SIR2 is an NAD-dependent lysine deacetylase. It was the first-discovered member of the Sirtuin protein family and it is highly conserved, with homologs found in organisms ranging from humans to bacteria and archaea. It interacts with a variety of protein substrates, but does not exhibit strong affinity for DNA, chromatin, or other silencer-binding factors. Instead, it relies on other SIR proteins to find its appropriate silencing target.
In the SIR protein complex, SIR2 removes acetyl groups from the lysine on histone tails H3 and H4, priming the nucleosome for chromatin packaging by the SIR3 component of the complex.