HDAC5_PONAB
ID HDAC5_PONAB Reviewed; 1122 AA.
AC Q5R902;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 88.
DE RecName: Full=Histone deacetylase 5;
DE Short=HD5;
DE EC=3.5.1.98;
GN Name=HDAC5;
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=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Responsible for the deacetylation of lysine residues on the
CC N-terminal part of the core histones (H2A, H2B, H3 and H4). 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. Involved in muscle maturation by
CC repressing transcription of myocyte enhancer MEF2C. During muscle
CC differentiation, it shuttles into the cytoplasm, allowing the
CC expression of myocyte enhancer factors (By similarity). Serves as a
CC corepressor of RARA and causes its deacetylation (By similarity). In
CC association with RARA, plays a role in the repression of microRNA-10a
CC and thereby in the inflammatory response (By similarity).
CC {ECO:0000250|UniProtKB:Q9UQL6}.
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 -!- SUBUNIT: Interacts with AHRR, BAHD1, BCOR, HDAC7, HDAC9, CTBP1, MEF2C,
CC NCOR2, NRIP1, PHB2 and a 14-3-3 chaperone protein. Interacts with BCL6,
CC DDIT3/CHOP, GRK5, KDM5B and MYOCD. Interacts with EP300 in the presence
CC of TFAP2C. Interacts with ANKRA2. Interacts with CUL7 (as part of the
CC 3M complex); negatively regulated by ANKRA2. Interacts with ZBTB7B; the
CC interaction allows the recruitment of HDAC4 on CD8 loci for
CC deacetylation and possible inhibition of CD8 genes expression (By
CC similarity). Interacts with RARA (By similarity).
CC {ECO:0000250|UniProtKB:Q9UQL6, ECO:0000250|UniProtKB:Q9Z2V6}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC Note=Shuttles between the nucleus and the cytoplasm. In muscle cells,
CC it shuttles into the cytoplasm during myocyte differentiation. The
CC export to cytoplasm depends on the interaction with a 14-3-3 chaperone
CC protein and is due to its phosphorylation at Ser-259 and Ser-498 by
CC AMPK, CaMK1 and SIK1 (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The nuclear export sequence mediates the shuttling between the
CC nucleus and the cytoplasm.
CC -!- PTM: Phosphorylated by AMPK, CaMK1, SIK1 and PRKD1 at Ser-259 and Ser-
CC 498. The phosphorylation is required for the export to the cytoplasm
CC and inhibition. Phosphorylated by the PKC kinases PKN1 and PKN2,
CC impairing nuclear import (By similarity). Phosphorylated by GRK5,
CC leading to nuclear export of HDAC5 and allowing MEF2-mediated
CC transcription (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Polyubiquitination however does not lead to its
CC degradation (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 2
CC subfamily. {ECO:0000305}.
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DR EMBL; CR859595; CAH91758.1; -; mRNA.
DR AlphaFoldDB; Q5R902; -.
DR SMR; Q5R902; -.
DR STRING; 9601.ENSPPYP00000009379; -.
DR eggNOG; KOG1343; Eukaryota.
DR InParanoid; Q5R902; -.
DR Proteomes; UP000001595; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0000118; C:histone deacetylase complex; IEA:InterPro.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0004407; F:histone deacetylase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016575; P:histone deacetylation; IEA:InterPro.
DR GO; GO:0009889; P:regulation of biosynthetic process; IEA:UniProt.
DR GO; GO:0040029; P:regulation of gene expression, epigenetic; IEA:InterPro.
DR GO; GO:0010830; P:regulation of myotube differentiation; ISS:UniProtKB.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProt.
DR Gene3D; 3.40.800.20; -; 1.
DR InterPro; IPR000286; His_deacetylse.
DR InterPro; IPR023801; His_deacetylse_dom.
DR InterPro; IPR037138; His_deacetylse_dom_sf.
DR InterPro; IPR024643; Hist_deacetylase_Gln_rich_N.
DR InterPro; IPR017320; Histone_deAcase_II_euk.
DR InterPro; IPR030703; Histone_deacetylase_5.
DR InterPro; IPR023696; Ureohydrolase_dom_sf.
DR PANTHER; PTHR45364; PTHR45364; 1.
DR PANTHER; PTHR45364:SF2; PTHR45364:SF2; 1.
DR Pfam; PF12203; HDAC4_Gln; 1.
DR Pfam; PF00850; Hist_deacetyl; 1.
DR PIRSF; PIRSF037911; HDAC_II_euk; 1.
DR PRINTS; PR01270; HDASUPER.
DR SUPFAM; SSF52768; SSF52768; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Chromatin regulator; Cytoplasm; Hydrolase; Isopeptide bond;
KW Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation; Zinc.
FT CHAIN 1..1122
FT /note="Histone deacetylase 5"
FT /id="PRO_0000357051"
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 196..281
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 302..343
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 481..504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 536..625
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 684..1028
FT /note="Histone deacetylase"
FT REGION 1097..1122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1081..1122
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 228..242
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 249..281
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 306..342
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 581..617
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 833
FT /evidence="ECO:0000250"
FT BINDING 696
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 698
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 704
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 781
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 259
FT /note="Phosphoserine; by AMPK, CaMK1, SIK1 and PKD/PRKD1"
FT /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT MOD_RES 292
FT /note="Phosphothreonine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT MOD_RES 498
FT /note="Phosphoserine; by AMPK, CaMK1, SIK1 and PKD/PRKD1"
FT /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT MOD_RES 533
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT MOD_RES 611
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT MOD_RES 661
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT MOD_RES 1108
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT CROSSLNK 35
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9UQL6"
SQ SEQUENCE 1122 AA; 121925 MW; 7143C2F3B508D37C CRC64;
MNSPNESDGM SGREPSLEIL PRTSLHSIPV TVEVKPVLPR AMPSSMGGGG GGSPSPVELR
GALVGSVDPT LREQLLQQEL LALKQQQQLQ KQLLFAEFQK QHDHLTRQHE VQLQKHLKQQ
QEMLAAKQQQ EMLAAKRQQE LEQQRQREQQ RQEELEKQRL EQQLLILRNK EKSKESAIAS
TEVKLRLQEF LLSKSKEPTP GGLNHSLPQH PKCWGAHHAS LDQSSPPQSG PPGTPPSYKL
PLPGPYDSRD DFPLRKTASE PNLKVRSRLK QKVAERRSSP LLRRKDGTVI STFKKRAVEI
TGAGPGASSV CNSAPGSGPS SPNSSHSTIA ENGFTGSVPN IPTEMLPQHR ALPLDSSSNQ
FSLYTSPSLP NISLGLQATV TVTNSHLTAS PKLSTQQEAE RQALQSLRQG GTLTGKFMST
SSIPGCLLGV ALEGDGSPHG HASLLQHVLL LEQARQQSTL IAVPLHGQSP LVTGERVATS
MRTVGKLPRH RPLSRTQSSP LPQSPQALQQ LVMQQQHQQF LEKQKQQQLQ LGKILTKTGE
LPRQPTTHPE ETEEELTEQQ EALLGEGALT MPREGSTESE STQEDLEEED EEEDGEEEED
CIQVKDEEGE SGAEEGPDLE EPGAGYKKLF SDAQPLQPLQ VYQAPLSLAT VPHQALGRTQ
SSPAAPGGMK SPPDQPVKHL FTTGVVYDTF MLKHQCMCGN THVHPEHAGR IQSTWSRLQE
TGLLSKCERI RGRKATLDEI QTVHSEYHTL LYGTSPLNRQ KVDSKKLLGP ISQKMYAVLP
CGGIGVDSDT VWNEMHSSSA VRMAVGCLLE LAFKVAAGEL KNGFAIIRPP GHHAEESTAM
GFCFFNSVAI TAKLLQQKLN VGKVLIVDWD IHHGNGTQQA FYNDPSVLYI SLHRYDNGNF
FPGSGAPEEV GGGPGVGYNV NVAWIGGVDP PIGDVEYLTA FRTVVMPIAH EFSPDVVLVS
AGFDAVEGHL SPLGGYSVTA RCFGHLTRQL MTLAGGRVVL ALEGGHDLTA ICDASEACVS
ALLSVELQPL DEAVLQQKPN INAVATLEKV IEIQSKHWSC VQKFAAGLGR SLREAQAGET
EEAETVSAMA LLSVGAEQAQ AAAAREHSPR PAEEPMEQEP AL
