Sirtuin family
IPR003000
Definition
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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