Aliases for SIRT4 Gene
External Ids for SIRT4 Gene
Previous GeneCards Identifiers for SIRT4 Gene
This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. 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 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. [provided by RefSeq, Jul 2008]
GeneCards Summary for SIRT4 Gene
SIRT4 (Sirtuin 4) is a Protein Coding gene. Diseases associated with SIRT4 include Body Mass Index Quantitative Trait Locus 11 and Diabetes Mellitus, Noninsulin-Dependent. Among its related pathways are NAD metabolism and DNA damage_NHEJ mechanisms of DSBs repair. Gene Ontology (GO) annotations related to this gene include NAD+ ADP-ribosyltransferase activity and NAD-dependent protein deacetylase activity. An important paralog of this gene is SIRT5.
UniProtKB/Swiss-Prot Summary for SIRT4 Gene
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 (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, PubMed:17715127). 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 (PubMed:23438705). Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1:PPARA interaction probably through the regulation of NAD(+) levels (PubMed:24043310). Down-regulates insulin secretion.
Silent information regulator (Sir2)-like family deacetylases (also known as sirtuins) are a group of enzymes closely related to histone deacetylases. These enzymes can be found in the cytoplasm, mitochondria or nucleus of the cell and are ubiquitously expressed.