The Silent Information Regulator (SIR2) family of genes are highly conserved from prokaryotes to eukaryotes and are involved in diverse processes, including transcriptional regulation, cell cycle progression, DNA-damage repair and aging. In S. cerevisiae, Sir2p deacetylates histones in an NAD-dependent manner, which regulates silencing at the telomeric, rDNA and silent mating-type loci. Sir2p is the founding member of a large family, designated sirtuins, which contain a conserved catalytic domain. The human homologues, which include SIRT1-7, are divided into four main branches: SIRT1-3 are class I, SIRT4 is class II, SIRT5 is class III and SIRT6-7 are class IV. SIRT3 is a NAD-dependent deacetylase that contains one deacetylase sirtuin-type domain. The SIRT3 protein is widely expressed and localizes to the mitochondira where it is processed by mitochondrial processing peptidase (MPP) to yield a final product. This processing is most-likely necessary for its enzymatic activity.
