HDAC3_MOUSE
ID HDAC3_MOUSE Reviewed; 428 AA.
AC O88895; O88896; Q3UM33;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 2.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Histone deacetylase 3 {ECO:0000305};
DE Short=HD3;
DE EC=3.5.1.98 {ECO:0000305|PubMed:23911289, ECO:0000305|PubMed:30279482};
DE AltName: Full=Protein deacetylase HDAC3;
DE EC=3.5.1.- {ECO:0000250|UniProtKB:O15379};
DE AltName: Full=Protein deacylase HDAC3;
DE EC=3.5.1.- {ECO:0000269|PubMed:30279482};
GN Name=Hdac3 {ECO:0000303|PubMed:10491319, ECO:0000312|MGI:MGI:1343091};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), AND NUCLEOTIDE
RP SEQUENCE [GENOMIC DNA] (ISOFORM LONG).
RC STRAIN=C3H/HeJ, and C57BL/6J;
RX PubMed=10491319; DOI=10.1006/bbrc.1999.1389;
RA Mahlknecht U., Hoelzer D., Bucala R., Verdin E.;
RT "Cloning and characterization of the murine histone deacetylase (HDAC3).";
RL Biochem. Biophys. Res. Commun. 263:482-490(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [5]
RP INTERACTION WITH HDAC7.
RX PubMed=10984530; DOI=10.1073/pnas.97.19.10330;
RA Downes M., Ordentlich P., Kao H.-Y., Alvarez J.G.A., Evans R.M.;
RT "Identification of a nuclear domain with deacetylase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:10330-10335(2000).
RN [6]
RP INTERACTION WITH HDAC9.
RX PubMed=11022042; DOI=10.1074/jbc.m007364200;
RA Zhang C.L., McKinsey T.A., Lu J.R., Olson E.N.;
RT "Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting
RT transcription repressor (MITR) contributes to transcriptional repression of
RT the MEF2 transcription factor.";
RL J. Biol. Chem. 276:35-39(2001).
RN [7]
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 [8]
RP INTERACTION WITH DACH1.
RX PubMed=12130660; DOI=10.1126/science.1073263;
RA Li X., Perissi V., Liu F., Rose D.W., Rosenfeld M.G.;
RT "Tissue-specific regulation of retinal and pituitary precursor cell
RT proliferation.";
RL Science 297:1180-1183(2002).
RN [9]
RP INTERACTION WITH HDAC9.
RX PubMed=15711539; DOI=10.1038/nn1408;
RA Mejat A., Ramond F., Bassel-Duby R., Khochbin S., Olson E.N., Schaeffer L.;
RT "Histone deacetylase 9 couples neuronal activity to muscle chromatin
RT acetylation and gene expression.";
RL Nat. Neurosci. 8:313-321(2005).
RN [10]
RP INTERACTION WITH GLIS2.
RX PubMed=16326862; DOI=10.1093/nar/gki985;
RA Kim S.-C., Kim Y.-S., Jetten A.M.;
RT "Kruppel-like zinc finger protein Gli-similar 2 (Glis2) represses
RT transcription through interaction with C-terminal binding protein 1
RT (CtBP1).";
RL Nucleic Acids Res. 33:6805-6815(2005).
RN [11]
RP INTERACTION WITH PRDM6.
RX PubMed=16537907; DOI=10.1128/mcb.26.7.2626-2636.2006;
RA Davis C.A., Haberland M., Arnold M.A., Sutherland L.B., McDonald O.G.,
RA Richardson J.A., Childs G., Harris S., Owens G.K., Olson E.N.;
RT "PRISM/PRDM6, a transcriptional repressor that promotes the proliferative
RT gene program in smooth muscle cells.";
RL Mol. Cell. Biol. 26:2626-2636(2006).
RN [12]
RP FUNCTION, AND INTERACTION WITH NCOR1.
RX PubMed=19037247; DOI=10.1038/nature07541;
RA Alenghat T., Meyers K., Mullican S.E., Leitner K., Adeniji-Adele A.,
RA Avila J., Bucan M., Ahima R.S., Kaestner K.H., Lazar M.A.;
RT "Nuclear receptor corepressor and histone deacetylase 3 govern circadian
RT metabolic physiology.";
RL Nature 456:997-1000(2008).
RN [13]
RP FUNCTION, SUMOYLATION, INTERACTION WITH NR2C1, AND SUBCELLULAR LOCATION.
RX PubMed=19204783; DOI=10.1371/journal.pone.0004363;
RA Gupta P., Ho P.C., Ha S.G., Lin Y.W., Wei L.N.;
RT "HDAC3 as a molecular chaperone for shuttling phosphorylated TR2 to PML: a
RT novel deacetylase activity-independent function of HDAC3.";
RL PLoS ONE 4:E4363-E4363(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [15]
RP INTERACTION WITH ZMYND15.
RX PubMed=20675388; DOI=10.1074/jbc.m110.116418;
RA Yan W., Si Y., Slaymaker S., Li J., Zheng H., Young D.L., Aslanian A.,
RA Saunders L., Verdin E., Charo I.F.;
RT "Zmynd15 encodes a histone deacetylase-dependent transcriptional repressor
RT essential for spermiogenesis and male fertility.";
RL J. Biol. Chem. 285:31418-31426(2010).
RN [16]
RP FUNCTION IN DEACETYLATION OF H3K27, AND CATALYTIC ACTIVITY.
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 [17]
RP INTERACTION WITH NKAPL.
RX PubMed=25875095; DOI=10.1371/journal.pone.0124293;
RA Okuda H., Kiuchi H., Takao T., Miyagawa Y., Tsujimura A., Nonomura N.,
RA Miyata H., Okabe M., Ikawa M., Kawakami Y., Goshima N., Wada M., Tanaka H.;
RT "A novel transcriptional factor Nkapl is a germ cell-specific suppressor of
RT Notch signaling and is indispensable for spermatogenesis.";
RL PLoS ONE 10:E0124293-E0124293(2015).
RN [18]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INTERACTION WITH
RP FBXL3; ARNTL AND CRY1, AND MUTAGENESIS OF 134-HIS--ALA-136 AND SER-424.
RX PubMed=26776516; DOI=10.1016/j.celrep.2015.12.076;
RA Shi G., Xie P., Qu Z., Zhang Z., Dong Z., An Y., Xing L., Liu Z., Dong Y.,
RA Xu G., Yang L., Liu Y., Xu Y.;
RT "Distinct roles of HDAC3 in the core circadian negative feedback loop are
RT critical for clock function.";
RL Cell Rep. 14:823-834(2016).
RN [19]
RP INTERACTION WITH SETD5.
RX PubMed=30455454; DOI=10.1038/s41593-018-0266-2;
RA Deliu E., Arecco N., Morandell J., Dotter C.P., Contreras X., Girardot C.,
RA Kaesper E.L., Kozlova A., Kishi K., Chiaradia I., Noh K.M., Novarino G.;
RT "Haploinsufficiency of the intellectual disability gene SETD5 disturbs
RT developmental gene expression and cognition.";
RL Nat. Neurosci. 21:1717-1727(2018).
RN [20]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30279482; DOI=10.1038/s41598-018-32927-9;
RA Kelly R.D.W., Chandru A., Watson P.J., Song Y., Blades M., Robertson N.S.,
RA Jamieson A.G., Schwabe J.W.R., Cowley S.M.;
RT "Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone
RT acetylation and crotonylation in vivo.";
RL Sci. Rep. 8:14690-14690(2018).
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:30279482). Histone deacetylation gives a tag for epigenetic
CC repression and plays an important role in transcriptional regulation,
CC cell cycle progression and developmental events (PubMed:23911289).
CC Histone deacetylases act via the formation of large multiprotein
CC complexes (PubMed:23911289). Participates in the BCL6 transcriptional
CC repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer
CC elements, antagonizing EP300 acetyltransferase activity and repressing
CC proximal gene expression (PubMed:23911289). Acts as a molecular
CC chaperone for shuttling phosphorylated NR2C1 to PML bodies for
CC sumoylation (PubMed:19204783). Contributes, together with XBP1 isoform
CC 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene
CC expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading
CC to endothelial cell (EC) survival under disturbed flow/oxidative stress
CC (By similarity). Regulates both the transcriptional activation and
CC repression phases of the circadian clock in a deacetylase activity-
CC independent manner (PubMed:26776516). During the activation phase,
CC promotes the accumulation of ubiquitinated ARNTL/BMAL1 at the E-boxes
CC and during the repression phase, blocks FBXL3-mediated CRY1/2
CC ubiquitination and promotes the interaction of CRY1 and ARNTL/BMAL1
CC (PubMed:26776516). The NCOR1-HDAC3 complex regulates the circadian
CC expression of the core clock gene ARTNL/BMAL1 and the genes involved in
CC lipid metabolism in the liver (PubMed:19037247). Also functions as
CC deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14 and
CC RARA (By similarity). Serves as a corepressor of RARA, mediating its
CC deacetylation and repression, leading to inhibition of RARE DNA element
CC binding (By similarity). In association with RARA, plays a role in the
CC repression of microRNA-10a and thereby in the inflammatory response (By
CC similarity). In addition to protein deacetylase activity, also acts as
CC protein-lysine deacylase by recognizing other acyl groups: catalyzes
CC removal of (2E)-butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-
CC hydroxyisobutyryl) acyl groups from lysine residues, leading to protein
CC decrotonylation and de-2-hydroxyisobutyrylation, respectively
CC (PubMed:30279482). Catalyzes decrotonylation of MAPRE1/EB1 (By
CC similarity). {ECO:0000250|UniProtKB:O15379,
CC ECO:0000269|PubMed:19037247, ECO:0000269|PubMed:19204783,
CC ECO:0000269|PubMed:23911289, ECO:0000269|PubMed:26776516,
CC ECO:0000269|PubMed:30279482}.
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:0000305|PubMed:23911289, ECO:0000305|PubMed:30279482};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58197;
CC Evidence={ECO:0000305|PubMed:23911289, ECO:0000305|PubMed:30279482};
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:0000250|UniProtKB:O15379};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58109;
CC Evidence={ECO:0000250|UniProtKB:O15379};
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:30279482};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69173;
CC Evidence={ECO:0000269|PubMed:30279482};
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:0000250|UniProtKB:O15379};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69177;
CC Evidence={ECO:0000250|UniProtKB:O15379};
CC -!- SUBUNIT: Interacts with HDAC7 and HDAC9 (PubMed:10984530,
CC PubMed:11022042, PubMed:15711539). Interacts with DAXX, KDM4A, HDAC10
CC and DACH1 (PubMed:12130660). Found in a complex with NCOR1 and NCOR2
CC (By similarity). Component of the N-Cor repressor complex, at least
CC composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (By
CC similarity). Interacts with BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY
CC (PubMed:16537907). Interacts with BTBD14B (By similarity). Interacts
CC with GLIS2 (PubMed:16326862). Interacts (via the DNA-binding domain)
CC with NR2C1; the interaction recruits phosphorylated NR2C1 to PML bodies
CC for sumoylation (PubMed:19204783). Component of the Notch corepressor
CC complex (By similarity). Interacts with CBFA2T3 and NKAP
CC (PubMed:11533236). Interacts with APEX1; the interaction is not
CC dependent on the acetylated status of APEX1 (By similarity). Interacts
CC with ZMYND15 (PubMed:20675388). Interacts with SMRT/NCOR2 and BCL6 on
CC DNA enhancer elements (By similarity). Interacts with INSM1 (By
CC similarity). Interacts with XBP1 isoform 1; the interaction occurs in
CC endothelial cell (EC) under disturbed flow (By similarity). Interacts
CC (via C-terminus) with CCAR2 (via N-terminus) (By similarity). Interacts
CC with and deacetylates MEF2D (By similarity). Interacts with BEND3 (By
CC similarity). Interacts with NKAPL (PubMed:25875095). Interacts with
CC DHX36; this interaction occurs in a RNA-dependent manner (By
CC similarity). Interacts weakly with CRY1; this interaction is enhanced
CC in the presence of FBXL3 (PubMed:26776516). Interacts with FBXL3 and
CC ARNTL/BMAL1 (PubMed:26776516). Interacts with NCOR1 (PubMed:19037247).
CC Interacts with RARA (By similarity). Interacts with SETD5
CC (PubMed:30455454). {ECO:0000250|UniProtKB:O15379,
CC ECO:0000250|UniProtKB:Q6P6W3, ECO:0000269|PubMed:10984530,
CC ECO:0000269|PubMed:11022042, ECO:0000269|PubMed:11533236,
CC ECO:0000269|PubMed:12130660, ECO:0000269|PubMed:15711539,
CC ECO:0000269|PubMed:16326862, ECO:0000269|PubMed:16537907,
CC ECO:0000269|PubMed:19037247, ECO:0000269|PubMed:19204783,
CC ECO:0000269|PubMed:20675388, ECO:0000269|PubMed:25875095,
CC ECO:0000269|PubMed:26776516, ECO:0000269|PubMed:30455454}.
CC -!- INTERACTION:
CC O88895; Q9Z2D6: Mecp2; NbExp=5; IntAct=EBI-302263, EBI-1188816;
CC O88895; Q9Z1E3: Nfkbia; NbExp=2; IntAct=EBI-302263, EBI-644427;
CC O88895; Q64104: Nr2e1; NbExp=2; IntAct=EBI-302263, EBI-15658561;
CC O88895; Q3TKT4: Smarca4; NbExp=2; IntAct=EBI-302263, EBI-1210244;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26776516}. Cytoplasm
CC {ECO:0000269|PubMed:26776516}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O15379}. Note=Colocalizes with XBP1 and AKT1 in
CC the cytoplasm. Predominantly expressed in the nucleus in the presence
CC of CCAR2 (By similarity). {ECO:0000250|UniProtKB:O15379}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=O88895-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=O88895-2; Sequence=VSP_002080;
CC -!- PTM: Sumoylated in vitro. {ECO:0000269|PubMed:19204783}.
CC -!- DISRUPTION PHENOTYPE: Liver-specific knockout mice exhibit low
CC amplitude of circadian rhythms, dampened E-box-driven transcription and
CC a significant reduction in the protein levels of ARNTL/BMAL1 and CRY1
CC in the liver. {ECO:0000269|PubMed:26776516}.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 1
CC subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC36305.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC36306.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC Sequence=AAC67258.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF074881; AAC36305.1; ALT_SEQ; mRNA.
DR EMBL; AF074882; AAC36306.1; ALT_SEQ; mRNA.
DR EMBL; AF079310; AAC67258.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AF079309; AAC67258.1; JOINED; Genomic_DNA.
DR EMBL; AK145158; BAE26265.1; -; mRNA.
DR EMBL; AC129315; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC139300; AAI39301.1; -; mRNA.
DR EMBL; BC139301; AAI39302.1; -; mRNA.
DR CCDS; CCDS37785.1; -. [O88895-1]
DR PIR; JC7102; JC7102.
DR RefSeq; NP_034541.2; NM_010411.2.
DR AlphaFoldDB; O88895; -.
DR SMR; O88895; -.
DR CORUM; O88895; -.
DR DIP; DIP-32547N; -.
DR IntAct; O88895; 21.
DR MINT; O88895; -.
DR STRING; 10090.ENSMUSP00000037981; -.
DR BindingDB; O88895; -.
DR ChEMBL; CHEMBL5142; -.
DR iPTMnet; O88895; -.
DR PhosphoSitePlus; O88895; -.
DR EPD; O88895; -.
DR MaxQB; O88895; -.
DR PaxDb; O88895; -.
DR PeptideAtlas; O88895; -.
DR PRIDE; O88895; -.
DR ProteomicsDB; 269819; -. [O88895-1]
DR ProteomicsDB; 269820; -. [O88895-2]
DR ProteomicsDB; 334754; -.
DR Antibodypedia; 3568; 978 antibodies from 48 providers.
DR DNASU; 15183; -.
DR Ensembl; ENSMUST00000043498; ENSMUSP00000037981; ENSMUSG00000024454. [O88895-1]
DR GeneID; 15183; -.
DR KEGG; mmu:15183; -.
DR UCSC; uc008erl.1; mouse.
DR CTD; 8841; -.
DR MGI; MGI:1343091; Hdac3.
DR VEuPathDB; HostDB:ENSMUSG00000024454; -.
DR eggNOG; KOG1342; Eukaryota.
DR GeneTree; ENSGT00940000160487; -.
DR HOGENOM; CLU_007727_7_6_1; -.
DR InParanoid; O88895; -.
DR OMA; GWLRAFH; -.
DR OrthoDB; 732770at2759; -.
DR TreeFam; TF352182; -.
DR BRENDA; 3.5.1.98; 3474.
DR Reactome; R-MMU-3214815; HDACs deacetylate histones.
DR Reactome; R-MMU-350054; Notch-HLH transcription pathway.
DR Reactome; R-MMU-400206; Regulation of lipid metabolism by PPARalpha.
DR Reactome; R-MMU-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR Reactome; R-MMU-9701898; STAT3 nuclear events downstream of ALK signaling.
DR Reactome; R-MMU-9707564; Cytoprotection by HMOX1.
DR BioGRID-ORCS; 15183; 28 hits in 82 CRISPR screens.
DR ChiTaRS; Hdac3; mouse.
DR PRO; PR:O88895; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; O88895; protein.
DR Bgee; ENSMUSG00000024454; Expressed in embryonic brain and 268 other tissues.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0000118; C:histone deacetylase complex; ISO:MGI.
DR GO; GO:0072686; C:mitotic spindle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0017053; C:transcription repressor complex; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:MGI.
DR GO; GO:0030332; F:cyclin binding; ISO:MGI.
DR GO; GO:0019213; F:deacetylase activity; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; TAS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0051020; F:GTPase binding; ISO:MGI.
DR GO; GO:0004407; F:histone deacetylase activity; IDA:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0160009; F:histone decrotonylase activity; IDA:UniProtKB.
DR GO; GO:0051059; F:NF-kappaB binding; ISO:MGI.
DR GO; GO:0160010; F:protein de-2-hydroxyisobutyrylase activity; ISO:MGI.
DR GO; GO:0160008; F:protein decrotonylase activity; ISO:MGI.
DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:MGI.
DR GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; ISO:MGI.
DR GO; GO:0071498; P:cellular response to fluid shear stress; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; TAS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:1903575; P:cornified envelope assembly; IMP:MGI.
DR GO; GO:0008544; P:epidermis development; IMP:MGI.
DR GO; GO:0061436; P:establishment of skin barrier; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0016575; P:histone deacetylation; IMP:MGI.
DR GO; GO:0070933; P:histone H4 deacetylation; IDA:MGI.
DR GO; GO:1990679; P:histone H4-K12 deacetylation; IDA:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:2000726; P:negative regulation of cardiac muscle cell differentiation; IMP:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0032692; P:negative regulation of interleukin-1 production; ISO:MGI.
DR GO; GO:0046329; P:negative regulation of JNK cascade; ISO:MGI.
DR GO; GO:0046826; P:negative regulation of protein export from nucleus; ISO:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IMP:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:2000676; P:positive regulation of type B pancreatic cell apoptotic process; ISO:MGI.
DR GO; GO:0006476; P:protein deacetylation; ISO:MGI.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IDA:MGI.
DR GO; GO:0040014; P:regulation of multicellular organism growth; IGI:MGI.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0051225; P:spindle assembly; ISO:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IGI:MGI.
DR Gene3D; 3.40.800.20; -; 1.
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 Pfam; PF00850; Hist_deacetyl; 1.
DR PIRSF; PIRSF037913; His_deacetylse_1; 1.
DR PRINTS; PR01270; HDASUPER.
DR PRINTS; PR01271; HISDACETLASE.
DR SUPFAM; SSF52768; SSF52768; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Biological rhythms; Chromatin regulator; Cytoplasm;
KW Hydrolase; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..428
FT /note="Histone deacetylase 3"
FT /id="PRO_0000114697"
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:0000250|UniProtKB:O15379"
FT VAR_SEQ 69..259
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:10491319"
FT /id="VSP_002080"
FT MUTAGEN 134..136
FT /note="HHA->QAS: Deacetylase-dead mutant. No effect on its
FT interaction with ARNTL/BMAL1, CRY1 and FBXL3 or its ability
FT to regulate the circadian clock."
FT /evidence="ECO:0000269|PubMed:26776516"
FT MUTAGEN 424
FT /note="S->A: Deacetylase-dead mutant. No effect on its
FT interaction with ARNTL/BMAL1, CRY1 and FBXL3 or its ability
FT to regulate the circadian clock."
FT /evidence="ECO:0000269|PubMed:26776516"
SQ SEQUENCE 428 AA; 48821 MW; 1CB84DE250C3BB2C 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
SQVVDFYQPT CIVLQCGADS LGCDRLGCFN LSIRGHGECV EYVKSFNIPL LVLGGGGYTV
RNVARCWTYE TSLLVEEAIS EELPYSEYFE YFAPDFTLHP DVSTRIENQN SRQYLDQIRQ
TIFENLKMLN HAPSVQIHDV PADLLTYDRT DEADAEERGP EENYSRPEAP NEFYDGDHDN
DKESDVEI
