ID HDAC8_MOUSE Reviewed; 377 AA.
AC Q8VH37; Q3V270; Q9D0K6;
DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 11-APR-2003, sequence version 2.
DT 27-MAR-2024, entry version 167.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Brain, Embryo, and Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pituitary;
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).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 58-206.
RA Ajamian F., Suuronen T., Salminen A.;
RT "Selective regulation of class I and II histone deacetylase expression in
RT cultured neural cells.";
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 195-223, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=C57BL/6J; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (APR-2007) to UniProtKB.
RN [5]
RP INTERACTION WITH CBFA2T3.
RX PubMed=11533236; DOI=10.1128/mcb.21.19.6470-6483.2001;
RA Amann J.M., Nip J., Strom D.K., Lutterbach B., Harada H., Lenny N.,
RA Downing J.R., Meyers S., Hiebert S.W.;
RT "ETO, a target of t(8;21) in acute leukemia, makes distinct contacts with
RT multiple histone deacetylases and binds mSin3A through its oligomerization
RT domain.";
RL Mol. Cell. Biol. 21:6470-6483(2001).
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. histone
CC deacetylase inhibitor. {ECO:0000250|UniProtKB:Q9BY41}.
CC -!- SUBUNIT: Interacts with CBFA2T3 (PubMed:11533236). Interacts with
CC phosphorylated SMG5/EST1B; this interaction protects SMG5 from
CC ubiquitin-mediated degradation (By similarity). Associates with alpha-
CC SMA (smooth muscle alpha-actin) (By similarity).
CC {ECO:0000250|UniProtKB:Q9BY41, ECO:0000269|PubMed:11533236}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8VH37-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VH37-2; Sequence=VSP_007178, VSP_007179;
CC -!- PTM: Phosphorylated by PKA on serine 39. Phosphorylation reduces
CC deacetylase activity observed preferentially on histones H3 and H4.
CC {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; AK011332; BAB27550.1; -; mRNA.
DR EMBL; AK131998; BAE20928.1; -; mRNA.
DR EMBL; BC061257; AAH61257.1; -; mRNA.
DR EMBL; AK034511; BAC28737.1; -; mRNA.
DR EMBL; AK041965; BAC31116.1; -; mRNA.
DR EMBL; AY066003; AAL47569.1; -; mRNA.
DR CCDS; CCDS41084.1; -. [Q8VH37-1]
DR RefSeq; NP_001300671.1; NM_001313742.1. [Q8VH37-2]
DR RefSeq; NP_081658.1; NM_027382.4. [Q8VH37-1]
DR AlphaFoldDB; Q8VH37; -.
DR SMR; Q8VH37; -.
DR BioGRID; 213982; 1.
DR IntAct; Q8VH37; 2.
DR MINT; Q8VH37; -.
DR STRING; 10090.ENSMUSP00000085226; -.
DR BindingDB; Q8VH37; -.
DR ChEMBL; CHEMBL2347; -.
DR PhosphoSitePlus; Q8VH37; -.
DR EPD; Q8VH37; -.
DR MaxQB; Q8VH37; -.
DR PaxDb; 10090-ENSMUSP00000085226; -.
DR PeptideAtlas; Q8VH37; -.
DR ProteomicsDB; 271498; -. [Q8VH37-1]
DR ProteomicsDB; 271499; -. [Q8VH37-2]
DR Pumba; Q8VH37; -.
DR DNASU; 70315; -.
DR Ensembl; ENSMUST00000087916.11; ENSMUSP00000085226.5; ENSMUSG00000067567.13. [Q8VH37-1]
DR GeneID; 70315; -.
DR KEGG; mmu:70315; -.
DR UCSC; uc009typ.1; mouse. [Q8VH37-1]
DR UCSC; uc009tyq.1; mouse. [Q8VH37-2]
DR AGR; MGI:1917565; -.
DR CTD; 55869; -.
DR MGI; MGI:1917565; Hdac8.
DR VEuPathDB; HostDB:ENSMUSG00000067567; -.
DR eggNOG; KOG1342; Eukaryota.
DR GeneTree; ENSGT00940000157843; -.
DR HOGENOM; CLU_007727_7_6_1; -.
DR InParanoid; Q8VH37; -.
DR OMA; CFWHSTG; -.
DR OrthoDB; 1327607at2759; -.
DR PhylomeDB; Q8VH37; -.
DR TreeFam; TF106175; -.
DR Reactome; R-MMU-2467813; Separation of Sister Chromatids.
DR Reactome; R-MMU-2500257; Resolution of Sister Chromatid Cohesion.
DR Reactome; R-MMU-350054; Notch-HLH transcription pathway.
DR BioGRID-ORCS; 70315; 4 hits in 80 CRISPR screens.
DR ChiTaRS; Hdac8; mouse.
DR PRO; PR:Q8VH37; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; Q8VH37; Protein.
DR Bgee; ENSMUSG00000067567; Expressed in wall of esophagus and 173 other cell types or tissues.
DR ExpressionAtlas; Q8VH37; baseline and differential.
DR Genevisible; Q8VH37; MM.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB.
DR GO; GO:0000118; C:histone deacetylase complex; TAS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; ISO:MGI.
DR GO; GO:0019213; F:deacetylase activity; ISO:MGI.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; TAS:UniProtKB.
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:MGI.
DR GO; GO:0051879; F:Hsp90 protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0033558; F:protein lysine deacetylase activity; ISO:MGI.
DR GO; GO:1904322; P:cellular response to forskolin; ISO:MGI.
DR GO; GO:0035984; P:cellular response to trichostatin A; ISO:MGI.
DR GO; GO:0006325; P:chromatin organization; TAS:UniProtKB.
DR GO; GO:0007064; P:mitotic sister chromatid cohesion; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:MGI.
DR GO; GO:0031400; P:negative regulation of protein modification process; ISO:MGI.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0031647; P:regulation of protein stability; ISO:MGI.
DR GO; GO:0032204; P:regulation of telomere maintenance; ISO:MGI.
DR GO; GO:1903496; P:response to 11-deoxycorticosterone; ISO:MGI.
DR CDD; cd10000; HDAC8; 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:SF39; HISTONE DEACETYLASE 8; 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 1: Evidence at protein level;
KW Alternative splicing; Chromatin regulator; Chromosome; Cytoplasm;
KW Direct protein sequencing; Hydrolase; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..377
FT /note="Histone deacetylase 8"
FT /id="PRO_0000114709"
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"
FT VAR_SEQ 246..253
FT /note="SVLKEVYQ -> RACFTRTP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_007178"
FT VAR_SEQ 254..377
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_007179"
FT CONFLICT 88
FT /note="E -> D (in Ref. 3; AAL47569)"
FT /evidence="ECO:0000305"
FT CONFLICT 118
FT /note="G -> A (in Ref. 3; AAL47569)"
FT /evidence="ECO:0000305"
FT CONFLICT 130
FT /note="K -> M (in Ref. 3; AAL47569)"
FT /evidence="ECO:0000305"
FT CONFLICT 170
FT /note="D -> E (in Ref. 3; AAL47569)"
FT /evidence="ECO:0000305"
FT CONFLICT 187
FT /note="D -> V (in Ref. 3; AAL47569)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 377 AA; 41772 MW; EEBD7B2517B235CD CRC64;
MEMPEEPANS 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
//
