Mutation of Tyr245 or Tyr305 in SET7/9 (Determine 4b ) alters its specificity from an H3 K4 mono-methylase to a tri- and di-methylase, respectively sixteen , 21 , whereas an Phe281Tyr mutation in the lysine-binding pocket of DIM-5 (Determine 4c ) converts this protein to an H3 K9 mono- or di-methylase 16 These mutations exemplify the F/Y change (Determine 1 ) that establishes SET-domain product specificities.

reference.comThe exception to the rule is the DOT1 household, members of which methylate K79 within the globular region of histone H3 and which are structurally not associated to SET-area proteins four - 6 Current work suggests that SET-domain-containing proteins methylate a few proteins in addition to histones (see later)