HST4_YEAST
ID HST4_YEAST Reviewed; 370 AA.
AC P53688; D6VSH4;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=NAD-dependent histone deacetylase HST4;
DE EC=2.3.1.286;
DE AltName: Full=Homologous to SIR2 protein 4;
DE AltName: Full=Regulatory protein SIR2 homolog 4;
GN Name=HST4; OrderedLocusNames=YDR191W; ORFNames=YD9346.03;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [4]
RP GENE NAME.
RC STRAIN=GRY 668;
RX PubMed=8810037;
RX DOI=10.1002/(sici)1097-0061(19960615)12:7<631::aid-yea960>3.0.co;2-8;
RA Derbyshire M.K., Weinstock K.G., Strathern J.N.;
RT "HST1, a new member of the SIR2 family of genes.";
RL Yeast 12:631-640(1996).
RN [5]
RP CHARACTERIZATION.
RX PubMed=7498786; DOI=10.1101/gad.9.23.2888;
RA Brachmann C.B., Sherman J.M., Devine S.E., Cameron E.E., Pillus L.,
RA Boeke J.D.;
RT "The SIR2 gene family, conserved from bacteria to humans, functions in
RT silencing, cell cycle progression, and chromosome stability.";
RL Genes Dev. 9:2888-2902(1995).
RN [6]
RP FUNCTION.
RX PubMed=10841563; DOI=10.1073/pnas.97.12.6658;
RA Smith J.S., Brachmann C.B., Celic I., Kenna M.A., Muhammad S., Starai V.J.,
RA Avalos J.L., Escalante-Semerena J.C., Grubmeyer C., Wolberger C.,
RA Boeke J.D.;
RT "A phylogenetically conserved NAD+-dependent protein deacetylase activity
RT in the Sir2 protein family.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:6658-6663(2000).
RN [7]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [8]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [9]
RP FUNCTION.
RX PubMed=16487579; DOI=10.1016/j.cell.2005.12.036;
RA Pan X., Ye P., Yuan D.S., Wang X., Bader J.S., Boeke J.D.;
RT "A DNA integrity network in the yeast Saccharomyces cerevisiae.";
RL Cell 124:1069-1081(2006).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17106263; DOI=10.4161/cc.5.22.3501;
RA Miller K.M., Maas N.L., Toczyski D.P.;
RT "Taking it off: regulation of H3 K56 acetylation by Hst3 and Hst4.";
RL Cell Cycle 5:2561-2565(2006).
RN [11]
RP FUNCTION.
RX PubMed=16815704; DOI=10.1016/j.cub.2006.06.023;
RA Celic I., Masumoto H., Griffith W.P., Meluh P., Cotter R.J., Boeke J.D.,
RA Verreault A.;
RT "The sirtuins Hst3 and Hst4p preserve genome integrity by controlling
RT histone H3 lysine 56 deacetylation.";
RL Curr. Biol. 16:1280-1289(2006).
CC -!- FUNCTION: NAD-dependent histone deacetylase, which contributes together
CC with HST3 to histone H3 'Lys-56' deacetylation, regulation of telomeric
CC silencing, proper cell cycle progression, DNA damage control, DNA
CC recombination, and genomic maintenance. {ECO:0000269|PubMed:10841563,
CC ECO:0000269|PubMed:16487579, ECO:0000269|PubMed:16815704,
CC ECO:0000269|PubMed:17106263}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-
CC ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767;
CC EC=2.3.1.286; Evidence={ECO:0000255|PROSITE-ProRule:PRU00236};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:17106263}.
CC -!- MISCELLANEOUS: Present with 377 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
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DR EMBL; Z48784; CAA88705.1; -; Genomic_DNA.
DR EMBL; AY557699; AAS56025.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA12034.1; -; Genomic_DNA.
DR PIR; S52699; S52699.
DR RefSeq; NP_010477.3; NM_001180499.3.
DR AlphaFoldDB; P53688; -.
DR SMR; P53688; -.
DR BioGRID; 32244; 101.
DR IntAct; P53688; 4.
DR STRING; 4932.YDR191W; -.
DR PaxDb; P53688; -.
DR PRIDE; P53688; -.
DR EnsemblFungi; YDR191W_mRNA; YDR191W; YDR191W.
DR GeneID; 851772; -.
DR KEGG; sce:YDR191W; -.
DR SGD; S000002599; HST4.
DR VEuPathDB; FungiDB:YDR191W; -.
DR eggNOG; KOG2684; Eukaryota.
DR HOGENOM; CLU_021544_1_2_1; -.
DR InParanoid; P53688; -.
DR OMA; AGTSCKI; -.
DR BioCyc; YEAST:G3O-29779-MON; -.
DR PRO; PR:P53688; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P53688; protein.
DR GO; GO:0000781; C:chromosome, telomeric region; IEA:GOC.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0031934; C:mating-type region heterochromatin; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:SGD.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:1990383; P:cellular response to biotin starvation; IMP:SGD.
DR GO; GO:0016575; P:histone deacetylation; IGI:SGD.
DR GO; GO:0071572; P:histone H3-K56 deacetylation; IBA:GO_Central.
DR GO; GO:0009299; P:mRNA transcription; IDA:SGD.
DR GO; GO:0098781; P:ncRNA transcription; IDA:SGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0031508; P:pericentric heterochromatin assembly; IBA:GO_Central.
DR GO; GO:0006282; P:regulation of DNA repair; IBA:GO_Central.
DR GO; GO:1990414; P:replication-born double-strand break repair via sister chromatid exchange; IMP:SGD.
DR GO; GO:0046459; P:short-chain fatty acid metabolic process; IMP:SGD.
DR GO; GO:0031509; P:subtelomeric heterochromatin assembly; IGI:SGD.
DR Gene3D; 3.30.1600.10; -; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW Metal-binding; NAD; Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Transferase; Zinc.
FT CHAIN 1..370
FT /note="NAD-dependent histone deacetylase HST4"
FT /id="PRO_0000110284"
FT DOMAIN 83..370
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 213
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 100..119
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 184..187
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 221
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 224
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 251
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 254
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 310..312
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 340..342
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT BINDING 363
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
SQ SEQUENCE 370 AA; 41765 MW; 86BB0238BFA914F1 CRC64;
MKQKFVLPIT PPSTAEKKPQ TENRCNENLK PRRLLPQLKK SVRNRKPRLS YRPELNSVFD
LDAYVDSTHL SKSQRHHMDR DAGFISYALN YSKRMVVVSG AGISVAAGIP DFRSSEGIFS
TVNGGSGKDL FDYNRVYGDE SMSLKFNQLM VSLFRLSKNC QPTKFHEMLN EFARDGRLLR
LYTQNIDGLD TQLPHLSTNV PLAKPIPSTV QLHGSIKHME CNKCLNIKPF DPELFKCDDK
FDSRTEIIPS CPQCEEYETV RKMAGLRSTG VGKLRPRVIL YNEVHPEGDF IGEIANNDLK
KRIDCLIIVG TSLKIPGVKN ICRQFAAKVH ANRGIVLYLN TSMPPKNVLD SLKFVDLVVL
GDCQHVTSLL
