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]
Function
Acts as NAD-dependent protein lipoamidase, biotinylase, deacetylase and ADP-ribosyl transferase (PubMed:16959573, PubMed:17715127, PubMed:24052263, PubMed:25525879).
Catalyzes more efficiently removal of lipoyl- and biotinyl- than acetyl-lysine modifications (PubMed:24052263, PubMed:25525879).
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 (PubMed:16959573, PubMed:17715127).
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 (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 (By similarity).
Does not seem to deacetylate PC (PubMed:23438705).
Controls fatty acid oxidation by inhibiting PPARA transcriptional activation (PubMed:24043310).
Impairs SIRT1-PPARA interaction probably through the regulation of NAD+ levels (PubMed:24043310).
Down-regulates insulin secretion (PubMed:17715127).
Biological Process
Biological Process cellular response to DNA damage stimulusISS:UniProtKB
Biological Process cellular response to hypoxiaIEA:Ensembl
Biological Process glutamine metabolic processISS:UniProtKB
Biological Process mitochondrion organizationTAS:Reactome
Biological Process negative regulation of cardiac muscle cell apoptotic processIEA:Ensembl
Biological Process negative regulation of fatty acid oxidationManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of insulin secretionManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process negative regulation of protein processing involved in protein targeting to mitochondrionIEA:Ensembl
Biological Process peptidyl-lysine deacetylationISS:UniProtKB
Biological Process positive regulation of lipid biosynthetic processISS:UniProtKB
Biological Process protein ADP-ribosylationISS:UniProtKB
Biological Process protein deacetylationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of glutamine family amino acid metabolic processIEA:Ensembl
Biological Process regulation of pyruvate dehydrogenase activityManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process tricarboxylic acid metabolic processISS:UniProtKB
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