Sirtuin 1 (SIRT1) Antibody – Rabbit Polyclonal

This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class I of the sirtuin family. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

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

Chromosomal Location of Human Ortholog: 10q21.3

Cellular Component: chromatin silencing complex; cytoplasm; cytosol; ESC/E(Z) complex; mitochondrion; nuclear chromatin; nuclear envelope; nuclear euchromatin; nuclear heterochromatin; nuclear inner membrane; nucleolus; 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; keratin filament binding; metal ion binding; mitogen-activated protein kinase binding; NAD+ ADP-ribosyltransferase activity; NAD+ 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; transcription corepressor activity; transcription factor binding

Biological Process: angiogenesis; behavioral response to starvation; cell aging; cell glucose homeostasis; cellular response to DNA damage stimulus; cellular response to hydrogen peroxide; cellular response to hypoxia; cellular response to ionizing radiation; cellular response to starvation; cellular response to tumor necrosis factor; cholesterol homeostasis; chromatin organization; chromatin silencing; chromatin silencing at rDNA; circadian regulation of gene expression; DNA repair; DNA replication; DNA synthesis involved in DNA repair; establishment of chromatin silencing; fatty acid homeostasis; histone deacetylation; histone H3-K9 deacetylation; intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; leptin-mediated signaling pathway; macrophage cytokine production; macrophage differentiation; maintenance of chromatin silencing; methylation-dependent chromatin silencing; muscle organ development; negative regulation of apoptosis; negative regulation of cAMP-dependent protein kinase activity; 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 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 cascade; negative regulation of TOR signaling; 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; ovulation from ovarian follicle; peptidyl-lysine acetylation; positive regulation of adaptive immune response; positive regulation of adipose tissue development; positive regulation of angiogenesis; positive regulation of apoptosis; positive regulation of cAMP-dependent protein kinase activity; positive regulation of cell proliferation; positive regulation of cellular senescence; positive regulation of cholesterol efflux; positive regulation of chromatin silencing; 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 histone H3-K9 methylation; positive regulation of insulin receptor signaling pathway; positive regulation of macroautophagy; positive regulation of macrophage apoptotic process; positive regulation of MHC class II biosynthetic process; positive regulation of phosphoinositide 3-kinase cascade; positive regulation of protein phosphorylation; positive regulation of smooth muscle cell differentiation; positive regulation of transcription from RNA polymerase II promoter; proteasomal ubiquitin-dependent protein catabolic process; protein ADP-ribosylation; protein deacetylation; protein destabilization; protein ubiquitination; pyrimidine dimer repair via nucleotide-excision repair; regulation of apoptosis; regulation of brown fat cell differentiation; regulation of cell proliferation; regulation of cellular response to heat; regulation of endodeoxyribonuclease activity; regulation of glucose metabolic process; regulation of lipid storage; regulation of mitotic cell cycle; regulation of protein import into nucleus, translocation; regulation of protein serine/threonine kinase activity; regulation of smooth muscle cell apoptotic process; response to hydrogen peroxide; response to insulin stimulus; response to leptin; response to oxidative stress; rRNA processing; single strand break repair; spermatogenesis; stress-induced premature senescence; transcription from RNA polymerase II promoter; triacylglycerol mobilization; viral process; white fat cell differentiation