PEETEEELRE HQALLDEPYL 

       550        560        570        580        590        600 
DRLPGQKEPS LAGVQVKQEP IESEEEEVEA TREAEPSQRP ATEQELLFRQ QALLLEQQRI 

       610        620        630        640        650        660 
HQLRNYQASM EAAGIPVSFG SHRPLSRAQS SPASATFPMS VQEPPTKPRF TTGLVYDTLM 

       670        680        690        700        710        720 
LKHQCTCGNT NSHPEHAGRI QSIWSRLQET GLRGKCECIR GRKATLEELQ TVHSEAHTLL 

       730        740        750        760        770        780 
YGTNPLNRQK LDSSLTSVFV RLPCGGVGVD SDTIWNEVHS SGAARLAVGC VVELVFKVAT 

       790        800        810        820        830        840 
GELKNGFAVV RPPGHHAEES TPMGFCYFNS VAIAAKLLQQ RLNVSKILIV DWDVHHGNGT 

       850        860        870        880        890        900 
QQAFYNDPNV LYMSLHRYDD GNFFPGSGAP DEVGTGPGVG FNVNMAFTGG LDPPMGDAEY 

       910        920        930        940        950        960 
LAAFRTVVMP IANEFAPDVV LVSSGFDAVE GHPTPLGGYN LSAKCFGYLT KQLMGLAGGR 

       970        980        990       1000       1010       1020 
IVLALEGGHD LTAICDASEA CVSALLGNEL EPLPEKVLHQ RPNANAVHSM EKVMGIHSEY 

      1030       1040       1050       1060       1070 
WRCLQRLSPT VGHSLIEAQK CENEEAETVT AMASLSVGVK PAEKRSEEEP MEEEPPL 

« Hide

References

« Hide 'large scale' references
[1]"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. expand/collapse author list , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
[2]"Expression pattern of rat histone deacetylases."
Wilquet V., Chavez M., Korbers R., Geerts A.
Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 55-208.
Strain: Wistar.
Tissue: Testis.
[3]"The POZ/BTB protein NAC1 interacts with two different histone deacetylases in neuronal-like cultures."
Korutla L., Wang P.J., Mackler S.A.
J. Neurochem. 94:786-793(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH BTBD14B.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AABR03067902 Genomic DNA. No translation available.
AABR03068091 Genomic DNA. No translation available.
AABR03070452 Genomic DNA. No translation available.
AF321132 mRNA. Translation: AAK11185.1.
RefSeqNP_445901.1. NM_053449.1.
UniGeneRn.23483.

3D structure databases

ProteinModelPortalQ99P99.
SMRQ99P99. Positions 62-128, 648-1044.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid264106. 4 interactions.

Chemistry

BindingDBQ99P99.
ChEMBLCHEMBL2095943.

PTM databases

PhosphoSiteQ99P99.

Proteomic databases

PaxDbQ99P99.
PRIDEQ99P99.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000027622; ENSRNOP00000027622; ENSRNOG00000020372.
GeneID363287.
KEGGrno:363287.
UCSCRGD:619979. rat.

Organism-specific databases

CTD9759.
RGD619979. Hdac4.

Phylogenomic databases

eggNOGCOG0123.
GeneTreeENSGT00530000062809.
HOGENOMHOG000232065.
HOVERGENHBG057100.
InParanoidQ99P99.
KOK11406.
OMAVSFGGHR.
OrthoDBEOG7RFTH5.
PhylomeDBQ99P99.
TreeFamTF106174.

Gene expression databases

GenevestigatorQ99P99.

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

NextBio683134.
PROQ99P99.

Entry information

Entry nameHDAC4_RAT
AccessionPrimary (citable) accession number: Q99P99
Entry history
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 20, 2007
Last modified: June 11, 2014
This is version 76 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