Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

NAD-dependent protein deacetylase sirtuin-1 (hSIRT1) (EC 3.5.1.-) (Regulatory protein SIR2 homolog 1) (SIR2-like protein 1) (hSIR2) [Cleaved into: SirtT1 75 kDa fragment (75SirT1)]

 SIR1_HUMAN              Reviewed;         747 AA.
Q96EB6; Q2XNF6; Q5JVQ0; Q9GZR9; Q9Y6F0;
31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
31-OCT-2003, sequence version 2.
30-AUG-2017, entry version 169.
RecName: Full=NAD-dependent protein deacetylase sirtuin-1;
Short=hSIRT1;
EC=3.5.1.-;
AltName: Full=Regulatory protein SIR2 homolog 1;
AltName: Full=SIR2-like protein 1;
Short=hSIR2;
Contains:
RecName: Full=SirtT1 75 kDa fragment;
Short=75SirT1;
Name=SIRT1; Synonyms=SIR2L1;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
TISSUE=Testis;
PubMed=10381378; DOI=10.1006/bbrc.1999.0897;
Frye R.A.;
"Characterization of five human cDNAs with homology to the yeast SIR2
gene: Sir2-like proteins (sirtuins) metabolize NAD and may have
protein ADP-ribosyltransferase activity.";
Biochem. Biophys. Res. Commun. 260:273-279(1999).
[2]
NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH HES1 AND HEY2, AND
MUTAGENESIS OF HIS-363.
PubMed=12535671; DOI=10.1016/S0006-291X(02)03020-6;
Takata T., Ishikawa F.;
"Human Sir2-related protein SIRT1 associates with the bHLH repressors
HES1 and HEY2 and is involved in HES1- and HEY2-mediated
transcriptional repression.";
Biochem. Biophys. Res. Commun. 301:250-257(2003).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-3.
NIEHS SNPs program;
Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15164054; DOI=10.1038/nature02462;
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J.,
Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D.,
Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S.,
Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L.,
Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S.,
Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L.,
Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J.,
Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M.,
Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S.,
Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M.,
Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A.,
Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T.,
Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I.,
Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T.,
Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W.,
Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H.,
Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L.,
Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K.,
Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T.,
Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
"The DNA sequence and comparative analysis of human chromosome 10.";
Nature 429:375-381(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 124-747.
TISSUE=Prostate;
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).
[6]
FUNCTION IN DEACETYLATION OF TP53, SUBCELLULAR LOCATION, AND
MUTAGENESIS OF HIS-363.
PubMed=11672523; DOI=10.1016/S0092-8674(01)00527-X;
Vaziri H., Dessain S.K., Ng Eaton E., Imai S., Frye R.A.,
Pandita T.K., Guarente L., Weinberg R.A.;
"hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase.";
Cell 107:149-159(2001).
[7]
FUNCTION, ENZYME ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH PML,
AND MUTAGENESIS OF HIS-363.
PubMed=12006491; DOI=10.1093/emboj/21.10.2383;
Langley E., Pearson M., Faretta M., Bauer U.-M., Frye R.A.,
Minucci S., Pelicci P.G., Kouzarides T.;
"Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular
senescence.";
EMBO J. 21:2383-2396(2002).
[8]
ENZYME REGULATION.
PubMed=12297502; DOI=10.1074/jbc.M205670200;
Bitterman K.J., Anderson R.M., Cohen H.Y., Latorre-Esteves M.,
Sinclair D.A.;
"Inhibition of silencing and accelerated aging by nicotinamide, a
putative negative regulator of yeast sir2 and human SIRT1.";
J. Biol. Chem. 277:45099-45107(2002).
[9]
ENZYME REGULATION.
PubMed=12939617; DOI=10.1038/nature01960;
Howitz K.T., Bitterman K.J., Cohen H.Y., Lamming D.W., Lavu S.,
Wood J.G., Zipkin R.E., Chung P., Kisielewski A., Zhang L.-L.,
Scherer B., Sinclair D.A.;
"Small molecule activators of sirtuins extend Saccharomyces cerevisiae
lifespan.";
Nature 425:191-196(2003).
[10]
FUNCTION.
PubMed=15152190; DOI=10.1038/sj.emboj.7600244;
Frye R.A., Mayo M.W.;
"Modulation of NF-kappaB-dependent transcription and cell survival by
the SIRT1 deacetylase.";
EMBO J. 23:2369-2380(2004).
[11]
FUNCTION IN DEACETYLATION OF FOXO3, AND FUNCTION IN REGULATION OF
FOXO3.
PubMed=14980222; DOI=10.1016/S0092-8674(04)00126-6;
Motta M.C., Divecha N., Lemieux M., Kamel C., Chen D., Gu W.,
Bultsma Y., McBurney M., Guarente L.;
"Mammalian SIRT1 represses forkhead transcription factors.";
Cell 116:551-563(2004).
[12]
FUNCTION IN DEACETYLATION OF MLLT7.
PubMed=15126506; DOI=10.1074/jbc.M401138200;
van der Horst A., Tertoolen L.G.J., de Vries-Smits L.M.M., Frye R.A.,
Medema R.H., Burgering B.M.T.;
"FOXO4 is acetylated upon peroxide stress and deacetylated by the
longevity protein hSir2(SIRT1).";
J. Biol. Chem. 279:28873-28879(2004).
[13]
FUNCTION, AND SUBCELLULAR LOCATION.
PubMed=15469825; DOI=10.1016/j.molcel.2004.08.031;
Vaquero A., Scher M., Lee D., Erdjument-Bromage H., Tempst P.,
Reinberg D.;
"Human SirT1 interacts with histone H1 and promotes formation of
facultative heterochromatin.";
Mol. Cell 16:93-105(2004).
[14]
FUNCTION IN DEACETYLATION OF FOXO3, AND FUNCTION IN REGULATION OF
FOXO3.
PubMed=14976264; DOI=10.1126/science.1094637;
Brunet A., Sweeney L.B., Sturgill J.F., Chua K.F., Greer P.L., Lin Y.,
Tran H., Ross S.E., Mostoslavsky R., Cohen H.Y., Hu L.S., Cheng H.L.,
Jedrychowski M.P., Gygi S.P., Sinclair D.A., Alt F.W., Greenberg M.E.;
"Stress-dependent regulation of FOXO transcription factors by the
SIRT1 deacetylase.";
Science 303:2011-2015(2004).
[15]
FUNCTION IN DEACETYLATION OF XRCC6, AND INDUCTION BY CR.
PubMed=15205477; DOI=10.1126/science.1099196;
Cohen H.Y., Miller C., Bitterman K.J., Wall N.R., Hekking B.,
Kessler B., Howitz K.T., Gorospe M., de Cabo R., Sinclair D.A.;
"Calorie restriction promotes mammalian cell survival by inducing the
SIRT1 deacetylase.";
Science 305:390-392(2004).
[16]
INTERACTION WITH FHL2, FUNCTION IN DEACETYLATION OF FOXO1, AND
FUNCTION IN REGULATION OF FOXO1.
PubMed=15692560; DOI=10.1038/sj.emboj.7600570;
Yang Y., Hou H., Haller E.M., Nicosia S.V., Bai W.;
"Suppression of FOXO1 activity by FHL2 through SIRT1-mediated
deacetylation.";
EMBO J. 24:1021-1032(2005).
[17]
FUNCTION, AND SUBCELLULAR LOCATION.
PubMed=16079181; DOI=10.1091/mbc.E05-01-0033;
Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I.;
"Evolutionarily conserved and nonconserved cellular localizations and
functions of human SIRT proteins.";
Mol. Biol. Cell 16:4623-4635(2005).
[18]
FUNCTION IN DEACETYLATION OF MEF2D, AND INTERACTION WITH HDAC4.
PubMed=16166628; DOI=10.1128/MCB.25.19.8456-8464.2005;
Zhao X., Sternsdorf T., Bolger T.A., Evans R.M., Yao T.-P.;
"Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-
mediated lysine modifications.";
Mol. Cell. Biol. 25:8456-8464(2005).
[19]
INTERACTION WITH HIV-1 TAT.
PubMed=15719057; DOI=10.1371/journal.pbio.0030041;
Pagans S., Pedal A., North B.J., Kaehlcke K., Marshall B.L., Dorr A.,
Hetzer-Egger C., Henklein P., Frye R., McBurney M.W., Hruby H.,
Jung M., Verdin E., Ott M.;
"SIRT1 regulates HIV transcription via Tat deacetylation.";
PLoS Biol. 3:210-220(2005).
[20]
ASSOCIATION WITH THE PRC4 COMPLEX, AND INTERACTION WITH SUZ12.
PubMed=15684044; DOI=10.1073/pnas.0409875102;
Kuzmichev A., Margueron R., Vaquero A., Preissner T.S., Scher M.,
Kirmizis A., Ouyang X., Brockdorff N., Abate-Shen C., Farnham P.J.,
Reinberg D.;
"Composition and histone substrates of polycomb repressive group
complexes change during cellular differentiation.";
Proc. Natl. Acad. Sci. U.S.A. 102:1859-1864(2005).
[21]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=16964243; DOI=10.1038/nbt1240;
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
"A probability-based approach for high-throughput protein
phosphorylation analysis and site localization.";
Nat. Biotechnol. 24:1285-1292(2006).
[22]
FUNCTION, AND INTERACTION WITH E2F1.
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).
[23]
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).
[24]
INTERACTION WITH TLE1.
PubMed=17680780; DOI=10.1042/BJ20070817;
Ghosh H.S., Spencer J.V., Ng B., McBurney M.W., Robbins P.D.;
"Sirt1 interacts with transducin-like enhancer of split-1 to inhibit
nuclear factor kappaB-mediated transcription.";
Biochem. J. 408:105-111(2007).
[25]
FUNCTION, AND MUTAGENESIS OF HIS-363.
PubMed=17290224; DOI=10.1038/sj.emboj.7601563;
Pedersen T.A., Bereshchenko O., Garcia-Silva S., Ermakova O., Kurz E.,
Mandrup S., Porse B.T., Nerlov C.;
"Distinct C/EBPalpha motifs regulate lipogenic and gluconeogenic gene
expression in vivo.";
EMBO J. 26:1081-1093(2007).
[26]
FUNCTION IN DEACETYLATION OF XRCC6, AND FUNCTION IN DNA REPAIR.
PubMed=17334224; DOI=10.1038/emm.2007.2;
Jeong J., Juhn K., Lee H., Kim S.H., Min B.H., Lee K.M., Cho M.H.,
Park G.H., Lee K.H.;
"SIRT1 promotes DNA repair activity and deacetylation of Ku70.";
Exp. Mol. Med. 39:8-13(2007).
[27]
FUNCTION IN DEACETYLATION OF TP73, AND FUNCTION IN REGULATION OF TP73.
PubMed=16998810; DOI=10.1002/jcp.20831;
Dai J.M., Wang Z.Y., Sun D.C., Lin R.X., Wang S.Q.;
"SIRT1 interacts with p73 and suppresses p73-dependent transcriptional
activity.";
J. Cell. Physiol. 210:161-166(2007).
[28]
FUNCTION IN AR-DEPENDENT REPRESSION.
PubMed=17505061; DOI=10.1210/me.2006-0467;
Dai Y., Ngo D., Forman L.W., Qin D.C., Jacob J., Faller D.V.;
"Sirtuin 1 is required for antagonist-induced transcriptional
repression of androgen-responsive genes by the androgen receptor.";
Mol. Endocrinol. 21:1807-1821(2007).
[29]
INTERACTION WITH RPS19BP1.
PubMed=17964266; DOI=10.1016/j.molcel.2007.08.030;
Kim E.-J., Kho J.-H., Kang M.-R., Um S.-J.;
"Active regulator of SIRT1 cooperates with SIRT1 and facilitates
suppression of p53 activity.";
Mol. Cell 28:277-290(2007).
[30]
ERRATUM.
Kim E.-J., Kho J.-H., Kang M.-R., Um S.-J.;
Mol. Cell 28:513-513(2007).
[31]
FUNCTION IN DEACETYLATION OF NR1H3 AND NR1H2.
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).
[32]
FUNCTION IN DEACETYLATION OF NBN, AND FUNCTION IN DNA REPAIR.
PubMed=17612497; DOI=10.1016/j.molcel.2007.05.029;
Yuan Z., Zhang X., Sengupta N., Lane W.S., Seto E.;
"SIRT1 regulates the function of the Nijmegen breakage syndrome
protein.";
Mol. Cell 27:149-162(2007).
[33]
FUNCTION IN DEACETYLATION OF HIC1.
PubMed=17283066; DOI=10.1128/MCB.01098-06;
Stankovic-Valentin N., Deltour S., Seeler J., Pinte S., Vergoten G.,
Guerardel C., Dejean A., Leprince D.;
"An acetylation/deacetylation-SUMOylation switch through a
phylogenetically conserved psiKXEP motif in the tumor suppressor HIC1
regulates transcriptional repression activity.";
Mol. Cell. Biol. 27:2661-2675(2007).
[34]
MUTAGENESIS OF HIS-363.
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).
[35]
FUNCTION.
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).
[36]
IDENTIFICATION IN THE ENOSC COMPLEX, FUNCTION, AND MUTAGENESIS OF
HIS-363.
PubMed=18485871; DOI=10.1016/j.cell.2008.03.030;
Murayama A., Ohmori K., Fujimura A., Minami H., Yasuzawa-Tanaka K.,
Kuroda T., Oie S., Daitoku H., Okuwaki M., Nagata K., Fukamizu A.,
Kimura K., Shimizu T., Yanagisawa J.;
"Epigenetic control of rDNA loci in response to intracellular energy
status.";
Cell 133:627-639(2008).
[37]
PHOSPHORYLATION AT SER-27 AND SER-47.
PubMed=18838864; DOI=10.4161/cc.7.19.6799;
Ford J., Ahmed S., Allison S., Jiang M., Milner J.;
"JNK2-dependent regulation of SIRT1 protein stability.";
Cell Cycle 7:3091-3097(2008).
[38]
INTERACTION WITH HIV-1 TAT, AND FUNCTION IN T-CELL ACTIVATION
(MICROBIAL INFECTION).
PubMed=18329615; DOI=10.1016/j.chom.2008.02.002;
Kwon H.S., Brent M.M., Getachew R., Jayakumar P., Chen L.F.,
Schnolzer M., McBurney M.W., Marmorstein R., Greene W.C., Ott M.;
"Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1
deacetylase and induces T cell hyperactivation.";
Cell Host Microbe 3:158-167(2008).
[39]
FUNCTION IN DEACETYLATION OF WRN, AND FUNCTION IN DNA DAMAGE.
PubMed=18203716; DOI=10.1074/jbc.M709707200;
Li K., Casta A., Wang R., Lozada E., Fan W., Kane S., Ge Q., Gu W.,
Orren D., Luo J.;
"Regulation of WRN protein cellular localization and enzymatic
activities by SIRT1-mediated deacetylation.";
J. Biol. Chem. 283:7590-7598(2008).
[40]
FUNCTION IN DEACETYLATION 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).
[41]
INTERACTION WITH CCAR2, ENZYME REGULATION, MUTAGENESIS OF HIS-363, AND
IDENTIFICATION BY MASS SPECTROMETRY.
PubMed=18235501; DOI=10.1038/nature06500;
Kim J.-E., Chen J., Lou Z.;
"DBC1 is a negative regulator of SIRT1.";
Nature 451:583-586(2008).
[42]
INTERACTION WITH CCAR2, AND ENZYME REGULATION.
PubMed=18235502; DOI=10.1038/nature06515;
Zhao W., Kruse J.-P., Tang Y., Jung S.Y., Qin J., Gu W.;
"Negative regulation of the deacetylase SIRT1 by DBC1.";
Nature 451:587-590(2008).
[43]
PHOSPHORYLATION AT SER-14; SER-26; SER-27; SER-47; SER-159; SER-162;
SER-172; SER-173; THR-530; THR-544; SER-545; THR-719 AND SER-747, AND
MUTAGENESIS OF THR-530 AND SER-540.
PubMed=19107194; DOI=10.1371/journal.pone.0004020;
Sasaki T., Maier B., Koclega K.D., Chruszcz M., Gluba W.,
Stukenberg P.T., Minor W., Scrable H.;
"Phosphorylation regulates SIRT1 function.";
PLoS ONE 3:E4020-E4020(2008).
[44]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-719, AND IDENTIFICATION
BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=18669648; DOI=10.1073/pnas.0805139105;
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
Elledge S.J., Gygi S.P.;
"A quantitative atlas of mitotic phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
[45]
FUNCTION IN DEACETYLATION OF ATG5; ATG7 AND MAP1LC3B, AND 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).
[46]
ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=19413330; DOI=10.1021/ac9004309;
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
Mohammed S.;
"Lys-N and trypsin cover complementary parts of the phosphoproteome in
a refined SCX-based approach.";
Anal. Chem. 81:4493-4501(2009).
[47]
PHOSPHORYLATION AT SER-659 AND SER-661, AND MUTAGENESIS OF SER-659;
SER-661 AND SER-684.
PubMed=19236849; DOI=10.1016/j.bbrc.2009.02.085;
Zschoernig B., Mahlknecht U.;
"Carboxy-terminal phosphorylation of SIRT1 by protein kinase CK2.";
Biochem. Biophys. Res. Commun. 381:372-377(2009).
[48]
FUNCTION.
PubMed=19220062; DOI=10.1021/bi802093g;
Du J., Jiang H., Lin H.;
"Investigating the ADP-ribosyltransferase activity of sirtuins with
NAD analogues and 32P-NAD.";
Biochemistry 48:2878-2890(2009).
[49]
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).
[50]
FUNCTION, AND INTERACTION WITH CREBZF.
PubMed=19690166; DOI=10.1074/jbc.M109.034165;
Xie Y.B., Park J.H., Kim D.K., Hwang J.H., Oh S., Park S.B., Shong M.,
Lee I.K., Choi H.S.;
"Transcriptional corepressor SMILE recruits SIRT1 to inhibit nuclear
receptor estrogen receptor-related receptor gamma transactivation.";
J. Biol. Chem. 284:28762-28774(2009).
[51]
FUNCTION IN DEACETYLATION OF MYC, AND FUNCTION IN REGULATION OF MYC.
PubMed=19364925; DOI=10.1083/jcb.200809167;
Yuan J., Minter-Dykhouse K., Lou Z.;
"A c-Myc-SIRT1 feedback loop regulates cell growth and
transformation.";
J. Cell Biol. 185:203-211(2009).
[52]
FUNCTION IN DEACETYLATION OF PCAF, AND FUNCTION IN DNA REPAIR.
PubMed=19188449; DOI=10.1128/MCB.00552-08;
Pediconi N., Guerrieri F., Vossio S., Bruno T., Belloni L.,
Schinzari V., Scisciani C., Fanciulli M., Levrero M.;
"hSirT1-dependent regulation of the PCAF-E2F1-p73 apoptotic pathway in
response to DNA damage.";
Mol. Cell. Biol. 29:1989-1998(2009).
[53]
PHOSPHORYLATION AT SER-27; SER-47 AND THR-530, MUTAGENESIS OF SER-27;
SER-47 AND THR-530, AND SUBCELLULAR LOCATION.
PubMed=20027304; DOI=10.1371/journal.pone.0008414;
Nasrin N., Kaushik V.K., Fortier E., Wall D., Pearson K.J.,
de Cabo R., Bordone L.;
"JNK1 phosphorylates SIRT1 and promotes its enzymatic activity.";
PLoS ONE 4:E8414-E8414(2009).
[54]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-530; SER-535 AND
THR-719, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].
TISSUE=Leukemic T-cell;
PubMed=19690332; DOI=10.1126/scisignal.2000007;
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
Rodionov V., Han D.K.;
"Quantitative phosphoproteomic analysis of T cell receptor signaling
reveals system-wide modulation of protein-protein interactions.";
Sci. Signal. 2:RA46-RA46(2009).
[55]
FUNCTION IN REGULATION OF STK11.
PubMed=20203304; DOI=10.1161/CIRCRESAHA.109.215483;
Zu Y., Liu L., Lee M.Y., Xu C., Liang Y., Man R.Y., Vanhoutte P.M.,
Wang Y.;
"SIRT1 promotes proliferation and prevents senescence through
targeting LKB1 in primary porcine aortic endothelial cells.";
Circ. Res. 106:1384-1393(2010).
[56]
FUNCTION IN DNA REPAIR HOMOLOGOUS RECOMBINATION.
PubMed=20097625; DOI=10.1016/j.dnarep.2009.12.020;
Uhl M., Csernok A., Aydin S., Kreienberg R., Wiesmuller L., Gatz S.A.;
"Role of SIRT1 in homologous recombination.";
DNA Repair 9:383-393(2010).
[57]
INTERACTION WITH FOS AND JUN.
PubMed=20042607; DOI=10.1074/jbc.M109.038604;
Zhang R., Chen H.Z., Liu J.J., Jia Y.Y., Zhang Z.Q., Yang R.F.,
Zhang Y., Xu J., Wei Y.S., Liu D.P., Liang C.C.;
"SIRT1 suppresses activator protein-1 transcriptional activity and
cyclooxygenase-2 expression in macrophages.";
J. Biol. Chem. 285:7097-7110(2010).
[58]
FUNCTION IN DEACETYLATION OF KAT5.
PubMed=20100829; DOI=10.1074/jbc.M109.087585;
Wang J., Chen J.;
"SIRT1 regulates autoacetylation and histone acetyltransferase
activity of TIP60.";
J. Biol. Chem. 285:11458-11464(2010).
[59]
SUBCELLULAR LOCATION.
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).
[60]
FUNCTION IN DEACETYLATION 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).
[61]
FUNCTION IN DEACETYLATION OF HIF1A, AND FUNCTION IN REGULATION OF
HIF1A.
PubMed=20620956; DOI=10.1016/j.molcel.2010.05.023;
Lim J.H., Lee Y.M., Chun Y.S., Chen J., Kim J.E., Park J.W.;
"Sirtuin 1 modulates cellular responses to hypoxia by deacetylating
hypoxia-inducible factor 1alpha.";
Mol. Cell 38:864-878(2010).
[62]
FUNCTION IN DEACETYLATION OF XPA.
PubMed=20670893; DOI=10.1016/j.molcel.2010.07.006;
Fan W., Luo J.;
"SIRT1 regulates UV-induced DNA repair through deacetylating XPA.";
Mol. Cell 39:247-258(2010).
[63]
FUNCTION IN DEACETYLATION OF APEX1, FUNCTION IN DNA REPAIR,
MUTAGENESIS OF HIS-363, INDUCTION, AND SUBCELLULAR LOCATION.
PubMed=19934257; DOI=10.1093/nar/gkp1039;
Yamamori T., DeRicco J., Naqvi A., Hoffman T.A., Mattagajasingh I.,
Kasuno K., Jung S.B., Kim C.S., Irani K.;
"SIRT1 deacetylates APE1 and regulates cellular base excision
repair.";
Nucleic Acids Res. 38:832-845(2010).
[64]
FUNCTION, AND INTERACTION WITH NR0B2.
PubMed=20375098; DOI=10.1093/nar/gkq227;
Chanda D., Xie Y.B., Choi H.S.;
"Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to
inhibit LRH-1 transactivation.";
Nucleic Acids Res. 38:4607-4619(2010).
[65]
INTERACTION WITH TSC2.
PubMed=20169165; DOI=10.1371/journal.pone.0009199;
Ghosh H.S., McBurney M., Robbins P.D.;
"SIRT1 negatively regulates the mammalian target of rapamycin.";
PLoS ONE 5:E9199-E9199(2010).
[66]
ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION (ISOFORM 2), INDUCTION
(ISOFORM 2), AND INTERACTION WITH TP53 AND RPS19BP1.
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).
[67]
FUNCTION IN DNA REPAIR, AND SUPPRESSION OF XPC.
PubMed=21149730; DOI=10.1073/pnas.1010377108;
Ming M., Shea C.R., Guo X., Li X., Soltani K., Han W., He Y.Y.;
"Regulation of global genome nucleotide excision repair by SIRT1
through xeroderma pigmentosum C.";
Proc. Natl. Acad. Sci. U.S.A. 107:22623-22628(2010).
[68]
ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
SCALE ANALYSIS] AT SER-14 AND SER-47, CLEAVAGE OF INITIATOR METHIONINE
[LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
SCALE ANALYSIS].
TISSUE=Cervix carcinoma;
PubMed=20068231; DOI=10.1126/scisignal.2000475;
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
Mann M.;
"Quantitative phosphoproteomics reveals widespread full
phosphorylation site occupancy during mitosis.";
Sci. Signal. 3:RA3-RA3(2010).
[69]
FUNCTION IN DEACETYLATION OF HMGCS1.
PubMed=21701047;
Hirschey M.D., Shimazu T., Capra J.A., Pollard K.S., Verdin E.;
"SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and
HMGCS1,2.";
Aging (Albany NY) 3:635-642(2011).
[70]
PROCESSING.
PubMed=21305533; DOI=10.1002/art.30279;
Dvir-Ginzberg M., Gagarina V., Lee E.J., Booth R., Gabay O.,
Hall D.J.;
"Tumor necrosis factor alpha-mediated cleavage and inactivation of
SirT1 in human osteoarthritic chondrocytes.";
Arthritis Rheum. 63:2363-2373(2011).
[71]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21269460; DOI=10.1186/1752-0509-5-17;
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
"Initial characterization of the human central proteome.";
BMC Syst. Biol. 5:17-17(2011).
[72]
FUNCTION IN DEACETYLATION OF XBP1, INTERACTION WITH 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).
[73]
FUNCTION IN DEACETYLATION OF MECOM.
PubMed=21555002; DOI=10.1016/j.bbagrm.2011.04.007;
Pradhan A.K., Kuila N., Singh S., Chakraborty S.;
"EVI1 up-regulates the stress responsive gene SIRT1 which triggers
deacetylation and degradation of EVI1.";
Biochim. Biophys. Acta 1809:269-275(2011).
[74]
INTERACTION WITH NR1I2.
PubMed=21933665; DOI=10.1016/j.bcp.2011.09.006;
Buler M., Aatsinki S.M., Skoumal R., Hakkola J.;
"Energy sensing factors PGC-1alpha and SIRT1 modulate PXR expression
and function.";
Biochem. Pharmacol. 82:2008-2015(2011).
[75]
FUNCTION IN DEACETYLATION OF MYC, AND FUNCTION IN REGULATION OF MYC.
PubMed=21807113; DOI=10.1016/j.biocel.2011.07.006;
Mao B., Zhao G., Lv X., Chen H.Z., Xue Z., Yang B., Liu D.P.,
Liang C.C.;
"Sirt1 deacetylates c-Myc and promotes c-Myc/Max association.";
Int. J. Biochem. Cell Biol. 43:1573-1581(2011).
[76]
PHOSPHORYLATION BY STK4/MST1.
PubMed=21212262; DOI=10.1074/jbc.M110.182543;
Yuan F., Xie Q., Wu J., Bai Y., Mao B., Dong Y., Bi W., Ji G., Tao W.,
Wang Y., Yuan Z.;
"MST1 promotes apoptosis through regulating Sirt1-dependent p53
deacetylation.";
J. Biol. Chem. 286:6940-6945(2011).
[77]
FUNCTION IN APOPTOSIS, PHOSPHORYLATION AT SER-47, AND MUTAGENESIS OF
SER-47 AND PHE-474.
PubMed=21471201; DOI=10.1074/jbc.M111.240598;
Back J.H., Rezvani H.R., Zhu Y., Guyonnet-Duperat V., Athar M.,
Ratner D., Kim A.L.;
"Cancer cell survival following DNA damage-mediated premature
senescence is regulated by mammalian target of rapamycin (mTOR)-
dependent Inhibition of sirtuin 1.";
J. Biol. Chem. 286:19100-19108(2011).
[78]
FUNCTION IN STABILIZATION OF SUV39H1.
PubMed=21504832; DOI=10.1016/j.molcel.2011.02.034;
Bosch-Presegue L., Raurell-Vila H., Marazuela-Duque A.,
Kane-Goldsmith N., Valle A., Oliver J., Serrano L., Vaquero A.;
"Stabilization of Suv39H1 by SirT1 is part of oxidative stress
response and ensures genome protection.";
Mol. Cell 42:210-223(2011).
[79]
FUNCTION IN DEACETYLATION OF DNMT1, AND FUNCTION IN REGULATION OF
DNMT1.
PubMed=21947282; DOI=10.1128/MCB.06147-11;
Peng L., Yuan Z., Ling H., Fukasawa K., Robertson K., Olashaw N.,
Koomen J., Chen J., Lane W.S., Seto E.;
"SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and
alters its activities.";
Mol. Cell. Biol. 31:4720-4734(2011).
[80]
FUNCTION IN REGULATION OF MYCN, AND INTERACTION WITH MYCN.
PubMed=21698133; DOI=10.1371/journal.pgen.1002135;
Marshall G.M., Liu P.Y., Gherardi S., Scarlett C.J., Bedalov A.,
Xu N., Iraci N., Valli E., Ling D., Thomas W., van Bekkum M.,
Sekyere E., Jankowski K., Trahair T., Mackenzie K.L., Haber M.,
Norris M.D., Biankin A.V., Perini G., Liu T.;
"SIRT1 promotes N-Myc oncogenesis through a positive feedback loop
involving the effects of MKP3 and ERK on N-Myc protein stability.";
PLoS Genet. 7:E1002135-E1002135(2011).
[81]
INTERACTION WITH HCFC1.
PubMed=21909281; DOI=10.1371/journal.pgen.1002235;
Rizki G., Iwata T.N., Li J., Riedel C.G., Picard C.L., Jan M.,
Murphy C.T., Lee S.S.;
"The evolutionarily conserved longevity determinants HCF-1 and SIR-
2.1/SIRT1 collaborate to regulate DAF-16/FOXO.";
PLoS Genet. 7:E1002235-E1002235(2011).
[82]
INTERACTION WITH SETD7, AND MUTAGENESIS OF LYS-233; LYS-235; LYS-236
AND LYS-238.
PubMed=21245319; DOI=10.1073/pnas.1019619108;
Liu X., Wang D., Zhao Y., Tu B., Zheng Z., Wang L., Wang H., Gu W.,
Roeder R.G., Zhu W.G.;
"Methyltransferase Set7/9 regulates p53 activity by interacting with
Sirtuin 1 (SIRT1).";
Proc. Natl. Acad. Sci. U.S.A. 108:1925-1930(2011).
[83]
FUNCTION IN DEACETYLATION OF AKT1, AND FUNCTION IN REGULATION OF AKT1.
PubMed=21775285; DOI=10.1126/scisignal.2001465;
Sundaresan N.R., Pillai V.B., Wolfgeher D., Samant S., Vasudevan P.,
Parekh V., Raghuraman H., Cunningham J.M., Gupta M., Gupta M.P.;
"The deacetylase SIRT1 promotes membrane localization and activation
of Akt and PDK1 during tumorigenesis and cardiac hypertrophy.";
Sci. Signal. 4:RA46-RA46(2011).
[84]
ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE
SCALE ANALYSIS] AT SER-14; SER-47 AND THR-719, CLEAVAGE OF INITIATOR
METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=21406692; DOI=10.1126/scisignal.2001570;
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
Blagoev B.;
"System-wide temporal characterization of the proteome and
phosphoproteome of human embryonic stem cell differentiation.";
Sci. Signal. 4:RS3-RS3(2011).
[85]
FUNCTION (SIRTT1 75 KDA FRAGMENT), AND SUBCELLULAR LOCATION (75SIRT1).
PubMed=21987377; DOI=10.1002/art.33407;
Oppenheimer H., Gabay O., Meir H., Haze A., Kandel L., Liebergall M.,
Gagarina V., Lee E.J., Dvir-Ginzberg M.;
"75kDa SirT1 blocks TNFalpha-mediated apoptosis in human
osteoarthritic chondrocytes.";
Arthritis Rheum. 64:718-728(2012).
[86]
FUNCTION IN DEACETYLATION OF CIITA.
PubMed=21890893; DOI=10.1093/nar/gkr651;
Wu X., Kong X., Chen D., Li H., Zhao Y., Xia M., Fang M., Li P.,
Fang F., Sun L., Tian W., Xu H., Yang Y., Qi X., Gao Y., Sha J.,
Chen Q., Xu Y.;
"SIRT1 links CIITA deacetylation to MHC II activation.";
Nucleic Acids Res. 39:9549-9558(2011).
[87]
FUNCTION IN DEACETYLATION OF PML.
PubMed=22274616; DOI=10.1038/emboj.2012.1;
Miki T., Xu Z., Chen-Goodspeed M., Liu M., Van Oort-Jansen A.,
Rea M.A., Zhao Z., Lee C.C., Chang K.S.;
"PML regulates PER2 nuclear localization and circadian function.";
EMBO J. 31:1427-1439(2012).
[88]
ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=22223895; DOI=10.1074/mcp.M111.015131;
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C.,
Meinnel T., Giglione C.;
"Comparative large-scale characterisation of plant vs. mammal proteins
reveals similar and idiosyncratic N-alpha acetylation features.";
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
[89]
FUNCTION IN DEACETYLATION OF FOXO3, AND FUNCTION IN REGULATION OF
FOXO3.
PubMed=21841822; DOI=10.1038/onc.2011.347;
Wang F., Chan C.H., Chen K., Guan X., Lin H.K., Tong Q.;
"Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3
ubiquitination and degradation.";
Oncogene 31:1546-1557(2012).
[90]
ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS
SPECTROMETRY [LARGE SCALE ANALYSIS].
PubMed=22814378; DOI=10.1073/pnas.1210303109;
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
Aldabe R.;
"N-terminal acetylome analyses and functional insights of the N-
terminal acetyltransferase NatB.";
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
[91]
INTERACTION WITH CCAR2.
PubMed=23352644; DOI=10.1016/j.canlet.2013.01.026;
Kim W., Kim J.E.;
"Deleted in breast cancer 1 (DBC1) deficiency results in apoptosis of
breast cancer cells through impaired responses to UV-induced DNA
damage.";
Cancer Lett. 333:180-186(2013).
[92]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-27; SER-47 AND
THR-719, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].
TISSUE=Cervix carcinoma, and Erythroleukemia;
PubMed=23186163; DOI=10.1021/pr300630k;
Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
Mohammed S.;
"Toward a comprehensive characterization of a human cancer cell
phosphoproteome.";
J. Proteome Res. 12:260-271(2013).
[93]
INTERACTION WITH PPARA.
PubMed=24043310; DOI=10.1128/MCB.00087-13;
Laurent G., de Boer V.C., Finley L.W., Sweeney M., Lu H., Schug T.T.,
Cen Y., Jeong S.M., Li X., Sauve A.A., Haigis M.C.;
"SIRT4 represses peroxisome proliferator-activated receptor alpha
activity to suppress hepatic fat oxidation.";
Mol. Cell. Biol. 33:4552-4561(2013).
[94]
FUNCTION.
PubMed=24415752; DOI=10.1074/jbc.M113.512913;
Nin V., Chini C.C., Escande C., Capellini V., Chini E.N.;
"Deleted in breast cancer 1 (DBC1) protein regulates hepatic
gluconeogenesis.";
J. Biol. Chem. 289:5518-5527(2014).
[95]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-27, AND
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D.,
Wang L., Ye M., Zou H.;
"An enzyme assisted RP-RPLC approach for in-depth analysis of human
liver phosphoproteome.";
J. Proteomics 96:253-262(2014).
[96]
INTERACTION WITH CCAR2 AND TP53, AND MUTAGENESIS OF 256-ILE-ILE-257
AND HIS-363.
PubMed=25406032; DOI=10.1038/ncomms6483;
Park J.H., Lee S.W., Yang S.W., Yoo H.M., Park J.M., Seong M.W.,
Ka S.H., Oh K.H., Jeon Y.J., Chung C.H.;
"Modification of DBC1 by SUMO2/3 is crucial for p53-mediated apoptosis
in response to DNA damage.";
Nat. Commun. 5:5483-5483(2014).
[97]
INTERACTION WITH CHEK2.
PubMed=25361978; DOI=10.1093/nar/gku1065;
Magni M., Ruscica V., Buscemi G., Kim J.E., Nachimuthu B.T.,
Fontanella E., Delia D., Zannini L.;
"Chk2 and REGgamma-dependent DBC1 regulation in DNA damage induced
apoptosis.";
Nucleic Acids Res. 42:13150-13160(2014).
[98]
FUNCTION IN DEACETYLATION OF CTNB1.
PubMed=24824780; DOI=10.1002/ijc.28967;
Pangon L., Mladenova D., Watkins L., Van Kralingen C., Currey N.,
Al-Sohaily S., Lecine P., Borg J.P., Kohonen-Corish M.R.;
"MCC inhibits beta-catenin transcriptional activity by sequestering
DBC1 in the cytoplasm.";
Int. J. Cancer 136:55-64(2015).
[99]
INTERACTION WITH NR1H3.
PubMed=25661920; DOI=10.1016/j.jsbmb.2015.02.001;
Sakurabashi A., Wada-Hiraike O., Hirano M., Fu H., Isono W.,
Fukuda T., Morita Y., Tanikawa M., Miyamoto Y., Oda K., Kawana K.,
Osuga Y., Fujii T.;
"CCAR2 negatively regulates nuclear receptor LXRalpha by competing
with SIRT1 deacetylase.";
J. Steroid Biochem. Mol. Biol. 149:80-88(2015).
-!- 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, metobolism,
apoptosis and autophagy. Can modulate chromatin function through
deacetylation of histones and can promote alterations in the
methylation of histones and DNA, leading to transcriptional
repression. Deacetylates a broad range of transcription factors
and coregulators, thereby regulating target gene expression
positively and negatively. Serves as a sensor of the cytosolic
ratio of NAD(+)/NADH which is altered by glucose deprivation and
metabolic changes associated with caloric restriction. 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). 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. 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. Deacetylates 'Lys-266' of SUV39H1, leading to its
activation. Inhibits skeletal muscle differentiation by
deacetylating PCAF and MYOD1. Deacetylates H2A and 'Lys-26' of
HIST1H1E. Deacetylates 'Lys-16' of histone H4 (in vitro). 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. Proposed to contribute to genomic
integrity via positive regulation of telomere length; however,
reports on localization to pericentromeric heterochromatin are
conflicting. Proposed to play a role in constitutive
heterochromatin (CH) formation and/or maintenance through
regulation of the available pool of nuclear SUV39H1. Upon
oxidative/metabolic stress decreases SUV39H1 degradation by
inhibiting SUV39H1 polyubiquitination by MDM2. 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.
Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to
induce transcription-dependent proapoptotic program and modulate
cell senescence. Deacetylates TAF1B and thereby represses rDNA
transcription by the RNA polymerase I. Deacetylates MYC, promotes
the association of MYC with MAX and decreases MYC stability
leading to compromised transformational capability. 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. Appears to have a similar effect on
MLLT7/FOXO4 in regulation of transcriptional activity and
apoptosis. Deacetylates DNMT1; thereby impairs DNMT1
methyltransferase-independent transcription repressor activity,
modulates DNMT1 cell cycle regulatory function and DNMT1-mediated
gene silencing. Deacetylates RELA/NF-kappa-B p65 thereby
inhibiting its transactivating potential and augments apoptosis in
response to TNF-alpha. Deacetylates HIF1A, KAT5/TIP60, RB1 and
HIC1. Deacetylates FOXO1 resulting in its nuclear retention and
enhancement of its transcriptional activity leading to increased
gluconeogenesis in liver. Inhibits E2F1 transcriptional activity
and apoptotic function, possibly by deacetylation. Involved in
HES1- and HEY2-mediated transcriptional repression. In cooperation
with MYCN seems to be involved in transcriptional repression of
DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at
'Ser-62'. Deacetylates MEF2D. Required for antagonist-mediated
transcription suppression of AR-dependent genes which may be
linked to local deacetylation of histone H3. Represses HNF1A-
mediated transcription. Required for the repression of ESRRG by
CREBZF. Modulates AP-1 transcription factor activity. 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. Involved in lipid metabolism. Implicated in regulation
of adipogenesis and fat mobilization in white adipocytes by
repression of PPARG which probably involves association with NCOR1
and SMRT/NCOR2. Deacetylates ACSS2 leading to its activation, and
HMGCS1. Involved in liver and muscle metabolism. Through
deacteylation and activation of PPARGC1A is required to activate
fatty acid oxidation in skeletel muscle under low-glucose
conditions and is involved in glucose homeostasis. Involved in
regulation of PPARA and fatty acid beta-oxidation in liver.
Involved in positive regulation of insulin secretion in pancreatic
beta cells in response to glucose; the function seems to imply
transcriptional repression of UCP2. Proposed to deacetylate IRS2
thereby facilitating its insulin-induced tyrosine phosphorylation.
Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its
stability and transactivation in lipogenic gene expression.
Involved in DNA damage response by repressing genes which are
involved in DNA repair, such as XPC and TP73, deacetylating
XRCC6/Ku70, and faciliting 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. 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. Transcriptional
suppression of TP73 probably involves E2F4 and PCAF. Deacetylates
WRN thereby regulating its helicase and exonuclease activities and
regulates WRN nuclear translocation in response to DNA damage.
Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular
AP endonuclease activity by promoting the association of APEX1 to
XRCC1. Increases p53/TP53-mediated transcription-independent
apoptosis by blocking nuclear translocation of cytoplasmic
p53/TP53 and probably redirecting it to mitochondria. Deacetylates
XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to sequester BAX
away from mitochondria thereby inhibiting stress-induced
apoptosis. Is involved in autophagy, presumably by deacetylating
ATG5, ATG7 and MAP1LC3B/ATG8. Deacetylates AKT1 which leads to
enhanced binding of AKT1 and PDK1 to PIP3 and promotes their
activation. 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. 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. In endothelial cells is shown to inhibit
STK11/LBK1 activity and to promote its degradation. Deacetylates
SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation.
Deacetylates CIITA and augments its MHC class II transactivation
and contributes to its stability. Deacteylates MECOM/EVI1.
Deacetylates PML at 'Lys-487' and this deacetylation promotes PML
control of PER2 nuclear localization. During the neurogenic
transition, repress selective NOTCH1-target genes through histone
deacetylation in a BCL6-dependent manner and leading to neuronal
differentiation. 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. Deacetylates ARNTL/BMAL1 and histones at the circadian
gene promoters in order to facilitate repression by inhibitory
components of the circadian oscillator. Deacetylates PER2,
facilitating its ubiquitination and degradation by the proteosome.
Protects cardiomyocytes against palmitate-induced apoptosis
(PubMed:11672523, PubMed:12006491, PubMed:14976264,
PubMed:14980222, PubMed:15126506, PubMed:15152190,
PubMed:15205477, PubMed:15469825, PubMed:15692560,
PubMed:16079181, PubMed:16166628, PubMed:16892051,
PubMed:16998810, PubMed:17283066, PubMed:17334224,
PubMed:17505061, PubMed:17612497, PubMed:17620057,
PubMed:17936707, PubMed:18203716, PubMed:18296641,
PubMed:18662546, PubMed:18687677, PubMed:19188449,
PubMed:19220062, PubMed:19364925, PubMed:19690166,
PubMed:19934257, PubMed:20097625, PubMed:20100829,
PubMed:20203304, PubMed:20375098, PubMed:20620956,
PubMed:20670893, PubMed:20817729, PubMed:21149730,
PubMed:21245319, PubMed:21471201, PubMed:21504832,
PubMed:21555002, PubMed:21698133, PubMed:21701047,
PubMed:21775285, PubMed:21807113, PubMed:21841822,
PubMed:21890893, PubMed:21909281, PubMed:21947282,
PubMed:22274616). Deacetylates XBP1 isoform 2; deacetylation
decreases protein stability of XBP1 isoform 2 and inhibits its
transcriptional activity (PubMed:20955178). Involved in the CCAR2-
mediated regulation of PCK1 and NR1D1 (PubMed:24415752).
Deacetylates CTNB1 at 'Lys-49' (PubMed:24824780). In POMC (pro-
opiomelanocortin) neurons, required for leptin-induced activation
of PI3K signaling (By similarity). {ECO:0000250|UniProtKB:Q923E4,
ECO:0000269|PubMed:11672523, ECO:0000269|PubMed:12006491,
ECO:0000269|PubMed:14976264, ECO:0000269|PubMed:14980222,
ECO:0000269|PubMed:15126506, ECO:0000269|PubMed:15152190,
ECO:0000269|PubMed:15205477, ECO:0000269|PubMed:15469825,
ECO:0000269|PubMed:15692560, ECO:0000269|PubMed:16079181,
ECO:0000269|PubMed:16166628, ECO:0000269|PubMed:16892051,
ECO:0000269|PubMed:16998810, ECO:0000269|PubMed:17283066,
ECO:0000269|PubMed:17290224, ECO:0000269|PubMed:17334224,
ECO:0000269|PubMed:17505061, ECO:0000269|PubMed:17612497,
ECO:0000269|PubMed:17620057, ECO:0000269|PubMed:17936707,
ECO:0000269|PubMed:18203716, ECO:0000269|PubMed:18296641,
ECO:0000269|PubMed:18662546, ECO:0000269|PubMed:18687677,
ECO:0000269|PubMed:19188449, ECO:0000269|PubMed:19220062,
ECO:0000269|PubMed:19364925, ECO:0000269|PubMed:19690166,
ECO:0000269|PubMed:19934257, ECO:0000269|PubMed:20097625,
ECO:0000269|PubMed:20100829, ECO:0000269|PubMed:20203304,
ECO:0000269|PubMed:20375098, ECO:0000269|PubMed:20620956,
ECO:0000269|PubMed:20670893, ECO:0000269|PubMed:20817729,
ECO:0000269|PubMed:20955178, ECO:0000269|PubMed:21149730,
ECO:0000269|PubMed:21245319, ECO:0000269|PubMed:21471201,
ECO:0000269|PubMed:21504832, ECO:0000269|PubMed:21555002,
ECO:0000269|PubMed:21698133, ECO:0000269|PubMed:21701047,
ECO:0000269|PubMed:21775285, ECO:0000269|PubMed:21807113,
ECO:0000269|PubMed:21841822, ECO:0000269|PubMed:21890893,
ECO:0000269|PubMed:21909281, ECO:0000269|PubMed:21947282,
ECO:0000269|PubMed:22274616, ECO:0000269|PubMed:24415752,
ECO:0000269|PubMed:24824780}.
-!- FUNCTION: Isoform 2: Isoform 2 is shown to deacetylate '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:0000269|PubMed:20975832}.
-!- FUNCTION: (Microbial infection) In case of HIV-1 infection,
interacts with and deacetylates the viral Tat protein. The viral
Tat protein inhibits SIRT1 deacetylation activity toward RELA/NF-
kappa-B p65, thereby potentiates its transcriptional activity and
SIRT1 is proposed to contribute to T-cell hyperactivation during
infection. {ECO:0000269|PubMed:18329615}.
-!- 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:0000269|PubMed:21987377}.
-!- CATALYTIC ACTIVITY: NAD(+) + an acetylprotein = nicotinamide + O-
acetyl-ADP-ribose + a protein. {ECO:0000255|PROSITE-
ProRule:PRU00236, ECO:0000269|PubMed:12006491}.
-!- COFACTOR:
Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
Note=Binds 1 zinc ion per subunit. {ECO:0000250};
-!- ENZYME REGULATION: Inhibited by nicotinamide. 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. Negatively regulated by
CCAR2. {ECO:0000269|PubMed:12297502, ECO:0000269|PubMed:12939617,
ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18235502}.
-!- SUBUNIT: Interacts with XBP1 isoform 2 (PubMed:20955178). Found in
a complex with PCAF and MYOD1. Interacts with FOXO1; the
interaction deacetylates FOXO1, resulting in its nuclear retention
and promotion of its transcriptional activity 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 HIV-1 tat. Interacts with BCL6; leads to a
epigenetic repression of specific target genes. Interacts with
CLOCK, ARNTL/BMAL1 and PER2 (By similarity). Interacts with PPARA;
the interaction seems to be modulated by NAD(+) levels
(PubMed:24043310). Interacts with NR1H3 and this interaction is
inhibited in the presence of CCAR2. Interacts with CHEK2.
Interacts with p53/TP53. Exhibits a preferential interaction with
sumoylated CCAR2 over its unmodified form.
{ECO:0000250|UniProtKB:Q923E4, ECO:0000269|PubMed:12006491,
ECO:0000269|PubMed:12535671, ECO:0000269|PubMed:15684044,
ECO:0000269|PubMed:15692560, ECO:0000269|PubMed:15719057,
ECO:0000269|PubMed:16166628, ECO:0000269|PubMed:16892051,
ECO:0000269|PubMed:17680780, ECO:0000269|PubMed:17964266,
ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18235502,
ECO:0000269|PubMed:18329615, ECO:0000269|PubMed:18485871,
ECO:0000269|PubMed:19356714, ECO:0000269|PubMed:19690166,
ECO:0000269|PubMed:20042607, ECO:0000269|PubMed:20169165,
ECO:0000269|PubMed:20375098, ECO:0000269|PubMed:20955178,
ECO:0000269|PubMed:20975832, ECO:0000269|PubMed:21245319,
ECO:0000269|PubMed:21698133, ECO:0000269|PubMed:21909281,
ECO:0000269|PubMed:21933665, ECO:0000269|PubMed:23352644,
ECO:0000269|PubMed:24043310, ECO:0000269|PubMed:25361978,
ECO:0000269|PubMed:25406032, ECO:0000269|PubMed:25661920}.
-!- INTERACTION:
Q13085:ACACA; NbExp=3; IntAct=EBI-1802965, EBI-717681;
P31749:AKT1; NbExp=5; IntAct=EBI-1802965, EBI-296087;
P27695:APEX1; NbExp=6; IntAct=EBI-1802965, EBI-1048805;
Q8N163:CCAR2; NbExp=9; IntAct=EBI-1802965, EBI-355410;
P33076:CIITA; NbExp=4; IntAct=EBI-1802965, EBI-1538819;
Q9NS37:CREBZF; NbExp=3; IntAct=EBI-1802965, EBI-632965;
P68400:CSNK2A1; NbExp=4; IntAct=EBI-1802965, EBI-347804;
P67870:CSNK2B; NbExp=5; IntAct=EBI-1802965, EBI-348169;
P26358:DNMT1; NbExp=11; IntAct=EBI-1802965, EBI-719459;
Q01094:E2F1; NbExp=3; IntAct=EBI-1802965, EBI-448924;
Q09472:EP300; NbExp=2; IntAct=EBI-1802965, EBI-447295;
Q14192:FHL2; NbExp=2; IntAct=EBI-1802965, EBI-701903;
Q12778:FOXO1; NbExp=3; IntAct=EBI-1802965, EBI-1108782;
Q9R1E0:Foxo1 (xeno); NbExp=2; IntAct=EBI-1802965, EBI-1371343;
O43524:FOXO3; NbExp=5; IntAct=EBI-1802965, EBI-1644164;
P98177:FOXO4; NbExp=3; IntAct=EBI-1802965, EBI-4481939;
P51610:HCFC1; NbExp=2; IntAct=EBI-1802965, EBI-396176;
Q14469:HES1; NbExp=4; IntAct=EBI-1802965, EBI-2832522;
Q9UBP5:HEY2; NbExp=3; IntAct=EBI-1802965, EBI-750630;
Q9Y4H2:IRS2; NbExp=2; IntAct=EBI-1802965, EBI-1049582;
Q92831:KAT2B; NbExp=3; IntAct=EBI-1802965, EBI-477430;
Q03112:MECOM; NbExp=2; IntAct=EBI-1802965, EBI-1384862;
P42345:MTOR; NbExp=2; IntAct=EBI-1802965, EBI-359260;
P01106:MYC; NbExp=4; IntAct=EBI-1802965, EBI-447544;
P04198:MYCN; NbExp=3; IntAct=EBI-1802965, EBI-878369;
O60934:NBN; NbExp=5; IntAct=EBI-1802965, EBI-494844;
Q60974:Ncor1 (xeno); NbExp=2; IntAct=EBI-1802965, EBI-349004;
Q02577:NHLH2; NbExp=2; IntAct=EBI-1802965, EBI-5378683;
Q9HAN9:NMNAT1; NbExp=3; IntAct=EBI-1802965, EBI-3917542;
Q15466:NR0B2; NbExp=6; IntAct=EBI-1802965, EBI-3910729;
Q60644:Nr1h2 (xeno); NbExp=2; IntAct=EBI-1802965, EBI-5276809;
Q9Z0Y9:Nr1h3 (xeno); NbExp=2; IntAct=EBI-1802965, EBI-5276764;
P27986:PIK3R1; NbExp=3; IntAct=EBI-1802965, EBI-79464;
P37238:Pparg (xeno); NbExp=3; IntAct=EBI-1802965, EBI-5260705;
P37238-1:Pparg (xeno); NbExp=2; IntAct=EBI-1802965, EBI-6267861;
P10276:RARA; NbExp=3; IntAct=EBI-1802965, EBI-413374;
Q04206:RELA; NbExp=5; IntAct=EBI-1802965, EBI-73886;
Q86WX3:RPS19BP1; NbExp=11; IntAct=EBI-1802965, EBI-4479407;
Q8N122:RPTOR; NbExp=3; IntAct=EBI-1802965, EBI-1567928;
O43159:RRP8; NbExp=3; IntAct=EBI-1802965, EBI-2008793;
Q13573:SNW1; NbExp=7; IntAct=EBI-1802965, EBI-632715;
P36956-3:SREBF1; NbExp=2; IntAct=EBI-1802965, EBI-948338;
O54864:Suv39h1 (xeno); NbExp=4; IntAct=EBI-1802965, EBI-302230;
P04608:tat (xeno); NbExp=3; IntAct=EBI-1802965, EBI-6164389;
Q04724:TLE1; NbExp=4; IntAct=EBI-1802965, EBI-711424;
P04637:TP53; NbExp=13; IntAct=EBI-1802965, EBI-366083;
O15350:TP73; NbExp=4; IntAct=EBI-1802965, EBI-389606;
P49815:TSC2; NbExp=2; IntAct=EBI-1802965, EBI-396587;
Q14191:WRN; NbExp=9; IntAct=EBI-1802965, EBI-368417;
P23025:XPA; NbExp=8; IntAct=EBI-1802965, EBI-295222;
P12956:XRCC6; NbExp=7; IntAct=EBI-1802965, EBI-353208;
-!- SUBCELLULAR LOCATION: Nucleus, PML body
{ECO:0000269|PubMed:12006491}. Cytoplasm
{ECO:0000269|PubMed:20027304}. Nucleus
{ECO:0000269|PubMed:11672523, ECO:0000269|PubMed:15469825,
ECO:0000269|PubMed:16079181, ECO:0000269|PubMed:19934257,
ECO:0000269|PubMed:20027304, ECO:0000269|PubMed:20167603,
ECO:0000269|PubMed:20955178}. Note=Recruited to the nuclear bodies
via its interaction with PML (PubMed:12006491). Colocalized with
APEX1 in the nucleus (PubMed:19934257). May be found in nucleolus,
nuclear euchromatin, heterochromatin and inner membrane
(PubMed:15469825). Shuttles between nucleus and cytoplasm (By
similarity). Colocalizes in the nucleus with XBP1 isoform 2
(PubMed:20955178). {ECO:0000250|UniProtKB:Q923E4,
ECO:0000269|PubMed:12006491, ECO:0000269|PubMed:15469825,
ECO:0000269|PubMed:19934257, ECO:0000269|PubMed:20955178}.
-!- SUBCELLULAR LOCATION: SirtT1 75 kDa fragment: Cytoplasm
{ECO:0000269|PubMed:21987377}. Mitochondrion
{ECO:0000269|PubMed:21987377}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q96EB6-1; Sequence=Displayed;
Name=2; Synonyms=delta-exon8;
IsoId=Q96EB6-2; Sequence=VSP_042189;
-!- TISSUE SPECIFICITY: Widely expressed.
{ECO:0000269|PubMed:10381378}.
-!- INDUCTION: Up-regulated by methyl methanesulfonate (MMS). In H293T
cells by presence of rat calorie restriction (CR) serum.
{ECO:0000269|PubMed:15205477, ECO:0000269|PubMed:19934257}.
-!- PTM: Methylated on multiple lysine residues; methylation is
enhanced after DNA damage and is dispensable for deacetylase
activity toward p53/TP53.
-!- PTM: Phosphorylated. Phosphorylated by STK4/MST1, resulting in
inhibition of SIRT1-mediated p53/TP53 deacetylation.
Phosphorylation by MAPK8/JNK1 at Ser-27, Ser-47, and Thr-530 leads
to increased nuclear localization and enzymatic activity.
Phosphorylation at Thr-530 by DYRK1A and DYRK3 activates
deacetylase activity and promotes cell survival. Phosphorylation
by mammalian target of rapamycin complex 1 (mTORC1) at Ser-47
inhibits deacetylation activity. Phosphorylated by CaMK2, leading
to increased p53/TP53 and NF-kappa-B p65/RELA deacetylation
activity (By similarity). Phosphorylation at Ser-27 implicating
MAPK9 is linked to protein stability. There is some ambiguity for
some phosphosites: Ser-159/Ser-162 and Thr-544/Ser-545.
{ECO:0000250|UniProtKB:Q923E4, ECO:0000269|PubMed:18838864,
ECO:0000269|PubMed:19107194, ECO:0000269|PubMed:19236849,
ECO:0000269|PubMed:20027304, ECO:0000269|PubMed:21212262,
ECO:0000269|PubMed:21471201}.
-!- PTM: Proteolytically cleaved by cathepsin B upon TNF-alpha
treatment to yield catalytic inactive but stable SirtT1 75 kDa
fragment (75SirT1).
-!- PTM: S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent
protein deacetylase activity. {ECO:0000250}.
-!- MISCELLANEOUS: Red wine, which contains resveratrol, may
participate in activation of sirtuin proteins, and may therefore
participate in an extended lifespan as it has been observed in
yeast.
-!- MISCELLANEOUS: Calf histone H1 is used as substrate in the in
vitro deacetylation assay (PubMed:15469825). As, in vivo,
interaction occurs between SIRT1 with HIST1H1E, deacetylation has
been validated only for HIST1H1E. {ECO:0000305|PubMed:15469825}.
-!- MISCELLANEOUS: The reported ADP-ribosyltransferase activity of
sirtuins is likely some inefficient side reaction of the
deacetylase activity and may not be physiologically relevant.
{ECO:0000305|PubMed:19220062}.
-!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
{ECO:0000305}.
-!- SEQUENCE CAUTION:
Sequence=AAH12499.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
-!- WEB RESOURCE: Name=NIEHS-SNPs;
URL="http://egp.gs.washington.edu/data/sirt1/";
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/SIRT1ID44006ch10q21.html";
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; AF083106; AAD40849.2; -; mRNA.
EMBL; AF235040; AAG38486.1; -; mRNA.
EMBL; DQ278604; ABB72675.1; -; Genomic_DNA.
EMBL; AL133551; CAI16036.1; -; Genomic_DNA.
EMBL; BC012499; AAH12499.1; ALT_INIT; mRNA.
CCDS; CCDS7273.1; -. [Q96EB6-1]
RefSeq; NP_001135970.1; NM_001142498.1.
RefSeq; NP_001300978.1; NM_001314049.1.
RefSeq; NP_036370.2; NM_012238.4. [Q96EB6-1]
UniGene; Hs.369779; -.
PDB; 4I5I; X-ray; 2.50 A; A/B=241-516.
PDB; 4IF6; X-ray; 2.25 A; A=234-510, B=641-665.
PDB; 4IG9; X-ray; 2.64 A; A/C/E/G=234-510, B/D/F/H=641-665.
PDB; 4KXQ; X-ray; 1.85 A; A=234-510, B=641-663.
PDB; 4ZZH; X-ray; 3.10 A; A=183-505.
PDB; 4ZZI; X-ray; 2.73 A; A=183-505.
PDB; 4ZZJ; X-ray; 2.74 A; A=183-505.
PDB; 5BTR; X-ray; 3.20 A; A/B/C=143-665.
PDBsum; 4I5I; -.
PDBsum; 4IF6; -.
PDBsum; 4IG9; -.
PDBsum; 4KXQ; -.
PDBsum; 4ZZH; -.
PDBsum; 4ZZI; -.
PDBsum; 4ZZJ; -.
PDBsum; 5BTR; -.
ProteinModelPortal; Q96EB6; -.
SMR; Q96EB6; -.
BioGrid; 116983; 259.
DIP; DIP-29757N; -.
IntAct; Q96EB6; 128.
MINT; MINT-3052322; -.
STRING; 9606.ENSP00000212015; -.
BindingDB; Q96EB6; -.
ChEMBL; CHEMBL4506; -.
DrugBank; DB05073; SRT501.
GuidetoPHARMACOLOGY; 2707; -.
iPTMnet; Q96EB6; -.
PhosphoSitePlus; Q96EB6; -.
BioMuta; SIRT1; -.
DMDM; 38258633; -.
EPD; Q96EB6; -.
MaxQB; Q96EB6; -.
PaxDb; Q96EB6; -.
PeptideAtlas; Q96EB6; -.
PRIDE; Q96EB6; -.
Ensembl; ENST00000212015; ENSP00000212015; ENSG00000096717. [Q96EB6-1]
GeneID; 23411; -.
KEGG; hsa:23411; -.
UCSC; uc001jnd.3; human. [Q96EB6-1]
CTD; 23411; -.
DisGeNET; 23411; -.
GeneCards; SIRT1; -.
HGNC; HGNC:14929; SIRT1.
HPA; CAB003855; -.
HPA; HPA006295; -.
HPA; HPA052351; -.
MIM; 604479; gene.
neXtProt; NX_Q96EB6; -.
OpenTargets; ENSG00000096717; -.
PharmGKB; PA37935; -.
eggNOG; KOG2684; Eukaryota.
eggNOG; COG0846; LUCA.
GeneTree; ENSGT00870000136443; -.
HOGENOM; HOG000038016; -.
HOVERGEN; HBG054192; -.
InParanoid; Q96EB6; -.
KO; K11411; -.
OMA; SDSGTCQ; -.
OrthoDB; EOG091G07CT; -.
PhylomeDB; Q96EB6; -.
TreeFam; TF105896; -.
Reactome; R-HSA-1368082; RORA activates gene expression.
Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
Reactome; R-HSA-400253; Circadian Clock.
Reactome; R-HSA-427359; SIRT1 negatively regulates rRNA Expression.
SignaLink; Q96EB6; -.
SIGNOR; Q96EB6; -.
GeneWiki; Sirtuin_1; -.
GenomeRNAi; 23411; -.
PRO; PR:Q96EB6; -.
Proteomes; UP000005640; Chromosome 10.
Bgee; ENSG00000096717; -.
CleanEx; HS_SIRT1; -.
ExpressionAtlas; Q96EB6; baseline and differential.
Genevisible; Q96EB6; HS.
GO; GO:0005677; C:chromatin silencing complex; IDA:UniProtKB.
GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
GO; GO:0005829; C:cytosol; IDA:HPA.
GO; GO:0005739; C:mitochondrion; IDA:HPA.
GO; GO:0000790; C:nuclear chromatin; IDA:UniProtKB.
GO; GO:0005635; C:nuclear envelope; IDA:BHF-UCL.
GO; GO:0005719; C:nuclear euchromatin; IDA:UniProtKB.
GO; GO:0005720; C:nuclear heterochromatin; IDA:UniProtKB.
GO; GO:0005637; C:nuclear inner membrane; IDA:UniProtKB.
GO; GO:0005730; C:nucleolus; IDA:BHF-UCL.
GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0016605; C:PML body; IDA:BHF-UCL.
GO; GO:0033553; C:rDNA heterochromatin; IDA:UniProtKB.
GO; GO:0043425; F:bHLH transcription factor binding; IPI:UniProtKB.
GO; GO:0001046; F:core promoter sequence-specific DNA binding; IEA:Ensembl.
GO; GO:0019213; F:deacetylase activity; IDA:UniProtKB.
GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
GO; GO:0042393; F:histone binding; IPI:UniProtKB.
GO; GO:0004407; F:histone deacetylase activity; IDA:BHF-UCL.
GO; GO:0043398; F:HLH domain binding; IPI:BHF-UCL.
GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL.
GO; GO:1990254; F:keratin filament binding; IPI:UniProtKB.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0051019; F:mitogen-activated protein kinase binding; IPI:BHF-UCL.
GO; GO:0070403; F:NAD+ binding; IEA:InterPro.
GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:BHF-UCL.
GO; GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); ISS:UniProtKB.
GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IDA:UniProtKB.
GO; GO:0035257; F:nuclear hormone receptor binding; IPI:UniProtKB.
GO; GO:0002039; F:p53 binding; IPI:BHF-UCL.
GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
GO; GO:0033558; F:protein deacetylase activity; IDA:UniProtKB.
GO; GO:0003714; F:transcription corepressor activity; IDA:BHF-UCL.
GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IEA:Ensembl.
GO; GO:0001525; P:angiogenesis; IDA:UniProtKB.
GO; GO:0042595; P:behavioral response to starvation; IEA:Ensembl.
GO; GO:0007569; P:cell aging; TAS:BHF-UCL.
GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:BHF-UCL.
GO; GO:0071456; P:cellular response to hypoxia; IMP:UniProtKB.
GO; GO:0071479; P:cellular response to ionizing radiation; ISS:UniProtKB.
GO; GO:0009267; P:cellular response to starvation; ISS:BHF-UCL.
GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
GO; GO:0035356; P:cellular triglyceride homeostasis; ISS:UniProtKB.
GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
GO; GO:0006325; P:chromatin organization; IMP:UniProtKB.
GO; GO:0006342; P:chromatin silencing; TAS:ProtInc.
GO; GO:0000183; P:chromatin silencing at rDNA; IDA:UniProtKB.
GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
GO; GO:0006281; P:DNA repair; TAS:BHF-UCL.
GO; GO:0006260; P:DNA replication; TAS:BHF-UCL.
GO; GO:0000731; P:DNA synthesis involved in DNA repair; ISS:UniProtKB.
GO; GO:0006343; P:establishment of chromatin silencing; IDA:BHF-UCL.
GO; GO:0055089; P:fatty acid homeostasis; ISS:UniProtKB.
GO; GO:0016575; P:histone deacetylation; IDA:UniProtKB.
GO; GO:0070932; P:histone H3 deacetylation; IDA:BHF-UCL.
GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:UniProtKB.
GO; GO:0033210; P:leptin-mediated signaling pathway; ISS:UniProtKB.
GO; GO:0010934; P:macrophage cytokine production; ISS:UniProtKB.
GO; GO:0030225; P:macrophage differentiation; ISS:UniProtKB.
GO; GO:0006344; P:maintenance of chromatin silencing; IMP:BHF-UCL.
GO; GO:0006346; P:methylation-dependent chromatin silencing; TAS:UniProtKB.
GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; IMP:BHF-UCL.
GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; IDA:UniProtKB.
GO; GO:0030308; P:negative regulation of cell growth; IMP:BHF-UCL.
GO; GO:2000655; P:negative regulation of cellular response to testosterone stimulus; IMP:BHF-UCL.
GO; GO:2000773; P:negative regulation of cellular senescence; IDA:UniProtKB.
GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IDA:BHF-UCL.
GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:BHF-UCL.
GO; GO:0010629; P:negative regulation of gene expression; IMP:CACAO.
GO; GO:0051097; P:negative regulation of helicase activity; IDA:UniProtKB.
GO; GO:0071441; P:negative regulation of histone H3-K14 acetylation; IMP:CACAO.
GO; GO:1900113; P:negative regulation of histone H3-K9 trimethylation; IEA:Ensembl.
GO; GO:2000619; P:negative regulation of histone H4-K16 acetylation; IMP:CACAO.
GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:BHF-UCL.
GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl.
GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; IMP:BHF-UCL.
GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; IDA:UniProtKB.
GO; GO:0042326; P:negative regulation of phosphorylation; IMP:UniProtKB.
GO; GO:0031393; P:negative regulation of prostaglandin biosynthetic process; ISS:UniProtKB.
GO; GO:1901984; P:negative regulation of protein acetylation; IMP:CACAO.
GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:UniProtKB.
GO; GO:0043433; P:negative regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL.
GO; GO:0032007; P:negative regulation of TOR signaling; IMP:UniProtKB.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
GO; GO:0001542; P:ovulation from ovarian follicle; IEA:Ensembl.
GO; GO:0018394; P:peptidyl-lysine acetylation; IMP:UniProtKB.
GO; GO:0034983; P:peptidyl-lysine deacetylation; IDA:BHF-UCL.
GO; GO:0002821; P:positive regulation of adaptive immune response; IDA:UniProtKB.
GO; GO:1904179; P:positive regulation of adipose tissue development; ISS:UniProtKB.
GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
GO; GO:2000481; P:positive regulation of cAMP-dependent protein kinase activity; IMP:UniProtKB.
GO; GO:0008284; P:positive regulation of cell proliferation; IMP:UniProtKB.
GO; GO:2000774; P:positive regulation of cellular senescence; IDA:UniProtKB.
GO; GO:0010875; P:positive regulation of cholesterol efflux; ISS:UniProtKB.
GO; GO:0031937; P:positive regulation of chromatin silencing; IMP:BHF-UCL.
GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IEA:Ensembl.
GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:AgBase.
GO; GO:0051574; P:positive regulation of histone H3-K9 methylation; IMP:UniProtKB.
GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IDA:UniProtKB.
GO; GO:0016239; P:positive regulation of macroautophagy; IDA:UniProtKB.
GO; GO:2000111; P:positive regulation of macrophage apoptotic process; ISS:UniProtKB.
GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IDA:UniProtKB.
GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; IEA:Ensembl.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB.
GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
GO; GO:0031648; P:protein destabilization; IDA:UniProtKB.
GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
GO; GO:0000720; P:pyrimidine dimer repair by nucleotide-excision repair; IMP:UniProtKB.
GO; GO:0042981; P:regulation of apoptotic process; IMP:UniProtKB.
GO; GO:0070857; P:regulation of bile acid biosynthetic process; ISS:UniProtKB.
GO; GO:0090335; P:regulation of brown fat cell differentiation; ISS:UniProtKB.
GO; GO:0042127; P:regulation of cell proliferation; IMP:BHF-UCL.
GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome.
GO; GO:0032071; P:regulation of endodeoxyribonuclease activity; IMP:UniProtKB.
GO; GO:0010906; P:regulation of glucose metabolic process; ISS:UniProtKB.
GO; GO:0010883; P:regulation of lipid storage; ISS:UniProtKB.
GO; GO:0007346; P:regulation of mitotic cell cycle; IDA:UniProtKB.
GO; GO:0035358; P:regulation of peroxisome proliferator activated receptor signaling pathway; ISS:BHF-UCL.
GO; GO:0033158; P:regulation of protein import into nucleus, translocation; IMP:UniProtKB.
GO; GO:0071900; P:regulation of protein serine/threonine kinase activity; IMP:AgBase.
GO; GO:0034391; P:regulation of smooth muscle cell apoptotic process; ISS:UniProtKB.
GO; GO:0042542; P:response to hydrogen peroxide; IDA:UniProtKB.
GO; GO:0032868; P:response to insulin; ISS:UniProtKB.
GO; GO:0044321; P:response to leptin; ISS:UniProtKB.
GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
GO; GO:0006364; P:rRNA processing; IEA:UniProtKB-KW.
GO; GO:0000012; P:single strand break repair; IMP:UniProtKB.
GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
GO; GO:0090400; P:stress-induced premature senescence; IMP:CACAO.
GO; GO:0006642; P:triglyceride mobilization; ISS:BHF-UCL.
GO; GO:0070914; P:UV-damage excision repair; IMP:CACAO.
GO; GO:0016032; P:viral process; IEA:UniProtKB-KW.
GO; GO:0050872; P:white fat cell differentiation; ISS:BHF-UCL.
Gene3D; 3.40.50.1220; -; 1.
InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
InterPro; IPR003000; Sirtuin.
InterPro; IPR026590; Ssirtuin_cat_dom.
Pfam; PF02146; SIR2; 1.
SUPFAM; SSF52467; SSF52467; 1.
PROSITE; PS50305; SIRTUIN; 1.
1: Evidence at protein level;
3D-structure; Acetylation; Alternative splicing; Apoptosis;
Biological rhythms; Complete proteome; Cytoplasm;
Developmental protein; Differentiation; Host-virus interaction;
Hydrolase; Metal-binding; Methylation; Mitochondrion; Myogenesis; NAD;
Nucleus; Phosphoprotein; Polymorphism; Reference proteome;
rRNA processing; S-nitrosylation; Transcription;
Transcription regulation; Zinc.
INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330,
ECO:0000244|PubMed:20068231,
ECO:0000244|PubMed:21406692,
ECO:0000244|PubMed:22223895,
ECO:0000244|PubMed:22814378}.
CHAIN 2 747 NAD-dependent protein deacetylase
sirtuin-1.
/FTId=PRO_0000110256.
CHAIN 2 533 SirtT1 75 kDa fragment.
/FTId=PRO_0000415289.
DOMAIN 244 498 Deacetylase sirtuin-type.
{ECO:0000255|PROSITE-ProRule:PRU00236}.
NP_BIND 261 280 NAD. {ECO:0000250}.
NP_BIND 345 348 NAD. {ECO:0000250}.
NP_BIND 440 442 NAD. {ECO:0000250}.
NP_BIND 465 467 NAD. {ECO:0000250}.
REGION 2 268 Interaction with HIST1H1E.
REGION 2 139 Interaction with CLOCK.
{ECO:0000250|UniProtKB:Q923E4}.
REGION 143 541 Interaction with CCAR2.
REGION 256 259 Required for interaction with the
sumoylated form of CCAR2.
{ECO:0000269|PubMed:25406032}.
REGION 538 540 Phosphorylated at one of three serine
residues.
MOTIF 32 39 Nuclear localization signal.
{ECO:0000250}.
MOTIF 138 145 Nuclear export signal. {ECO:0000250}.
MOTIF 223 230 Nuclear localization signal.
{ECO:0000250}.
MOTIF 425 431 Nuclear export signal. {ECO:0000250}.
COMPBIAS 54 98 Ala-rich.
COMPBIAS 122 127 Poly-Asp.
COMPBIAS 128 134 Poly-Glu.
ACT_SITE 363 363 Proton acceptor.
METAL 371 371 Zinc. {ECO:0000255|PROSITE-
ProRule:PRU00236}.
METAL 374 374 Zinc. {ECO:0000255|PROSITE-
ProRule:PRU00236}.
METAL 395 395 Zinc. {ECO:0000255|PROSITE-
ProRule:PRU00236}.
METAL 398 398 Zinc. {ECO:0000255|PROSITE-
ProRule:PRU00236}.
BINDING 482 482 NAD; via amide nitrogen. {ECO:0000250}.
MOD_RES 2 2 N-acetylalanine.
{ECO:0000244|PubMed:19413330,
ECO:0000244|PubMed:20068231,
ECO:0000244|PubMed:21406692,
ECO:0000244|PubMed:22223895,
ECO:0000244|PubMed:22814378}.
MOD_RES 14 14 Phosphoserine.
{ECO:0000244|PubMed:20068231,
ECO:0000244|PubMed:21406692,
ECO:0000244|PubMed:23186163,
ECO:0000244|PubMed:24275569,
ECO:0000269|PubMed:19107194}.
MOD_RES 26 26 Phosphoserine.
{ECO:0000269|PubMed:19107194}.
MOD_RES 27 27 Phosphoserine; by MAPK8.
{ECO:0000244|PubMed:23186163,
ECO:0000244|PubMed:24275569,
ECO:0000269|PubMed:18838864,
ECO:0000269|PubMed:19107194,
ECO:0000269|PubMed:20027304}.
MOD_RES 47 47 Phosphoserine; by MAPK8.
{ECO:0000244|PubMed:16964243,
ECO:0000244|PubMed:20068231,
ECO:0000244|PubMed:21406692,
ECO:0000244|PubMed:23186163,
ECO:0000269|PubMed:18838864,
ECO:0000269|PubMed:19107194,
ECO:0000269|PubMed:20027304,
ECO:0000269|PubMed:21471201}.
MOD_RES 159 159 Phosphoserine.
{ECO:0000305|PubMed:19107194}.
MOD_RES 162 162 Phosphoserine.
{ECO:0000305|PubMed:19107194}.
MOD_RES 172 172 Phosphoserine.
{ECO:0000269|PubMed:19107194}.
MOD_RES 173 173 Phosphoserine.
{ECO:0000269|PubMed:19107194}.
MOD_RES 395 395 S-nitrosocysteine.
{ECO:0000250|UniProtKB:Q923E4}.
MOD_RES 398 398 S-nitrosocysteine.
{ECO:0000250|UniProtKB:Q923E4}.
MOD_RES 530 530 Phosphothreonine; by DYRK1A, DYRK3 and
MAPK8. {ECO:0000244|PubMed:19690332,
ECO:0000269|PubMed:19107194,
ECO:0000269|PubMed:20027304}.
MOD_RES 535 535 Phosphoserine.
{ECO:0000244|PubMed:19690332}.
MOD_RES 544 544 Phosphothreonine.
{ECO:0000305|PubMed:19107194}.
MOD_RES 545 545 Phosphoserine.
{ECO:0000305|PubMed:19107194}.
MOD_RES 659 659 Phosphoserine; by CaMK2.
{ECO:0000250|UniProtKB:Q923E4}.
MOD_RES 661 661 Phosphoserine; by CaMK2.
{ECO:0000305|PubMed:19236849}.
MOD_RES 719 719 Phosphothreonine.
{ECO:0000244|PubMed:18669648,
ECO:0000244|PubMed:19690332,
ECO:0000244|PubMed:21406692,
ECO:0000244|PubMed:23186163,
ECO:0000269|PubMed:19107194}.
MOD_RES 747 747 Phosphoserine.
{ECO:0000269|PubMed:19107194}.
VAR_SEQ 454 639 Missing (in isoform 2). {ECO:0000305}.
/FTId=VSP_042189.
VARIANT 3 3 D -> E (in dbSNP:rs35671182).
{ECO:0000269|Ref.3}.
/FTId=VAR_025148.
VARIANT 484 484 V -> D (in dbSNP:rs1063111).
/FTId=VAR_051976.
MUTAGEN 27 27 S->A: Greatly diminishes phosphorylation
by MAPK8; when associated with A-47 and
A-530. {ECO:0000269|PubMed:20027304}.
MUTAGEN 47 47 S->A: Blocks residue phosphorylation,
restores deacetylation activity and
inhibits DNA damage-induced apoptosis.
{ECO:0000269|PubMed:20027304,
ECO:0000269|PubMed:21471201}.
MUTAGEN 47 47 S->A: Greatly diminishes phosphorylation
by MAPK8; when associated with A-27 and
A-530. {ECO:0000269|PubMed:20027304,
ECO:0000269|PubMed:21471201}.
MUTAGEN 233 233 K->R: Impairs in vitro methylation by
SETD7; when associated with R-235, R-236
and R-238. {ECO:0000269|PubMed:21245319}.
MUTAGEN 235 235 K->R: Impairs in vitro methylation by
SETD7; when associated with R-233, R-236
and R-238. {ECO:0000269|PubMed:21245319}.
MUTAGEN 236 236 K->R: Impairs in vitro methylation by
SETD7; when associated with R-233, R-235
and R-238. {ECO:0000269|PubMed:21245319}.
MUTAGEN 238 238 K->R: Impairs in vitro methylation by
SETD7; when associated with R-233, R-235a
and R-236. {ECO:0000269|PubMed:21245319}.
MUTAGEN 256 257 II->KK: Loss of interaction with the
sumoylated form of CCAR2. No effect on
its deacetylation activity.
{ECO:0000269|PubMed:25406032}.
MUTAGEN 363 363 H->Y: Loss of function. Reduces the
interaction with CCAR2 and APEX1.
Increases acetylation of APEX1.
{ECO:0000269|PubMed:11672523,
ECO:0000269|PubMed:12006491,
ECO:0000269|PubMed:12535671,
ECO:0000269|PubMed:17290224,
ECO:0000269|PubMed:18004385,
ECO:0000269|PubMed:18235501,
ECO:0000269|PubMed:18485871,
ECO:0000269|PubMed:19934257,
ECO:0000269|PubMed:25406032}.
MUTAGEN 474 474 F->A: Abolishes phosphorylation at Ser-
47, restores deacetylation activity and
inhibits DNA damage-induced apoptosis.
{ECO:0000269|PubMed:21471201}.
MUTAGEN 530 530 T->A: Greatly diminishes phosphorylation
by MAPK8; when associated with A-27 and
A-47. {ECO:0000269|PubMed:19107194,
ECO:0000269|PubMed:20027304}.
MUTAGEN 530 530 T->A: Reduces in vitro phosphorylation by
CDK1. Impairs cell proliferation and cell
cycle progression; when associated with
A-540. {ECO:0000269|PubMed:19107194,
ECO:0000269|PubMed:20027304}.
MUTAGEN 540 540 S->A: Reduces in vitro phosphorylation by
CDK1. Impairs cell proliferation and cell
cycle progression; when associated with
A-530. {ECO:0000269|PubMed:19107194}.
MUTAGEN 659 659 S->A: Reduces in vitro phosphorylation by
CaMK2; when associated with S-661.
Greatly reduces in vivo phosphorylation;
when associated with A-661.
{ECO:0000269|PubMed:19236849}.
MUTAGEN 661 661 S->A: Reduces in vitro phosphorylation by
CaMK2; when associated with S-659.
Greatly reduces in vivo phosphorylation;
when associated with A-659.
{ECO:0000269|PubMed:19236849}.
MUTAGEN 684 684 S->A: No effect on phosphorylation (in
vitro and in vivo).
{ECO:0000269|PubMed:19236849}.
CONFLICT 386 389 DIFN -> ALFS (in Ref. 5; AAH12499).
{ECO:0000305}.
HELIX 184 194 {ECO:0000244|PDB:4ZZI}.
HELIX 198 205 {ECO:0000244|PDB:4ZZI}.
HELIX 217 228 {ECO:0000244|PDB:4ZZI}.
HELIX 243 252 {ECO:0000244|PDB:4KXQ}.
STRAND 254 260 {ECO:0000244|PDB:4KXQ}.
HELIX 262 268 {ECO:0000244|PDB:4KXQ}.
STRAND 273 275 {ECO:0000244|PDB:4KXQ}.
TURN 276 278 {ECO:0000244|PDB:4IG9}.
HELIX 279 286 {ECO:0000244|PDB:4KXQ}.
STRAND 290 292 {ECO:0000244|PDB:4KXQ}.
HELIX 293 297 {ECO:0000244|PDB:4KXQ}.
HELIX 299 304 {ECO:0000244|PDB:4KXQ}.
HELIX 307 312 {ECO:0000244|PDB:4KXQ}.
HELIX 313 316 {ECO:0000244|PDB:4KXQ}.
STRAND 318 320 {ECO:0000244|PDB:4I5I}.
HELIX 325 335 {ECO:0000244|PDB:4KXQ}.
STRAND 339 344 {ECO:0000244|PDB:4KXQ}.
HELIX 350 354 {ECO:0000244|PDB:4KXQ}.
STRAND 358 361 {ECO:0000244|PDB:4KXQ}.
STRAND 364 371 {ECO:0000244|PDB:4KXQ}.
TURN 372 374 {ECO:0000244|PDB:4KXQ}.
STRAND 377 379 {ECO:0000244|PDB:4KXQ}.
HELIX 380 382 {ECO:0000244|PDB:4KXQ}.
HELIX 384 388 {ECO:0000244|PDB:4KXQ}.
STRAND 396 398 {ECO:0000244|PDB:4KXQ}.
STRAND 406 411 {ECO:0000244|PDB:4KXQ}.
HELIX 420 429 {ECO:0000244|PDB:4KXQ}.
TURN 430 432 {ECO:0000244|PDB:4KXQ}.
STRAND 435 440 {ECO:0000244|PDB:4KXQ}.
HELIX 448 450 {ECO:0000244|PDB:4KXQ}.
HELIX 451 454 {ECO:0000244|PDB:4KXQ}.
STRAND 461 467 {ECO:0000244|PDB:4KXQ}.
STRAND 475 480 {ECO:0000244|PDB:4KXQ}.
HELIX 482 493 {ECO:0000244|PDB:4KXQ}.
HELIX 495 500 {ECO:0000244|PDB:4KXQ}.
STRAND 506 510 {ECO:0000244|PDB:5BTR}.
STRAND 643 645 {ECO:0000244|PDB:4KXQ}.
TURN 646 648 {ECO:0000244|PDB:4KXQ}.
STRAND 649 651 {ECO:0000244|PDB:4KXQ}.
HELIX 656 658 {ECO:0000244|PDB:4KXQ}.
SEQUENCE 747 AA; 81681 MW; 2D3BEA6D73DA229F CRC64;
MADEAALALQ PGGSPSAAGA DREAASSPAG EPLRKRPRRD GPGLERSPGE PGGAAPEREV
PAAARGCPGA AAAALWREAE AEAAAAGGEQ EAQATAAAGE GDNGPGLQGP SREPPLADNL
YDEDDDDEGE EEEEAAAAAI GYRDNLLFGD EIITNGFHSC ESDEEDRASH ASSSDWTPRP
RIGPYTFVQQ HLMIGTDPRT ILKDLLPETI PPPELDDMTL WQIVINILSE PPKRKKRKDI
NTIEDAVKLL QECKKIIVLT GAGVSVSCGI PDFRSRDGIY ARLAVDFPDL PDPQAMFDIE
YFRKDPRPFF KFAKEIYPGQ FQPSLCHKFI ALSDKEGKLL RNYTQNIDTL EQVAGIQRII
QCHGSFATAS CLICKYKVDC EAVRGDIFNQ VVPRCPRCPA DEPLAIMKPE IVFFGENLPE
QFHRAMKYDK DEVDLLIVIG SSLKVRPVAL IPSSIPHEVP QILINREPLP HLHFDVELLG
DCDVIINELC HRLGGEYAKL CCNPVKLSEI TEKPPRTQKE LAYLSELPPT PLHVSEDSSS
PERTSPPDSS VIVTLLDQAA KSNDDLDVSE SKGCMEEKPQ EVQTSRNVES IAEQMENPDL
KNVGSSTGEK NERTSVAGTV RKCWPNRVAK EQISRRLDGN QYLFLPPNRY IFHGAEVYSD
SEDDVLSSSS CGSNSDSGTC QSPSLEEPME DESEIEEFYN GLEDEPDVPE RAGGAGFGTD
GDDQEAINEA ISVKQEVTDM NYPSNKS


Related products :

Catalog number Product name Quantity
18-003-43079 NAD-dependent deacetylase sirtuin-1 - EC 3.5.1.-; hSIRT1; hSIR2; SIR2-like protein 1 Polyclonal 0.05 mg Aff Pur
18-003-43079 NAD-dependent deacetylase sirtuin-1 - EC 3.5.1.-; hSIRT1; hSIR2; SIR2-like protein 1 Polyclonal 0.1 mg Protein A
EIAAB38505 Homo sapiens,hSIR2,hSIRT1,Human,NAD-dependent deacetylase sirtuin-1,SIR2L1,SIR2-like protein 1,SIRT1
18-003-43078 NAD-dependent deacetylase sirtuin-2 - EC 3.5.1.-; SIR2-like; SIR2-like protein 2 Polyclonal 0.05 mg Aff Pur
18-003-43078 NAD-dependent deacetylase sirtuin-2 - EC 3.5.1.-; SIR2-like; SIR2-like protein 2 Polyclonal 0.1 mg Protein A
EIAAB38504 Mouse,mSIR2a,Mus musculus,NAD-dependent deacetylase sirtuin-1,Sir2,SIR2alpha,Sir2l1,SIR2-like protein 1,Sirt1
18-003-43080 NAD-dependent deacetylase sirtuin-3. mitochondrial - EC 3.5.1.-; SIR2-like protein 3; hSIRT3 Polyclonal 0.1 mg Protein A
18-003-43080 NAD-dependent deacetylase sirtuin-3. mitochondrial - EC 3.5.1.-; SIR2-like protein 3; hSIRT3 Polyclonal 0.05 mg Aff Pur
EIAAB38513 Mouse,Mus musculus,NAD-dependent deacetylase sirtuin-6,Sir2l6,SIR2-like protein 6,Sirt6
EIAAB38510 Mouse,Mus musculus,NAD-dependent deacetylase sirtuin-5,Sir2l5,SIR2-like protein 5,Sirt5
EIAAB38516 Mouse,Mus musculus,NAD-dependent deacetylase sirtuin-7,Sir2l7,SIR2-like protein 7,Sirt7
EIAAB38511 Homo sapiens,Human,NAD-dependent deacetylase sirtuin-5,SIR2L5,SIR2-like protein 5,SIRT5
E0430r ELISA NAD-dependent deacetylase sirtuin-2,Rat,Rattus norvegicus,Sir2l2,SIR2-like protein 2,Sirt2 96T
U0430r CLIA NAD-dependent deacetylase sirtuin-2,Rat,Rattus norvegicus,Sir2l2,SIR2-like protein 2,Sirt2 96T
E0430r ELISA kit NAD-dependent deacetylase sirtuin-2,Rat,Rattus norvegicus,Sir2l2,SIR2-like protein 2,Sirt2 96T
EIAAB38515 Homo sapiens,Human,NAD-dependent deacetylase sirtuin-7,SIR2L7,SIR2-like protein 7,SIRT7
EIAAB38514 Homo sapiens,Human,NAD-dependent deacetylase sirtuin-6,SIR2L6,SIR2-like protein 6,SIRT6
U0430m CLIA Mouse,mSIR2L2,Mus musculus,NAD-dependent deacetylase sirtuin-2,Sir2l2,SIR2-like protein 2,Sirt2 96T
E2135m ELISA Mouse,mSIR2L3,Mus musculus,NAD-dependent deacetylase sirtuin-3,Sir2l3,SIR2-like protein 3,Sirt3 96T
E2135m ELISA kit Mouse,mSIR2L3,Mus musculus,NAD-dependent deacetylase sirtuin-3,Sir2l3,SIR2-like protein 3,Sirt3 96T
U2135m CLIA kit Mouse,mSIR2L3,Mus musculus,NAD-dependent deacetylase sirtuin-3,Sir2l3,SIR2-like protein 3,Sirt3 96T
U2135m CLIA Mouse,mSIR2L3,Mus musculus,NAD-dependent deacetylase sirtuin-3,Sir2l3,SIR2-like protein 3,Sirt3 96T
E0430m ELISA kit Mouse,mSIR2L2,Mus musculus,NAD-dependent deacetylase sirtuin-2,Sir2l2,SIR2-like protein 2,Sirt2 96T
E0430m ELISA Mouse,mSIR2L2,Mus musculus,NAD-dependent deacetylase sirtuin-2,Sir2l2,SIR2-like protein 2,Sirt2 96T
U0430h CLIA Homo sapiens,Human,NAD-dependent deacetylase sirtuin-2,SIR2L,SIR2L2,SIR2-like protein 2,SIRT2 96T


 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur





GENTAUR Ltd.
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017

BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG

france@gentaur.com | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: 0035929830070
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur