SIR1_HUMAN
ID SIR1_HUMAN Reviewed; 747 AA.
AC Q96EB6; Q2XNF6; Q5JVQ0; Q9GZR9; Q9Y6F0;
DT 31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=NAD-dependent protein deacetylase sirtuin-1 {ECO:0000305};
DE Short=hSIRT1;
DE EC=2.3.1.286 {ECO:0000269|PubMed:12006491, ECO:0000269|PubMed:30409912, ECO:0000269|PubMed:32034146};
DE AltName: Full=NAD-dependent protein deacylase sirtuin-1 {ECO:0000305};
DE EC=2.3.1.- {ECO:0000269|PubMed:28497810};
DE AltName: Full=Regulatory protein SIR2 homolog 1;
DE AltName: Full=SIR2-like protein 1;
DE Short=hSIR2;
DE Contains:
DE RecName: Full=SirtT1 75 kDa fragment {ECO:0000303|PubMed:21987377};
DE Short=75SirT1 {ECO:0000303|PubMed:21987377};
GN Name=SIRT1 {ECO:0000303|PubMed:12535671, ECO:0000312|HGNC:HGNC:14929};
GN Synonyms=SIR2L1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=10381378; DOI=10.1006/bbrc.1999.0897;
RA Frye R.A.;
RT "Characterization of five human cDNAs with homology to the yeast SIR2 gene:
RT Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-
RT ribosyltransferase activity.";
RL Biochem. Biophys. Res. Commun. 260:273-279(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH HES1 AND HEY2,
RP MUTAGENESIS OF HIS-363, AND ACTIVE SITE.
RX PubMed=12535671; DOI=10.1016/s0006-291x(02)03020-6;
RA Takata T., Ishikawa F.;
RT "Human Sir2-related protein SIRT1 associates with the bHLH repressors HES1
RT and HEY2 and is involved in HES1- and HEY2-mediated transcriptional
RT repression.";
RL Biochem. Biophys. Res. Commun. 301:250-257(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLU-3.
RG NIEHS SNPs program;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 124-747.
RC TISSUE=Prostate;
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 [6]
RP FUNCTION IN DEACETYLATION OF TP53, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP HIS-363, AND ACTIVE SITE.
RX PubMed=11672523; DOI=10.1016/s0092-8674(01)00527-x;
RA Vaziri H., Dessain S.K., Ng Eaton E., Imai S., Frye R.A., Pandita T.K.,
RA Guarente L., Weinberg R.A.;
RT "hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase.";
RL Cell 107:149-159(2001).
RN [7]
RP FUNCTION, ENZYME ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH PML,
RP MUTAGENESIS OF HIS-363, AND ACTIVE SITE.
RX PubMed=12006491; DOI=10.1093/emboj/21.10.2383;
RA Langley E., Pearson M., Faretta M., Bauer U.-M., Frye R.A., Minucci S.,
RA Pelicci P.G., Kouzarides T.;
RT "Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular
RT senescence.";
RL EMBO J. 21:2383-2396(2002).
RN [8]
RP ACTIVITY REGULATION.
RX PubMed=12297502; DOI=10.1074/jbc.m205670200;
RA Bitterman K.J., Anderson R.M., Cohen H.Y., Latorre-Esteves M.,
RA Sinclair D.A.;
RT "Inhibition of silencing and accelerated aging by nicotinamide, a putative
RT negative regulator of yeast sir2 and human SIRT1.";
RL J. Biol. Chem. 277:45099-45107(2002).
RN [9]
RP ACTIVITY REGULATION.
RX PubMed=12939617; DOI=10.1038/nature01960;
RA Howitz K.T., Bitterman K.J., Cohen H.Y., Lamming D.W., Lavu S., Wood J.G.,
RA Zipkin R.E., Chung P., Kisielewski A., Zhang L.-L., Scherer B.,
RA Sinclair D.A.;
RT "Small molecule activators of sirtuins extend Saccharomyces cerevisiae
RT lifespan.";
RL Nature 425:191-196(2003).
RN [10]
RP FUNCTION.
RX PubMed=15152190; DOI=10.1038/sj.emboj.7600244;
RA Frye R.A., Mayo M.W.;
RT "Modulation of NF-kappaB-dependent transcription and cell survival by the
RT SIRT1 deacetylase.";
RL EMBO J. 23:2369-2380(2004).
RN [11]
RP FUNCTION IN DEACETYLATION OF FOXO3, AND FUNCTION IN REGULATION OF FOXO3.
RX PubMed=14980222; DOI=10.1016/s0092-8674(04)00126-6;
RA Motta M.C., Divecha N., Lemieux M., Kamel C., Chen D., Gu W., Bultsma Y.,
RA McBurney M., Guarente L.;
RT "Mammalian SIRT1 represses forkhead transcription factors.";
RL Cell 116:551-563(2004).
RN [12]
RP FUNCTION IN DEACETYLATION OF MLLT7.
RX PubMed=15126506; DOI=10.1074/jbc.m401138200;
RA van der Horst A., Tertoolen L.G.J., de Vries-Smits L.M.M., Frye R.A.,
RA Medema R.H., Burgering B.M.T.;
RT "FOXO4 is acetylated upon peroxide stress and deacetylated by the longevity
RT protein hSir2(SIRT1).";
RL J. Biol. Chem. 279:28873-28879(2004).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15469825; DOI=10.1016/j.molcel.2004.08.031;
RA Vaquero A., Scher M., Lee D., Erdjument-Bromage H., Tempst P., Reinberg D.;
RT "Human SirT1 interacts with histone H1 and promotes formation of
RT facultative heterochromatin.";
RL Mol. Cell 16:93-105(2004).
RN [14]
RP FUNCTION IN DEACETYLATION OF FOXO3, AND FUNCTION IN REGULATION OF FOXO3.
RX PubMed=14976264; DOI=10.1126/science.1094637;
RA Brunet A., Sweeney L.B., Sturgill J.F., Chua K.F., Greer P.L., Lin Y.,
RA Tran H., Ross S.E., Mostoslavsky R., Cohen H.Y., Hu L.S., Cheng H.L.,
RA Jedrychowski M.P., Gygi S.P., Sinclair D.A., Alt F.W., Greenberg M.E.;
RT "Stress-dependent regulation of FOXO transcription factors by the SIRT1
RT deacetylase.";
RL Science 303:2011-2015(2004).
RN [15]
RP FUNCTION IN DEACETYLATION OF XRCC6, AND INDUCTION BY CR.
RX PubMed=15205477; DOI=10.1126/science.1099196;
RA Cohen H.Y., Miller C., Bitterman K.J., Wall N.R., Hekking B., Kessler B.,
RA Howitz K.T., Gorospe M., de Cabo R., Sinclair D.A.;
RT "Calorie restriction promotes mammalian cell survival by inducing the SIRT1
RT deacetylase.";
RL Science 305:390-392(2004).
RN [16]
RP INTERACTION WITH FHL2, FUNCTION IN DEACETYLATION OF FOXO1, AND FUNCTION IN
RP REGULATION OF FOXO1.
RX PubMed=15692560; DOI=10.1038/sj.emboj.7600570;
RA Yang Y., Hou H., Haller E.M., Nicosia S.V., Bai W.;
RT "Suppression of FOXO1 activity by FHL2 through SIRT1-mediated
RT deacetylation.";
RL EMBO J. 24:1021-1032(2005).
RN [17]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16079181; DOI=10.1091/mbc.e05-01-0033;
RA Michishita E., Park J.Y., Burneskis J.M., Barrett J.C., Horikawa I.;
RT "Evolutionarily conserved and nonconserved cellular localizations and
RT functions of human SIRT proteins.";
RL Mol. Biol. Cell 16:4623-4635(2005).
RN [18]
RP FUNCTION IN DEACETYLATION OF MEF2D, AND INTERACTION WITH HDAC4.
RX PubMed=16166628; DOI=10.1128/mcb.25.19.8456-8464.2005;
RA Zhao X., Sternsdorf T., Bolger T.A., Evans R.M., Yao T.-P.;
RT "Regulation of MEF2 by histone deacetylase 4- and SIRT1 deacetylase-
RT mediated lysine modifications.";
RL Mol. Cell. Biol. 25:8456-8464(2005).
RN [19]
RP INTERACTION WITH HIV-1 TAT (MICROBIAL INFECTION).
RX PubMed=15719057; DOI=10.1371/journal.pbio.0030041;
RA Pagans S., Pedal A., North B.J., Kaehlcke K., Marshall B.L., Dorr A.,
RA Hetzer-Egger C., Henklein P., Frye R., McBurney M.W., Hruby H., Jung M.,
RA Verdin E., Ott M.;
RT "SIRT1 regulates HIV transcription via Tat deacetylation.";
RL PLoS Biol. 3:210-220(2005).
RN [20]
RP ASSOCIATION WITH THE PRC4 COMPLEX, AND INTERACTION WITH SUZ12.
RX PubMed=15684044; DOI=10.1073/pnas.0409875102;
RA Kuzmichev A., Margueron R., Vaquero A., Preissner T.S., Scher M.,
RA Kirmizis A., Ouyang X., Brockdorff N., Abate-Shen C., Farnham P.J.,
RA Reinberg D.;
RT "Composition and histone substrates of polycomb repressive group complexes
RT change during cellular differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1859-1864(2005).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [22]
RP FUNCTION, AND INTERACTION WITH E2F1.
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 [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 INTERACTION WITH TLE1.
RX PubMed=17680780; DOI=10.1042/bj20070817;
RA Ghosh H.S., Spencer J.V., Ng B., McBurney M.W., Robbins P.D.;
RT "Sirt1 interacts with transducin-like enhancer of split-1 to inhibit
RT nuclear factor kappaB-mediated transcription.";
RL Biochem. J. 408:105-111(2007).
RN [25]
RP FUNCTION, MUTAGENESIS OF HIS-363, AND ACTIVE SITE.
RX PubMed=17290224; DOI=10.1038/sj.emboj.7601563;
RA Pedersen T.A., Bereshchenko O., Garcia-Silva S., Ermakova O., Kurz E.,
RA Mandrup S., Porse B.T., Nerlov C.;
RT "Distinct C/EBPalpha motifs regulate lipogenic and gluconeogenic gene
RT expression in vivo.";
RL EMBO J. 26:1081-1093(2007).
RN [26]
RP FUNCTION IN DEACETYLATION OF XRCC6, AND FUNCTION IN DNA REPAIR.
RX PubMed=17334224; DOI=10.1038/emm.2007.2;
RA Jeong J., Juhn K., Lee H., Kim S.H., Min B.H., Lee K.M., Cho M.H.,
RA Park G.H., Lee K.H.;
RT "SIRT1 promotes DNA repair activity and deacetylation of Ku70.";
RL Exp. Mol. Med. 39:8-13(2007).
RN [27]
RP FUNCTION IN DEACETYLATION OF TP73, AND FUNCTION IN REGULATION OF TP73.
RX PubMed=16998810; DOI=10.1002/jcp.20831;
RA Dai J.M., Wang Z.Y., Sun D.C., Lin R.X., Wang S.Q.;
RT "SIRT1 interacts with p73 and suppresses p73-dependent transcriptional
RT activity.";
RL J. Cell. Physiol. 210:161-166(2007).
RN [28]
RP FUNCTION IN AR-DEPENDENT REPRESSION.
RX PubMed=17505061; DOI=10.1210/me.2006-0467;
RA Dai Y., Ngo D., Forman L.W., Qin D.C., Jacob J., Faller D.V.;
RT "Sirtuin 1 is required for antagonist-induced transcriptional repression of
RT androgen-responsive genes by the androgen receptor.";
RL Mol. Endocrinol. 21:1807-1821(2007).
RN [29]
RP INTERACTION WITH RPS19BP1.
RX PubMed=17964266; DOI=10.1016/j.molcel.2007.08.030;
RA Kim E.-J., Kho J.-H., Kang M.-R., Um S.-J.;
RT "Active regulator of SIRT1 cooperates with SIRT1 and facilitates
RT suppression of p53 activity.";
RL Mol. Cell 28:277-290(2007).
RN [30]
RP ERRATUM OF PUBMED:17964266.
RA Kim E.-J., Kho J.-H., Kang M.-R., Um S.-J.;
RL Mol. Cell 28:513-513(2007).
RN [31]
RP FUNCTION IN DEACETYLATION OF NR1H3 AND NR1H2.
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 [32]
RP FUNCTION IN DEACETYLATION OF NBN, AND FUNCTION IN DNA REPAIR.
RX PubMed=17612497; DOI=10.1016/j.molcel.2007.05.029;
RA Yuan Z., Zhang X., Sengupta N., Lane W.S., Seto E.;
RT "SIRT1 regulates the function of the Nijmegen breakage syndrome protein.";
RL Mol. Cell 27:149-162(2007).
RN [33]
RP FUNCTION IN DEACETYLATION OF HIC1.
RX PubMed=17283066; DOI=10.1128/mcb.01098-06;
RA Stankovic-Valentin N., Deltour S., Seeler J., Pinte S., Vergoten G.,
RA Guerardel C., Dejean A., Leprince D.;
RT "An acetylation/deacetylation-SUMOylation switch through a phylogenetically
RT conserved psiKXEP motif in the tumor suppressor HIC1 regulates
RT transcriptional repression activity.";
RL Mol. Cell. Biol. 27:2661-2675(2007).
RN [34]
RP FUNCTION, MUTAGENESIS OF HIS-363, AND ACTIVE SITE.
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 [35]
RP FUNCTION.
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 [36]
RP IDENTIFICATION IN THE ENOSC COMPLEX, FUNCTION, MUTAGENESIS OF HIS-363, AND
RP ACTIVE SITE.
RX PubMed=18485871; DOI=10.1016/j.cell.2008.03.030;
RA Murayama A., Ohmori K., Fujimura A., Minami H., Yasuzawa-Tanaka K.,
RA Kuroda T., Oie S., Daitoku H., Okuwaki M., Nagata K., Fukamizu A.,
RA Kimura K., Shimizu T., Yanagisawa J.;
RT "Epigenetic control of rDNA loci in response to intracellular energy
RT status.";
RL Cell 133:627-639(2008).
RN [37]
RP PHOSPHORYLATION AT SER-27 AND SER-47.
RX PubMed=18838864; DOI=10.4161/cc.7.19.6799;
RA Ford J., Ahmed S., Allison S., Jiang M., Milner J.;
RT "JNK2-dependent regulation of SIRT1 protein stability.";
RL Cell Cycle 7:3091-3097(2008).
RN [38]
RP INTERACTION WITH HIV-1 TAT (MICROBIAL INFECTION), AND FUNCTION IN T-CELL
RP ACTIVATION (MICROBIAL INFECTION).
RX PubMed=18329615; DOI=10.1016/j.chom.2008.02.002;
RA Kwon H.S., Brent M.M., Getachew R., Jayakumar P., Chen L.F., Schnolzer M.,
RA McBurney M.W., Marmorstein R., Greene W.C., Ott M.;
RT "Human immunodeficiency virus type 1 Tat protein inhibits the SIRT1
RT deacetylase and induces T cell hyperactivation.";
RL Cell Host Microbe 3:158-167(2008).
RN [39]
RP FUNCTION IN DEACETYLATION OF WRN, AND FUNCTION IN DNA DAMAGE.
RX PubMed=18203716; DOI=10.1074/jbc.m709707200;
RA Li K., Casta A., Wang R., Lozada E., Fan W., Kane S., Ge Q., Gu W.,
RA Orren D., Luo J.;
RT "Regulation of WRN protein cellular localization and enzymatic activities
RT by SIRT1-mediated deacetylation.";
RL J. Biol. Chem. 283:7590-7598(2008).
RN [40]
RP FUNCTION IN DEACETYLATION OF 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 [41]
RP INTERACTION WITH CCAR2, ACTIVITY REGULATION, MUTAGENESIS OF HIS-363, ACTIVE
RP SITE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18235501; DOI=10.1038/nature06500;
RA Kim J.-E., Chen J., Lou Z.;
RT "DBC1 is a negative regulator of SIRT1.";
RL Nature 451:583-586(2008).
RN [42]
RP INTERACTION WITH CCAR2, AND ACTIVITY REGULATION.
RX PubMed=18235502; DOI=10.1038/nature06515;
RA Zhao W., Kruse J.-P., Tang Y., Jung S.Y., Qin J., Gu W.;
RT "Negative regulation of the deacetylase SIRT1 by DBC1.";
RL Nature 451:587-590(2008).
RN [43]
RP PHOSPHORYLATION AT SER-14; SER-26; SER-27; SER-47; SER-159; SER-162;
RP SER-172; SER-173; THR-530; THR-544; SER-545; THR-719 AND SER-747, AND
RP MUTAGENESIS OF THR-530 AND SER-540.
RX PubMed=19107194; DOI=10.1371/journal.pone.0004020;
RA Sasaki T., Maier B., Koclega K.D., Chruszcz M., Gluba W., Stukenberg P.T.,
RA Minor W., Scrable H.;
RT "Phosphorylation regulates SIRT1 function.";
RL PLoS ONE 3:E4020-E4020(2008).
RN [44]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-719, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [45]
RP FUNCTION IN DEACETYLATION OF ATG5; ATG7 AND MAP1LC3B, AND FUNCTION IN
RP 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 [46]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [47]
RP PHOSPHORYLATION AT SER-659 AND SER-661, AND MUTAGENESIS OF SER-659; SER-661
RP AND SER-684.
RX PubMed=19236849; DOI=10.1016/j.bbrc.2009.02.085;
RA Zschoernig B., Mahlknecht U.;
RT "Carboxy-terminal phosphorylation of SIRT1 by protein kinase CK2.";
RL Biochem. Biophys. Res. Commun. 381:372-377(2009).
RN [48]
RP FUNCTION.
RX PubMed=19220062; DOI=10.1021/bi802093g;
RA Du J., Jiang H., Lin H.;
RT "Investigating the ADP-ribosyltransferase activity of sirtuins with NAD
RT analogues and 32P-NAD.";
RL Biochemistry 48:2878-2890(2009).
RN [49]
RP 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 [50]
RP FUNCTION, AND INTERACTION WITH CREBZF.
RX PubMed=19690166; DOI=10.1074/jbc.m109.034165;
RA Xie Y.B., Park J.H., Kim D.K., Hwang J.H., Oh S., Park S.B., Shong M.,
RA Lee I.K., Choi H.S.;
RT "Transcriptional corepressor SMILE recruits SIRT1 to inhibit nuclear
RT receptor estrogen receptor-related receptor gamma transactivation.";
RL J. Biol. Chem. 284:28762-28774(2009).
RN [51]
RP FUNCTION IN DEACETYLATION OF MYC, AND FUNCTION IN REGULATION OF MYC.
RX PubMed=19364925; DOI=10.1083/jcb.200809167;
RA Yuan J., Minter-Dykhouse K., Lou Z.;
RT "A c-Myc-SIRT1 feedback loop regulates cell growth and transformation.";
RL J. Cell Biol. 185:203-211(2009).
RN [52]
RP FUNCTION IN DEACETYLATION OF PCAF, AND FUNCTION IN DNA REPAIR.
RX PubMed=19188449; DOI=10.1128/mcb.00552-08;
RA Pediconi N., Guerrieri F., Vossio S., Bruno T., Belloni L., Schinzari V.,
RA Scisciani C., Fanciulli M., Levrero M.;
RT "hSirT1-dependent regulation of the PCAF-E2F1-p73 apoptotic pathway in
RT response to DNA damage.";
RL Mol. Cell. Biol. 29:1989-1998(2009).
RN [53]
RP PHOSPHORYLATION AT SER-27; SER-47 AND THR-530, MUTAGENESIS OF SER-27;
RP SER-47 AND THR-530, AND SUBCELLULAR LOCATION.
RX PubMed=20027304; DOI=10.1371/journal.pone.0008414;
RA Nasrin N., Kaushik V.K., Fortier E., Wall D., Pearson K.J., de Cabo R.,
RA Bordone L.;
RT "JNK1 phosphorylates SIRT1 and promotes its enzymatic activity.";
RL PLoS ONE 4:E8414-E8414(2009).
RN [54]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-530; SER-535 AND THR-719, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [55]
RP FUNCTION IN REGULATION OF STK11.
RX PubMed=20203304; DOI=10.1161/circresaha.109.215483;
RA Zu Y., Liu L., Lee M.Y., Xu C., Liang Y., Man R.Y., Vanhoutte P.M.,
RA Wang Y.;
RT "SIRT1 promotes proliferation and prevents senescence through targeting
RT LKB1 in primary porcine aortic endothelial cells.";
RL Circ. Res. 106:1384-1393(2010).
RN [56]
RP FUNCTION IN DNA REPAIR HOMOLOGOUS RECOMBINATION.
RX PubMed=20097625; DOI=10.1016/j.dnarep.2009.12.020;
RA Uhl M., Csernok A., Aydin S., Kreienberg R., Wiesmuller L., Gatz S.A.;
RT "Role of SIRT1 in homologous recombination.";
RL DNA Repair 9:383-393(2010).
RN [57]
RP INTERACTION WITH FOS AND JUN.
RX PubMed=20042607; DOI=10.1074/jbc.m109.038604;
RA Zhang R., Chen H.Z., Liu J.J., Jia Y.Y., Zhang Z.Q., Yang R.F., Zhang Y.,
RA Xu J., Wei Y.S., Liu D.P., Liang C.C.;
RT "SIRT1 suppresses activator protein-1 transcriptional activity and
RT cyclooxygenase-2 expression in macrophages.";
RL J. Biol. Chem. 285:7097-7110(2010).
RN [58]
RP FUNCTION IN DEACETYLATION OF KAT5.
RX PubMed=20100829; DOI=10.1074/jbc.m109.087585;
RA Wang J., Chen J.;
RT "SIRT1 regulates autoacetylation and histone acetyltransferase activity of
RT TIP60.";
RL J. Biol. Chem. 285:11458-11464(2010).
RN [59]
RP SUBCELLULAR LOCATION.
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 [60]
RP FUNCTION IN DEACETYLATION 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 [61]
RP FUNCTION IN DEACETYLATION OF HIF1A, AND FUNCTION IN REGULATION OF HIF1A.
RX PubMed=20620956; DOI=10.1016/j.molcel.2010.05.023;
RA Lim J.H., Lee Y.M., Chun Y.S., Chen J., Kim J.E., Park J.W.;
RT "Sirtuin 1 modulates cellular responses to hypoxia by deacetylating
RT hypoxia-inducible factor 1alpha.";
RL Mol. Cell 38:864-878(2010).
RN [62]
RP FUNCTION IN DEACETYLATION OF XPA.
RX PubMed=20670893; DOI=10.1016/j.molcel.2010.07.006;
RA Fan W., Luo J.;
RT "SIRT1 regulates UV-induced DNA repair through deacetylating XPA.";
RL Mol. Cell 39:247-258(2010).
RN [63]
RP FUNCTION IN DEACETYLATION OF APEX1, FUNCTION IN DNA REPAIR, MUTAGENESIS OF
RP HIS-363, ACTIVE SITE, INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19934257; DOI=10.1093/nar/gkp1039;
RA Yamamori T., DeRicco J., Naqvi A., Hoffman T.A., Mattagajasingh I.,
RA Kasuno K., Jung S.B., Kim C.S., Irani K.;
RT "SIRT1 deacetylates APE1 and regulates cellular base excision repair.";
RL Nucleic Acids Res. 38:832-845(2010).
RN [64]
RP FUNCTION, AND INTERACTION WITH NR0B2.
RX PubMed=20375098; DOI=10.1093/nar/gkq227;
RA Chanda D., Xie Y.B., Choi H.S.;
RT "Transcriptional corepressor SHP recruits SIRT1 histone deacetylase to
RT inhibit LRH-1 transactivation.";
RL Nucleic Acids Res. 38:4607-4619(2010).
RN [65]
RP INTERACTION WITH TSC2.
RX PubMed=20169165; DOI=10.1371/journal.pone.0009199;
RA Ghosh H.S., McBurney M., Robbins P.D.;
RT "SIRT1 negatively regulates the mammalian target of rapamycin.";
RL PLoS ONE 5:E9199-E9199(2010).
RN [66]
RP ALTERNATIVE SPLICING (ISOFORM 2), FUNCTION (ISOFORM 2), INDUCTION (ISOFORM
RP 2), AND INTERACTION WITH TP53 AND RPS19BP1.
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 [67]
RP FUNCTION IN DNA REPAIR, AND SUPPRESSION OF XPC.
RX PubMed=21149730; DOI=10.1073/pnas.1010377108;
RA Ming M., Shea C.R., Guo X., Li X., Soltani K., Han W., He Y.Y.;
RT "Regulation of global genome nucleotide excision repair by SIRT1 through
RT xeroderma pigmentosum C.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:22623-22628(2010).
RN [68]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-14 AND SER-47, CLEAVAGE OF INITIATOR METHIONINE [LARGE
RP SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [69]
RP FUNCTION IN DEACETYLATION OF HMGCS1.
RX PubMed=21701047; DOI=10.18632/aging.100339;
RA Hirschey M.D., Shimazu T., Capra J.A., Pollard K.S., Verdin E.;
RT "SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and
RT HMGCS1,2.";
RL Aging (Albany NY) 3:635-642(2011).
RN [70]
RP PROCESSING.
RX PubMed=21305533; DOI=10.1002/art.30279;
RA Dvir-Ginzberg M., Gagarina V., Lee E.J., Booth R., Gabay O., Hall D.J.;
RT "Tumor necrosis factor alpha-mediated cleavage and inactivation of SirT1 in
RT human osteoarthritic chondrocytes.";
RL Arthritis Rheum. 63:2363-2373(2011).
RN [71]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [72]
RP FUNCTION IN DEACETYLATION OF XBP1, INTERACTION WITH XBP1, AND SUBCELLULAR
RP 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 [73]
RP FUNCTION IN DEACETYLATION OF MECOM.
RX PubMed=21555002; DOI=10.1016/j.bbagrm.2011.04.007;
RA Pradhan A.K., Kuila N., Singh S., Chakraborty S.;
RT "EVI1 up-regulates the stress responsive gene SIRT1 which triggers
RT deacetylation and degradation of EVI1.";
RL Biochim. Biophys. Acta 1809:269-275(2011).
RN [74]
RP INTERACTION WITH NR1I2.
RX PubMed=21933665; DOI=10.1016/j.bcp.2011.09.006;
RA Buler M., Aatsinki S.M., Skoumal R., Hakkola J.;
RT "Energy sensing factors PGC-1alpha and SIRT1 modulate PXR expression and
RT function.";
RL Biochem. Pharmacol. 82:2008-2015(2011).
RN [75]
RP FUNCTION IN DEACETYLATION OF MYC, AND FUNCTION IN REGULATION OF MYC.
RX PubMed=21807113; DOI=10.1016/j.biocel.2011.07.006;
RA Mao B., Zhao G., Lv X., Chen H.Z., Xue Z., Yang B., Liu D.P., Liang C.C.;
RT "Sirt1 deacetylates c-Myc and promotes c-Myc/Max association.";
RL Int. J. Biochem. Cell Biol. 43:1573-1581(2011).
RN [76]
RP PHOSPHORYLATION BY STK4/MST1.
RX PubMed=21212262; DOI=10.1074/jbc.m110.182543;
RA Yuan F., Xie Q., Wu J., Bai Y., Mao B., Dong Y., Bi W., Ji G., Tao W.,
RA Wang Y., Yuan Z.;
RT "MST1 promotes apoptosis through regulating Sirt1-dependent p53
RT deacetylation.";
RL J. Biol. Chem. 286:6940-6945(2011).
RN [77]
RP FUNCTION IN APOPTOSIS, PHOSPHORYLATION AT SER-47, AND MUTAGENESIS OF SER-47
RP AND PHE-474.
RX PubMed=21471201; DOI=10.1074/jbc.m111.240598;
RA Back J.H., Rezvani H.R., Zhu Y., Guyonnet-Duperat V., Athar M., Ratner D.,
RA Kim A.L.;
RT "Cancer cell survival following DNA damage-mediated premature senescence is
RT regulated by mammalian target of rapamycin (mTOR)-dependent Inhibition of
RT sirtuin 1.";
RL J. Biol. Chem. 286:19100-19108(2011).
RN [78]
RP FUNCTION IN STABILIZATION OF SUV39H1.
RX PubMed=21504832; DOI=10.1016/j.molcel.2011.02.034;
RA Bosch-Presegue L., Raurell-Vila H., Marazuela-Duque A., Kane-Goldsmith N.,
RA Valle A., Oliver J., Serrano L., Vaquero A.;
RT "Stabilization of Suv39H1 by SirT1 is part of oxidative stress response and
RT ensures genome protection.";
RL Mol. Cell 42:210-223(2011).
RN [79]
RP FUNCTION IN DEACETYLATION OF DNMT1, AND FUNCTION IN REGULATION OF DNMT1.
RX PubMed=21947282; DOI=10.1128/mcb.06147-11;
RA Peng L., Yuan Z., Ling H., Fukasawa K., Robertson K., Olashaw N.,
RA Koomen J., Chen J., Lane W.S., Seto E.;
RT "SIRT1 deacetylates the DNA methyltransferase 1 (DNMT1) protein and alters
RT its activities.";
RL Mol. Cell. Biol. 31:4720-4734(2011).
RN [80]
RP FUNCTION IN REGULATION OF MYCN, AND INTERACTION WITH MYCN.
RX PubMed=21698133; DOI=10.1371/journal.pgen.1002135;
RA Marshall G.M., Liu P.Y., Gherardi S., Scarlett C.J., Bedalov A., Xu N.,
RA Iraci N., Valli E., Ling D., Thomas W., van Bekkum M., Sekyere E.,
RA Jankowski K., Trahair T., Mackenzie K.L., Haber M., Norris M.D.,
RA Biankin A.V., Perini G., Liu T.;
RT "SIRT1 promotes N-Myc oncogenesis through a positive feedback loop
RT involving the effects of MKP3 and ERK on N-Myc protein stability.";
RL PLoS Genet. 7:E1002135-E1002135(2011).
RN [81]
RP INTERACTION WITH HCFC1.
RX PubMed=21909281; DOI=10.1371/journal.pgen.1002235;
RA Rizki G., Iwata T.N., Li J., Riedel C.G., Picard C.L., Jan M., Murphy C.T.,
RA Lee S.S.;
RT "The evolutionarily conserved longevity determinants HCF-1 and SIR-
RT 2.1/SIRT1 collaborate to regulate DAF-16/FOXO.";
RL PLoS Genet. 7:E1002235-E1002235(2011).
RN [82]
RP INTERACTION WITH SETD7, METHYLATION, AND MUTAGENESIS OF LYS-233; LYS-235;
RP LYS-236 AND LYS-238.
RX PubMed=21245319; DOI=10.1073/pnas.1019619108;
RA Liu X., Wang D., Zhao Y., Tu B., Zheng Z., Wang L., Wang H., Gu W.,
RA Roeder R.G., Zhu W.G.;
RT "Methyltransferase Set7/9 regulates p53 activity by interacting with
RT Sirtuin 1 (SIRT1).";
RL Proc. Natl. Acad. Sci. U.S.A. 108:1925-1930(2011).
RN [83]
RP FUNCTION IN DEACETYLATION OF AKT1, AND FUNCTION IN REGULATION OF AKT1.
RX PubMed=21775285; DOI=10.1126/scisignal.2001465;
RA Sundaresan N.R., Pillai V.B., Wolfgeher D., Samant S., Vasudevan P.,
RA Parekh V., Raghuraman H., Cunningham J.M., Gupta M., Gupta M.P.;
RT "The deacetylase SIRT1 promotes membrane localization and activation of Akt
RT and PDK1 during tumorigenesis and cardiac hypertrophy.";
RL Sci. Signal. 4:RA46-RA46(2011).
RN [84]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-14; SER-47 AND THR-719, CLEAVAGE OF INITIATOR METHIONINE
RP [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [85]
RP FUNCTION (SIRTT1 75 KDA FRAGMENT), AND SUBCELLULAR LOCATION (75SIRT1).
RX PubMed=21987377; DOI=10.1002/art.33407;
RA Oppenheimer H., Gabay O., Meir H., Haze A., Kandel L., Liebergall M.,
RA Gagarina V., Lee E.J., Dvir-Ginzberg M.;
RT "75kDa SirT1 blocks TNFalpha-mediated apoptosis in human osteoarthritic
RT chondrocytes.";
RL Arthritis Rheum. 64:718-728(2012).
RN [86]
RP FUNCTION IN DEACETYLATION OF CIITA.
RX PubMed=21890893; DOI=10.1093/nar/gkr651;
RA Wu X., Kong X., Chen D., Li H., Zhao Y., Xia M., Fang M., Li P., Fang F.,
RA Sun L., Tian W., Xu H., Yang Y., Qi X., Gao Y., Sha J., Chen Q., Xu Y.;
RT "SIRT1 links CIITA deacetylation to MHC II activation.";
RL Nucleic Acids Res. 39:9549-9558(2011).
RN [87]
RP FUNCTION IN DEACETYLATION OF PML.
RX PubMed=22274616; DOI=10.1038/emboj.2012.1;
RA Miki T., Xu Z., Chen-Goodspeed M., Liu M., Van Oort-Jansen A., Rea M.A.,
RA Zhao Z., Lee C.C., Chang K.S.;
RT "PML regulates PER2 nuclear localization and circadian function.";
RL EMBO J. 31:1427-1439(2012).
RN [88]
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 [89]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [90]
RP FUNCTION IN DEACETYLATION OF FOXO3, AND FUNCTION IN REGULATION OF FOXO3.
RX PubMed=21841822; DOI=10.1038/onc.2011.347;
RA Wang F., Chan C.H., Chen K., Guan X., Lin H.K., Tong Q.;
RT "Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3
RT ubiquitination and degradation.";
RL Oncogene 31:1546-1557(2012).
RN [91]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [92]
RP INTERACTION WITH CCAR2.
RX PubMed=23352644; DOI=10.1016/j.canlet.2013.01.026;
RA Kim W., Kim J.E.;
RT "Deleted in breast cancer 1 (DBC1) deficiency results in apoptosis of
RT breast cancer cells through impaired responses to UV-induced DNA damage.";
RL Cancer Lett. 333:180-186(2013).
RN [93]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-27; SER-47 AND
RP THR-719, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [94]
RP INTERACTION WITH PPARA.
RX PubMed=24043310; DOI=10.1128/mcb.00087-13;
RA Laurent G., de Boer V.C., Finley L.W., Sweeney M., Lu H., Schug T.T.,
RA Cen Y., Jeong S.M., Li X., Sauve A.A., Haigis M.C.;
RT "SIRT4 represses peroxisome proliferator-activated receptor alpha activity
RT to suppress hepatic fat oxidation.";
RL Mol. Cell. Biol. 33:4552-4561(2013).
RN [95]
RP FUNCTION.
RX PubMed=24415752; DOI=10.1074/jbc.m113.512913;
RA Nin V., Chini C.C., Escande C., Capellini V., Chini E.N.;
RT "Deleted in breast cancer 1 (DBC1) protein regulates hepatic
RT gluconeogenesis.";
RL J. Biol. Chem. 289:5518-5527(2014).
RN [96]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14 AND SER-27, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [97]
RP INTERACTION WITH CCAR2 AND TP53, MUTAGENESIS OF 256-ILE-ILE-257 AND
RP HIS-363, AND ACTIVE SITE.
RX PubMed=25406032; DOI=10.1038/ncomms6483;
RA Park J.H., Lee S.W., Yang S.W., Yoo H.M., Park J.M., Seong M.W., Ka S.H.,
RA Oh K.H., Jeon Y.J., Chung C.H.;
RT "Modification of DBC1 by SUMO2/3 is crucial for p53-mediated apoptosis in
RT response to DNA damage.";
RL Nat. Commun. 5:5483-5483(2014).
RN [98]
RP INTERACTION WITH CHEK2.
RX PubMed=25361978; DOI=10.1093/nar/gku1065;
RA Magni M., Ruscica V., Buscemi G., Kim J.E., Nachimuthu B.T., Fontanella E.,
RA Delia D., Zannini L.;
RT "Chk2 and REGgamma-dependent DBC1 regulation in DNA damage induced
RT apoptosis.";
RL Nucleic Acids Res. 42:13150-13160(2014).
RN [99]
RP FUNCTION IN DEACETYLATION OF CTNB1.
RX PubMed=24824780; DOI=10.1002/ijc.28967;
RA Pangon L., Mladenova D., Watkins L., Van Kralingen C., Currey N.,
RA Al-Sohaily S., Lecine P., Borg J.P., Kohonen-Corish M.R.;
RT "MCC inhibits beta-catenin transcriptional activity by sequestering DBC1 in
RT the cytoplasm.";
RL Int. J. Cancer 136:55-64(2015).
RN [100]
RP INTERACTION WITH NR1H3.
RX PubMed=25661920; DOI=10.1016/j.jsbmb.2015.02.001;
RA Sakurabashi A., Wada-Hiraike O., Hirano M., Fu H., Isono W., Fukuda T.,
RA Morita Y., Tanikawa M., Miyamoto Y., Oda K., Kawana K., Osuga Y., Fujii T.;
RT "CCAR2 negatively regulates nuclear receptor LXRalpha by competing with
RT SIRT1 deacetylase.";
RL J. Steroid Biochem. Mol. Biol. 149:80-88(2015).
RN [101]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVE SITE, AND MUTAGENESIS OF HIS-363.
RX PubMed=28497810; DOI=10.1038/cr.2017.68;
RA Wei W., Liu X., Chen J., Gao S., Lu L., Zhang H., Ding G., Wang Z.,
RA Chen Z., Shi T., Li J., Yu J., Wong J.;
RT "Class I histone deacetylases are major histone decrotonylases: evidence
RT for critical and broad function of histone crotonylation in
RT transcription.";
RL Cell Res. 27:898-915(2017).
RN [102]
RP INTERACTION WITH PACS2.
RX PubMed=29656858; DOI=10.1016/j.ajhg.2018.03.005;
RG DDD Study;
RG C4RCD Research Group;
RA Olson H.E., Jean-Marcais N., Yang E., Heron D., Tatton-Brown K.,
RA van der Zwaag P.A., Bijlsma E.K., Krock B.L., Backer E., Kamsteeg E.J.,
RA Sinnema M., Reijnders M.R.F., Bearden D., Begtrup A., Telegrafi A.,
RA Lunsing R.J., Burglen L., Lesca G., Cho M.T., Smith L.A., Sheidley B.R.,
RA Moufawad El Achkar C., Pearl P.L., Poduri A., Skraban C.M., Tarpinian J.,
RA Nesbitt A.I., Fransen van de Putte D.E., Ruivenkamp C.A.L., Rump P.,
RA Chatron N., Sabatier I., De Bellescize J., Guibaud L., Sweetser D.A.,
RA Waxler J.L., Wierenga K.J., Donadieu J., Narayanan V., Ramsey K.M.,
RA Nava C., Riviere J.B., Vitobello A., Tran Mau-Them F., Philippe C.,
RA Bruel A.L., Duffourd Y., Thomas L., Lelieveld S.H., Schuurs-Hoeijmakers J.,
RA Brunner H.G., Keren B., Thevenon J., Faivre L., Thomas G.,
RA Thauvin-Robinet C.;
RT "A recurrent de novo PACS2 heterozygous missense variant causes neonatal-
RT onset developmental epileptic encephalopathy, facial dysmorphism, and
RT cerebellar dysgenesis.";
RL Am. J. Hum. Genet. 102:995-1007(2018).
RN [103]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29765047; DOI=10.1038/s41467-018-04363-w;
RA Li T.Y., Song L., Sun Y., Li J., Yi C., Lam S.M., Xu D., Zhou L., Li X.,
RA Yang Y., Zhang C.S., Xie C., Huang X., Shui G., Lin S.Y., Reue K.,
RA Lin S.C.;
RT "Tip60-mediated lipin 1 acetylation and ER translocation determine
RT triacylglycerol synthesis rate.";
RL Nat. Commun. 9:1916-1916(2018).
RN [104]
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 [105]
RP INTERACTION WITH PUS7.
RX PubMed=31451225; DOI=10.1016/j.bbrc.2019.08.097;
RA Dalal S., Deshmukh P., Unni S., Padavattan S., Padmanabhan B.;
RT "Biochemical insight into pseudouridine synthase 7 (PUS7) as a novel
RT interactor of sirtuin, SIRT1.";
RL Biochem. Biophys. Res. Commun. 518:598-604(2019).
RN [106]
RP FUNCTION.
RX PubMed=31722219; DOI=10.1016/j.celrep.2019.10.028;
RA Wang T., Zou Y., Huang N., Teng J., Chen J.;
RT "CCDC84 Acetylation Oscillation Regulates Centrosome Duplication by
RT Modulating HsSAS-6 Degradation.";
RL Cell Rep. 29:2078-2091.e5(2019).
RN [107]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=30409912; DOI=10.1074/jbc.ra118.003844;
RA Zhao G., Cheng Y., Gui P., Cui M., Liu W., Wang W., Wang X., Ali M.,
RA Dou Z., Niu L., Liu H., Anderson L., Ruan K., Hong J., Yao X.;
RT "Dynamic acetylation of the kinetochore-associated protein HEC1 ensures
RT accurate microtubule-kinetochore attachment.";
RL J. Biol. Chem. 294:576-592(2019).
RN [108]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-363.
RX PubMed=32538779; DOI=10.7554/elife.55828;
RA Meng F., Qian M., Peng B., Peng L., Wang X., Zheng K., Liu Z., Tang X.,
RA Zhang S., Sun S., Cao X., Pang Q., Zhao B., Ma W., Songyang Z., Xu B.,
RA Zhu W.G., Xu X., Liu B.;
RT "Synergy between SIRT1 and SIRT6 helps recognize DNA breaks and potentiates
RT the DNA damage response and repair in humans and mice.";
RL Elife 9:0-0(2020).
RN [109]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF HIS-363.
RX PubMed=32034146; DOI=10.1038/s41467-020-14564-x;
RA Wang J., He H., Chen B., Jiang G., Cao L., Jiang H., Zhang G., Chen J.,
RA Huang J., Yang B., Zhou C., Liu T.;
RT "Acetylation of XPF by TIP60 facilitates XPF-ERCC1 complex assembly and
RT activation.";
RL Nat. Commun. 11:786-786(2020).
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:11672523, PubMed:12006491, PubMed:14976264, PubMed:14980222,
CC PubMed:15126506, PubMed:15152190, PubMed:15205477, PubMed:15469825,
CC PubMed:15692560, PubMed:16079181, PubMed:16166628, PubMed:16892051,
CC PubMed:16998810, PubMed:17283066, PubMed:17290224, PubMed:17334224,
CC PubMed:17505061, PubMed:17612497, PubMed:17620057, PubMed:17936707,
CC PubMed:18203716, PubMed:18296641, PubMed:18662546, PubMed:18687677,
CC PubMed:19188449, PubMed:19220062, PubMed:19364925, PubMed:19690166,
CC PubMed:19934257, PubMed:20097625, PubMed:20100829, PubMed:20203304,
CC PubMed:20375098, PubMed:20620956, PubMed:20670893, PubMed:20817729,
CC PubMed:20955178, PubMed:21149730, PubMed:21245319, PubMed:21471201,
CC PubMed:21504832, PubMed:21555002, PubMed:21698133, PubMed:21701047,
CC PubMed:21775285, PubMed:21807113, PubMed:21841822, PubMed:21890893,
CC PubMed:21947282, PubMed:22274616, PubMed:24415752, PubMed:24824780,
CC PubMed:29765047, PubMed:30409912). Can modulate chromatin function
CC through deacetylation of histones and can promote alterations in the
CC methylation of histones and DNA, leading to transcriptional repression
CC (PubMed:15469825). Deacetylates a broad range of transcription factors
CC and coregulators, thereby regulating target gene expression positively
CC and negatively (PubMed:15152190, PubMed:14980222, PubMed:14976264).
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 (PubMed:15205477). 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) (By similarity). Component of the
CC eNoSC (energy-dependent nucleolar silencing) complex, a complex that
CC mediates silencing of rDNA in response to intracellular energy status
CC and acts by recruiting histone-modifying enzymes (PubMed:18485871). The
CC eNoSC complex is able to sense the energy status of cell: upon glucose
CC starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading
CC to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9'
CC (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA
CC locus (PubMed:18485871, PubMed:21504832). Deacetylates 'Lys-266' of
CC SUV39H1, leading to its activation (PubMed:21504832). Inhibits skeletal
CC muscle differentiation by deacetylating PCAF and MYOD1
CC (PubMed:19188449). Deacetylates H2A and 'Lys-26' of H1-4
CC (PubMed:15469825). Deacetylates 'Lys-16' of histone H4 (in vitro).
CC Involved in NR0B2/SHP corepression function through chromatin
CC remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP
CC thereby stimulating histone H3 and H4 deacetylation leading to
CC transcriptional repression (PubMed:20375098). Proposed to contribute to
CC genomic integrity via positive regulation of telomere length; however,
CC reports on localization to pericentromeric heterochromatin are
CC conflicting (By similarity). Proposed to play a role in constitutive
CC heterochromatin (CH) formation and/or maintenance through regulation of
CC the available pool of nuclear SUV39H1 (PubMed:15469825,
CC PubMed:18004385). Upon oxidative/metabolic stress decreases SUV39H1
CC degradation by inhibiting SUV39H1 polyubiquitination by MDM2
CC (PubMed:18004385, PubMed:21504832). This increase in SUV39H1 levels
CC enhances SUV39H1 turnover in CH, which in turn seems to accelerate
CC renewal of the heterochromatin which correlates with greater genomic
CC integrity during stress response (PubMed:18004385, PubMed:21504832).
CC Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce
CC transcription-dependent proapoptotic program and modulate cell
CC senescence (PubMed:11672523, PubMed:12006491). Deacetylates TAF1B and
CC thereby represses rDNA transcription by the RNA polymerase I (By
CC similarity). Deacetylates MYC, promotes the association of MYC with MAX
CC and decreases MYC stability leading to compromised transformational
CC capability (PubMed:19364925, PubMed:21807113). Deacetylates FOXO3 in
CC response to oxidative stress thereby increasing its ability to induce
CC cell cycle arrest and resistance to oxidative stress but inhibiting
CC FOXO3-mediated induction of apoptosis transcriptional activity; also
CC leading to FOXO3 ubiquitination and protesomal degradation
CC (PubMed:14980222, PubMed:14976264, PubMed:21841822). Appears to have a
CC similar effect on MLLT7/FOXO4 in regulation of transcriptional activity
CC and apoptosis (PubMed:15126506). Deacetylates DNMT1; thereby impairs
CC DNMT1 methyltransferase-independent transcription repressor activity,
CC modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene
CC silencing (PubMed:21947282). Deacetylates RELA/NF-kappa-B p65 thereby
CC inhibiting its transactivating potential and augments apoptosis in
CC response to TNF-alpha (PubMed:15152190). Deacetylates HIF1A,
CC KAT5/TIP60, RB1 and HIC1 (PubMed:17620057, PubMed:17283066,
CC PubMed:20100829, PubMed:20620956). Deacetylates FOXO1 resulting in its
CC nuclear retention and enhancement of its transcriptional activity
CC leading to increased gluconeogenesis in liver (PubMed:15692560).
CC Inhibits E2F1 transcriptional activity and apoptotic function, possibly
CC by deacetylation (PubMed:16892051). Involved in HES1- and HEY2-mediated
CC transcriptional repression (PubMed:12535671). In cooperation with MYCN
CC seems to be involved in transcriptional repression of DUSP6/MAPK3
CC leading to MYCN stabilization by phosphorylation at 'Ser-62'
CC (PubMed:21698133). Deacetylates MEF2D (PubMed:16166628). Required for
CC antagonist-mediated transcription suppression of AR-dependent genes
CC which may be linked to local deacetylation of histone H3
CC (PubMed:17505061). Represses HNF1A-mediated transcription (By
CC similarity). Required for the repression of ESRRG by CREBZF
CC (PubMed:19690166). Deacetylates NR1H3 and NR1H2 and deacetylation of
CC NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR
CC target genes, promotes NR1H3 proteosomal degradation and results in
CC cholesterol efflux; a promoter clearing mechanism after reach round of
CC transcription is proposed (PubMed:17936707). Involved in lipid
CC metabolism: deacetylates LPIN1, thereby inhibiting diacylglycerol
CC synthesis (PubMed:20817729, PubMed:29765047). Implicated in regulation
CC of adipogenesis and fat mobilization in white adipocytes by repression
CC of PPARG which probably involves association with NCOR1 and SMRT/NCOR2
CC (By similarity). Deacetylates p300/EP300 and PRMT1 (By similarity).
CC Deacetylates ACSS2 leading to its activation, and HMGCS1 deacetylation
CC (PubMed:21701047). Involved in liver and muscle metabolism. Through
CC deacetylation and activation of PPARGC1A is required to activate fatty
CC acid oxidation in skeletal muscle under low-glucose conditions and is
CC involved in glucose homeostasis (PubMed:23142079). Involved in
CC regulation of PPARA and fatty acid beta-oxidation in liver. Involved in
CC positive regulation of insulin secretion in pancreatic beta cells in
CC response to glucose; the function seems to imply transcriptional
CC repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating
CC its insulin-induced tyrosine phosphorylation. Deacetylates SREBF1
CC isoform SREBP-1C thereby decreasing its stability and transactivation
CC in lipogenic gene expression (PubMed:17290224, PubMed:20817729).
CC Involved in DNA damage response by repressing genes which are involved
CC in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and
CC facilitating recruitment of additional factors to sites of damaged DNA,
CC such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair
CC and SIRT1-deacetylated XPA interacts with RPA2 (PubMed:15205477,
CC PubMed:17334224, PubMed:16998810, PubMed:17612497, PubMed:20670893,
CC PubMed:21149730). Also involved in DNA repair of DNA double-strand
CC breaks by homologous recombination and specifically single-strand
CC annealing independently of XRCC6/Ku70 and NBN (PubMed:15205477,
CC PubMed:17334224, PubMed:20097625). Promotes DNA double-strand breaks by
CC mediating deacetylation of SIRT6 (PubMed:32538779). Transcriptional
CC suppression of XPC probably involves an E2F4:RBL2 suppressor complex
CC and protein kinase B (AKT) signaling. Transcriptional suppression of
CC TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby
CC regulating its helicase and exonuclease activities and regulates WRN
CC nuclear translocation in response to DNA damage (PubMed:18203716).
CC Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP
CC endonuclease activity by promoting the association of APEX1 to XRCC1
CC (PubMed:19934257). Catalyzes deacetylation of ERCC4/XPF, thereby
CC impairing interaction with ERCC1 and nucleotide excision repair (NER)
CC (PubMed:32034146). Increases p53/TP53-mediated transcription-
CC independent apoptosis by blocking nuclear translocation of cytoplasmic
CC p53/TP53 and probably redirecting it to mitochondria. Deacetylates
CC XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to sequester BAX away
CC from mitochondria thereby inhibiting stress-induced apoptosis. Is
CC involved in autophagy, presumably by deacetylating ATG5, ATG7 and
CC MAP1LC3B/ATG8 (PubMed:18296641). Deacetylates AKT1 which leads to
CC enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation
CC (PubMed:21775285). Proposed to play role in regulation of STK11/LBK1-
CC dependent AMPK signaling pathways implicated in cellular senescence
CC which seems to involve the regulation of the acetylation status of
CC STK11/LBK1. Can deacetylate STK11/LBK1 and thereby increase its
CC activity, cytoplasmic localization and association with STRAD; however,
CC the relevance of such activity in normal cells is unclear
CC (PubMed:18687677, PubMed:20203304). In endothelial cells is shown to
CC inhibit STK11/LBK1 activity and to promote its degradation.
CC Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its
CC degradation. Deacetylates CIITA and augments its MHC class II
CC transactivation and contributes to its stability (PubMed:21890893).
CC Deacetylates MECOM/EVI1 (PubMed:21555002). Deacetylates PML at 'Lys-
CC 487' and this deacetylation promotes PML control of PER2 nuclear
CC localization (PubMed:22274616). During the neurogenic transition,
CC represses selective NOTCH1-target genes through histone deacetylation
CC in a BCL6-dependent manner and leading to neuronal differentiation.
CC Regulates the circadian expression of several core clock genes,
CC including ARNTL/BMAL1, RORC, PER2 and CRY1 and plays a critical role in
CC maintaining a controlled rhythmicity in histone acetylation, thereby
CC contributing to circadian chromatin remodeling (PubMed:18662546).
CC Deacetylates ARNTL/BMAL1 and histones at the circadian gene promoters
CC in order to facilitate repression by inhibitory components of the
CC circadian oscillator (By similarity). Deacetylates PER2, facilitating
CC its ubiquitination and degradation by the proteosome (By similarity).
CC Protects cardiomyocytes against palmitate-induced apoptosis (By
CC similarity). Deacetylates XBP1 isoform 2; deacetylation decreases
CC protein stability of XBP1 isoform 2 and inhibits its transcriptional
CC activity (PubMed:20955178). 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 (PubMed:24415752). Deacetylates CTNB1 at 'Lys-49'
CC (PubMed:24824780). In POMC (pro-opiomelanocortin) neurons, required for
CC leptin-induced activation of PI3K signaling (By similarity). In
CC addition to protein deacetylase activity, also acts as protein-lysine
CC deacylase by mediating protein depropionylation and decrotonylation
CC (PubMed:28497810). Mediates depropionylation of Osterix (SP7) (By
CC similarity). Catalyzes decrotonylation of histones; it however does not
CC represent a major histone decrotonylase (PubMed:28497810). Deacetylates
CC SOX9; promoting SOX9 nuclear localization and transactivation activity
CC (By similarity). Involved in the regulation of centrosome duplication.
CC Deacetylates CENATAC in G1 phase, allowing for SASS6 accumulation on
CC the centrosome and subsequent procentriole assembly (PubMed:31722219).
CC Deacetylates NDC80/HEC1 (PubMed:30409912).
CC {ECO:0000250|UniProtKB:Q923E4, ECO:0000269|PubMed:11672523,
CC ECO:0000269|PubMed:12006491, ECO:0000269|PubMed:12535671,
CC ECO:0000269|PubMed:14976264, ECO:0000269|PubMed:14980222,
CC ECO:0000269|PubMed:15126506, ECO:0000269|PubMed:15152190,
CC ECO:0000269|PubMed:15205477, ECO:0000269|PubMed:15469825,
CC ECO:0000269|PubMed:15692560, ECO:0000269|PubMed:16079181,
CC ECO:0000269|PubMed:16166628, ECO:0000269|PubMed:16892051,
CC ECO:0000269|PubMed:16998810, ECO:0000269|PubMed:17283066,
CC ECO:0000269|PubMed:17290224, ECO:0000269|PubMed:17334224,
CC ECO:0000269|PubMed:17505061, ECO:0000269|PubMed:17612497,
CC ECO:0000269|PubMed:17620057, ECO:0000269|PubMed:17936707,
CC ECO:0000269|PubMed:18203716, ECO:0000269|PubMed:18296641,
CC ECO:0000269|PubMed:18485871, ECO:0000269|PubMed:18662546,
CC ECO:0000269|PubMed:18687677, ECO:0000269|PubMed:19188449,
CC ECO:0000269|PubMed:19220062, ECO:0000269|PubMed:19364925,
CC ECO:0000269|PubMed:19690166, ECO:0000269|PubMed:19934257,
CC ECO:0000269|PubMed:20097625, ECO:0000269|PubMed:20100829,
CC ECO:0000269|PubMed:20203304, ECO:0000269|PubMed:20375098,
CC ECO:0000269|PubMed:20620956, ECO:0000269|PubMed:20670893,
CC ECO:0000269|PubMed:20817729, ECO:0000269|PubMed:20955178,
CC ECO:0000269|PubMed:21149730, ECO:0000269|PubMed:21245319,
CC ECO:0000269|PubMed:21471201, ECO:0000269|PubMed:21504832,
CC ECO:0000269|PubMed:21555002, ECO:0000269|PubMed:21698133,
CC ECO:0000269|PubMed:21701047, ECO:0000269|PubMed:21775285,
CC ECO:0000269|PubMed:21807113, ECO:0000269|PubMed:21841822,
CC ECO:0000269|PubMed:21890893, ECO:0000269|PubMed:21947282,
CC ECO:0000269|PubMed:22274616, ECO:0000269|PubMed:23142079,
CC ECO:0000269|PubMed:24415752, ECO:0000269|PubMed:24824780,
CC ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:29765047,
CC ECO:0000269|PubMed:30193097, ECO:0000269|PubMed:30409912,
CC ECO:0000269|PubMed:31722219, ECO:0000269|PubMed:32034146,
CC ECO:0000269|PubMed:32538779}.
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:0000269|PubMed:20975832}.
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:0000269|PubMed:21987377}.
CC -!- FUNCTION: (Microbial infection) In case of HIV-1 infection, interacts
CC with and deacetylates the viral Tat protein. The viral Tat protein
CC inhibits SIRT1 deacetylation activity toward RELA/NF-kappa-B p65,
CC thereby potentiates its transcriptional activity and SIRT1 is proposed
CC to contribute to T-cell hyperactivation during infection.
CC {ECO:0000269|PubMed:18329615}.
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:12006491, ECO:0000269|PubMed:29765047,
CC ECO:0000269|PubMed:30409912, ECO:0000269|PubMed:32034146,
CC ECO:0000269|PubMed:32538779};
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:0000250|UniProtKB:Q923E4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23501;
CC Evidence={ECO:0000250|UniProtKB:Q923E4};
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:0000269|PubMed:28497810};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:69333;
CC Evidence={ECO:0000269|PubMed:28497810};
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: Inhibited by nicotinamide. Activated by
CC resveratrol (3,5,4'-trihydroxy-trans-stilbene), butein (3,4,2',4'-
CC tetrahydroxychalcone), piceatannol (3,5,3',4'-tetrahydroxy-trans-
CC stilbene), Isoliquiritigenin (4,2',4'-trihydroxychalcone), fisetin
CC (3,7,3',4'-tetrahydroxyflavone) and quercetin (3,5,7,3',4'-
CC pentahydroxyflavone). MAPK8/JNK1 and RPS19BP1/AROS act as positive
CC regulators of deacetylation activity. Negatively regulated by CCAR2.
CC {ECO:0000269|PubMed:12297502, ECO:0000269|PubMed:12939617,
CC ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18235502}.
CC -!- SUBUNIT: Interacts with XBP1 isoform 2 (PubMed:20955178). Found in a
CC complex with PCAF and MYOD1. Interacts with FOXO1; the interaction
CC deacetylates FOXO1, resulting in its nuclear retention and promotion of
CC its transcriptional activity Component of the eNoSC complex, composed
CC of SIRT1, SUV39H1 and RRP8. Interacts with HES1, HEY2 and PML.
CC Interacts with RPS19BP1/AROS. Interacts with CCAR2 (via N-terminus);
CC the 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 BCL6; leads to a epigenetic repression of specific
CC target genes. Interacts with CLOCK, ARNTL/BMAL1 and PER2 (By
CC similarity). Interacts with PPARA; the interaction seems to be
CC modulated by NAD(+) levels (PubMed:24043310). Interacts with NR1H3 and
CC this interaction is inhibited in the presence of CCAR2. Interacts with
CC CHEK2. Interacts with p53/TP53. Exhibits a preferential interaction
CC with sumoylated CCAR2 over its unmodified form. Interacts with PACS2
CC (PubMed:29656858). Interacts with SIRT7 (By similarity). Interacts with
CC PUS7 (PubMed:31451225). {ECO:0000250|UniProtKB:Q923E4,
CC ECO:0000269|PubMed:12006491, ECO:0000269|PubMed:12535671,
CC ECO:0000269|PubMed:15684044, ECO:0000269|PubMed:15692560,
CC ECO:0000269|PubMed:16166628, ECO:0000269|PubMed:16892051,
CC ECO:0000269|PubMed:17680780, ECO:0000269|PubMed:17964266,
CC ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18235502,
CC ECO:0000269|PubMed:18485871, ECO:0000269|PubMed:19356714,
CC ECO:0000269|PubMed:19690166, ECO:0000269|PubMed:20042607,
CC ECO:0000269|PubMed:20169165, ECO:0000269|PubMed:20375098,
CC ECO:0000269|PubMed:20955178, ECO:0000269|PubMed:20975832,
CC ECO:0000269|PubMed:21245319, ECO:0000269|PubMed:21698133,
CC ECO:0000269|PubMed:21909281, ECO:0000269|PubMed:21933665,
CC ECO:0000269|PubMed:23352644, ECO:0000269|PubMed:24043310,
CC ECO:0000269|PubMed:25361978, ECO:0000269|PubMed:25406032,
CC ECO:0000269|PubMed:25661920, ECO:0000269|PubMed:29656858,
CC ECO:0000269|PubMed:31451225}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Tat.
CC {ECO:0000269|PubMed:15719057, ECO:0000269|PubMed:18329615}.
CC -!- INTERACTION:
CC Q96EB6; Q13085: ACACA; NbExp=3; IntAct=EBI-1802965, EBI-717681;
CC Q96EB6; P31749: AKT1; NbExp=5; IntAct=EBI-1802965, EBI-296087;
CC Q96EB6; P27695: APEX1; NbExp=6; IntAct=EBI-1802965, EBI-1048805;
CC Q96EB6; O95352: ATG7; NbExp=3; IntAct=EBI-1802965, EBI-987834;
CC Q96EB6; Q8N163: CCAR2; NbExp=16; IntAct=EBI-1802965, EBI-355410;
CC Q96EB6; P33076: CIITA; NbExp=4; IntAct=EBI-1802965, EBI-1538819;
CC Q96EB6; Q9NS37: CREBZF; NbExp=3; IntAct=EBI-1802965, EBI-632965;
CC Q96EB6; Q9Y5P2: CSAG3; NbExp=8; IntAct=EBI-1802965, EBI-26354757;
CC Q96EB6; P68400: CSNK2A1; NbExp=5; IntAct=EBI-1802965, EBI-347804;
CC Q96EB6; P67870: CSNK2B; NbExp=5; IntAct=EBI-1802965, EBI-348169;
CC Q96EB6; P26358: DNMT1; NbExp=11; IntAct=EBI-1802965, EBI-719459;
CC Q96EB6; O14640: DVL1; NbExp=2; IntAct=EBI-1802965, EBI-723489;
CC Q96EB6; Q92997: DVL3; NbExp=3; IntAct=EBI-1802965, EBI-739789;
CC Q96EB6; Q01094: E2F1; NbExp=3; IntAct=EBI-1802965, EBI-448924;
CC Q96EB6; Q09472: EP300; NbExp=4; IntAct=EBI-1802965, EBI-447295;
CC Q96EB6; Q14192: FHL2; NbExp=2; IntAct=EBI-1802965, EBI-701903;
CC Q96EB6; Q12778: FOXO1; NbExp=4; IntAct=EBI-1802965, EBI-1108782;
CC Q96EB6; O43524: FOXO3; NbExp=5; IntAct=EBI-1802965, EBI-1644164;
CC Q96EB6; P98177: FOXO4; NbExp=3; IntAct=EBI-1802965, EBI-4481939;
CC Q96EB6; P51610: HCFC1; NbExp=2; IntAct=EBI-1802965, EBI-396176;
CC Q96EB6; Q14469: HES1; NbExp=4; IntAct=EBI-1802965, EBI-2832522;
CC Q96EB6; Q9UBP5: HEY2; NbExp=3; IntAct=EBI-1802965, EBI-750630;
CC Q96EB6; Q9Y4H2: IRS2; NbExp=2; IntAct=EBI-1802965, EBI-1049582;
CC Q96EB6; Q92831: KAT2B; NbExp=3; IntAct=EBI-1802965, EBI-477430;
CC Q96EB6; Q03164: KMT2A; NbExp=5; IntAct=EBI-1802965, EBI-591370;
CC Q96EB6; Q9GZQ8: MAP1LC3B; NbExp=2; IntAct=EBI-1802965, EBI-373144;
CC Q96EB6; Q03112: MECOM; NbExp=2; IntAct=EBI-1802965, EBI-1384862;
CC Q96EB6; P42345: MTOR; NbExp=2; IntAct=EBI-1802965, EBI-359260;
CC Q96EB6; P01106: MYC; NbExp=4; IntAct=EBI-1802965, EBI-447544;
CC Q96EB6; P04198: MYCN; NbExp=3; IntAct=EBI-1802965, EBI-878369;
CC Q96EB6; O60934: NBN; NbExp=5; IntAct=EBI-1802965, EBI-494844;
CC Q96EB6; Q02577: NHLH2; NbExp=2; IntAct=EBI-1802965, EBI-5378683;
CC Q96EB6; Q9HAN9: NMNAT1; NbExp=3; IntAct=EBI-1802965, EBI-3917542;
CC Q96EB6; Q15466: NR0B2; NbExp=6; IntAct=EBI-1802965, EBI-3910729;
CC Q96EB6; P27986: PIK3R1; NbExp=3; IntAct=EBI-1802965, EBI-79464;
CC Q96EB6; P37231: PPARG; NbExp=5; IntAct=EBI-1802965, EBI-781384;
CC Q96EB6; P10276: RARA; NbExp=3; IntAct=EBI-1802965, EBI-413374;
CC Q96EB6; Q04206: RELA; NbExp=5; IntAct=EBI-1802965, EBI-73886;
CC Q96EB6; Q86WX3: RPS19BP1; NbExp=11; IntAct=EBI-1802965, EBI-4479407;
CC Q96EB6; Q8N122: RPTOR; NbExp=3; IntAct=EBI-1802965, EBI-1567928;
CC Q96EB6; O43159: RRP8; NbExp=3; IntAct=EBI-1802965, EBI-2008793;
CC Q96EB6; Q8WTS6: SETD7; NbExp=11; IntAct=EBI-1802965, EBI-1268586;
CC Q96EB6; Q13573: SNW1; NbExp=7; IntAct=EBI-1802965, EBI-632715;
CC Q96EB6; P36956-3: SREBF1; NbExp=2; IntAct=EBI-1802965, EBI-948338;
CC Q96EB6; O43463: SUV39H1; NbExp=5; IntAct=EBI-1802965, EBI-349968;
CC Q96EB6; Q04724: TLE1; NbExp=4; IntAct=EBI-1802965, EBI-711424;
CC Q96EB6; P04637: TP53; NbExp=18; IntAct=EBI-1802965, EBI-366083;
CC Q96EB6; O15350: TP73; NbExp=4; IntAct=EBI-1802965, EBI-389606;
CC Q96EB6; P49815: TSC2; NbExp=2; IntAct=EBI-1802965, EBI-396587;
CC Q96EB6; Q14191: WRN; NbExp=9; IntAct=EBI-1802965, EBI-368417;
CC Q96EB6; P23025: XPA; NbExp=8; IntAct=EBI-1802965, EBI-295222;
CC Q96EB6; P12956: XRCC6; NbExp=7; IntAct=EBI-1802965, EBI-353208;
CC Q96EB6; Q9R1E0: Foxo1; Xeno; NbExp=2; IntAct=EBI-1802965, EBI-1371343;
CC Q96EB6; Q60974: Ncor1; Xeno; NbExp=2; IntAct=EBI-1802965, EBI-349004;
CC Q96EB6; Q60644: Nr1h2; Xeno; NbExp=2; IntAct=EBI-1802965, EBI-5276809;
CC Q96EB6; Q9Z0Y9: Nr1h3; Xeno; NbExp=2; IntAct=EBI-1802965, EBI-5276764;
CC Q96EB6; P37238: Pparg; Xeno; NbExp=3; IntAct=EBI-1802965, EBI-5260705;
CC Q96EB6; P37238-1: Pparg; Xeno; NbExp=2; IntAct=EBI-1802965, EBI-6267861;
CC Q96EB6; P04608: tat; Xeno; NbExp=3; IntAct=EBI-1802965, EBI-6164389;
CC -!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000269|PubMed:12006491}.
CC Cytoplasm {ECO:0000269|PubMed:20027304}. Nucleus
CC {ECO:0000269|PubMed:11672523, ECO:0000269|PubMed:15469825,
CC ECO:0000269|PubMed:16079181, ECO:0000269|PubMed:19934257,
CC ECO:0000269|PubMed:20027304, ECO:0000269|PubMed:20167603,
CC ECO:0000269|PubMed:20955178}. Note=Recruited to the nuclear bodies via
CC its interaction with PML (PubMed:12006491). Colocalized with APEX1 in
CC the nucleus (PubMed:19934257). May be found in nucleolus, nuclear
CC euchromatin, heterochromatin and inner membrane (PubMed:15469825).
CC Shuttles between nucleus and cytoplasm (By similarity). Colocalizes in
CC the nucleus with XBP1 isoform 2 (PubMed:20955178).
CC {ECO:0000250|UniProtKB:Q923E4, ECO:0000269|PubMed:12006491,
CC ECO:0000269|PubMed:15469825, ECO:0000269|PubMed:19934257,
CC ECO:0000269|PubMed:20955178}.
CC -!- SUBCELLULAR LOCATION: [SirtT1 75 kDa fragment]: Cytoplasm
CC {ECO:0000269|PubMed:21987377}. Mitochondrion
CC {ECO:0000269|PubMed:21987377}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96EB6-1; Sequence=Displayed;
CC Name=2; Synonyms=delta-exon8;
CC IsoId=Q96EB6-2; Sequence=VSP_042189;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10381378}.
CC -!- INDUCTION: Up-regulated by methyl methanesulfonate (MMS). In H293T
CC cells by presence of rat calorie restriction (CR) serum.
CC {ECO:0000269|PubMed:15205477, ECO:0000269|PubMed:19934257}.
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:0000269|PubMed:21245319}.
CC -!- PTM: Phosphorylated. Phosphorylated by STK4/MST1, resulting in
CC inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by
CC MAPK8/JNK1 at Ser-27, Ser-47, and Thr-530 leads to increased nuclear
CC localization and enzymatic activity. Phosphorylation at Thr-530 by
CC DYRK1A and DYRK3 activates deacetylase activity and promotes cell
CC survival. Phosphorylation by mammalian target of rapamycin complex 1
CC (mTORC1) at Ser-47 inhibits deacetylation activity. Phosphorylated by
CC CaMK2, leading to increased p53/TP53 and NF-kappa-B p65/RELA
CC deacetylation activity (By similarity). Phosphorylation at Ser-27
CC implicating MAPK9 is linked to protein stability. There is some
CC ambiguity for some phosphosites: Ser-159/Ser-162 and Thr-544/Ser-545.
CC {ECO:0000250|UniProtKB:Q923E4, ECO:0000269|PubMed:18838864,
CC ECO:0000269|PubMed:19107194, ECO:0000269|PubMed:19236849,
CC ECO:0000269|PubMed:20027304, ECO:0000269|PubMed:21212262,
CC ECO:0000269|PubMed:21471201}.
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:0000269|PubMed:21987377}.
CC -!- PTM: S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent
CC protein deacetylase activity. {ECO:0000250|UniProtKB:Q923E4}.
CC -!- PTM: Acetylated at various Lys residues. Deacetylated via an
CC autocatalytic mechanism. Autodeacetylation at Lys-238 promotes its
CC protein deacetylase activity. {ECO:0000250|UniProtKB:Q923E4}.
CC -!- MISCELLANEOUS: Red wine, which contains resveratrol, may participate in
CC activation of sirtuin proteins, and may therefore participate in an
CC extended lifespan as it has been observed in yeast.
CC -!- MISCELLANEOUS: Calf histone H1 is used as substrate in the in vitro
CC deacetylation assay (PubMed:15469825). As, in vivo, interaction occurs
CC between SIRT1 with H1-4, deacetylation has been validated only for H1-
CC 4. {ECO:0000305|PubMed:15469825}.
CC -!- MISCELLANEOUS: The reported ADP-ribosyltransferase activity of sirtuins
CC is likely some inefficient side reaction of the deacetylase activity
CC and may not be physiologically relevant. {ECO:0000305|PubMed:19220062}.
CC -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH12499.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/sirt1/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SIRT1ID44006ch10q21.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF083106; AAD40849.2; -; mRNA.
DR EMBL; AF235040; AAG38486.1; -; mRNA.
DR EMBL; DQ278604; ABB72675.1; -; Genomic_DNA.
DR EMBL; AL133551; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012499; AAH12499.1; ALT_INIT; mRNA.
DR CCDS; CCDS7273.1; -. [Q96EB6-1]
DR RefSeq; NP_001135970.1; NM_001142498.1.
DR RefSeq; NP_001300978.1; NM_001314049.1.
DR RefSeq; NP_036370.2; NM_012238.4. [Q96EB6-1]
DR PDB; 4I5I; X-ray; 2.50 A; A/B=241-516.
DR PDB; 4IF6; X-ray; 2.25 A; A=234-510, B=641-665.
DR PDB; 4IG9; X-ray; 2.64 A; A/C/E/G=234-510, B/D/F/H=641-665.
DR PDB; 4KXQ; X-ray; 1.85 A; A=234-510, B=641-663.
DR PDB; 4ZZH; X-ray; 3.10 A; A=183-505.
DR PDB; 4ZZI; X-ray; 2.73 A; A=183-505.
DR PDB; 4ZZJ; X-ray; 2.74 A; A=183-505.
DR PDB; 5BTR; X-ray; 3.20 A; A/B/C=143-665.
DR PDBsum; 4I5I; -.
DR PDBsum; 4IF6; -.
DR PDBsum; 4IG9; -.
DR PDBsum; 4KXQ; -.
DR PDBsum; 4ZZH; -.
DR PDBsum; 4ZZI; -.
DR PDBsum; 4ZZJ; -.
DR PDBsum; 5BTR; -.
DR AlphaFoldDB; Q96EB6; -.
DR SMR; Q96EB6; -.
DR BioGRID; 116983; 368.
DR ComplexPortal; CPX-467; eNoSc complex.
DR CORUM; Q96EB6; -.
DR DIP; DIP-29757N; -.
DR IntAct; Q96EB6; 182.
DR MINT; Q96EB6; -.
DR STRING; 9606.ENSP00000212015; -.
DR BindingDB; Q96EB6; -.
DR ChEMBL; CHEMBL4506; -.
DR DrugBank; DB15493; Cambinol.
DR DrugBank; DB02709; Resveratrol.
DR DrugBank; DB13978; Selisistat.
DR DrugCentral; Q96EB6; -.
DR GuidetoPHARMACOLOGY; 2707; -.
DR GlyGen; Q96EB6; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q96EB6; -.
DR MetOSite; Q96EB6; -.
DR PhosphoSitePlus; Q96EB6; -.
DR BioMuta; SIRT1; -.
DR DMDM; 38258633; -.
DR EPD; Q96EB6; -.
DR jPOST; Q96EB6; -.
DR MassIVE; Q96EB6; -.
DR MaxQB; Q96EB6; -.
DR PaxDb; Q96EB6; -.
DR PeptideAtlas; Q96EB6; -.
DR PRIDE; Q96EB6; -.
DR ProteomicsDB; 76393; -. [Q96EB6-1]
DR ProteomicsDB; 76394; -. [Q96EB6-2]
DR Antibodypedia; 1637; 1162 antibodies from 52 providers.
DR DNASU; 23411; -.
DR Ensembl; ENST00000212015.11; ENSP00000212015.6; ENSG00000096717.12. [Q96EB6-1]
DR GeneID; 23411; -.
DR KEGG; hsa:23411; -.
DR MANE-Select; ENST00000212015.11; ENSP00000212015.6; NM_012238.5; NP_036370.2.
DR UCSC; uc001jnd.3; human. [Q96EB6-1]
DR CTD; 23411; -.
DR DisGeNET; 23411; -.
DR GeneCards; SIRT1; -.
DR HGNC; HGNC:14929; SIRT1.
DR HPA; ENSG00000096717; Low tissue specificity.
DR MIM; 604479; gene.
DR neXtProt; NX_Q96EB6; -.
DR OpenTargets; ENSG00000096717; -.
DR PharmGKB; PA37935; -.
DR VEuPathDB; HostDB:ENSG00000096717; -.
DR eggNOG; KOG2684; Eukaryota.
DR GeneTree; ENSGT00940000159406; -.
DR HOGENOM; CLU_016587_0_0_1; -.
DR InParanoid; Q96EB6; -.
DR OMA; ESECSAD; -.
DR OrthoDB; 751525at2759; -.
DR PhylomeDB; Q96EB6; -.
DR TreeFam; TF105896; -.
DR BioCyc; MetaCyc:ENSG00000096717-MON; -.
DR BRENDA; 2.3.1.286; 2681.
DR PathwayCommons; Q96EB6; -.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-HSA-400253; Circadian Clock.
DR Reactome; R-HSA-427359; SIRT1 negatively regulates rRNA expression.
DR Reactome; R-HSA-9617629; Regulation of FOXO transcriptional activity by acetylation.
DR Reactome; R-HSA-9707616; Heme signaling.
DR SABIO-RK; Q96EB6; -.
DR SignaLink; Q96EB6; -.
DR SIGNOR; Q96EB6; -.
DR BioGRID-ORCS; 23411; 21 hits in 1093 CRISPR screens.
DR GeneWiki; Sirtuin_1; -.
DR GenomeRNAi; 23411; -.
DR Pharos; Q96EB6; Tchem.
DR PRO; PR:Q96EB6; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q96EB6; protein.
DR Bgee; ENSG00000096717; Expressed in calcaneal tendon and 190 other tissues.
DR ExpressionAtlas; Q96EB6; baseline and differential.
DR Genevisible; Q96EB6; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0005677; C:chromatin silencing complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0061773; C:eNoSc complex; IPI:ComplexPortal.
DR GO; GO:0000791; C:euchromatin; IDA:UniProtKB.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0000792; C:heterochromatin; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005635; C:nuclear envelope; IDA:BHF-UCL.
DR GO; GO:0005637; C:nuclear inner membrane; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IDA:BHF-UCL.
DR GO; GO:0033553; C:rDNA heterochromatin; IDA:UniProtKB.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:UniProtKB.
DR GO; GO:0019213; F:deacetylase activity; IDA:UniProtKB.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0042393; F:histone binding; IPI:UniProtKB.
DR GO; GO:0004407; F:histone deacetylase activity; IDA:BHF-UCL.
DR GO; GO:0043398; F:HLH domain binding; IPI:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL.
DR GO; GO:1990254; F:keratin filament binding; IPI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0070403; F:NAD+ binding; IBA:GO_Central.
DR GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:UniProtKB.
DR GO; GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); ISS:UniProtKB.
DR GO; GO:0160012; F:NAD-dependent histone decrotonylase activity; IDA:UniProtKB.
DR GO; GO:0034979; F:NAD-dependent protein deacetylase activity; IDA:UniProtKB.
DR GO; GO:0016922; F:nuclear receptor binding; IPI:UniProtKB.
DR GO; GO:0002039; F:p53 binding; IPI:BHF-UCL.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IEA:Ensembl.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0033558; F:protein lysine deacetylase activity; IDA:UniProtKB.
DR GO; GO:0106231; F:protein-propionyllysine depropionylase activity; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:BHF-UCL.
DR GO; GO:0001525; P:angiogenesis; IDA:UniProtKB.
DR GO; GO:0042595; P:behavioral response to starvation; IEA:Ensembl.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0042149; P:cellular response to glucose starvation; IMP:ComplexPortal.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:BHF-UCL.
DR GO; GO:0071456; P:cellular response to hypoxia; IMP:UniProtKB.
DR GO; GO:0071479; P:cellular response to ionizing radiation; ISS:UniProtKB.
DR GO; GO:1990830; P:cellular response to leukemia inhibitory factor; IEA:Ensembl.
DR GO; GO:0009267; P:cellular response to starvation; ISS:BHF-UCL.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:UniProtKB.
DR GO; GO:0035356; P:cellular triglyceride homeostasis; ISS:UniProtKB.
DR GO; GO:0042632; P:cholesterol homeostasis; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IMP:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0006346; P:DNA methylation-dependent heterochromatin assembly; TAS:UniProtKB.
DR GO; GO:0000731; P:DNA synthesis involved in DNA repair; ISS:UniProtKB.
DR GO; GO:0097009; P:energy homeostasis; IMP:ComplexPortal.
DR GO; GO:0055089; P:fatty acid homeostasis; ISS:UniProtKB.
DR GO; GO:0031507; P:heterochromatin assembly; IDA:BHF-UCL.
DR GO; GO:0016575; P:histone deacetylation; IDA:UniProtKB.
DR GO; GO:0070932; P:histone H3 deacetylation; IDA:BHF-UCL.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:UniProtKB.
DR GO; GO:0033210; P:leptin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0030225; P:macrophage differentiation; ISS:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; IDA:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; IMP:ComplexPortal.
DR GO; GO:0030308; P:negative regulation of cell growth; IMP:BHF-UCL.
DR GO; GO:2000655; P:negative regulation of cellular response to testosterone stimulus; IMP:BHF-UCL.
DR GO; GO:2000773; P:negative regulation of cellular senescence; IDA:UniProtKB.
DR GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; IDA:BHF-UCL.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; ISS:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:AgBase.
DR GO; GO:0051097; P:negative regulation of helicase activity; IDA:UniProtKB.
DR GO; GO:0071441; P:negative regulation of histone H3-K14 acetylation; IMP:CACAO.
DR GO; GO:1900113; P:negative regulation of histone H3-K9 trimethylation; IEA:Ensembl.
DR GO; GO:2000619; P:negative regulation of histone H4-K16 acetylation; IMP:CACAO.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IDA:UniProtKB.
DR GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISS:BHF-UCL.
DR GO; GO:1901215; P:negative regulation of neuron death; IEA:Ensembl.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:UniProtKB.
DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; IMP:BHF-UCL.
DR GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; IDA:UniProtKB.
DR GO; GO:0042326; P:negative regulation of phosphorylation; IMP:UniProtKB.
DR GO; GO:0031393; P:negative regulation of prostaglandin biosynthetic process; ISS:UniProtKB.
DR GO; GO:1901984; P:negative regulation of protein acetylation; IMP:AgBase.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:UniProtKB.
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:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001542; P:ovulation from ovarian follicle; IEA:Ensembl.
DR GO; GO:0018394; P:peptidyl-lysine acetylation; IMP:UniProtKB.
DR GO; GO:0034983; P:peptidyl-lysine deacetylation; IDA:BHF-UCL.
DR GO; GO:0002821; P:positive regulation of adaptive immune response; IDA:UniProtKB.
DR GO; GO:1904179; P:positive regulation of adipose tissue development; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IDA:BHF-UCL.
DR GO; GO:2000481; P:positive regulation of cAMP-dependent protein kinase activity; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:2000774; P:positive regulation of cellular senescence; IDA:UniProtKB.
DR GO; GO:0010875; P:positive regulation of cholesterol efflux; ISS:UniProtKB.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IMP:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:AgBase.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IDA:UniProtKB.
DR GO; GO:0031065; P:positive regulation of histone deacetylation; IMP:ComplexPortal.
DR GO; GO:0051574; P:positive regulation of histone H3-K9 methylation; IMP:UniProtKB.
DR GO; GO:0031062; P:positive regulation of histone methylation; IMP:ComplexPortal.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IDA:UniProtKB.
DR GO; GO:2000111; P:positive regulation of macrophage apoptotic process; ISS:UniProtKB.
DR GO; GO:0060907; P:positive regulation of macrophage cytokine production; ISS:UniProtKB.
DR GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; IDA:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; IEA:Ensembl.
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; IMP:UniProtKB.
DR GO; GO:0006476; P:protein deacetylation; IDA:UniProtKB.
DR GO; GO:0106230; P:protein depropionylation; ISS:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0000720; P:pyrimidine dimer repair by nucleotide-excision repair; IMP:UniProtKB.
DR GO; GO:0000183; P:rDNA heterochromatin assembly; IDA:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0070857; P:regulation of bile acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0090335; P:regulation of brown fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome.
DR GO; GO:0010824; P:regulation of centrosome duplication; IDA:UniProtKB.
DR GO; GO:0032071; P:regulation of endodeoxyribonuclease activity; IMP:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; ISS:UniProtKB.
DR GO; GO:0010883; P:regulation of lipid storage; ISS:UniProtKB.
DR GO; GO:0007346; P:regulation of mitotic cell cycle; IDA:UniProtKB.
DR GO; GO:0035358; P:regulation of peroxisome proliferator activated receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0071900; P:regulation of protein serine/threonine kinase activity; IMP:AgBase.
DR GO; GO:0034391; P:regulation of smooth muscle cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0046015; P:regulation of transcription by glucose; IMP:ComplexPortal.
DR GO; GO:0042542; P:response to hydrogen peroxide; IDA:UniProtKB.
DR GO; GO:0032868; P:response to insulin; ISS:UniProtKB.
DR GO; GO:0044321; P:response to leptin; ISS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0000012; P:single strand break repair; IMP:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0090400; P:stress-induced premature senescence; IMP:CACAO.
DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0006642; P:triglyceride mobilization; ISS:BHF-UCL.
DR GO; GO:0070914; P:UV-damage excision repair; IMP:CACAO.
DR GO; GO:0050872; P:white fat cell differentiation; ISS: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 3D-structure; Acetylation; Alternative splicing; Apoptosis;
KW Biological rhythms; Cytoplasm; Developmental protein; Differentiation;
KW Host-virus interaction; Metal-binding; Methylation; Mitochondrion;
KW Myogenesis; NAD; Nucleus; Phosphoprotein; Reference proteome;
KW S-nitrosylation; Transcription; Transcription regulation; Transferase;
KW Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..747
FT /note="NAD-dependent protein deacetylase sirtuin-1"
FT /id="PRO_0000110256"
FT CHAIN 2..533
FT /note="SirtT1 75 kDa fragment"
FT /id="PRO_0000415289"
FT DOMAIN 244..498
FT /note="Deacetylase sirtuin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT REGION 1..135
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2..268
FT /note="Interaction with H1-4"
FT /evidence="ECO:0000269|PubMed:15469825"
FT REGION 2..139
FT /note="Interaction with CLOCK"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT REGION 143..541
FT /note="Interaction with CCAR2"
FT REGION 256..259
FT /note="Required for interaction with the sumoylated form of
FT CCAR2"
FT /evidence="ECO:0000269|PubMed:25406032"
FT REGION 523..549
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 538..540
FT /note="Phosphorylated at one of three serine residues"
FT REGION 562..587
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 663..726
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 32..39
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 138..145
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOTIF 223..230
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 425..431
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 28..45
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 119..135
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 532..549
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 563..583
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 663..686
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 687..703
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 363
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:11672523,
FT ECO:0000269|PubMed:12006491, ECO:0000269|PubMed:12535671,
FT ECO:0000269|PubMed:17290224, ECO:0000269|PubMed:18004385,
FT ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18485871,
FT ECO:0000269|PubMed:19934257, ECO:0000269|PubMed:25406032,
FT ECO:0000269|PubMed:28497810"
FT BINDING 261..280
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 345..348
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 371
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 374
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 395
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 398
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
FT BINDING 440..442
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 465..467
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
FT BINDING 482
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19107194,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19107194"
FT MOD_RES 27
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000269|PubMed:18838864,
FT ECO:0000269|PubMed:19107194, ECO:0000269|PubMed:20027304,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 47
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000269|PubMed:18838864,
FT ECO:0000269|PubMed:19107194, ECO:0000269|PubMed:20027304,
FT ECO:0000269|PubMed:21471201, ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 159
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:19107194"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:19107194"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19107194"
FT MOD_RES 173
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19107194"
FT MOD_RES 238
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 377
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 395
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 398
FT /note="S-nitrosocysteine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 430
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 513
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 530
FT /note="Phosphothreonine; by DYRK1A, DYRK3 and MAPK8"
FT /evidence="ECO:0000269|PubMed:19107194,
FT ECO:0000269|PubMed:20027304, ECO:0007744|PubMed:19690332"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 544
FT /note="Phosphothreonine"
FT /evidence="ECO:0000305|PubMed:19107194"
FT MOD_RES 545
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:19107194"
FT MOD_RES 610
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 659
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000250|UniProtKB:Q923E4"
FT MOD_RES 661
FT /note="Phosphoserine; by CaMK2"
FT /evidence="ECO:0000305|PubMed:19236849"
FT MOD_RES 719
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:19107194,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 747
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:19107194"
FT VAR_SEQ 454..639
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_042189"
FT VARIANT 3
FT /note="D -> E (in dbSNP:rs35671182)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_025148"
FT VARIANT 484
FT /note="V -> D (in dbSNP:rs1063111)"
FT /id="VAR_051976"
FT MUTAGEN 27
FT /note="S->A: Greatly diminishes phosphorylation by MAPK8;
FT when associated with A-47 and A-530."
FT /evidence="ECO:0000269|PubMed:20027304"
FT MUTAGEN 47
FT /note="S->A: Blocks residue phosphorylation, restores
FT deacetylation activity and inhibits DNA damage-induced
FT apoptosis."
FT /evidence="ECO:0000269|PubMed:20027304,
FT ECO:0000269|PubMed:21471201"
FT MUTAGEN 47
FT /note="S->A: Greatly diminishes phosphorylation by MAPK8;
FT when associated with A-27 and A-530."
FT /evidence="ECO:0000269|PubMed:20027304,
FT ECO:0000269|PubMed:21471201"
FT MUTAGEN 233
FT /note="K->R: Impairs in vitro methylation by SETD7; when
FT associated with R-235, R-236 and R-238."
FT /evidence="ECO:0000269|PubMed:21245319"
FT MUTAGEN 235
FT /note="K->R: Impairs in vitro methylation by SETD7; when
FT associated with R-233, R-236 and R-238."
FT /evidence="ECO:0000269|PubMed:21245319"
FT MUTAGEN 236
FT /note="K->R: Impairs in vitro methylation by SETD7; when
FT associated with R-233, R-235 and R-238."
FT /evidence="ECO:0000269|PubMed:21245319"
FT MUTAGEN 238
FT /note="K->R: Impairs in vitro methylation by SETD7; when
FT associated with R-233, R-235a and R-236."
FT /evidence="ECO:0000269|PubMed:21245319"
FT MUTAGEN 256..257
FT /note="II->KK: Loss of interaction with the sumoylated form
FT of CCAR2. No effect on its deacetylation activity."
FT /evidence="ECO:0000269|PubMed:25406032"
FT MUTAGEN 363
FT /note="H->Y: Loss of function; abolishes both protein
FT deacetylase and decrotonylase activities. Reduces the
FT interaction with CCAR2 and APEX1. Increases acetylation of
FT APEX1."
FT /evidence="ECO:0000269|PubMed:11672523,
FT ECO:0000269|PubMed:12006491, ECO:0000269|PubMed:12535671,
FT ECO:0000269|PubMed:17290224, ECO:0000269|PubMed:18004385,
FT ECO:0000269|PubMed:18235501, ECO:0000269|PubMed:18485871,
FT ECO:0000269|PubMed:19934257, ECO:0000269|PubMed:25406032,
FT ECO:0000269|PubMed:28497810, ECO:0000269|PubMed:32034146,
FT ECO:0000269|PubMed:32538779"
FT MUTAGEN 474
FT /note="F->A: Abolishes phosphorylation at Ser-47, restores
FT deacetylation activity and inhibits DNA damage-induced
FT apoptosis."
FT /evidence="ECO:0000269|PubMed:21471201"
FT MUTAGEN 530
FT /note="T->A: Greatly diminishes phosphorylation by MAPK8;
FT when associated with A-27 and A-47."
FT /evidence="ECO:0000269|PubMed:19107194,
FT ECO:0000269|PubMed:20027304"
FT MUTAGEN 530
FT /note="T->A: Reduces in vitro phosphorylation by CDK1.
FT Impairs cell proliferation and cell cycle progression; when
FT associated with A-540."
FT /evidence="ECO:0000269|PubMed:19107194,
FT ECO:0000269|PubMed:20027304"
FT MUTAGEN 540
FT /note="S->A: Reduces in vitro phosphorylation by CDK1.
FT Impairs cell proliferation and cell cycle progression; when
FT associated with A-530."
FT /evidence="ECO:0000269|PubMed:19107194"
FT MUTAGEN 659
FT /note="S->A: Reduces in vitro phosphorylation by CaMK2;
FT when associated with S-661. Greatly reduces in vivo
FT phosphorylation; when associated with A-661."
FT /evidence="ECO:0000269|PubMed:19236849"
FT MUTAGEN 661
FT /note="S->A: Reduces in vitro phosphorylation by CaMK2;
FT when associated with S-659. Greatly reduces in vivo
FT phosphorylation; when associated with A-659."
FT /evidence="ECO:0000269|PubMed:19236849"
FT MUTAGEN 684
FT /note="S->A: No effect on phosphorylation (in vitro and in
FT vivo)."
FT /evidence="ECO:0000269|PubMed:19236849"
FT CONFLICT 386..389
FT /note="DIFN -> ALFS (in Ref. 5; AAH12499)"
FT /evidence="ECO:0000305"
FT HELIX 184..194
FT /evidence="ECO:0007829|PDB:4ZZI"
FT HELIX 198..205
FT /evidence="ECO:0007829|PDB:4ZZI"
FT HELIX 217..228
FT /evidence="ECO:0007829|PDB:4ZZI"
FT HELIX 243..252
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 254..260
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 262..268
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 273..275
FT /evidence="ECO:0007829|PDB:4KXQ"
FT TURN 276..278
FT /evidence="ECO:0007829|PDB:4IG9"
FT HELIX 279..286
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 293..297
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 299..304
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 307..312
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 313..316
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:4I5I"
FT HELIX 325..335
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 339..344
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 350..354
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 358..361
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 364..371
FT /evidence="ECO:0007829|PDB:4KXQ"
FT TURN 372..374
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 377..379
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 380..382
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 384..388
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 396..398
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 406..411
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 420..429
FT /evidence="ECO:0007829|PDB:4KXQ"
FT TURN 430..432
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 435..440
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 448..450
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 451..454
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 461..467
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 475..480
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 482..493
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 495..500
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 506..510
FT /evidence="ECO:0007829|PDB:5BTR"
FT STRAND 643..645
FT /evidence="ECO:0007829|PDB:4KXQ"
FT TURN 646..648
FT /evidence="ECO:0007829|PDB:4KXQ"
FT STRAND 649..651
FT /evidence="ECO:0007829|PDB:4KXQ"
FT HELIX 656..658
FT /evidence="ECO:0007829|PDB:4KXQ"
SQ 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
