![]() |
|
PROSITE documentation PDOC50305 [for PROSITE entry PS50305] |
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.
The profile we developed covers the complete catalytic core domain.
Last update:May 2022 / Profile and text revised.
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). | |
PubMed ID | 7498786 |
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. | |
Source | Biochemistry 40:15456-15463(2001). | |
PubMed ID | 11747420 | |
DOI | 10.1021/bi011858j |
3 | Authors | Gasser S.M. Cockell M.M. |
Title | The molecular biology of the SIR proteins. | |
Source | Gene 279:1-16(2001). | |
PubMed ID | 11722841 |
4 | Authors | Frye R.A. |
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). | |
PubMed ID | 10381378 | |
DOI | 10.1006/bbrc.1999.0897 |
5 | Authors | Min J. Landry J. Sternglanz R. Xu R.M. |
Title | Crystal structure of a SIR2 homolog-NAD complex. | |
Source | Cell 105:269-279(2001). | |
PubMed ID | 11336676 |
6 | Authors | Ka D. Oh H. Park E. Kim J.H. Bae E. |
Title | Structural and functional evidence of bacterial antiphage protection by Thoeris defense system via NAD(+) degradation. | |
Source | Nat. Commun. 11:2816-2816(2020). | |
PubMed ID | 32499527 | |
DOI | 10.1038/s41467-020-16703-w |