| Type: | Family | Name: | Sirtuin, class II |
| Description: | The sirtuin (also known as Sir2) family is broadly conserved from bacteria to human. Yeast Sir2 (silent mating-type information regulation 2), the founding member, was first isolated as part of the SIR complex requiredfor maintaining a modified chromatin structure at telomeres. Sir2 functions in transcriptional silencing, cell cycle progression, and chromosome stability[]. Although most sirtuins in eukaryotic cells are located in the nucleus,others are cytoplasmic or mitochondrial. This family is divided into five classes (I-IV and U) on the basis of a phylogenetic analysis of 60 sirtuins from a wide array of organisms []. Class I and class IV are further divided into three and two subgroups, respectively. The U-class sirtuins are found only in Gram-positive bacteria []. The S. cerevisiae genome encodes five sirtuins, Sir2 and four additional proteins termed 'homologues of sir two' (Hst1p-Hst4p) []. The human genome encodes seven sirtuins, with representatives from classes I-IV [,].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 []. In nuclear sirtuinsthis deacetylation reaction is mainly directed against histones acetylated lysines [].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 [, ].The 3D-structure of an archaeal sirtuin in complex with NAD reveals that the protein consists of a large domain having a Rossmann fold anda small domain containing a three-stranded zinc ribbon motif. NAD is bound in a pocket between the two domains []. | Short Name: | Sirtuin_class_II |
