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Protein

Histone deacetylase 4

Gene

Hdac4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi665 – 6651ZincBy similarity
Metal bindingi667 – 6671ZincBy similarity
Metal bindingi673 – 6731ZincBy similarity
Metal bindingi744 – 7441ZincBy similarity
Active sitei796 – 7961By similarity

GO - Molecular functioni

  1. core promoter binding Source: RGD
  2. histone deacetylase activity Source: RGD
  3. NAD-dependent histone deacetylase activity (H3-K14 specific) Source: UniProtKB-EC
  4. NAD-dependent histone deacetylase activity (H3-K18 specific) Source: UniProtKB-EC
  5. NAD-dependent histone deacetylase activity (H3-K9 specific) Source: UniProtKB-EC
  6. NAD-dependent histone deacetylase activity (H4-K16 specific) Source: UniProtKB-EC
  7. potassium ion binding Source: Ensembl
  8. sequence-specific DNA binding Source: Ensembl
  9. transcription corepressor activity Source: Ensembl
  10. transcription factor binding Source: RGD
  11. zinc ion binding Source: Ensembl

GO - Biological processi

  1. cellular response to mechanical stimulus Source: RGD
  2. cellular response to parathyroid hormone stimulus Source: RGD
  3. cellular response to tumor necrosis factor Source: RGD
  4. chromatin remodeling Source: Ensembl
  5. histone deacetylation Source: RGD
  6. negative regulation of cell proliferation Source: Ensembl
  7. negative regulation of glycolytic process Source: Ensembl
  8. negative regulation of myotube differentiation Source: Ensembl
  9. negative regulation of osteoblast differentiation Source: Ensembl
  10. negative regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  11. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  12. osteoblast development Source: Ensembl
  13. peptidyl-lysine deacetylation Source: Ensembl
  14. positive regulation of lamellipodium assembly Source: RGD
  15. positive regulation of neuron apoptotic process Source: RGD
  16. positive regulation of protein sumoylation Source: Ensembl
  17. positive regulation of reactive oxygen species biosynthetic process Source: RGD
  18. positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  19. positive regulation of smooth muscle cell migration Source: RGD
  20. positive regulation of smooth muscle cell proliferation Source: RGD
  21. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  22. regulation of cardiac muscle contraction by calcium ion signaling Source: Ensembl
  23. regulation of gene expression, epigenetic Source: Ensembl
  24. regulation of protein binding Source: Ensembl
  25. regulation of skeletal muscle fiber development Source: Ensembl
  26. response to denervation involved in regulation of muscle adaptation Source: Ensembl
  27. response to drug Source: RGD
  28. response to interleukin-1 Source: Ensembl
  29. skeletal system development Source: Ensembl
  30. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Hydrolase, Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Histone deacetylase 4 (EC:3.5.1.98)
Short name:
HD4
Gene namesi
Name:Hdac4
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 9

Organism-specific databases

RGDi619979. Hdac4.

Subcellular locationi

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).By similarity

GO - Cellular componenti

  1. A band Source: MGI
  2. actomyosin Source: Ensembl
  3. cytoplasm Source: RGD
  4. cytosol Source: RGD
  5. histone deacetylase complex Source: InterPro
  6. neuromuscular junction Source: Ensembl
  7. nucleus Source: RGD
  8. protein complex Source: RGD
  9. sarcomere Source: MGI
  10. transcriptional repressor complex Source: Ensembl
  11. Z disc Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10771077Histone deacetylase 4PRO_0000281034Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei245 – 2451Phosphoserine; by CaMK4 and SIK1By similarity
Modified residuei349 – 3491PhosphoserineBy similarity
Modified residuei466 – 4661Phosphoserine; by CaMK4 and SIK1By similarity
Cross-linki557 – 557Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)By similarity
Modified residuei563 – 5631PhosphoserineBy similarity
Modified residuei630 – 6301Phosphoserine; by CaMK4By similarity
Modified residuei631 – 6311PhosphoserineBy similarity

Post-translational modificationi

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

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ99P99.
PRIDEiQ99P99.

PTM databases

PhosphoSiteiQ99P99.

Expressioni

Gene expression databases

GenevestigatoriQ99P99.

Interactioni

Subunit structurei

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. Interacts with EP300 in the presence of TFAP2C (By similarity).By similarity

Protein-protein interaction databases

BioGridi264106. 4 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ99P99.
SMRiQ99P99. Positions 62-128, 648-1044.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni117 – 312196Interaction with MEF2ABy similarityAdd
BLAST
Regioni653 – 1077425Histone deacetylaseBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili66 – 169104Sequence AnalysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1044 – 107734Nuclear export signalBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi465 – 50036Gln-richAdd
BLAST
Compositional biasi562 – 5698Poly-Glu

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiCOG0123.
GeneTreeiENSGT00530000062809.
HOGENOMiHOG000232065.
HOVERGENiHBG057100.
InParanoidiQ99P99.
KOiK11406.
OMAiDHQFSMP.
OrthoDBiEOG7RFTH5.
PhylomeDBiQ99P99.
TreeFamiTF106174.

Family and domain databases

Gene3Di3.40.800.20. 1 hit.
InterProiIPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR024643. Hist_deacetylase_Gln_rich_N.
IPR017320. Histone_deAcase_II_euk.
[Graphical view]
PANTHERiPTHR10625. PTHR10625. 1 hit.
PfamiPF12203. HDAC4_Gln. 1 hit.
PF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFiPIRSF037911. HDAC_II_euk. 1 hit.
PRINTSiPR01270. HDASUPER.

Sequencei

Sequence statusi: Complete.

Q99P99-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPAAVPMD
60 70 80 90 100
LRLDHQFSLP LEPALREQQL QQELLALKQK QQIQRQILIA EFQRQHEQLS
110 120 130 140 150
RQHEAQLHEH IKQQQEMLAM KHQQELLEHQ RKLERHRQEQ ELEKQHREQK
160 170 180 190 200
LQQLKNKEKG KESAVASTEV KMKLQEFVLN KKKALAHRNL NHCMSSDPRY
210 220 230 240 250
WYGKTQHSSL DQSSPPQSGV SASYNHPVLG MYDAKDDFPL RKTASEPNLK
260 270 280 290 300
LRSRLKQKVA ERRSSPLLRR KDGPVATALK KRPLDVTDSA CSSAPGSGPS
310 320 330 340 350
SPNSSSGNVS TENGIAPTVP STPAETSLAH RLVTREGSVA PLPLYTSPSL
360 370 380 390 400
PNITLGLPAT GPAAGAAGQQ DAERLALPAL QQRISLFPGT HLTPYLSTSP
410 420 430 440 450
LERDGGAAHN PLLQHMVLLE QPPTQTPLVT GLGALPLHTQ SLVGADRVSP
460 470 480 490 500
SIHKLRQHRP LGRTQSAPLP QNAQALQHLV IQQQHQQFLE KHKQQFQQQQ
510 520 530 540 550
LHLSKMISKP SEPPRQPESH PEETEEELRE HQALLDEPYL DRLPGQKEPS
560 570 580 590 600
LAGVQVKQEP IESEEEEVEA TREAEPSQRP ATEQELLFRQ QALLLEQQRI
610 620 630 640 650
HQLRNYQASM EAAGIPVSFG SHRPLSRAQS SPASATFPMS VQEPPTKPRF
660 670 680 690 700
TTGLVYDTLM LKHQCTCGNT NSHPEHAGRI QSIWSRLQET GLRGKCECIR
710 720 730 740 750
GRKATLEELQ TVHSEAHTLL YGTNPLNRQK LDSSLTSVFV RLPCGGVGVD
760 770 780 790 800
SDTIWNEVHS SGAARLAVGC VVELVFKVAT GELKNGFAVV RPPGHHAEES
810 820 830 840 850
TPMGFCYFNS VAIAAKLLQQ RLNVSKILIV DWDVHHGNGT QQAFYNDPNV
860 870 880 890 900
LYMSLHRYDD GNFFPGSGAP DEVGTGPGVG FNVNMAFTGG LDPPMGDAEY
910 920 930 940 950
LAAFRTVVMP IANEFAPDVV LVSSGFDAVE GHPTPLGGYN LSAKCFGYLT
960 970 980 990 1000
KQLMGLAGGR IVLALEGGHD LTAICDASEA CVSALLGNEL EPLPEKVLHQ
1010 1020 1030 1040 1050
RPNANAVHSM EKVMGIHSEY WRCLQRLSPT VGHSLIEAQK CENEEAETVT
1060 1070
AMASLSVGVK PAEKRSEEEP MEEEPPL
Length:1,077
Mass (Da):118,652
Last modified:March 20, 2007 - v2
Checksum:i88127299D9962DBA
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03067902 Genomic DNA. No translation available.
AABR03068091 Genomic DNA. No translation available.
AABR03070452 Genomic DNA. No translation available.
AF321132 mRNA. Translation: AAK11185.1.
RefSeqiNP_445901.1. NM_053449.1.
UniGeneiRn.23483.

Genome annotation databases

EnsembliENSRNOT00000027622; ENSRNOP00000027622; ENSRNOG00000020372.
GeneIDi363287.
KEGGirno:363287.
UCSCiRGD:619979. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03067902 Genomic DNA. No translation available.
AABR03068091 Genomic DNA. No translation available.
AABR03070452 Genomic DNA. No translation available.
AF321132 mRNA. Translation: AAK11185.1.
RefSeqiNP_445901.1. NM_053449.1.
UniGeneiRn.23483.

3D structure databases

ProteinModelPortaliQ99P99.
SMRiQ99P99. Positions 62-128, 648-1044.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi264106. 4 interactions.

Chemistry

ChEMBLiCHEMBL2095943.

PTM databases

PhosphoSiteiQ99P99.

Proteomic databases

PaxDbiQ99P99.
PRIDEiQ99P99.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000027622; ENSRNOP00000027622; ENSRNOG00000020372.
GeneIDi363287.
KEGGirno:363287.
UCSCiRGD:619979. rat.

Organism-specific databases

CTDi9759.
RGDi619979. Hdac4.

Phylogenomic databases

eggNOGiCOG0123.
GeneTreeiENSGT00530000062809.
HOGENOMiHOG000232065.
HOVERGENiHBG057100.
InParanoidiQ99P99.
KOiK11406.
OMAiDHQFSMP.
OrthoDBiEOG7RFTH5.
PhylomeDBiQ99P99.
TreeFamiTF106174.

Miscellaneous databases

NextBioi683134.
PROiQ99P99.

Gene expression databases

GenevestigatoriQ99P99.

Family and domain databases

Gene3Di3.40.800.20. 1 hit.
InterProiIPR000286. His_deacetylse.
IPR023801. His_deacetylse_dom.
IPR024643. Hist_deacetylase_Gln_rich_N.
IPR017320. Histone_deAcase_II_euk.
[Graphical view]
PANTHERiPTHR10625. PTHR10625. 1 hit.
PfamiPF12203. HDAC4_Gln. 1 hit.
PF00850. Hist_deacetyl. 1 hit.
[Graphical view]
PIRSFiPIRSF037911. HDAC_II_euk. 1 hit.
PRINTSiPR01270. HDASUPER.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiHDAC4_RAT
AccessioniPrimary (citable) accession number: Q99P99
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 20, 2007
Last sequence update: March 20, 2007
Last modified: March 4, 2015
This is version 82 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.