Recombinant Mouse NAD-dependent protein deacetylase sirtuin-4 (Sirt4)

1. Loss of sirtuin 4 leads to elevated glucose- and leucine-stimulated insulin levels and accelerated age-induced insulin resistance in mice from multiple genetic backgrounds. PMID: 28726069
2. SIRT4 is downregulated in cardiomyocytes after myocardial ischemia-reperfusion (MI-R), ameliorates MI-R injury, preserves mitochondrial function and reduces cardiomyocyte apoptosis after MI-R. PMID: 29777709
3. Data suggest that high-fat diet (HFD) alters regulation of expression of sirtuins (Sirt4 and Sirt7) and enzymes in NAD biosynthetic pathway (Tdo2 and Nnmt); these alterations are more prominent in liver as compared to white adipose tissue or skeletal muscle; Tdo2 and Nnmt may serve as markers of HFD consumption. (Tdo2 = tryptophan 2,3-dioxygenase; Nnmt = nicotinamide N-methyltransferase) PMID: 27592202
4. These findings identify a robust enzymatic activity for SIRT4, uncover a mechanism controlling branched-chain amino acid flux, and position SIRT4 as a crucial player maintaining insulin secretion and glucose homeostasis during aging. PMID: 28380376
5. miR-497 modulates cardiac hypertrophy by targeting Sirt4 and may serve as a potential therapeutic substance in the course. PMID: 27992564
6. Until now, a mammalian cellular lipoamidase has not been characterized; this study discovered that SIRT4 can function with this enzymatic capacity in the mitochondria, and that PDH is a biological substrate; compared to its catalytic efficiency for deacetylation, SIRT4 exhibits far superior enzymatic activity for lipoyl- and biotinyl-lysine modifications. PMID: 25525879
7. The results of this study indicated a critical and novel stress response role for SIRT4 in promoting proper glutamate transport capacity and protecting against excitotoxicity PMID: 25196144
8. regulates ATP levels via ANT2 and a feedback loop involving AMPK PMID: 24296486
9. these results highlight the tumor-suppressive role of SIRT4 in Myc-induced B cell lymphoma and suggest that SIRT4 may be a potential target against Myc-induced and/or glutamine-dependent cancers. PMID: 24368766
10. The enhanced fatty acid oxidation observed in SIRT4 knockout hepatocytes requires functional SIRT1, demonstrating a clear cross talk between mitochondrial and nuclear sirtuins. PMID: 24043310
11. Data uncover SIRT4 as an important component of the DNA damage response pathway that orchestrates a metabolic block in glutamine metabolism, cell cycle arrest, and tumor suppression. PMID: 23562301
12. SIRT4 represses fatty acid oxidation and stimulates lipogenesis. SIRT4 deacetylates and represses malonyl CoA decarboxylase, regulating malonyl coA levels. PMID: 23746352
13. Data demonstrate that SIRT4 inhibition increases fat oxidative capacity in liver and mitochondrial function in muscle. PMID: 20685656
14. controls insulin secretion in pancreatic beta cells; also transfers an ADP-ribosyl group from NAD to histones PMID: 16959562
15. NAD analogues and 32P-NAD were used to study the ADP-ribosyltransferase activity of several different sirtuins, including yeast Sir2, human SirT1, mouse SirT4, and mouse SirT6. PMID: 19220062
16. Fluorescence in situ hybridization analysis identified a single genomic locus for murine Sirt4 gene on chromosome 5F and is neighbored by the PLA2G1B and PXN genes. PMID: 19306844

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KEGG: mmu:75387

STRING: 10090.ENSMUSP00000107697

UniGene: Mm.332616