SIRT5

This gene encodes a member of the sirtuin family of proteins, homologs to the yeast Sir2 protein. Members of the sirtuin family are characterized by a sirtuin core domain and grouped into four classes. The functions of human sirtuins have not yet been determined; however, yeast sirtuin proteins are known to regulate epigenetic gene silencing and suppress recombination of rDNA. Studies suggest that the human sirtuins may function as intracellular regulatory proteins with mono-ADP-ribosyltransferase activity. The protein encoded by this gene is included in class III of the sirtuin family. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2010]

Sirtuin 5

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.

Biological Process mitochondrion organizationTAS:Reactome
Biological Process negative regulation of cardiac muscle cell apoptotic processIEA:Ensembl
Biological Process negative regulation of reactive oxygen species metabolic processManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process peptidyl-lysine demalonylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process peptidyl-lysine desuccinylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein ADP-ribosylationBy SimilarityISS:GO_Central
Biological Process protein deacetylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein deglutarylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein demalonylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process protein desuccinylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of ketone biosynthetic processISS:UniProtKB
Biological Process response to nutrient levelsIEA:Ensembl

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