Sites of exon 3 mutations and predicted effects on SHP-2 structure. (A) Schematic of the PTPN11 gene with functional domains. The amino acid sequence of the N-SH2 domain is highlighted below. The interaction sites between the N-SH2 and PTP domains are indicated in red. The sites of the exon 3 mutations reported here are indicated by the arrowheads. (B) The catalytic cysteine, Cys459, is shown (green dots), as are 2 of the residues mutated in leukemia samples, D61 and E76 (red dots). These residues make critical contacts with the catalytic domain, and the residues' mutation is predicted to disrupt the inhibition of the catalytic domain by the amino-terminal SH2 domain. The N-terminal SH2 domain is shown in blue, the C-terminal SH2 domain in yellow, and the catalytic domain in pink. The figure was generated using Swiss-PdbViewer.