SIRT1 Active Protein

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.

Protein type: Deacetylase; Apoptosis; EC 3.5.1.-; Nuclear receptor co-regulator

Chromosomal Location of Human Ortholog: 10q21.3

Cellular Component: nucleoplasm; chromatin silencing complex; PML body; mitochondrion; ESC/E(Z) complex; nuclear chromatin; cytoplasm; nucleolus; nuclear inner membrane; nuclear envelope; nuclear heterochromatin; nucleus

Molecular Function: deacetylase activity; protein C-terminus binding; identical protein binding; histone binding; p53 binding; metal ion binding; protein deacetylase activity; transcription factor binding; protein binding; NAD-dependent histone deacetylase activity (H3-K9 specific); enzyme binding; NAD-dependent histone deacetylase activity; bHLH transcription factor binding; mitogen-activated protein kinase binding; histone deacetylase activity; transcription corepressor activity; HLH domain binding; NAD+ ADP-ribosyltransferase activity

Biological Process: establishment and/or maintenance of chromatin architecture; muscle development; viral reproduction; positive regulation of apoptosis; regulation of mitotic cell cycle; positive regulation of caspase activity; protein ubiquitination; negative regulation of prostaglandin biosynthetic process; negative regulation of DNA damage response, signal transduction by p53 class mediator; negative regulation of gene expression, epigenetic; behavioral response to starvation; positive regulation of adaptive immune response; positive regulation of histone H3-K9 methylation; positive regulation of DNA repair; transcription, DNA-dependent; negative regulation of transcription factor activity; pyrimidine dimer repair via nucleotide-excision repair; cell aging; negative regulation of I-kappaB kinase/NF-kappaB cascade; ovulation from ovarian follicle; cellular response to starvation; negative regulation of fat cell differentiation; regulation of endodeoxyribonuclease activity; cholesterol homeostasis; protein amino acid ADP-ribosylation; methylation-dependent chromatin silencing; inhibition of NF-kappaB transcription factor; maintenance of chromatin silencing; regulation of protein import into nucleus, translocation; negative regulation of phosphorylation; positive regulation of transcription from RNA polymerase II promoter; response to oxidative stress; triacylglycerol mobilization; negative regulation of transcription, DNA-dependent; rRNA processing; peptidyl-lysine acetylation; negative regulation of apoptosis; chromatin silencing at rDNA; proteasomal ubiquitin-dependent protein catabolic process; establishment of chromatin silencing; chromatin silencing; negative regulation of transcription from RNA polymerase II promoter; regulation of gene expression, epigenetic; response to insulin stimulus; DNA synthesis during DNA repair; protein amino acid deacetylation; positive regulation of MHC class II biosynthetic process; positive regulation of cell proliferation; angiogenesis; circadian regulation of gene expression; DNA replication; DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis; positive regulation of chromatin silencing; single strand break repair; negative regulation of TOR signaling pathway; negative regulation of protein kinase B signaling cascade; protein destabilization; histone deacetylation; DNA repair; regulation of cell proliferation; negative regulation of helicase activity; response to hydrogen peroxide; fatty acid homeostasis; white fat cell differentiation; cell glucose homeostasis; spermatogenesis; gene expression; positive regulation of protein amino acid phosphorylation; positive regulation of insulin receptor signaling pathway; negative regulation of cell growth; negative regulation of transforming growth factor beta receptor signaling pathway; response to DNA damage stimulus; positive regulation of macroautophagy