ID:SIR5_HUMAN DESCRIPTION: RecName: Full=NAD-dependent protein deacylase sirtuin-5, mitochondrial; EC=3.5.1.-; AltName: Full=Regulatory protein SIR2 homolog 5; AltName: Full=SIR2-like protein 5; Flags: Precursor; FUNCTION: NAD-dependent lysine demalonylase and desuccinylase that specifically removes malonyl and succinyl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Has weak NAD- dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro. CATALYTIC ACTIVITY: NAD(+) + a malonylprotein = nicotinamide + O- malonyl-ADP-ribose + a protein. CATALYTIC ACTIVITY: NAD(+) + a succinylprotein = nicotinamide + O- succinyl-ADP-ribose + a protein. COFACTOR: Binds 1 zinc ion per subunit. ENZYME REGULATION: Inhibited by suramin. BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=6.1 uM for a synthetic histone H3K9 malonyllysine peptide; KM=5.8 uM for a synthetic histone H3K9 succinyllysine peptide; KM=8.7 uM for a synthetic GLUD1 peptide malonylated at 'Lys- 503'; KM=14 uM for a synthetic GLUD1 peptide succinylated at 'Lys- 503'; KM=150 uM for a synthetic ACSS1 peptide malonylated at 'Lys- 628'; KM=450 uM for a synthetic ACSS1 peptide succinylated at 'Lys- 628'; SUBUNIT: Interacts with CPS1 (By similarity). Monomer. Homodimer. Forms homodimers upon suramin binding. SUBCELLULAR LOCATION: Mitochondrion matrix. Mitochondrion intermembrane space. SUBCELLULAR LOCATION: Isoform 1: Cytoplasm. Mitochondrion. SUBCELLULAR LOCATION: Isoform 2: Mitochondrion. TISSUE SPECIFICITY: Widely expressed. DOMAIN: In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity (PubMed:22076378). SIMILARITY: Belongs to the sirtuin family. Class III subfamily. SIMILARITY: Contains 1 deacetylase sirtuin-type domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9NXA8
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0003950 NAD+ ADP-ribosyltransferase activity GO:0008270 zinc ion binding GO:0016787 hydrolase activity GO:0034979 NAD-dependent protein deacetylase activity GO:0036054 protein-malonyllysine demalonylase activity GO:0036055 protein-succinyllysine desuccinylase activity GO:0046872 metal ion binding GO:0061697 protein-glutaryllysine deglutarylase activity GO:0070403 NAD+ binding
Biological Process: GO:0006342 chromatin silencing GO:0006471 protein ADP-ribosylation GO:0006476 protein deacetylation GO:0007005 mitochondrion organization GO:0010566 regulation of ketone biosynthetic process GO:0010667 negative regulation of cardiac muscle cell apoptotic process GO:0031667 response to nutrient levels GO:0036046 protein demalonylation GO:0036047 peptidyl-lysine demalonylation GO:0036048 protein desuccinylation GO:0036049 peptidyl-lysine desuccinylation GO:0061698 protein deglutarylation GO:0061699 peptidyl-lysine deglutarylation GO:2000378 negative regulation of reactive oxygen species metabolic process
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
