Anti-Sirt1(Sir2) Antibody, clone 3-10 Antibody, rabbit monoclonal clone 3-10, from rabbit

NAD-dependent protein deacetylase sirtuin-1 (UniProt: Q923E4; also known as Regulatory protein SIR2 homolog 1, SIR2-like protein 1, SIR2alpha, Sir2, mSIR2a, Sirt-1) is encoded by the Sirt1 (also known as Sir2l1) gene (Gene ID: 93759) in murine species. Sirt1 is a NAD-dependent protein deacetylase that is widely expressed and links transcriptional regulation directly to intracellular energetics. In liver, Sirt1 is expressed in a circadian manner with maximal and minimal levels reaching at around Zeitgeber time (ZT) 16 and ZT4, respectively and its deacetylase activity is also regulated in a circadian manner that peaks at ZT15. It participates in the coordination of several cellular functions such as cell cycle, response to DNA damage, metabolism, apoptosis, and autophagy. It is shown to modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. It deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression in both positive and negative manner. Sirt1 serves as a sensor of the cytosolic ratio of NAD+/NADH, which is altered by glucose deprivation and metabolic changes associated with caloric restriction. Sirt1 has four nucleotide (NAD)-binding regions and four zinc binding sites. It is reported to shuttle between nucleus and cytoplasm. Sir1 is proteolytically cleaved by cathepsin B upon TNF-alpha treatment to yield a catalytic inactive but stable 75 kDa fragment (aa 2-525). Sirt1 can be phosphorylated by multiple protein kinases. It is phosphorylated by STK4/MST1 that results in inhibition of SIRT1-mediated p53/TP53 deacetylation and phosphorylation by MAPK8/JNK1 at serine 46 and threonine 522 is reported to increase its nuclear localization and enzymatic activity. Sirt1 phosphorylation at threonine 522 by DYRK1A and DYRK3 activates its deacetylase activity and can promote cell survival.