CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-009040
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Histone deacetylase 4 
Protein Synonyms/Alias
 HD4 
Gene Name
 HDAC4 
Gene Synonyms/Alias
 KIAA0288 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
236VLGMYDAKDDFPLRKacetylation[1]
559AQAGVQVKQEPIESDsumoylation[2, 3, 4]
737RQKLDSKKLLGSLASubiquitination[5]
1026KVMEIHSKYWRCLQRubiquitination[5]
Reference
 [1] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [2] Polymeric chains of SUMO-2 and SUMO-3 are conjugated to protein substrates by SAE1/SAE2 and Ubc9.
 Tatham MH, Jaffray E, Vaughan OA, Desterro JM, Botting CH, Naismith JH, Hay RT.
 J Biol Chem. 2001 Sep 21;276(38):35368-74. [PMID: 11451954]
 [3] The SUMO E3 ligase RanBP2 promotes modification of the HDAC4 deacetylase.
 Kirsh O, Seeler JS, Pichler A, Gast A, Müller S, Miska E, Mathieu M, Harel-Bellan A, Kouzarides T, Melchior F, Dejean A.
 EMBO J. 2002 Jun 3;21(11):2682-91. [PMID: 12032081]
 [4] Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-mediated lysine modifications.
 Zhao X, Sternsdorf T, Bolger TA, Evans RM, Yao TP.
 Mol Cell Biol. 2005 Oct;25(19):8456-64. [PMID: 16166628]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 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. 
Sequence Annotation
 REGION 118 313 Interaction with MEF2A.
 REGION 655 1084 Histone deacetylase.
 MOTIF 1051 1084 Nuclear export signal (By similarity).
 ACT_SITE 803 803 By similarity.
 METAL 667 667 Zinc (By similarity).
 METAL 669 669 Zinc (By similarity).
 METAL 675 675 Zinc (By similarity).
 METAL 751 751 Zinc (By similarity).
 MOD_RES 246 246 Phosphoserine; by CaMK4 and SIK1.
 MOD_RES 350 350 Phosphoserine.
 MOD_RES 467 467 Phosphoserine; by CaMK4 and SIK1.
 MOD_RES 565 565 Phosphoserine.
 MOD_RES 632 632 Phosphoserine; by CaMK4.
 MOD_RES 633 633 Phosphoserine.
 CROSSLNK 559 559 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Chromatin regulator; Coiled coil; Complete proteome; Cytoplasm; Hydrolase; Isopeptide bond; Mental retardation; Metal-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repressor; Transcription; Transcription regulation; Ubl conjugation; Zinc. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1084 AA 
Protein Sequence
MSSQSHPDGL SGRDQPVELL NPARVNHMPS TVDVATALPL QVAPSAVPMD LRLDHQFSLP 60
VAEPALREQQ LQQELLALKQ KQQIQRQILI AEFQRQHEQL SRQHEAQLHE HIKQQQEMLA 120
MKHQQELLEH QRKLERHRQE QELEKQHREQ KLQQLKNKEK GKESAVASTE VKMKLQEFVL 180
NKKKALAHRN LNHCISSDPR YWYGKTQHSS LDQSSPPQSG VSTSYNHPVL GMYDAKDDFP 240
LRKTASEPNL KLRSRLKQKV AERRSSPLLR RKDGPVVTAL KKRPLDVTDS ACSSAPGSGP 300
SSPNNSSGSV SAENGIAPAV PSIPAETSLA HRLVAREGSA APLPLYTSPS LPNITLGLPA 360
TGPSAGTAGQ QDAERLTLPA LQQRLSLFPG THLTPYLSTS PLERDGGAAH SPLLQHMVLL 420
EQPPAQAPLV TGLGALPLHA QSLVGADRVS PSIHKLRQHR PLGRTQSAPL PQNAQALQHL 480
VIQQQHQQFL EKHKQQFQQQ QLQMNKIIPK PSEPARQPES HPEETEEELR EHQALLDEPY 540
LDRLPGQKEA HAQAGVQVKQ EPIESDEEEA EPPREVEPGQ RQPSEQELLF RQQALLLEQQ 600
RIHQLRNYQA SMEAAGIPVS FGGHRPLSRA QSSPASATFP VSVQEPPTKP RFTTGLVYDT 660
LMLKHQCTCG SSSSHPEHAG RIQSIWSRLQ ETGLRGKCEC IRGRKATLEE LQTVHSEAHT 720
LLYGTNPLNR QKLDSKKLLG SLASVFVRLP CGGVGVDSDT IWNEVHSAGA ARLAVGCVVE 780
LVFKVATGEL KNGFAVVRPP GHHAEESTPM GFCYFNSVAV AAKLLQQRLS VSKILIVDWD 840
VHHGNGTQQA FYSDPSVLYM SLHRYDDGNF FPGSGAPDEV GTGPGVGFNV NMAFTGGLDP 900
PMGDAEYLAA FRTVVMPIAS EFAPDVVLVS SGFDAVEGHP TPLGGYNLSA RCFGYLTKQL 960
MGLAGGRIVL ALEGGHDLTA ICDASEACVS ALLGNELDPL PEKVLQQRPN ANAVRSMEKV 1020
MEIHSKYWRC LQRTTSTAGR SLIEAQTCEN EEAETVTAMA SLSVGVKPAE KRPDEEPMEE 1080
EPPL 1084 
Gene Ontology
 GO:0031672; C:A band; IEA:Compara.
 GO:0042641; C:actomyosin; IEA:Compara.
 GO:0005737; C:cytoplasm; IDA:BHF-UCL.
 GO:0005829; C:cytosol; IEA:Compara.
 GO:0000118; C:histone deacetylase complex; IDA:BHF-UCL.
 GO:0031594; C:neuromuscular junction; IEA:Compara.
 GO:0017053; C:transcriptional repressor complex; IDA:BHF-UCL.
 GO:0030018; C:Z disc; IEA:Compara.
 GO:0003677; F:DNA binding; IEA:Compara.
 GO:0004407; F:histone deacetylase activity; IDA:BHF-UCL.
 GO:0032041; F:NAD-dependent histone deacetylase activity (H3-K14 specific); IEA:EC.
 GO:0097372; F:NAD-dependent histone deacetylase activity (H3-K18 specific); IEA:EC.
 GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); IEA:EC.
 GO:0046970; F:NAD-dependent histone deacetylase activity (H4-K16 specific); IEA:EC.
 GO:0030955; F:potassium ion binding; IDA:BHF-UCL.
 GO:0003714; F:transcription corepressor activity; IEA:Compara.
 GO:0008270; F:zinc ion binding; IDA:BHF-UCL.
 GO:0030183; P:B cell differentiation; TAS:UniProtKB.
 GO:0014898; P:cardiac muscle hypertrophy in response to stress; TAS:BHF-UCL.
 GO:0006338; P:chromatin remodeling; IDA:BHF-UCL.
 GO:0070932; P:histone H3 deacetylation; IDA:BHF-UCL.
 GO:0070933; P:histone H4 deacetylation; IDA:BHF-UCL.
 GO:0006954; P:inflammatory response; TAS:UniProtKB.
 GO:0008285; P:negative regulation of cell proliferation; IEA:Compara.
 GO:0045820; P:negative regulation of glycolysis; ISS:BHF-UCL.
 GO:0010832; P:negative regulation of myotube differentiation; IMP:BHF-UCL.
 GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Compara.
 GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IMP:BHF-UCL.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:0007399; P:nervous system development; TAS:UniProtKB.
 GO:0002076; P:osteoblast development; IEA:Compara.
 GO:0034983; P:peptidyl-lysine deacetylation; IDA:BHF-UCL.
 GO:0008284; P:positive regulation of cell proliferation; IMP:BHF-UCL.
 GO:0033235; P:positive regulation of protein sumoylation; IDA:UniProtKB.
 GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IMP:BHF-UCL.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
 GO:0010882; P:regulation of cardiac muscle contraction by calcium ion signaling; IEA:Compara.
 GO:0043393; P:regulation of protein binding; IMP:BHF-UCL.
 GO:0014894; P:response to denervation involved in regulation of muscle adaptation; ISS:BHF-UCL.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0070555; P:response to interleukin-1; IMP:BHF-UCL.
 GO:0001501; P:skeletal system development; IEA:Compara.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR019154; Arb2_domain.
 IPR000286; His_deacetylse.
 IPR023801; His_deacetylse_dom.
 IPR024643; Hist_deacetylase_Gln_rich_N.
 IPR017320; Histone_deAcase_II_euk. 
Pfam
 PF09757; Arb2
 PF12203; HDAC4_Gln
 PF00850; Hist_deacetyl 
SMART
  
PROSITE
  
PRINTS
 PR01270; HDASUPER.