Sirtuin family, catalytic core domain
IPR026590
Definition
This entry represents the complete catalytic core domain of sirtuin proteins. 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 [[cite:PMID:10873683], [cite: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 [[cite:PMID:11722841], [cite: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.
7 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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