NAD-dependent protein deacetylase sirtuin-1 (EC 2 3 1 286) (NAD-dependent protein deacylase sirtuin-1) (EC 2 3 1 -) (Regulatory protein SIR2 homolog 1) (SIR2-like protein 1) (SIR2alpha) (Sir2) (mSIR2a) [Cleaved into: SirtT1 75 kDa fragment (75SirT1)]

 SIR1_MOUSE              Reviewed;         737 AA.
 Q923E4; Q9QXG8;
 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
 31-OCT-2003, sequence version 2.
 10-FEB-2021, entry version 188.
 RecName: Full=NAD-dependent protein deacetylase sirtuin-1;
          EC=2.3.1.286 {ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:28883095};
 AltName: Full=NAD-dependent protein deacylase sirtuin-1;
          EC=2.3.1.- {ECO:0000305|PubMed:30026585};
 AltName: Full=Regulatory protein SIR2 homolog 1;
 AltName: Full=SIR2-like protein 1;
 AltName: Full=SIR2alpha;
          Short=Sir2;
          Short=mSIR2a;
 Contains:
   RecName: Full=SirtT1 75 kDa fragment;
            Short=75SirT1;
 Name=Sirt1; Synonyms=Sir2l1;
 Mus musculus (Mouse).
 Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
 Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
 Murinae; Mus; Mus.
 NCBI_TaxID=10090;
 [1]
 NUCLEOTIDE SEQUENCE [MRNA].
 STRAIN=Swiss Webster / NIH;
 PubMed=10693811; DOI=10.1038/35001622;
 Imai S., Armstrong C.M., Kaeberlein M., Guarente L.;
 "Transcriptional silencing and longevity protein Sir2 is an NAD-dependent
 histone deacetylase.";
 Nature 403:795-800(2000).
 [2]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 545-737.
 TISSUE=Mammary tumor;
 PubMed=15489334; DOI=10.1101/gr.2596504;
 The MGC Project Team;
 "The status, quality, and expansion of the NIH full-length cDNA project:
 the Mammalian Gene Collection (MGC).";
 Genome Res. 14:2121-2127(2004).
 [3]
 FUNCTION, INTERACTION WITH TP53, ACTIVITY REGULATION, ACTIVE SITE, AND
 MUTAGENESIS OF HIS-355.
 PubMed=11672522; DOI=10.1016/s0092-8674(01)00524-4;
 Luo J., Nikolaev A.Y., Imai S., Chen D., Su F., Shiloh A., Guarente L.,
 Gu W.;
 "Negative control of p53 by Sir2alpha promotes cell survival under
 stress.";
 Cell 107:137-148(2001).
 [4]
 FUNCTION IN DEACETYLATION OF TAF1B.
 PubMed=11250901; DOI=10.1093/emboj/20.6.1353;
 Muth V., Nadaud S., Grummt I., Voit R.;
 "Acetylation of TAF(I)68, a subunit of TIF-IB/SL1, activates RNA polymerase
 I transcription.";
 EMBO J. 20:1353-1362(2001).
 [5]
 FUNCTION.
 PubMed=12651913;
 McBurney M.W., Yang X., Jardine K., Bieman M., Th'ng J., Lemieux M.;
 "The absence of SIR2alpha protein has no effect on global gene silencing in
 mouse embryonic stem cells.";
 Mol. Cancer Res. 1:402-409(2003).
 [6]
 TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
 PubMed=12482959; DOI=10.1128/mcb.23.1.38-54.2003;
 McBurney M.W., Yang X., Jardine K., Hixon M., Boekelheide K., Webb J.R.,
 Lansdorp P.M., Lemieux M.;
 "The mammalian SIR2alpha protein has a role in embryogenesis and
 gametogenesis.";
 Mol. Cell. Biol. 23:38-54(2003).
 [7]
 FUNCTION, INTERACTION WITH MYOD1 AND PCAF, MUTAGENESIS OF HIS-355, AND
 ACTIVE SITE.
 PubMed=12887892; DOI=10.1016/s1097-2765(03)00226-0;
 Fulco M., Schiltz R.L., Iezzi S., King M.T., Zhao P., Kashiwaya Y.,
 Hoffman E., Veech R.L., Sartorelli V.;
 "Sir2 regulates skeletal muscle differentiation as a potential sensor of
 the redox state.";
 Mol. Cell 12:51-62(2003).
 [8]
 FUNCTION.
 PubMed=12960381; DOI=10.1073/pnas.1934713100;
 Cheng H.-L., Mostoslavsky R., Saito S., Manis J.P., Gu Y., Patel P.,
 Bronson R., Appella E., Alt F.W., Chua K.F.;
 "Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-
 deficient mice.";
 Proc. Natl. Acad. Sci. U.S.A. 100:10794-10799(2003).
 [9]
 FUNCTION IN ADIPODIGENESIS, FUNCTION IN FAT MOBILIZATION, AND INTERACTION
 WITH PPARG AND NCOR1.
 PubMed=15175761; DOI=10.1038/nature02583;
 Picard F., Kurtev M., Chung N., Topark-Ngarm A., Senawong T.,
 Machado De Oliveira R., Leid M., McBurney M.W., Guarente L.;
 "Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-
 gamma.";
 Nature 429:771-776(2004).
 [10]
 FUNCTION IN DEACETYLATION OF ACSS2, AND FUNCTION IN REGULATION OF ACCS2.
 PubMed=16790548; DOI=10.1073/pnas.0604392103;
 Hallows W.C., Lee S., Denu J.M.;
 "Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases.";
 Proc. Natl. Acad. Sci. U.S.A. 103:10230-10235(2006).
 [11]
 FUNCTION IN DEACETYLATION OF NR1H3 AND NR1H2, AND FUNCTION IN REGULATION OF
 NR1H3.
 PubMed=17936707; DOI=10.1016/j.molcel.2007.07.032;
 Li X., Zhang S., Blander G., Tse J.G., Krieger M., Guarente L.;
 "SIRT1 deacetylates and positively regulates the nuclear receptor LXR.";
 Mol. Cell 28:91-106(2007).
 [12]
 FUNCTION IN APOPTOSIS.
 PubMed=18371449; DOI=10.1016/j.stem.2008.01.002;
 Han M.K., Song E.K., Guo Y., Ou X., Mantel C., Broxmeyer H.E.;
 "SIRT1 regulates apoptosis and Nanog expression in mouse embryonic stem
 cells by controlling p53 subcellular localization.";
 Cell Stem Cell 2:241-251(2008).
 [13]
 INTERACTION WITH FOXO1, FUNCTION IN DEACETYLATION OF FOXO1, MUTAGENESIS OF
 HIS-355, AND ACTIVE SITE.
 PubMed=15220471; DOI=10.1073/pnas.0400593101;
 Daitoku H., Hatta M., Matsuzaki H., Aratani S., Ohshima T., Miyagishi M.,
 Nakajima T., Fukamizu A.;
 "Silent information regulator 2 potentiates Foxo1-mediated transcription
 through its deacetylase activity.";
 Proc. Natl. Acad. Sci. U.S.A. 101:10042-10047(2004).
 [14]
 INTERACTION WITH HIC1.
 PubMed=16269335; DOI=10.1016/j.cell.2005.08.011;
 Chen W.Y., Wang D.H., Yen R.C., Luo J., Gu W., Baylin S.B.;
 "Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent
 DNA-damage responses.";
 Cell 123:437-448(2005).
 [15]
 FUNCTION IN REGULATION OF INSULIN SECRETION.
 PubMed=16098828; DOI=10.1016/j.cmet.2005.07.001;
 Moynihan K.A., Grimm A.A., Plueger M.M., Bernal-Mizrachi E., Ford E.,
 Cras-Meneur C., Permutt M.A., Imai S.;
 "Increased dosage of mammalian Sir2 in pancreatic beta cells enhances
 glucose-stimulated insulin secretion in mice.";
 Cell Metab. 2:105-117(2005).
 [16]
 FUNCTION.
 PubMed=15632193; DOI=10.1074/jbc.m408748200;
 Bouras T., Fu M., Sauve A.A., Wang F., Quong A.A., Perkins N.D., Hay R.T.,
 Gu W., Pestell R.G.;
 "SIRT1 deacetylation and repression of p300 involves lysine residues
 1020/1024 within the cell cycle regulatory domain 1.";
 J. Biol. Chem. 280:10264-10276(2005).
 [17]
 FUNCTION IN REGULATION OF FOXO1.
 PubMed=15788402; DOI=10.1074/jbc.m412357200;
 Frescas D., Valenti L., Accili D.;
 "Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-
 dependent deacetylation promotes expression of glucogenetic genes.";
 J. Biol. Chem. 280:20589-20595(2005).
 [18]
 FUNCTION IN DEACETYLATION OF PPARGC1A, FUNCTION IN REGULATION OF GLUCOSE
 HOMEOSTASIS, AND INDUCTION.
 PubMed=15744310; DOI=10.1038/nature03354;
 Rodgers J.T., Lerin C., Haas W., Gygi S.P., Spiegelman B.M., Puigserver P.;
 "Nutrient control of glucose homeostasis through a complex of PGC-1alpha
 and SIRT1.";
 Nature 434:113-118(2005).
 [19]
 INDUCTION.
 PubMed=16224023; DOI=10.1126/science.1117728;
 Nisoli E., Tonello C., Cardile A., Cozzi V., Bracale R., Tedesco L.,
 Falcone S., Valerio A., Cantoni O., Clementi E., Moncada S., Carruba M.O.;
 "Calorie restriction promotes mitochondrial biogenesis by inducing the
 expression of eNOS.";
 Science 310:314-317(2005).
 [20]
 FUNCTION, INTERACTION WITH E2F1, MUTAGENESIS OF HIS-355, AND ACTIVE SITE.
 PubMed=16892051; DOI=10.1038/ncb1468;
 Wang C., Chen L., Hou X., Li Z., Kabra N., Ma Y., Nemoto S., Finkel T.,
 Gu W., Cress W.D., Chen J.;
 "Interactions between E2F1 and SirT1 regulate apoptotic response to DNA
 damage.";
 Nat. Cell Biol. 8:1025-1031(2006).
 [21]
 FUNCTION IN REGULATION OF INSULIN SECRETION.
 PubMed=16366736; DOI=10.1371/journal.pbio.0040031;
 Bordone L., Motta M.C., Picard F., Robinson A., Jhala U.S., Apfeld J.,
 McDonagh T., Lemieux M., McBurney M., Szilvasi A., Easlon E.J., Lin S.J.,
 Guarente L.;
 "Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta
 cells.";
 PLoS Biol. 4:E31-E31(2006).
 [22]
 FUNCTION IN DEACETYLATION OF RB1.
 PubMed=17620057; DOI=10.1042/bj20070151;
 Wong S., Weber J.D.;
 "Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1.";
 Biochem. J. 407:451-460(2007).
 [23]
 FUNCTION IN DEACETYLATION OF PPARGC1A, AND FUNCTION IN REGULATION OF MUSCLE
 METABOLISM.
 PubMed=17347648; DOI=10.1038/sj.emboj.7601633;
 Gerhart-Hines Z., Rodgers J.T., Bare O., Lerin C., Kim S.H.,
 Mostoslavsky R., Alt F.W., Wu Z., Puigserver P.;
 "Metabolic control of muscle mitochondrial function and fatty acid
 oxidation through SIRT1/PGC-1alpha.";
 EMBO J. 26:1913-1923(2007).
 [24]
 FUNCTION IN DEACETYLATION OF SMAD7.
 PubMed=17098745; DOI=10.1074/jbc.m605904200;
 Kume S., Haneda M., Kanasaki K., Sugimoto T., Araki S., Isshiki K.,
 Isono M., Uzu T., Guarente L., Kashiwagi A., Koya D.;
 "SIRT1 inhibits transforming growth factor beta-induced apoptosis in
 glomerular mesangial cells via Smad7 deacetylation.";
 J. Biol. Chem. 282:151-158(2007).
 [25]
 SUBCELLULAR LOCATION, AND MUTAGENESIS OF 38-ARG-ARG-39; 138-LEU--LEU-145;
 227-LYS--LYS-230 AND 425-VAL--ILE-431.
 PubMed=17197703; DOI=10.1074/jbc.m609554200;
 Tanno M., Sakamoto J., Miura T., Shimamoto K., Horio Y.;
 "Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase
 SIRT1.";
 J. Biol. Chem. 282:6823-6832(2007).
 [26]
 FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH IRS1 AND IRS2.
 PubMed=17901049; DOI=10.1074/jbc.m706644200;
 Zhang J.;
 "The direct involvement of SirT1 in insulin-induced insulin receptor
 substrate-2 tyrosine phosphorylation.";
 J. Biol. Chem. 282:34356-34364(2007).
 [27]
 FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
 PubMed=18004385; DOI=10.1038/nature06268;
 Vaquero A., Scher M., Erdjument-Bromage H., Tempst P., Serrano L.,
 Reinberg D.;
 "SIRT1 regulates the histone methyl-transferase SUV39H1 during
 heterochromatin formation.";
 Nature 450:440-444(2007).
 [28]
 FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND INTERACTION WITH CLOCK;
 ARNTL AND PER2.
 PubMed=18662546; DOI=10.1016/j.cell.2008.06.050;
 Asher G., Gatfield D., Stratmann M., Reinke H., Dibner C., Kreppel F.,
 Mostoslavsky R., Alt F.W., Schibler U.;
 "SIRT1 regulates circadian clock gene expression through PER2
 deacetylation.";
 Cell 134:317-328(2008).
 [29]
 FUNCTION, INDUCTION, AND INTERACTION WITH CLOCK AND ARNTL.
 PubMed=18662547; DOI=10.1016/j.cell.2008.07.002;
 Nakahata Y., Kaluzova M., Grimaldi B., Sahar S., Hirayama J., Chen D.,
 Guarente L.P., Sassone-Corsi P.;
 "The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin
 remodeling and circadian control.";
 Cell 134:329-340(2008).
 [30]
 FUNCTION.
 PubMed=18477450; DOI=10.1016/j.devcel.2008.02.004;
 Fulco M., Cen Y., Zhao P., Hoffman E.P., McBurney M.W., Sauve A.A.,
 Sartorelli V.;
 "Glucose restriction inhibits skeletal myoblast differentiation by
 activating SIRT1 through AMPK-mediated regulation of Nampt.";
 Dev. Cell 14:661-673(2008).
 [31]
 DISRUPTION PHENOTYPE.
 PubMed=18687325; DOI=10.1016/j.yexcr.2008.07.011;
 Sequeira J., Boily G., Bazinet S., Saliba S., He X., Jardine K.,
 Kennedy C., Staines W., Rousseaux C., Mueller R., McBurney M.W.;
 "sirt1-null mice develop an autoimmune-like condition.";
 Exp. Cell Res. 314:3069-3074(2008).
 [32]
 FUNCTION IN DEACETYLATION OF STK11, AND FUNCTION IN POSSIBLE REGULATION OF
 STK11.
 PubMed=18687677; DOI=10.1074/jbc.m805711200;
 Lan F., Cacicedo J.M., Ruderman N., Ido Y.;
 "SIRT1 modulation of the acetylation status, cytosolic localization, and
 activity of LKB1. Possible role in AMP-activated protein kinase
 activation.";
 J. Biol. Chem. 283:27628-27635(2008).
 [33]
 DISRUPTION PHENOTYPE.
 PubMed=18270565; DOI=10.1371/journal.pone.0001571;
 Coussens M., Maresh J.G., Yanagimachi R., Maeda G., Allsopp R.;
 "Sirt1 deficiency attenuates spermatogenesis and germ cell function.";
 PLoS ONE 3:E1571-E1571(2008).
 [34]
 FUNCTION IN AUTOPHAGY.
 PubMed=18296641; DOI=10.1073/pnas.0712145105;
 Lee I.H., Cao L., Mostoslavsky R., Lombard D.B., Liu J., Bruns N.E.,
 Tsokos M., Alt F.W., Finkel T.;
 "A role for the NAD-dependent deacetylase Sirt1 in the regulation of
 autophagy.";
 Proc. Natl. Acad. Sci. U.S.A. 105:3374-3379(2008).
 [35]
 FUNCTION IN REGULATION OF PPARA, AND INTERACTION WITH PPARA.
 PubMed=19356714; DOI=10.1016/j.cmet.2009.02.006;
 Purushotham A., Schug T.T., Xu Q., Surapureddi S., Guo X., Li X.;
 "Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and
 results in hepatic steatosis and inflammation.";
 Cell Metab. 9:327-338(2009).
 [36]
 INTERACTION WITH NMNAT1.
 PubMed=19478080; DOI=10.1074/jbc.m109.016469;
 Zhang T., Berrocal J.G., Frizzell K.M., Gamble M.J., DuMond M.E.,
 Krishnakumar R., Yang T., Sauve A.A., Kraus W.L.;
 "Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene
 promoters.";
 J. Biol. Chem. 284:20408-20417(2009).
 [37]
 PHOSPHORYLATION AT SER-649, AND MUTAGENESIS OF SER-154; SER-649; SER-651
 AND SER-683.
 PubMed=19680552; DOI=10.1371/journal.pone.0006611;
 Kang H., Jung J.W., Kim M.K., Chung J.H.;
 "CK2 is the regulator of SIRT1 substrate-binding affinity, deacetylase
 activity and cellular response to DNA-damage.";
 PLoS ONE 4:E6611-E6611(2009).
 [38]
 FUNCTION, AND INTERACTION WITH ARNTL.
 PubMed=19299583; DOI=10.1126/science.1171641;
 Ramsey K.M., Yoshino J., Brace C.S., Abrassart D., Kobayashi Y.,
 Marcheva B., Hong H.K., Chong J.L., Buhr E.D., Lee C., Takahashi J.S.,
 Imai S., Bass J.;
 "Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis.";
 Science 324:651-654(2009).
 [39]
 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151 AND SER-154, AND
 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
 TISSUE=Kidney, Lung, Spleen, and Testis;
 PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
 Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
 Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
 "A tissue-specific atlas of mouse protein phosphorylation and expression.";
 Cell 143:1174-1189(2010).
 [40]
 FUNCTION, AND DISRUPTION PHENOTYPE.
 PubMed=20620997; DOI=10.1016/j.cmet.2010.05.010;
 Ramadori G., Fujikawa T., Fukuda M., Anderson J., Morgan D.A.,
 Mostoslavsky R., Stuart R.C., Perello M., Vianna C.R., Nillni E.A.,
 Rahmouni K., Coppari R.;
 "SIRT1 deacetylase in POMC neurons is required for homeostatic defenses
 against diet-induced obesity.";
 Cell Metab. 12:78-87(2010).
 [41]
 FUNCTION IN DEACETYLATION OF SREBF1, AND FUNCTION IN REGULATION OF SREBF1.
 PubMed=20817729; DOI=10.1074/jbc.m110.122978;
 Ponugoti B., Kim D.H., Xiao Z., Smith Z., Miao J., Zang M., Wu S.Y.,
 Chiang C.M., Veenstra T.D., Kemper J.K.;
 "SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic
 lipid metabolism.";
 J. Biol. Chem. 285:33959-33970(2010).
 [42]
 FUNCTION IN TELOMERE MAINTENANCE.
 PubMed=21187328; DOI=10.1083/jcb.201005160;
 Palacios J.A., Herranz D., De Bonis M.L., Velasco S., Serrano M.,
 Blasco M.A.;
 "SIRT1 contributes to telomere maintenance and augments global homologous
 recombination.";
 J. Cell Biol. 191:1299-1313(2010).
 [43]
 PHOSPHORYLATION AT THR-522, MUTAGENESIS OF THR-522, FUNCTION, AND CATALYTIC
 ACTIVITY.
 PubMed=20167603; DOI=10.1074/jbc.m110.102574;
 Guo X., Williams J.G., Schug T.T., Li X.;
 "DYRK1A and DYRK3 promote cell survival through phosphorylation and
 activation of SIRT1.";
 J. Biol. Chem. 285:13223-13232(2010).
 [44]
 S-NITROSYLATION AT CYS-387 AND CYS-390, AND MUTAGENESIS OF CYS-363;
 CYS-366; CYS-387 AND CYS-390.
 PubMed=20972425; DOI=10.1038/ncb2114;
 Kornberg M.D., Sen N., Hara M.R., Juluri K.R., Nguyen J.V., Snowman A.M.,
 Law L., Hester L.D., Snyder S.H.;
 "GAPDH mediates nitrosylation of nuclear proteins.";
 Nat. Cell Biol. 12:1094-1100(2010).
 [45]
 INTERACTION WITH FOXO1.
 PubMed=20668652; DOI=10.1371/journal.pone.0011786;
 Goitre L., Balzac F., Degani S., Degan P., Marchi S., Pinton P.,
 Retta S.F.;
 "KRIT1 regulates the homeostasis of intracellular reactive oxygen
 species.";
 PLoS ONE 5:E11786-E11786(2010).
 [46]
 ALTERNATIVE SPLICING (ISOFORM 2).
 PubMed=20975832; DOI=10.1371/journal.pone.0013502;
 Lynch C.J., Shah Z.H., Allison S.J., Ahmed S.U., Ford J., Warnock L.J.,
 Li H., Serrano M., Milner J.;
 "SIRT1 undergoes alternative splicing in a novel auto-regulatory loop with
 p53.";
 PLoS ONE 5:E13502-E13502(2010).
 [47]
 FUNCTION, AND INTERACTION WITH HNF1A.
 PubMed=21176092; DOI=10.1111/j.1474-9726.2010.00667.x;
 Grimm A.A., Brace C.S., Wang T., Stormo G.D., Imai S.;
 "A nutrient-sensitive interaction between Sirt1 and HNF-1alpha regulates
 Crp expression.";
 Aging Cell 10:305-317(2011).
 [48]
 FUNCTION IN DEACETYLATION OF XBP1, AND SUBCELLULAR LOCATION.
 PubMed=20955178; DOI=10.1042/bj20101293;
 Wang F.M., Chen Y.J., Ouyang H.J.;
 "Regulation of unfolded protein response modulator XBP1s by acetylation and
 deacetylation.";
 Biochem. J. 433:245-252(2011).
 [49]
 FUNCTION IN AUTOPHAGY, AND DISRUPTION PHENOTYPE.
 PubMed=21189328; DOI=10.1158/0008-5472.can-10-3172;
 Powell M.J., Casimiro M.C., Cordon-Cardo C., He X., Yeow W.S., Wang C.,
 McCue P.A., McBurney M.W., Pestell R.G.;
 "Disruption of a Sirt1-dependent autophagy checkpoint in the prostate
 results in prostatic intraepithelial neoplasia lesion formation.";
 Cancer Res. 71:964-975(2011).
 [50]
 FUNCTION IN PALMITATE-INDUCED APOPTOSIS, INDUCTION, AND DOWN-REGULATION BY
 PALMITATE.
 PubMed=21622680; DOI=10.1093/cvr/cvr145;
 Zhu H., Yang Y., Wang Y., Li J., Schiller P.W., Peng T.;
 "MicroRNA-195 promotes palmitate-induced apoptosis in cardiomyocytes by
 down-regulating Sirt1.";
 Cardiovasc. Res. 92:75-84(2011).
 [51]
 INTERACTION WITH FOXO1.
 PubMed=22510882; DOI=10.1038/emboj.2012.97;
 Nakae J., Cao Y., Hakuno F., Takemori H., Kawano Y., Sekioka R., Abe T.,
 Kiyonari H., Tanaka T., Sakai J., Takahashi S., Itoh H.;
 "Novel repressor regulates insulin sensitivity through interaction with
 Foxo1.";
 EMBO J. 31:2275-2295(2012).
 [52]
 FUNCTION IN NEUROGENESIS, AND INTERACTION WITH BCL6.
 PubMed=23160044; DOI=10.1038/nn.3264;
 Tiberi L., van den Ameele J., Dimidschstein J., Piccirilli J., Gall D.,
 Herpoel A., Bilheu A., Bonnefont J., Iacovino M., Kyba M., Bouschet T.,
 Vanderhaeghen P.;
 "BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression
 of selective Notch targets.";
 Nat. Neurosci. 15:1627-1635(2012).
 [53]
 FUNCTION.
 PubMed=26910618; DOI=10.1111/acel.12456;
 Bar Oz M., Kumar A., Elayyan J., Reich E., Binyamin M., Kandel L.,
 Liebergall M., Steinmeyer J., Lefebvre V., Dvir-Ginzberg M.;
 "Acetylation reduces SOX9 nuclear entry and ACAN gene transactivation in
 human chondrocytes.";
 Aging Cell 15:499-508(2016).
 [54]
 INTERACTION WITH SIRT7.
 PubMed=28842251; DOI=10.1016/j.bbrc.2017.08.081;
 Ianni A., Hoelper S., Krueger M., Braun T., Bober E.;
 "Sirt7 stabilizes rDNA heterochromatin through recruitment of DNMT1 and
 Sirt1.";
 Biochem. Biophys. Res. Commun. 492:434-440(2017).
 [55]
 FUNCTION, AND CATALYTIC ACTIVITY.
 PubMed=28883095; DOI=10.1242/jcs.206904;
 Lai Y., Li J., Li X., Zou C.;
 "Lipopolysaccharide modulates p300 and Sirt1 to promote PRMT1 stability via
 an SCFFbxl17-recognized acetyldegron.";
 J. Cell Sci. 130:3578-3587(2017).
 [56]
 FUNCTION, CATALYTIC ACTIVITY, ACETYLATION AT LYS-230; LYS-369; LYS-422;
 LYS-505 AND LYS-600, AND MUTAGENESIS OF LYS-230; LYS-369; LYS-505 AND
 LYS-600.
 PubMed=28923965; DOI=10.1073/pnas.1706945114;
 Fang J., Ianni A., Smolka C., Vakhrusheva O., Nolte H., Krueger M.,
 Wietelmann A., Simonet N.G., Adrian-Segarra J.M., Vaquero A., Braun T.,
 Bober E.;
 "Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic
 activation of Sirt1.";
 Proc. Natl. Acad. Sci. U.S.A. 114:E8352-E8361(2017).
 [57]
 FUNCTION IN DEACETYLATION OF PCK1.
 PubMed=30193097; DOI=10.1016/j.molcel.2018.07.031;
 Latorre-Muro P., Baeza J., Armstrong E.A., Hurtado-Guerrero R., Corzana F.,
 Wu L.E., Sinclair D.A., Lopez-Buesa P., Carrodeguas J.A., Denu J.M.;
 "Dynamic acetylation of phosphoenolpyruvate carboxykinase toggles enzyme
 activity between gluconeogenic and anaplerotic reactions.";
 Mol. Cell 71:718-732(2018).
 [58]
 FUNCTION, AND CATALYTIC ACTIVITY.
 PubMed=30026585; DOI=10.1038/s41467-018-05187-4;
 Fukuda M., Yoshizawa T., Karim M.F., Sobuz S.U., Korogi W., Kobayasi D.,
 Okanishi H., Tasaki M., Ono K., Sawa T., Sato Y., Chirifu M., Masuda T.,
 Nakamura T., Tanoue H., Nakashima K., Kobashigawa Y., Morioka H., Bober E.,
 Ohtsuki S., Yamagata Y., Ando Y., Oike Y., Araki N., Takeda S., Mizuta H.,
 Yamagata K.;
 "SIRT7 has a critical role in bone formation by regulating lysine acylation
 of SP7/Osterix.";
 Nat. Commun. 9:2833-2833(2018).
 -!- FUNCTION: NAD-dependent protein deacetylase that links transcriptional
     regulation directly to intracellular energetics and participates in the
     coordination of several separated cellular functions such as cell
     cycle, response to DNA damage, metabolism, apoptosis and autophagy
     (PubMed:11250901, PubMed:11672522, PubMed:12651913, PubMed:12887892,
     PubMed:12960381, PubMed:15175761, PubMed:15220471, PubMed:15632193,
     PubMed:15744310, PubMed:15788402, PubMed:16098828, PubMed:16366736,
     PubMed:16790548, PubMed:16892051, PubMed:17098745, PubMed:17347648,
     PubMed:17620057, PubMed:17901049, PubMed:17936707, PubMed:18004385,
     PubMed:18296641, PubMed:18371449, PubMed:18477450, PubMed:18662546,
     PubMed:18662547, PubMed:18687677, PubMed:19299583, PubMed:19356714,
     PubMed:20817729, PubMed:21176092, PubMed:21187328, PubMed:21189328,
     PubMed:21622680, PubMed:23160044, PubMed:20167603, PubMed:28883095).
     Can modulate chromatin function through deacetylation of histones and
     can promote alterations in the methylation of histones and DNA, leading
     to transcriptional repression (By similarity). Deacetylates a broad
     range of transcription factors and coregulators, thereby regulating
     target gene expression positively and negatively (By similarity).
     Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is
     altered by glucose deprivation and metabolic changes associated with
     caloric restriction (By similarity). Is essential in skeletal muscle
     cell differentiation and in response to low nutrients mediates the
     inhibitory effect on skeletal myoblast differentiation which also
     involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide
     phosphoribosyltransferase (NAMPT) (PubMed:12887892, PubMed:18477450).
     Component of the eNoSC (energy-dependent nucleolar silencing) complex,
     a complex that mediates silencing of rDNA in response to intracellular
     energy status and acts by recruiting histone-modifying enzymes (By
     similarity). The eNoSC complex is able to sense the energy status of
     cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio
     activates SIRT1, leading to histone H3 deacetylation followed by
     dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation
     of silent chromatin in the rDNA locus (PubMed:18004385). Deacetylates
     'Lys-266' of SUV39H1, leading to its activation (By similarity).
     Inhibits skeletal muscle differentiation by deacetylating PCAF and
     MYOD1 (PubMed:12887892). Deacetylates H2A and 'Lys-26' of H1-4 (By
     similarity). Deacetylates 'Lys-16' of histone H4 (in vitro) (By
     similarity). Involved in NR0B2/SHP corepression function through
     chromatin remodeling: Recruited to LRH1 target gene promoters by
     NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading
     to transcriptional repression (By similarity). Proposed to contribute
     to genomic integrity via positive regulation of telomere length;
     however, reports on localization to pericentromeric heterochromatin are
     conflicting (PubMed:21187328). Proposed to play a role in constitutive
     heterochromatin (CH) formation and/or maintenance through regulation of
     the available pool of nuclear SUV39H1 (By similarity). Upon
     oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting
     SUV39H1 polyubiquitination by MDM2 (By similarity). This increase in
     SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to
     accelerate renewal of the heterochromatin which correlates with greater
     genomic integrity during stress response (By similarity). Deacetylates
     'Lys-382' of p53/TP53 and impairs its ability to induce transcription-
     dependent proapoptotic program and modulate cell senescence
     (PubMed:11672522, PubMed:12960381). Deacetylates TAF1B and thereby
     represses rDNA transcription by the RNA polymerase I (PubMed:11250901).
     Deacetylates MYC, promotes the association of MYC with MAX and
     decreases MYC stability leading to compromised transformational
     capability (By similarity). Deacetylates FOXO3 in response to oxidative
     stress thereby increasing its ability to induce cell cycle arrest and
     resistance to oxidative stress but inhibiting FOXO3-mediated induction
     of apoptosis transcriptional activity; also leading to FOXO3
     ubiquitination and protesomal degradation (By similarity). Appears to
     have a similar effect on MLLT7/FOXO4 in regulation of transcriptional
     activity and apoptosis (By similarity). Deacetylates DNMT1; thereby
     impairs DNMT1 methyltransferase-independent transcription repressor
     activity, modulates DNMT1 cell cycle regulatory function and DNMT1-
     mediated gene silencing (By similarity). Deacetylates RELA/NF-kappa-B
     p65 thereby inhibiting its transactivating potential and augments
     apoptosis in response to TNF-alpha (By similarity). Deacetylates HIF1A,
     KAT5/TIP60, RB1 and HIC1 (PubMed:17620057). Deacetylates FOXO1, which
     increases its DNA binding ability and enhances its transcriptional
     activity leading to increased gluconeogenesis in liver
     (PubMed:15220471, PubMed:15788402). Inhibits E2F1 transcriptional
     activity and apoptotic function, possibly by deacetylation
     (PubMed:16892051). Involved in HES1- and HEY2-mediated transcriptional
     repression (By similarity). In cooperation with MYCN seems to be
     involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN
     stabilization by phosphorylation at 'Ser-62' (By similarity).
     Deacetylates MEF2D (By similarity). Required for antagonist-mediated
     transcription suppression of AR-dependent genes which may be linked to
     local deacetylation of histone H3 (By similarity). Represses HNF1A-
     mediated transcription (PubMed:21176092). Required for the repression
     of ESRRG by CREBZF (By similarity). Deacetylates NR1H3 and NR1H2 and
     deacetylation of NR1H3 at 'Lys-434' positively regulates transcription
     of NR1H3:RXR target genes, promotes NR1H3 proteosomal degradation and
     results in cholesterol efflux; a promoter clearing mechanism after
     reach round of transcription is proposed (PubMed:17936707). Involved in
     lipid metabolism (By similarity). Implicated in regulation of
     adipogenesis and fat mobilization in white adipocytes by repression of
     PPARG which probably involves association with NCOR1 and SMRT/NCOR2
     (PubMed:15175761). Deacetylates p300/EP300 and PRMT1 (PubMed:15632193,
     PubMed:28883095). Deacetylates ACSS2 leading to its activation, and
     HMGCS1 deacetylation (PubMed:16790548). Involved in liver and muscle
     metabolism (By similarity). Through deacetylation and activation of
     PPARGC1A is required to activate fatty acid oxidation in skeletal
     muscle under low-glucose conditions and is involved in glucose
     homeostasis (PubMed:15744310, PubMed:17347648). Involved in regulation
     of PPARA and fatty acid beta-oxidation in liver (PubMed:19356714).
     Involved in positive regulation of insulin secretion in pancreatic beta
     cells in response to glucose; the function seems to imply
     transcriptional repression of UCP2 (PubMed:16098828, PubMed:16366736,
     PubMed:17901049). Proposed to deacetylate IRS2 thereby facilitating its
     insulin-induced tyrosine phosphorylation (PubMed:17901049).
     Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability
     and transactivation in lipogenic gene expression (By similarity).
     Involved in DNA damage response by repressing genes which are involved
     in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and
     facilitating recruitment of additional factors to sites of damaged DNA,
     such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair
     and SIRT1-deacetylated XPA interacts with RPA2 (By similarity). Also
     involved in DNA repair of DNA double-strand breaks by homologous
     recombination and specifically single-strand annealing independently of
     XRCC6/Ku70 and NBN. Transcriptional suppression of XPC probably
     involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT)
     signaling (By similarity). Transcriptional suppression of TP73 probably
     involves E2F4 and PCAF (By similarity). Deacetylates WRN thereby
     regulating its helicase and exonuclease activities and regulates WRN
     nuclear translocation in response to DNA damage (By similarity).
     Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP
     endonuclease activity by promoting the association of APEX1 to XRCC1
     (By similarity). Increases p53/TP53-mediated transcription-independent
     apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and
     probably redirecting it to mitochondria (By similarity). Deacetylates
     XRCC6/Ku70 at 'Lys-537' and 'Lys-540' causing it to sequester BAX away
     from mitochondria thereby inhibiting stress-induced apoptosis (By
     similarity). Is involved in autophagy, presumably by deacetylating
     ATG5, ATG7 and MAP1LC3B/ATG8 (PubMed:18296641, PubMed:21189328).
     Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to
     PIP3 and promotes their activation (By similarity). Proposed to play
     role in regulation of STK11/LBK1-dependent AMPK signaling pathways
     implicated in cellular senescence which seems to involve the regulation
     of the acetylation status of STK11/LBK1 (PubMed:18687677). Can
     deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic
     localization and association with STRAD; however, the relevance of such
     activity in normal cells is unclear (By similarity). In endothelial
     cells is shown to inhibit STK11/LBK1 activity and to promote its
     degradation (By similarity). Deacetylates SMAD7 at 'Lys-64' and 'Lys-
     70' thereby promoting its degradation (PubMed:17098745). Deacetylates
     CIITA and augments its MHC class II transactivation and contributes to
     its stability (By similarity). Deacetylates MECOM/EVI1 (By similarity).
     Deacetylates PML at 'Lys-487' and this deacetylation promotes PML
     control of PER2 nuclear localization (By similarity). During the
     neurogenic transition, represses selective NOTCH1-target genes through
     histone deacetylation in a BCL6-dependent manner and leading to
     neuronal differentiation (By similarity). Regulates the circadian
     expression of several core clock genes, including ARNTL/BMAL1, RORC,
     PER2 and CRY1 and plays a critical role in maintaining a controlled
     rhythmicity in histone acetylation, thereby contributing to circadian
     chromatin remodeling (PubMed:18662546, PubMed:18662547,
     PubMed:19299583). Deacetylates ARNTL/BMAL1 and histones at the
     circadian gene promoters in order to facilitate repression by
     inhibitory components of the circadian oscillator (PubMed:18662546,
     PubMed:18662547, PubMed:19299583). Deacetylates PER2, facilitating its
     ubiquitination and degradation by the proteosome (PubMed:18662546).
     Protects cardiomyocytes against palmitate-induced apoptosis
     (PubMed:21622680). Deacetylates XBP1 isoform 2; deacetylation decreases
     protein stability of XBP1 isoform 2 and inhibits its transcriptional
     activity (By similarity). Deacetylates PCK1 and directs its activity
     toward phosphoenolpyruvate production promoting gluconeogenesis
     (PubMed:30193097). Involved in the CCAR2-mediated regulation of PCK1
     and NR1D1 (By similarity). Deacetylates CTNB1 at 'Lys-49' (By
     similarity). In POMC (pro-opiomelanocortin) neurons, required for
     leptin-induced activation of PI3K signaling (PubMed:20620997). In
     addition to protein deacetylase activity, also acts as protein-lysine
     deacylase: acts as a protein depropionylase by mediating
     depropionylation of Osterix (SP7) (PubMed:30026585). Deacetylates SOX9;
     promoting SOX9 nuclear localization and transactivation activity
     (PubMed:26910618). Involved in the regulation of centrosome
     duplication. Deacetylates CENATAC in G1 phase, allowing for SASS6
     accumulation on the centrosome and subsequent procentriole assembly (By
     similarity). {ECO:0000250|UniProtKB:Q96EB6,
     ECO:0000269|PubMed:11250901, ECO:0000269|PubMed:11672522,
     ECO:0000269|PubMed:12651913, ECO:0000269|PubMed:12887892,
     ECO:0000269|PubMed:12960381, ECO:0000269|PubMed:15175761,
     ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:15632193,
     ECO:0000269|PubMed:15744310, ECO:0000269|PubMed:15788402,
     ECO:0000269|PubMed:16098828, ECO:0000269|PubMed:16366736,
     ECO:0000269|PubMed:16790548, ECO:0000269|PubMed:16892051,
     ECO:0000269|PubMed:17098745, ECO:0000269|PubMed:17347648,
     ECO:0000269|PubMed:17620057, ECO:0000269|PubMed:17901049,
     ECO:0000269|PubMed:17936707, ECO:0000269|PubMed:18004385,
     ECO:0000269|PubMed:18296641, ECO:0000269|PubMed:18371449,
     ECO:0000269|PubMed:18477450, ECO:0000269|PubMed:18662546,
     ECO:0000269|PubMed:18662547, ECO:0000269|PubMed:18687677,
     ECO:0000269|PubMed:19299583, ECO:0000269|PubMed:19356714,
     ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:20620997,
     ECO:0000269|PubMed:20817729, ECO:0000269|PubMed:21176092,
     ECO:0000269|PubMed:21187328, ECO:0000269|PubMed:21189328,
     ECO:0000269|PubMed:21622680, ECO:0000269|PubMed:23160044,
     ECO:0000269|PubMed:26910618, ECO:0000269|PubMed:28883095,
     ECO:0000269|PubMed:30026585, ECO:0000269|PubMed:30193097}.
 -!- FUNCTION: [Isoform 2]: Deacetylates 'Lys-382' of p53/TP53, however with
     lower activity than isoform 1. In combination, the two isoforms exert
     an additive effect. Isoform 2 regulates p53/TP53 expression and
     cellular stress response and is in turn repressed by p53/TP53
     presenting a SIRT1 isoform-dependent auto-regulatory loop.
     {ECO:0000250|UniProtKB:Q96EB6}.
 -!- FUNCTION: [SirtT1 75 kDa fragment]: Catalytically inactive 75SirT1 may
     be involved in regulation of apoptosis. May be involved in protecting
     chondrocytes from apoptotic death by associating with cytochrome C and
     interfering with apoptosome assembly. {ECO:0000250|UniProtKB:Q96EB6}.
 -!- CATALYTIC ACTIVITY:
     Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-
       ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
       Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731,
       ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
       ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767;
       EC=2.3.1.286; Evidence={ECO:0000255|PROSITE-ProRule:PRU00236,
       ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:28883095,
       ECO:0000269|PubMed:28923965};
 -!- CATALYTIC ACTIVITY:
     Reaction=H2O + N(6)-propanoyl-L-lysyl-[protein] + NAD(+) = 3''-O-
       propanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
       Xref=Rhea:RHEA:23500, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13758,
       ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
       ChEBI:CHEBI:57540, ChEBI:CHEBI:138019, ChEBI:CHEBI:145015;
       Evidence={ECO:0000305|PubMed:30026585};
     PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23501;
       Evidence={ECO:0000305|PubMed:30026585};
 -!- COFACTOR:
     Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
       Evidence={ECO:0000250|UniProtKB:Q8IXJ6};
     Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q8IXJ6};
 -!- ACTIVITY REGULATION: Activated by resveratrol (3,5,4'-trihydroxy-trans-
     stilbene), butein (3,4,2',4'-tetrahydroxychalcone), piceatannol
     (3,5,3',4'-tetrahydroxy-trans-stilbene), Isoliquiritigenin (4,2',4'-
     trihydroxychalcone), fisetin (3,7,3',4'-tetrahydroxyflavone) and
     quercetin (3,5,7,3',4'-pentahydroxyflavone). MAPK8/JNK1 and
     RPS19BP1/AROS act as positive regulators of deacetylation activity (By
     similarity). Inhibited by nicotinamide. Negatively regulated by CCAR2
     (By similarity). {ECO:0000250|UniProtKB:Q96EB6}.
 -!- SUBUNIT: Interacts with XBP1 isoform 2 (By similarity). Found in a
     complex with PCAF and MYOD1 Component of the eNoSC complex, composed of
     SIRT1, SUV39H1 and RRP8. Interacts with HES1, HEY2 and PML. Interacts
     with RPS19BP1/AROS. Interacts with CCAR2 (via N-terminus); the
     interaction disrupts the interaction between SIRT1 and p53/TP53.
     Interacts with SETD7; the interaction induces the dissociation of SIRT1
     from p53/TP53 and increases p53/TP53 activity. Interacts with MYCN,
     NR1I2, CREBZF, TSC2, TLE1, FOS, JUN, NR0B2, PPARG, NCOR, IRS1, IRS2 and
     NMNAT1. Interacts with HNF1A; the interaction occurs under nutrient
     restriction. Interacts with SUZ12; the interaction mediates the
     association with the PRC4 histone methylation complex which is specific
     as an association with PCR2 and PCR3 complex variants is not found.
     Interacts with FOXO1; the interaction deacetylates FOXO1, enhances its
     DNA-binding ability and increases its transcriptional activity.
     Interacts with BCL6; leads to a epigenetic repression of specific
     target genes. Interacts with CLOCK, ARNTL/BMAL1 and PER2. Interacts
     with PPARA; the interaction seems to be modulated by NAD(+) levels.
     Interacts with NR1H3 and this interaction is inhibited in the presence
     of CCAR2. Interacts with CHEK2 and p53/TP53. Exhibits a preferential
     interaction with sumoylated CCAR2 over its unmodified form (By
     similarity). Interacts with PACS2 (By similarity). Interacts with SIRT7
     (PubMed:28842251, PubMed:28923965). {ECO:0000250|UniProtKB:Q96EB6,
     ECO:0000269|PubMed:11672522, ECO:0000269|PubMed:12887892,
     ECO:0000269|PubMed:15175761, ECO:0000269|PubMed:15220471,
     ECO:0000269|PubMed:16269335, ECO:0000269|PubMed:16892051,
     ECO:0000269|PubMed:17901049, ECO:0000269|PubMed:18662546,
     ECO:0000269|PubMed:18662547, ECO:0000269|PubMed:19299583,
     ECO:0000269|PubMed:19356714, ECO:0000269|PubMed:19478080,
     ECO:0000269|PubMed:20668652, ECO:0000269|PubMed:21176092,
     ECO:0000269|PubMed:22510882, ECO:0000269|PubMed:23160044,
     ECO:0000269|PubMed:28842251, ECO:0000269|PubMed:28923965}.
 -!- INTERACTION:
     Q923E4; O08785: Clock; NbExp=11; IntAct=EBI-1802585, EBI-79859;
     Q923E4; Q61214: Dyrk1a; NbExp=4; IntAct=EBI-1802585, EBI-80344;
     Q923E4; Q922Y0: Dyrk3; NbExp=7; IntAct=EBI-1802585, EBI-5242007;
     Q923E4; Q9R1Y5: Hic1; NbExp=2; IntAct=EBI-1802585, EBI-5236187;
     Q923E4; P22361: Hnf1a; NbExp=5; IntAct=EBI-1802585, EBI-5272860;
     Q923E4; P81122: Irs2; NbExp=2; IntAct=EBI-1802585, EBI-1369862;
     Q923E4; Q60974: Ncor1; NbExp=3; IntAct=EBI-1802585, EBI-349004;
     Q923E4; Q64221: Nhlh2; NbExp=2; IntAct=EBI-1802585, EBI-5378529;
     Q923E4; Q62227: Nr0b2; NbExp=2; IntAct=EBI-1802585, EBI-4310440;
     Q923E4; P37238: Pparg; NbExp=2; IntAct=EBI-1802585, EBI-5260705;
     Q923E4; O70343: Ppargc1a; NbExp=6; IntAct=EBI-1802585, EBI-1371053;
     Q923E4; O35253: Smad7; NbExp=6; IntAct=EBI-1802585, EBI-5274835;
     Q923E4; Q9WTN3: Srebf1; NbExp=2; IntAct=EBI-1802585, EBI-5273743;
     Q923E4; Q01094: E2F1; Xeno; NbExp=3; IntAct=EBI-1802585, EBI-448924;
     Q923E4; Q12778: FOXO1; Xeno; NbExp=2; IntAct=EBI-1802585, EBI-1108782;
     Q923E4; P06400: RB1; Xeno; NbExp=4; IntAct=EBI-1802585, EBI-491274;
     Q923E4; P28749: RBL1; Xeno; NbExp=2; IntAct=EBI-1802585, EBI-971402;
     Q923E4; Q08999: RBL2; Xeno; NbExp=2; IntAct=EBI-1802585, EBI-971439;
     Q923E4; P04637: TP53; Xeno; NbExp=4; IntAct=EBI-1802585, EBI-366083;
 -!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000250|UniProtKB:Q96EB6}.
     Cytoplasm {ECO:0000269|PubMed:17197703, ECO:0000269|PubMed:17901049}.
     Nucleus {ECO:0000269|PubMed:17197703, ECO:0000269|PubMed:17901049,
     ECO:0000269|PubMed:18004385, ECO:0000269|PubMed:18662546,
     ECO:0000269|PubMed:20955178}. Note=Colocalizes in the nucleus with XBP1
     isoform 2. Recruited to the nuclear bodies via its interaction with
     PML. Colocalized with APEX1 in the nucleus. May be found in nucleolus,
     nuclear euchromatin, heterochromatin and inner membrane (By
     similarity). Shuttles between nucleus and cytoplasm (PubMed:17197703).
     {ECO:0000250|UniProtKB:Q96EB6, ECO:0000269|PubMed:17197703}.
 -!- SUBCELLULAR LOCATION: [SirtT1 75 kDa fragment]: Cytoplasm
     {ECO:0000250|UniProtKB:Q96EB6}. Mitochondrion
     {ECO:0000250|UniProtKB:Q96EB6}.
 -!- ALTERNATIVE PRODUCTS:
     Event=Alternative splicing; Named isoforms=2;
     Name=1;
       IsoId=Q923E4-1; Sequence=Displayed;
     Name=2; Synonyms=delta-exon8;
       IsoId=Q923E4-2; Sequence=VSP_042190;
 -!- TISSUE SPECIFICITY: Widely expressed. Weakly expressed in liver and
     skeletal muscle. {ECO:0000269|PubMed:12482959}.
 -!- INDUCTION: By calorie restriction which induces endothelial nitric
     oxide synthase (eNOS) expression. Induced in liver by pyruvate during
     fasting. Expressed in a circadian manner in the liver with maximal and
     minimal levels reached at around Zeitgeber time (ZT) 16 and ZT4,
     respectively. Its deacetylase activity in the liver is also regulated
     in a circadian manner, with a peak at ZT15. Down-regulated by
     palmitate; palmitate down-regulation is mediated by the induction of
     miR-195 that directly targets SIRT1. {ECO:0000269|PubMed:15744310,
     ECO:0000269|PubMed:16224023, ECO:0000269|PubMed:18662546,
     ECO:0000269|PubMed:18662547, ECO:0000269|PubMed:21622680}.
 -!- PTM: Methylated on multiple lysine residues; methylation is enhanced
     after DNA damage and is dispensable for deacetylase activity toward
     p53/TP53. {ECO:0000250|UniProtKB:Q96EB6}.
 -!- PTM: Phosphorylated. Phosphorylated by STK4/MST1, resulting in
     inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by
     MAPK8/JNK1 at Ser-46 and Thr-522 leads to increased nuclear
     localization and enzymatic activity. Phosphorylation at Thr-522 by
     DYRK1A and DYRK3 activates deacetylase activity and promotes cell
     survival (PubMed:20167603). Phosphorylation by mammalian target of
     rapamycin complex 1 (mTORC1) at Ser-46 inhibits deacetylation activity.
     Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B
     p65/RELA deacetylation activity (By similarity).
     {ECO:0000250|UniProtKB:Q96EB6, ECO:0000269|PubMed:20167603}.
 -!- PTM: Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to
     yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1).
     {ECO:0000250|UniProtKB:Q96EB6}.
 -!- PTM: S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent
     protein deacetylase activity. {ECO:0000269|PubMed:20972425}.
 -!- PTM: Acetylated at various Lys residues (PubMed:28923965). Deacetylated
     via an autocatalytic mechanism (PubMed:28923965). Autodeacetylation at
     Lys-230 promotes its protein deacetylase activity (PubMed:28923965).
     {ECO:0000269|PubMed:28923965}.
 -!- DISRUPTION PHENOTYPE: High degree of embryonic and postnatal lethality.
     Decreased levels of histone H3 containing a trimethyl group at its
     lysine 9 position (H3K9me3) in regions of heterochromatin. Attenuates
     spermatogenesis but not oogenesis with reduced numbers of mature sperm
     and spermatogenic precursors. Mice develop an autoimmune-like condition
     with late onset diabetes insipidus. Prostatic intraepithelial neoplasia
     associated with reduced autophagy. Conditional knockout in POMC neurons
     leads to an increase of body weight compare to controls when animals
     are challenged with high-fat diet (PubMed:20620997).
     {ECO:0000269|PubMed:12482959, ECO:0000269|PubMed:18004385,
     ECO:0000269|PubMed:18270565, ECO:0000269|PubMed:18687325,
     ECO:0000269|PubMed:20620997, ECO:0000269|PubMed:21189328}.
 -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
     {ECO:0000305}.
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 ---------------------------------------------------------------------------
 EMBL; AF214646; AAF24983.1; -; mRNA.
 EMBL; BC006584; AAH06584.1; -; mRNA.
 CCDS; CCDS23898.1; -. [Q923E4-1]
 RefSeq; NP_062786.1; NM_019812.3. [Q923E4-1]
 SMR; Q923E4; -.
 BioGRID; 220297; 47.
 ComplexPortal; CPX-468; eNoSc complex.
 CORUM; Q923E4; -.
 DIP; DIP-47052N; -.
 IntAct; Q923E4; 48.
 STRING; 10090.ENSMUSP00000101082; -.
 iPTMnet; Q923E4; -.
 PhosphoSitePlus; Q923E4; -.
 EPD; Q923E4; -.
 jPOST; Q923E4; -.
 PaxDb; Q923E4; -.
 PeptideAtlas; Q923E4; -.
 PRIDE; Q923E4; -.
 Antibodypedia; 1637; 1096 antibodies.
 DNASU; 93759; -.
 Ensembl; ENSMUST00000020257; ENSMUSP00000020257; ENSMUSG00000020063. [Q923E4-1]
 Ensembl; ENSMUST00000120239; ENSMUSP00000112595; ENSMUSG00000020063. [Q923E4-1]
 Ensembl; ENSMUST00000177694; ENSMUSP00000137565; ENSMUSG00000020063. [Q923E4-2]
 GeneID; 93759; -.
 KEGG; mmu:93759; -.
 UCSC; uc007fke.2; mouse. [Q923E4-1]
 CTD; 23411; -.
 MGI; MGI:2135607; Sirt1.
 eggNOG; KOG2684; Eukaryota.
 GeneTree; ENSGT00940000159406; -.
 HOGENOM; CLU_016587_0_0_1; -.
 InParanoid; Q923E4; -.
 PhylomeDB; Q923E4; -.
 BRENDA; 3.5.1.98; 3474.
 Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response.
 Reactome; R-MMU-9617629; Regulation of FOXO transcriptional activity by acetylation.
 BioGRID-ORCS; 93759; 2 hits in 20 CRISPR screens.
 ChiTaRS; Sirt1; mouse.
 PRO; PR:Q923E4; -.
 Proteomes; UP000000589; Chromosome 10.
 RNAct; Q923E4; protein.
 Bgee; ENSMUSG00000020063; Expressed in cleaving embryo and 288 other tissues.
 Genevisible; Q923E4; MM.
 GO; GO:0030424; C:axon; ISO:MGI.
 GO; GO:0000785; C:chromatin; IDA:UniProtKB.
 GO; GO:0005677; C:chromatin silencing complex; ISO:MGI.
 GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
 GO; GO:0005829; C:cytosol; ISO:MGI.
 GO; GO:0035098; C:ESC/E(Z) complex; IEA:Ensembl.
 GO; GO:0030426; C:growth cone; ISO:MGI.
 GO; GO:0005739; C:mitochondrion; IDA:MGI.
 GO; GO:0000790; C:nuclear chromatin; ISO:MGI.
 GO; GO:0005635; C:nuclear envelope; ISO:MGI.
 GO; GO:0005719; C:nuclear euchromatin; ISS:UniProtKB.
 GO; GO:0005720; C:nuclear heterochromatin; IDA:UniProtKB.
 GO; GO:0005637; C:nuclear inner membrane; ISS:UniProtKB.
 GO; GO:0005730; C:nucleolus; IEA:Ensembl.
 GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
 GO; GO:0005634; C:nucleus; IDA:UniProtKB.
 GO; GO:0016605; C:PML body; ISO:MGI.
 GO; GO:0032991; C:protein-containing complex; IDA:MGI.
 GO; GO:0033553; C:rDNA heterochromatin; ISO:MGI.
 GO; GO:0043425; F:bHLH transcription factor binding; ISS:UniProtKB.
 GO; GO:0019213; F:deacetylase activity; IMP:UniProtKB.
 GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
 GO; GO:0042393; F:histone binding; ISO:MGI.
 GO; GO:0004407; F:histone deacetylase activity; ISO:MGI.
 GO; GO:0043398; F:HLH domain binding; ISO:MGI.
 GO; GO:0042802; F:identical protein binding; ISO:MGI.
 GO; GO:1990254; F:keratin filament binding; ISO:MGI.
 GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:MGI.
 GO; GO:0070403; F:NAD+ binding; IBA:GO_Central.
 GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:MGI.
 GO; GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); IDA:UniProtKB.
 GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IDA:UniProtKB.
 GO; GO:0035257; F:nuclear hormone receptor binding; ISO:MGI.
 GO; GO:0002039; F:p53 binding; IPI:BHF-UCL.
 GO; GO:1990841; F:promoter-specific chromatin binding; IDA:MGI.
 GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
 GO; GO:0033558; F:protein deacetylase activity; IDA:UniProtKB.
 GO; GO:0019904; F:protein domain specific binding; IPI:BHF-UCL.
 GO; GO:0043422; F:protein kinase B binding; ISO:MGI.
 GO; GO:0106231; F:protein-propionyllysine depropionylase activity; IMP:UniProtKB.
 GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
 GO; GO:0003713; F:transcription coactivator activity; IDA:BHF-UCL.
 GO; GO:0003714; F:transcription corepressor activity; IMP:BHF-UCL.
 GO; GO:0008134; F:transcription factor binding; ISO:MGI.
 GO; GO:0001525; P:angiogenesis; IMP:UniProtKB.
 GO; GO:0042595; P:behavioral response to starvation; IMP:MGI.
 GO; GO:0001678; P:cellular glucose homeostasis; IMP:UniProtKB.
 GO; GO:1904646; P:cellular response to amyloid-beta; ISO:MGI.
 GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:MGI.
 GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI.
 GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
 GO; GO:0071479; P:cellular response to ionizing radiation; IMP:UniProtKB.
 GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
 GO; GO:0009267; P:cellular response to starvation; IMP:BHF-UCL.
 GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
 GO; GO:0035356; P:cellular triglyceride homeostasis; IMP:UniProtKB.
 GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
 GO; GO:0006325; P:chromatin organization; ISO:MGI.
 GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
 GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
 GO; GO:0000731; P:DNA synthesis involved in DNA repair; IMP:UniProtKB.
 GO; GO:0097009; P:energy homeostasis; ISO:MGI.
 GO; GO:0055089; P:fatty acid homeostasis; IMP:UniProtKB.
 GO; GO:0031507; P:heterochromatin assembly; ISO:MGI.
 GO; GO:0070829; P:heterochromatin maintenance; ISO:MGI.
 GO; GO:0016575; P:histone deacetylation; IDA:UniProtKB.
 GO; GO:0070932; P:histone H3 deacetylation; ISO:MGI.
 GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB.
 GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:UniProtKB.
 GO; GO:0033210; P:leptin-mediated signaling pathway; IMP:UniProtKB.
 GO; GO:0010934; P:macrophage cytokine production; IMP:UniProtKB.
 GO; GO:0030225; P:macrophage differentiation; IMP:UniProtKB.
 GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
 GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; ISO:MGI.
 GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
 GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; ISS:UniProtKB.
 GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISO:MGI.
 GO; GO:0060548; P:negative regulation of cell death; ISO:MGI.
 GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
 GO; GO:2000655; P:negative regulation of cellular response to testosterone stimulus; ISO:MGI.
 GO; GO:2000773; P:negative regulation of cellular senescence; ISS:UniProtKB.
 GO; GO:0043392; P:negative regulation of DNA binding; ISO:MGI.
 GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; ISO:MGI.
 GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:ParkinsonsUK-UCL.
 GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:BHF-UCL.
 GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; ISO:MGI.
 GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
 GO; GO:0060125; P:negative regulation of growth hormone secretion; ISO:MGI.
 GO; GO:0051097; P:negative regulation of helicase activity; ISO:MGI.
 GO; GO:0071441; P:negative regulation of histone H3-K14 acetylation; ISO:MGI.
 GO; GO:1900113; P:negative regulation of histone H3-K9 trimethylation; IDA:BHF-UCL.
 GO; GO:2000619; P:negative regulation of histone H4-K16 acetylation; ISO:MGI.
 GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
 GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:BHF-UCL.
 GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
 GO; GO:1901215; P:negative regulation of neuron death; IGI:MGI.
 GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
 GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; ISO:MGI.
 GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; ISS:UniProtKB.
 GO; GO:0042326; P:negative regulation of phosphorylation; IMP:UniProtKB.
 GO; GO:0031393; P:negative regulation of prostaglandin biosynthetic process; IMP:UniProtKB.
 GO; GO:1901984; P:negative regulation of protein acetylation; ISO:MGI.
 GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:UniProtKB.
 GO; GO:1900181; P:negative regulation of protein localization to nucleus; ISO:MGI.
 GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; ISO:MGI.
 GO; GO:0032007; P:negative regulation of TOR signaling; IMP:UniProtKB.
 GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
 GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
 GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
 GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:MGI.
 GO; GO:0001542; P:ovulation from ovarian follicle; IMP:MGI.
 GO; GO:0018394; P:peptidyl-lysine acetylation; ISO:MGI.
 GO; GO:0034983; P:peptidyl-lysine deacetylation; ISO:MGI.
 GO; GO:0002821; P:positive regulation of adaptive immune response; ISS:UniProtKB.
 GO; GO:1904179; P:positive regulation of adipose tissue development; IMP:UniProtKB.
 GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
 GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
 GO; GO:0097755; P:positive regulation of blood vessel diameter; ISO:MGI.
 GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI.
 GO; GO:2000481; P:positive regulation of cAMP-dependent protein kinase activity; IDA:UniProtKB.
 GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; ISO:MGI.
 GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
 GO; GO:2000774; P:positive regulation of cellular senescence; ISS:UniProtKB.
 GO; GO:0010875; P:positive regulation of cholesterol efflux; IMP:UniProtKB.
 GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
 GO; GO:0045739; P:positive regulation of DNA repair; ISS:UniProtKB.
 GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:MGI.
 GO; GO:0045722; P:positive regulation of gluconeogenesis; ISO:MGI.
 GO; GO:0010460; P:positive regulation of heart rate; ISO:MGI.
 GO; GO:0051574; P:positive regulation of histone H3-K9 methylation; ISO:MGI.
 GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISS:UniProtKB.
 GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
 GO; GO:0016239; P:positive regulation of macroautophagy; IDA:UniProtKB.
 GO; GO:2000111; P:positive regulation of macrophage apoptotic process; IMP:UniProtKB.
 GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISO:MGI.
 GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
 GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:UniProtKB.
 GO; GO:0090312; P:positive regulation of protein deacetylation; ISO:MGI.
 GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
 GO; GO:0014858; P:positive regulation of skeletal muscle cell proliferation; ISO:MGI.
 GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; IMP:BHF-UCL.
 GO; GO:2000614; P:positive regulation of thyroid-stimulating hormone secretion; ISO:MGI.
 GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
 GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
 GO; GO:0006476; P:protein deacetylation; IDA:BHF-UCL.
 GO; GO:0106230; P:protein depropionylation; IDA:UniProtKB.
 GO; GO:0031648; P:protein destabilization; IDA:UniProtKB.
 GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
 GO; GO:0000720; P:pyrimidine dimer repair by nucleotide-excision repair; IMP:UniProtKB.
 GO; GO:0000183; P:rDNA heterochromatin assembly; ISO:MGI.
 GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
 GO; GO:0070857; P:regulation of bile acid biosynthetic process; IMP:UniProtKB.
 GO; GO:0090335; P:regulation of brown fat cell differentiation; IMP:UniProtKB.
 GO; GO:0042127; P:regulation of cell population proliferation; ISO:MGI.
 GO; GO:0010824; P:regulation of centrosome duplication; ISS:UniProtKB.
 GO; GO:0032071; P:regulation of endodeoxyribonuclease activity; ISS:UniProtKB.
 GO; GO:0010906; P:regulation of glucose metabolic process; IMP:UniProtKB.
 GO; GO:0010883; P:regulation of lipid storage; IMP:UniProtKB.
 GO; GO:0007346; P:regulation of mitotic cell cycle; ISS:UniProtKB.
 GO; GO:0035358; P:regulation of peroxisome proliferator activated receptor signaling pathway; IMP:BHF-UCL.
 GO; GO:0071900; P:regulation of protein serine/threonine kinase activity; ISO:MGI.
 GO; GO:0034391; P:regulation of smooth muscle cell apoptotic process; IDA:UniProtKB.
 GO; GO:0045471; P:response to ethanol; ISO:MGI.
 GO; GO:0042542; P:response to hydrogen peroxide; ISS:UniProtKB.
 GO; GO:0032868; P:response to insulin; IDA:UniProtKB.
 GO; GO:0044321; P:response to leptin; IMP:UniProtKB.
 GO; GO:0006979; P:response to oxidative stress; ISO:MGI.
 GO; GO:0000012; P:single strand break repair; ISS:UniProtKB.
 GO; GO:0007283; P:spermatogenesis; IMP:MGI.
 GO; GO:0090400; P:stress-induced premature senescence; ISO:MGI.
 GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:MGI.
 GO; GO:0006642; P:triglyceride mobilization; IMP:BHF-UCL.
 GO; GO:0070914; P:UV-damage excision repair; ISO:MGI.
 GO; GO:0050872; P:white fat cell differentiation; IMP:BHF-UCL.
 Gene3D; 3.30.1600.10; -; 1.
 InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
 InterPro; IPR003000; Sirtuin.
 InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
 InterPro; IPR026590; Ssirtuin_cat_dom.
 Pfam; PF02146; SIR2; 1.
 SUPFAM; SSF52467; SSF52467; 1.
 PROSITE; PS50305; SIRTUIN; 1.
 1: Evidence at protein level;
 Acetylation; Alternative splicing; Apoptosis; Biological rhythms;
 Cytoplasm; Developmental protein; Differentiation; Metal-binding;
 Mitochondrion; Myogenesis; NAD; Nucleus; Phosphoprotein;
 Reference proteome; S-nitrosylation; Transcription;
 Transcription regulation; Transferase; Zinc.
 INIT_MET        1
                 /note="Removed"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 CHAIN           2..737
                 /note="NAD-dependent protein deacetylase sirtuin-1"
                 /id="PRO_0000110257"
 CHAIN           2..525
                 /note="SirtT1 75 kDa fragment"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
                 /id="PRO_0000415290"
 DOMAIN          236..490
                 /note="Deacetylase sirtuin-type"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
 NP_BIND         253..272
                 /note="NAD"
                 /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
 NP_BIND         337..340
                 /note="NAD"
                 /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
 NP_BIND         432..434
                 /note="NAD"
                 /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
 NP_BIND         457..459
                 /note="NAD"
                 /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
 REGION          2..268
                 /note="Interaction with H1-4"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 REGION          2..131
                 /note="Interaction with CLOCK"
                 /evidence="ECO:0000269|PubMed:18662547"
 REGION          135..533
                 /note="Interaction with CCAR2"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 REGION          248..251
                 /note="Required for interaction with the sumoylated form of
                 CCAR2"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOTIF           32..39
                 /note="Nuclear localization signal"
 MOTIF           138..145
                 /note="Nuclear export signal"
 MOTIF           223..230
                 /note="Nuclear localization signal"
 MOTIF           425..431
                 /note="Nuclear export signal"
 COMPBIAS        2..131
                 /note="Ala-rich"
 COMPBIAS        155..158
                 /note="Poly-Asp"
 ACT_SITE        355
                 /note="Proton acceptor"
                 /evidence="ECO:0000269|PubMed:11672522,
                 ECO:0000269|PubMed:12887892, ECO:0000269|PubMed:15220471,
                 ECO:0000269|PubMed:16892051"
 METAL           363
                 /note="Zinc"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
 METAL           366
                 /note="Zinc"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
 METAL           387
                 /note="Zinc"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
 METAL           390
                 /note="Zinc"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
 BINDING         474
                 /note="NAD; via amide nitrogen"
                 /evidence="ECO:0000250"
 MOD_RES         2
                 /note="N-acetylalanine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         14
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         25
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         46
                 /note="Phosphoserine; by MAPK8"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         151
                 /note="Phosphoserine"
                 /evidence="ECO:0000244|PubMed:21183079"
 MOD_RES         154
                 /note="Phosphoserine"
                 /evidence="ECO:0000244|PubMed:21183079"
 MOD_RES         164
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         165
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         230
                 /note="N6-acetyllysine"
                 /evidence="ECO:0000269|PubMed:28923965"
 MOD_RES         369
                 /note="N6-acetyllysine"
                 /evidence="ECO:0000269|PubMed:28923965"
 MOD_RES         387
                 /note="S-nitrosocysteine"
                 /evidence="ECO:0000269|PubMed:20972425"
 MOD_RES         390
                 /note="S-nitrosocysteine"
                 /evidence="ECO:0000269|PubMed:20972425"
 MOD_RES         422
                 /note="N6-acetyllysine"
                 /evidence="ECO:0000305|PubMed:28923965"
 MOD_RES         505
                 /note="N6-acetyllysine"
                 /evidence="ECO:0000305|PubMed:28923965"
 MOD_RES         522
                 /note="Phosphothreonine; by DYRK1A, DYRK3 and MAPK8"
                 /evidence="ECO:0000269|PubMed:20167603"
 MOD_RES         527
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         536
                 /note="Phosphothreonine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         600
                 /note="N6-acetyllysine"
                 /evidence="ECO:0000305|PubMed:28923965"
 MOD_RES         649
                 /note="Phosphoserine; by CaMK2"
                 /evidence="ECO:0000269|PubMed:19680552"
 MOD_RES         651
                 /note="Phosphoserine; by CaMK2"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         737
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 VAR_SEQ         446..629
                 /note="Missing (in isoform 2)"
                 /evidence="ECO:0000305"
                 /id="VSP_042190"
 MUTAGEN         37..38
                 /note="RR->AA: Abolishes nuclear localization; when
                 associated with A-227; A-228; A-229 and A-230."
 MUTAGEN         138..145
                 /note="LLLTDGLL->AAATGAA: Abolishes nuclear export; when
                 associated with A-425; A-427; A-428; A-429; A-430 and A-
                 431."
                 /evidence="ECO:0000269|PubMed:17197703"
 MUTAGEN         154
                 /note="S->A: Abolishes in vitro phosphorylation by CaMK2;
                 when associated with A-649; A-651 and A-683."
                 /evidence="ECO:0000269|PubMed:19680552"
 MUTAGEN         227..230
                 /note="KKRK->AAAA: Abolishes nuclear localization; when
                 associated with A-37 and A-38."
                 /evidence="ECO:0000269|PubMed:17197703"
 MUTAGEN         230
                 /note="K->R: Decreased acetylation, leading to increased
                 protein deacetylase activity."
                 /evidence="ECO:0000269|PubMed:28923965"
 MUTAGEN         355
                 /note="H->Y: Loss of deacetylation activity. Loss of
                 inhibition of E2F1 and loss of coactivation of FOXO1-
                 mediated transcription."
                 /evidence="ECO:0000269|PubMed:11672522,
                 ECO:0000269|PubMed:12887892, ECO:0000269|PubMed:15220471,
                 ECO:0000269|PubMed:16892051"
 MUTAGEN         363
                 /note="C->S: Does not affect S-nitrosylation."
                 /evidence="ECO:0000269|PubMed:20972425"
 MUTAGEN         366
                 /note="C->S: Does not affect S-nitrosylation."
                 /evidence="ECO:0000269|PubMed:20972425"
 MUTAGEN         369
                 /note="K->R: Does not affect protein deacetylase activity."
                 /evidence="ECO:0000269|PubMed:28923965"
 MUTAGEN         387
                 /note="C->S: Impairs S-nitrosylation. Abolishes S-
                 nitrosylation; when associated with S-390."
                 /evidence="ECO:0000269|PubMed:20972425"
 MUTAGEN         390
                 /note="C->S: Impairs S-nitrosylation. Abolishes S-
                 nitrosylation; when associated with S-387."
                 /evidence="ECO:0000269|PubMed:20972425"
 MUTAGEN         425..431
                 /note="VDLLIVI->ADAAAAA: Abolishes nuclear export; when
                 associated with A-138; A-139; A-140; A-144 and A-145."
                 /evidence="ECO:0000269|PubMed:17197703"
 MUTAGEN         505
                 /note="K->R: Does not affect protein deacetylase activity."
                 /evidence="ECO:0000269|PubMed:28923965"
 MUTAGEN         522
                 /note="T->D: Increased deacetylase activity toward p53/TP53
                 and increases resistance to genotoxic stress (mimicks
                 residue phosphorylation)."
                 /evidence="ECO:0000269|PubMed:20167603"
 MUTAGEN         522
                 /note="T->V: Reduces phosphorylation. Impairs deacetylase
                 activity toward p53/TP53 and decreases resistance to
                 genotoxic stress. Does not change nuclear localization."
                 /evidence="ECO:0000269|PubMed:20167603"
 MUTAGEN         600
                 /note="K->R: Does not affect protein deacetylase activity."
                 /evidence="ECO:0000269|PubMed:28923965"
 MUTAGEN         649
                 /note="S->A: Abolishes in vitro phosphorylation by CaMK2;
                 when associated with A-154; A-651 and A-683."
                 /evidence="ECO:0000269|PubMed:19680552"
 MUTAGEN         651
                 /note="S->A: Abolishes in vitro phosphorylation by CaMK2;
                 when associated with A-154; A-649 and A-683."
                 /evidence="ECO:0000269|PubMed:19680552"
 MUTAGEN         683
                 /note="S->A: Abolishes in vitro phosphorylation by CaMK2;
                 when associated with A-154; A-649 and A-651."
                 /evidence="ECO:0000269|PubMed:19680552"
 SEQUENCE   737 AA;  80372 MW;  7F15625E29433119 CRC64;
 MADEVALALQ AAGSPSAAAA MEAASQPADE PLRKRPRRDG PGLGRSPGEP SAAVAPAAAG
 CEAASAAAPA ALWREAAGAA ASAEREAPAT AVAGDGDNGS GLRREPRAAD DFDDDEGEEE
 DEAAAAAAAA AIGYRDNLLL TDGLLTNGFH SCESDDDDRT SHASSSDWTP RPRIGPYTFV
 QQHLMIGTDP RTILKDLLPE TIPPPELDDM TLWQIVINIL SEPPKRKKRK DINTIEDAVK
 LLQECKKIIV LTGAGVSVSC GIPDFRSRDG IYARLAVDFP DLPDPQAMFD IEYFRKDPRP
 FFKFAKEIYP GQFQPSLCHK FIALSDKEGK LLRNYTQNID TLEQVAGIQR ILQCHGSFAT
 ASCLICKYKV DCEAVRGDIF NQVVPRCPRC PADEPLAIMK PEIVFFGENL PEQFHRAMKY
 DKDEVDLLIV IGSSLKVRPV ALIPSSIPHE VPQILINREP LPHLHFDVEL LGDCDVIINE
 LCHRLGGEYA KLCCNPVKLS EITEKPPRPQ KELVHLSELP PTPLHISEDS SSPERTVPQD
 SSVIATLVDQ ATNNNVNDLE VSESSCVEEK PQEVQTSRNV ENINVENPDF KAVGSSTADK
 NERTSVAETV RKCWPNRLAK EQISKRLEGN QYLFVPPNRY IFHGAEVYSD SEDDVLSSSS
 CGSNSDSGTC QSPSLEEPLE DESEIEEFYN GLEDDTERPE CAGGSGFGAD GGDQEVVNEA
 IATRQELTDV NYPSDKS

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