Protein Domain : Sirtuin, class III IPR027546

Type	Family
Description	This entry represents the Sirtuin family, class III subfamily. Proteins in this subfamily include the NAD-dependent protein deacylase sirtuin-5. Sirtuin-5 is the NAD-dependent lysine demalonylase and desuccinylase that specifically removes malonyl and succinyl groups on target proteins [ ].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 required for maintaining a modified chromatin structure at telomeres. Sir2 functionsin 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 sirtuins this 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 and a small domain containing a three-stranded zinc ribbon motif. NAD is bound in a pocket between the two domains [ ].
Short Name	Sirtuin_class_III