Fig. 3

SH2 mutations in IDBC and pan-cancers. (a) The folded SH2 comprises a central anti-parallel sheet, consisting of the three β-strands (βB, βC, and βD, cyan), sandwiched between two α-helices (αI and αII, dark red). The bound phosphopeptide (thin dark lines) straddles the sheet in such a manner that the phosphotyrosine (pY) binding pocket lies on one side, whereas the binding pocket for the residues in the positions C-terminal to pY lies on the other side. The two R residues in αI (R αI2) and in βB (R βB5) make key contact with pY. This ribbon representation is redrawn based on the folded structure of the C-terminal SH2 domain in P85 α (PDB accession number: 1QAD). N, N-terminal end. (b) The positional distribution of SH2 mutations in pan-cancers. Analysis was made based on cancer genome data downloaded from the COSMIC database ([33], accessed 20 August 2017) and sequence alignment of the 23 SH2 domains having mutations in the 468 patients (Supplementary Document, page 15). The horizontal axis represents the peptide sequence containing the first 80 amino acids of the C-terminal instance of the SH2 domain in P85 α. Structural elements are colored in the same way as in Panel a. (c) The SH2 mutations occurring in the 468 patients are from 23 proteins (Table S5). (d) The Kaplan–Meier survival analysis for the SH2 domain. The log rank p-value for 0.173