The sirtuin family is broadly conserved from bacteria to human. Yeast SIR2, the founding member, was first isolated as part of the SIR complex required for maintaining a modified chromatin structure at telomeres. SIR2 functions in transcriptional silencing, cell cycle progression, and chromosome stability [1]. Although most sirtuins in eukaryotic cells are located in the nucleus, others are cytoplasmic or mitochondrial.

Sirtuins are responsible for a newly classified chemical reaction, NAD-dependent protein deacetylation. The final products of the reaction are the deacetylated peptide and an acetyl ADP-ribose [2]. In nuclear sirtuins this deacetylation reaction is mainly directed against histones acetylated lysines [3].

Sirtuins typically consist of two optional and highly variable N- and C-terminal domain (50-300 aa) and a conserved catalytic core domain (~250 aa). Mutagenesis experiments suggest that the N- and C-terminal regions help direct catalytic core domain to different targets [3,4].

The 3D-structure of an archaeal sirtuin in complex with NAD (see <PDB:1ICI>) reveals that the protein consists of a large domain having a Rossmann fold and a small domain containing a three-stranded zinc ribbon motif. NAD is bound in a pocket between the two domains [5].

Proteins currently known to belong to this family are listed below.

• Yeast SIR2.
• Yeast HST1 to HST4.
• Mammalian Sirtuins 1 to 5.
• Drosophila Sir2 protein.
• Bacterial CobB that regulates the function of acyl-CoA synthetase by lysine deacetlyation.
• Bacterial ThsA, an NAD(+)-cleaving enzyme of the Thoeris defense system with antiphage function [6].

The profile we developed covers the complete catalytic core domain.