SIRT5
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).
Function
NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins (PubMed:21908771, PubMed:22076378, PubMed:24703693, PubMed:29180469). Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting (PubMed:22076378, PubMed:24703693). Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species (PubMed:24140062). Activates SHMT2 by mediating its desuccinylation (PubMed:29180469). Modulates ketogenesis through the desuccinylation and activation of HMGCS2 (By similarity). 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 such as UOX.
Sequence Similarities
Belongs to the sirtuin family. Class III subfamily.
Tissue Specificity
Widely expressed.
Cellular localization
- Mitochondrion matrix
- Mitochondrion intermembrane space
- Cytoplasm
- Cytosol
- Nucleus
- Mainly mitochondrial. Also present extramitochondrially, with a fraction present in the cytosol and very small amounts also detected in the nucleus.
- Isoform 1
- Cytoplasm
- Mitochondrion
- Isoform 2
- Mitochondrion
Alternative names
SIR2L5, SIRT5, Regulatory protein SIR2 homolog 5, SIR2-like protein 5