{PDOC50305}
{PS50305; SIRTUIN}
{BEGIN}
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* Sirtuin catalytic domain profile *
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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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: May 2022 / Profile and text revised.

-Expert(s) to contact by email:
           Cockell K.; moira.cockell@isrec.unil.ch

[ 1] Brachmann C.B., Sherman J.M., Devine S.E., Cameron E.E., Pillus L.,
     Boeke J.D.
     "The SIR2 gene family, conserved from bacteria to humans, functions in
     silencing, cell cycle progression, and chromosome stability."
     Genes Dev. 9:2888-2902(1995).
     PubMed=7498786
[ 2] Sauve A.A., Celic I., Avalos J., Deng H., Boeke J.D., Schramm V.L.
     "Chemistry of gene silencing: the mechanism of NAD+-dependent
     deacetylation reactions."
     Biochemistry 40:15456-15463(2001).
     PubMed=11747420; DOI=10.1021/bi011858j
[ 3] Gasser S.M., Cockell M.M.
     "The molecular biology of the SIR proteins."
     Gene 279:1-16(2001).
     PubMed=11722841
[ 4] Frye R.A.
     "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."
     Biochem. Biophys. Res. Commun. 260:273-279(1999).
     PubMed=10381378; DOI=10.1006/bbrc.1999.0897
[ 5] Min J., Landry J., Sternglanz R., Xu R.M.
     "Crystal structure of a SIR2 homolog-NAD complex."
     Cell 105:269-279(2001).
     PubMed=11336676
[ 6] Ka D., Oh H., Park E., Kim J.H., Bae E.
     "Structural and functional evidence of bacterial antiphage protection
     by Thoeris defense system via NAD(+) degradation."
     Nat. Commun. 11:2816-2816(2020).
     PubMed=32499527; DOI=10.1038/s41467-020-16703-w

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