SIRT1 an NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics. Participates in the coordination of several separate 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. 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: 10q21.3
Cellular Component:  chromatin; chromatin silencing complex; cytoplasm; cytosol; eNoSc complex; euchromatin; fibrillar center; heterochromatin; mitochondrion; nuclear envelope; nuclear inner membrane; nucleolus; nucleoplasm; nucleus; PML body; rDNA heterochromatin
Molecular Function:  bHLH transcription factor binding; deacetylase activity; DNA-binding transcription factor binding; enzyme binding; histone binding; histone deacetylase activity; HLH domain binding; identical protein binding; keratin filament binding; metal ion binding; mitogen-activated protein kinase binding; NAD+ ADP-ribosyltransferase activity; NAD+ binding; NAD+-protein ADP-ribosyltransferase activity; NAD-dependent histone deacetylase activity; NAD-dependent histone decrotonylase activity; NAD-dependent histone H3K9 deacetylase activity; NAD-dependent protein deacetylase activity; nuclear receptor binding; p53 binding; promoter-specific chromatin binding; protein binding; protein C-terminus binding; protein lysine deacetylase activity; protein-propionyllysine depropionylase activity; RNA polymerase II cis-regulatory region sequence-specific DNA binding; transcription coactivator activity; transcription corepressor activity
Biological Process:  angiogenesis; behavioral response to starvation; cellular glucose homeostasis; cellular response to DNA damage stimulus; cellular response to glucose starvation; cellular response to hydrogen peroxide; cellular response to hypoxia; cellular response to ionizing radiation; cellular response to leukemia inhibitory factor; cellular response to starvation; cellular response to tumor necrosis factor; cellular triglyceride homeostasis; cholesterol homeostasis; chromatin organization; circadian regulation of gene expression; DNA methylation-dependent heterochromatin formation; DNA synthesis involved in DNA repair; energy homeostasis; fatty acid homeostasis; heterochromatin formation; histone deacetylation; histone H3 deacetylation; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; leptin-mediated signaling pathway; macrophage differentiation; muscle organ development; negative regulation of androgen receptor signaling pathway; negative regulation of apoptotic process; negative regulation of cAMP-dependent protein kinase activity; negative regulation of cell cycle; negative regulation of cell growth; negative regulation of cellular response to testosterone stimulus; negative regulation of cellular senescence; negative regulation of DNA damage response, signal transduction by p53 class mediator; negative regulation of DNA-binding transcription factor activity; negative regulation of DNA-templated transcription; negative regulation of fat cell differentiation; negative regulation of gene expression; negative regulation of helicase activity; negative regulation of histone H3-K14 acetylation; negative regulation of histone H3-K9 trimethylation; negative regulation of histone H4-K16 acetylation; negative regulation of I-kappaB kinase/NF-kappaB signaling; negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; negative regulation of neuron death; negative regulation of NF-kappaB transcription factor activity; negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; negative regulation of peptidyl-lysine acetylation; negative regulation of phosphorylation; negative regulation of prostaglandin biosynthetic process; negative regulation of protein acetylation; negative regulation of protein kinase B signaling; negative regulation of TOR signaling; negative regulation of transcription by RNA polymerase II; negative regulation of transforming growth factor beta receptor signaling pathway; ovulation from ovarian follicle; peptidyl-lysine acetylation; peptidyl-lysine deacetylation; positive regulation of adaptive immune response; positive regulation of adipose tissue development; positive regulation of angiogenesis; positive regulation of apoptotic process; positive regulation of blood vessel endothelial cell migration; positive regulation of cAMP-dependent protein kinase activity; positive regulation of cell population proliferation; positive regulation of cellular senescence; positive regulation of cholesterol efflux; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; positive regulation of DNA repair; positive regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway; positive regulation of endothelial cell proliferation; positive regulation of gluconeogenesis; positive regulation of histone deacetylation; positive regulation of histone H3-K9 methylation; positive regulation of histone methylation; positive regulation of insulin receptor signaling pathway; positive regulation of macroautophagy; positive regulation of macrophage apoptotic process; positive regulation of macrophage cytokine production; positive regulation of MHC class II biosynthetic process; positive regulation of phosphatidylinositol 3-kinase signaling; positive regulation of protein phosphorylation; positive regulation of smooth muscle cell differentiation; positive regulation of transcription by RNA polymerase II; proteasome-mediated ubiquitin-dependent protein catabolic process; protein deacetylation; protein depropionylation; protein destabilization; protein ubiquitination; pyrimidine dimer repair by nucleotide-excision repair; rDNA heterochromatin formation; regulation of apoptotic process; regulation of bile acid biosynthetic process; regulation of brown fat cell differentiation; regulation of cell population proliferation; regulation of cellular response to heat; regulation of centrosome duplication; regulation of endodeoxyribonuclease activity; regulation of glucose metabolic process; regulation of lipid storage; regulation of mitotic cell cycle; regulation of peroxisome proliferator activated receptor signaling pathway; regulation of protein serine/threonine kinase activity; regulation of smooth muscle cell apoptotic process; regulation of transcription by glucose; response to hydrogen peroxide; response to insulin; response to leptin; response to oxidative stress; single strand break repair; spermatogenesis; stress-induced premature senescence; transforming growth factor beta receptor signaling pathway; triglyceride mobilization; UV-damage excision repair; white fat cell differentiation
Reference #:  Q96EB6 (UniProtKB)
Alt. Names/Synonyms: 75SirT1; hSIR2; hSIRT1; NAD-dependent deacetylase sirtuin-1; NAD-dependent protein deacetylase sirtuin-1; NAD-dependent protein deacylase sirtuin-1; Regulatory protein SIR2 homolog 1; SIR1; SIR2; sir2-like 1; SIR2-like protein 1; SIR2alpha; SIR2L1; SIRT1; SirtT1 75 kDa fragment; sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae); sirtuin 1; sirtuin type 1
Gene Symbols: SIRT1
Molecular weight: 81,681 Da
Basal Isoelectric point: 4.55  Predict pI for various phosphorylation states
CST Pathways:  AMPK Signaling  |  Protein Acetylation
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

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