DISEASES

Disease-gene associations mined from literature

Literature on SIRT4

SIRT4 [ENSP00000202967]

NAD-dependent protein lipoamidase sirtuin-4, mitochondrial; Acts as NAD-dependent protein lipoamidase, ADP-ribosyl transferase and deacetylase. 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 . 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 . In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation. 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 (By similarity). Does not seem to deacetylate PC . Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1:PPARA interaction probably through the regulation of NAD(+) levels . Down-regulates insulin secretion. ECO:0000269|PubMed:17715127, ECO:0000269|PubMed:23438705, ECO:0000269|PubMed:23562301, ECO:0000269|PubMed:23663782,; Belongs to the sirtuin family. Class II subfamily.

Synonyms:  SIRT4,  SIRT4p,  hSIRT4,  F5H4X9,  Q9Y6E7 ...

Linkouts:  STRING  Pharos  UniProt  OMIM