Histone deacetylase 4

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityⁱ

• H₂O

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  • See the description of this molecule in ChEBI.

  + N⁶-acetyl-L-lysyl-[histone]

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  = acetate

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  • See the description of this molecule in ChEBI.

  + L-lysyl-[histone]

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  • Search chemical reactions in Rhea for this molecule.
  EC:3.5.1.98
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  • See the description of this EC number in ENZYME.
  Source: Rhea

  • Search for this reaction in UniProtKB.
  • See the description of this reaction in Rhea.

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  H₂O

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  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  

  +

  N⁶-acetyl-L-lysyl-[histone]

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  • Search chemical reactions in Rhea for this molecule.

  

  N⁶-acetyl-L-lysine residue

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  • See the description of this molecule in ChEBI.

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  =

  acetate

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  • Search chemical reactions in Rhea for this molecule.
  • See the description of this molecule in ChEBI.

  zoom

  +

  L-lysyl-[histone]

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  • Search chemical reactions in Rhea for this molecule.

  

  L-lysine residue

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  • See the description of this molecule in ChEBI.

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Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• activating transcription factor binding Source: RGD
• chromatin binding Source: RGD
• DNA binding Source: RGD
• histone deacetylase activity Source: RGD
• histone deacetylase binding Source: RGD
• identical protein binding Source: RGD
• NAD-dependent histone deacetylase activity (H3-K14 specific) Source: UniProtKB-EC
• potassium ion binding Source: RGD
• promoter-specific chromatin binding Source: RGD <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • "Histone deacetylation during brain development is essential for permanent masculinization of sexual behavior."
    Matsuda K.I., Mori H., Nugent B.M., Pfaff D.W., McCarthy M.M., Kawata M.
    Endocrinology 152:2760-2767(2011) [PubMed] [Europe PMC] [Abstract]
• protein deacetylase activity Source: RGD
• protein kinase binding Source: RGD
• repressing transcription factor binding Source: RGD
• RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: RGD
• RNA polymerase II transcription factor binding Source: RGD
• SUMO transferase activity Source: RGD
• transcription corepressor activity Source: RGD
• transcription factor binding Source: RGD <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Calcium/calmodulin-dependent protein kinase activates serum response factor transcription activity by its dissociation from histone deacetylase, HDAC4. Implications in cardiac muscle gene regulation during hypertrophy."
    Davis F.J., Gupta M., Camoretti-Mercado B., Schwartz R.J., Gupta M.P.
    J Biol Chem 278:20047-20058(2003) [PubMed] [Europe PMC] [Abstract]
  • "HDAC4 represses matrix metalloproteinase-13 transcription in osteoblastic cells, and parathyroid hormone controls this repression."
    Shimizu E., Selvamurugan N., Westendorf J.J., Olson E.N., Partridge N.C.
    J Biol Chem 285:9616-9626(2010) [PubMed] [Europe PMC] [Abstract]
• zinc ion binding Source: RGD

GO - Biological processⁱ

• cellular response to mechanical stimulus Source: RGD <p>Inferred from Expression Pattern</p> <p>Covers cases where the annotation is inferred from the timing or location of expression of a gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "Histone deacetylases modulate vascular smooth muscle cell migration induced by cyclic mechanical strain."
    Yan Z.Q., Yao Q.P., Zhang M.L., Qi Y.X., Guo Z.Y., Shen B.R., Jiang Z.L.
    J Biomech 42:945-948(2009) [PubMed] [Europe PMC] [Abstract]
• cellular response to parathyroid hormone stimulus Source: RGDInferred from expression patternⁱ
  • "HDAC4 represses matrix metalloproteinase-13 transcription in osteoblastic cells, and parathyroid hormone controls this repression."
    Shimizu E., Selvamurugan N., Westendorf J.J., Olson E.N., Partridge N.C.
    J Biol Chem 285:9616-9626(2010) [PubMed] [Europe PMC] [Abstract]
• cellular response to tumor necrosis factor Source: RGDInferred from expression patternⁱ
  • "HDAC4 mediates development of hypertension via vascular inflammation in spontaneous hypertensive rats."
    Usui T., Okada M., Mizuno W., Oda M., Ide N., Morita T., Hara Y., Yamawaki H.
    Am J Physiol Heart Circ Physiol 302:H1894-904(2012) [PubMed] [Europe PMC] [Abstract]
• chromatin remodeling Source: RGD
• histone deacetylation Source: RGD
• histone H3 deacetylation Source: RGD
• histone H4 deacetylation Source: RGD
• negative regulation of cell population proliferation Source: RGD
• negative regulation of DNA-binding transcription factor activity Source: RGD
• negative regulation of glycolytic process Source: RGD
• negative regulation of myotube differentiation Source: RGD
• negative regulation of osteoblast differentiation Source: RGD
• negative regulation of pri-miRNA transcription by RNA polymerase II Source: RGD
• negative regulation of transcription, DNA-templated Source: RGD
• negative regulation of transcription by RNA polymerase II Source: RGD
• osteoblast development Source: RGD
• peptidyl-lysine deacetylation Source: RGD
• positive regulation of cell population proliferation Source: RGD
• positive regulation of DNA-binding transcription factor activity Source: RGD
• positive regulation of lamellipodium assembly Source: RGD <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "Histone deacetylase 4 controls neointimal hyperplasia via stimulating proliferation and migration of vascular smooth muscle cells."
    Usui T., Morita T., Okada M., Yamawaki H.
    Hypertension 63:397-403(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of male mating behavior Source: RGDInferred from mutant phenotypeⁱ
  • "Histone deacetylation during brain development is essential for permanent masculinization of sexual behavior."
    Matsuda K.I., Mori H., Nugent B.M., Pfaff D.W., McCarthy M.M., Kawata M.
    Endocrinology 152:2760-2767(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of neuron apoptotic process Source: RGDInferred from mutant phenotypeⁱ
  • "Epigenetic modulation of neuronal apoptosis and cognitive functions in sepsis-associated encephalopathy."
    Fang J., Lian Y., Xie K., Cai S., Wen P.
    Neurol Sci 35:283-288(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein sumoylation Source: RGD
• positive regulation of reactive oxygen species biosynthetic process Source: RGDInferred from mutant phenotypeⁱ
  • "Histone deacetylase 4 controls neointimal hyperplasia via stimulating proliferation and migration of vascular smooth muscle cells."
    Usui T., Morita T., Okada M., Yamawaki H.
    Hypertension 63:397-403(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of smooth muscle cell migration Source: RGDInferred from mutant phenotypeⁱ
  • "Histone deacetylase 4 controls neointimal hyperplasia via stimulating proliferation and migration of vascular smooth muscle cells."
    Usui T., Morita T., Okada M., Yamawaki H.
    Hypertension 63:397-403(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of smooth muscle cell proliferation Source: RGDInferred from mutant phenotypeⁱ
  • "Histone deacetylase 4 controls neointimal hyperplasia via stimulating proliferation and migration of vascular smooth muscle cells."
    Usui T., Morita T., Okada M., Yamawaki H.
    Hypertension 63:397-403(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription, DNA-templated Source: RGD
• positive regulation of transcription by RNA polymerase II Source: RGD
• protein deacetylation Source: RGD
• regulation of cardiac muscle contraction by calcium ion signaling Source: RGD
• regulation of gene expression, epigenetic Source: RGD
• regulation of protein binding Source: RGD
• regulation of skeletal muscle fiber development Source: RGD
• regulation of striated muscle cell differentiation Source: RGD
• response to denervation involved in regulation of muscle adaptation Source: RGD
• response to drug Source: RGDInferred from direct assayⁱ
  • "CaM kinase II selectively signals to histone deacetylase 4 during cardiomyocyte hypertrophy."
    Backs J., Song K., Bezprozvannaya S., Chang S., Olson E.N.
    J Clin Invest 116:1853-1864(2006) [PubMed] [Europe PMC] [Abstract]
• response to interleukin-1 Source: RGD
• skeletal system development Source: RGD

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

Chemistry databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

Gene expression databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

GO - Molecular functionⁱ

• activating transcription factor binding Source: RGD
• histone deacetylase binding Source: RGD
• identical protein binding Source: RGD
• protein kinase binding Source: RGD
• repressing transcription factor binding Source: RGD
• RNA polymerase II transcription factor binding Source: RGD
• transcription factor binding Source: RGDInferred from physical interactionⁱ
  • "Calcium/calmodulin-dependent protein kinase activates serum response factor transcription activity by its dissociation from histone deacetylase, HDAC4. Implications in cardiac muscle gene regulation during hypertrophy."
    Davis F.J., Gupta M., Camoretti-Mercado B., Schwartz R.J., Gupta M.P.
    J Biol Chem 278:20047-20058(2003) [PubMed] [Europe PMC] [Abstract]
  • "HDAC4 represses matrix metalloproteinase-13 transcription in osteoblastic cells, and parathyroid hormone controls this repression."
    Shimizu E., Selvamurugan N., Westendorf J.J., Olson E.N., Partridge N.C.
    J Biol Chem 285:9616-9626(2010) [PubMed] [Europe PMC] [Abstract]

Protein-protein interaction databases

Chemistry databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

3D structure databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Region

Coiled coil

Motif

Compositional bias

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domainⁱ

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesⁱ

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequenceⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

        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                          

Sequence databases

Genome annotation databases

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous databases

Gene expression databases

Family and domain databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationⁱ

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousⁱ

Keywords - Technical termⁱ

Documents

1. SIMILARITY comments
   Index of protein domains and families