ITK and cancer: Moreover, in addition to the PKCγ M501I mutant, we could identify 29 other cancer mutations hitting the DFG+1 site, eight of which with analogous substitutions of large hydrophobic residues with β-branched aliphatic residues (Haspin L669I, DDR1 M793I, ITK M503V, TRKA M671T, IRAK3 M314I/M341V/M341T, and BRAF L597V), the type of substitution that most likely leads to a specificity switch from a preference for phosphorylating Ser to Thr (Figure S4; Table S1).