HDAC4_MOUSE
ID HDAC4_MOUSE Reviewed; 1076 AA.
AC Q6NZM9; Q3TRZ9; Q3U2J3; Q3V3Y4;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Histone deacetylase 4;
DE Short=HD4;
DE EC=3.5.1.98;
GN Name=Hdac4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Dendritic cell, Epididymis, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH HDAC7.
RX PubMed=10984530; DOI=10.1073/pnas.97.19.10330;
RA Downes M., Ordentlich P., Kao H.-Y., Alvarez J.G.A., Evans R.M.;
RT "Identification of a nuclear domain with deacetylase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:10330-10335(2000).
RN [4]
RP INTERACTION WITH MYOCD.
RX PubMed=15601857; DOI=10.1128/mcb.25.1.364-376.2005;
RA Cao D., Wang Z., Zhang C.L., Oh J., Xing W., Li S., Richardson J.A.,
RA Wang D.Z., Olson E.N.;
RT "Modulation of smooth muscle gene expression by association of histone
RT acetyltransferases and deacetylases with myocardin.";
RL Mol. Cell. Biol. 25:364-376(2005).
RN [5]
RP INTERACTION WITH AHRR.
RX PubMed=17949687; DOI=10.1016/j.bbrc.2007.09.131;
RA Oshima M., Mimura J., Yamamoto M., Fujii-Kuriyama Y.;
RT "Molecular mechanism of transcriptional repression of AhR repressor
RT involving ANKRA2, HDAC4, and HDAC5.";
RL Biochem. Biophys. Res. Commun. 364:276-282(2007).
RN [6]
RP PHOSPHORYLATION BY CAMK2D.
RX PubMed=17923476; DOI=10.1074/jbc.m707083200;
RA Zhang T., Kohlhaas M., Backs J., Mishra S., Phillips W., Dybkova N.,
RA Chang S., Ling H., Bers D.M., Maier L.S., Olson E.N., Brown J.H.;
RT "CaMKIIdelta isoforms differentially affect calcium handling but similarly
RT regulate HDAC/MEF2 transcriptional responses.";
RL J. Biol. Chem. 282:35078-35087(2007).
RN [7]
RP PHOSPHORYLATION AT SER-245 AND SER-465.
RX PubMed=17468767; DOI=10.1038/nm1573;
RA Berdeaux R., Goebel N., Banaszynski L., Takemori H., Wandless T.,
RA Shelton G.D., Montminy M.;
RT "SIK1 is a class II HDAC kinase that promotes survival of skeletal
RT myocytes.";
RL Nat. Med. 13:597-603(2007).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-465, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-209 AND SER-562, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP INTERACTION WITH DHX36.
RX PubMed=21590736; DOI=10.1002/jbmr.426;
RA Kim H.N., Lee J.H., Bae S.C., Ryoo H.M., Kim H.H., Ha H., Lee Z.H.;
RT "Histone deacetylase inhibitor MS-275 stimulates bone formation in part by
RT enhancing Dhx36-mediated TNAP transcription.";
RL J. Bone Miner. Res. 26:2161-2173(2011).
RN [11]
RP INTERACTION WITH SIK3, AND SUBCELLULAR LOCATION.
RX PubMed=22318228; DOI=10.1242/dev.072652;
RA Sasagawa S., Takemori H., Uebi T., Ikegami D., Hiramatsu K., Ikegawa S.,
RA Yoshikawa H., Tsumaki N.;
RT "SIK3 is essential for chondrocyte hypertrophy during skeletal development
RT in mice.";
RL Development 139:1153-1163(2012).
RN [12]
RP INTERACTION WITH ZBTB7B.
RX PubMed=22730529; DOI=10.4049/jimmunol.1201077;
RA Rui J., Liu H., Zhu X., Cui Y., Liu X.;
RT "Epigenetic silencing of CD8 genes by ThPOK-mediated deacetylation during
RT CD4 T cell differentiation.";
RL J. Immunol. 189:1380-1390(2012).
CC -!- FUNCTION: Responsible for the deacetylation of lysine residues on the
CC N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone
CC deacetylation gives a tag for epigenetic repression and plays an
CC important role in transcriptional regulation, cell cycle progression
CC and developmental events. Histone deacetylases act via the formation of
CC large multiprotein complexes. Involved in muscle maturation via its
CC interaction with the myocyte enhancer factors such as MEF2A, MEF2C and
CC MEF2D. Deacetylates HSPA1A and HSPA1A at 'Lys-77' leading to their
CC preferential binding to co-chaperone STUB1.
CC {ECO:0000250|UniProtKB:P56524}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[histone] = acetate + L-lysyl-
CC [histone]; Xref=Rhea:RHEA:58196, Rhea:RHEA-COMP:9845, Rhea:RHEA-
CC COMP:11338, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:61930; EC=3.5.1.98;
CC -!- SUBUNIT: Homodimer. Homodimerization via its N-terminal domain (By
CC similarity). Interacts with HDAC7 (PubMed:10984530). Interacts with
CC MEF2A, MEF2C, MEF2D, MORC2 and NR2C1. Interacts with a 14-3-3 chaperone
CC protein in a phosphorylation dependent manner. Interacts with BTBD14B.
CC Interacts with KDM5B. Interacts (via PxLPxI/L motif) with ANKRA2 (via
CC ankyrin repeats). Interacts with CUL7 (as part of the 3M complex);
CC negatively regulated by ANKRA2. Interacts with EP300 in the presence of
CC TFAP2C (By similarity). Interacts with AHRR (PubMed:17949687).
CC Interacts with MYOCD (PubMed:15601857). Interacts with HSPA1A and
CC HSPA1B leading to their deacetylation at 'Lys-77' (By similarity).
CC Interacts with ZBTB7B; the interaction allows the recruitment of HDAC4
CC on CD8 loci for deacetylation and possible inhibition of CD8 genes
CC expression (PubMed:22730529). Interacts with DHX36 (PubMed:21590736).
CC Interacts with SIK3; this interaction leads to HDAC4 retention in the
CC cytoplasm (PubMed:22318228). Interacts with ZNF638 (By similarity).
CC {ECO:0000250|UniProtKB:P56524, ECO:0000250|UniProtKB:Q99P99,
CC ECO:0000269|PubMed:10984530, ECO:0000269|PubMed:15601857,
CC ECO:0000269|PubMed:17949687, ECO:0000269|PubMed:21590736,
CC ECO:0000269|PubMed:22318228, ECO:0000269|PubMed:22730529}.
CC -!- INTERACTION:
CC Q6NZM9; P23242: Gja1; NbExp=2; IntAct=EBI-646397, EBI-298630;
CC Q6NZM9; Q08775: Runx2; NbExp=3; IntAct=EBI-646397, EBI-903354;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22318228}. Cytoplasm
CC {ECO:0000269|PubMed:22318228}. Note=Shuttles between the nucleus and
CC the cytoplasm. Upon muscle cells differentiation, it accumulates in the
CC nuclei of myotubes, suggesting a positive role of nuclear HDAC4 in
CC muscle differentiation. The export to cytoplasm depends on the
CC interaction with a 14-3-3 chaperone protein and is due to its
CC phosphorylation at Ser-245, Ser-465 and Ser-629 by CaMK4 and SIK1. The
CC nuclear localization probably depends on sumoylation (By similarity).
CC Interaction with SIK3 leads to HDAC4 retention in the cytoplasm
CC (PubMed:22318228). {ECO:0000250, ECO:0000269|PubMed:22318228}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q6NZM9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6NZM9-2; Sequence=VSP_023952, VSP_023953;
CC -!- DOMAIN: The nuclear export sequence mediates the shuttling between the
CC nucleus and the cytoplasm. {ECO:0000250}.
CC -!- DOMAIN: The PxLPxI/L motif mediates interaction with ankyrin repeats of
CC ANKRA2. {ECO:0000250|UniProtKB:P56524}.
CC -!- PTM: Phosphorylated by CaMK4 at Ser-245, Ser-465 and Ser-629.
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 high-
CC affinity docking site for 14-3-3 (By similarity).
CC {ECO:0000250|UniProtKB:P56524}.
CC -!- PTM: Sumoylation on Lys-556 is promoted by the E3 SUMO-protein ligase
CC RANBP2, and prevented by phosphorylation by CaMK4.
CC {ECO:0000269|PubMed:17468767, ECO:0000269|PubMed:17923476}.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2
CC subfamily. {ECO:0000305}.
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DR EMBL; AK029933; BAE43272.1; -; mRNA.
DR EMBL; AK155250; BAE33147.1; -; mRNA.
DR EMBL; AK162369; BAE36877.1; -; mRNA.
DR EMBL; BC066052; AAH66052.1; -; mRNA.
DR CCDS; CCDS48324.1; -. [Q6NZM9-1]
DR RefSeq; NP_997108.1; NM_207225.2. [Q6NZM9-1]
DR RefSeq; XP_017174977.1; XM_017319488.1. [Q6NZM9-1]
DR AlphaFoldDB; Q6NZM9; -.
DR SMR; Q6NZM9; -.
DR BioGRID; 229009; 385.
DR CORUM; Q6NZM9; -.
DR DIP; DIP-36317N; -.
DR IntAct; Q6NZM9; 365.
DR MINT; Q6NZM9; -.
DR STRING; 10090.ENSMUSP00000095249; -.
DR BindingDB; Q6NZM9; -.
DR ChEMBL; CHEMBL3832944; -.
DR iPTMnet; Q6NZM9; -.
DR PhosphoSitePlus; Q6NZM9; -.
DR EPD; Q6NZM9; -.
DR jPOST; Q6NZM9; -.
DR MaxQB; Q6NZM9; -.
DR PaxDb; Q6NZM9; -.
DR PeptideAtlas; Q6NZM9; -.
DR PRIDE; Q6NZM9; -.
DR ProteomicsDB; 269683; -. [Q6NZM9-1]
DR ProteomicsDB; 269684; -. [Q6NZM9-2]
DR Antibodypedia; 3835; 1253 antibodies from 51 providers.
DR DNASU; 208727; -.
DR Ensembl; ENSMUST00000008995; ENSMUSP00000008995; ENSMUSG00000026313. [Q6NZM9-1]
DR Ensembl; ENSMUST00000097644; ENSMUSP00000095249; ENSMUSG00000026313. [Q6NZM9-1]
DR GeneID; 208727; -.
DR KEGG; mmu:208727; -.
DR UCSC; uc007cbe.2; mouse. [Q6NZM9-2]
DR UCSC; uc007cbf.2; mouse. [Q6NZM9-1]
DR CTD; 9759; -.
DR MGI; MGI:3036234; Hdac4.
DR VEuPathDB; HostDB:ENSMUSG00000026313; -.
DR eggNOG; KOG1343; Eukaryota.
DR GeneTree; ENSGT00940000157440; -.
DR HOGENOM; CLU_006530_2_0_1; -.
DR InParanoid; Q6NZM9; -.
DR OMA; AEESTPX; -.
DR OrthoDB; 1484694at2759; -.
DR PhylomeDB; Q6NZM9; -.
DR TreeFam; TF106174; -.
DR Reactome; R-MMU-350054; Notch-HLH transcription pathway.
DR Reactome; R-MMU-4090294; SUMOylation of intracellular receptors.
DR Reactome; R-MMU-4551638; SUMOylation of chromatin organization proteins.
DR Reactome; R-MMU-8951936; RUNX3 regulates p14-ARF.
DR BioGRID-ORCS; 208727; 1 hit in 78 CRISPR screens.
DR PRO; PR:Q6NZM9; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q6NZM9; protein.
DR Bgee; ENSMUSG00000026313; Expressed in ear vesicle and 235 other tissues.
DR ExpressionAtlas; Q6NZM9; baseline and differential.
DR Genevisible; Q6NZM9; MM.
DR GO; GO:0031672; C:A band; ISO:MGI.
DR GO; GO:0042641; C:actomyosin; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0000118; C:histone deacetylase complex; ISO:MGI.
DR GO; GO:0031594; C:neuromuscular junction; IDA:MGI.
DR GO; GO:0016607; C:nuclear speck; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0030017; C:sarcomere; ISO:MGI.
DR GO; GO:0017053; C:transcription repressor complex; ISO:MGI.
DR GO; GO:0030018; C:Z disc; ISO:MGI.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0004407; F:histone deacetylase activity; ISO:MGI.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0030955; F:potassium ion binding; ISO:MGI.
DR GO; GO:1990841; F:promoter-specific chromatin binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0019789; F:SUMO transferase activity; ISO:MGI.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:MGI.
DR GO; GO:0003714; F:transcription corepressor activity; IGI:MGI.
DR GO; GO:0008270; F:zinc ion binding; ISO:MGI.
DR GO; GO:0008283; P:cell population proliferation; IDA:MGI.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0006338; P:chromatin remodeling; ISO:MGI.
DR GO; GO:0016575; P:histone deacetylation; ISO:MGI.
DR GO; GO:0070932; P:histone H3 deacetylation; ISO:MGI.
DR GO; GO:0070933; P:histone H4 deacetylation; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0045820; P:negative regulation of glycolytic process; IMP:BHF-UCL.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; IMP:BHF-UCL.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; ISO:MGI.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0002076; P:osteoblast development; IMP:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IMP:MGI.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0010592; P:positive regulation of lamellipodium assembly; ISO:MGI.
DR GO; GO:1902437; P:positive regulation of male mating behavior; ISO:MGI.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0033235; P:positive regulation of protein sumoylation; ISS:UniProtKB.
DR GO; GO:1903428; P:positive regulation of reactive oxygen species biosynthetic process; ISO:MGI.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:BHF-UCL.
DR GO; GO:0006476; P:protein deacetylation; ISO:MGI.
DR GO; GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; IMP:MGI.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; ISO:MGI.
DR GO; GO:0043393; P:regulation of protein binding; ISO:MGI.
DR GO; GO:0048742; P:regulation of skeletal muscle fiber development; IGI:MGI.
DR GO; GO:1902809; P:regulation of skeletal muscle fiber differentiation; IGI:MGI.
DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; IMP:BHF-UCL.
DR GO; GO:0070555; P:response to interleukin-1; ISO:MGI.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0001501; P:skeletal system development; IMP:MGI.
DR Gene3D; 3.40.800.20; -; 1.
DR InterPro; IPR033660; HDAC4/7.
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; PTHR45364; PTHR45364; 1.
DR PANTHER; PTHR45364:SF3; PTHR45364:SF3; 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 Alternative splicing; Chromatin regulator; Coiled coil; Cytoplasm;
KW Hydrolase; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation; Zinc.
FT CHAIN 1..1076
FT /note="Histone deacetylase 4"
FT /id="PRO_0000281033"
FT REGION 117..312
FT /note="Interaction with MEF2A"
FT /evidence="ECO:0000250"
FT REGION 132..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 205..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 239..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 506..529
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 541..580
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 622..645
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 652..1076
FT /note="Histone deacetylase"
FT /evidence="ECO:0000250"
FT COILED 66..169
FT /evidence="ECO:0000255"
FT MOTIF 348..353
FT /note="PxLPxI/L motif; mediates interaction with ANKRA2 and
FT 14-3-3 proteins"
FT /evidence="ECO:0000250|UniProtKB:P56524"
FT MOTIF 1043..1076
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 205..224
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 239..278
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 290..317
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 514..529
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 795
FT /evidence="ECO:0000250"
FT BINDING 664
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 666
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 672
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 743
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 245
FT /note="Phosphoserine; by CaMK4 and SIK1"
FT /evidence="ECO:0000269|PubMed:17468767"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56524"
FT MOD_RES 465
FT /note="Phosphoserine; by CaMK4 and SIK1"
FT /evidence="ECO:0000269|PubMed:17468767,
FT ECO:0007744|PubMed:19131326"
FT MOD_RES 562
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 629
FT /note="Phosphoserine; by CaMK4"
FT /evidence="ECO:0000250|UniProtKB:P56524"
FT MOD_RES 630
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56524"
FT CROSSLNK 556
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..171
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023952"
FT VAR_SEQ 732
FT /note="S -> SKKLLG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023953"
FT CONFLICT 569
FT /note="A -> S (in Ref. 1; BAE33147)"
FT /evidence="ECO:0000305"
FT CONFLICT 904
FT /note="R -> K (in Ref. 1; BAE33147)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1076 AA; 118562 MW; A3CCC3CCCBB903A0 CRC64;
MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPTAVPMD LRLDHQFSLP
LEPALREQQL QQELLALKQK QQIQRQILIA EFQRQHEQLS RQHEAQLHEH IKQQQEMLAM
KHQQELLEHQ RKLERHRQEQ ELEKQHREQK LQQLKNKEKG KESAVASTEV KMKLQEFVLN
KKKALAHRNL NHCISSDPRY WYGKTQHSSL DQSSPPQSGV SASYNHPVLG MYDAKDDFPL
RKTASEPNLK LRSRLKQKVA ERRSSPLLRR KDGPVATALK KRPLDVTDSA CSSAPGSGPS
SPNSSSGNVS TENGIAPTVP SAPAETSLAH RLVTREGSVA PLPLYTSPSL PNITLGLPAT
GPAAGAAGQQ DAERLALPAL QQRILFPGTH LTPYLSTSPL ERDGAAAHNP LLQHMVLLEQ
PPTQTPLVTG LGALPLHSQS LVGADRVSPS IHKLRQHRPL GRTQSAPLPQ NAQALQHLVI
QQQHQQFLEK HKQQFQQQQL HLSKIISKPS EPPRQPESHP EETEEELREH QALLDEPYLD
RLPGQKEPSL AGVQVKQEPI ESEEEEAEAT RETEPGQRPA TEQELLFRQQ ALLLEQQRIH
QLRNYQASME AAGIPVSFGS HRPLSRAQSS PASATFPMSV QEPPTKPRFT TGLVYDTLML
KHQCTCGNTN SHPEHAGRIQ SIWSRLQETG LRGKCECIRG RKATLEELQT VHSEAHTLLY
GTNPLNRQKL DSSLTSVFVR LPCGGVGVDS DTIWNEVHSS GAARLAVGCV VELVFKVATG
ELKNGFAVVR PPGHHAEEST PMGFCYFNSV AVAAKLLQQR LNVSKILIVD WDVHHGNGTQ
QAFYNDPNVL YMSLHRYDDG NFFPGSGAPD EVGTGPGVGF NVNMAFTGGL EPPMGDAEYL
AAFRTVVMPI ANEFAPDVVL VSSGFDAVEG HPTPLGGYNL SAKCFGYLTK QLMGLAGGRL
VLALEGGHDL TAICDASEAC VSALLGNELE PLPEKVLHQR PNANAVHSME KVMDIHSKYW
RCLQRLSSTV GHSLIEAQKC EKEEAETVTA MASLSVGVKP AEKRSEEEPM EEEPPL
