A protein sequence alignment of the SET domains of several representative histone lysine methyltransferases (HKMT) grouped according to their histone-lysine specificity. All sequences are human with the exceptions of Saccharomyces cerevisiae SET1 and SET2, Schizosaccharomyces pombe CLR4, and Neurospora DIM-5. See Table 2 for the family designations of each human protein shown. The alignment between SET7/9 and DIM-5 is based on their structures . The white text on a black background denotes invariant residues; black text on a gray background indicates conserved residues. The involvement of invariant residues in binding to AdoMet and the target lysine, catalysis, the structural pseudoknot (see Figure 3), an intra-molecular interacting salt bridge, and a F/Y switch controlling whether the product is a mono-, di- or tri-methylated histone  are indicated.