PROSITE documentation PDOC50305 [for PROSITE entry PS50305]Sirtuin catalytic domain profile
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.
- Yeast SIR2.
- Yeast HST1 to HST4.
- Mammalian Sirtuins 1 to 5.
- Drosophila Sir2 protein.
- Bacterial CobB that regulates the function of acyl-CoA synthetase by lysine deacetlyation.
- Bacterial ThsA, an NAD(+)-cleaving enzyme of the Thoeris defense system with antiphage function [6].
The profile we developed covers the complete catalytic core domain.
Last update:May 2022 / Profile and text revised.
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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 |
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