SIR2_YEAST
ID SIR2_YEAST Reviewed; 562 AA.
AC P06700; D6VRV4;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=NAD-dependent histone deacetylase SIR2;
DE EC=2.3.1.286;
DE AltName: Full=Regulatory protein SIR2;
DE AltName: Full=Silent information regulator 2;
GN Name=SIR2; Synonyms=MAR1; OrderedLocusNames=YDL042C; ORFNames=D2714;
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 [GENOMIC DNA].
RX PubMed=6098447; DOI=10.1002/j.1460-2075.1984.tb02214.x;
RA Shore D., Squire M., Nasmyth K.A.;
RT "Characterization of two genes required for the position-effect control of
RT yeast mating-type genes.";
RL EMBO J. 3:2817-2823(1984).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9046088;
RX DOI=10.1002/(sici)1097-0061(199701)13:1<65::aid-yea50>3.0.co;2-t;
RA Saren A.-M., Laamanen P., Lejarcegui J.B., Paulin L.;
RT "The sequence of a 36.7 kb segment on the left arm of chromosome IV from
RT Saccharomyces cerevisiae reveals 20 non-overlapping open reading frames
RT (ORFs) including SIT4, FAD1, NAM1, RNA11, SIR2, NAT1, PRP9, ACT2 and MPS1
RT and 11 new ORFs.";
RL Yeast 13:65-71(1997).
RN [3]
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 [4]
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 [5]
RP SUBCELLULAR LOCATION.
RX PubMed=9214640; DOI=10.1093/emboj/16.11.3243;
RA Gotta M., Strahl-Bolsinger S., Renauld H., Laroche T., Kennedy B.K.,
RA Grunstein M., Gasser S.M.;
RT "Localization of Sir2p: the nucleolus as a compartment for silent
RT information regulators.";
RL EMBO J. 16:3243-3255(1997).
RN [6]
RP PRELIMINARY FUNCTION.
RX PubMed=10619427; DOI=10.1016/s0092-8674(00)81671-2;
RA Tanny J.C., Dowd G.J., Huang J., Hilz H., Moazed D.;
RT "An enzymatic activity in the yeast Sir2 protein that is essential for gene
RT silencing.";
RL Cell 99:735-745(1999).
RN [7]
RP FUNCTION.
RX PubMed=10693811; DOI=10.1038/35001622;
RA Imai S., Armstrong C.M., Kaeberlein M., Guarente L.;
RT "Transcriptional silencing and longevity protein Sir2 is an NAD-dependent
RT histone deacetylase.";
RL Nature 403:795-800(2000).
RN [8]
RP FUNCTION.
RX PubMed=9278054; DOI=10.1038/42288;
RA Tsukamoto Y., Kato J., Ikeda H.;
RT "Silencing factors participate in DNA repair and recombination in
RT Saccharomyces cerevisiae.";
RL Nature 388:900-903(1997).
RN [9]
RP INTERACTION WITH SIR3 AND SIR4.
RX PubMed=9122169; DOI=10.1073/pnas.94.6.2186;
RA Moazed D., Kistler A., Axelrod A., Rine J., Johnson A.D.;
RT "Silent information regulator protein complexes in Saccharomyces
RT cerevisiae: a SIR2/SIR4 complex and evidence for a regulatory domain in
RT SIR4 that inhibits its interaction with SIR3.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2186-2191(1997).
RN [10]
RP IDENTIFICATION IN A RENT COMPLEX WITH CDC14.
RX PubMed=10219244; DOI=10.1016/s0092-8674(00)80733-3;
RA Shou W., Seol J.H., Shevchenko A., Baskerville C., Moazed D., Chen Z.W.S.,
RA Jang J., Shevchenko A., Charbonneau H., Deshaies R.J.;
RT "Exit from mitosis is triggered by Tem1-dependent release of the protein
RT phosphatase Cdc14 from nucleolar RENT complex.";
RL Cell 97:233-244(1999).
RN [11]
RP IDENTIFICATION IN A RENT COMPLEX WITH NET1.
RX PubMed=10219245; DOI=10.1016/s0092-8674(00)80734-5;
RA Straight A.F., Shou W., Dowd G.J., Turck C.W., Deshaies R.J., Johnson A.D.,
RA Moazed D.;
RT "Net1, a Sir2-associated nucleolar protein required for rDNA silencing and
RT nucleolar integrity.";
RL Cell 97:245-256(1999).
RN [12]
RP INTERACTION WITH ZDS2.
RX PubMed=10662670; DOI=10.1016/s0960-9822(00)00298-0;
RA Roy N., Runge K.W.;
RT "Two paralogs involved in transcriptional silencing that antagonistically
RT control yeast life span.";
RL Curr. Biol. 10:111-114(2000).
RN [13]
RP MECHANISM OF TRANSCRIPTION REPRESSION.
RX PubMed=11348596; DOI=10.1016/s0092-8674(01)00329-4;
RA Sekinger E.A., Gross D.S.;
RT "Silenced chromatin is permissive to activator binding and PIC
RT recruitment.";
RL Cell 105:403-414(2001).
RN [14]
RP REVIEW.
RX PubMed=11722841; DOI=10.1016/s0378-1119(01)00741-7;
RA Gasser S.M., Cockell M.M.;
RT "The molecular biology of the SIR proteins.";
RL Gene 279:1-16(2001).
RN [15]
RP INTERACTION WITH ESC8.
RX PubMed=12399377; DOI=10.1093/genetics/162.2.633;
RA Cuperus G., Shore D.;
RT "Restoration of silencing in Saccharomyces cerevisiae by tethering of a
RT novel Sir2-interacting protein, Esc8.";
RL Genetics 162:633-645(2002).
RN [16]
RP MUTAGENESIS OF ARG-139; GLY-270 AND PHE-296.
RX PubMed=12399383; DOI=10.1093/genetics/162.2.721;
RA Garcia S.N., Pillus L.;
RT "A unique class of conditional sir2 mutants displays distinct silencing
RT defects in Saccharomyces cerevisiae.";
RL Genetics 162:721-736(2002).
RN [17]
RP FUNCTION, AND INTERACTION WITH FOB1.
RX PubMed=12923057; DOI=10.1101/gad.1108403;
RA Huang J., Moazed D.;
RT "Association of the RENT complex with nontranscribed and coding regions of
RT rDNA and a regional requirement for the replication fork block protein Fob1
RT in rDNA silencing.";
RL Genes Dev. 17:2162-2176(2003).
RN [18]
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 [19]
RP ACTIVITY REGULATION.
RX PubMed=12939617; DOI=10.1038/nature01960;
RA Howitz K.T., Bitterman K.J., Cohen H.Y., Lamming D.W., Lavu S., Wood J.G.,
RA Zipkin R.E., Chung P., Kisielewski A., Zhang L.-L., Scherer B.,
RA Sinclair D.A.;
RT "Small molecule activators of sirtuins extend Saccharomyces cerevisiae
RT lifespan.";
RL Nature 425:191-196(2003).
RN [20]
RP FUNCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=15274642; DOI=10.1021/bi049592e;
RA Borra M.T., Langer M.R., Slama J.T., Denu J.M.;
RT "Substrate specificity and kinetic mechanism of the Sir2 family of NAD+-
RT dependent histone/protein deacetylases.";
RL Biochemistry 43:9877-9887(2004).
RN [21]
RP INTERACTION WITH MCM10.
RX PubMed=16328881; DOI=10.1007/s11033-005-2312-x;
RA Douglas N.L., Dozier S.K., Donato J.J.;
RT "Dual roles for Mcm10 in DNA replication initiation and silencing at the
RT mating-type loci.";
RL Mol. Biol. Rep. 32:197-204(2005).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [23]
RP FUNCTION, AND INTERACTION WITH SLX5/HEX3.
RX PubMed=18086879; DOI=10.1128/mcb.01291-07;
RA Darst R.P., Garcia S.N., Koch M.R., Pillus L.;
RT "Slx5 promotes transcriptional silencing and is required for robust growth
RT in the absence of Sir2.";
RL Mol. Cell. Biol. 28:1361-1372(2008).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [25]
RP FUNCTION.
RX PubMed=19220062; DOI=10.1021/bi802093g;
RA Du J., Jiang H., Lin H.;
RT "Investigating the ADP-ribosyltransferase activity of sirtuins with NAD
RT analogues and 32P-NAD.";
RL Biochemistry 48:2878-2890(2009).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [27]
RP INTERACTION WITH NSI1.
RX PubMed=22362748; DOI=10.1093/nar/gks188;
RA Ha C.W., Sung M.K., Huh W.K.;
RT "Nsi1 plays a significant role in the silencing of ribosomal DNA in
RT Saccharomyces cerevisiae.";
RL Nucleic Acids Res. 40:4892-4903(2012).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 209-562 IN COMPLEX WITH ZINC AND
RP NICOTINAMIDE.
RA Hall B.E., Buchberger J.R., Gerber S.A., Ambrosio A.L.B., Gygi S.P.,
RA Filman D., Moazed D., Ellenberger T.;
RT "Autoregulation of the yeast Sir2 deacetylase by reaction and trapping of a
RT pseudosubstrate motif in the active site.";
RL Submitted (JUN-2006) to the PDB data bank.
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 87-562 IN COMPLEX WITH SIR4;
RP ADP-RIBOSE AND ZINC.
RX PubMed=23307867; DOI=10.1101/gad.208140.112;
RA Hsu H.C., Wang C.L., Wang M., Yang N., Chen Z., Sternglanz R., Xu R.M.;
RT "Structural basis for allosteric stimulation of Sir2 activity by Sir4
RT binding.";
RL Genes Dev. 27:64-73(2013).
CC -!- FUNCTION: NAD-dependent deacetylase, which participates in a wide range
CC of cellular events including chromosome silencing, chromosome
CC segregation, DNA recombination and the determination of life span.
CC Involved in transcriptional repression of the silent mating-type loci
CC HML and HMR and telomeric silencing via its association with SIR3 and
CC SIR4. Plays a central role in ribosomal DNA (rDNA) silencing via its
CC association with the RENT complex, preventing hyperrecombination, and
CC repressing transcription from foreign promoters, which contributes to
CC extending life span. Probably represses transcription via the formation
CC of heterochromatin structure, which involves the compaction of
CC chromatin fiber into a more condensed form, although this complex in at
CC least one case can still bind euchromatic levels of positive
CC transcription regulators. Although it displays some NAD-dependent
CC histone deacetylase activity on histone H3K9Ac and H3K14Ac and histone
CC H4K16Ac in vitro, such activity is unclear in vivo and may not be
CC essential. {ECO:0000269|PubMed:10693811, ECO:0000269|PubMed:12923057,
CC ECO:0000269|PubMed:15274642, ECO:0000269|PubMed:18086879,
CC ECO:0000269|PubMed:19220062, ECO:0000269|PubMed:9278054}.
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;
CC Evidence={ECO:0000269|PubMed:23307867};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:23307867};
CC -!- ACTIVITY REGULATION: Its activity is increased by calorie restriction,
CC which slows the pace of aging and increases maximum lifespan. Activated
CC by resveratrol (3,5,4'-trihydroxy-trans-stilbene), which is found in
CC red wine. {ECO:0000269|PubMed:12939617}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=29.3 uM for NAD(+) {ECO:0000269|PubMed:15274642};
CC KM=239 uM for a synthetic histone H3K9 acetyllysine peptide
CC {ECO:0000269|PubMed:15274642};
CC KM=420 uM for a synthetic histone H3K14 acetyllysine peptide
CC {ECO:0000269|PubMed:15274642};
CC KM=140 uM for a synthetic histone H4K5 acetyllysine peptide
CC {ECO:0000269|PubMed:15274642};
CC KM=54 uM for a synthetic histone H4K8 acetyllysine peptide
CC {ECO:0000269|PubMed:15274642};
CC KM=105 uM for a synthetic histone H4K12 acetyllysine peptide
CC {ECO:0000269|PubMed:15274642};
CC KM=17 uM for a synthetic histone H4K16 acetyllysine peptide
CC {ECO:0000269|PubMed:15274642};
CC -!- SUBUNIT: Homomultimer. Forms a complex with SIR3 and SIR4
CC (PubMed:9122169). Component of the RENT complex, at least composed of
CC SIR2, CDC14 and NET1 (PubMed:10219244, PubMed:10219245). The RENT
CC complex interacts with FOB1 (PubMed:12923057). Interacts with ESC8
CC (PubMed:12399377). Interacts with and ZDS2 (PubMed:10662670). Interacts
CC with MCM10 (PubMed:16328881). Interacts with SLX5 (PubMed:18086879).
CC Interacts with NSI1 (PubMed:22362748). {ECO:0000269|PubMed:10219244,
CC ECO:0000269|PubMed:10219245, ECO:0000269|PubMed:10662670,
CC ECO:0000269|PubMed:12399377, ECO:0000269|PubMed:12923057,
CC ECO:0000269|PubMed:16328881, ECO:0000269|PubMed:18086879,
CC ECO:0000269|PubMed:22362748, ECO:0000269|PubMed:9122169}.
CC -!- INTERACTION:
CC P06700; Q00684: CDC14; NbExp=5; IntAct=EBI-17219, EBI-4192;
CC P06700; P22146: GAS1; NbExp=2; IntAct=EBI-17219, EBI-7327;
CC P06700; P11978: SIR4; NbExp=7; IntAct=EBI-17219, EBI-17237;
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:9214640}.
CC Note=Associated with nucleolar chromatin. Preferentially bound to the
CC spacer regions of the rDNA repeats through its interaction with NET1.
CC -!- MISCELLANEOUS: Its stability is directly linked to life span, which is
CC extended when it is present in high dosage. Conversely, its absence
CC shortens life span.
CC -!- MISCELLANEOUS: The reported ADP-ribosyltransferase activity of sirtuins
CC is likely some inefficient side reaction of the deacetylase activity
CC and may not be physiologically relevant. {ECO:0000305|PubMed:19220062}.
CC -!- MISCELLANEOUS: Present with 3350 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}.
CC -!- CAUTION: Was originally thought to be an ADP-ribosyltransferase.
CC {ECO:0000305|PubMed:10619427}.
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=In vino vita? - Issue 40 of
CC November 2003;
CC URL="https://web.expasy.org/spotlight/back_issues/040";
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DR EMBL; X01419; CAA25667.1; -; Genomic_DNA.
DR EMBL; Z71781; CAA96447.1; -; Genomic_DNA.
DR EMBL; Z74090; CAA98600.1; -; Genomic_DNA.
DR EMBL; BK006938; DAA11814.1; -; Genomic_DNA.
DR PIR; S05891; RGBYS2.
DR RefSeq; NP_010242.1; NM_001180101.1.
DR PDB; 2HJH; X-ray; 1.85 A; A/B=209-562.
DR PDB; 4IAO; X-ray; 2.90 A; A/B=87-562.
DR PDBsum; 2HJH; -.
DR PDBsum; 4IAO; -.
DR AlphaFoldDB; P06700; -.
DR SMR; P06700; -.
DR BioGRID; 32017; 379.
DR ComplexPortal; CPX-1669; RENT complex.
DR ComplexPortal; CPX-1811; Sir2-3-4 silent chromatin complex.
DR DIP; DIP-596N; -.
DR IntAct; P06700; 49.
DR MINT; P06700; -.
DR STRING; 4932.YDL042C; -.
DR BindingDB; P06700; -.
DR ChEMBL; CHEMBL3275; -.
DR iPTMnet; P06700; -.
DR MaxQB; P06700; -.
DR PaxDb; P06700; -.
DR PRIDE; P06700; -.
DR EnsemblFungi; YDL042C_mRNA; YDL042C; YDL042C.
DR GeneID; 851520; -.
DR KEGG; sce:YDL042C; -.
DR SGD; S000002200; SIR2.
DR VEuPathDB; FungiDB:YDL042C; -.
DR eggNOG; KOG2684; Eukaryota.
DR GeneTree; ENSGT00940000159406; -.
DR HOGENOM; CLU_023643_5_0_1; -.
DR InParanoid; P06700; -.
DR OMA; PYCYKKR; -.
DR BioCyc; MetaCyc:MON3O-4152; -.
DR BioCyc; YEAST:MON3O-4152; -.
DR Reactome; R-SCE-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-SCE-427359; SIRT1 negatively regulates rRNA expression.
DR SABIO-RK; P06700; -.
DR EvolutionaryTrace; P06700; -.
DR PRO; PR:P06700; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P06700; protein.
DR GO; GO:0005677; C:chromatin silencing complex; IDA:SGD.
DR GO; GO:0000781; C:chromosome, telomeric region; IDA:SGD.
DR GO; GO:0000792; C:heterochromatin; IDA:SGD.
DR GO; GO:0005730; C:nucleolus; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0030869; C:RENT complex; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0070403; F:NAD+ binding; IBA:GO_Central.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:SGD.
DR GO; GO:0032041; F:NAD-dependent histone deacetylase activity (H3-K14 specific); IDA:SGD.
DR GO; GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); IDA:SGD.
DR GO; GO:0046970; F:NAD-dependent histone deacetylase activity (H4-K16 specific); IDA:SGD.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IDA:SGD.
DR GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:SGD.
DR GO; GO:0097695; P:establishment of protein-containing complex localization to telomere; IMP:SGD.
DR GO; GO:0031047; P:gene silencing by RNA; IMP:CACAO.
DR GO; GO:1904524; P:negative regulation of DNA amplification; IMP:SGD.
DR GO; GO:0045910; P:negative regulation of DNA recombination; IMP:SGD.
DR GO; GO:0008156; P:negative regulation of DNA replication; IMP:SGD.
DR GO; GO:0000183; P:rDNA heterochromatin assembly; IMP:SGD.
DR GO; GO:0097752; P:regulation of DNA stability; IMP:SGD.
DR GO; GO:0030466; P:silent mating-type cassette heterochromatin assembly; IMP:SGD.
DR GO; GO:0007062; P:sister chromatid cohesion; IMP:SGD.
DR GO; GO:0031509; P:subtelomeric heterochromatin assembly; IMP:SGD.
DR GO; GO:0034398; P:telomere tethering at nuclear periphery; IMP:SGD.
DR Gene3D; 3.30.1600.10; -; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR007654; NAD-dep_histone_deAcase_SIR2_N.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF04574; DUF592; 1.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Chromatin regulator; DNA damage; DNA repair; Metal-binding;
KW NAD; Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Transferase; Zinc.
FT CHAIN 1..562
FT /note="NAD-dependent histone deacetylase SIR2"
FT /id="PRO_0000110280"
FT DOMAIN 245..529
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 1..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..28
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 29..54
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 364
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 262..281
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23307867, ECO:0000269|Ref.28"
FT BINDING 344..347
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P53686"
FT BINDING 372
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23307867, ECO:0000269|Ref.28"
FT BINDING 375
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23307867, ECO:0000269|Ref.28"
FT BINDING 396
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23307867, ECO:0000269|Ref.28"
FT BINDING 399
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23307867, ECO:0000269|Ref.28"
FT BINDING 471..473
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23307867"
FT BINDING 496..498
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23307867"
FT BINDING 513
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:23307867"
FT MUTAGEN 139
FT /note="R->K: Defects in telomeric silencing."
FT /evidence="ECO:0000269|PubMed:12399383"
FT MUTAGEN 270
FT /note="G->E: Defects in telomeric silencing."
FT /evidence="ECO:0000269|PubMed:12399383"
FT MUTAGEN 296
FT /note="F->L: Defects in telomeric silencing."
FT /evidence="ECO:0000269|PubMed:12399383"
FT HELIX 102..105
FT /evidence="ECO:0007829|PDB:4IAO"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:4IAO"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:4IAO"
FT HELIX 132..154
FT /evidence="ECO:0007829|PDB:4IAO"
FT HELIX 163..170
FT /evidence="ECO:0007829|PDB:4IAO"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:4IAO"
FT HELIX 178..187
FT /evidence="ECO:0007829|PDB:4IAO"
FT STRAND 213..217
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 244..253
FT /evidence="ECO:0007829|PDB:2HJH"
FT STRAND 255..261
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 263..269
FT /evidence="ECO:0007829|PDB:2HJH"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 280..283
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 284..287
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 292..296
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 298..303
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 306..311
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 312..315
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 324..334
FT /evidence="ECO:0007829|PDB:2HJH"
FT STRAND 338..343
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 349..352
FT /evidence="ECO:0007829|PDB:2HJH"
FT TURN 357..359
FT /evidence="ECO:0007829|PDB:2HJH"
FT STRAND 360..362
FT /evidence="ECO:0007829|PDB:2HJH"
FT STRAND 365..372
FT /evidence="ECO:0007829|PDB:2HJH"
FT TURN 373..375
FT /evidence="ECO:0007829|PDB:2HJH"
FT STRAND 378..380
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 381..384
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 385..389
FT /evidence="ECO:0007829|PDB:2HJH"
FT TURN 397..399
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 400..406
FT /evidence="ECO:0007829|PDB:2HJH"
FT TURN 417..420
FT /evidence="ECO:0007829|PDB:4IAO"
FT TURN 433..436
FT /evidence="ECO:0007829|PDB:2HJH"
FT STRAND 437..442
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 451..460
FT /evidence="ECO:0007829|PDB:2HJH"
FT TURN 461..463
FT /evidence="ECO:0007829|PDB:2HJH"
FT STRAND 466..471
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 479..481
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 482..485
FT /evidence="ECO:0007829|PDB:2HJH"
FT STRAND 492..498
FT /evidence="ECO:0007829|PDB:2HJH"
FT STRAND 506..511
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 513..524
FT /evidence="ECO:0007829|PDB:2HJH"
FT HELIX 533..537
FT /evidence="ECO:0007829|PDB:2HJH"
FT STRAND 541..547
FT /evidence="ECO:0007829|PDB:2HJH"
FT STRAND 550..555
FT /evidence="ECO:0007829|PDB:2HJH"
SQ SEQUENCE 562 AA; 63262 MW; 52E6937533654586 CRC64;
MTIPHMKYAV SKTSENKVSN TVSPTQDKDA IRKQPDDIIN NDEPSHKKIK VAQPDSLRET
NTTDPLGHTK AALGEVASME LKPTNDMDPL AVSAASVVSM SNDVLKPETP KGPIIISKNP
SNGIFYGPSF TKRESLNARM FLKYYGAHKF LDTYLPEDLN SLYIYYLIKL LGFEVKDQAL
IGTINSIVHI NSQERVQDLG SAISVTNVED PLAKKQTVRL IKDLQRAINK VLCTRLRLSN
FFTIDHFIQK LHTARKILVL TGAGVSTSLG IPDFRSSEGF YSKIKHLGLD DPQDVFNYNI
FMHDPSVFYN IANMVLPPEK IYSPLHSFIK MLQMKGKLLR NYTQNIDNLE SYAGISTDKL
VQCHGSFATA TCVTCHWNLP GERIFNKIRN LELPLCPYCY KKRREYFPEG YNNKVGVAAS
QGSMSERPPY ILNSYGVLKP DITFFGEALP NKFHKSIRED ILECDLLICI GTSLKVAPVS
EIVNMVPSHV PQVLINRDPV KHAEFDLSLL GYCDDIAAMV AQKCGWTIPH KKWNDLKNKN
FKCQEKDKGV YVVTSDEHPK TL
