Fig. 2.

SH2 domains cluster into families based on peptide binding. A, hierarchical two-dimensional clustering of physiological ligands and 50 SH2 domains reveals clusters of SH2 domains motifs. The relative intensities of the SH2-peptide interaction is indicated by the color: intensities greater than 3× the mean, red; intensities between 1× and 3× mean, gray; intensities less than <1× mean, black. Circled in yellow are core clusters of peptides for the Crk, Grb2, and Brk/Src families of SH2 domains. B, families of SH2 domains recognize a core cluster of peptides that define the consensus binding motif for that family as indicated (X = any natural amino acid). The consensus motifs determined for physiological peptide binding closely resemble motifs identified using peptide libraries (10, 13, 20, 61).