Sirtuin family (IPR003000)

Short name: Sirtuin

Overlapping homologous superfamilies

Family relationships


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 functions in transcriptional silencing, cell cycle progression, and chromosome stability [PMID: 7498786]. 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 [PMID: 10873683]. 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 [PMID: 10873683]. The S. cerevisiae genome encodes five sirtuins, Sir2 and four additional proteins termed 'homologues of sir two' (Hst1p-Hst4p) [PMID: 7498786]. The human genome encodes seven sirtuins, with representatives from classes I-IV [PMID: 10873683,PMID: 15128440].

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 [PMID: 11747420]. In nuclear sirtuins this deacetylation reaction is mainly directed against histones acetylated lysines [PMID: 11722841].

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 [PMID: 11722841, PMID: 10381378].

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 [PMID: 11336676].

GO terms

Biological Process

No terms assigned in this category.

Molecular Function

GO:0070403 NAD+ binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.