UniprotKB/SwissProt ID: Q8R216 (Q8R216)
Gene Name:
Sirt4
Organism: Mus musculus (Mouse)
Function: Acts as a NAD-dependent protein lipoamidase, biotinylase, deacetylase and ADP-ribosyl transferase (PubMed:19220062). Catalyzes more efficiently removal of lipoyl- and biotinyl- than acetyl-lysine modifications. Inhibits the pyruvate dehydrogenase complex (PDH) activity via the enzymatic hydrolysis of the lipoamide cofactor from the E2 component, DLAT, in a phosphorylation-independent manner (PubMed:25525879). Catalyzes the transfer of ADP-ribosyl groups onto target proteins, including mitochondrial GLUD1, inhibiting GLUD1 enzyme activity. Acts as a negative regulator of mitochondrial glutamine metabolism by mediating mono ADP-ribosylation of GLUD1: expressed in response to DNA damage and negatively regulates anaplerosis by inhibiting GLUD1, leading to block metabolism of glutamine into tricarboxylic acid cycle and promoting cell cycle arrest (PubMed:16959573). In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation (PubMed:23663782). Acts as a tumor suppressor (PubMed:23562301, PubMed:23663782). Also acts as a NAD-dependent protein deacetylase: mediates deacetylation of 'Lys-471' of MLYCD, inhibiting its activity, thereby acting as a regulator of lipid homeostasis (PubMed:23746352). Does not seem to deacetylate PC (PubMed:23438705). Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1-PPARA interaction probably through the regulation of NAD(+) levels (PubMed:20685656, PubMed:24043310). Down-regulates insulin secretion (By similarity)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Mitochondrion matrix
|
|
|
