Target Background
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],catalytic activity:NAD(+) + an acetylprotein = nicotinamide + O-acetyl-ADP-ribose + a protein.,cofactor:Binds 1 zinc ion per subunit.,enzyme regulation:Inhibited by nicotinamide. 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). RPS19BP1/AROS acts as a positive regulator of deacetylation activity.,function:NAD-dependent deacetylase, which regulates processes such as apoptosis and muscle differentiation by deacetylating key proteins. Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce proapoptotic program and modulate cell senescence. Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I. Involved in HES1- and HEY2-mediated transcriptional repression. Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1. May serve as a sensor of the cytosolic ratio of NAD(+)/NADH, which is essential in skeletal muscle cell differentiation. Despite some ability to deacetylate histones in vitro, such activity is either weak or inexistent in vivo. In case of HIV-1 infection, interacts with and deacetylates the viral Tat protein.,miscellaneous:Red wine, which contains resveratrol, may participate in activation of sirtuin proteins, and may therefore participate in an extended lifespan as it has been observed in yeast.,similarity:Belongs to the sirtuin family.,similarity:Contains 1 deacetylase sirtuin-type domain.,subcellular location:Recruited to the nuclear bodies via its interaction with PML.,subunit:Interacts with TAF1B. Found in a complex with PCAF and MYOD1 (By similarity). Interacts with MLLT7/FOXO4, HES1, HEY2, p53/TP53 and PML. Interacts with RPS19BP1/AROS.,tissue specificity:Widely expressed.,
