ID HDAC3_HUMAN Reviewed; 428 AA.
AC O15379; D3DQE1; O43268; Q9UEI5; Q9UEV0;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 27-MAR-2024, entry version 234.
DE RecName: Full=Histone deacetylase 3;
DE Short=HD3;
DE EC=3.5.1.98 {ECO:0000269|PubMed:28497810, ECO:0000305|PubMed:23911289};
DE AltName: Full=Protein deacetylase HDAC3;
DE EC=3.5.1.- {ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:25301942, ECO:0000305|PubMed:21030595, ECO:0000305|PubMed:21444723};
DE AltName: Full=Protein deacylase HDAC3 {ECO:0000305};
DE EC=3.5.1.- {ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:29192674, ECO:0000269|PubMed:34608293};
DE AltName: Full=RPD3-2;
DE AltName: Full=SMAP45;
GN Name=HDAC3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC TISSUE=Spleen, and T-cell;
RX PubMed=9464271; DOI=10.1006/bbrc.1997.8033;
RA Dangond F., Hafler D.A., Tong J.K., Randall J., Kojima R., Utku N.,
RA Gullans S.R.;
RT "Differential display cloning of a novel human histone deacetylase (HDAC3)
RT cDNA from PHA-activated immune cells.";
RL Biochem. Biophys. Res. Commun. 242:648-652(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Fibroblast;
RX PubMed=9346952; DOI=10.1074/jbc.272.44.28001;
RA Yang W.-M., Yao Y.-L., Sun J.-M., Davie J.R., Seto E.;
RT "Isolation and characterization of cDNAs corresponding to an additional
RT member of the human histone deacetylase gene family.";
RL J. Biol. Chem. 272:28001-28007(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9501169; DOI=10.1073/pnas.95.6.2795;
RA Emiliani S., Fischle W., van Lint C., Al-Abed Y., Verdin E.;
RT "Characterization of a human RPD3 ortholog, HDAC3.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:2795-2800(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX PubMed=10051405; DOI=10.1006/geno.1998.5645;
RA Mahlknecht U., Emiliani S., Najfeld V., Young S., Verdin E.;
RT "Genomic organization and chromosomal localization of the human histone
RT deacetylase 3 gene.";
RL Genomics 56:197-202(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [7]
RP INTERACTION WITH HHV-5 IMMEDIATE EARLY PROTEIN IE1 (MICROBIAL INFECTION).
RX PubMed=15572445; DOI=10.1073/pnas.0407933101;
RA Nevels M., Paulus C., Shenk T.;
RT "Human cytomegalovirus immediate-early 1 protein facilitates viral
RT replication by antagonizing histone deacetylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:17234-17239(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-353 AND 407-428.
RA Lynch E.D., Lee M.K., King M.-C.;
RL Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP INTERACTION WITH NRIP1.
RX PubMed=11006275; DOI=10.1074/jbc.m004821200;
RA Wei L.-N., Hu X., Chandra D., Seto E., Farooqui M.;
RT "Receptor-interacting protein 140 directly recruits histone deacetylases
RT for gene silencing.";
RL J. Biol. Chem. 275:40782-40787(2000).
RN [10]
RP INTERACTION WITH DAXX.
RX PubMed=10669754; DOI=10.1128/mcb.20.5.1784-1796.2000;
RA Li H., Leo C., Zhu J., Wu X., O'Neil J., Park E.-J., Chen J.D.;
RT "Sequestration and inhibition of Daxx-mediated transcriptional repression
RT by PML.";
RL Mol. Cell. Biol. 20:1784-1796(2000).
RN [11]
RP INTERACTION WITH HDAC9.
RX PubMed=10655483; DOI=10.1073/pnas.97.3.1056;
RA Zhou X., Richon V.M., Rifkind R.A., Marks P.A.;
RT "Identification of a transcriptional repressor related to the noncatalytic
RT domain of histone deacetylases 4 and 5.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:1056-1061(2000).
RN [12]
RP IDENTIFICATION IN A COMPLEX WITH NCOR1 AND NCOR2.
RX PubMed=10860984; DOI=10.1073/pnas.97.13.7202;
RA Wen Y.-D., Perissi V., Staszewski L.M., Yang W.-M., Krones A., Glass C.K.,
RA Rosenfeld M.G., Seto E.;
RT "The histone deacetylase-3 complex contains nuclear receptor
RT corepressors.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7202-7207(2000).
RN [13]
RP INTERACTION WITH HDAC7.
RX PubMed=11466315; DOI=10.1074/jbc.m104935200;
RA Fischle W., Dequiedt F., Fillion M., Hendzel M.J., Voelter W., Verdin E.;
RT "Human HDAC7 histone deacetylase activity is associated with HDAC3 in
RT vivo.";
RL J. Biol. Chem. 276:35826-35835(2001).
RN [14]
RP INTERACTION WITH CBFA2T3.
RX PubMed=11533236; DOI=10.1128/mcb.21.19.6470-6483.2001;
RA Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N.,
RA Downing J.R., Meyers S., Hiebert S.W.;
RT "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with
RT multiple histone deacetylases and binds mSin3A through its oligomerization
RT domain.";
RL Mol. Cell. Biol. 21:6470-6483(2001).
RN [15]
RP INTERACTION WITH HDAC10.
RX PubMed=11861901; DOI=10.1093/nar/30.5.1114;
RA Tong J.J., Liu J., Bertos N.R., Yang X.-J.;
RT "Identification of HDAC10, a novel class II human histone deacetylase
RT containing a leucine-rich domain.";
RL Nucleic Acids Res. 30:1114-1123(2002).
RN [16]
RP SUMOYLATION.
RX PubMed=12032081; DOI=10.1093/emboj/21.11.2682;
RA Kirsh O., Seeler J.-S., Pichler A., Gast A., Mueller S., Miska E.,
RA Mathieu M., Harel-Bellan A., Kouzarides T., Melchior F., Dejean A.;
RT "The SUMO E3 ligase RanBP2 promotes modification of the HDAC4
RT deacetylase.";
RL EMBO J. 21:2682-2691(2002).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND COMPONENT OF THE N-COR COMPLEX
RP WITH NCOR2 AND TBL1X.
RX PubMed=10809664;
RA Guenther M.G., Lane W.S., Fischle W., Verdin E., Lazar M.A.,
RA Shiekhattar R.;
RT "A core SMRT corepressor complex containing HDAC3 and TBL1, a WD40-repeat
RT protein linked to deafness.";
RL Genes Dev. 14:1048-1057(2000).
RN [18]
RP COMPONENT OF THE N-COR COMPLEX WITH NCOR2 AND HDAC3.
RX PubMed=10944117; DOI=10.1093/emboj/19.16.4342;
RA Li J., Wang J., Wang J., Nawaz Z., Liu J.M., Qin J., Wong J.;
RT "Both corepressor proteins SMRT and N-CoR exist in large protein complexes
RT containing HDAC3.";
RL EMBO J. 19:4342-4350(2000).
RN [19]
RP INTERACTION WITH BCOR.
RX PubMed=10898795;
RA Huynh K.D., Fischle W., Verdin E., Bardwell V.J.;
RT "BCoR, a novel corepressor involved in BCL-6 repression.";
RL Genes Dev. 14:1810-1823(2000).
RN [20]
RP COMPONENT OF THE N-COR COMPLEX WITH NCOR1; NCOR2; GPS2; TBL1R AND TBL1X.
RX PubMed=11931768; DOI=10.1016/s1097-2765(02)00468-9;
RA Zhang J., Kalkum M., Chait B.T., Roeder R.G.;
RT "The N-CoR-HDAC3 nuclear receptor corepressor complex inhibits the JNK
RT pathway through the integral subunit GPS2.";
RL Mol. Cell 9:611-623(2002).
RN [21]
RP COMPONENT OF THE N-COR COMPLEX WITH TBL1R; TBL1X AND CORO2A.
RX PubMed=12628926; DOI=10.1093/emboj/cdg120;
RA Yoon H.-G., Chan D.W., Huang Z.-Q., Li J., Fondell J.D., Qin J., Wong J.;
RT "Purification and functional characterization of the human N-CoR complex:
RT the roles of HDAC3, TBL1 and TBLR1.";
RL EMBO J. 22:1336-1346(2003).
RN [22]
RP INTERACTION WITH APEX1.
RX PubMed=14633989; DOI=10.1093/emboj/cdg595;
RA Bhakat K.K., Izumi T., Yang S.H., Hazra T.K., Mitra S.;
RT "Role of acetylated human AP-endonuclease (APE1/Ref-1) in regulation of the
RT parathyroid hormone gene.";
RL EMBO J. 22:6299-6309(2003).
RN [23]
RP INTERACTION WITH DACH1.
RX PubMed=14525983; DOI=10.1074/jbc.m310021200;
RA Wu K., Yang Y., Wang C., Davoli M.A., D'Amico M., Li A., Cveklova K.,
RA Kozmik Z., Lisanti M.P., Russell R.G., Cvekl A., Pestell R.G.;
RT "DACH1 inhibits transforming growth factor-beta signaling through binding
RT Smad4.";
RL J. Biol. Chem. 278:51673-51684(2003).
RN [24]
RP INTERACTION WITH SRY.
RX PubMed=15297880; DOI=10.1038/sj.emboj.7600352;
RA Thevenet L., Mejean C., Moniot B., Bonneaud N., Galeotti N.,
RA Aldrian-Herrada G., Poulat F., Berta P., Benkirane M., Boizet-Bonhoure B.;
RT "Regulation of human SRY subcellular distribution by its
RT acetylation/deacetylation.";
RL EMBO J. 23:3336-3345(2004).
RN [25]
RP INTERACTION WITH KDM4A.
RX PubMed=15927959; DOI=10.1074/jbc.m413687200;
RA Gray S.G., Iglesias A.H., Lizcano F., Villanueva R., Camelo S., Jingu H.,
RA Teh B.T., Koibuchi N., Chin W.W., Kokkotou E., Dangond F.;
RT "Functional characterization of JMJD2A, a histone deacetylase- and
RT retinoblastoma-binding protein.";
RL J. Biol. Chem. 280:28507-28518(2005).
RN [26]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15653507; DOI=10.1126/science.1105166;
RA Yuan Z.L., Guan Y.J., Chatterjee D., Chin Y.E.;
RT "Stat3 dimerization regulated by reversible acetylation of a single lysine
RT residue.";
RL Science 307:269-273(2005).
RN [27]
RP INTERACTION WITH INSM1.
RX PubMed=16569215; DOI=10.1042/bj20051669;
RA Liu W.D., Wang H.W., Muguira M., Breslin M.B., Lan M.S.;
RT "INSM1 functions as a transcriptional repressor of the neuroD/beta2 gene
RT through the recruitment of cyclin D1 and histone deacetylases.";
RL Biochem. J. 397:169-177(2006).
RN [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [29]
RP INTERACTION WITH INSM1.
RX PubMed=18417529; DOI=10.1677/joe-08-0001;
RA Wang H.W., Muguira M., Liu W.D., Zhang T., Chen C., Aucoin R.,
RA Breslin M.B., Lan M.S.;
RT "Identification of an INSM1-binding site in the insulin promoter: negative
RT regulation of the insulin gene transcription.";
RL J. Endocrinol. 198:29-39(2008).
RN [30]
RP INTERACTION WITH DHX36.
RX PubMed=18279852; DOI=10.1016/j.yexcr.2008.01.006;
RA Iwamoto F., Stadler M., Chalupnikova K., Oakeley E., Nagamine Y.;
RT "Transcription-dependent nucleolar cap localization and possible nuclear
RT function of DExH RNA helicase RHAU.";
RL Exp. Cell Res. 314:1378-1391(2008).
RN [31]
RP INTERACTION WITH NKAP.
RX PubMed=19409814; DOI=10.1016/j.immuni.2009.02.011;
RA Pajerowski A.G., Nguyen C., Aghajanian H., Shapiro M.J., Shapiro V.S.;
RT "NKAP is a transcriptional repressor of notch signaling and is required for
RT T cell development.";
RL Immunity 30:696-707(2009).
RN [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-424, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [33]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH CCAR2 AND MEF2D, AND
RP SUBCELLULAR LOCATION.
RX PubMed=21030595; DOI=10.1074/jbc.m110.153270;
RA Chini C.C., Escande C., Nin V., Chini E.N.;
RT "HDAC3 is negatively regulated by the nuclear protein DBC1.";
RL J. Biol. Chem. 285:40830-40837(2010).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [35]
RP INTERACTION WITH BEND3.
RX PubMed=21914818; DOI=10.1242/jcs.086603;
RA Sathyan K.M., Shen Z., Tripathi V., Prasanth K.V., Prasanth S.G.;
RT "A BEN-domain-containing protein associates with heterochromatin and
RT represses transcription.";
RL J. Cell Sci. 124:3149-3163(2011).
RN [36]
RP FUNCTION IN DEACETYLATION OF MAPK14.
RX PubMed=21444723; DOI=10.1128/mcb.01205-10;
RA Pillai V.B., Sundaresan N.R., Samant S.A., Wolfgeher D., Trivedi C.M.,
RA Gupta M.P.;
RT "Acetylation of a conserved lysine residue in the ATP binding pocket of p38
RT augments its kinase activity during hypertrophy of cardiomyocytes.";
RL Mol. Cell. Biol. 31:2349-2363(2011).
RN [37]
RP FUNCTION IN DEACETYLATION OF H3K27, CATALYTIC ACTIVITY, AND IDENTIFICATION
RP IN A COMPLEX WITH BCL6 AND NCOR2.
RX PubMed=23911289; DOI=10.1016/j.celrep.2013.06.016;
RA Hatzi K., Jiang Y., Huang C., Garrett-Bakelman F., Gearhart M.D.,
RA Giannopoulou E.G., Zumbo P., Kirouac K., Bhaskara S., Polo J.M.,
RA Kormaksson M., Mackerell A.D. Jr., Xue F., Mason C.E., Hiebert S.W.,
RA Prive G.G., Cerchietti L., Bardwell V.J., Elemento O., Melnick A.;
RT "A hybrid mechanism of action for BCL6 in B cells defined by formation of
RT functionally distinct complexes at enhancers and promoters.";
RL Cell Rep. 4:578-588(2013).
RN [38]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-424, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [39]
RP FUNCTION, INTERACTION WITH XBP1, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=25190803; DOI=10.1074/jbc.m114.571984;
RA Martin D., Li Y., Yang J., Wang G., Margariti A., Jiang Z., Yu H.,
RA Zampetaki A., Hu Y., Xu Q., Zeng L.;
RT "Unspliced X-box-binding protein 1 (XBP1) protects endothelial cells from
RT oxidative stress through interaction with histone deacetylase 3.";
RL J. Biol. Chem. 289:30625-30634(2014).
RN [40]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF TYR-298.
RX PubMed=25301942; DOI=10.1074/jbc.m114.575266;
RA Yi J., Huang X., Yang Y., Zhu W.G., Gu W., Luo J.;
RT "Regulation of histone acetyltransferase TIP60 function by histone
RT deacetylase 3.";
RL J. Biol. Chem. 289:33878-33886(2014).
RN [41]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 130-ALA--GLY-132.
RX PubMed=28497810; DOI=10.1038/cr.2017.68;
RA Wei W., Liu X., Chen J., Gao S., Lu L., Zhang H., Ding G., Wang Z.,
RA Chen Z., Shi T., Li J., Yu J., Wong J.;
RT "Class I histone deacetylases are major histone decrotonylases: evidence
RT for critical and broad function of histone crotonylation in
RT transcription.";
RL Cell Res. 27:898-915(2017).
RN [42]
RP FUNCTION, AND INTERACTION WITH RARA.
RX PubMed=28167758; DOI=10.1073/pnas.1621425114;
RA Lee D.Y., Lin T.E., Lee C.I., Zhou J., Huang Y.H., Lee P.L., Shih Y.T.,
RA Chien S., Chiu J.J.;
RT "MicroRNA-10a is crucial for endothelial response to different flow
RT patterns via interaction of retinoid acid receptors and histone
RT deacetylases.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:2072-2077(2017).
RN [43]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29192674; DOI=10.1038/cr.2017.149;
RA Huang H., Luo Z., Qi S., Huang J., Xu P., Wang X., Gao L., Li F., Wang J.,
RA Zhao W., Gu W., Chen Z., Dai L., Dai J., Zhao Y.;
RT "Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation
RT pathway.";
RL Cell Res. 28:111-125(2018).
RN [44]
RP FUNCTION, AND DEUBIQUITINATION BY USP38.
RX PubMed=32404892; DOI=10.1038/s41389-020-0234-z;
RA Zhan W., Liao X., Liu J., Tian T., Yu L., Li R.;
RT "USP38 regulates the stemness and chemoresistance of human colorectal
RT cancer via regulation of HDAC3.";
RL Oncogenesis 9:48-48(2020).
RN [45]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 130-ALA--GLY-132.
RX PubMed=34608293; DOI=10.1038/s41589-021-00875-7;
RA Song X., Yang F., Liu X., Xia P., Yin W., Wang Z., Wang Y., Yuan X.,
RA Dou Z., Jiang K., Ma M., Hu B., Zhang R., Xu C., Zhang Z., Ruan K.,
RA Tian R., Li L., Liu T., Hill D.L., Zang J., Liu X., Li J., Cheng J.,
RA Yao X.;
RT "Dynamic crotonylation of EB1 by TIP60 ensures accurate spindle positioning
RT in mitosis.";
RL Nat. Chem. Biol. 17:1314-1323(2021).
CC -!- FUNCTION: Histone deacetylase that catalyzes the deacetylation of
CC lysine residues on the N-terminal part of the core histones (H2A, H2B,
CC H3 and H4), and some other non-histone substrates (PubMed:23911289,
CC PubMed:21030595, PubMed:21444723, PubMed:25301942, PubMed:28497810,
CC PubMed:28167758, PubMed:32404892). Histone deacetylation gives a tag
CC for epigenetic repression and plays an important role in
CC transcriptional regulation, cell cycle progression and developmental
CC events (PubMed:23911289). Histone deacetylases act via the formation of
CC large multiprotein complexes (PubMed:23911289). Participates in the
CC BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-
CC 27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase
CC activity and repressing proximal gene expression (PubMed:23911289).
CC Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML
CC bodies for sumoylation (By similarity). Contributes, together with XBP1
CC isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription
CC factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling
CC pathway leading to endothelial cell (EC) survival under disturbed
CC flow/oxidative stress (PubMed:25190803). Regulates both the
CC transcriptional activation and repression phases of the circadian clock
CC in a deacetylase activity-independent manner (By similarity). During
CC the activation phase, promotes the accumulation of ubiquitinated BMAL1
CC at the E-boxes and during the repression phase, blocks FBXL3-mediated
CC CRY1/2 ubiquitination and promotes the interaction of CRY1 and BMAL1
CC (By similarity). The NCOR1-HDAC3 complex regulates the circadian
CC expression of the core clock gene BMAL1 and the genes involved in lipid
CC metabolism in the liver (By similarity). Also functions as a
CC deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14, RARA
CC and STAT3 (PubMed:15653507, PubMed:21030595, PubMed:21444723,
CC PubMed:25301942, PubMed:28167758). Serves as a corepressor of RARA,
CC mediating its deacetylation and repression, leading to inhibition of
CC RARE DNA element binding (PubMed:28167758). In association with RARA,
CC plays a role in the repression of microRNA-10a and thereby in the
CC inflammatory response (PubMed:28167758). In addition to protein
CC deacetylase activity, also acts as a protein-lysine deacylase by
CC recognizing other acyl groups: catalyzes removal of (2E)-butenoyl
CC (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups
CC from lysine residues, leading to protein decrotonylation and de-2-
CC hydroxyisobutyrylation, respectively (PubMed:28497810, PubMed:29192674,
CC PubMed:34608293). Catalyzes decrotonylation of MAPRE1/EB1
CC (PubMed:34608293). {ECO:0000250|UniProtKB:O88895,
CC ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:21030595,
CC ECO:0000269|PubMed:21444723, ECO:0000269|PubMed:23911289,
CC ECO:0000269|PubMed:25190803, ECO:0000269|PubMed:25301942,
CC ECO:0000269|PubMed:28167758, ECO:0000269|PubMed:28497810,
CC ECO:0000269|PubMed:29192674, ECO:0000269|PubMed:32404892,
CC ECO:0000269|PubMed:34608293}.
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 Evidence={ECO:0000269|PubMed:28497810, ECO:0000305|PubMed:23911289};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58197;
CC Evidence={ECO:0000269|PubMed:28497810, ECO:0000305|PubMed:23911289};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] = acetate + L-lysyl-
CC [protein]; Xref=Rhea:RHEA:58108, Rhea:RHEA-COMP:9752, Rhea:RHEA-
CC COMP:10731, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969, ChEBI:CHEBI:30089,
CC ChEBI:CHEBI:61930; Evidence={ECO:0000269|PubMed:15653507,
CC ECO:0000269|PubMed:25301942, ECO:0000305|PubMed:21030595,
CC ECO:0000305|PubMed:21444723};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58109;
CC Evidence={ECO:0000269|PubMed:15653507, ECO:0000269|PubMed:25301942,
CC ECO:0000305|PubMed:21030595, ECO:0000305|PubMed:21444723};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-(2E)-butenoyl-L-lysyl-[protein] = (2E)-2-butenoate
CC + L-lysyl-[protein]; Xref=Rhea:RHEA:69172, Rhea:RHEA-COMP:9752,
CC Rhea:RHEA-COMP:13707, ChEBI:CHEBI:15377, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:35899, ChEBI:CHEBI:137954;
CC Evidence={ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:34608293};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69173;
CC Evidence={ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:34608293};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-(2-hydroxyisobutanoyl)-L-lysyl-[protein] = 2-
CC hydroxy-2-methylpropanoate + L-lysyl-[protein]; Xref=Rhea:RHEA:69176,
CC Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:15921, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:19641, ChEBI:CHEBI:29969, ChEBI:CHEBI:144968;
CC Evidence={ECO:0000269|PubMed:29192674};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69177;
CC Evidence={ECO:0000269|PubMed:29192674};
CC -!- SUBUNIT: Interacts with HDAC7 and HDAC9 (PubMed:11466315,
CC PubMed:10655483). Interacts with DAXX, KDM4A, HDAC10 and DACH1
CC (PubMed:10669754, PubMed:11861901, PubMed:14525983, PubMed:15927959).
CC Found in a complex with NCOR1 and NCOR2 (PubMed:10860984). Component of
CC the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3,
CC TBL1X, TBL1R, CORO2A and GPS2 (PubMed:11931768). Interacts with BCOR,
CC MJD2A/JHDM3A, NRIP1, PRDM6 and SRY (PubMed:10898795, PubMed:11006275,
CC PubMed:15297880). Interacts with BTBD14B (By similarity). Interacts
CC with GLIS2 (By similarity). Interacts (via the DNA-binding domain) with
CC NR2C1; the interaction recruits phosphorylated NR2C1 to PML bodies for
CC sumoylation (By similarity). Component of the Notch corepressor complex
CC (PubMed:19409814). Interacts with CBFA2T3 and NKAP (PubMed:11533236,
CC PubMed:19409814). Interacts with APEX1; the interaction is not
CC dependent on the acetylated status of APEX1 (PubMed:14633989).
CC Interacts with ZMYND15 (By similarity). Interacts with SMRT/NCOR2 and
CC BCL6 on DNA enhancer elements (PubMed:23911289). Interacts with INSM1
CC (PubMed:16569215, PubMed:18417529). Interacts with XBP1 isoform 1; the
CC interaction occurs in endothelial cell (EC) under disturbed flow
CC (PubMed:25190803). Interacts (via C-terminus) with CCAR2 (via N-
CC terminus) (PubMed:21030595). Interacts with and deacetylates MEF2D
CC (PubMed:21030595). Interacts with BEND3 (PubMed:21914818). Interacts
CC with NKAPL (By similarity). Interacts with DHX36; this interaction
CC occurs in a RNA-dependent manner (PubMed:18279852). Interacts weakly
CC with CRY1; this interaction is enhanced in the presence of FBXL3 (By
CC similarity). Interacts with FBXL3 and BMAL1 (By similarity). Interacts
CC with NCOR1 (By similarity). Interacts with RARA (PubMed:28167758).
CC Interacts with SETD5 (By similarity). {ECO:0000250|UniProtKB:O88895,
CC ECO:0000250|UniProtKB:Q6P6W3, ECO:0000269|PubMed:10655483,
CC ECO:0000269|PubMed:10669754, ECO:0000269|PubMed:10860984,
CC ECO:0000269|PubMed:10898795, ECO:0000269|PubMed:11006275,
CC ECO:0000269|PubMed:11466315, ECO:0000269|PubMed:11533236,
CC ECO:0000269|PubMed:11861901, ECO:0000269|PubMed:11931768,
CC ECO:0000269|PubMed:14525983, ECO:0000269|PubMed:14633989,
CC ECO:0000269|PubMed:15297880, ECO:0000269|PubMed:15927959,
CC ECO:0000269|PubMed:16569215, ECO:0000269|PubMed:18279852,
CC ECO:0000269|PubMed:18417529, ECO:0000269|PubMed:19409814,
CC ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:21914818,
CC ECO:0000269|PubMed:23911289, ECO:0000269|PubMed:25190803,
CC ECO:0000269|PubMed:28167758}.
CC -!- SUBUNIT: (Microbial infection) Interacts with human cytomegalovirus
CC (HHV-5) immediate early protein IE1; this interaction decreases histone
CC acetylation and allows transcriptional activation by the virus.
CC {ECO:0000269|PubMed:15572445}.
CC -!- INTERACTION:
CC O15379; O43823: AKAP8; NbExp=10; IntAct=EBI-607682, EBI-1237481;
CC O15379; Q9ULX6: AKAP8L; NbExp=5; IntAct=EBI-607682, EBI-357530;
CC O15379; Q9UKG1: APPL1; NbExp=2; IntAct=EBI-607682, EBI-741243;
CC O15379; P24385: CCND1; NbExp=3; IntAct=EBI-607682, EBI-375001;
CC O15379; P23771: GATA3; NbExp=7; IntAct=EBI-607682, EBI-6664760;
CC O15379; Q13227: GPS2; NbExp=6; IntAct=EBI-607682, EBI-713355;
CC O15379; Q13547: HDAC1; NbExp=2; IntAct=EBI-607682, EBI-301834;
CC O15379; O60341: KDM1A; NbExp=4; IntAct=EBI-607682, EBI-710124;
CC O15379; Q969R5: L3MBTL2; NbExp=6; IntAct=EBI-607682, EBI-739909;
CC O15379; P43356: MAGEA2B; NbExp=4; IntAct=EBI-607682, EBI-5650739;
CC O15379; Q9UIS9: MBD1; NbExp=3; IntAct=EBI-607682, EBI-867196;
CC O15379; P01106: MYC; NbExp=6; IntAct=EBI-607682, EBI-447544;
CC O15379; O75376: NCOR1; NbExp=5; IntAct=EBI-607682, EBI-347233;
CC O15379; Q9Y618: NCOR2; NbExp=13; IntAct=EBI-607682, EBI-80830;
CC O15379; Q15466: NR0B2; NbExp=2; IntAct=EBI-607682, EBI-3910729;
CC O15379; P48552: NRIP1; NbExp=2; IntAct=EBI-607682, EBI-746484;
CC O15379; P00558: PGK1; NbExp=2; IntAct=EBI-607682, EBI-709599;
CC O15379; P00558-1: PGK1; NbExp=3; IntAct=EBI-607682, EBI-16177310;
CC O15379; P60510: PPP4C; NbExp=2; IntAct=EBI-607682, EBI-1046072;
CC O15379; Q15022: SUZ12; NbExp=7; IntAct=EBI-607682, EBI-1264675;
CC O15379; O09106: Hdac1; Xeno; NbExp=2; IntAct=EBI-607682, EBI-301912;
CC O15379; P08393: ICP0; Xeno; NbExp=3; IntAct=EBI-607682, EBI-6148881;
CC O15379; Q60974: Ncor1; Xeno; NbExp=2; IntAct=EBI-607682, EBI-349004;
CC O15379; Q8CBD1: Nrip1; Xeno; NbExp=2; IntAct=EBI-607682, EBI-1771626;
CC O15379; P12504: vif; Xeno; NbExp=2; IntAct=EBI-607682, EBI-779991;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:21030595}. Cytoplasm
CC {ECO:0000269|PubMed:25190803}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:21030595}. Note=Colocalizes with XBP1 and AKT1 in
CC the cytoplasm (PubMed:25190803). Predominantly expressed in the nucleus
CC in the presence of CCAR2 (PubMed:21030595).
CC {ECO:0000269|PubMed:21030595, ECO:0000269|PubMed:25190803}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=RPD3-2B;
CC IsoId=O15379-1; Sequence=Displayed;
CC Name=2; Synonyms=RPD3-2A;
CC IsoId=O15379-2; Sequence=VSP_002079;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- INDUCTION: Up-regulated by disturbed flow in umbilical vein endothelial
CC cells in vitro (PubMed:25190803).
CC -!- PTM: Sumoylated in vitro. {ECO:0000269|PubMed:12032081}.
CC -!- PTM: Deubiquitinated on 'Lys-63'-linked ubiquitin chains by USP38;
CC leading to a decreased level of histone acetylation.
CC {ECO:0000269|PubMed:32404892}.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 1
CC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/40804/HDAC3";
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DR EMBL; U66914; AAC52038.1; -; mRNA.
DR EMBL; U75697; AAB88241.1; -; mRNA.
DR EMBL; U75696; AAB88240.1; -; mRNA.
DR EMBL; AF005482; AAB87752.1; -; mRNA.
DR EMBL; AF039703; AAC98927.1; -; mRNA.
DR EMBL; AF059650; AAC26509.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61915.1; -; Genomic_DNA.
DR EMBL; CH471062; EAW61916.1; -; Genomic_DNA.
DR EMBL; BC000614; AAH00614.1; -; mRNA.
DR EMBL; AF053138; AAC08351.1; -; Genomic_DNA.
DR EMBL; AF053137; AAC08351.1; JOINED; Genomic_DNA.
DR EMBL; AF053139; AAC08352.1; -; Genomic_DNA.
DR CCDS; CCDS4264.1; -. [O15379-1]
DR PIR; JC5834; JC5834.
DR RefSeq; NP_003874.2; NM_003883.3. [O15379-1]
DR PDB; 4A69; X-ray; 2.06 A; A/B=1-376.
DR PDBsum; 4A69; -.
DR AlphaFoldDB; O15379; -.
DR SMR; O15379; -.
DR BioGRID; 114368; 304.
DR CORUM; O15379; -.
DR DIP; DIP-24253N; -.
DR IntAct; O15379; 114.
DR MINT; O15379; -.
DR STRING; 9606.ENSP00000302967; -.
DR BindingDB; O15379; -.
DR ChEMBL; CHEMBL1829; -.
DR DrugBank; DB12565; Abexinostat.
DR DrugBank; DB05015; Belinostat.
DR DrugBank; DB01262; Decitabine.
DR DrugBank; DB11841; Entinostat.
DR DrugBank; DB12645; Givinostat.
DR DrugBank; DB11830; Mocetinostat.
DR DrugBank; DB06603; Panobinostat.
DR DrugBank; DB06819; Phenylbutyric acid.
DR DrugBank; DB05223; Pracinostat.
DR DrugBank; DB03766; Propanoic acid.
DR DrugBank; DB12847; Pyroxamide.
DR DrugBank; DB06176; Romidepsin.
DR DrugBank; DB00313; Valproic acid.
DR DrugBank; DB02546; Vorinostat.
DR DrugCentral; O15379; -.
DR GuidetoPHARMACOLOGY; 2617; -.
DR GlyGen; O15379; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O15379; -.
DR PhosphoSitePlus; O15379; -.
DR BioMuta; HDAC3; -.
DR EPD; O15379; -.
DR jPOST; O15379; -.
DR MassIVE; O15379; -.
DR MaxQB; O15379; -.
DR PaxDb; 9606-ENSP00000302967; -.
DR PeptideAtlas; O15379; -.
DR ProteomicsDB; 48618; -. [O15379-1]
DR ProteomicsDB; 48619; -. [O15379-2]
DR Pumba; O15379; -.
DR Antibodypedia; 3568; 1134 antibodies from 48 providers.
DR DNASU; 8841; -.
DR Ensembl; ENST00000305264.8; ENSP00000302967.3; ENSG00000171720.10. [O15379-1]
DR GeneID; 8841; -.
DR KEGG; hsa:8841; -.
DR MANE-Select; ENST00000305264.8; ENSP00000302967.3; NM_003883.4; NP_003874.2.
DR UCSC; uc003llf.3; human. [O15379-1]
DR AGR; HGNC:4854; -.
DR CTD; 8841; -.
DR DisGeNET; 8841; -.
DR GeneCards; HDAC3; -.
DR HGNC; HGNC:4854; HDAC3.
DR HPA; ENSG00000171720; Low tissue specificity.
DR MIM; 605166; gene.
DR neXtProt; NX_O15379; -.
DR OpenTargets; ENSG00000171720; -.
DR PharmGKB; PA29228; -.
DR VEuPathDB; HostDB:ENSG00000171720; -.
DR eggNOG; KOG1342; Eukaryota.
DR GeneTree; ENSGT00940000160487; -.
DR HOGENOM; CLU_007727_7_6_1; -.
DR InParanoid; O15379; -.
DR OMA; GWLRAFH; -.
DR OrthoDB; 1327607at2759; -.
DR PhylomeDB; O15379; -.
DR TreeFam; TF352182; -.
DR BRENDA; 3.5.1.98; 2681.
DR PathwayCommons; O15379; -.
DR Reactome; R-HSA-1368071; NR1D1 (REV-ERBA) represses gene expression.
DR Reactome; R-HSA-193670; p75NTR negatively regulates cell cycle via SC1.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-3214815; HDACs deacetylate histones.
DR Reactome; R-HSA-350054; Notch-HLH transcription pathway.
DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation.
DR Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis.
DR Reactome; R-HSA-400206; Regulation of lipid metabolism by PPARalpha.
DR Reactome; R-HSA-400253; Circadian Clock.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR Reactome; R-HSA-8940973; RUNX2 regulates osteoblast differentiation.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-HSA-9022537; Loss of MECP2 binding ability to the NCoR/SMRT complex.
DR Reactome; R-HSA-9022692; Regulation of MECP2 expression and activity.
DR Reactome; R-HSA-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR Reactome; R-HSA-9609690; HCMV Early Events.
DR Reactome; R-HSA-9701898; STAT3 nuclear events downstream of ALK signaling.
DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR Reactome; R-HSA-9707616; Heme signaling.
DR SABIO-RK; O15379; -.
DR SignaLink; O15379; -.
DR SIGNOR; O15379; -.
DR BioGRID-ORCS; 8841; 747 hits in 1178 CRISPR screens.
DR ChiTaRS; HDAC3; human.
DR GeneWiki; HDAC3; -.
DR GenomeRNAi; 8841; -.
DR Pharos; O15379; Tclin.
DR PRO; PR:O15379; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O15379; Protein.
DR Bgee; ENSG00000171720; Expressed in right hemisphere of cerebellum and 199 other cell types or tissues.
DR ExpressionAtlas; O15379; baseline and differential.
DR Genevisible; O15379; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0000118; C:histone deacetylase complex; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0017053; C:transcription repressor complex; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0031490; F:chromatin DNA binding; IEA:Ensembl.
DR GO; GO:0030332; F:cyclin binding; IPI:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; TAS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0004407; F:histone deacetylase activity; IDA:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:UniProtKB.
DR GO; GO:0160009; F:histone decrotonylase activity; IDA:UniProtKB.
DR GO; GO:0051059; F:NF-kappaB binding; IPI:UniProtKB.
DR GO; GO:0160010; F:protein de-2-hydroxyisobutyrylase activity; IDA:UniProtKB.
DR GO; GO:0160008; F:protein decrotonylase activity; IDA:UniProtKB.
DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:UniProtKB.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; IPI:UniProtKB.
DR GO; GO:0071498; P:cellular response to fluid shear stress; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; TAS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:1903575; P:cornified envelope assembly; IEA:Ensembl.
DR GO; GO:0140861; P:DNA repair-dependent chromatin remodeling; IDA:UniProt.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IDA:UniProt.
DR GO; GO:0061436; P:establishment of skin barrier; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:2000726; P:negative regulation of cardiac muscle cell differentiation; IEA:Ensembl.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IMP:UniProtKB.
DR GO; GO:0046329; P:negative regulation of JNK cascade; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IDA:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IEA:Ensembl.
DR GO; GO:0031647; P:regulation of protein stability; IDA:UniProtKB.
DR GO; GO:0051225; P:spindle assembly; IMP:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR CDD; cd10005; HDAC3; 1.
DR Gene3D; 3.40.800.20; Histone deacetylase domain; 1.
DR IDEAL; IID00428; -.
DR InterPro; IPR000286; His_deacetylse.
DR InterPro; IPR003084; His_deacetylse_1.
DR InterPro; IPR023801; His_deacetylse_dom.
DR InterPro; IPR037138; His_deacetylse_dom_sf.
DR InterPro; IPR023696; Ureohydrolase_dom_sf.
DR PANTHER; PTHR10625:SF25; HISTONE DEACETYLASE 3; 1.
DR PANTHER; PTHR10625; HISTONE DEACETYLASE HDAC1-RELATED; 1.
DR Pfam; PF00850; Hist_deacetyl; 1.
DR PIRSF; PIRSF037913; His_deacetylse_1; 1.
DR PRINTS; PR01270; HDASUPER.
DR PRINTS; PR01271; HISDACETLASE.
DR SUPFAM; SSF52768; Arginase/deacetylase; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Biological rhythms;
KW Chromatin regulator; Cytoplasm; Host-virus interaction; Hydrolase; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..428
FT /note="Histone deacetylase 3"
FT /id="PRO_0000114696"
FT REGION 3..316
FT /note="Histone deacetylase"
FT REGION 388..428
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 388..405
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 411..428
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 135
FT /evidence="ECO:0000250|UniProtKB:Q13547"
FT MOD_RES 424
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..15
FT /note="MAKTVAYFYDPDVGN -> MIVFKPYQASQHDMCR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9346952"
FT /id="VSP_002079"
FT VARIANT 411
FT /note="N -> S (in dbSNP:rs34901743)"
FT /id="VAR_033988"
FT MUTAGEN 130..132
FT /note="AGG->VRPP: Impaired protein deacetylase activity
FT without affecting the protein decrotonylase activity."
FT /evidence="ECO:0000269|PubMed:28497810,
FT ECO:0000269|PubMed:34608293"
FT MUTAGEN 298
FT /note="Y->F: Strongly decreased protein deacetylase
FT activity."
FT /evidence="ECO:0000269|PubMed:25301942"
FT CONFLICT 359
FT /note="R -> L (in Ref. 1; AAC52038)"
FT /evidence="ECO:0000305"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:4A69"
FT TURN 11..14
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 27..38
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 41..44
FT /evidence="ECO:0007829|PDB:4A69"
FT STRAND 45..48
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 55..58
FT /evidence="ECO:0007829|PDB:4A69"
FT TURN 59..61
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 64..72
FT /evidence="ECO:0007829|PDB:4A69"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 82..88
FT /evidence="ECO:0007829|PDB:4A69"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 100..119
FT /evidence="ECO:0007829|PDB:4A69"
FT STRAND 124..128
FT /evidence="ECO:0007829|PDB:4A69"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 149..157
FT /evidence="ECO:0007829|PDB:4A69"
FT TURN 158..160
FT /evidence="ECO:0007829|PDB:4A69"
FT STRAND 164..168
FT /evidence="ECO:0007829|PDB:4A69"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 175..180
FT /evidence="ECO:0007829|PDB:4A69"
FT TURN 181..183
FT /evidence="ECO:0007829|PDB:4A69"
FT STRAND 185..194
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:4A69"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 229..247
FT /evidence="ECO:0007829|PDB:4A69"
FT STRAND 250..255
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 273..284
FT /evidence="ECO:0007829|PDB:4A69"
FT STRAND 290..293
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 300..314
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 329..332
FT /evidence="ECO:0007829|PDB:4A69"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:4A69"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:4A69"
FT HELIX 352..367
FT /evidence="ECO:0007829|PDB:4A69"
SQ SEQUENCE 428 AA; 48848 MW; 94485C1EBDCF5AD0 CRC64;
MAKTVAYFYD PDVGNFHYGA GHPMKPHRLA LTHSLVLHYG LYKKMIVFKP YQASQHDMCR
FHSEDYIDFL QRVSPTNMQG FTKSLNAFNV GDDCPVFPGL FEFCSRYTGA SLQGATQLNN
KICDIAINWA GGLHHAKKFE ASGFCYVNDI VIGILELLKY HPRVLYIDID IHHGDGVQEA
FYLTDRVMTV SFHKYGNYFF PGTGDMYEVG AESGRYYCLN VPLRDGIDDQ SYKHLFQPVI
NQVVDFYQPT CIVLQCGADS LGCDRLGCFN LSIRGHGECV EYVKSFNIPL LVLGGGGYTV
RNVARCWTYE TSLLVEEAIS EELPYSEYFE YFAPDFTLHP DVSTRIENQN SRQYLDQIRQ
TIFENLKMLN HAPSVQIHDV PADLLTYDRT DEADAEERGP EENYSRPEAP NEFYDGDHDN
DKESDVEI
//
