ID   HDAC3_PONAB             Reviewed;         428 AA.
AC   Q5RB76;
DT   14-OCT-2008, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   27-MAR-2024, entry version 108.
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   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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 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 BMAL1. The NCOR1-HDAC3 complex
CC       regulates the circadian expression of the core clock gene BMAL1 and the
CC       genes involved in lipid metabolism in the liver (By similarity). Also
CC       functions as a deacetylase for non-histone targets, such as KAT5,
CC       MEF2D, MAPK14, RARA and STAT3. 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 a 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 HDAC7 and HDAC9. Interacts with HDAC10, DAXX
CC       and DACH1. Found in a complex with NCOR1 and NCOR2. Component of the N-
CC       Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X,
CC       TBL1R, CORO2A and GPS2. Interacts with BCOR, MJD2A/JHDM3A, NRIP1, PRDM6
CC       and SRY. Interacts with BTBD14B. Interacts with GLIS2. Interacts (via
CC       the DNA-binding domain) with NR2C1; the interaction recruits
CC       phosphorylated NR2C1 to PML bodies for sumoylation. Component of the
CC       Notch corepressor complex. Interacts with CBFA2T3 and NKAP. Interacts
CC       with APEX1; the interaction is not dependent on the acetylated status
CC       of APEX1. Interacts with and deacetylates MAPK14. Interacts with
CC       ZMYND15. Interacts with SMRT/NCOR2 and BCL6 on DNA enhancer elements.
CC       Interacts with INSM1. Interacts with XBP1; the interaction occurs in
CC       endothelial cell (EC) under disturbed flow. Interacts (via C-terminus)
CC       with CCAR2 (via N-terminus). Interacts with and deacetylates MEF2D.
CC       Interacts with BEND3. Interacts with NKAPL. Interacts with DHX36; this
CC       interaction occurs in a RNA-dependent manner (By similarity). Interacts
CC       weakly with CRY1; this interaction is enhanced in the presence of FBXL3
CC       (By similarity). Interacts with FBXL3 and BMAL1 (By similarity).
CC       Interacts with NCOR1 (By similarity). Interacts with RARA (By
CC       similarity). Interacts with SETD5 (By similarity).
CC       {ECO:0000250|UniProtKB:O15379, ECO:0000250|UniProtKB:O88895}.
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   -!- PTM: Deubiquitinated on 'Lys-63'-linked ubiquitin chains by USP38;
CC       leading to a decreased level of histone acetylation.
CC       {ECO:0000250|UniProtKB:O15379}.
CC   -!- PTM: Sumoylated in vitro. {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; CR858777; CAH90984.1; -; mRNA.
DR   RefSeq; NP_001125568.1; NM_001132096.1.
DR   AlphaFoldDB; Q5RB76; -.
DR   SMR; Q5RB76; -.
DR   STRING; 9601.ENSPPYP00000017772; -.
DR   GeneID; 100172482; -.
DR   KEGG; pon:100172482; -.
DR   CTD; 8841; -.
DR   eggNOG; KOG1342; Eukaryota.
DR   InParanoid; Q5RB76; -.
DR   OrthoDB; 1327607at2759; -.
DR   Proteomes; UP000001595; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0000118; C:histone deacetylase complex; IEA:UniProt.
DR   GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR   GO; GO:0017053; C:transcription repressor complex; ISS:UniProtKB.
DR   GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR   GO; GO:0140297; F:DNA-binding transcription factor binding; IEA:UniProt.
DR   GO; GO:0004407; F:histone deacetylase activity; IEA:UniProtKB-EC.
DR   GO; GO:0160009; F:histone decrotonylase activity; ISS:UniProtKB.
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; ISS:UniProtKB.
DR   GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR   GO; GO:0071498; P:cellular response to fluid shear stress; ISS:UniProtKB.
DR   GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
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:0006476; P:protein deacetylation; ISS:UniProtKB.
DR   GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR   GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR   CDD; cd10005; HDAC3; 1.
DR   Gene3D; 3.40.800.20; Histone deacetylase domain; 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   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   2: Evidence at transcript level;
KW   Biological rhythms; Chromatin regulator; Cytoplasm; 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_0000352678"
FT   REGION          3..316
FT                   /note="Histone deacetylase"
FT   REGION          388..428
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        389..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"
SQ   SEQUENCE   428 AA;  48809 MW;  B0D84DC866B0C91F 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 HAPSVQIRDV PAGLLTYDRT DEADAEERGP EENYSRPEAP NEFYDGDHDN
     DKESDVEI
//