SIR1_MOUSE
ID SIR1_MOUSE Reviewed; 737 AA.
AC Q923E4; Q9QXG8;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 194.
DE RecName: Full=NAD-dependent protein deacetylase sirtuin-1;
DE EC=2.3.1.286 {ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:28883095};
DE AltName: Full=NAD-dependent protein deacylase sirtuin-1 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000305|PubMed:30026585};
DE AltName: Full=Regulatory protein SIR2 homolog 1;
DE AltName: Full=SIR2-like protein 1;
DE AltName: Full=SIR2alpha;
DE Short=Sir2;
DE Short=mSIR2a;
DE Contains:
DE RecName: Full=SirtT1 75 kDa fragment;
DE Short=75SirT1;
GN Name=Sirt1; Synonyms=Sir2l1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Swiss Webster / NIH;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 545-737.
RC TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION, INTERACTION WITH TP53, ACTIVITY REGULATION, ACTIVE SITE, AND
RP MUTAGENESIS OF HIS-355.
RX PubMed=11672522; DOI=10.1016/s0092-8674(01)00524-4;
RA Luo J., Nikolaev A.Y., Imai S., Chen D., Su F., Shiloh A., Guarente L.,
RA Gu W.;
RT "Negative control of p53 by Sir2alpha promotes cell survival under
RT stress.";
RL Cell 107:137-148(2001).
RN [4]
RP FUNCTION IN DEACETYLATION OF TAF1B.
RX PubMed=11250901; DOI=10.1093/emboj/20.6.1353;
RA Muth V., Nadaud S., Grummt I., Voit R.;
RT "Acetylation of TAF(I)68, a subunit of TIF-IB/SL1, activates RNA polymerase
RT I transcription.";
RL EMBO J. 20:1353-1362(2001).
RN [5]
RP FUNCTION.
RX PubMed=12651913;
RA McBurney M.W., Yang X., Jardine K., Bieman M., Th'ng J., Lemieux M.;
RT "The absence of SIR2alpha protein has no effect on global gene silencing in
RT mouse embryonic stem cells.";
RL Mol. Cancer Res. 1:402-409(2003).
RN [6]
RP TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=12482959; DOI=10.1128/mcb.23.1.38-54.2003;
RA McBurney M.W., Yang X., Jardine K., Hixon M., Boekelheide K., Webb J.R.,
RA Lansdorp P.M., Lemieux M.;
RT "The mammalian SIR2alpha protein has a role in embryogenesis and
RT gametogenesis.";
RL Mol. Cell. Biol. 23:38-54(2003).
RN [7]
RP FUNCTION, INTERACTION WITH MYOD1 AND PCAF, MUTAGENESIS OF HIS-355, AND
RP ACTIVE SITE.
RX PubMed=12887892; DOI=10.1016/s1097-2765(03)00226-0;
RA Fulco M., Schiltz R.L., Iezzi S., King M.T., Zhao P., Kashiwaya Y.,
RA Hoffman E., Veech R.L., Sartorelli V.;
RT "Sir2 regulates skeletal muscle differentiation as a potential sensor of
RT the redox state.";
RL Mol. Cell 12:51-62(2003).
RN [8]
RP FUNCTION.
RX PubMed=12960381; DOI=10.1073/pnas.1934713100;
RA Cheng H.-L., Mostoslavsky R., Saito S., Manis J.P., Gu Y., Patel P.,
RA Bronson R., Appella E., Alt F.W., Chua K.F.;
RT "Developmental defects and p53 hyperacetylation in Sir2 homolog (SIRT1)-
RT deficient mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:10794-10799(2003).
RN [9]
RP FUNCTION IN ADIPODIGENESIS, FUNCTION IN FAT MOBILIZATION, AND INTERACTION
RP WITH PPARG AND NCOR1.
RX PubMed=15175761; DOI=10.1038/nature02583;
RA Picard F., Kurtev M., Chung N., Topark-Ngarm A., Senawong T.,
RA Machado De Oliveira R., Leid M., McBurney M.W., Guarente L.;
RT "Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-
RT gamma.";
RL Nature 429:771-776(2004).
RN [10]
RP FUNCTION IN DEACETYLATION OF PPARGC1A, AND MUTAGENESIS OF GLY-261.
RX PubMed=15716268; DOI=10.1074/jbc.m501485200;
RA Nemoto S., Fergusson M.M., Finkel T.;
RT "SIRT1 functionally interacts with the metabolic regulator and
RT transcriptional coactivator PGC-1{alpha}.";
RL J. Biol. Chem. 280:16456-16460(2005).
RN [11]
RP FUNCTION IN DEACETYLATION OF ACSS2, AND FUNCTION IN REGULATION OF ACCS2.
RX PubMed=16790548; DOI=10.1073/pnas.0604392103;
RA Hallows W.C., Lee S., Denu J.M.;
RT "Sirtuins deacetylate and activate mammalian acetyl-CoA synthetases.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:10230-10235(2006).
RN [12]
RP FUNCTION IN DEACETYLATION OF NR1H3 AND NR1H2, AND FUNCTION IN REGULATION OF
RP NR1H3.
RX PubMed=17936707; DOI=10.1016/j.molcel.2007.07.032;
RA Li X., Zhang S., Blander G., Tse J.G., Krieger M., Guarente L.;
RT "SIRT1 deacetylates and positively regulates the nuclear receptor LXR.";
RL Mol. Cell 28:91-106(2007).
RN [13]
RP FUNCTION IN APOPTOSIS.
RX PubMed=18371449; DOI=10.1016/j.stem.2008.01.002;
RA Han M.K., Song E.K., Guo Y., Ou X., Mantel C., Broxmeyer H.E.;
RT "SIRT1 regulates apoptosis and Nanog expression in mouse embryonic stem
RT cells by controlling p53 subcellular localization.";
RL Cell Stem Cell 2:241-251(2008).
RN [14]
RP INTERACTION WITH FOXO1, FUNCTION IN DEACETYLATION OF FOXO1, MUTAGENESIS OF
RP HIS-355, AND ACTIVE SITE.
RX PubMed=15220471; DOI=10.1073/pnas.0400593101;
RA Daitoku H., Hatta M., Matsuzaki H., Aratani S., Ohshima T., Miyagishi M.,
RA Nakajima T., Fukamizu A.;
RT "Silent information regulator 2 potentiates Foxo1-mediated transcription
RT through its deacetylase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10042-10047(2004).
RN [15]
RP INTERACTION WITH HIC1.
RX PubMed=16269335; DOI=10.1016/j.cell.2005.08.011;
RA Chen W.Y., Wang D.H., Yen R.C., Luo J., Gu W., Baylin S.B.;
RT "Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent
RT DNA-damage responses.";
RL Cell 123:437-448(2005).
RN [16]
RP FUNCTION IN REGULATION OF INSULIN SECRETION.
RX PubMed=16098828; DOI=10.1016/j.cmet.2005.07.001;
RA Moynihan K.A., Grimm A.A., Plueger M.M., Bernal-Mizrachi E., Ford E.,
RA Cras-Meneur C., Permutt M.A., Imai S.;
RT "Increased dosage of mammalian Sir2 in pancreatic beta cells enhances
RT glucose-stimulated insulin secretion in mice.";
RL Cell Metab. 2:105-117(2005).
RN [17]
RP FUNCTION.
RX PubMed=15632193; DOI=10.1074/jbc.m408748200;
RA Bouras T., Fu M., Sauve A.A., Wang F., Quong A.A., Perkins N.D., Hay R.T.,
RA Gu W., Pestell R.G.;
RT "SIRT1 deacetylation and repression of p300 involves lysine residues
RT 1020/1024 within the cell cycle regulatory domain 1.";
RL J. Biol. Chem. 280:10264-10276(2005).
RN [18]
RP FUNCTION IN REGULATION OF FOXO1.
RX PubMed=15788402; DOI=10.1074/jbc.m412357200;
RA Frescas D., Valenti L., Accili D.;
RT "Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-
RT dependent deacetylation promotes expression of glucogenetic genes.";
RL J. Biol. Chem. 280:20589-20595(2005).
RN [19]
RP FUNCTION IN DEACETYLATION OF PPARGC1A, FUNCTION IN REGULATION OF GLUCOSE
RP HOMEOSTASIS, AND INDUCTION.
RX PubMed=15744310; DOI=10.1038/nature03354;
RA Rodgers J.T., Lerin C., Haas W., Gygi S.P., Spiegelman B.M., Puigserver P.;
RT "Nutrient control of glucose homeostasis through a complex of PGC-1alpha
RT and SIRT1.";
RL Nature 434:113-118(2005).
RN [20]
RP INDUCTION.
RX PubMed=16224023; DOI=10.1126/science.1117728;
RA Nisoli E., Tonello C., Cardile A., Cozzi V., Bracale R., Tedesco L.,
RA Falcone S., Valerio A., Cantoni O., Clementi E., Moncada S., Carruba M.O.;
RT "Calorie restriction promotes mitochondrial biogenesis by inducing the
RT expression of eNOS.";
RL Science 310:314-317(2005).
RN [21]
RP FUNCTION, INTERACTION WITH E2F1, MUTAGENESIS OF HIS-355, AND ACTIVE SITE.
RX PubMed=16892051; DOI=10.1038/ncb1468;
RA Wang C., Chen L., Hou X., Li Z., Kabra N., Ma Y., Nemoto S., Finkel T.,
RA Gu W., Cress W.D., Chen J.;
RT "Interactions between E2F1 and SirT1 regulate apoptotic response to DNA
RT damage.";
RL Nat. Cell Biol. 8:1025-1031(2006).
RN [22]
RP FUNCTION IN REGULATION OF INSULIN SECRETION.
RX PubMed=16366736; DOI=10.1371/journal.pbio.0040031;
RA Bordone L., Motta M.C., Picard F., Robinson A., Jhala U.S., Apfeld J.,
RA McDonagh T., Lemieux M., McBurney M., Szilvasi A., Easlon E.J., Lin S.J.,
RA Guarente L.;
RT "Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta
RT cells.";
RL PLoS Biol. 4:E31-E31(2006).
RN [23]
RP FUNCTION IN DEACETYLATION OF RB1.
RX PubMed=17620057; DOI=10.1042/bj20070151;
RA Wong S., Weber J.D.;
RT "Deacetylation of the retinoblastoma tumour suppressor protein by SIRT1.";
RL Biochem. J. 407:451-460(2007).
RN [24]
RP FUNCTION IN DEACETYLATION OF PPARGC1A, AND FUNCTION IN REGULATION OF MUSCLE
RP METABOLISM.
RX PubMed=17347648; DOI=10.1038/sj.emboj.7601633;
RA Gerhart-Hines Z., Rodgers J.T., Bare O., Lerin C., Kim S.H.,
RA Mostoslavsky R., Alt F.W., Wu Z., Puigserver P.;
RT "Metabolic control of muscle mitochondrial function and fatty acid
RT oxidation through SIRT1/PGC-1alpha.";
RL EMBO J. 26:1913-1923(2007).
RN [25]
RP FUNCTION IN DEACETYLATION OF SMAD7.
RX PubMed=17098745; DOI=10.1074/jbc.m605904200;
RA Kume S., Haneda M., Kanasaki K., Sugimoto T., Araki S., Isshiki K.,
RA Isono M., Uzu T., Guarente L., Kashiwagi A., Koya D.;
RT "SIRT1 inhibits transforming growth factor beta-induced apoptosis in
RT glomerular mesangial cells via Smad7 deacetylation.";
RL J. Biol. Chem. 282:151-158(2007).
RN [26]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF 38-ARG-ARG-39; 138-LEU--LEU-145;
RP 227-LYS--LYS-230 AND 425-VAL--ILE-431.
RX PubMed=17197703; DOI=10.1074/jbc.m609554200;
RA Tanno M., Sakamoto J., Miura T., Shimamoto K., Horio Y.;
RT "Nucleocytoplasmic shuttling of the NAD+-dependent histone deacetylase
RT SIRT1.";
RL J. Biol. Chem. 282:6823-6832(2007).
RN [27]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH IRS1 AND IRS2.
RX PubMed=17901049; DOI=10.1074/jbc.m706644200;
RA Zhang J.;
RT "The direct involvement of SirT1 in insulin-induced insulin receptor
RT substrate-2 tyrosine phosphorylation.";
RL J. Biol. Chem. 282:34356-34364(2007).
RN [28]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=18004385; DOI=10.1038/nature06268;
RA Vaquero A., Scher M., Erdjument-Bromage H., Tempst P., Serrano L.,
RA Reinberg D.;
RT "SIRT1 regulates the histone methyl-transferase SUV39H1 during
RT heterochromatin formation.";
RL Nature 450:440-444(2007).
RN [29]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND INTERACTION WITH CLOCK;
RP ARNTL AND PER2.
RX PubMed=18662546; DOI=10.1016/j.cell.2008.06.050;
RA Asher G., Gatfield D., Stratmann M., Reinke H., Dibner C., Kreppel F.,
RA Mostoslavsky R., Alt F.W., Schibler U.;
RT "SIRT1 regulates circadian clock gene expression through PER2
RT deacetylation.";
RL Cell 134:317-328(2008).
RN [30]
RP FUNCTION, INDUCTION, AND INTERACTION WITH CLOCK AND ARNTL.
RX PubMed=18662547; DOI=10.1016/j.cell.2008.07.002;
RA Nakahata Y., Kaluzova M., Grimaldi B., Sahar S., Hirayama J., Chen D.,
RA Guarente L.P., Sassone-Corsi P.;
RT "The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin
RT remodeling and circadian control.";
RL Cell 134:329-340(2008).
RN [31]
RP FUNCTION.
RX PubMed=18477450; DOI=10.1016/j.devcel.2008.02.004;
RA Fulco M., Cen Y., Zhao P., Hoffman E.P., McBurney M.W., Sauve A.A.,
RA Sartorelli V.;
RT "Glucose restriction inhibits skeletal myoblast differentiation by
RT activating SIRT1 through AMPK-mediated regulation of Nampt.";
RL Dev. Cell 14:661-673(2008).
RN [32]
RP DISRUPTION PHENOTYPE.
RX PubMed=18687325; DOI=10.1016/j.yexcr.2008.07.011;
RA Sequeira J., Boily G., Bazinet S., Saliba S., He X., Jardine K.,
RA Kennedy C., Staines W., Rousseaux C., Mueller R., McBurney M.W.;
RT "sirt1-null mice develop an autoimmune-like condition.";
RL Exp. Cell Res. 314:3069-3074(2008).
RN [33]
RP FUNCTION IN DEACETYLATION OF STK11, AND FUNCTION IN POSSIBLE REGULATION OF
RP STK11.
RX PubMed=18687677; DOI=10.1074/jbc.m805711200;
RA Lan F., Cacicedo J.M., Ruderman N., Ido Y.;
RT "SIRT1 modulation of the acetylation status, cytosolic localization, and
RT activity of LKB1. Possible role in AMP-activated protein kinase
RT activation.";
RL J. Biol. Chem. 283:27628-27635(2008).
RN [34]
RP DISRUPTION PHENOTYPE.
RX PubMed=18270565; DOI=10.1371/journal.pone.0001571;
RA Coussens M., Maresh J.G., Yanagimachi R., Maeda G., Allsopp R.;
RT "Sirt1 deficiency attenuates spermatogenesis and germ cell function.";
RL PLoS ONE 3:E1571-E1571(2008).
RN [35]
RP FUNCTION IN AUTOPHAGY.
RX PubMed=18296641; DOI=10.1073/pnas.0712145105;
RA Lee I.H., Cao L., Mostoslavsky R., Lombard D.B., Liu J., Bruns N.E.,
RA Tsokos M., Alt F.W., Finkel T.;
RT "A role for the NAD-dependent deacetylase Sirt1 in the regulation of
RT autophagy.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:3374-3379(2008).
RN [36]
RP FUNCTION IN REGULATION OF PPARA, AND INTERACTION WITH PPARA.
RX PubMed=19356714; DOI=10.1016/j.cmet.2009.02.006;
RA Purushotham A., Schug T.T., Xu Q., Surapureddi S., Guo X., Li X.;
RT "Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and
RT results in hepatic steatosis and inflammation.";
RL Cell Metab. 9:327-338(2009).
RN [37]
RP INTERACTION WITH NMNAT1.
RX PubMed=19478080; DOI=10.1074/jbc.m109.016469;
RA Zhang T., Berrocal J.G., Frizzell K.M., Gamble M.J., DuMond M.E.,
RA Krishnakumar R., Yang T., Sauve A.A., Kraus W.L.;
RT "Enzymes in the NAD+ salvage pathway regulate SIRT1 activity at target gene
RT promoters.";
RL J. Biol. Chem. 284:20408-20417(2009).
RN [38]
RP PHOSPHORYLATION AT SER-649, AND MUTAGENESIS OF SER-154; SER-649; SER-651
RP AND SER-683.
RX PubMed=19680552; DOI=10.1371/journal.pone.0006611;
RA Kang H., Jung J.W., Kim M.K., Chung J.H.;
RT "CK2 is the regulator of SIRT1 substrate-binding affinity, deacetylase
RT activity and cellular response to DNA-damage.";
RL PLoS ONE 4:E6611-E6611(2009).
RN [39]
RP FUNCTION, AND INTERACTION WITH ARNTL.
RX PubMed=19299583; DOI=10.1126/science.1171641;
RA Ramsey K.M., Yoshino J., Brace C.S., Abrassart D., Kobayashi Y.,
RA Marcheva B., Hong H.K., Chong J.L., Buhr E.D., Lee C., Takahashi J.S.,
RA Imai S., Bass J.;
RT "Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis.";
RL Science 324:651-654(2009).
RN [40]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-151 AND SER-154, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [41]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20620997; DOI=10.1016/j.cmet.2010.05.010;
RA Ramadori G., Fujikawa T., Fukuda M., Anderson J., Morgan D.A.,
RA Mostoslavsky R., Stuart R.C., Perello M., Vianna C.R., Nillni E.A.,
RA Rahmouni K., Coppari R.;
RT "SIRT1 deacetylase in POMC neurons is required for homeostatic defenses
RT against diet-induced obesity.";
RL Cell Metab. 12:78-87(2010).
RN [42]
RP FUNCTION IN DEACETYLATION OF SREBF1, AND FUNCTION IN REGULATION OF SREBF1.
RX PubMed=20817729; DOI=10.1074/jbc.m110.122978;
RA Ponugoti B., Kim D.H., Xiao Z., Smith Z., Miao J., Zang M., Wu S.Y.,
RA Chiang C.M., Veenstra T.D., Kemper J.K.;
RT "SIRT1 deacetylates and inhibits SREBP-1C activity in regulation of hepatic
RT lipid metabolism.";
RL J. Biol. Chem. 285:33959-33970(2010).
RN [43]
RP FUNCTION IN TELOMERE MAINTENANCE.
RX PubMed=21187328; DOI=10.1083/jcb.201005160;
RA Palacios J.A., Herranz D., De Bonis M.L., Velasco S., Serrano M.,
RA Blasco M.A.;
RT "SIRT1 contributes to telomere maintenance and augments global homologous
RT recombination.";
RL J. Cell Biol. 191:1299-1313(2010).
RN [44]
RP PHOSPHORYLATION AT THR-522, MUTAGENESIS OF THR-522, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=20167603; DOI=10.1074/jbc.m110.102574;
RA Guo X., Williams J.G., Schug T.T., Li X.;
RT "DYRK1A and DYRK3 promote cell survival through phosphorylation and
RT activation of SIRT1.";
RL J. Biol. Chem. 285:13223-13232(2010).
RN [45]
RP S-NITROSYLATION AT CYS-387 AND CYS-390, AND MUTAGENESIS OF CYS-363;
RP CYS-366; CYS-387 AND CYS-390.
RX PubMed=20972425; DOI=10.1038/ncb2114;
RA Kornberg M.D., Sen N., Hara M.R., Juluri K.R., Nguyen J.V., Snowman A.M.,
RA Law L., Hester L.D., Snyder S.H.;
RT "GAPDH mediates nitrosylation of nuclear proteins.";
RL Nat. Cell Biol. 12:1094-1100(2010).
RN [46]
RP INTERACTION WITH FOXO1.
RX PubMed=20668652; DOI=10.1371/journal.pone.0011786;
RA Goitre L., Balzac F., Degani S., Degan P., Marchi S., Pinton P.,
RA Retta S.F.;
RT "KRIT1 regulates the homeostasis of intracellular reactive oxygen
RT species.";
RL PLoS ONE 5:E11786-E11786(2010).
RN [47]
RP ALTERNATIVE SPLICING (ISOFORM 2).
RX PubMed=20975832; DOI=10.1371/journal.pone.0013502;
RA Lynch C.J., Shah Z.H., Allison S.J., Ahmed S.U., Ford J., Warnock L.J.,
RA Li H., Serrano M., Milner J.;
RT "SIRT1 undergoes alternative splicing in a novel auto-regulatory loop with
RT p53.";
RL PLoS ONE 5:E13502-E13502(2010).
RN [48]
RP FUNCTION, AND INTERACTION WITH HNF1A.
RX PubMed=21176092; DOI=10.1111/j.1474-9726.2010.00667.x;
RA Grimm A.A., Brace C.S., Wang T., Stormo G.D., Imai S.;
RT "A nutrient-sensitive interaction between Sirt1 and HNF-1alpha regulates
RT Crp expression.";
RL Aging Cell 10:305-317(2011).
RN [49]
RP FUNCTION IN DEACETYLATION OF XBP1, AND SUBCELLULAR LOCATION.
RX PubMed=20955178; DOI=10.1042/bj20101293;
RA Wang F.M., Chen Y.J., Ouyang H.J.;
RT "Regulation of unfolded protein response modulator XBP1s by acetylation and
RT deacetylation.";
RL Biochem. J. 433:245-252(2011).
RN [50]
RP FUNCTION IN AUTOPHAGY, AND DISRUPTION PHENOTYPE.
RX PubMed=21189328; DOI=10.1158/0008-5472.can-10-3172;
RA Powell M.J., Casimiro M.C., Cordon-Cardo C., He X., Yeow W.S., Wang C.,
RA McCue P.A., McBurney M.W., Pestell R.G.;
RT "Disruption of a Sirt1-dependent autophagy checkpoint in the prostate
RT results in prostatic intraepithelial neoplasia lesion formation.";
RL Cancer Res. 71:964-975(2011).
RN [51]
RP FUNCTION IN PALMITATE-INDUCED APOPTOSIS, INDUCTION, AND DOWN-REGULATION BY
RP PALMITATE.
RX PubMed=21622680; DOI=10.1093/cvr/cvr145;
RA Zhu H., Yang Y., Wang Y., Li J., Schiller P.W., Peng T.;
RT "MicroRNA-195 promotes palmitate-induced apoptosis in cardiomyocytes by
RT down-regulating Sirt1.";
RL Cardiovasc. Res. 92:75-84(2011).
RN [52]
RP INTERACTION WITH FOXO1.
RX PubMed=22510882; DOI=10.1038/emboj.2012.97;
RA Nakae J., Cao Y., Hakuno F., Takemori H., Kawano Y., Sekioka R., Abe T.,
RA Kiyonari H., Tanaka T., Sakai J., Takahashi S., Itoh H.;
RT "Novel repressor regulates insulin sensitivity through interaction with
RT Foxo1.";
RL EMBO J. 31:2275-2295(2012).
RN [53]
RP FUNCTION IN DEACETYLATION OF PPARGC1A.
RX PubMed=23142079; DOI=10.1016/j.molcel.2012.09.030;
RA Dominy J.E. Jr., Lee Y., Jedrychowski M.P., Chim H., Jurczak M.J.,
RA Camporez J.P., Ruan H.B., Feldman J., Pierce K., Mostoslavsky R.,
RA Denu J.M., Clish C.B., Yang X., Shulman G.I., Gygi S.P., Puigserver P.;
RT "The deacetylase Sirt6 activates the acetyltransferase GCN5 and suppresses
RT hepatic gluconeogenesis.";
RL Mol. Cell 48:900-913(2012).
RN [54]
RP FUNCTION IN NEUROGENESIS, AND INTERACTION WITH BCL6.
RX PubMed=23160044; DOI=10.1038/nn.3264;
RA Tiberi L., van den Ameele J., Dimidschstein J., Piccirilli J., Gall D.,
RA Herpoel A., Bilheu A., Bonnefont J., Iacovino M., Kyba M., Bouschet T.,
RA Vanderhaeghen P.;
RT "BCL6 controls neurogenesis through Sirt1-dependent epigenetic repression
RT of selective Notch targets.";
RL Nat. Neurosci. 15:1627-1635(2012).
RN [55]
RP FUNCTION.
RX PubMed=26910618; DOI=10.1111/acel.12456;
RA Bar Oz M., Kumar A., Elayyan J., Reich E., Binyamin M., Kandel L.,
RA Liebergall M., Steinmeyer J., Lefebvre V., Dvir-Ginzberg M.;
RT "Acetylation reduces SOX9 nuclear entry and ACAN gene transactivation in
RT human chondrocytes.";
RL Aging Cell 15:499-508(2016).
RN [56]
RP INTERACTION WITH SIRT7.
RX PubMed=28842251; DOI=10.1016/j.bbrc.2017.08.081;
RA Ianni A., Hoelper S., Krueger M., Braun T., Bober E.;
RT "Sirt7 stabilizes rDNA heterochromatin through recruitment of DNMT1 and
RT Sirt1.";
RL Biochem. Biophys. Res. Commun. 492:434-440(2017).
RN [57]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=28883095; DOI=10.1242/jcs.206904;
RA Lai Y., Li J., Li X., Zou C.;
RT "Lipopolysaccharide modulates p300 and Sirt1 to promote PRMT1 stability via
RT an SCFFbxl17-recognized acetyldegron.";
RL J. Cell Sci. 130:3578-3587(2017).
RN [58]
RP FUNCTION, CATALYTIC ACTIVITY, ACETYLATION AT LYS-230; LYS-369; LYS-422;
RP LYS-505 AND LYS-600, AND MUTAGENESIS OF LYS-230; LYS-369; LYS-505 AND
RP LYS-600.
RX PubMed=28923965; DOI=10.1073/pnas.1706945114;
RA Fang J., Ianni A., Smolka C., Vakhrusheva O., Nolte H., Krueger M.,
RA Wietelmann A., Simonet N.G., Adrian-Segarra J.M., Vaquero A., Braun T.,
RA Bober E.;
RT "Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic
RT activation of Sirt1.";
RL Proc. Natl. Acad. Sci. U.S.A. 114:E8352-E8361(2017).
RN [59]
RP FUNCTION IN DEACETYLATION OF PCK1.
RX PubMed=30193097; DOI=10.1016/j.molcel.2018.07.031;
RA Latorre-Muro P., Baeza J., Armstrong E.A., Hurtado-Guerrero R., Corzana F.,
RA Wu L.E., Sinclair D.A., Lopez-Buesa P., Carrodeguas J.A., Denu J.M.;
RT "Dynamic acetylation of phosphoenolpyruvate carboxykinase toggles enzyme
RT activity between gluconeogenic and anaplerotic reactions.";
RL Mol. Cell 71:718-732(2018).
RN [60]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30026585; DOI=10.1038/s41467-018-05187-4;
RA Fukuda M., Yoshizawa T., Karim M.F., Sobuz S.U., Korogi W., Kobayasi D.,
RA Okanishi H., Tasaki M., Ono K., Sawa T., Sato Y., Chirifu M., Masuda T.,
RA Nakamura T., Tanoue H., Nakashima K., Kobashigawa Y., Morioka H., Bober E.,
RA Ohtsuki S., Yamagata Y., Ando Y., Oike Y., Araki N., Takeda S., Mizuta H.,
RA Yamagata K.;
RT "SIRT7 has a critical role in bone formation by regulating lysine acylation
RT of SP7/Osterix.";
RL Nat. Commun. 9:2833-2833(2018).
CC -!- FUNCTION: NAD-dependent protein deacetylase that links transcriptional
CC regulation directly to intracellular energetics and participates in the
CC coordination of several separated cellular functions such as cell
CC cycle, response to DNA damage, metabolism, apoptosis and autophagy
CC (PubMed:11250901, PubMed:11672522, PubMed:12651913, PubMed:12887892,
CC PubMed:12960381, PubMed:15175761, PubMed:15220471, PubMed:15632193,
CC PubMed:15744310, PubMed:15788402, PubMed:16098828, PubMed:16366736,
CC PubMed:16790548, PubMed:16892051, PubMed:17098745, PubMed:17347648,
CC PubMed:17620057, PubMed:17901049, PubMed:17936707, PubMed:18004385,
CC PubMed:18296641, PubMed:18371449, PubMed:18477450, PubMed:18662546,
CC PubMed:18662547, PubMed:18687677, PubMed:19299583, PubMed:19356714,
CC PubMed:20817729, PubMed:21176092, PubMed:21187328, PubMed:21189328,
CC PubMed:21622680, PubMed:23160044, PubMed:20167603, PubMed:28883095).
CC Can modulate chromatin function through deacetylation of histones and
CC can promote alterations in the methylation of histones and DNA, leading
CC to transcriptional repression (By similarity). Deacetylates a broad
CC range of transcription factors and coregulators, thereby regulating
CC target gene expression positively and negatively (By similarity).
CC Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is
CC altered by glucose deprivation and metabolic changes associated with
CC caloric restriction (By similarity). Is essential in skeletal muscle
CC cell differentiation and in response to low nutrients mediates the
CC inhibitory effect on skeletal myoblast differentiation which also
CC involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide
CC phosphoribosyltransferase (NAMPT) (PubMed:12887892, PubMed:18477450).
CC Component of the eNoSC (energy-dependent nucleolar silencing) complex,
CC a complex that mediates silencing of rDNA in response to intracellular
CC energy status and acts by recruiting histone-modifying enzymes (By
CC similarity). The eNoSC complex is able to sense the energy status of
CC cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio
CC activates SIRT1, leading to histone H3 deacetylation followed by
CC dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation
CC of silent chromatin in the rDNA locus (PubMed:18004385). Deacetylates
CC 'Lys-266' of SUV39H1, leading to its activation (By similarity).
CC Inhibits skeletal muscle differentiation by deacetylating PCAF and
CC MYOD1 (PubMed:12887892). Deacetylates H2A and 'Lys-26' of H1-4 (By
CC similarity). Deacetylates 'Lys-16' of histone H4 (in vitro) (By
CC similarity). Involved in NR0B2/SHP corepression function through
CC chromatin remodeling: Recruited to LRH1 target gene promoters by
CC NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading
CC to transcriptional repression (By similarity). Proposed to contribute
CC to genomic integrity via positive regulation of telomere length;
CC however, reports on localization to pericentromeric heterochromatin are
CC conflicting (PubMed:21187328). Proposed to play a role in constitutive
CC heterochromatin (CH) formation and/or maintenance through regulation of
CC the available pool of nuclear SUV39H1 (By similarity). Upon
CC oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting
CC SUV39H1 polyubiquitination by MDM2 (By similarity). This increase in
CC SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to
CC accelerate renewal of the heterochromatin which correlates with greater
CC genomic integrity during stress response (By similarity). Deacetylates
CC 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-
CC dependent proapoptotic program and modulate cell senescence
CC (PubMed:11672522, PubMed:12960381). Deacetylates TAF1B and thereby
CC represses rDNA transcription by the RNA polymerase I (PubMed:11250901).
CC Deacetylates MYC, promotes the association of MYC with MAX and
CC decreases MYC stability leading to compromised transformational
CC capability (By similarity). Deacetylates FOXO3 in response to oxidative
CC stress thereby increasing its ability to induce cell cycle arrest and
CC resistance to oxidative stress but inhibiting FOXO3-mediated induction
CC of apoptosis transcriptional activity; also leading to FOXO3
CC ubiquitination and protesomal degradation (By similarity). Appears to
CC have a similar effect on MLLT7/FOXO4 in regulation of transcriptional
CC activity and apoptosis (By similarity). Deacetylates DNMT1; thereby
CC impairs DNMT1 methyltransferase-independent transcription repressor
CC activity, modulates DNMT1 cell cycle regulatory function and DNMT1-
CC mediated gene silencing (By similarity). Deacetylates RELA/NF-kappa-B
CC p65 thereby inhibiting its transactivating potential and augments
CC apoptosis in response to TNF-alpha (By similarity). Deacetylates HIF1A,
CC KAT5/TIP60, RB1 and HIC1 (PubMed:17620057). Deacetylates FOXO1, which
CC increases its DNA binding ability and enhances its transcriptional
CC activity leading to increased gluconeogenesis in liver
CC (PubMed:15220471, PubMed:15788402). Inhibits E2F1 transcriptional
CC activity and apoptotic function, possibly by deacetylation
CC (PubMed:16892051). Involved in HES1- and HEY2-mediated transcriptional
CC repression (By similarity). In cooperation with MYCN seems to be
CC involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN
CC stabilization by phosphorylation at 'Ser-62' (By similarity).
CC Deacetylates MEF2D (By similarity). Required for antagonist-mediated
CC transcription suppression of AR-dependent genes which may be linked to
CC local deacetylation of histone H3 (By similarity). Represses HNF1A-
CC mediated transcription (PubMed:21176092). Required for the repression
CC of ESRRG by CREBZF (By similarity). Deacetylates NR1H3 and NR1H2 and
CC deacetylation of NR1H3 at 'Lys-434' positively regulates transcription
CC of NR1H3:RXR target genes, promotes NR1H3 proteosomal degradation and
CC results in cholesterol efflux; a promoter clearing mechanism after
CC reach round of transcription is proposed (PubMed:17936707). Involved in
CC lipid metabolism: deacetylates LPIN1, thereby inhibiting diacylglycerol
CC synthesis (By similarity). Implicated in regulation of adipogenesis and
CC fat mobilization in white adipocytes by repression of PPARG which
CC probably involves association with NCOR1 and SMRT/NCOR2
CC (PubMed:15175761). Deacetylates p300/EP300 and PRMT1 (PubMed:15632193,
CC PubMed:28883095). Deacetylates ACSS2 leading to its activation, and
CC HMGCS1 deacetylation (PubMed:16790548). Involved in liver and muscle
CC metabolism (By similarity). Through deacetylation and activation of
CC PPARGC1A is required to activate fatty acid oxidation in skeletal
CC muscle under low-glucose conditions and is involved in glucose
CC homeostasis (PubMed:15716268, PubMed:15744310, PubMed:17347648,
CC PubMed:23142079). Involved in regulation of PPARA and fatty acid beta-
CC oxidation in liver (PubMed:19356714). Involved in positive regulation
CC of insulin secretion in pancreatic beta cells in response to glucose;
CC the function seems to imply transcriptional repression of UCP2
CC (PubMed:16098828, PubMed:16366736, PubMed:17901049). Proposed to
CC deacetylate IRS2 thereby facilitating its insulin-induced tyrosine
CC phosphorylation (PubMed:17901049). Deacetylates SREBF1 isoform SREBP-1C
CC thereby decreasing its stability and transactivation in lipogenic gene
CC expression (By similarity). Involved in DNA damage response by
CC repressing genes which are involved in DNA repair, such as XPC and
CC TP73, deacetylating XRCC6/Ku70, and facilitating recruitment of
CC additional factors to sites of damaged DNA, such as SIRT1-deacetylated
CC NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA
CC interacts with RPA2 (By similarity). Also involved in DNA repair of DNA
CC double-strand breaks by homologous recombination and specifically
CC single-strand annealing independently of XRCC6/Ku70 and NBN (By
CC similarity). Promotes DNA double-strand breaks by mediating
CC deacetylation of SIRT6 (By similarity). Transcriptional suppression of
CC XPC probably involves an E2F4:RBL2 suppressor complex and protein
CC kinase B (AKT) signaling (By similarity). Transcriptional suppression
CC of TP73 probably involves E2F4 and PCAF (By similarity). Deacetylates
CC WRN thereby regulating its helicase and exonuclease activities and
CC regulates WRN nuclear translocation in response to DNA damage (By
CC similarity). Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates
CC cellular AP endonuclease activity by promoting the association of APEX1
CC to XRCC1 (By similarity). Catalyzes deacetylation of ERCC4/XPF, thereby
CC impairing interaction with ERCC1 and nucleotide excision repair (NER)
CC (By similarity). Increases p53/TP53-mediated transcription-independent
CC apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and
CC probably redirecting it to mitochondria (By similarity). Deacetylates
CC XRCC6/Ku70 at 'Lys-537' and 'Lys-540' causing it to sequester BAX away
CC from mitochondria thereby inhibiting stress-induced apoptosis (By
CC similarity). Is involved in autophagy, presumably by deacetylating
CC ATG5, ATG7 and MAP1LC3B/ATG8 (PubMed:18296641, PubMed:21189328).
CC Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to
CC PIP3 and promotes their activation (By similarity). Proposed to play
CC role in regulation of STK11/LBK1-dependent AMPK signaling pathways
CC implicated in cellular senescence which seems to involve the regulation
CC of the acetylation status of STK11/LBK1 (PubMed:18687677). Can
CC deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic
CC localization and association with STRAD; however, the relevance of such
CC activity in normal cells is unclear (By similarity). In endothelial
CC cells is shown to inhibit STK11/LBK1 activity and to promote its
CC degradation (By similarity). Deacetylates SMAD7 at 'Lys-64' and 'Lys-
CC 70' thereby promoting its degradation (PubMed:17098745). Deacetylates
CC CIITA and augments its MHC class II transactivation and contributes to
CC its stability (By similarity). Deacetylates MECOM/EVI1 (By similarity).
CC Deacetylates PML at 'Lys-487' and this deacetylation promotes PML
CC control of PER2 nuclear localization (By similarity). During the
CC neurogenic transition, represses selective NOTCH1-target genes through
CC histone deacetylation in a BCL6-dependent manner and leading to
CC neuronal differentiation (By similarity). Regulates the circadian
CC expression of several core clock genes, including ARNTL/BMAL1, RORC,
CC PER2 and CRY1 and plays a critical role in maintaining a controlled
CC rhythmicity in histone acetylation, thereby contributing to circadian
CC chromatin remodeling (PubMed:18662546, PubMed:18662547,
CC PubMed:19299583). Deacetylates ARNTL/BMAL1 and histones at the
CC circadian gene promoters in order to facilitate repression by
CC inhibitory components of the circadian oscillator (PubMed:18662546,
CC PubMed:18662547, PubMed:19299583). Deacetylates PER2, facilitating its
CC ubiquitination and degradation by the proteosome (PubMed:18662546).
CC Protects cardiomyocytes against palmitate-induced apoptosis
CC (PubMed:21622680). Deacetylates XBP1 isoform 2; deacetylation decreases
CC protein stability of XBP1 isoform 2 and inhibits its transcriptional
CC activity (By similarity). Deacetylates PCK1 and directs its activity
CC toward phosphoenolpyruvate production promoting gluconeogenesis
CC (PubMed:30193097). Involved in the CCAR2-mediated regulation of PCK1
CC and NR1D1 (By similarity). Deacetylates CTNB1 at 'Lys-49' (By
CC similarity). In POMC (pro-opiomelanocortin) neurons, required for
CC leptin-induced activation of PI3K signaling (PubMed:20620997). In
CC addition to protein deacetylase activity, also acts as protein-lysine
CC deacylase by mediating protein depropionylation and decrotonylation
CC (PubMed:30026585). Mediates depropionylation of Osterix (SP7)
CC (PubMed:30026585). Catalyzes decrotonylation of histones; it however
CC does not represent a major histone decrotonylase (By similarity).
CC Deacetylates SOX9; promoting SOX9 nuclear localization and
CC transactivation activity (PubMed:26910618). Involved in the regulation
CC of centrosome duplication. Deacetylates CENATAC in G1 phase, allowing
CC for SASS6 accumulation on the centrosome and subsequent procentriole
CC assembly (By similarity). Deacetylates NDC80/HEC1 (By similarity).
CC {ECO:0000250|UniProtKB:Q96EB6, ECO:0000269|PubMed:11250901,
CC ECO:0000269|PubMed:11672522, ECO:0000269|PubMed:12651913,
CC ECO:0000269|PubMed:12887892, ECO:0000269|PubMed:12960381,
CC ECO:0000269|PubMed:15175761, ECO:0000269|PubMed:15220471,
CC ECO:0000269|PubMed:15632193, ECO:0000269|PubMed:15716268,
CC ECO:0000269|PubMed:15744310, ECO:0000269|PubMed:15788402,
CC ECO:0000269|PubMed:16098828, ECO:0000269|PubMed:16366736,
CC ECO:0000269|PubMed:16790548, ECO:0000269|PubMed:16892051,
CC ECO:0000269|PubMed:17098745, ECO:0000269|PubMed:17347648,
CC ECO:0000269|PubMed:17620057, ECO:0000269|PubMed:17901049,
CC ECO:0000269|PubMed:17936707, ECO:0000269|PubMed:18004385,
CC ECO:0000269|PubMed:18296641, ECO:0000269|PubMed:18371449,
CC ECO:0000269|PubMed:18477450, ECO:0000269|PubMed:18662546,
CC ECO:0000269|PubMed:18662547, ECO:0000269|PubMed:18687677,
CC ECO:0000269|PubMed:19299583, ECO:0000269|PubMed:19356714,
CC ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:20620997,
CC ECO:0000269|PubMed:20817729, ECO:0000269|PubMed:21176092,
CC ECO:0000269|PubMed:21187328, ECO:0000269|PubMed:21189328,
CC ECO:0000269|PubMed:21622680, ECO:0000269|PubMed:23142079,
CC ECO:0000269|PubMed:23160044, ECO:0000269|PubMed:26910618,
CC ECO:0000269|PubMed:28883095, ECO:0000269|PubMed:30026585,
CC ECO:0000269|PubMed:30193097}.
CC -!- FUNCTION: [Isoform 2]: Deacetylates 'Lys-382' of p53/TP53, however with
CC lower activity than isoform 1. In combination, the two isoforms exert
CC an additive effect. Isoform 2 regulates p53/TP53 expression and
CC cellular stress response and is in turn repressed by p53/TP53
CC presenting a SIRT1 isoform-dependent auto-regulatory loop.
CC {ECO:0000250|UniProtKB:Q96EB6}.
CC -!- FUNCTION: [SirtT1 75 kDa fragment]: Catalytically inactive 75SirT1 may
CC be involved in regulation of apoptosis. May be involved in protecting
CC chondrocytes from apoptotic death by associating with cytochrome C and
CC interfering with apoptosome assembly. {ECO:0000250|UniProtKB:Q96EB6}.
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 ECO:0000269|PubMed:20167603, ECO:0000269|PubMed:28883095,
CC ECO:0000269|PubMed:28923965};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-propanoyl-L-lysyl-[protein] + NAD(+) = 3''-O-
CC propanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:23500, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13758,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:138019, ChEBI:CHEBI:145015;
CC Evidence={ECO:0000305|PubMed:30026585};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23501;
CC Evidence={ECO:0000305|PubMed:30026585};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N(6)-(2E)-butenoyl-L-lysyl-[protein] + NAD(+) = 2''-O-
CC (2E)-but-2-enoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
CC Xref=Rhea:RHEA:69332, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13707,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:137954, ChEBI:CHEBI:183235;
CC Evidence={ECO:0000250|UniProtKB:Q96EB6};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69333;
CC Evidence={ECO:0000250|UniProtKB:Q96EB6};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q8IXJ6};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q8IXJ6};
CC -!- ACTIVITY REGULATION: Activated by resveratrol (3,5,4'-trihydroxy-trans-
CC stilbene), butein (3,4,2',4'-tetrahydroxychalcone), piceatannol
CC (3,5,3',4'-tetrahydroxy-trans-stilbene), Isoliquiritigenin (4,2',4'-
CC trihydroxychalcone), fisetin (3,7,3',4'-tetrahydroxyflavone) and
CC quercetin (3,5,7,3',4'-pentahydroxyflavone). MAPK8/JNK1 and
CC RPS19BP1/AROS act as positive regulators of deacetylation activity (By
CC similarity). Inhibited by nicotinamide. Negatively regulated by CCAR2
CC (By similarity). {ECO:0000250|UniProtKB:Q96EB6}.
CC -!- SUBUNIT: Interacts with XBP1 isoform 2 (By similarity). Found in a
CC complex with PCAF and MYOD1 Component of the eNoSC complex, composed of
CC SIRT1, SUV39H1 and RRP8. Interacts with HES1, HEY2 and PML. Interacts
CC with RPS19BP1/AROS. Interacts with CCAR2 (via N-terminus); the
CC interaction disrupts the interaction between SIRT1 and p53/TP53.
CC Interacts with SETD7; the interaction induces the dissociation of SIRT1
CC from p53/TP53 and increases p53/TP53 activity. Interacts with MYCN,
CC NR1I2, CREBZF, TSC2, TLE1, FOS, JUN, NR0B2, PPARG, NCOR, IRS1, IRS2 and
CC NMNAT1. Interacts with HNF1A; the interaction occurs under nutrient
CC restriction. Interacts with SUZ12; the interaction mediates the
CC association with the PRC4 histone methylation complex which is specific
CC as an association with PCR2 and PCR3 complex variants is not found.
CC Interacts with FOXO1; the interaction deacetylates FOXO1, enhances its
CC DNA-binding ability and increases its transcriptional activity.
CC Interacts with BCL6; leads to a epigenetic repression of specific
CC target genes. Interacts with CLOCK, ARNTL/BMAL1 and PER2. Interacts
CC with PPARA; the interaction seems to be modulated by NAD(+) levels.
CC Interacts with NR1H3 and this interaction is inhibited in the presence
CC of CCAR2. Interacts with CHEK2 and p53/TP53. Exhibits a preferential
CC interaction with sumoylated CCAR2 over its unmodified form (By
CC similarity). Interacts with PACS2 (By similarity). Interacts with SIRT7
CC (PubMed:28842251, PubMed:28923965). Interacts with PUS7 (By
CC similarity). {ECO:0000250|UniProtKB:Q96EB6,
CC ECO:0000269|PubMed:11672522, ECO:0000269|PubMed:12887892,
CC ECO:0000269|PubMed:15175761, ECO:0000269|PubMed:15220471,
CC ECO:0000269|PubMed:16269335, ECO:0000269|PubMed:16892051,
CC ECO:0000269|PubMed:17901049, ECO:0000269|PubMed:18662546,
CC ECO:0000269|PubMed:18662547, ECO:0000269|PubMed:19299583,
CC ECO:0000269|PubMed:19356714, ECO:0000269|PubMed:19478080,
CC ECO:0000269|PubMed:20668652, ECO:0000269|PubMed:21176092,
CC ECO:0000269|PubMed:22510882, ECO:0000269|PubMed:23160044,
CC ECO:0000269|PubMed:28842251, ECO:0000269|PubMed:28923965}.
CC -!- INTERACTION:
CC Q923E4; O08785: Clock; NbExp=11; IntAct=EBI-1802585, EBI-79859;
CC Q923E4; Q61214: Dyrk1a; NbExp=4; IntAct=EBI-1802585, EBI-80344;
CC Q923E4; Q922Y0: Dyrk3; NbExp=7; IntAct=EBI-1802585, EBI-5242007;
CC Q923E4; Q9R1Y5: Hic1; NbExp=2; IntAct=EBI-1802585, EBI-5236187;
CC Q923E4; P22361: Hnf1a; NbExp=5; IntAct=EBI-1802585, EBI-5272860;
CC Q923E4; P81122: Irs2; NbExp=2; IntAct=EBI-1802585, EBI-1369862;
CC Q923E4; Q60974: Ncor1; NbExp=3; IntAct=EBI-1802585, EBI-349004;
CC Q923E4; Q64221: Nhlh2; NbExp=2; IntAct=EBI-1802585, EBI-5378529;
CC Q923E4; Q62227: Nr0b2; NbExp=2; IntAct=EBI-1802585, EBI-4310440;
CC Q923E4; P37238: Pparg; NbExp=2; IntAct=EBI-1802585, EBI-5260705;
CC Q923E4; O70343: Ppargc1a; NbExp=6; IntAct=EBI-1802585, EBI-1371053;
CC Q923E4; O35253: Smad7; NbExp=6; IntAct=EBI-1802585, EBI-5274835;
CC Q923E4; Q9WTN3: Srebf1; NbExp=2; IntAct=EBI-1802585, EBI-5273743;
CC Q923E4; Q01094: E2F1; Xeno; NbExp=3; IntAct=EBI-1802585, EBI-448924;
CC Q923E4; Q12778: FOXO1; Xeno; NbExp=2; IntAct=EBI-1802585, EBI-1108782;
CC Q923E4; P06400: RB1; Xeno; NbExp=4; IntAct=EBI-1802585, EBI-491274;
CC Q923E4; P28749: RBL1; Xeno; NbExp=2; IntAct=EBI-1802585, EBI-971402;
CC Q923E4; Q08999: RBL2; Xeno; NbExp=2; IntAct=EBI-1802585, EBI-971439;
CC Q923E4; P04637: TP53; Xeno; NbExp=4; IntAct=EBI-1802585, EBI-366083;
CC -!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000250|UniProtKB:Q96EB6}.
CC Cytoplasm {ECO:0000269|PubMed:17197703, ECO:0000269|PubMed:17901049}.
CC Nucleus {ECO:0000269|PubMed:17197703, ECO:0000269|PubMed:17901049,
CC ECO:0000269|PubMed:18004385, ECO:0000269|PubMed:18662546,
CC ECO:0000269|PubMed:20955178}. Note=Colocalizes in the nucleus with XBP1
CC isoform 2. Recruited to the nuclear bodies via its interaction with
CC PML. Colocalized with APEX1 in the nucleus. May be found in nucleolus,
CC nuclear euchromatin, heterochromatin and inner membrane (By
CC similarity). Shuttles between nucleus and cytoplasm (PubMed:17197703).
CC {ECO:0000250|UniProtKB:Q96EB6, ECO:0000269|PubMed:17197703}.
CC -!- SUBCELLULAR LOCATION: [SirtT1 75 kDa fragment]: Cytoplasm
CC {ECO:0000250|UniProtKB:Q96EB6}. Mitochondrion
CC {ECO:0000250|UniProtKB:Q96EB6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q923E4-1; Sequence=Displayed;
CC Name=2; Synonyms=delta-exon8;
CC IsoId=Q923E4-2; Sequence=VSP_042190;
CC -!- TISSUE SPECIFICITY: Widely expressed. Weakly expressed in liver and
CC skeletal muscle. {ECO:0000269|PubMed:12482959}.
CC -!- INDUCTION: By calorie restriction which induces endothelial nitric
CC oxide synthase (eNOS) expression. Induced in liver by pyruvate during
CC fasting. Expressed in a circadian manner in the liver with maximal and
CC minimal levels reached at around Zeitgeber time (ZT) 16 and ZT4,
CC respectively. Its deacetylase activity in the liver is also regulated
CC in a circadian manner, with a peak at ZT15. Down-regulated by
CC palmitate; palmitate down-regulation is mediated by the induction of
CC miR-195 that directly targets SIRT1. {ECO:0000269|PubMed:15744310,
CC ECO:0000269|PubMed:16224023, ECO:0000269|PubMed:18662546,
CC ECO:0000269|PubMed:18662547, ECO:0000269|PubMed:21622680}.
CC -!- PTM: Methylated on multiple lysine residues; methylation is enhanced
CC after DNA damage and is dispensable for deacetylase activity toward
CC p53/TP53. {ECO:0000250|UniProtKB:Q96EB6}.
CC -!- PTM: Phosphorylated. Phosphorylated by STK4/MST1, resulting in
CC inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by
CC MAPK8/JNK1 at Ser-46 and Thr-522 leads to increased nuclear
CC localization and enzymatic activity. Phosphorylation at Thr-522 by
CC DYRK1A and DYRK3 activates deacetylase activity and promotes cell
CC survival (PubMed:20167603). Phosphorylation by mammalian target of
CC rapamycin complex 1 (mTORC1) at Ser-46 inhibits deacetylation activity.
CC Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B
CC p65/RELA deacetylation activity (By similarity).
CC {ECO:0000250|UniProtKB:Q96EB6, ECO:0000269|PubMed:20167603}.
CC -!- PTM: Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to
CC yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1).
CC {ECO:0000250|UniProtKB:Q96EB6}.
CC -!- PTM: S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent
CC protein deacetylase activity. {ECO:0000269|PubMed:20972425}.
CC -!- PTM: Acetylated at various Lys residues (PubMed:28923965). Deacetylated
CC via an autocatalytic mechanism (PubMed:28923965). Autodeacetylation at
CC Lys-230 promotes its protein deacetylase activity (PubMed:28923965).
CC {ECO:0000269|PubMed:28923965}.
CC -!- DISRUPTION PHENOTYPE: High degree of embryonic and postnatal lethality.
CC Decreased levels of histone H3 containing a trimethyl group at its
CC lysine 9 position (H3K9me3) in regions of heterochromatin. Attenuates
CC spermatogenesis but not oogenesis with reduced numbers of mature sperm
CC and spermatogenic precursors. Mice develop an autoimmune-like condition
CC with late onset diabetes insipidus. Prostatic intraepithelial neoplasia
CC associated with reduced autophagy. Conditional knockout in POMC neurons
CC leads to an increase of body weight compare to controls when animals
CC are challenged with high-fat diet (PubMed:20620997).
CC {ECO:0000269|PubMed:12482959, ECO:0000269|PubMed:18004385,
CC ECO:0000269|PubMed:18270565, ECO:0000269|PubMed:18687325,
CC ECO:0000269|PubMed:20620997, ECO:0000269|PubMed:21189328}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
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DR EMBL; AF214646; AAF24983.1; -; mRNA.
DR EMBL; BC006584; AAH06584.1; -; mRNA.
DR CCDS; CCDS23898.1; -. [Q923E4-1]
DR RefSeq; NP_062786.1; NM_019812.3. [Q923E4-1]
DR AlphaFoldDB; Q923E4; -.
DR SMR; Q923E4; -.
DR BioGRID; 220297; 52.
DR ComplexPortal; CPX-468; eNoSc complex.
DR CORUM; Q923E4; -.
DR DIP; DIP-47052N; -.
DR IntAct; Q923E4; 53.
DR STRING; 10090.ENSMUSP00000101082; -.
DR iPTMnet; Q923E4; -.
DR PhosphoSitePlus; Q923E4; -.
DR EPD; Q923E4; -.
DR jPOST; Q923E4; -.
DR MaxQB; Q923E4; -.
DR PaxDb; Q923E4; -.
DR PeptideAtlas; Q923E4; -.
DR PRIDE; Q923E4; -.
DR ProteomicsDB; 257181; -. [Q923E4-1]
DR ProteomicsDB; 257182; -. [Q923E4-2]
DR Antibodypedia; 1637; 1162 antibodies from 52 providers.
DR DNASU; 93759; -.
DR Ensembl; ENSMUST00000020257; ENSMUSP00000020257; ENSMUSG00000020063. [Q923E4-1]
DR Ensembl; ENSMUST00000120239; ENSMUSP00000112595; ENSMUSG00000020063. [Q923E4-1]
DR Ensembl; ENSMUST00000177694; ENSMUSP00000137565; ENSMUSG00000020063. [Q923E4-2]
DR GeneID; 93759; -.
DR KEGG; mmu:93759; -.
DR UCSC; uc007fke.2; mouse. [Q923E4-1]
DR CTD; 23411; -.
DR MGI; MGI:2135607; Sirt1.
DR VEuPathDB; HostDB:ENSMUSG00000020063; -.
DR eggNOG; KOG2684; Eukaryota.
DR GeneTree; ENSGT00940000159406; -.
DR HOGENOM; CLU_016587_0_0_1; -.
DR InParanoid; Q923E4; -.
DR OMA; ESECSAD; -.
DR PhylomeDB; Q923E4; -.
DR BRENDA; 2.3.1.286; 3474.
DR Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-MMU-427359; SIRT1 negatively regulates rRNA expression.
DR Reactome; R-MMU-9617629; Regulation of FOXO transcriptional activity by acetylation.
DR BioGRID-ORCS; 93759; 2 hits in 112 CRISPR screens.
DR ChiTaRS; Sirt1; mouse.
DR PRO; PR:Q923E4; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q923E4; protein.
DR Bgee; ENSMUSG00000020063; Expressed in cleaving embryo and 256 other tissues.
DR ExpressionAtlas; Q923E4; baseline and differential.
DR Genevisible; Q923E4; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005677; C:chromatin silencing complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0061773; C:eNoSc complex; ISO:MGI.
DR GO; GO:0035098; C:ESC/E(Z) complex; ISO:MGI.
DR GO; GO:0000791; C:euchromatin; ISS:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0030426; C:growth cone; ISO:MGI.
DR GO; GO:0000792; C:heterochromatin; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005635; C:nuclear envelope; ISO:MGI.
DR GO; GO:0005637; C:nuclear inner membrane; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0033553; C:rDNA heterochromatin; ISO:MGI.
DR GO; GO:0043425; F:bHLH transcription factor binding; ISS:UniProtKB.
DR GO; GO:0019213; F:deacetylase activity; IMP:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISO:MGI.
DR GO; GO:0004407; F:histone deacetylase activity; ISO:MGI.
DR GO; GO:0043398; F:HLH domain binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:1990254; F:keratin filament binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:MGI.
DR GO; GO:0070403; F:NAD+ binding; IBA:GO_Central.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:MGI.
DR GO; GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); IDA:UniProtKB.
DR GO; GO:0160012; F:NAD-dependent histone decrotonylase activity; ISS:UniProtKB.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IDA:UniProtKB.
DR GO; GO:0016922; F:nuclear receptor binding; ISO:MGI.
DR GO; GO:0002039; F:p53 binding; IPI:BHF-UCL.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; IPI:BHF-UCL.
DR GO; GO:0043422; F:protein kinase B binding; ISO:MGI.
DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:UniProtKB.
DR GO; GO:0106231; F:protein-propionyllysine depropionylase activity; IMP:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:BHF-UCL.
DR GO; GO:0003714; F:transcription corepressor activity; IMP:BHF-UCL.
DR GO; GO:0001525; P:angiogenesis; IMP:UniProtKB.
DR GO; GO:0042595; P:behavioral response to starvation; IMP:MGI.
DR GO; GO:0001678; P:cellular glucose homeostasis; IMP:UniProtKB.
DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:MGI.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISO:MGI.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0071456; P:cellular response to hypoxia; ISS:UniProtKB.
DR GO; GO:0071479; P:cellular response to ionizing radiation; IMP:UniProtKB.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEP:MGI.
DR GO; GO:0009267; P:cellular response to starvation; IMP:BHF-UCL.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISS:UniProtKB.
DR GO; GO:0035356; P:cellular triglyceride homeostasis; IMP:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; IMP:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; ISO:MGI.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; IMP:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; ISO:MGI.
DR GO; GO:0055089; P:fatty acid homeostasis; IMP:UniProtKB.
DR GO; GO:0031507; P:heterochromatin assembly; ISO:MGI.
DR GO; GO:0016575; P:histone deacetylation; IDA:UniProtKB.
DR GO; GO:0070932; P:histone H3 deacetylation; ISO:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:UniProtKB.
DR GO; GO:0033210; P:leptin-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0030225; P:macrophage differentiation; IMP:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; ISS:UniProtKB.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISO:MGI.
DR GO; GO:0060548; P:negative regulation of cell death; ISO:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR GO; GO:2000655; P:negative regulation of cellular response to testosterone stimulus; ISO:MGI.
DR GO; GO:2000773; P:negative regulation of cellular senescence; ISS:UniProtKB.
DR GO; GO:0043392; P:negative regulation of DNA binding; ISO:MGI.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; ISO:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:ParkinsonsUK-UCL.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:BHF-UCL.
DR GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0060125; P:negative regulation of growth hormone secretion; ISO:MGI.
DR GO; GO:0051097; P:negative regulation of helicase activity; ISO:MGI.
DR GO; GO:0071441; P:negative regulation of histone H3-K14 acetylation; ISO:MGI.
DR GO; GO:1900113; P:negative regulation of histone H3-K9 trimethylation; IDA:BHF-UCL.
DR GO; GO:2000619; P:negative regulation of histone H4-K16 acetylation; ISO:MGI.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISS:UniProtKB.
DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:BHF-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:1901215; P:negative regulation of neuron death; IGI:MGI.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; ISO:MGI.
DR GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; ISS:UniProtKB.
DR GO; GO:0042326; P:negative regulation of phosphorylation; IMP:UniProtKB.
DR GO; GO:0031393; P:negative regulation of prostaglandin biosynthetic process; IMP:UniProtKB.
DR GO; GO:1901984; P:negative regulation of protein acetylation; ISO:MGI.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:UniProtKB.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; ISO:MGI.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; ISO:MGI.
DR GO; GO:0032007; P:negative regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:MGI.
DR GO; GO:0001542; P:ovulation from ovarian follicle; IMP:MGI.
DR GO; GO:0018394; P:peptidyl-lysine acetylation; ISO:MGI.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; ISO:MGI.
DR GO; GO:0002821; P:positive regulation of adaptive immune response; ISS:UniProtKB.
DR GO; GO:1904179; P:positive regulation of adipose tissue development; IMP:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:2000481; P:positive regulation of cAMP-dependent protein kinase activity; IDA:UniProtKB.
DR GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:2000774; P:positive regulation of cellular senescence; ISS:UniProtKB.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; IMP:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:MGI.
DR GO; GO:0045739; P:positive regulation of DNA repair; ISS:UniProtKB.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:MGI.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IMP:UniProtKB.
DR GO; GO:0010460; P:positive regulation of heart rate; ISO:MGI.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; ISO:MGI.
DR GO; GO:0051574; P:positive regulation of histone H3-K9 methylation; ISO:MGI.
DR GO; GO:0031062; P:positive regulation of histone methylation; ISO:MGI.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; ISO:MGI.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IDA:UniProtKB.
DR GO; GO:2000111; P:positive regulation of macrophage apoptotic process; IMP:UniProtKB.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; IMP:UniProtKB.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISO:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:UniProtKB.
DR GO; GO:0090312; P:positive regulation of protein deacetylation; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:0014858; P:positive regulation of skeletal muscle cell proliferation; ISO:MGI.
DR GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; IMP:BHF-UCL.
DR GO; GO:2000614; P:positive regulation of thyroid-stimulating hormone secretion; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0006476; P:protein deacetylation; IDA:BHF-UCL.
DR GO; GO:0106230; P:protein depropionylation; IDA:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0000720; P:pyrimidine dimer repair by nucleotide-excision repair; IMP:UniProtKB.
DR GO; GO:0000183; P:rDNA heterochromatin assembly; ISO:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0070857; P:regulation of bile acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0090335; P:regulation of brown fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0010824; P:regulation of centrosome duplication; ISS:UniProtKB.
DR GO; GO:0032071; P:regulation of endodeoxyribonuclease activity; ISS:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IMP:UniProtKB.
DR GO; GO:0010883; P:regulation of lipid storage; IMP:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0035358; P:regulation of peroxisome proliferator activated receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0071900; P:regulation of protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0034391; P:regulation of smooth muscle cell apoptotic process; IDA:UniProtKB.
DR GO; GO:0046015; P:regulation of transcription by glucose; ISO:MGI.
DR GO; GO:0045471; P:response to ethanol; ISO:MGI.
DR GO; GO:0042542; P:response to hydrogen peroxide; ISS:UniProtKB.
DR GO; GO:0032868; P:response to insulin; IDA:UniProtKB.
DR GO; GO:0044321; P:response to leptin; IMP:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; ISO:MGI.
DR GO; GO:0000012; P:single strand break repair; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR GO; GO:0090400; P:stress-induced premature senescence; ISO:MGI.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:MGI.
DR GO; GO:0006642; P:triglyceride mobilization; IMP:BHF-UCL.
DR GO; GO:0070914; P:UV-damage excision repair; ISO:MGI.
DR GO; GO:0042311; P:vasodilation; ISO:MGI.
DR GO; GO:0050872; P:white fat cell differentiation; IMP:BHF-UCL.
DR Gene3D; 3.30.1600.10; -; 1.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR003000; Sirtuin.
DR InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
DR InterPro; IPR026590; Ssirtuin_cat_dom.
DR Pfam; PF02146; SIR2; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR PROSITE; PS50305; SIRTUIN; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Apoptosis; Biological rhythms;
KW Cytoplasm; Developmental protein; Differentiation; Metal-binding;
KW Mitochondrion; Myogenesis; NAD; Nucleus; Phosphoprotein;
KW Reference proteome; S-nitrosylation; Transcription;
KW Transcription regulation; Transferase; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT CHAIN 2..737
FT /note="NAD-dependent protein deacetylase sirtuin-1"
FT /id="PRO_0000110257"
FT CHAIN 2..525
FT /note="SirtT1 75 kDa fragment"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT /id="PRO_0000415290"
FT DOMAIN 236..490
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..268
FT /note="Interaction with H1-4"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT REGION 2..131
FT /note="Interaction with CLOCK"
FT /evidence="ECO:0000269|PubMed:18662547"
FT REGION 75..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 135..533
FT /note="Interaction with CCAR2"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT REGION 152..171
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 248..251
FT /note="Required for interaction with the sumoylated form of
FT CCAR2"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT REGION 514..539
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 653..713
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 32..39
FT /note="Nuclear localization signal"
FT MOTIF 138..145
FT /note="Nuclear export signal"
FT MOTIF 223..230
FT /note="Nuclear localization signal"
FT MOTIF 425..431
FT /note="Nuclear export signal"
FT COMPBIAS 28..42
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 524..539
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 653..676
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 677..691
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 355
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:11672522,
FT ECO:0000269|PubMed:12887892, ECO:0000269|PubMed:15220471,
FT ECO:0000269|PubMed:16892051"
FT BINDING 253..272
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 337..340
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 363
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 366
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 387
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 390
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 432..434
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 457..459
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 474
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 46
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 151
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 154
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 165
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 230
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:28923965"
FT MOD_RES 369
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:28923965"
FT MOD_RES 387
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000269|PubMed:20972425"
FT MOD_RES 390
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000269|PubMed:20972425"
FT MOD_RES 422
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000305|PubMed:28923965"
FT MOD_RES 505
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000305|PubMed:28923965"
FT MOD_RES 522
FT /note="Phosphothreonine; by DYRK1A, DYRK3 and MAPK8"
FT /evidence="ECO:0000269|PubMed:20167603"
FT MOD_RES 527
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 536
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 600
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000305|PubMed:28923965"
FT MOD_RES 649
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000269|PubMed:19680552"
FT MOD_RES 651
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT MOD_RES 737
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96EB6"
FT VAR_SEQ 446..629
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_042190"
FT MUTAGEN 37..38
FT /note="RR->AA: Abolishes nuclear localization; when
FT associated with A-227; A-228; A-229 and A-230."
FT MUTAGEN 138..145
FT /note="LLLTDGLL->AAATGAA: Abolishes nuclear export; when
FT associated with A-425; A-427; A-428; A-429; A-430 and A-
FT 431."
FT /evidence="ECO:0000269|PubMed:17197703"
FT MUTAGEN 154
FT /note="S->A: Abolishes in vitro phosphorylation by CaMK2;
FT when associated with A-649; A-651 and A-683."
FT /evidence="ECO:0000269|PubMed:19680552"
FT MUTAGEN 227..230
FT /note="KKRK->AAAA: Abolishes nuclear localization; when
FT associated with A-37 and A-38."
FT /evidence="ECO:0000269|PubMed:17197703"
FT MUTAGEN 230
FT /note="K->R: Decreased acetylation, leading to increased
FT protein deacetylase activity."
FT /evidence="ECO:0000269|PubMed:28923965"
FT MUTAGEN 261
FT /note="G->A: Abolished ADP-ribosyltransferase activity in
FT vitro without affecting the NAD-dependent protein
FT deacetylase activity."
FT /evidence="ECO:0000269|PubMed:15716268"
FT MUTAGEN 355
FT /note="H->Y: Loss of deacetylation activity. Loss of
FT inhibition of E2F1 and loss of coactivation of FOXO1-
FT mediated transcription."
FT /evidence="ECO:0000269|PubMed:11672522,
FT ECO:0000269|PubMed:12887892, ECO:0000269|PubMed:15220471,
FT ECO:0000269|PubMed:16892051"
FT MUTAGEN 363
FT /note="C->S: Does not affect S-nitrosylation."
FT /evidence="ECO:0000269|PubMed:20972425"
FT MUTAGEN 366
FT /note="C->S: Does not affect S-nitrosylation."
FT /evidence="ECO:0000269|PubMed:20972425"
FT MUTAGEN 369
FT /note="K->R: Does not affect protein deacetylase activity."
FT /evidence="ECO:0000269|PubMed:28923965"
FT MUTAGEN 387
FT /note="C->S: Impairs S-nitrosylation. Abolishes S-
FT nitrosylation; when associated with S-390."
FT /evidence="ECO:0000269|PubMed:20972425"
FT MUTAGEN 390
FT /note="C->S: Impairs S-nitrosylation. Abolishes S-
FT nitrosylation; when associated with S-387."
FT /evidence="ECO:0000269|PubMed:20972425"
FT MUTAGEN 425..431
FT /note="VDLLIVI->ADAAAAA: Abolishes nuclear export; when
FT associated with A-138; A-139; A-140; A-144 and A-145."
FT /evidence="ECO:0000269|PubMed:17197703"
FT MUTAGEN 505
FT /note="K->R: Does not affect protein deacetylase activity."
FT /evidence="ECO:0000269|PubMed:28923965"
FT MUTAGEN 522
FT /note="T->D: Increased deacetylase activity toward p53/TP53
FT and increases resistance to genotoxic stress (mimicks
FT residue phosphorylation)."
FT /evidence="ECO:0000269|PubMed:20167603"
FT MUTAGEN 522
FT /note="T->V: Reduces phosphorylation. Impairs deacetylase
FT activity toward p53/TP53 and decreases resistance to
FT genotoxic stress. Does not change nuclear localization."
FT /evidence="ECO:0000269|PubMed:20167603"
FT MUTAGEN 600
FT /note="K->R: Does not affect protein deacetylase activity."
FT /evidence="ECO:0000269|PubMed:28923965"
FT MUTAGEN 649
FT /note="S->A: Abolishes in vitro phosphorylation by CaMK2;
FT when associated with A-154; A-651 and A-683."
FT /evidence="ECO:0000269|PubMed:19680552"
FT MUTAGEN 651
FT /note="S->A: Abolishes in vitro phosphorylation by CaMK2;
FT when associated with A-154; A-649 and A-683."
FT /evidence="ECO:0000269|PubMed:19680552"
FT MUTAGEN 683
FT /note="S->A: Abolishes in vitro phosphorylation by CaMK2;
FT when associated with A-154; A-649 and A-651."
FT /evidence="ECO:0000269|PubMed:19680552"
SQ 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
