HDAC3_RAT
ID HDAC3_RAT Reviewed; 428 AA.
AC Q6P6W3; Q99PA0;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Histone deacetylase 3;
DE Short=HD3;
DE EC=3.5.1.98 {ECO:0000250|UniProtKB:O15379};
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:0000250|UniProtKB:O15379};
GN Name=Hdac3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Wistar; TISSUE=Testis;
RA Wilquet V., Chavez M., Korbers R., Geerts A.;
RT "Expression pattern of rat histone deacetylases.";
RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 [3]
RP INTERACTION WITH BTBD14B.
RX PubMed=16033423; DOI=10.1111/j.1471-4159.2005.03206.x;
RA Korutla L., Wang P.J., Mackler S.A.;
RT "The POZ/BTB protein NAC1 interacts with two different histone deacetylases
RT in neuronal-like cultures.";
RL J. Neurochem. 94:786-793(2005).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-424, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. Histone
CC deacetylation gives a tag for epigenetic repression and plays an
CC important role in transcriptional regulation, cell cycle progression
CC and developmental events. Histone deacetylases act via the formation of
CC large multiprotein complexes. 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 (By similarity). Acts as a molecular chaperone
CC for shuttling phosphorylated NR2C1 to PML bodies for sumoylation (By
CC similarity). Contributes, together with XBP1 isoform 1, to the
CC 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. During the activation phase, promotes the
CC accumulation of ubiquitinated ARNTL/BMAL1 at the E-boxes and during the
CC repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and
CC promotes the interaction of CRY1 and ARNTL/BMAL1. The NCOR1-HDAC3
CC complex regulates the circadian expression of the core clock gene
CC ARTNL/BMAL1 and the genes involved in lipid metabolism in the liver (By
CC similarity). Also functions as deacetylase for non-histone targets,
CC such as KAT5, MEF2D, MAPK14 and RARA. Serves as a corepressor of RARA,
CC mediating its deacetylation and repression, leading to inhibition of
CC RARE DNA element binding. In association with RARA, plays a role in the
CC repression of microRNA-10a and thereby in the inflammatory response. In
CC addition to protein deacetylase activity, also acts as protein-lysine
CC deacylase by recognizing other acyl groups: catalyzes removal of (2E)-
CC butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl
CC groups from lysine residues, leading to protein decrotonylation and de-
CC 2-hydroxyisobutyrylation, respectively (By similarity). Catalyzes
CC decrotonylation of MAPRE1/EB1 (By similarity).
CC {ECO:0000250|UniProtKB:O15379, ECO:0000250|UniProtKB:O88895}.
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:0000250|UniProtKB:O15379};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58197;
CC Evidence={ECO:0000250|UniProtKB:O15379};
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:0000250|UniProtKB:O15379};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69173;
CC Evidence={ECO:0000250|UniProtKB:O15379};
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 BTBD14B (PubMed:16033423). Interacts with HDAC7
CC and HDAC9. Interacts with HDAC10, DAXX and DACH1. Found in a complex
CC with NCOR1 and NCOR2. Component of the N-Cor repressor complex, at
CC least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2.
CC Interacts with BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY. Interacts with
CC GLIS2. Interacts (via the DNA-binding domain) with NR2C1; the
CC interaction recruits phosphorylated NR2C1 to PML bodies for
CC sumoylation. Component of the Notch corepressor complex. Interacts with
CC CBFA2T3 and NKAP. Interacts with APEX1; the interaction is not
CC dependent on the acetylated status of APEX1. Interacts with and
CC deacetylates MAPK14. Interacts with ZMYND15. Interacts with SMRT/NCOR2
CC and BCL6 on DNA enhancer elements. Interacts with INSM1. Interacts with
CC XBP1; the interaction occurs in endothelial cell (EC) under disturbed
CC flow. Interacts (via C-terminus) with CCAR2 (via N-terminus). Interacts
CC with and deacetylates MEF2D (By similarity). Interacts with BEND3 (By
CC similarity). Interacts with NKAPL (By similarity). 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 (By similarity). Interacts with FBXL3 and
CC ARNTL/BMAL1 (By similarity). Interacts with NCOR1 (By similarity).
CC Interacts with RARA (By similarity). Interacts with SETD5 (By
CC similarity). {ECO:0000250|UniProtKB:O15379,
CC ECO:0000250|UniProtKB:O88895, ECO:0000269|PubMed:16033423}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O15379}. Cytoplasm
CC {ECO:0000250|UniProtKB:O15379}. 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 -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; AF321131; AAK11184.1; -; mRNA.
DR EMBL; BC061988; AAH61988.1; -; mRNA.
DR RefSeq; NP_445900.1; NM_053448.1.
DR AlphaFoldDB; Q6P6W3; -.
DR SMR; Q6P6W3; -.
DR BioGRID; 250009; 2.
DR STRING; 10116.ENSRNOP00000057161; -.
DR BindingDB; Q6P6W3; -.
DR ChEMBL; CHEMBL2095943; -.
DR DrugCentral; Q6P6W3; -.
DR iPTMnet; Q6P6W3; -.
DR PhosphoSitePlus; Q6P6W3; -.
DR PRIDE; Q6P6W3; -.
DR GeneID; 84578; -.
DR KEGG; rno:84578; -.
DR UCSC; RGD:619977; rat.
DR CTD; 8841; -.
DR RGD; 619977; Hdac3.
DR eggNOG; KOG1342; Eukaryota.
DR InParanoid; Q6P6W3; -.
DR OrthoDB; 732770at2759; -.
DR PhylomeDB; Q6P6W3; -.
DR Reactome; R-RNO-350054; Notch-HLH transcription pathway.
DR Reactome; R-RNO-400206; Regulation of lipid metabolism by PPARalpha.
DR Reactome; R-RNO-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR Reactome; R-RNO-9701898; STAT3 nuclear events downstream of ALK signaling.
DR Reactome; R-RNO-9707564; Cytoprotection by HMOX1.
DR PRO; PR:Q6P6W3; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0000785; C:chromatin; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0000118; C:histone deacetylase complex; ISO:RGD.
DR GO; GO:0072686; C:mitotic spindle; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0017053; C:transcription repressor complex; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IMP:RGD.
DR GO; GO:0031490; F:chromatin DNA binding; ISO:RGD.
DR GO; GO:0030332; F:cyclin binding; ISO:RGD.
DR GO; GO:0019213; F:deacetylase activity; IDA:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0051020; F:GTPase binding; IPI:RGD.
DR GO; GO:0004407; F:histone deacetylase activity; ISO:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:RGD.
DR GO; GO:0160009; F:histone decrotonylase activity; ISS:UniProtKB.
DR GO; GO:0051059; F:NF-kappaB binding; ISO:RGD.
DR GO; GO:0160010; F:protein de-2-hydroxyisobutyrylase activity; ISS:UniProtKB.
DR GO; GO:0160008; F:protein decrotonylase activity; ISS:UniProtKB.
DR GO; GO:0033558; F:protein lysine deacetylase activity; ISO:RGD.
DR GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR GO; GO:0001222; F:transcription corepressor binding; ISO:RGD.
DR GO; GO:0071498; P:cellular response to fluid shear stress; ISS:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0071374; P:cellular response to parathyroid hormone stimulus; IEP:RGD.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:1903575; P:cornified envelope assembly; ISO:RGD.
DR GO; GO:0008544; P:epidermis development; ISO:RGD.
DR GO; GO:0061436; P:establishment of skin barrier; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0016575; P:histone deacetylation; ISO:RGD.
DR GO; GO:0070932; P:histone H3 deacetylation; IEP:RGD.
DR GO; GO:0070933; P:histone H4 deacetylation; ISO:RGD.
DR GO; GO:1990679; P:histone H4-K12 deacetylation; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:2000726; P:negative regulation of cardiac muscle cell differentiation; ISO:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0032692; P:negative regulation of interleukin-1 production; IMP:RGD.
DR GO; GO:0046329; P:negative regulation of JNK cascade; ISO:RGD.
DR GO; GO:0046826; P:negative regulation of protein export from nucleus; IMP:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
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; ISS: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; IMP:RGD.
DR GO; GO:0006476; P:protein deacetylation; ISO:RGD.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; ISO:RGD.
DR GO; GO:0040014; P:regulation of multicellular organism growth; ISO:RGD.
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:0071548; P:response to dexamethasone; IEP:RGD.
DR GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0051225; P:spindle assembly; ISO:RGD.
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 Biological rhythms; Chromatin regulator; Cytoplasm; Hydrolase; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..428
FT /note="Histone deacetylase 3"
FT /id="PRO_0000281030"
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:22673903"
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
