A SET domain is a protein domain found in many methyltransferases that modify lysine residues in histones and other proteins. It contributes to the catalytic machinery that transfers a methyl group to a selected target. The domain's presence suggests a family relationship, but does not by itself specify which residue a particular enzyme modifies.
In 2000, experiments on SUV39H1 and related proteins identified histone H3 lysine 9 methylation activity. Mutational and biochemical analysis localized the catalytic requirement to the SET domain together with adjacent cysteine-rich regions.[ref]
Regulation of chromatin structure by site-specific histone H3 methyltransferases by S. Rea and others. Abstract: H3 lysine 9 specificity, SET dependence and adjacent regions
This linked a recognizable sequence region to a concrete chemical reaction on chromatin, while also showing why isolating a domain name from its surrounding structure can oversimplify enzyme function. New to topics? Read the docs here!