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NAD-dependent protein deacetylase sirtuin-1



Mus musculus (Mouse)
Reviewed-Annotation score: -Experimental evidence at protein leveli


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 HIST1H1E. Deacetylates 'Lys-16' of histone H4 (in vitro). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression. Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting. Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1. Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response. Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence. Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I. Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability. Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity; also leading to FOXO3 ubiquitination and protesomal degradation. Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis. Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing. Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha. Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1. Deacetylates FOXO1, which increases its DNA binding ability and enhances its transcriptional activity leading to increased gluconeogenesis in liver. Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation. Involved in HES1- and HEY2-mediated transcriptional repression. In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62'. Deacetylates MEF2D. Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3. Represses HNF1A-mediated transcription. Required for the repression of ESRRG by CREBZF. Modulates AP-1 transcription factor activity. Deacetylates NR1H3 AND NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteosomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed. Involved in lipid metabolism. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2. Deacetylates ACSS2 leading to its activation, and HMGCS1. Involved in liver and muscle metabolism. Through deacteylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletel muscle under low-glucose conditions and is involved in glucose homeostasis. Involved in regulation of PPARA and fatty acid beta-oxidation in liver. Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating its insulin-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression. Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and faciliting recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2. Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN. Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1. Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-537' and 'Lys-540' 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, repress selective NOTCH1-target genes through histone deacetylation in a BCL6-dependent manner and leading to neuronal differentiation. Regulates the circadian expression of several core clock genes, including ARNTL/BMAL1, RORC, PER2 and CRY1 and plays a critical role in maintaining a controlled rhythmicity in histone acetylation, thereby contributing to circadian chromatin remodeling. Deacetylates ARNTL/BMAL1 and histones at the circadian gene promoters in order to facilitate repression by inhibitory components of the circadian oscillator. Deacetylates PER2, facilitating its ubiquitination and degradation by the proteosome. Protects cardiomyocytes against palmitate-induced apoptosis (PubMed:11250901, PubMed:11672522, PubMed:12651913, PubMed:12887892, PubMed:12960381, PubMed:15175761, PubMed:15220471, PubMed:15632193, PubMed:15744310, PubMed:15788402, PubMed:16098828, PubMed:16366736, PubMed:16790548, PubMed:16892051, PubMed:17098745, PubMed:17347648, PubMed:17620057, PubMed:17901049, PubMed:17936707, PubMed:18004385, PubMed:18296641, PubMed:18371449, PubMed:18477450, PubMed:18662546, PubMed:18662547, PubMed:18687677, PubMed:19299583, PubMed:19356714, PubMed:20817729, PubMed:21176092, PubMed:21187328, PubMed:21189328, PubMed:21622680, PubMed:23160044, PubMed:20167603). Deacetylates XBP1 isoform 2; deacetylation decreases protein stability of XBP1 isoform 2 and inhibits its transcriptional activity. Involved in the CCAR2-mediated regulation of PCK1 and NR1D1. Deacetylates CTNB1 at 'Lys-49' (By similarity). In POMC (pro-opiomelanocortin) neurons, required for leptin-induced activation of PI3K signaling (PubMed:20620997).By similarity36 Publications
Isoform 2: Isoform 2 is shown to deacetylate 'Lys-382' of p53/TP53, however with lower activity than isoform 1. In combination, the two isoforms exert an additive effect. Isoform 2 regulates p53/TP53 expression and cellular stress response and is in turn repressed by p53/TP53 presenting a SIRT1 isoform-dependent auto-regulatory loop.By similarity
SirtT1 75 kDa fragment: catalytically inactive 75SirT1 may be involved in regulation of apoptosis. May be involved in protecting chondrocytes from apoptotic death by associating with cytochrome C and interfering with apoptosome assembly.By similarity

Catalytic activityi

NAD+ + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.PROSITE-ProRule annotation1 Publication


Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Activated by resveratrol (3,5,4'-trihydroxy-trans-stilbene), butein (3,4,2',4'-tetrahydroxychalcone), piceatannol (3,5,3',4'-tetrahydroxy-trans-stilbene), Isoliquiritigenin (4,2',4'-trihydroxychalcone), fisetin (3,7,3',4'-tetrahydroxyflavone) and quercetin (3,5,7,3',4'-pentahydroxyflavone). MAPK8/JNK1 and RPS19BP1/AROS act as positive regulators of deacetylation activity (By similarity). Inhibited by nicotinamide. Negatively regulated by CCAR2 (By similarity).By similarity


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei355Proton acceptor1
Metal bindingi363ZincPROSITE-ProRule annotation1
Metal bindingi366ZincPROSITE-ProRule annotation1
Metal bindingi387ZincPROSITE-ProRule annotation1
Metal bindingi390ZincPROSITE-ProRule annotation1
Binding sitei474NAD; via amide nitrogenBy similarity1


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi253 – 272NADBy similarityAdd BLAST20
Nucleotide bindingi337 – 340NADBy similarity4
Nucleotide bindingi432 – 434NADBy similarity3
Nucleotide bindingi457 – 459NADBy similarity3

GO - Molecular functioni

  • bHLH transcription factor binding Source: UniProtKB
  • core promoter sequence-specific DNA binding Source: UniProtKB
  • deacetylase activity Source: UniProtKB
  • enzyme binding Source: UniProtKB
  • histone binding Source: MGI
  • histone deacetylase activity Source: MGI
  • HLH domain binding Source: MGI
  • identical protein binding Source: MGI
  • keratin filament binding Source: MGI
  • metal ion binding Source: UniProtKB-KW
  • mitogen-activated protein kinase binding Source: MGI
  • NAD+ binding Source: InterPro
  • NAD-dependent histone deacetylase activity Source: MGI
  • NAD-dependent histone deacetylase activity (H3-K9 specific) Source: UniProtKB
  • NAD-dependent protein deacetylase activity Source: UniProtKB
  • nuclear hormone receptor binding Source: MGI
  • p53 binding Source: BHF-UCL
  • protein C-terminus binding Source: MGI
  • protein deacetylase activity Source: UniProtKB
  • protein domain specific binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: BHF-UCL
  • transcription corepressor activity Source: BHF-UCL
  • transcription factor binding Source: MGI

GO - Biological processi

  • angiogenesis Source: UniProtKB
  • behavioral response to starvation Source: MGI
  • cellular glucose homeostasis Source: UniProtKB
  • cellular response to DNA damage stimulus Source: MGI
  • cellular response to hydrogen peroxide Source: MGI
  • cellular response to hypoxia Source: UniProtKB
  • cellular response to ionizing radiation Source: UniProtKB
  • cellular response to leukemia inhibitory factor Source: MGI
  • cellular response to starvation Source: BHF-UCL
  • cellular response to tumor necrosis factor Source: UniProtKB
  • cellular triglyceride homeostasis Source: UniProtKB
  • cholesterol homeostasis Source: UniProtKB
  • chromatin organization Source: MGI
  • chromatin silencing at rDNA Source: MGI
  • circadian regulation of gene expression Source: UniProtKB
  • circadian rhythm Source: UniProtKB
  • DNA synthesis involved in DNA repair Source: UniProtKB
  • establishment of chromatin silencing Source: MGI
  • fatty acid homeostasis Source: UniProtKB
  • histone deacetylation Source: UniProtKB
  • histone H3 deacetylation Source: MGI
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
  • leptin-mediated signaling pathway Source: UniProtKB
  • macrophage cytokine production Source: UniProtKB
  • macrophage differentiation Source: UniProtKB
  • maintenance of chromatin silencing Source: MGI
  • muscle organ development Source: UniProtKB-KW
  • negative regulation of androgen receptor signaling pathway Source: MGI
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cAMP-dependent protein kinase activity Source: UniProtKB
  • negative regulation of cell growth Source: MGI
  • negative regulation of cellular response to testosterone stimulus Source: MGI
  • negative regulation of cellular senescence Source: UniProtKB
  • negative regulation of DNA binding transcription factor activity Source: ParkinsonsUK-UCL
  • negative regulation of DNA damage response, signal transduction by p53 class mediator Source: MGI
  • negative regulation of fat cell differentiation Source: BHF-UCL
  • negative regulation of gene expression Source: MGI
  • negative regulation of helicase activity Source: MGI
  • negative regulation of histone H3-K14 acetylation Source: MGI
  • negative regulation of histone H3-K9 trimethylation Source: BHF-UCL
  • negative regulation of histone H4-K16 acetylation Source: MGI
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: BHF-UCL
  • negative regulation of neuron death Source: MGI
  • negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway Source: MGI
  • negative regulation of peptidyl-lysine acetylation Source: UniProtKB
  • negative regulation of phosphorylation Source: UniProtKB
  • negative regulation of prostaglandin biosynthetic process Source: UniProtKB
  • negative regulation of protein acetylation Source: MGI
  • negative regulation of protein kinase B signaling Source: UniProtKB
  • negative regulation of TOR signaling Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: MGI
  • negative regulation of transcription by RNA polymerase II Source: BHF-UCL
  • negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKB
  • ovulation from ovarian follicle Source: MGI
  • peptidyl-lysine acetylation Source: MGI
  • peptidyl-lysine deacetylation Source: MGI
  • positive regulation of adaptive immune response Source: UniProtKB
  • positive regulation of adipose tissue development Source: UniProtKB
  • positive regulation of angiogenesis Source: MGI
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of blood vessel endothelial cell migration Source: MGI
  • positive regulation of cAMP-dependent protein kinase activity Source: UniProtKB
  • positive regulation of cell proliferation Source: UniProtKB
  • positive regulation of cellular senescence Source: UniProtKB
  • positive regulation of cholesterol efflux Source: UniProtKB
  • positive regulation of chromatin silencing Source: MGI
  • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • positive regulation of DNA repair Source: UniProtKB
  • positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway Source: UniProtKB
  • positive regulation of endothelial cell proliferation Source: MGI
  • positive regulation of histone H3-K9 methylation Source: MGI
  • positive regulation of insulin receptor signaling pathway Source: UniProtKB
  • positive regulation of macroautophagy Source: UniProtKB
  • positive regulation of macrophage apoptotic process Source: UniProtKB
  • positive regulation of MHC class II biosynthetic process Source: MGI
  • positive regulation of phosphatidylinositol 3-kinase signaling Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of smooth muscle cell differentiation Source: BHF-UCL
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein deacetylation Source: BHF-UCL
  • protein destabilization Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • pyrimidine dimer repair by nucleotide-excision repair Source: UniProtKB
  • regulation of apoptotic process Source: UniProtKB
  • regulation of bile acid biosynthetic process Source: UniProtKB
  • regulation of brown fat cell differentiation Source: UniProtKB
  • regulation of cell proliferation Source: MGI
  • regulation of endodeoxyribonuclease activity Source: UniProtKB
  • regulation of glucose metabolic process Source: UniProtKB
  • regulation of lipid storage Source: UniProtKB
  • regulation of mitotic cell cycle Source: UniProtKB
  • regulation of peroxisome proliferator activated receptor signaling pathway Source: BHF-UCL
  • regulation of protein import into nucleus, translocation Source: MGI
  • regulation of protein serine/threonine kinase activity Source: MGI
  • regulation of smooth muscle cell apoptotic process Source: UniProtKB
  • response to hydrogen peroxide Source: UniProtKB
  • response to insulin Source: UniProtKB
  • response to leptin Source: UniProtKB
  • response to oxidative stress Source: MGI
  • rRNA processing Source: UniProtKB-KW
  • single strand break repair Source: UniProtKB
  • spermatogenesis Source: MGI
  • stress-induced premature senescence Source: MGI
  • transforming growth factor beta receptor signaling pathway Source: MGI
  • triglyceride mobilization Source: BHF-UCL
  • UV-damage excision repair Source: MGI
  • white fat cell differentiation Source: BHF-UCL


Molecular functionDevelopmental protein, Hydrolase
Biological processApoptosis, Biological rhythms, Differentiation, Myogenesis, rRNA processing, Transcription, Transcription regulation
LigandMetal-binding, NAD, Zinc

Enzyme and pathway databases

BRENDAi3.5.1.98 3474
ReactomeiR-MMU-3371453 Regulation of HSF1-mediated heat shock response
R-MMU-427359 SIRT1 negatively regulates rRNA expression

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent protein deacetylase sirtuin-1 (EC:3.5.1.-1 Publication)
Alternative name(s):
Regulatory protein SIR2 homolog 1
SIR2-like protein 1
Short name:
Short name:
Cleaved into the following chain:
SirtT1 75 kDa fragment
Short name:
Gene namesi
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:2135607 Sirt1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Mitochondrion, Nucleus

Pathology & Biotechi

Disruption phenotypei

High degree of embryonic and postnatal lethality. Decreased levels of histone H3 containing a trimethyl group at its lysine 9 position (H3K9me3) in regions of heterochromatin. Attenuates spermatogenesis but not oogenesis with reduced numbers of mature sperm and spermatogenic precursors. Mice develop an autoimmune-like condition with late onset diabetes insipidus. Prostatic intraepithelial neoplasia associated with reduced autophagy. Conditional knockout in POMC neurons leads to an increase of body weight compare to controls when animals are challenged with high-fat diet (PubMed:20620997).6 Publications


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi37 – 38RR → AA: Abolishes nuclear localization; when associated with A-227; A-228; A-229 and A-230. 2
Mutagenesisi138 – 145LLLTDGLL → AAATGAA: Abolishes nuclear export; when associated with A-425; A-427; A-428; A-429; A-430 and A-431. 1 Publication8
Mutagenesisi154S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-649; A-651 and A-683. 1 Publication1
Mutagenesisi227 – 230KKRK → AAAA: Abolishes nuclear localization; when associated with A-37 and A-38. 1 Publication4
Mutagenesisi355H → Y: Loss of deacetylation activity. Loss of inhibition of E2F1 and loss of coactivation of FOXO1-mediated transcription. 4 Publications1
Mutagenesisi363C → S: Does not affect S-nitrosylation. 1 Publication1
Mutagenesisi366C → S: Does not affect S-nitrosylation. 1 Publication1
Mutagenesisi387C → S: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with S-390. 1 Publication1
Mutagenesisi390C → S: Impairs S-nitrosylation. Abolishes S-nitrosylation; when associated with S-387. 1 Publication1
Mutagenesisi425 – 431VDLLIVI → ADAAAAA: Abolishes nuclear export; when associated with A-138; A-139; A-140; A-144 and A-145. 1 Publication7
Mutagenesisi522T → D: Increased deacetylase activity toward p53/TP53 and increases resistance to genotoxic stress (mimicks residue phosphorylation). 1 Publication1
Mutagenesisi522T → V: Reduces phosphorylation. Impairs deacetylase activity toward p53/TP53 and decreases resistance to genotoxic stress. Does not change nuclear localization. 1 Publication1
Mutagenesisi649S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-651 and A-683. 1 Publication1
Mutagenesisi651S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-649 and A-683. 1 Publication1
Mutagenesisi683S → A: Abolishes in vitro phosphorylation by CaMK2; when associated with A-154; A-649 and A-651. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001102572 – 737NAD-dependent protein deacetylase sirtuin-1Add BLAST736
ChainiPRO_00004152902 – 525SirtT1 75 kDa fragmentBy similarityAdd BLAST524

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei14PhosphoserineBy similarity1
Modified residuei25PhosphoserineBy similarity1
Modified residuei46Phosphoserine; by MAPK8By similarity1
Modified residuei151PhosphoserineCombined sources1
Modified residuei154PhosphoserineCombined sources1
Modified residuei164PhosphoserineBy similarity1
Modified residuei165PhosphoserineBy similarity1
Modified residuei387S-nitrosocysteine1 Publication1
Modified residuei390S-nitrosocysteine1 Publication1
Modified residuei522Phosphothreonine; by DYRK1A, DYRK3 and MAPK81 Publication1
Modified residuei527PhosphoserineBy similarity1
Modified residuei536PhosphothreonineBy similarity1
Modified residuei649Phosphoserine; by CaMK21 Publication1
Modified residuei651Phosphoserine; by CaMK2By similarity1
Modified residuei737PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated. Phosphorylated by STK4/MST1, resulting in inhibition of SIRT1-mediated p53/TP53 deacetylation. Phosphorylation by MAPK8/JNK1 at Ser-46 and Thr-522 leads to increased nuclear localization and enzymatic activity. Phosphorylation at Thr-522 by DYRK1A and DYRK3 activates deacetylase activity and promotes cell survival (PubMed:20167603). Phosphorylation by mammalian target of rapamycin complex 1 (mTORC1) at Ser-46 inhibits deacetylation activity. Phosphorylated by CaMK2, leading to increased p53/TP53 and NF-kappa-B p65/RELA deacetylation activity (By similarity).By similarity1 Publication
Proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield catalytic inactive but stable SirtT1 75 kDa fragment (75SirT1).By similarity
S-nitrosylated by GAPDH, leading to inhibit the NAD-dependent protein deacetylase activity.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein, S-nitrosylation

Proteomic databases


PTM databases



Tissue specificityi

Widely expressed. Weakly expressed in liver and skeletal muscle.1 Publication


By calorie restriction which induces endothelial nitric oxide synthase (eNOS) expression. Induced in liver by pyruvate during fasting. Expressed in a circadian manner in the liver with maximal and minimal levels reached at around Zeitgeber time (ZT) 16 and ZT4, respectively. Its deacetylase activity in the liver is also regulated in a circadian manner, with a peak at ZT15. Down-regulated by palmitate; palmitate down-regulation is mediated by the induction of miR-195 that directly targets SIRT1.5 Publications

Gene expression databases

ExpressionAtlasiQ923E4 baseline and differential
GenevisibleiQ923E4 MM


Subunit structurei

Interacts with XBP1 isoform 2 (By similarity). Found in a complex with PCAF and MYOD1 Component of the eNoSC complex, composed of SIRT1, SUV39H1 and RRP8. Interacts with HES1, HEY2 and PML. Interacts with RPS19BP1/AROS. Interacts with CCAR2 (via N-terminus); the interaction disrupts the interaction between SIRT1 and p53/TP53. Interacts with SETD7; the interaction induces the dissociation of SIRT1 from p53/TP53 and increases p53/TP53 activity. Interacts with MYCN, NR1I2, CREBZF, TSC2, TLE1, FOS, JUN, NR0B2, PPARG, NCOR, IRS1, IRS2 and NMNAT1. Interacts with HNF1A; the interaction occurs under nutrient restriction. Interacts with SUZ12; the interaction mediates the association with the PRC4 histone methylation complex which is specific as an association with PCR2 and PCR3 complex variants is not found. Interacts with FOXO1; the interaction deacetylates FOXO1, enhances its DNA-binding ability and increases its transcriptional activity. Interacts with BCL6; leads to a epigenetic repression of specific target genes. Interacts with CLOCK, ARNTL/BMAL1 and PER2. Interacts with PPARA; the interaction seems to be modulated by NAD+ levels. Interacts with NR1H3 and this interaction is inhibited in the presence of CCAR2. Interacts with CHEK2 and p53/TP53. Exhibits a preferential interaction with sumoylated CCAR2 over its unmodified form (By similarity).By similarity16 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi220297, 45 interactors
IntActiQ923E4, 49 interactors


3D structure databases


Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini236 – 490Deacetylase sirtuin-typePROSITE-ProRule annotationAdd BLAST255


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni2 – 268Interaction with HIST1H1EAdd BLAST267
Regioni2 – 131Interaction with CLOCK1 PublicationAdd BLAST130
Regioni135 – 533Interaction with CCAR2By similarityAdd BLAST399
Regioni248 – 251Required for interaction with the sumoylated form of CCAR2By similarity4


Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi32 – 39Nuclear localization signal8
Motifi138 – 145Nuclear export signal8
Motifi223 – 230Nuclear localization signal8
Motifi425 – 431Nuclear export signal7

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi2 – 131Ala-richAdd BLAST130
Compositional biasi155 – 158Poly-Asp4

Sequence similaritiesi

Belongs to the sirtuin family. Class I subfamily.Curated

Phylogenomic databases

eggNOGiKOG2684 Eukaryota

Family and domain databases

Gene3Di3.30.1600.10, 2 hits
InterProiView protein in InterPro
IPR029035 DHS-like_NAD/FAD-binding_dom
IPR003000 Sirtuin
IPR026591 Sirtuin_cat_small_dom_sf
IPR026590 Ssirtuin_cat_dom
PfamiView protein in Pfam
PF02146 SIR2, 1 hit
SUPFAMiSSF52467 SSF52467, 1 hit
PROSITEiView protein in PROSITE
PS50305 SIRTUIN, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q923E4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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Mass (Da):80,372
Last modified:October 31, 2003 - v2
Isoform 2 (identifier: Q923E4-2) [UniParc]FASTAAdd to basket
Also known as: delta-exon8

The sequence of this isoform differs from the canonical sequence as follows:
     446-629: Missing.

Show »
Mass (Da):59,875

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_042190446 – 629Missing in isoform 2. CuratedAdd BLAST184

Sequence databases

Select the link destinations:
Links Updated
AF214646 mRNA Translation: AAF24983.1
BC006584 mRNA Translation: AAH06584.1
CCDSiCCDS23898.1 [Q923E4-1]
RefSeqiNP_062786.1, NM_019812.3 [Q923E4-1]

Genome annotation databases

EnsembliENSMUST00000020257; ENSMUSP00000020257; ENSMUSG00000020063 [Q923E4-1]
ENSMUST00000120239; ENSMUSP00000112595; ENSMUSG00000020063 [Q923E4-1]
ENSMUST00000177694; ENSMUSP00000137565; ENSMUSG00000020063 [Q923E4-2]
UCSCiuc007fke.2 mouse [Q923E4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSIR1_MOUSE
AccessioniPrimary (citable) accession number: Q923E4
Secondary accession number(s): Q9QXG8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 31, 2003
Last sequence update: October 31, 2003
Last modified: May 23, 2018
This is version 166 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program


Keywords - Technical termi

Complete proteome, Reference proteome

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