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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  + N⁶-acetyl-L-lysyl-[histone]

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  = acetate

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  + L-lysyl-[histone]

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  EC:3.5.1.98
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  Source: Rhea

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  H₂O

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  N⁶-acetyl-L-lysyl-[histone]

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  N⁶-acetyl-L-lysine residue

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  acetate

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  L-lysyl-[histone]

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  L-lysine residue

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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: RGDInferred from sequence orthologyⁱ
  • "Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases."
    Lu J., McKinsey T.A., Zhang C.L., Olson E.N.
    Mol. Cell 6:233-244(2000) [PubMed] [Europe PMC] [Abstract]
• chromatin binding Source: RGDInferred from sequence orthologyⁱ
  • "Leptin-mediated increases in catecholamine signaling reduce adipose tissue inflammation via activation of macrophage HDAC4."
    Luan B., Goodarzi M.O., Phillips N.G., Guo X., Chen Y.D., Yao J., Allison M., Rotter J.I., Shaw R., Montminy M.
    Cell Metab. 19:1058-1065(2014) [PubMed] [Europe PMC] [Abstract]
• DNA binding Source: RGDInferred from sequence orthologyⁱ
  • "The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment."
    Dai Y.S., Xu J., Molkentin J.D.
    Mol. Cell. Biol. 25:9936-9948(2005) [PubMed] [Europe PMC] [Abstract]
• histone deacetylase activity Source: RGDInferred from sequence orthologyⁱ
  • "Three proteins define a class of human histone deacetylases related to yeast Hda1p."
    Grozinger C.M., Hassig C.A., Schreiber S.L.
    Proc. Natl. Acad. Sci. U.S.A. 96:4868-4873(1999) [PubMed] [Europe PMC] [Abstract]
  • "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization."
    Grozinger C.M., Schreiber S.L.
    Proc. Natl. Acad. Sci. U.S.A. 97:7835-7840(2000) [PubMed] [Europe PMC] [Abstract]
• histone deacetylase binding Source: RGDInferred from sequence orthologyⁱ
  • "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization."
    Grozinger C.M., Schreiber S.L.
    Proc. Natl. Acad. Sci. U.S.A. 97:7835-7840(2000) [PubMed] [Europe PMC] [Abstract]
  • "The histone deacetylase 9 gene encodes multiple protein isoforms."
    Petrie K., Guidez F., Howell L., Healy L., Waxman S., Greaves M., Zelent A.
    J. Biol. Chem. 278:16059-16072(2003) [PubMed] [Europe PMC] [Abstract]
• identical protein binding Source: RGDInferred from sequence orthologyⁱ
  • "Crystal structure of a conserved N-terminal domain of histone deacetylase 4 reveals functional insights into glutamine-rich domains."
    Guo L., Han A., Bates D.L., Cao J., Chen L.
    Proc. Natl. Acad. Sci. U.S.A. 104:4297-4302(2007) [PubMed] [Europe PMC] [Abstract]
• NAD-dependent histone deacetylase activity (H3-K14 specific) Source: UniProtKB-EC
• potassium ion binding Source: RGDInferred from sequence orthologyⁱ
  • "Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain."
    Bottomley M.J., Lo Surdo P., Di Giovine P., Cirillo A., Scarpelli R., Ferrigno F., Jones P., Neddermann P., De Francesco R., Steinkuhler C., Gallinari P., Carfi A.
    J. Biol. Chem. 283:26694-26704(2008) [PubMed] [Europe PMC] [Abstract]
• 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: RGDInferred from sequence orthologyⁱ
  • "HDAC4 and PCAF bind to cardiac sarcomeres and play a role in regulating myofilament contractile activity."
    Gupta M.P., Samant S.A., Smith S.H., Shroff S.G.
    J. Biol. Chem. 283:10135-10146(2008) [PubMed] [Europe PMC] [Abstract]
  • "Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain."
    Bottomley M.J., Lo Surdo P., Di Giovine P., Cirillo A., Scarpelli R., Ferrigno F., Jones P., Neddermann P., De Francesco R., Steinkuhler C., Gallinari P., Carfi A.
    J. Biol. Chem. 283:26694-26704(2008) [PubMed] [Europe PMC] [Abstract]
• protein kinase binding Source: RGDInferred from sequence orthologyⁱ
  • "SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes."
    Berdeaux R., Goebel N., Banaszynski L., Takemori H., Wandless T., Shelton G.D., Montminy M.
    Nat. Med. 13:597-603(2007) [PubMed] [Europe PMC] [Abstract]
• repressing transcription factor binding Source: RGDInferred from sequence orthologyⁱ
  • "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR."
    Fischle W., Dequiedt F., Hendzel M.J., Guenther M.G., Lazar M.A., Voelter W., Verdin E.
    Mol. Cell 9:45-57(2002) [PubMed] [Europe PMC] [Abstract]
• RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: RGDInferred from sequence orthologyⁱ
  • "Differential regulation of estrogen receptor alpha expression in breast cancer cells by metastasis-associated protein 1."
    Kang H.J., Lee M.H., Kang H.L., Kim S.H., Ahn J.R., Na H., Na T.Y., Kim Y.N., Seong J.K., Lee M.O.
    Cancer Res. 74:1484-1494(2014) [PubMed] [Europe PMC] [Abstract]
• RNA polymerase II transcription factor binding Source: RGDInferred from sequence orthologyⁱ
  • "Involvement of Epac1/Rap1/CaMKI/HDAC5 signaling cascade in the regulation of placental cell fusion."
    Chang C.W., Cheong M.L., Chang G.D., Tsai M.S., Chen H.
    Mol. Hum. Reprod. 19:745-755(2013) [PubMed] [Europe PMC] [Abstract]
• SUMO transferase activity Source: RGDInferred from sequence orthologyⁱ
  • "Parallel SUMOylation-dependent pathways mediate gene- and signal-specific transrepression by LXRs and PPARgamma."
    Ghisletti S., Huang W., Ogawa S., Pascual G., Lin M.E., Willson T.M., Rosenfeld M.G., Glass C.K.
    Mol. Cell 25:57-70(2007) [PubMed] [Europe PMC] [Abstract]
• transcription corepressor activity Source: RGDInferred from sequence orthologyⁱ
  • "Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3."
    Kang J.S., Alliston T., Delston R., Derynck R.
    EMBO J. 24:2543-2555(2005) [PubMed] [Europe PMC] [Abstract]
• 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: RGDInferred from sequence orthologyⁱ
  • "Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain."
    Bottomley M.J., Lo Surdo P., Di Giovine P., Cirillo A., Scarpelli R., Ferrigno F., Jones P., Neddermann P., De Francesco R., Steinkuhler C., Gallinari P., Carfi A.
    J. Biol. Chem. 283:26694-26704(2008) [PubMed] [Europe PMC] [Abstract]

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: RGDInferred from sequence orthologyⁱ
  • "HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism."
    Mottet D., Pirotte S., Lamour V., Hagedorn M., Javerzat S., Bikfalvi A., Bellahcene A., Verdin E., Castronovo V.
    Oncogene 28:243-256(2009) [PubMed] [Europe PMC] [Abstract]
• histone deacetylation Source: RGDInferred from sequence orthologyⁱ
  • "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization."
    Grozinger C.M., Schreiber S.L.
    Proc. Natl. Acad. Sci. U.S.A. 97:7835-7840(2000) [PubMed] [Europe PMC] [Abstract]
  • "HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism."
    Mottet D., Pirotte S., Lamour V., Hagedorn M., Javerzat S., Bikfalvi A., Bellahcene A., Verdin E., Castronovo V.
    Oncogene 28:243-256(2009) [PubMed] [Europe PMC] [Abstract]
• histone H3 deacetylation Source: RGDInferred from sequence orthologyⁱ
  • "The histone deacetylase 9 gene encodes multiple protein isoforms."
    Petrie K., Guidez F., Howell L., Healy L., Waxman S., Greaves M., Zelent A.
    J. Biol. Chem. 278:16059-16072(2003) [PubMed] [Europe PMC] [Abstract]
• histone H4 deacetylation Source: RGDInferred from sequence orthologyⁱ
  • "The histone deacetylase 9 gene encodes multiple protein isoforms."
    Petrie K., Guidez F., Howell L., Healy L., Waxman S., Greaves M., Zelent A.
    J. Biol. Chem. 278:16059-16072(2003) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cell population proliferation Source: RGDInferred from sequence orthologyⁱ
  • "Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis."
    Vega R.B., Matsuda K., Oh J., Barbosa A.C., Yang X., Meadows E., McAnally J., Pomajzl C., Shelton J.M., Richardson J.A., Karsenty G., Olson E.N.
    Cell 119:555-566(2004) [PubMed] [Europe PMC] [Abstract]
• negative regulation of DNA-binding transcription factor activity Source: RGDInferred from sequence orthologyⁱ
  • "HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism."
    Mottet D., Pirotte S., Lamour V., Hagedorn M., Javerzat S., Bikfalvi A., Bellahcene A., Verdin E., Castronovo V.
    Oncogene 28:243-256(2009) [PubMed] [Europe PMC] [Abstract]
• negative regulation of glycolytic process Source: RGDInferred from sequence orthologyⁱ
  • "A histone deacetylase 4/myogenin positive feedback loop coordinates denervation-dependent gene induction and suppression."
    Tang H., Macpherson P., Marvin M., Meadows E., Klein W.H., Yang X.J., Goldman D.
    Mol. Biol. Cell 20:1120-1131(2009) [PubMed] [Europe PMC] [Abstract]
• negative regulation of myotube differentiation Source: RGDInferred from sequence orthologyⁱ
  • "Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases."
    Lu J., McKinsey T.A., Zhang C.L., Olson E.N.
    Mol. Cell 6:233-244(2000) [PubMed] [Europe PMC] [Abstract]
• negative regulation of osteoblast differentiation Source: RGDInferred from sequence orthologyⁱ
  • "Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3."
    Kang J.S., Alliston T., Delston R., Derynck R.
    EMBO J. 24:2543-2555(2005) [PubMed] [Europe PMC] [Abstract]
• negative regulation of pri-miRNA transcription by RNA polymerase II Source: RGDInferred from sequence orthologyⁱ
  • "Elevated microRNA-155 promotes foam cell formation by targeting HBP1 in atherogenesis."
    Tian F.J., An L.N., Wang G.K., Zhu J.Q., Li Q., Zhang Y.Y., Zeng A., Zou J., Zhu R.F., Han X.S., Shen N., Yang H.T., Zhao X.X., Huang S., Qin Y.W., Jing Q.
    Cardiovasc. Res. 103:100-110(2014) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription, DNA-templated Source: RGDInferred from sequence orthologyⁱ
  • "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization."
    Grozinger C.M., Schreiber S.L.
    Proc. Natl. Acad. Sci. U.S.A. 97:7835-7840(2000) [PubMed] [Europe PMC] [Abstract]
  • "Androgen receptor corepressor-19 kDa (ARR19), a leucine-rich protein that represses the transcriptional activity of androgen receptor through recruitment of histone deacetylase."
    Jeong B.C., Hong C.Y., Chattopadhyay S., Park J.H., Gong E.Y., Kim H.J., Chun S.Y., Lee K.
    Mol. Endocrinol. 18:13-25(2004) [PubMed] [Europe PMC] [Abstract]
  • "The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment."
    Dai Y.S., Xu J., Molkentin J.D.
    Mol. Cell. Biol. 25:9936-9948(2005) [PubMed] [Europe PMC] [Abstract]
  • "FOXP3 up-regulates p21 expression by site-specific inhibition of histone deacetylase 2/histone deacetylase 4 association to the locus."
    Liu R., Wang L., Chen G., Katoh H., Chen C., Liu Y., Zheng P.
    Cancer Res. 69:2252-2259(2009) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transcription by RNA polymerase II Source: RGDInferred from sequence orthologyⁱ
  • "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization."
    Grozinger C.M., Schreiber S.L.
    Proc. Natl. Acad. Sci. U.S.A. 97:7835-7840(2000) [PubMed] [Europe PMC] [Abstract]
  • "Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis."
    Vega R.B., Matsuda K., Oh J., Barbosa A.C., Yang X., Meadows E., McAnally J., Pomajzl C., Shelton J.M., Richardson J.A., Karsenty G., Olson E.N.
    Cell 119:555-566(2004) [PubMed] [Europe PMC] [Abstract]
  • "Modulation of smooth muscle gene expression by association of histone acetyltransferases and deacetylases with myocardin."
    Cao D., Wang Z., Zhang C.L., Oh J., Xing W., Li S., Richardson J.A., Wang D.Z., Olson E.N.
    Mol. Cell. Biol. 25:364-376(2005) [PubMed] [Europe PMC] [Abstract]
  • "PC4 coactivates MyoD by relieving the histone deacetylase 4-mediated inhibition of myocyte enhancer factor 2C."
    Micheli L., Leonardi L., Conti F., Buanne P., Canu N., Caruso M., Tirone F.
    Mol. Cell. Biol. 25:2242-2259(2005) [PubMed] [Europe PMC] [Abstract]
  • "Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3."
    Kang J.S., Alliston T., Delston R., Derynck R.
    EMBO J. 24:2543-2555(2005) [PubMed] [Europe PMC] [Abstract]
  • "Class II histone deacetylases confer signal responsiveness to the ankyrin-repeat proteins ANKRA2 and RFXANK."
    McKinsey T.A., Kuwahara K., Bezprozvannaya S., Olson E.N.
    Mol. Biol. Cell 17:438-447(2006) [PubMed] [Europe PMC] [Abstract]
  • "MEF2C transcription factor controls chondrocyte hypertrophy and bone development."
    Arnold M.A., Kim Y., Czubryt M.P., Phan D., McAnally J., Qi X., Shelton J.M., Richardson J.A., Bassel-Duby R., Olson E.N.
    Dev. Cell 12:377-389(2007) [PubMed] [Europe PMC] [Abstract]
  • "The histone deacetylase HDAC4 connects neural activity to muscle transcriptional reprogramming."
    Cohen T.J., Waddell D.S., Barrientos T., Lu Z., Feng G., Cox G.A., Bodine S.C., Yao T.P.
    J. Biol. Chem. 282:33752-33759(2007) [PubMed] [Europe PMC] [Abstract]
  • "HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism."
    Mottet D., Pirotte S., Lamour V., Hagedorn M., Javerzat S., Bikfalvi A., Bellahcene A., Verdin E., Castronovo V.
    Oncogene 28:243-256(2009) [PubMed] [Europe PMC] [Abstract]
  • "FOXP3 up-regulates p21 expression by site-specific inhibition of histone deacetylase 2/histone deacetylase 4 association to the locus."
    Liu R., Wang L., Chen G., Katoh H., Chen C., Liu Y., Zheng P.
    Cancer Res. 69:2252-2259(2009) [PubMed] [Europe PMC] [Abstract]
• osteoblast development Source: RGDInferred from sequence orthologyⁱ
  • "Repression of Runx2 function by TGF-beta through recruitment of class II histone deacetylases by Smad3."
    Kang J.S., Alliston T., Delston R., Derynck R.
    EMBO J. 24:2543-2555(2005) [PubMed] [Europe PMC] [Abstract]
• peptidyl-lysine deacetylation Source: RGDInferred from sequence orthologyⁱ
  • "Structural and functional analysis of the human HDAC4 catalytic domain reveals a regulatory structural zinc-binding domain."
    Bottomley M.J., Lo Surdo P., Di Giovine P., Cirillo A., Scarpelli R., Ferrigno F., Jones P., Neddermann P., De Francesco R., Steinkuhler C., Gallinari P., Carfi A.
    J. Biol. Chem. 283:26694-26704(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell population proliferation Source: RGDInferred from sequence orthologyⁱ
  • "HDAC4 represses p21(WAF1/Cip1) expression in human cancer cells through a Sp1-dependent, p53-independent mechanism."
    Mottet D., Pirotte S., Lamour V., Hagedorn M., Javerzat S., Bikfalvi A., Bellahcene A., Verdin E., Castronovo V.
    Oncogene 28:243-256(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of DNA-binding transcription factor activity Source: RGDInferred from sequence orthologyⁱ
  • "Transcriptional activation of hypoxia-inducible factor-1alpha by HDAC4 and HDAC5 involves differential recruitment of p300 and FIH-1."
    Seo H.W., Kim E.J., Na H., Lee M.O.
    FEBS Lett. 583:55-60(2009) [PubMed] [Europe PMC] [Abstract]
• 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: RGDInferred from sequence orthologyⁱ
  • "Sumoylation of the zinc finger protein ZXDC enhances the function of its transcriptional activation domain."
    Jambunathan S., Fontes J.D.
    Biol. Chem. 388:965-972(2007) [PubMed] [Europe PMC] [Abstract]
• 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: RGDInferred from sequence orthologyⁱ
  • "A histone deacetylase 4/myogenin positive feedback loop coordinates denervation-dependent gene induction and suppression."
    Tang H., Macpherson P., Marvin M., Meadows E., Klein W.H., Yang X.J., Goldman D.
    Mol. Biol. Cell 20:1120-1131(2009) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transcription by RNA polymerase II Source: RGDInferred from sequence orthologyⁱ
  • "Transcriptional activation of hypoxia-inducible factor-1alpha by HDAC4 and HDAC5 involves differential recruitment of p300 and FIH-1."
    Seo H.W., Kim E.J., Na H., Lee M.O.
    FEBS Lett. 583:55-60(2009) [PubMed] [Europe PMC] [Abstract]
  • "A histone deacetylase 4/myogenin positive feedback loop coordinates denervation-dependent gene induction and suppression."
    Tang H., Macpherson P., Marvin M., Meadows E., Klein W.H., Yang X.J., Goldman D.
    Mol. Biol. Cell 20:1120-1131(2009) [PubMed] [Europe PMC] [Abstract]
• protein deacetylation Source: RGDInferred from sequence orthologyⁱ
  • "ARD1-mediated Hsp70 acetylation balances stress-induced protein refolding and degradation."
    Seo J.H., Park J.H., Lee E.J., Vo T.T., Choi H., Kim J.Y., Jang J.K., Wee H.J., Lee H.S., Jang S.H., Park Z.Y., Jeong J., Lee K.J., Seok S.H., Park J.Y., Lee B.J., Lee M.N., Oh G.T., Kim K.W.
    Nat. Commun. 7:12882-12882(2016) [PubMed] [Europe PMC] [Abstract]
• regulation of cardiac muscle contraction by calcium ion signaling Source: RGDInferred from sequence orthologyⁱ
  • "HDAC4 and PCAF bind to cardiac sarcomeres and play a role in regulating myofilament contractile activity."
    Gupta M.P., Samant S.A., Smith S.H., Shroff S.G.
    J. Biol. Chem. 283:10135-10146(2008) [PubMed] [Europe PMC] [Abstract]
• regulation of gene expression, epigenetic Source: RGDInferred from sequence orthologyⁱ
  • "Differential regulation of estrogen receptor alpha expression in breast cancer cells by metastasis-associated protein 1."
    Kang H.J., Lee M.H., Kang H.L., Kim S.H., Ahn J.R., Na H., Na T.Y., Kim Y.N., Seong J.K., Lee M.O.
    Cancer Res. 74:1484-1494(2014) [PubMed] [Europe PMC] [Abstract]
• regulation of protein binding Source: RGDInferred from sequence orthologyⁱ
  • "Transcriptional activation of hypoxia-inducible factor-1alpha by HDAC4 and HDAC5 involves differential recruitment of p300 and FIH-1."
    Seo H.W., Kim E.J., Na H., Lee M.O.
    FEBS Lett. 583:55-60(2009) [PubMed] [Europe PMC] [Abstract]
• regulation of skeletal muscle fiber development Source: RGDInferred from sequence orthologyⁱ
  • "Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers."
    Potthoff M.J., Wu H., Arnold M.A., Shelton J.M., Backs J., McAnally J., Richardson J.A., Bassel-Duby R., Olson E.N.
    J. Clin. Invest. 117:2459-2467(2007) [PubMed] [Europe PMC] [Abstract]
• regulation of striated muscle cell differentiation Source: RGDInferred from sequence orthologyⁱ
  • "Histone deacetylase degradation and MEF2 activation promote the formation of slow-twitch myofibers."
    Potthoff M.J., Wu H., Arnold M.A., Shelton J.M., Backs J., McAnally J., Richardson J.A., Bassel-Duby R., Olson E.N.
    J. Clin. Invest. 117:2459-2467(2007) [PubMed] [Europe PMC] [Abstract]
• response to denervation involved in regulation of muscle adaptation Source: RGDInferred from sequence orthologyⁱ
  • "A histone deacetylase 4/myogenin positive feedback loop coordinates denervation-dependent gene induction and suppression."
    Tang H., Macpherson P., Marvin M., Meadows E., Klein W.H., Yang X.J., Goldman D.
    Mol. Biol. Cell 20:1120-1131(2009) [PubMed] [Europe PMC] [Abstract]
• 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: RGDInferred from sequence orthologyⁱ
  • "Activation of ROS/NF-kappaB and Ca2+/CaM kinase II are necessary for VCAM-1 induction in IL-1beta-treated human tracheal smooth muscle cells."
    Luo S.F., Chang C.C., Lee I.T., Lee C.W., Lin W.N., Lin C.C., Yang C.M.
    Toxicol. Appl. Pharmacol. 237:8-21(2009) [PubMed] [Europe PMC] [Abstract]
• skeletal system development Source: RGDInferred from sequence orthologyⁱ
  • "Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis."
    Vega R.B., Matsuda K., Oh J., Barbosa A.C., Yang X., Meadows E., McAnally J., Pomajzl C., Shelton J.M., Richardson J.A., Karsenty G., Olson E.N.
    Cell 119:555-566(2004) [PubMed] [Europe PMC] [Abstract]

<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: RGDInferred from sequence orthologyⁱ
  • "Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases."
    Lu J., McKinsey T.A., Zhang C.L., Olson E.N.
    Mol. Cell 6:233-244(2000) [PubMed] [Europe PMC] [Abstract]
• histone deacetylase binding Source: RGDInferred from sequence orthologyⁱ
  • "Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization."
    Grozinger C.M., Schreiber S.L.
    Proc. Natl. Acad. Sci. U.S.A. 97:7835-7840(2000) [PubMed] [Europe PMC] [Abstract]
  • "The histone deacetylase 9 gene encodes multiple protein isoforms."
    Petrie K., Guidez F., Howell L., Healy L., Waxman S., Greaves M., Zelent A.
    J. Biol. Chem. 278:16059-16072(2003) [PubMed] [Europe PMC] [Abstract]
• identical protein binding Source: RGDInferred from sequence orthologyⁱ
  • "Crystal structure of a conserved N-terminal domain of histone deacetylase 4 reveals functional insights into glutamine-rich domains."
    Guo L., Han A., Bates D.L., Cao J., Chen L.
    Proc. Natl. Acad. Sci. U.S.A. 104:4297-4302(2007) [PubMed] [Europe PMC] [Abstract]
• protein kinase binding Source: RGDInferred from sequence orthologyⁱ
  • "SIK1 is a class II HDAC kinase that promotes survival of skeletal myocytes."
    Berdeaux R., Goebel N., Banaszynski L., Takemori H., Wandless T., Shelton G.D., Montminy M.
    Nat. Med. 13:597-603(2007) [PubMed] [Europe PMC] [Abstract]
• repressing transcription factor binding Source: RGDInferred from sequence orthologyⁱ
  • "Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR."
    Fischle W., Dequiedt F., Hendzel M.J., Guenther M.G., Lazar M.A., Voelter W., Verdin E.
    Mol. Cell 9:45-57(2002) [PubMed] [Europe PMC] [Abstract]
• RNA polymerase II transcription factor binding Source: RGDInferred from sequence orthologyⁱ
  • "Involvement of Epac1/Rap1/CaMKI/HDAC5 signaling cascade in the regulation of placental cell fusion."
    Chang C.W., Cheong M.L., Chang G.D., Tsai M.S., Chen H.
    Mol. Hum. Reprod. 19:745-755(2013) [PubMed] [Europe PMC] [Abstract]
• 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