The human SIRT1 gene encodes a NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics; it has a role in regulation of diverse processes, such as cell cycle, response to DNA damage, metabolism, apoptosis and autophagy; it targets histones and a wide range of transcription factors and coregulators. There is a single orthologous gene in Drosophila, Dmel\Sirt1, for which classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated.
The human SIRT1 gene has not been introduced into flies.
Animals homozygous for loss-of-function mutations of Dmel\Sirt1 exhibit age-progressive metabolic phenotypes similar to those of type 2 diabetes, including decreased survival under starvation conditions, hyperglycemia, and development of insulin resistance. Physical and genetic interactions have been described for Dmel\Sirt1; see below and in the gene report for Sirt1. One of the genes characterized as physically interacting with Sirt1 is Dmel\Hnf4, the fly ortholog of human HNF4; this human gene is implicated in type 1 maturity-onset diabetes of the young (MODY1; see FBhh0000480).
[updated Jan. 2017 by FlyBase; FBrf0222196]
SIRT1 encodes a NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metobolism, apoptosis and autophagy; targets histones and a wide range of transcription factors and coregulators. [Gene Cards, SIRT1; 2017.01.30]
One to one (1 human to 1 Drosophila); lower-scoring orthologs exist in both species.
High-scoring ortholog of human SIRT1 (1 Drosophila to 1 human); lower-scoring orthologs exist in both species. Dmel\Sirt1 shares 39% identity and 51% similarity with human SIRT1.
