SIRT5 Antibody – Rabbit Polyclonal

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. Ref.2 Ref.3 Ref.4

Catalytic activity: NAD+ + a malonylprotein = nicotinamide + O-malonyl-ADP-ribose + a protein. HAMAP-Rule MF_03160NAD+ + a succinylprotein = nicotinamide + O-succinyl-ADP-ribose + a protein. HAMAP-Rule MF_03160

Cofactor: Binds 1 zinc ion per subunit

By similarity. HAMAP-Rule MF_03160

Subunit structure: Monomer. Homodimer. Interacts with CPS1. Ref.2

Subcellular location: Mitochondrion Ref.2.

Tissue specificity: Detected in brain, liver, heart, kidney, lung, thymus, spleen, skeletal muscle, intestine, pancreas and testis (at protein level). Ref.2

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

By similarity. HAMAP-Rule MF_03160

Disruption phenotype: No visible phenotype. After 48 hours of fasting, the absence of Cps1 activation leads to elevated blood ammonia levels, possibly due to the presence of succinylation at 'Lys-1291' in Cps1. Ref.2 Ref.3 Ref.4

Sequence similarities: Belongs to the sirtuin family. Class III subfamily.Contains 1 deacetylase sirtuin-type domain.