HDAC3_PONAB
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 03-AUG-2022, entry version 101.
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 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 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 ARNTL/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 -!- 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; 732770at2759; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
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: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:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR GO; GO:0071498; P:cellular response to fluid shear stress; ISS:UniProtKB.
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:0016575; P:histone deacetylation; IEA:InterPro.
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 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 2: Evidence at transcript 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_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
