|PROSITE documentation PDOC50305|
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 . 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 . 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 [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 .
Proteins currently known to belong to this family are listed below.
The profile we developed covers the complete catalytic core domain.Last update:
April 2002 / First entry.Expert(s) to contact by email:
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Brachmann C.B. Sherman J.M. Devine S.E. Cameron E.E. Pillus L. Boeke J.D.|
|Title||The SIR2 gene family, conserved from bacteria to humans, functions in silencing, cell cycle progression, and chromosome stability.|
|Source||Genes Dev. 9:2888-2902(1995).|
|2||Authors||Sauve A.A. Celic I. Avalos J. Deng H. Boeke J.D. Schramm V.L.|
|Title||Chemistry of gene silencing: the mechanism of NAD+-dependent deacetylation reactions.|
|3||Authors||Gasser S.M. Cockell M.M.|
|Title||The molecular biology of the SIR proteins.|
|Title||Characterization of five human cDNAs with homology to the yeast SIR2 gene: Sir2-like proteins (sirtuins) metabolize NAD and may have protein ADP-ribosyltransferase activity.|
|Source||Biochem. Biophys. Res. Commun. 260:273-279(1999).|
|5||Authors||Min J. Landry J. Sternglanz R. Xu R.M.|
|Title||Crystal structure of a SIR2 homolog-NAD complex.|