Protein: NAD-dependent protein deacetylase sirtuin-3 (EC 2.3.1.286) (NAD-dependent protein delactylase sirtuin-3) (EC 2.3.1.-) (Regulatory protein SIR2 homolog 3) (SIR2-like protein 3) (mSIR2L3) (Q8R104)
Organism: Mus musculus (Mouse)
Function: NAD-dependent protein deacetylase. Activates or deactivates mitochondrial target proteins by deacetylating key lysine residues. Known targets include ACSS1, IDH, GDH, PDHA1, SOD2, LCAD, SDHA and the ATP synthase subunit ATP5PO. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels. In response to metabolic stress, deacetylates transcription factor FOXO3 and recruits FOXO3 and mitochondrial RNA polymerase POLRMT to mtDNA to promote mtDNA transcription. Acts as a regulator of ceramide metabolism by mediating deacetylation of ceramide synthases CERS1, CERS2 and CERS6, thereby increasing their activity and promoting mitochondrial ceramide accumulation.
Subcellular location: [Isoform L]: Mitochondrion matrix {ECO:0000269|PubMed:19241369, ECO:0000269|PubMed:19333382, ECO:0000269|PubMed:23283301}.; SUBCELLULAR LOCATION: [Isoform S]: Cytoplasm {ECO:0000269|PubMed:11056054}.
Sequence: MALDPLGAVVLQSIMALSGRLALAALRLWGPGGGRRPISLCVGASGGFGGGGSSEKKFSLQDVAELLRTRACSRVVVMVGAGISTPSGIPDFRSPGSGLYSNLQQYDIPYPEAIFELGFFFHNPKPFFMLAKELYPGHYRPNVTHYFLRLLHDKELLLRLYTQNIDGLERASGIPASKLVEAHGTFVTATCTVCRRSFPGEDIWADVMADRVPRCPVCTGVVKPDIVFFGEQLPARFLLHMADFALADLLLILGTSLEVEPFASLSEAVQKSVPRLLINRDLVGPFVLSPRRKDVVQLGDVVHGVERLVDLLGWTQELLDLMQRERGKLDGQDR
InterPro domains: - IPR050134: NAD-dependent sirtuin protein deacylases (family) [56-317]
- IPR029035: DHS-like NAD/FAD-binding domain superfamily (homologous_superfamily) [58-329]
- IPR003000: Sirtuin family (family) [80-261]
- IPR017328: Sirtuin, class I (family) [52-334]
- IPR026591: Sirtuin, catalytic core small domain superfamily (homologous_superfamily) [86-234]
- IPR026590: Sirtuin family, catalytic core domain (domain) [53-315]
Interaction partners: - NAD-dependent protein lipoamidase sirtuin-4, mitochondrial
- Forkhead box protein O3
- NAD-dependent protein deacylase sirtuin-5, mitochondrial
- Acetyl-coenzyme A synthetase 2-like, mitochondrial
- NADH dehydrogenase 1 alpha subcomplex subunit 9, mitochondrial
- Nicotinamide phosphoribosyltransferase
- NAD-dependent protein deacylase sirtuin-6
- NAD-dependent protein deacetylase sirtuin-7
- Superoxide dismutase, mitochondrial
- NAD-dependent protein deacetylase sirtuin-2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0016787 (hydrolase activity), GO:0140096 (catalytic activity, acting on a protein), GO:0005515 (protein binding), GO:0016810 (hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds), GO:0033558 (protein lysine deacetylase activity), GO:0019213 (deacetylase activity), GO:0004407 (histone deacetylase activity), GO:0016811 (hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0032501 (multicellular organismal process), GO:0048869 (cellular developmental process), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0048522 (positive regulation of cellular process), GO:1901564 (organonitrogen compound metabolic process), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0048731 (system development), GO:0019538 (protein metabolic process), GO:0016043 (cellular component organization), GO:0043170 (macromolecule metabolic process), GO:0036211 (protein modification process), GO:0022008 (neurogenesis), GO:0043412 (macromolecule modification), GO:0030030 (cell projection organization), GO:0007399 (nervous system development), GO:0030182 (neuron differentiation), GO:0048666 (neuron development), GO:0031175 (neuron projection development), GO:0048699 (generation of neurons), GO:0098732 (macromolecule deacylation), GO:0120036 (plasma membrane bounded cell projection organization), GO:0018193 (peptidyl-amino acid modification), GO:0035601 (protein deacylation), GO:0018108 (peptidyl-tyrosine phosphorylation), GO:0006525 (arginine metabolic process), GO:0006476 (protein deacetylation)
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)