ID   HDAC5_CRIGR             Reviewed;        1111 AA.
AC   Q80ZH1;
DT   16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2003, sequence version 1.
DT   27-MAR-2024, entry version 105.
DE   RecName: Full=Histone deacetylase 5;
DE            Short=HD5;
DE            EC=3.5.1.98;
GN   Name=HDAC5;
OS   Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC   Cricetidae; Cricetinae; Cricetulus.
OX   NCBI_TaxID=10029;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Ovary;
RX   PubMed=15525819; DOI=10.1093/glycob/cwi011;
RA   Chen W., Tang J., Stanley P.;
RT   "Suppressors of alpha(1,3)fucosylation identified by expression cloning in
RT   the LEC11B gain-of-function CHO mutant.";
RL   Glycobiology 15:259-269(2005).
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-250 and Ser-489 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-250 and Ser-
CC       489. 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; AY145846; AAN46420.1; -; mRNA.
DR   RefSeq; NP_001233710.1; NM_001246781.1.
DR   RefSeq; XP_007643219.1; XM_007645029.2.
DR   AlphaFoldDB; Q80ZH1; -.
DR   SMR; Q80ZH1; -.
DR   PaxDb; 10029-NP_001233710-1; -.
DR   GeneID; 100689350; -.
DR   KEGG; cge:100689350; -.
DR   CTD; 10014; -.
DR   eggNOG; KOG1343; Eukaryota.
DR   OrthoDB; 124800at2759; -.
DR   Proteomes; UP000694386; Unplaced.
DR   Proteomes; UP001108280; Chromosome 7.
DR   GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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:0000122; P:negative regulation of transcription by RNA polymerase II; IEA:InterPro.
DR   GO; GO:0010830; P:regulation of myotube differentiation; ISS:UniProtKB.
DR   GO; GO:0050896; P:response to stimulus; IEA:UniProt.
DR   CDD; cd10007; HDAC5; 1.
DR   Gene3D; 6.10.250.1550; -; 1.
DR   Gene3D; 3.40.800.20; Histone deacetylase domain; 1.
DR   InterPro; IPR046949; HDAC4/5/7/9.
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; IPR023696; Ureohydrolase_dom_sf.
DR   PANTHER; PTHR45364:SF11; HISTONE DEACETYLASE; 1.
DR   PANTHER; PTHR45364; HISTONE DEACETYLASE 9-RELATED; 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; Arginase/deacetylase; 1.
PE   2: Evidence at transcript level;
KW   Acetylation; Chromatin regulator; Cytoplasm; Hydrolase; Isopeptide bond;
KW   Metal-binding; Nucleus; Phosphoprotein; Repressor; Transcription;
KW   Transcription regulation; Ubl conjugation; Zinc.
FT   CHAIN           1..1111
FT                   /note="Histone deacetylase 5"
FT                   /id="PRO_0000357050"
FT   REGION          40..63
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          107..136
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          187..272
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          474..495
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          527..611
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          645..666
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          671..1017
FT                   /note="Histone deacetylase"
FT   REGION          1086..1111
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           1070..1109
FT                   /note="Nuclear export signal"
FT                   /evidence="ECO:0000250"
FT   COMPBIAS        240..272
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        572..606
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        822
FT                   /evidence="ECO:0000250"
FT   BINDING         685
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         687
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         693
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   BINDING         770
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         250
FT                   /note="Phosphoserine; by AMPK, CaMK1, SIK1 and PKD/PRKD1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT   MOD_RES         283
FT                   /note="Phosphothreonine; by PKC"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT   MOD_RES         489
FT                   /note="Phosphoserine; by AMPK, CaMK1, SIK1 and PKD/PRKD1"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT   MOD_RES         524
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT   MOD_RES         600
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT   MOD_RES         650
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9UQL6"
FT   MOD_RES         1097
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   1111 AA;  120988 MW;  52559AE959E190E6 CRC64;
     MNSPNESDGM PGREPSLEIL PRTPLHSIPV AVEVKPVLPG AMPSSMGGGG GGSPSPVELR
     GALAGPMDPA LREQQLQQEL LVLKQQQQLQ KQLLFAEFQK QHDHLTRQHE VQLQKHLKQQ
     QEMLAAKRQQ ELEQQRQREQ QRQEELEKQR LEQQLLILRN KEKSKESAIA STEVKLRLQE
     FLLSKSKEPT PGSLNHSLPQ HPKCWGAHHA SLDQSSPPQS GPPGTPPSYK LPLLGPYDSR
     DDFPLRKTAS EPNLKVRSRL KQKVAERRSS PLLRRKDGTV ISTFKKRAVE ITGTGPGVSS
     VCNSAPGSGP SSPNSSHSAI AENGFTGSVP NIPTEMLPQH RALPLDSSPN QFSLYTSPSL
     PNISLGLQAT VTVTNSHLTA SPKLSTQQEA ERQALQSLRQ GGTLTGKFMS TSSIPGCLLG
     VTLEGDTSPH GHASLLQHVL LLEQARQQST LIAVPLHGQS PLVTGERVAT SMRTVGKLPR
     HRPLSRTQSS PLPQSPQALQ QLVMQQQHQQ FLEKQKQQQM QLGKILTKTG ELPRQPTTHP
     EETEEELTEQ QEALLGEGAL TMPREGSTES ESTQEDLEEE EDEEEEDEDC IQVKDEEGES
     GPDEGPDLEE SSAGYKKLFT DAQQLQPLQV YQAPLSLATV PHQALGRTQS SPAAPGSMKS
     PPDQPTKHLF TTGVVYDTFM LKHQCMCGNT HVHPEHAGRI QSIWSRLQET GLLSKCERIR
     GRKATLDEIQ TVHSEYHTLL YGTSPLNRQK LDSKKLLGPI SQKMYAMLPC GGIGVDSDTV
     WNEMHSSSAV RMAVGCLVEL AFKVAAGELK NGFAIIRPPG HHAEESTAMG FCFFNSVAIT
     AKLLQQKLNV GKVLIVDWDI HHGNGTQQAF YDDPSVLYIS LHRYDNGNFF PGSGAPEEVG
     GGPGMGYNVN VAWTGGVDPP IGDVEYLTAF RTVVMPIAHE FSPDVVLVSA GFDAVEGHLS
     PLGGYSVTAR CFGHLTRQLM TLAGGRVVLA LEGGHDLTAI CDASEACVSA LLSVELQPLD
     EAVLQQKPSI NAVATLEKVI EIQSKHWSCV QRFATGLGCS LQEAQAGETE EAETVSAMAL
     LSVGAEQAQA VATQEHSPRP AEEPMEQEPT L
//