Sirtuin 1

4I5I, 4IF6, 4IG9, 4KXQ, 4ZZH, 4ZZI, 4ZZJ, 5BTR2341193759ENSG00000096717ENSMUSG00000020063Q96EB6Q923E4NM_001142498NM_001314049NM_012238NM_001159589NM_001159590NM_019812NP_001135970NP_001300978NP_036370NP_001153061NP_062786Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene. Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene. SIRT1 stands for sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae), referring to the fact that its sirtuin homolog (biological equivalent across species) in yeast (S. cerevisiae) is Sir2. SIRT1 is an enzyme that deacetylates proteins that contribute to cellular regulation (reaction to stressors, longevity). Sirtuin 1 is a member of the sirtuin family of proteins, homologs of the Sir2 gene in S. cerevisiae. 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. Sirtuin 1 is downregulated in cells that have high insulin resistance and inducing its expression increases insulin sensitivity, suggesting the molecule is associated with improving insulin sensitivity. Furthermore, SIRT1 was shown to de-acetylate and affect the activity of both members of the PGC1-alpha/ERR-alpha complex, which are essential metabolic regulatory transcription factors. In mammals, SIRT1 has been shown to deacetylate and thereby deactivate the p53 protein. SIRT1 also stimulates autophagy by preventing acetylation of proteins (via deacetylation) required for autophagy as demonstrated in cultured cells and embryonic and neonatal tissues. This function provides a link between sirtuin expression and the cellular response to limited nutrients due to caloric restriction. Furthermore, SIRT1 was shown to de-acetylate and affect the activity of both members of the PGC1-alpha/ERR-alpha complex, which are essential metabolic regulatory transcription factors. Human aging is characterized by a chronic, low-grade inflammation level and NF-κB is the main transcriptional regulator of genes related to inflammation. SIRT1 inhibits NF-κB-regulated gene expression by deacetylating the RelA/p65 subunit of NF-κB at lysine 310. SIRT1 plays a role in activating T helper 17 cells, which contribute to autoimmune disease; efforts to activate SIRT1 therapeutically may trigger or exacerbate autoimmune disease. Sirtuin 1 has been shown to interact with HEY2, PGC1-alpha, ERR-alpha, and AIRE. Mir-132 microRNA has been reported to interact with Sirtuin 1 mRNA, so as to reduce protein expression. This has been linked to insulin resistance in the obese. Human Sirt1 has been reported having 136 direct interactions in Interactomic studies involved in numerous processes.