HDAC8_RAT
ID HDAC8_RAT Reviewed; 377 AA.
AC B1WC68;
DT 24-NOV-2009, integrated into UniProtKB/Swiss-Prot.
DT 20-MAY-2008, sequence version 1.
DT 03-AUG-2022, entry version 89.
DE RecName: Full=Histone deacetylase 8;
DE Short=HD8;
DE EC=3.5.1.98 {ECO:0000250|UniProtKB:Q9BY41};
DE AltName: Full=Protein deacetylase HDAC8 {ECO:0000305};
DE EC=3.5.1.- {ECO:0000250|UniProtKB:Q9BY41};
DE AltName: Full=Protein decrotonylase HDAC8 {ECO:0000305};
DE EC=3.5.1.- {ECO:0000250|UniProtKB:Q9BY41};
GN Name=Hdac8;
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 [LARGE SCALE MRNA].
RC TISSUE=Spleen;
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).
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). Histone deacetylation gives a tag for epigenetic repression
CC and plays an important role in transcriptional regulation, cell cycle
CC progression and developmental events. Histone deacetylases act via the
CC formation of large multiprotein complexes. Also involved in the
CC deacetylation of cohesin complex protein SMC3 regulating release of
CC cohesin complexes from chromatin. May play a role in smooth muscle cell
CC contractility. In addition to protein deacetylase activity, also has
CC protein-lysine deacylase activity: acts as a protein decrotonylase by
CC mediating decrotonylation ((2E)-butenoyl) of histones.
CC {ECO:0000250|UniProtKB:Q9BY41}.
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:Q9BY41};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58197;
CC Evidence={ECO:0000250|UniProtKB:Q9BY41};
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:Q9BY41};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58109;
CC Evidence={ECO:0000250|UniProtKB:Q9BY41};
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:Q9BY41};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69173;
CC Evidence={ECO:0000250|UniProtKB:Q9BY41};
CC -!- COFACTOR:
CC Name=a divalent metal cation; Xref=ChEBI:CHEBI:60240;
CC Evidence={ECO:0000250|UniProtKB:Q9BY41};
CC Note=Binds 1 divalent metal cation per subunit.
CC {ECO:0000250|UniProtKB:Q9BY41};
CC -!- ACTIVITY REGULATION: Its activity is inhibited by trichostatin A (TSA)
CC and butyrate, 2 well known histone deacetylase inhibitors.
CC {ECO:0000250|UniProtKB:Q9BY41}.
CC -!- SUBUNIT: Interacts with CBFA2T3. Interacts with phosphorylated
CC SMG5/EST1B; this interaction protects SMG5 from ubiquitin-mediated
CC degradation. Associates with alpha-SMA (smooth muscle alpha-actin) (By
CC similarity). {ECO:0000250|UniProtKB:Q9BY41}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9BY41}.
CC Chromosome {ECO:0000250|UniProtKB:Q9BY41}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9BY41}. Note=Excluded from the nucleoli. Found
CC in the cytoplasm of cells showing smooth muscle differentiation.
CC {ECO:0000250|UniProtKB:Q9BY41}.
CC -!- PTM: Phosphorylated by PKA on serine 39. Phosphorylation reduces
CC deacetylase activity observed preferentially on histones H3 and H4 (By
CC similarity). {ECO:0000250|UniProtKB:Q9BY41}.
CC -!- SIMILARITY: Belongs to the histone deacetylase family. HD type 1
CC subfamily. {ECO:0000305}.
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DR EMBL; BC162023; AAI62023.1; -; mRNA.
DR RefSeq; NP_001119845.2; NM_001126373.2.
DR AlphaFoldDB; B1WC68; -.
DR SMR; B1WC68; -.
DR STRING; 10116.ENSRNOP00000004224; -.
DR iPTMnet; B1WC68; -.
DR PhosphoSitePlus; B1WC68; -.
DR PaxDb; B1WC68; -.
DR PeptideAtlas; B1WC68; -.
DR PRIDE; B1WC68; -.
DR Ensembl; ENSRNOT00000004224; ENSRNOP00000004224; ENSRNOG00000003122.
DR GeneID; 363481; -.
DR KEGG; rno:363481; -.
DR UCSC; RGD:1562895; rat.
DR CTD; 55869; -.
DR RGD; 1562895; Hdac8.
DR eggNOG; KOG1342; Eukaryota.
DR GeneTree; ENSGT00940000157843; -.
DR HOGENOM; CLU_007727_7_6_1; -.
DR InParanoid; B1WC68; -.
DR OMA; CFWHSTG; -.
DR OrthoDB; 732770at2759; -.
DR PhylomeDB; B1WC68; -.
DR TreeFam; TF106175; -.
DR Reactome; R-RNO-2467813; Separation of Sister Chromatids.
DR Reactome; R-RNO-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-RNO-350054; Notch-HLH transcription pathway.
DR PRO; PR:B1WC68; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000003122; Expressed in colon and 18 other tissues.
DR Genevisible; B1WC68; RN.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000118; C:histone deacetylase complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0003682; F:chromatin binding; IDA:RGD.
DR GO; GO:0019213; F:deacetylase activity; IDA:RGD.
DR GO; GO:0004407; F:histone deacetylase activity; ISS:UniProtKB.
DR GO; GO:0160009; F:histone decrotonylase activity; ISS:UniProtKB.
DR GO; GO:0030544; F:Hsp70 protein binding; ISO:RGD.
DR GO; GO:0051879; F:Hsp90 protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1904322; P:cellular response to forskolin; IDA:RGD.
DR GO; GO:0035984; P:cellular response to trichostatin A; IDA:RGD.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0016575; P:histone deacetylation; IEA:InterPro.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:RGD.
DR GO; GO:2000616; P:negative regulation of histone H3-K9 acetylation; IMP:RGD.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IMP:RGD.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:RGD.
DR GO; GO:0071922; P:regulation of cohesin loading; ISS:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; ISO:RGD.
DR GO; GO:0032204; P:regulation of telomere maintenance; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:1903496; P:response to 11-deoxycorticosterone; IDA:RGD.
DR GO; GO:0007062; P:sister chromatid cohesion; 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 Chromatin regulator; Chromosome; Cytoplasm; Hydrolase; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..377
FT /note="Histone deacetylase 8"
FT /id="PRO_0000389508"
FT REGION 14..324
FT /note="Histone deacetylase"
FT ACT_SITE 143
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q9BY41"
FT BINDING 101
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9BY41"
FT BINDING 151
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9BY41"
FT BINDING 178
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q9BY41"
FT BINDING 180
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q9BY41"
FT BINDING 267
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000250|UniProtKB:Q9BY41"
FT BINDING 306
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9BY41"
FT MOD_RES 39
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BY41"
SQ SEQUENCE 377 AA; 41754 MW; AC7D7A3114663505 CRC64;
MEIPEEPANS GHSLPPVYIY SPEYVSICDS LVKVPKRASM VHSLIEAYAL HKQMRIVKPK
VASMEEMATF HTDAYLQHLQ KVSQEGDEDH PDSIEYGLGY DCPATEGIFD YAAAIGGGTI
TAAQCLIDGK CKVAINWSGG WHHAKKDEAS GFCYLNDAVL GILRLRRKFD RILYVDLDLH
HGDGVEDAFS FTSKVMTVSL HKFSPGFFPG TGDMSDVGLG KGRYYSVNVP IQDGIQDEKY
YHICESVLKE VYQAFNPKAV VLQLGADTIA GDPMCSFNMT PVGIGKCLKY VLQWQLATLI
LGGGGYNLAN TARCWTYLTG VILGKTLSSE IPDHEFFTAY GPDYVLEITP SCRPDRNEPH
RIQQILNYIK GNLKHVV
