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SIRT1 an NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separate cellular functions such as cell cycle, response to DNA damage, metobolism, apoptosis and autophagy. 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. 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. Elevation of NAD(+)/NADP(+) ratio activates SIRT1. Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG. Involved in liver and muscle metabolism. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and ATG8. Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation. Widely expressed. Inhibited by nicotinamide. Belongs to the sirtuin family. Class I subfamily. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Apoptosis; Deacetylase; EC 3.5.1.-; Nuclear receptor co-regulator
Chromosomal Location of Human Ortholog: 10|10 B4
Cellular Component: axon; chromatin; chromatin silencing complex; cytoplasm; cytosol; ESC/E(Z) complex; growth cone; mitochondrion; nuclear chromatin; nuclear envelope; nuclear heterochromatin; nuclear inner membrane; nucleoplasm; nucleus; PML body
Molecular Function: bHLH transcription factor binding; deacetylase activity; enzyme binding; histone binding; histone deacetylase activity; HLH domain binding; identical protein binding; mitogen-activated protein kinase binding; NAD-dependent histone deacetylase activity; NAD-dependent histone deacetylase activity (H3-K9 specific); nuclear hormone receptor binding; p53 binding; protein binding; protein C-terminus binding; protein deacetylase activity; protein domain specific binding; protein kinase B binding; transcription corepressor activity; transcription factor binding
Biological Process: angiogenesis; behavioral response to starvation; cell glucose homeostasis; cellular response to starvation; cholesterol homeostasis; chromatin silencing at rDNA; circadian regulation of gene expression; circadian rhythm; DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis; DNA damage response, signal transduction resulting in induction of apoptosis; DNA synthesis during DNA repair; establishment and/or maintenance of chromatin architecture; establishment of chromatin silencing; fatty acid homeostasis; histone deacetylation; inhibition of NF-kappaB transcription factor; leptin-mediated signaling pathway; macrophage differentiation; maintenance of chromatin silencing; negative regulation of apoptosis; negative regulation of cell growth; negative regulation of DNA binding; negative regulation of DNA damage response, signal transduction by p53 class mediator; negative regulation of fat cell differentiation; negative regulation of growth hormone secretion; negative regulation of helicase activity; negative regulation of I-kappaB kinase/NF-kappaB cascade; negative regulation of neuron apoptosis; negative regulation of phosphorylation; negative regulation of prostaglandin biosynthetic process; negative regulation of protein kinase B signaling cascade; negative regulation of TOR signaling pathway; negative regulation of transcription factor activity; negative regulation of transcription from RNA polymerase II promoter; negative regulation of transcription, DNA-dependent; negative regulation of transforming growth factor beta receptor signaling pathway; negative regulation of tumor necrosis factor production; ovulation from ovarian follicle; peptidyl-lysine acetylation; positive regulation of adaptive immune response; positive regulation of angiogenesis; positive regulation of apoptosis; positive regulation of caspase activity; positive regulation of cell proliferation; positive regulation of chromatin silencing; positive regulation of DNA repair; positive regulation of endothelial cell proliferation; positive regulation of gluconeogenesis; positive regulation of heart rate; positive regulation of histone H3-K9 methylation; positive regulation of insulin receptor signaling pathway; positive regulation of macroautophagy; positive regulation of MHC class II biosynthetic process; positive regulation of phosphoinositide 3-kinase cascade; positive regulation of protein amino acid phosphorylation; positive regulation of skeletal muscle cell proliferation; positive regulation of smooth muscle cell differentiation; positive regulation of transcription from RNA polymerase II promoter; proteasomal ubiquitin-dependent protein catabolic process; protein amino acid deacetylation; protein destabilization; protein ubiquitination; pyrimidine dimer repair via nucleotide-excision repair; regulation of apoptosis; regulation of cell proliferation; regulation of endodeoxyribonuclease activity; regulation of mitotic cell cycle; regulation of protein import into nucleus, translocation; response to DNA damage stimulus; response to ethanol; response to hydrogen peroxide; response to insulin stimulus; response to oxidative stress; single strand break repair; spermatogenesis; triacylglycerol mobilization; white fat cell differentiation
Reference #:  Q923E4 (UniProtKB)
Alt. Names/Synonyms: AA673258; MGC150273; mSIR2a; NAD-dependent deacetylase sirtuin-1; Sir2; sir2-like 1; SIR2-like protein 1; Sir2a; SIR2alpha; Sir2l1; Sirt1; sirtuin 1 ((silent mating type information regulation 2, homolog) 1; sirtuin 1 (silent mating type information regulation 2, homolog) 1 (S. cerevisiae)
Gene Symbols: Sirt1
Molecular weight: 80,372 Da
Basal Isoelectric point: 4.6  Predict pI for various phosphorylation states
CST Pathways:  AMPK Signaling  |  Protein Acetylation
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
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