NAD-dependent protein deacetylase sirtuin-1 (EC 2 3 1 286) (NAD-dependent protein deacylase sirtuin-1) (EC 2 3 1 -)

 SIR1_RAT                Reviewed;         555 AA.
 A0A0G2JZ79;
 08-JUN-2016, integrated into UniProtKB/Swiss-Prot.
 08-JUN-2016, sequence version 2.
 17-JUN-2020, entry version 41.
 RecName: Full=NAD-dependent protein deacetylase sirtuin-1 {ECO:0000250|UniProtKB:Q923E4};
          EC=2.3.1.286 {ECO:0000250|UniProtKB:Q96EB6};
 AltName: Full=NAD-dependent protein deacylase sirtuin-1;
          EC=2.3.1.- {ECO:0000250|UniProtKB:Q923E4};
 Name=Sirt1 {ECO:0000312|RGD:1308542};
 Rattus norvegicus (Rat).
 Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
 Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
 Murinae; Rattus.
 NCBI_TaxID=10116;
 [1]
 NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
 STRAIN=Brown Norway;
 PubMed=15057822; DOI=10.1038/nature02426;
 Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
 Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
 Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
 Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
 Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
 Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
 Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
 Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
 Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
 Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
 Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
 Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
 Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
 Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
 Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
 Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
 Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
 Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
 Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
 Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
 Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
 Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
 Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
 Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
 Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
 Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
 Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
 Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
 Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
 Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
 Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
 Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
 Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
 Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
 Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
 Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
 Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
 Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
 Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
 Mockrin S., Collins F.S.;
 "Genome sequence of the Brown Norway rat yields insights into mammalian
 evolution.";
 Nature 428:493-521(2004).
 -!- FUNCTION: NAD-dependent protein deacetylase that links transcriptional
     regulation directly to intracellular energetics and participates in the
     coordination of several separated cellular functions such as cell
     cycle, response to DNA damage, metabolism, apoptosis and autophagy. Can
     modulate chromatin function through deacetylation of histones and can
     promote alterations in the methylation of histones and DNA, leading to
     transcriptional repression. Deacetylates a broad range of transcription
     factors and coregulators, thereby regulating target gene expression
     positively and negatively. Serves as a sensor of the cytosolic ratio of
     NAD(+)/NADH which is altered by glucose deprivation and metabolic
     changes associated with caloric restriction. Is essential in skeletal
     muscle cell differentiation and in response to low nutrients mediates
     the inhibitory effect on skeletal myoblast differentiation which also
     involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide
     phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-
     dependent nucleolar silencing) complex, a complex that mediates
     silencing of rDNA in response to intracellular energy status and acts
     by recruiting histone-modifying enzymes. The eNoSC complex is able to
     sense the energy status of cell: upon glucose starvation, elevation of
     NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3
     deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by
     SUV39H1 and the formation of silent chromatin in the rDNA locus.
     Deacetylates 'Lys-266' of SUV39H1, leading to its activation. Inhibits
     skeletal muscle differentiation by deacetylating PCAF and MYOD1.
     Deacetylates H2A and 'Lys-26' of H1-4. Deacetylates 'Lys-16' of histone
     H4 (in vitro). Involved in NR0B2/SHP corepression function through
     chromatin remodeling: Recruited to LRH1 target gene promoters by
     NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading
     to transcriptional repression. Proposed to contribute to genomic
     integrity via positive regulation of telomere length; however, reports
     on localization to pericentromeric heterochromatin are conflicting.
     Proposed to play a role in constitutive heterochromatin (CH) formation
     and/or maintenance through regulation of the available pool of nuclear
     SUV39H1. Upon oxidative/metabolic stress decreases SUV39H1 degradation
     by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in
     SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to
     accelerate renewal of the heterochromatin which correlates with greater
     genomic integrity during stress response. Deacetylates 'Lys-382' of
     p53/TP53 and impairs its ability to induce transcription-dependent
     proapoptotic program and modulate cell senescence. Deacetylates TAF1B
     and thereby represses rDNA transcription by the RNA polymerase I.
     Deacetylates MYC, promotes the association of MYC with MAX and
     decreases MYC stability leading to compromised transformational
     capability. Deacetylates FOXO3 in response to oxidative stress thereby
     increasing its ability to induce cell cycle arrest and resistance to
     oxidative stress but inhibiting FOXO3-mediated induction of apoptosis
     transcriptional activity; also leading to FOXO3 ubiquitination and
     protesomal degradation. Appears to have a similar effect on MLLT7/FOXO4
     in regulation of transcriptional activity and apoptosis. Deacetylates
     DNMT1; thereby impairs DNMT1 methyltransferase-independent
     transcription repressor activity, modulates DNMT1 cell cycle regulatory
     function and DNMT1-mediated gene silencing. Deacetylates RELA/NF-kappa-
     B p65 thereby inhibiting its transactivating potential and augments
     apoptosis in response to TNF-alpha. Deacetylates HIF1A, KAT5/TIP60, RB1
     and HIC1. Deacetylates FOXO1 resulting in its nuclear retention and
     enhancement of its transcriptional activity leading to increased
     gluconeogenesis in liver. Inhibits E2F1 transcriptional activity and
     apoptotic function, possibly by deacetylation. Involved in HES1- and
     HEY2-mediated transcriptional repression. In cooperation with MYCN
     seems to be involved in transcriptional repression of DUSP6/MAPK3
     leading to MYCN stabilization by phosphorylation at 'Ser-62'.
     Deacetylates MEF2D. Required for antagonist-mediated transcription
     suppression of AR-dependent genes which may be linked to local
     deacetylation of histone H3. Represses HNF1A-mediated transcription.
     Required for the repression of ESRRG by CREBZF. Deacetylates NR1H3 AND
     NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates
     transcription of NR1H3:RXR target genes, promotes NR1H3 proteosomal
     degradation and results in cholesterol efflux; a promoter clearing
     mechanism after reach round of transcription is proposed. Involved in
     lipid metabolism. Implicated in regulation of adipogenesis and fat
     mobilization in white adipocytes by repression of PPARG which probably
     involves association with NCOR1 and SMRT/NCOR2. Deacetylates p300/EP300
     and PRMT1. Deacetylates ACSS2 leading to its activation, and HMGCS1
     deacetylation. Involved in liver and muscle metabolism. Through
     deacetylation and activation of PPARGC1A is required to activate fatty
     acid oxidation in skeletal muscle under low-glucose conditions and is
     involved in glucose homeostasis. Involved in regulation of PPARA and
     fatty acid beta-oxidation in liver. Involved in positive regulation of
     insulin secretion in pancreatic beta cells in response to glucose; the
     function seems to imply transcriptional repression of UCP2. Proposed to
     deacetylate IRS2 thereby facilitating its insulin-induced tyrosine
     phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby
     decreasing its stability and transactivation in lipogenic gene
     expression. Involved in DNA damage response by repressing genes which
     are involved in DNA repair, such as XPC and TP73, deacetylating
     XRCC6/Ku70, and facilitating recruitment of additional factors to sites
     of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to
     initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2.
     Also involved in DNA repair of DNA double-strand breaks by homologous
     recombination and specifically single-strand annealing independently of
     XRCC6/Ku70 and NBN. Transcriptional suppression of XPC probably
     involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT)
     signaling. Transcriptional suppression of TP73 probably involves E2F4
     and PCAF. Deacetylates WRN thereby regulating its helicase and
     exonuclease activities and regulates WRN nuclear translocation in
     response to DNA damage. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and
     stimulates cellular AP endonuclease activity by promoting the
     association of APEX1 to XRCC1. Increases p53/TP53-mediated
     transcription-independent apoptosis by blocking nuclear translocation
     of cytoplasmic p53/TP53 and probably redirecting it to mitochondria.
     Deacetylates XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to
     sequester BAX away from mitochondria thereby inhibiting stress-induced
     apoptosis. Is involved in autophagy, presumably by deacetylating ATG5,
     ATG7 and MAP1LC3B/ATG8. Deacetylates AKT1 which leads to enhanced
     binding of AKT1 and PDK1 to PIP3 and promotes their activation.
     Proposed to play role in regulation of STK11/LBK1-dependent AMPK
     signaling pathways implicated in cellular senescence which seems to
     involve the regulation of the acetylation status of STK11/LBK1. Can
     deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic
     localization and association with STRAD; however, the relevance of such
     activity in normal cells is unclear. In endothelial cells is shown to
     inhibit STK11/LBK1 activity and to promote its degradation.
     Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its
     degradation. Deacetylates CIITA and augments its MHC class II
     transactivation and contributes to its stability. Deacetylates
     MECOM/EVI1. Deacetylates PML at 'Lys-487' and this deacetylation
     promotes PML control of PER2 nuclear localization. During the
     neurogenic transition, represses selective NOTCH1-target genes through
     histone deacetylation in a BCL6-dependent manner and leading to
     neuronal differentiation. Regulates the circadian expression of several
     core clock genes, including ARNTL/BMAL1, RORC, PER2 and CRY1 and plays
     a critical role in maintaining a controlled rhythmicity in histone
     acetylation, thereby contributing to circadian chromatin remodeling.
     Deacetylates ARNTL/BMAL1 and histones at the circadian gene promoters
     in order to facilitate repression by inhibitory components of the
     circadian oscillator. Deacetylates PER2, facilitating its
     ubiquitination and degradation by the proteosome. Protects
     cardiomyocytes against palmitate-induced apoptosis. Deacetylates XBP1
     isoform 2; deacetylation decreases protein stability of XBP1 isoform 2
     and inhibits its transcriptional activity. Deacetylates PCK1 and
     directs its activity toward phosphoenolpyruvate production promoting
     gluconeogenesis. Involved in the CCAR2-mediated regulation of PCK1 and
     NR1D1. Deacetylates CTNB1 at 'Lys-49'. In POMC (pro-opiomelanocortin)
     neurons, required for leptin-induced activation of PI3K signaling. In
     addition to protein deacetylase activity, also acts as protein-lysine
     deacylase: acts as a protein depropionylase by mediating
     depropionylation of Osterix (SP7). Deacetylates SOX9; promoting SOX9
     nuclear localization and transactivation activity.
     {ECO:0000250|UniProtKB:Q923E4, ECO:0000250|UniProtKB:Q96EB6}.
 -!- CATALYTIC ACTIVITY:
     Reaction=H2O + N(6)-acetyl-L-lysyl-[protein] + NAD(+) = 2''-O-acetyl-
       ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
       Xref=Rhea:RHEA:43636, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10731,
       ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
       ChEBI:CHEBI:57540, ChEBI:CHEBI:61930, ChEBI:CHEBI:83767;
       EC=2.3.1.286; Evidence={ECO:0000250|UniProtKB:Q96EB6,
       ECO:0000255|PROSITE-ProRule:PRU00236};
 -!- CATALYTIC ACTIVITY:
     Reaction=H2O + N(6)-propanoyl-L-lysyl-[protein] + NAD(+) = 3''-O-
       propanoyl-ADP-D-ribose + L-lysyl-[protein] + nicotinamide;
       Xref=Rhea:RHEA:23500, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:13758,
       ChEBI:CHEBI:15377, ChEBI:CHEBI:17154, ChEBI:CHEBI:29969,
       ChEBI:CHEBI:57540, ChEBI:CHEBI:138019, ChEBI:CHEBI:145015;
       Evidence={ECO:0000250|UniProtKB:Q923E4};
     PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23501;
       Evidence={ECO:0000250|UniProtKB:Q923E4};
 -!- COFACTOR:
     Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
       Evidence={ECO:0000250|UniProtKB:Q8IXJ6};
     Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q8IXJ6};
 -!- ACTIVITY REGULATION: Inhibited by nicotinamide. Activated by
     resveratrol (3,5,4'-trihydroxy-trans-stilbene), butein (3,4,2',4'-
     tetrahydroxychalcone), piceatannol (3,5,3',4'-tetrahydroxy-trans-
     stilbene), Isoliquiritigenin (4,2',4'-trihydroxychalcone), fisetin
     (3,7,3',4'-tetrahydroxyflavone) and quercetin (3,5,7,3',4'-
     pentahydroxyflavone). MAPK8/JNK1 and RPS19BP1/AROS act as positive
     regulators of deacetylation activity. Negatively regulated by CCAR2.
     {ECO:0000250|UniProtKB:Q96EB6}.
 -!- SUBUNIT: Interacts with XBP1 isoform 2 (By similarity). Found in a
     complex with PCAF and MYOD1. Interacts with FOXO1; the interaction
     deacetylates FOXO1, resulting in its nuclear retention and promotion of
     its transcriptional activity Component of the eNoSC complex, composed
     of SIRT1, SUV39H1 and RRP8. Interacts with HES1, HEY2 and PML.
     Interacts with RPS19BP1/AROS. Interacts with CCAR2 (via N-terminus);
     the interaction disrupts the interaction between SIRT1 and p53/TP53.
     Interacts with SETD7; the interaction induces the dissociation of SIRT1
     from p53/TP53 and increases p53/TP53 activity. Interacts with MYCN,
     NR1I2, CREBZF, TSC2, TLE1, FOS, JUN, NR0B2, PPARG, NCOR, IRS1, IRS2 and
     NMNAT1. Interacts with HNF1A; the interaction occurs under nutrient
     restriction. Interacts with SUZ12; the interaction mediates the
     association with the PRC4 histone methylation complex which is specific
     as an association with PCR2 and PCR3 complex variants is not found.
     Interacts with HIV-1 tat. Interacts with BCL6; leads to a epigenetic
     repression of specific target genes. Interacts with CLOCK, ARNTL/BMAL1
     and PER2 (By similarity). Interacts with PPARA; the interaction seems
     to be modulated by NAD(+) levels. Interacts with NR1H3 and this
     interaction is inhibited in the presence of CCAR2. Interacts with
     CHEK2. Interacts with p53/TP53. Exhibits a preferential interaction
     with sumoylated CCAR2 over its unmodified form (By similarity).
     Interacts with PACS2 (By similarity). Interacts with SIRT7 (By
     similarity). {ECO:0000250|UniProtKB:Q923E4,
     ECO:0000250|UniProtKB:Q96EB6}.
 -!- SUBCELLULAR LOCATION: Nucleus, PML body {ECO:0000250|UniProtKB:Q96EB6}.
     Cytoplasm {ECO:0000250|UniProtKB:Q96EB6}. Nucleus
     {ECO:0000250|UniProtKB:Q96EB6}. Note=Recruited to the nuclear bodies
     via its interaction with PML. Colocalized with APEX1 in the nucleus.
     May be found in nucleolus, nuclear euchromatin, heterochromatin and
     inner membrane (By similarity). Shuttles between nucleus and cytoplasm
     (By similarity). Colocalizes in the nucleus with XBP1 isoform 2 (By
     similarity). {ECO:0000250|UniProtKB:Q923E4,
     ECO:0000250|UniProtKB:Q96EB6}.
 -!- PTM: Methylated on multiple lysine residues; methylation is enhanced
     after DNA damage and is dispensable for deacetylase activity toward
     p53/TP53. {ECO:0000250|UniProtKB:Q96EB6}.
 -!- PTM: Phosphorylated. Phosphorylated by STK4/MST1, resulting in
     inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by
     MAPK8/JNK1 at Thr-338 leads to increased nuclear localization and
     enzymatic activity. Phosphorylation at Thr-338 by DYRK1A and DYRK3
     activates deacetylase activity and promotes cell survival.
     Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B
     p65/RELA deacetylation activity (By similarity).
     {ECO:0000250|UniProtKB:Q923E4, ECO:0000250|UniProtKB:Q96EB6}.
 -!- PTM: S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent
     protein deacetylase activity. {ECO:0000250|UniProtKB:Q923E4}.
 -!- PTM: Acetylated at various Lys residues. Deacetylated via an
     autocatalytic mechanism. Autodeacetylation at Lys-46 promotes its
     protein deacetylase activity. {ECO:0000250|UniProtKB:Q923E4}.
 -!- MISCELLANEOUS: Red wine, which contains resveratrol, may participate in
     activation of sirtuin proteins, and may therefore contribute to an
     extended lifespan as has been observed in yeast.
     {ECO:0000250|UniProtKB:Q96EB6}.
 -!- MISCELLANEOUS: Calf histone H1 is used as substrate in the in vitro
     deacetylation assay. As, in vivo, interaction occurs between SIRT1 with
     H1-4, deacetylation has been validated only for H1-4.
     {ECO:0000250|UniProtKB:Q96EB6}.
 -!- MISCELLANEOUS: The reported ADP-ribosyltransferase activity of sirtuins
     is likely to be an inefficient side reaction of the deacetylase
     activity and may not be physiologically relevant.
     {ECO:0000250|UniProtKB:Q96EB6}.
 -!- SIMILARITY: Belongs to the sirtuin family. Class I subfamily.
     {ECO:0000305}.
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 EMBL; AABR07044925; -; NOT_ANNOTATED_CDS; Genomic_DNA.
 SMR; A0A0G2JZ79; -.
 STRING; 10116.ENSRNOP00000000427; -.
 PaxDb; A0A0G2JZ79; -.
 RGD; 1308542; Sirt1.
 PRO; PR:A0A0G2JZ79; -.
 Proteomes; UP000002494; Unplaced.
 Bgee; ENSRNOG00000051592; Expressed in lung and 8 other tissues.
 GO; GO:0030424; C:axon; IDA:RGD.
 GO; GO:0005623; C:cell; IEA:GOC.
 GO; GO:0000785; C:chromatin; ISO:RGD.
 GO; GO:0005677; C:chromatin silencing complex; ISO:RGD.
 GO; GO:0005737; C:cytoplasm; ISO:RGD.
 GO; GO:0005829; C:cytosol; IDA:RGD.
 GO; GO:0030426; C:growth cone; IDA:RGD.
 GO; GO:0005739; C:mitochondrion; ISO:RGD.
 GO; GO:0000790; C:nuclear chromatin; ISO:RGD.
 GO; GO:0005635; C:nuclear envelope; ISO:RGD.
 GO; GO:0005719; C:nuclear euchromatin; ISO:RGD.
 GO; GO:0005720; C:nuclear heterochromatin; ISO:RGD.
 GO; GO:0005637; C:nuclear inner membrane; ISO:RGD.
 GO; GO:0005730; C:nucleolus; ISO:RGD.
 GO; GO:0005654; C:nucleoplasm; IBA:GO_Central.
 GO; GO:0005634; C:nucleus; IDA:RGD.
 GO; GO:0016605; C:PML body; ISO:RGD.
 GO; GO:0033553; C:rDNA heterochromatin; ISO:RGD.
 GO; GO:0043425; F:bHLH transcription factor binding; ISO:RGD.
 GO; GO:0019213; F:deacetylase activity; ISO:RGD.
 GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
 GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL.
 GO; GO:0042393; F:histone binding; ISO:RGD.
 GO; GO:0004407; F:histone deacetylase activity; ISO:RGD.
 GO; GO:0043398; F:HLH domain binding; ISO:RGD.
 GO; GO:0042802; F:identical protein binding; ISO:RGD.
 GO; GO:1990254; F:keratin filament binding; ISO:RGD.
 GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:RGD.
 GO; GO:0070403; F:NAD+ binding; IBA:GO_Central.
 GO; GO:0017136; F:NAD-dependent histone deacetylase activity; IDA:RGD.
 GO; GO:0046969; F:NAD-dependent histone deacetylase activity (H3-K9 specific); ISO:RGD.
 GO; GO:0034979; F:NAD-dependent protein deacetylase activity; ISO:RGD.
 GO; GO:0035257; F:nuclear hormone receptor binding; ISO:RGD.
 GO; GO:0002039; F:p53 binding; ISO:RGD.
 GO; GO:0008022; F:protein C-terminus binding; ISO:RGD.
 GO; GO:0033558; F:protein deacetylase activity; ISO:RGD.
 GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
 GO; GO:0043422; F:protein kinase B binding; IDA:RGD.
 GO; GO:0106231; F:protein-propionyllysine depropionylase activity; ISS:UniProtKB.
 GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
 GO; GO:0003714; F:transcription corepressor activity; ISO:RGD.
 GO; GO:0008134; F:transcription factor binding; ISO:RGD.
 GO; GO:0001525; P:angiogenesis; ISO:RGD.
 GO; GO:0042595; P:behavioral response to starvation; ISO:RGD.
 GO; GO:0007569; P:cell aging; IEP:RGD.
 GO; GO:0001678; P:cellular glucose homeostasis; ISO:RGD.
 GO; GO:1904646; P:cellular response to amyloid-beta; IMP:ARUK-UCL.
 GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
 GO; GO:1904644; P:cellular response to curcumin; IEP:RGD.
 GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
 GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
 GO; GO:0071456; P:cellular response to hypoxia; ISO:RGD.
 GO; GO:0071479; P:cellular response to ionizing radiation; ISO:RGD.
 GO; GO:1990830; P:cellular response to leukemia inhibitory factor; ISO:RGD.
 GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
 GO; GO:1904648; P:cellular response to rotenone; IEP:RGD.
 GO; GO:0009267; P:cellular response to starvation; ISO:RGD.
 GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:RGD.
 GO; GO:0071303; P:cellular response to vitamin B3; IEP:RGD.
 GO; GO:0035356; P:cellular triglyceride homeostasis; ISO:RGD.
 GO; GO:0042632; P:cholesterol homeostasis; ISO:RGD.
 GO; GO:0006325; P:chromatin organization; ISO:RGD.
 GO; GO:0000183; P:chromatin silencing at rDNA; ISO:RGD.
 GO; GO:0032922; P:circadian regulation of gene expression; ISO:RGD.
 GO; GO:0007623; P:circadian rhythm; ISO:RGD.
 GO; GO:0000731; P:DNA synthesis involved in DNA repair; ISO:RGD.
 GO; GO:0006343; P:establishment of chromatin silencing; ISO:RGD.
 GO; GO:0055089; P:fatty acid homeostasis; ISO:RGD.
 GO; GO:0016575; P:histone deacetylation; ISO:RGD.
 GO; GO:0070932; P:histone H3 deacetylation; IMP:RGD.
 GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISO:RGD.
 GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:RGD.
 GO; GO:0033210; P:leptin-mediated signaling pathway; ISO:RGD.
 GO; GO:0010934; P:macrophage cytokine production; ISO:RGD.
 GO; GO:0030225; P:macrophage differentiation; ISO:RGD.
 GO; GO:0006344; P:maintenance of chromatin silencing; ISO:RGD.
 GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
 GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; ISO:RGD.
 GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
 GO; GO:2000480; P:negative regulation of cAMP-dependent protein kinase activity; ISO:RGD.
 GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:RGD.
 GO; GO:0060548; P:negative regulation of cell death; IMP:RGD.
 GO; GO:0030308; P:negative regulation of cell growth; ISO:RGD.
 GO; GO:2000655; P:negative regulation of cellular response to testosterone stimulus; ISO:RGD.
 GO; GO:2000773; P:negative regulation of cellular senescence; ISO:RGD.
 GO; GO:0043392; P:negative regulation of DNA binding; IMP:RGD.
 GO; GO:0043518; P:negative regulation of DNA damage response, signal transduction by p53 class mediator; ISO:RGD.
 GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
 GO; GO:0045599; P:negative regulation of fat cell differentiation; ISO:RGD.
 GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; IMP:RGD.
 GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
 GO; GO:0060125; P:negative regulation of growth hormone secretion; IMP:RGD.
 GO; GO:0051097; P:negative regulation of helicase activity; ISO:RGD.
 GO; GO:0071441; P:negative regulation of histone H3-K14 acetylation; ISO:RGD.
 GO; GO:1900113; P:negative regulation of histone H3-K9 trimethylation; ISO:RGD.
 GO; GO:2000619; P:negative regulation of histone H4-K16 acetylation; ISO:RGD.
 GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; ISO:RGD.
 GO; GO:1902166; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:RGD.
 GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:ARUK-UCL.
 GO; GO:1901215; P:negative regulation of neuron death; ISO:RGD.
 GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:RGD.
 GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; ISO:RGD.
 GO; GO:2000757; P:negative regulation of peptidyl-lysine acetylation; ISO:RGD.
 GO; GO:0042326; P:negative regulation of phosphorylation; ISO:RGD.
 GO; GO:0031393; P:negative regulation of prostaglandin biosynthetic process; ISO:RGD.
 GO; GO:1901984; P:negative regulation of protein acetylation; IMP:RGD.
 GO; GO:0051898; P:negative regulation of protein kinase B signaling; ISO:RGD.
 GO; GO:1900181; P:negative regulation of protein localization to nucleus; IMP:RGD.
 GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IMP:RGD.
 GO; GO:0032007; P:negative regulation of TOR signaling; ISO:RGD.
 GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
 GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
 GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
 GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:RGD.
 GO; GO:0001542; P:ovulation from ovarian follicle; ISO:RGD.
 GO; GO:0018394; P:peptidyl-lysine acetylation; ISO:RGD.
 GO; GO:0034983; P:peptidyl-lysine deacetylation; ISO:RGD.
 GO; GO:0002821; P:positive regulation of adaptive immune response; ISO:RGD.
 GO; GO:1904179; P:positive regulation of adipose tissue development; ISO:RGD.
 GO; GO:0045766; P:positive regulation of angiogenesis; ISO:RGD.
 GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
 GO; GO:0097755; P:positive regulation of blood vessel diameter; IMP:RGD.
 GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD.
 GO; GO:2000481; P:positive regulation of cAMP-dependent protein kinase activity; ISO:RGD.
 GO; GO:0061051; P:positive regulation of cell growth involved in cardiac muscle cell development; IMP:RGD.
 GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
 GO; GO:2000774; P:positive regulation of cellular senescence; ISO:RGD.
 GO; GO:0010875; P:positive regulation of cholesterol efflux; ISO:RGD.
 GO; GO:0031937; P:positive regulation of chromatin silencing; ISO:RGD.
 GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISO:RGD.
 GO; GO:0045739; P:positive regulation of DNA repair; ISO:RGD.
 GO; GO:1902237; P:positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; ISO:RGD.
 GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:RGD.
 GO; GO:0045722; P:positive regulation of gluconeogenesis; IMP:RGD.
 GO; GO:0010460; P:positive regulation of heart rate; IMP:RGD.
 GO; GO:0051574; P:positive regulation of histone H3-K9 methylation; ISO:RGD.
 GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISO:RGD.
 GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:RGD.
 GO; GO:0016239; P:positive regulation of macroautophagy; ISO:RGD.
 GO; GO:2000111; P:positive regulation of macrophage apoptotic process; ISO:RGD.
 GO; GO:0045348; P:positive regulation of MHC class II biosynthetic process; ISO:RGD.
 GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD.
 GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; ISO:RGD.
 GO; GO:0090312; P:positive regulation of protein deacetylation; IMP:RGD.
 GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
 GO; GO:0014858; P:positive regulation of skeletal muscle cell proliferation; IMP:RGD.
 GO; GO:0051152; P:positive regulation of smooth muscle cell differentiation; ISO:RGD.
 GO; GO:2000614; P:positive regulation of thyroid-stimulating hormone secretion; IMP:RGD.
 GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
 GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; ISO:RGD.
 GO; GO:0006476; P:protein deacetylation; IDA:RGD.
 GO; GO:0106230; P:protein depropionylation; ISS:UniProtKB.
 GO; GO:0031648; P:protein destabilization; ISO:RGD.
 GO; GO:0016567; P:protein ubiquitination; ISO:RGD.
 GO; GO:0000720; P:pyrimidine dimer repair by nucleotide-excision repair; ISO:RGD.
 GO; GO:0042981; P:regulation of apoptotic process; ISO:RGD.
 GO; GO:0070857; P:regulation of bile acid biosynthetic process; ISO:RGD.
 GO; GO:0090335; P:regulation of brown fat cell differentiation; ISO:RGD.
 GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
 GO; GO:0032071; P:regulation of endodeoxyribonuclease activity; ISO:RGD.
 GO; GO:0010906; P:regulation of glucose metabolic process; ISO:RGD.
 GO; GO:0010883; P:regulation of lipid storage; ISO:RGD.
 GO; GO:0007346; P:regulation of mitotic cell cycle; ISO:RGD.
 GO; GO:0035358; P:regulation of peroxisome proliferator activated receptor signaling pathway; ISO:RGD.
 GO; GO:0071900; P:regulation of protein serine/threonine kinase activity; ISO:RGD.
 GO; GO:0034391; P:regulation of smooth muscle cell apoptotic process; ISO:RGD.
 GO; GO:0045471; P:response to ethanol; IDA:RGD.
 GO; GO:1902617; P:response to fluoride; IEP:RGD.
 GO; GO:0042542; P:response to hydrogen peroxide; ISO:RGD.
 GO; GO:0032868; P:response to insulin; ISO:RGD.
 GO; GO:1904373; P:response to kainic acid; IEP:RGD.
 GO; GO:0044321; P:response to leptin; ISO:RGD.
 GO; GO:0010046; P:response to mycotoxin; IEP:RGD.
 GO; GO:0031667; P:response to nutrient levels; IEP:RGD.
 GO; GO:0006979; P:response to oxidative stress; ISO:RGD.
 GO; GO:1904638; P:response to resveratrol; IEP:RGD.
 GO; GO:0000012; P:single strand break repair; ISO:RGD.
 GO; GO:0007283; P:spermatogenesis; ISO:RGD.
 GO; GO:0090400; P:stress-induced premature senescence; ISO:RGD.
 GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD.
 GO; GO:0006642; P:triglyceride mobilization; ISO:RGD.
 GO; GO:0070914; P:UV-damage excision repair; ISO:RGD.
 GO; GO:0050872; P:white fat cell differentiation; ISO:RGD.
 Gene3D; 3.30.1600.10; -; 1.
 InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
 InterPro; IPR003000; Sirtuin.
 InterPro; IPR026591; Sirtuin_cat_small_dom_sf.
 InterPro; IPR026590; Ssirtuin_cat_dom.
 Pfam; PF02146; SIR2; 1.
 SUPFAM; SSF52467; SSF52467; 1.
 PROSITE; PS50305; SIRTUIN; 1.
 3: Inferred from homology;
 Acetylation; Apoptosis; Biological rhythms; Cytoplasm;
 Developmental protein; Differentiation; Metal-binding; Methylation;
 Myogenesis; NAD; Nucleus; Phosphoprotein; Reference proteome;
 S-nitrosylation; Transcription; Transcription regulation; Transferase;
 Zinc.
 CHAIN           1..555
                 /note="NAD-dependent protein deacetylase sirtuin-1"
                 /id="PRO_0000436411"
 DOMAIN          52..306
                 /note="Deacetylase sirtuin-type"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
 NP_BIND         69..88
                 /note="NAD"
                 /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
 NP_BIND         153..156
                 /note="NAD"
                 /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
 NP_BIND         248..250
                 /note="NAD"
                 /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
 NP_BIND         273..275
                 /note="NAD"
                 /evidence="ECO:0000250|UniProtKB:Q8IXJ6"
 REGION          64..67
                 /note="Required for interaction with the sumoylated form of
                 CCAR2"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOTIF           39..46
                 /note="Nuclear localization signal"
                 /evidence="ECO:0000250|UniProtKB:Q923E4"
 MOTIF           241..247
                 /note="Nuclear export signal"
                 /evidence="ECO:0000250|UniProtKB:Q923E4"
 ACT_SITE        171
                 /note="Proton acceptor"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
 METAL           179
                 /note="Zinc"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
 METAL           182
                 /note="Zinc"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
 METAL           203
                 /note="Zinc"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
 METAL           206
                 /note="Zinc"
                 /evidence="ECO:0000255|PROSITE-ProRule:PRU00236"
 BINDING         290
                 /note="NAD; via amide nitrogen"
                 /evidence="ECO:0000250"
 MOD_RES         46
                 /note="N6-acetyllysine"
                 /evidence="ECO:0000250|UniProtKB:Q923E4"
 MOD_RES         185
                 /note="N6-acetyllysine"
                 /evidence="ECO:0000250|UniProtKB:Q923E4"
 MOD_RES         203
                 /note="S-nitrosocysteine"
                 /evidence="ECO:0000250|UniProtKB:Q923E4"
 MOD_RES         206
                 /note="S-nitrosocysteine"
                 /evidence="ECO:0000250|UniProtKB:Q923E4"
 MOD_RES         238
                 /note="N6-acetyllysine"
                 /evidence="ECO:0000250|UniProtKB:Q923E4"
 MOD_RES         321
                 /note="N6-acetyllysine"
                 /evidence="ECO:0000250|UniProtKB:Q923E4"
 MOD_RES         338
                 /note="Phosphothreonine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         343
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         352
                 /note="Phosphothreonine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         417
                 /note="N6-acetyllysine"
                 /evidence="ECO:0000250|UniProtKB:Q923E4"
 MOD_RES         466
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q923E4"
 MOD_RES         468
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 MOD_RES         552
                 /note="Phosphoserine"
                 /evidence="ECO:0000250|UniProtKB:Q96EB6"
 SEQUENCE   555 AA;  62059 MW;  A408C8A746AB812F CRC64;
 MIGTDPRTIL KDLLPETIPP PELDDMTLWQ IVINILSEPP KRKKRKDINT IEDAVKLLQE
 CKKIIVLTGA GVSVSCGIPD FRSRDGIYAR LAVDFPDLPD PQAMFDIEYF RKDPRPFFKF
 AKEIYPGQFQ PSLCHKFIAL SDKEGKLLRN YTQNIDTLEQ VAGIQRIIQC HGSFATASCL
 ICKYKVDCEA VRGDIFNQVV PRCPRCPADE PLAIMKPEIV FFGENLPEQF HRAMKYDKDE
 VDLLIVIGSS LKVRPVALIP SSIPHEVPQI LINREPLPHL HFDVELLGDC DVIINELCHR
 LGGEYAKLCC NPVKLSEITE KPPRTQKELV HLSELPPTPL HISEDSSSPE RTVPQDSSVI
 ATLVDQTIKN KVDDLEVSEP KSCVEEKSQE VQTYRNVESI NVENPDFKAV GSSTGDKNER
 TSVAETVRKC WPNRLAKEQI SKRLDGNQYL FVPPNRYIFH GAEVYSDSED DALSSSSCGS
 NSDSGTCQSP SLEEPLEDES EIEEFYNGLE DDADRPECAG GSGADGGDQE AVNEAIAMKQ
 ELTDVNCTPD KSEHY

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