This gene encodes a member of the sirtuin family of proteins which are homologs of the Sir2 gene in budding yeast. 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 fully 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 IV of the sirtuin family.
SIRT4 is a mitochondrial ADP-ribosyltransferase that inhibits mitochondrial glutamate dehydrogenase 1 activity, thereby downregulating insulin secretion in response to amino acids. It has been shown that SIRT4 regulates fatty acid oxidation and mitochondrial gene expression in liver and muscle cells.
^ abFrye RA (June 1999). "Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity". Biochem. Biophys. Res. Commun. 260 (1): 273–9. doi:10.1006/bbrc.1999.0897. PMID10381378.
Ahuja N, Schwer B, Carobbio S, et al. (2007). "Regulation of insulin secretion by SIRT4, a mitochondrial ADP-ribosyltransferase". J. Biol. Chem. 282 (46): 33583–92. doi:10.1074/jbc.M705488200. PMID17715127.