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 27-MAR-2024, entry version 231. DE RecName: Full=NAD-dependent histone deacetylase SIR2; DE EC=2.3.1.286 {ECO:0000255|PROSITE-ProRule:PRU00236}; 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 399. 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; 4932-YDL042C; -. DR PeptideAtlas; P06700; -. DR EnsemblFungi; YDL042C_mRNA; YDL042C; YDL042C. DR GeneID; 851520; -. DR KEGG; sce:YDL042C; -. DR AGR; SGD:S000002200; -. 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; MFLKYYG; -. DR OrthoDB; 10545at2759; -. DR BioCyc; MetaCyc:MONOMER3O-4152; -. DR BioCyc; YEAST:MONOMER3O-4152; -. DR Reactome; R-SCE-3371453; Regulation of HSF1-mediated heat shock response. DR SABIO-RK; P06700; -. DR BioGRID-ORCS; 851520; 10 hits in 10 CRISPR screens. 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 H3K14 deacetylase activity; IDA:SGD. DR GO; GO:0046969; F:NAD-dependent histone H3K9 deacetylase activity; IDA:SGD. DR GO; GO:0046970; F:NAD-dependent histone H4K16 deacetylase activity; 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:0031507; P:heterochromatin formation; NAS:ComplexPortal. 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 formation; IMP:SGD. DR GO; GO:0097752; P:regulation of DNA stability; IMP:SGD. DR GO; GO:0031047; P:regulatory ncRNA-mediated gene silencing; IMP:CACAO. DR GO; GO:0030466; P:silent mating-type cassette heterochromatin formation; IMP:SGD. DR GO; GO:0007062; P:sister chromatid cohesion; IMP:SGD. DR GO; GO:0031509; P:subtelomeric heterochromatin formation; IMP:SGD. DR GO; GO:0034398; P:telomere tethering at nuclear periphery; IMP:SGD. DR CDD; cd01408; SIRT1; 1. DR Gene3D; 1.20.120.1710; -; 1. DR Gene3D; 3.30.1600.10; SIR2/SIRT2 'Small Domain; 1. DR Gene3D; 3.40.50.1220; TPP-binding domain; 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 PANTHER; PTHR11085:SF14; NAD-DEPENDENT PROTEIN DEACETYLASE SIRTUIN-1; 1. DR PANTHER; PTHR11085; NAD-DEPENDENT PROTEIN DEACYLASE SIRTUIN-5, MITOCHONDRIAL-RELATED; 1. DR Pfam; PF04574; DUF592; 1. DR Pfam; PF02146; SIR2; 1. DR SUPFAM; SSF52467; DHS-like NAD/FAD-binding domain; 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 237..527 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 //