SIRT5 Human

Sirtuin-5 (SIRT5) is a member of the sirtuin family of proteins, which are homologs to the yeast Sir2 protein. These proteins are characterized by a sirtuin core domain and belong to the class III histone deacetylases (HDACs), which are dependent on nicotinamide adenine dinucleotide (NAD+) as a co-factor for their enzymatic activities .

The SIRT5 gene is located on human chromosome 6p23 and consists of eight exons. The gene encodes two isoforms of the protein, one with 310 amino acids and another with 299 amino acids . The recombinant form of SIRT5 is typically expressed in Escherichia coli and has a molecular weight of approximately 59.8 kDa .

SIRT5 exhibits multiple enzymatic activities, including deacetylase, desuccinylase, demalonylase, and deglutarylase activities. These activities enable SIRT5 to remove acetyl, succinyl, malonyl, and glutaryl groups from lysine residues on proteins . This versatility in substrate specificity allows SIRT5 to play a crucial role in various cellular processes.

SIRT5 is primarily localized to the mitochondria, where it is involved in regulating several metabolic pathways. One of its key functions is the regulation of carbamoyl phosphate synthetase 1 (CPS1), an essential enzyme in the urea cycle. SIRT5 deacetylates CPS1, thereby stimulating its enzymatic activity and facilitating the detoxification of ammonia in the liver .

Additionally, SIRT5 has been shown to interact with and deacetylate cytochrome c, a component of the electron transport chain, suggesting a role in energy metabolism . Large-scale profiling studies have identified over 700 protein substrates for SIRT5, indicating its widespread influence on mitochondrial and cellular functions .

SIRT5 is overexpressed in non-small cell lung cancer (NSCLC) and may contribute to cancer growth . Its role in regulating metabolic pathways and maintaining cellular homeostasis makes it a potential target for therapeutic interventions in various diseases, including cancer and metabolic disorders.