Protein: NAD-dependent protein lipoamidase sirtuin-4, mitochondrial (A6J1T8)
Organism: Rattus norvegicus (Rat)
Function: Acts as NAD-dependent protein lipoamidase, biotinylase, deacetylase and ADP-ribosyl transferase. 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. 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. 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
Subcellular location: Mitochondrion matrix
InterPro domains:
- IPR003000: Sirtuin family (family) [59-264]
- IPR026587: Sirtuin, class II (family) [35-308]
- IPR026591: Sirtuin, catalytic core small domain superfamily (homologous_superfamily) [69-234]
- IPR050134: NAD-dependent sirtuin protein deacylases (family) [36-308]
- IPR026590: Sirtuin family, catalytic core domain (domain) [34-311]
- IPR029035: DHS-like NAD/FAD-binding domain superfamily (homologous_superfamily) [21-309]
Sequence:
MRGLIFRPTRGRWITQMSQLRSHGSTGLFVPPSPPLDHEKIKELQRFISLSKKLLVMTGAGISTESGIPDYRSEKVGLYARTDRRPIQHIDFIRSAPVRQRYWARNFVGWPQFSSHQPNPAHWALSNWEKLGKLHWLVTQNVDALHSKAGNQRLTELHGCMHRVLCLSCGEQTARRVLQDRFQALNPSWSAEAQGVAPDGDVFLTEEQVRSFRVPCCDRCGGPLKPDVVFFGDTVNPDKVDFVHQRVKEADSLLVVGSSLQVYSGYRFILTAREKKLPIAILNIGPTRSDDLACLKLDSRCGELLPLIDPQ
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0140096 (catalytic activity, acting on a protein), GO:0016787 (hydrolase activity), GO:0005515 (protein binding), GO:0033558 (protein lysine deacetylase activity), GO:0019213 (deacetylase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0009628 (response to abiotic stimulus), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0048523 (negative regulation of cellular process), GO:0009892 (negative regulation of metabolic process), GO:0001666 (response to hypoxia), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0060548 (negative regulation of cell death), GO:0010941 (regulation of cell death), GO:0070887 (cellular response to chemical stimulus), GO:0033554 (cellular response to stress), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0070482 (response to oxygen levels), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0071456 (cellular response to hypoxia), GO:0071453 (cellular response to oxygen levels), GO:0051246 (regulation of protein metabolic process), GO:0043069 (negative regulation of programmed cell death), GO:0043067 (regulation of programmed cell death), GO:0036293 (response to decreased oxygen levels), GO:0051248 (negative regulation of protein metabolic process), GO:0010629 (negative regulation of gene expression), GO:0010468 (regulation of gene expression), GO:0042981 (regulation of apoptotic process), GO:0036294 (cellular response to decreased oxygen levels), GO:0030162 (regulation of proteolysis), GO:0043066 (negative regulation of apoptotic process), GO:0045861 (negative regulation of proteolysis), GO:1903317 (regulation of protein maturation), GO:1903318 (negative regulation of protein maturation), GO:0070613 (regulation of protein processing), GO:0010660 (regulation of muscle cell apoptotic process), GO:0010656 (negative regulation of muscle cell apoptotic process), GO:0010955 (negative regulation of protein processing), GO:0010662 (regulation of striated muscle cell apoptotic process), GO:0010664 (negative regulation of striated muscle cell apoptotic process), GO:0010667 (negative regulation of cardiac muscle cell apoptotic process), GO:0010665 (regulation of cardiac muscle cell apoptotic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0005739 (mitochondrion), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle)