SIRT5 [SEP] found in taxon
as co-factor of enzymatic activities. SIRT5 is one of the three sirtuins localized primarily to the mitochondrion.
Structure.
Alternative splicing of this gene results in two transcript variants. The protein structure of SIRT5 has been resolved and shows high degrees of structural conservation with other sirtuins, such as the ancestral yeast protein and human SIRT2.
Function.
SIRT5 has been found to exhibit enzymatic activities as a deacetylase, desuccinylase, and demalonylase, capable of removing acetyl, succinyl, and malonyl groups from the lysine residues
of proteins. SIRT5 deacetylases and regulates carbamoyl phosphate synthetase (CPS1), the rate-limiting and initiating step of the urea cycle in liver mitochondria. Deacetylation of CPS1 stimulates its enzymatic activity. Mice with deletion of SIRT5 show elevated ammonia levels after a prolonged fast, whereas in contrast, mice overexpressing SIRT5 show increased CPS1 activity, suggesting one of the functions of SIRT5 may be to regulate the urea cycle. SIRT5 also interacts with and deacetylates cytochrome c. Large-scale profiling studies of SIRT5 deacetylase activity have uncovered over 700 protein