Histone deacetylase 3

<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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  + L-lysyl-[histone]

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  EC:3.5.1.98
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  • See the description of this EC number in ENZYME.
  Source: Rhea

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  • See the description of this reaction in 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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  zoom

  +

  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

• chromatin binding Source: MGI <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
  • "The histone-binding code of nuclear receptor co-repressors matches the substrate specificity of histone deacetylase 3."
    Hartman H.B., Yu J., Alenghat T., Ishizuka T., Lazar M.A.
    EMBO Rep. 6:445-451(2005) [PubMed] [Europe PMC] [Abstract]
  • "Histone deacetylase 3 modulates Tbx5 activity to regulate early cardiogenesis."
    Lewandowski S.L., Janardhan H.P., Smee K.M., Bachman M., Sun Z., Lazar M.A., Trivedi C.M.
    Hum. Mol. Genet. 23:3801-3809(2014) [PubMed] [Europe PMC] [Abstract]
• chromatin DNA binding Source: MGIInferred from direct assayⁱ
  • "Pitx2 is functionally important in the early stages of vascular smooth muscle cell differentiation."
    Shang Y., Yoshida T., Amendt B.A., Martin J.F., Owens G.K.
    J. Cell Biol. 181:461-473(2008) [PubMed] [Europe PMC] [Abstract]
• cyclin binding Source: MGI
• deacetylase activity Source: MGI
• DNA binding Source: MGIInferred from direct assayⁱ
  • "A corepressor/coactivator exchange complex required for transcriptional activation by nuclear receptors and other regulated transcription factors."
    Perissi V., Aggarwal A., Glass C.K., Rose D.W., Rosenfeld M.G.
    Cell 116:511-526(2004) [PubMed] [Europe PMC] [Abstract]
  • "Corepressors selectively control the transcriptional activity of PPARgamma in adipocytes."
    Guan H.P., Ishizuka T., Chui P.C., Lehrke M., Lazar M.A.
    Genes Dev. 19:453-461(2005) [PubMed] [Europe PMC] [Abstract]
• enzyme binding Source: MGI
• GTPase binding Source: MGI
• histone deacetylase activity Source: MGI
• histone deacetylase binding Source: MGI
• NAD-dependent histone deacetylase activity (H3-K14 specific) Source: UniProtKB-EC
• NF-kappaB binding Source: MGI
• protein deacetylase activity Source: MGIInferred from direct assayⁱ
  • "Histone deacetylase 3 interacts with and deacetylates myocyte enhancer factor 2."
    Gregoire S., Xiao L., Nie J., Zhang X., Xu M., Li J., Wong J., Seto E., Yang X.J.
    Mol. Cell. Biol. 27:1280-1295(2007) [PubMed] [Europe PMC] [Abstract]
  • "Histone deacetylase 3 modulates Tbx5 activity to regulate early cardiogenesis."
    Lewandowski S.L., Janardhan H.P., Smee K.M., Bachman M., Sun Z., Lazar M.A., Trivedi C.M.
    Hum. Mol. Genet. 23:3801-3809(2014) [PubMed] [Europe PMC] [Abstract]
  • "Leucine-rich repeat kinase 2 exacerbates neuronal cytotoxicity through phosphorylation of histone deacetylase 3 and histone deacetylation."
    Han K.A., Shin W.H., Jung S., Seol W., Seo H., Ko C., Chung K.C.
    Hum. Mol. Genet. 26:1-18(2017) [PubMed] [Europe PMC] [Abstract]
• transcription corepressor activity Source: UniProtKB
• transcription factor binding Source: MGIInferred from direct assayⁱ
  • "Histone deacetylase 3 interacts with and deacetylates myocyte enhancer factor 2."
    Gregoire S., Xiao L., Nie J., Zhang X., Xu M., Li J., Wong J., Seto E., Yang X.J.
    Mol. Cell. Biol. 27:1280-1295(2007) [PubMed] [Europe PMC] [Abstract]

GO - Biological processⁱ

• cellular response to fluid shear stress Source: UniProtKB
• chromatin organization Source: UniProtKB <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#tas">GO evidence code guide</a></p> Traceable author statementⁱ
  • "Class II histone deacetylases: versatile regulators."
    Verdin E., Dequiedt F., Kasler H.G.
    Trends Genet. 19:286-293(2003) [PubMed] [Europe PMC] [Abstract]
• circadian regulation of gene expression Source: UniProtKB <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
  • Ref.15

    "Distinct roles of HDAC3 in the core circadian negative feedback loop are critical for clock function."
    Shi G., Xie P., Qu Z., Zhang Z., Dong Z., An Y., Xing L., Liu Z., Dong Y., Xu G., Yang L., Liu Y., Xu Y.
    Cell Rep. 14:823-834(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INTERACTION WITH FBXL3; ARNTL AND CRY1, MUTAGENESIS OF 134-HIS--ALA-136 AND SER-424.
• histone deacetylation Source: MGIInferred from mutant phenotypeⁱ
  • "The histone-binding code of nuclear receptor co-repressors matches the substrate specificity of histone deacetylase 3."
    Hartman H.B., Yu J., Alenghat T., Ishizuka T., Lazar M.A.
    EMBO Rep. 6:445-451(2005) [PubMed] [Europe PMC] [Abstract]
• histone H3 deacetylation Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief. Bioinformatics 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• histone H4 deacetylation Source: MGIInferred from direct assayⁱ
  • "Leucine-rich repeat kinase 2 exacerbates neuronal cytotoxicity through phosphorylation of histone deacetylase 3 and histone deacetylation."
    Han K.A., Shin W.H., Jung S., Seol W., Seo H., Ko C., Chung K.C.
    Hum. Mol. Genet. 26:1-18(2017) [PubMed] [Europe PMC] [Abstract]
• histone H4-K12 deacetylation Source: MGIInferred from direct assayⁱ
  • "Leucine-rich repeat kinase 2 exacerbates neuronal cytotoxicity through phosphorylation of histone deacetylase 3 and histone deacetylation."
    Han K.A., Shin W.H., Jung S., Seol W., Seo H., Ko C., Chung K.C.
    Hum. Mol. Genet. 26:1-18(2017) [PubMed] [Europe PMC] [Abstract]
• negative regulation of cardiac muscle cell differentiation Source: MGIInferred from mutant phenotypeⁱ
  • "Histone deacetylase 3 modulates Tbx5 activity to regulate early cardiogenesis."
    Lewandowski S.L., Janardhan H.P., Smee K.M., Bachman M., Sun Z., Lazar M.A., Trivedi C.M.
    Hum. Mol. Genet. 23:3801-3809(2014) [PubMed] [Europe PMC] [Abstract]
• negative regulation of DNA-binding transcription factor activity Source: MGIInferred from direct assayⁱ
  • "Histone deacetylase 3 modulates Tbx5 activity to regulate early cardiogenesis."
    Lewandowski S.L., Janardhan H.P., Smee K.M., Bachman M., Sun Z., Lazar M.A., Trivedi C.M.
    Hum. Mol. Genet. 23:3801-3809(2014) [PubMed] [Europe PMC] [Abstract]
• negative regulation of interleukin-1 production Source: MGI
• negative regulation of JNK cascade Source: MGI
• negative regulation of protein export from nucleus Source: MGI
• negative regulation of transcription, DNA-templated Source: MGI
• negative regulation of transcription by RNA polymerase II Source: MGI <p>Inferred from Genetic Interaction</p> <p>Used to describe "traditional" genetic interactions such as suppressors and synthetic lethals as well as other techniques such as functional complementation, rescue experiments, or inferences about a gene drawn from the phenotype of a mutation in a different gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#igi">GO evidence code guide</a></p> Inferred from genetic interactionⁱ
  • "Histone deacetylase 3 interacts with and deacetylates myocyte enhancer factor 2."
    Gregoire S., Xiao L., Nie J., Zhang X., Xu M., Li J., Wong J., Seto E., Yang X.J.
    Mol. Cell. Biol. 27:1280-1295(2007) [PubMed] [Europe PMC] [Abstract]
  • "NFATc1 mediates HDAC-dependent transcriptional repression of osteocalcin expression during osteoblast differentiation."
    Choo M.K., Yeo H., Zayzafoon M.
    Bone 45:579-589(2009) [PubMed] [Europe PMC] [Abstract]
  • "Histone deacetylase 3 modulates Tbx5 activity to regulate early cardiogenesis."
    Lewandowski S.L., Janardhan H.P., Smee K.M., Bachman M., Sun Z., Lazar M.A., Trivedi C.M.
    Hum. Mol. Genet. 23:3801-3809(2014) [PubMed] [Europe PMC] [Abstract]
• negative regulation of tumor necrosis factor production Source: MGI
• positive regulation of cold-induced thermogenesis Source: YuBioLabInferred from mutant phenotypeⁱ
  • "Histone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge."
    Emmett M.J., Lim H.W., Jager J., Richter H.J., Adlanmerini M., Peed L.C., Briggs E.R., Steger D.J., Ma T., Sims C.A., Baur J.A., Pei L., Won K.J., Seale P., Gerhart-Hines Z., Lazar M.A.
    Nature 546:544-548(2017) [PubMed] [Europe PMC] [Abstract]
• positive regulation of neuron apoptotic process Source: MGI
• positive regulation of protein import into nucleus Source: UniProtKB
• positive regulation of protein phosphorylation Source: UniProtKB
• positive regulation of protein ubiquitination Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.15

    "Distinct roles of HDAC3 in the core circadian negative feedback loop are critical for clock function."
    Shi G., Xie P., Qu Z., Zhang Z., Dong Z., An Y., Xing L., Liu Z., Dong Y., Xu G., Yang L., Liu Y., Xu Y.
    Cell Rep. 14:823-834(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INTERACTION WITH FBXL3; ARNTL AND CRY1, MUTAGENESIS OF 134-HIS--ALA-136 AND SER-424.
• positive regulation of TOR signaling Source: UniProtKB
• positive regulation of transcription by RNA polymerase II Source: UniProtKB
• positive regulation of type B pancreatic cell apoptotic process Source: MGI
• protein deacetylation Source: MGI
• regulation of circadian rhythm Source: UniProtKBInferred from mutant phenotypeⁱ
  • Ref.15

    "Distinct roles of HDAC3 in the core circadian negative feedback loop are critical for clock function."
    Shi G., Xie P., Qu Z., Zhang Z., Dong Z., An Y., Xing L., Liu Z., Dong Y., Xu G., Yang L., Liu Y., Xu Y.
    Cell Rep. 14:823-834(2016) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INTERACTION WITH FBXL3; ARNTL AND CRY1, MUTAGENESIS OF 134-HIS--ALA-136 AND SER-424.
• regulation of mitotic cell cycle Source: MGIInferred from direct assayⁱ
  • "Cloning and expression of a murine histone deacetylase 3 (mHdac3) cDNA and mapping to a region of conserved synteny between murine chromosome 18 and human chromosome 5."
    Dangond F., Foerznler D., Weremowicz S., Morton C.C., Beier D.R., Gullans S.R.
    Mol. Cell Biol. Res. Commun. 2:91-96(1999) [PubMed] [Europe PMC] [Abstract]
• regulation of multicellular organism growth Source: MGIInferred from genetic interactionⁱ
  • Ref.9

    "Nuclear receptor corepressor and histone deacetylase 3 govern circadian metabolic physiology."
    Alenghat T., Meyers K., Mullican S.E., Leitner K., Adeniji-Adele A., Avila J., Bucan M., Ahima R.S., Kaestner K.H., Lazar M.A.
    Nature 456:997-1000(2008) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, INTERACTION WITH NCOR1.
• regulation of protein stability Source: UniProtKB
• spindle assembly Source: MGI

<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

<p>This subsection of the 'Pathology and Biotech' section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypeⁱ

Mutagenesis

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 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

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• cyclin binding Source: MGI
• enzyme binding Source: MGI
• GTPase binding Source: MGI
• histone deacetylase binding Source: MGI
• NF-kappaB binding Source: MGI
• transcription factor binding Source: MGIInferred from direct assayⁱ
  • "Histone deacetylase 3 interacts with and deacetylates myocyte enhancer factor 2."
    Gregoire S., Xiao L., Nie J., Zhang X., Xu M., Li J., Wong J., Seto E., Yang X.J.
    Mol. Cell. Biol. 27:1280-1295(2007) [PubMed] [Europe PMC] [Abstract]

Protein-protein interaction databases

Chemistry databases

Miscellaneous 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

<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

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>Sequences (2+)ⁱ

<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.

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

        10         20         30         40         50
MAKTVAYFYD PDVGNFHYGA GHPMKPHRLA LTHSLVLHYG LYKKMIVFKP 
        60         70         80         90        100
YQASQHDMCR FHSEDYIDFL QRVSPTNMQG FTKSLNAFNV GDDCPVFPGL 
       110        120        130        140        150
FEFCSRYTGA SLQGATQLNN KICDIAINWA GGLHHAKKFE ASGFCYVNDI 
       160        170        180        190        200
VIGILELLKY HPRVLYIDID IHHGDGVQEA FYLTDRVMTV SFHKYGNYFF 
       210        220        230        240        250
PGTGDMYEVG AESGRYYCLN VPLRDGIDDQ SYKHLFQPVI SQVVDFYQPT 
       260        270        280        290        300
CIVLQCGADS LGCDRLGCFN LSIRGHGECV EYVKSFNIPL LVLGGGGYTV 
       310        320        330        340        350
RNVARCWTYE TSLLVEEAIS EELPYSEYFE YFAPDFTLHP DVSTRIENQN 
       360        370        380        390        400
SRQYLDQIRQ TIFENLKMLN HAPSVQIHDV PADLLTYDRT DEADAEERGP 
       410        420 
EENYSRPEAP NEFYDGDHDN DKES                             

        10         20         30         40         50
MAKTVAYFYD PDVGNFHYGA GHPMKPHRLA LTHSLVLHYG LYKKMIVFKP 
        60         70         80         90        100
YQASQHDMCR FHSEDYIDSL GCDRLGCFNL SIRGHGECVE YVKSFNIPLL 
       110        120        130        140        150
VLGGGGYTVR NVARCWTYET SLLVEEAISE ELPYSEYFEY FAPDFTLHPD 
       160        170        180        190        200
VSTRIENQNS RQYLDQIRQT IFENLKMLNH APSVQIHDVP ADLLTYDRTD 
       210        220        230 
EADAEERGPE ENYSRPEAPN EFYDGDHDND KES                   

Alternative sequence

Sequence databases

Keywords - Coding sequence diversityⁱ

<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

• 100% Identity
• 90% Identity
• 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

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Miscellaneous 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
2. MGD cross-references
   Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot