GenomeNet

Database: UniProt/SWISS-PROT
Entry: HDAC4_RAT
LinkDB: HDAC4_RAT
Original site: HDAC4_RAT 
ID   HDAC4_RAT               Reviewed;        1077 AA.
AC   Q99P99;
DT   20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT   20-MAR-2007, sequence version 2.
DT   10-OCT-2018, entry version 112.
DE   RecName: Full=Histone deacetylase 4;
DE            Short=HD4;
DE            EC=3.5.1.98;
GN   Name=Hdac4;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T.,
RA   Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A.,
RA   Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M.,
RA   Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K.,
RA   Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S.,
RA   Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J.,
RA   Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y.,
RA   Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A.,
RA   Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J.,
RA   D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R.,
RA   Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A.,
RA   Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E.,
RA   Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E.,
RA   Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D.,
RA   Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M.,
RA   Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O.,
RA   Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O.,
RA   Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H.,
RA   Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S.,
RA   Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J.,
RA   Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E.,
RA   Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F.,
RA   Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K.,
RA   Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S.,
RA   Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M.,
RA   Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M.,
RA   Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A.,
RA   Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S.,
RA   Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G.,
RA   Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H.,
RA   Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R.,
RA   Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M.,
RA   Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H.,
RA   Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S.,
RA   Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into
RT   mammalian evolution.";
RL   Nature 428:493-521(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 55-208.
RC   STRAIN=Wistar; TISSUE=Testis;
RA   Wilquet V., Chavez M., Korbers R., Geerts A.;
RT   "Expression pattern of rat histone deacetylases.";
RL   Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   INTERACTION WITH BTBD14B.
RX   PubMed=16033423; DOI=10.1111/j.1471-4159.2005.03206.x;
RA   Korutla L., Wang P.J., Mackler S.A.;
RT   "The POZ/BTB protein NAC1 interacts with two different histone
RT   deacetylases in neuronal-like cultures.";
RL   J. Neurochem. 94:786-793(2005).
RN   [4]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-563 AND SER-630, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A.,
RA   Lundby C., Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14
RT   different rat organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: Responsible for the deacetylation of lysine residues on
CC       the N-terminal part of the core histones (H2A, H2B, H3 and H4).
CC       Histone deacetylation gives a tag for epigenetic repression and
CC       plays an important role in transcriptional regulation, cell cycle
CC       progression and developmental events. Histone deacetylases act via
CC       the formation of large multiprotein complexes. Involved in muscle
CC       maturation via its interaction with the myocyte enhancer factors
CC       such as MEF2A, MEF2C and MEF2D. Deacetylates HSPA1A and HSPA1B at
CC       'Lys-77' leading to their preferential binding to co-chaperone
CC       STUB1. {ECO:0000250|UniProtKB:P56524}.
CC   -!- CATALYTIC ACTIVITY: Hydrolysis of an N(6)-acetyl-lysine residue of
CC       a histone to yield a deacetylated histone.
CC   -!- SUBUNIT: Homodimer. Homodimerization via its N-terminal domain.
CC       Interacts with HDAC7. Interacts with MEF2A, MEF2C, MEF2D, MORC2
CC       and NR2C1. Interacts with a 14-3-3 chaperone protein in a
CC       phosphorylation dependent manner. Interacts with KDM5B and AHRR
CC       (By similarity). Interacts with BTBD14B (PubMed:16033423).
CC       Interacts with MYOCD. Interacts (via PxLPxI/L motif) with ANKRA2
CC       (via ankyrin repeats). Interacts with CUL7 (as part of the 3M
CC       complex); negatively regulated by ANKRA2. Interacts with EP300 in
CC       the presence of TFAP2C. Interacts with HSPA1A and HSPA1B leading
CC       to their deacetylation at 'Lys-77' (By similarity). Interacts with
CC       ZBTB7B; the interaction allows the recruitment of HDAC4 on CD8
CC       loci for deacetylation and possible inhibition of CD8 genes
CC       expression (By similarity). Interacts with DHX36 (By similarity).
CC       {ECO:0000250|UniProtKB:P56524, ECO:0000250|UniProtKB:Q6NZM9,
CC       ECO:0000269|PubMed:16033423}.
CC   -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Note=Shuttles between
CC       the nucleus and the cytoplasm. Upon muscle cells differentiation,
CC       it accumulates in the nuclei of myotubes, suggesting a positive
CC       role of nuclear HDAC4 in muscle differentiation. The export to
CC       cytoplasm depends on the interaction with a 14-3-3 chaperone
CC       protein and is due to its phosphorylation at Ser-245, Ser-466 and
CC       Ser-630 by CaMK4 and SIK1. The nuclear localization probably
CC       depends on sumoylation (By similarity). {ECO:0000250}.
CC   -!- DOMAIN: The nuclear export sequence mediates the shuttling between
CC       the nucleus and the cytoplasm. {ECO:0000250}.
CC   -!- DOMAIN: The PxLPxI/L motif mediates interaction with ankyrin
CC       repeats of ANKRA2. {ECO:0000250|UniProtKB:P56524}.
CC   -!- PTM: Phosphorylated by CaMK4 at Ser-245, Ser-466 and Ser-630.
CC       Phosphorylation at other residues by CaMK2D is required for the
CC       interaction with 14-3-3. Phosphorylation at Ser-349, within the
CC       PxLPxI/L motif, impairs the binding of ANKRA2 but generates a
CC       high-affinity docking site for 14-3-3 (By similarity).
CC       {ECO:0000250|UniProtKB:P56524}.
CC   -!- PTM: Sumoylation on Lys-557 is promoted by the E3 SUMO-protein
CC       ligase RANBP2, and prevented by phosphorylation by CaMK4.
CC   -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2
CC       subfamily. {ECO:0000305}.
DR   EMBL; AABR03067902; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR03068091; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AABR03070452; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AF321132; AAK11185.1; -; mRNA.
DR   RefSeq; NP_445901.1; NM_053449.1.
DR   UniGene; Rn.23483; -.
DR   ProteinModelPortal; Q99P99; -.
DR   SMR; Q99P99; -.
DR   BioGrid; 264106; 4.
DR   CORUM; Q99P99; -.
DR   STRING; 10116.ENSRNOP00000027622; -.
DR   BindingDB; Q99P99; -.
DR   ChEMBL; CHEMBL2095943; -.
DR   iPTMnet; Q99P99; -.
DR   PhosphoSitePlus; Q99P99; -.
DR   PaxDb; Q99P99; -.
DR   PRIDE; Q99P99; -.
DR   Ensembl; ENSRNOT00000027622; ENSRNOP00000027622; ENSRNOG00000020372.
DR   GeneID; 363287; -.
DR   KEGG; rno:363287; -.
DR   UCSC; RGD:619979; rat.
DR   CTD; 9759; -.
DR   RGD; 619979; Hdac4.
DR   eggNOG; KOG1343; Eukaryota.
DR   eggNOG; COG0123; LUCA.
DR   GeneTree; ENSGT00530000062809; -.
DR   HOGENOM; HOG000232065; -.
DR   HOVERGEN; HBG057100; -.
DR   InParanoid; Q99P99; -.
DR   KO; K11406; -.
DR   OMA; KCECIRG; -.
DR   OrthoDB; EOG091G0EQO; -.
DR   PhylomeDB; Q99P99; -.
DR   TreeFam; TF106174; -.
DR   Reactome; R-RNO-4090294; SUMOylation of intracellular receptors.
DR   Reactome; R-RNO-4551638; SUMOylation of chromatin organization proteins.
DR   Reactome; R-RNO-8951936; RUNX3 regulates p14-ARF.
DR   PRO; PR:Q99P99; -.
DR   Proteomes; UP000002494; Chromosome 9.
DR   Bgee; ENSRNOG00000020372; Expressed in 10 organ(s), highest expression level in skeletal muscle tissue.
DR   Genevisible; Q99P99; RN.
DR   GO; GO:0031672; C:A band; IDA:MGI.
DR   GO; GO:0042641; C:actomyosin; IEA:Ensembl.
DR   GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR   GO; GO:0005829; C:cytosol; IDA:RGD.
DR   GO; GO:0000118; C:histone deacetylase complex; IEA:Ensembl.
DR   GO; GO:0031594; C:neuromuscular junction; IEA:Ensembl.
DR   GO; GO:0005634; C:nucleus; IDA:RGD.
DR   GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR   GO; GO:0030017; C:sarcomere; IDA:MGI.
DR   GO; GO:0017053; C:transcriptional repressor complex; IEA:Ensembl.
DR   GO; GO:0030018; C:Z disc; IDA:MGI.
DR   GO; GO:0033613; F:activating transcription factor binding; IEA:Ensembl.
DR   GO; GO:0004407; F:histone deacetylase activity; IMP:RGD.
DR   GO; GO:0042826; F:histone deacetylase binding; IEA:Ensembl.
DR   GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR   GO; GO:0032041; F:NAD-dependent histone deacetylase activity (H3-K14 specific); IEA:UniProtKB-EC.
DR   GO; GO:0030955; F:potassium ion binding; IEA:Ensembl.
DR   GO; GO:1990841; F:promoter-specific chromatin binding; IDA:RGD.
DR   GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR   GO; GO:0070491; F:repressing transcription factor binding; IEA:Ensembl.
DR   GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; IEA:Ensembl.
DR   GO; GO:0001085; F:RNA polymerase II transcription factor binding; IEA:Ensembl.
DR   GO; GO:0003714; F:transcription corepressor activity; IEA:Ensembl.
DR   GO; GO:0008134; F:transcription factor binding; IPI:RGD.
DR   GO; GO:0008270; F:zinc ion binding; IEA:Ensembl.
DR   GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR   GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEP:RGD.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IEP:RGD.
DR   GO; GO:0006338; P:chromatin remodeling; IEA:Ensembl.
DR   GO; GO:0016575; P:histone deacetylation; IMP:RGD.
DR   GO; GO:0070933; P:histone H4 deacetylation; IEA:Ensembl.
DR   GO; GO:0008285; P:negative regulation of cell proliferation; IEA:Ensembl.
DR   GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR   GO; GO:0045820; P:negative regulation of glycolytic process; IEA:Ensembl.
DR   GO; GO:0010832; P:negative regulation of myotube differentiation; IEA:Ensembl.
DR   GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl.
DR   GO; GO:1902894; P:negative regulation of pri-miRNA transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0002076; P:osteoblast development; IEA:Ensembl.
DR   GO; GO:0034983; P:peptidyl-lysine deacetylation; IEA:Ensembl.
DR   GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR   GO; GO:0010592; P:positive regulation of lamellipodium assembly; IMP:RGD.
DR   GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR   GO; GO:0033235; P:positive regulation of protein sumoylation; IEA:Ensembl.
DR   GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; IMP:RGD.
DR   GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
DR   GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR   GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; IEA:Ensembl.
DR   GO; GO:0040029; P:regulation of gene expression, epigenetic; IEA:Ensembl.
DR   GO; GO:0043393; P:regulation of protein binding; IEA:Ensembl.
DR   GO; GO:0048742; P:regulation of skeletal muscle fiber development; IEA:Ensembl.
DR   GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; IEA:Ensembl.
DR   GO; GO:0042493; P:response to drug; IDA:RGD.
DR   GO; GO:0070555; P:response to interleukin-1; IEA:Ensembl.
DR   GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR   GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.800.20; -; 1.
DR   InterPro; IPR033660; HDAC4.
DR   InterPro; IPR000286; His_deacetylse.
DR   InterPro; IPR023801; His_deacetylse_dom.
DR   InterPro; IPR037138; His_deacetylse_dom_sf.
DR   InterPro; IPR024643; Hist_deacetylase_Gln_rich_N.
DR   InterPro; IPR017320; Histone_deAcase_II_euk.
DR   InterPro; IPR023696; Ureohydrolase_dom_sf.
DR   PANTHER; PTHR10625; PTHR10625; 1.
DR   PANTHER; PTHR10625:SF100; PTHR10625:SF100; 1.
DR   Pfam; PF12203; HDAC4_Gln; 1.
DR   Pfam; PF00850; Hist_deacetyl; 1.
DR   PIRSF; PIRSF037911; HDAC_II_euk; 1.
DR   PRINTS; PR01270; HDASUPER.
DR   SUPFAM; SSF52768; SSF52768; 1.
PE   1: Evidence at protein level;
KW   Chromatin regulator; Coiled coil; Complete proteome; Cytoplasm;
KW   Hydrolase; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW   Reference proteome; Repressor; Transcription;
KW   Transcription regulation; Ubl conjugation; Zinc.
FT   CHAIN         1   1077       Histone deacetylase 4.
FT                                /FTId=PRO_0000281034.
FT   REGION      117    312       Interaction with MEF2A. {ECO:0000250}.
FT   REGION      653   1077       Histone deacetylase. {ECO:0000250}.
FT   COILED       66    169       {ECO:0000255}.
FT   MOTIF       348    353       PxLPxI/L motif; mediates interaction with
FT                                ANKRA2 and 14-3-3 proteins.
FT                                {ECO:0000250|UniProtKB:P56524}.
FT   MOTIF      1044   1077       Nuclear export signal. {ECO:0000250}.
FT   COMPBIAS    465    500       Gln-rich.
FT   COMPBIAS    562    569       Poly-Glu.
FT   ACT_SITE    796    796       {ECO:0000250}.
FT   METAL       665    665       Zinc. {ECO:0000250}.
FT   METAL       667    667       Zinc. {ECO:0000250}.
FT   METAL       673    673       Zinc. {ECO:0000250}.
FT   METAL       744    744       Zinc. {ECO:0000250}.
FT   MOD_RES     209    209       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q6NZM9}.
FT   MOD_RES     245    245       Phosphoserine; by CaMK4 and SIK1.
FT                                {ECO:0000250|UniProtKB:P56524}.
FT   MOD_RES     349    349       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P56524}.
FT   MOD_RES     466    466       Phosphoserine; by CaMK4 and SIK1.
FT                                {ECO:0000250|UniProtKB:P56524}.
FT   MOD_RES     563    563       Phosphoserine.
FT                                {ECO:0000244|PubMed:22673903}.
FT   MOD_RES     630    630       Phosphoserine.
FT                                {ECO:0000244|PubMed:22673903}.
FT   MOD_RES     631    631       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:P56524}.
FT   CROSSLNK    557    557       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO).
FT                                {ECO:0000250}.
SQ   SEQUENCE   1077 AA;  118652 MW;  88127299D9962DBA CRC64;
     MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPAAVPMD LRLDHQFSLP
     LEPALREQQL QQELLALKQK QQIQRQILIA EFQRQHEQLS RQHEAQLHEH IKQQQEMLAM
     KHQQELLEHQ RKLERHRQEQ ELEKQHREQK LQQLKNKEKG KESAVASTEV KMKLQEFVLN
     KKKALAHRNL NHCMSSDPRY WYGKTQHSSL DQSSPPQSGV SASYNHPVLG MYDAKDDFPL
     RKTASEPNLK LRSRLKQKVA ERRSSPLLRR KDGPVATALK KRPLDVTDSA CSSAPGSGPS
     SPNSSSGNVS TENGIAPTVP STPAETSLAH RLVTREGSVA PLPLYTSPSL PNITLGLPAT
     GPAAGAAGQQ DAERLALPAL QQRISLFPGT HLTPYLSTSP LERDGGAAHN PLLQHMVLLE
     QPPTQTPLVT GLGALPLHTQ SLVGADRVSP SIHKLRQHRP LGRTQSAPLP QNAQALQHLV
     IQQQHQQFLE KHKQQFQQQQ LHLSKMISKP SEPPRQPESH PEETEEELRE HQALLDEPYL
     DRLPGQKEPS LAGVQVKQEP IESEEEEVEA TREAEPSQRP ATEQELLFRQ QALLLEQQRI
     HQLRNYQASM EAAGIPVSFG SHRPLSRAQS SPASATFPMS VQEPPTKPRF TTGLVYDTLM
     LKHQCTCGNT NSHPEHAGRI QSIWSRLQET GLRGKCECIR GRKATLEELQ TVHSEAHTLL
     YGTNPLNRQK LDSSLTSVFV RLPCGGVGVD SDTIWNEVHS SGAARLAVGC VVELVFKVAT
     GELKNGFAVV RPPGHHAEES TPMGFCYFNS VAIAAKLLQQ RLNVSKILIV DWDVHHGNGT
     QQAFYNDPNV LYMSLHRYDD GNFFPGSGAP DEVGTGPGVG FNVNMAFTGG LDPPMGDAEY
     LAAFRTVVMP IANEFAPDVV LVSSGFDAVE GHPTPLGGYN LSAKCFGYLT KQLMGLAGGR
     IVLALEGGHD LTAICDASEA CVSALLGNEL EPLPEKVLHQ RPNANAVHSM EKVMGIHSEY
     WRCLQRLSPT VGHSLIEAQK CENEEAETVT AMASLSVGVK PAEKRSEEEP MEEEPPL
//
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