Fig. 1: SHP2 activation and dysregulation by mutations. | Nature Communications

Fig. 1: SHP2 activation and dysregulation by mutations.

From: Deep mutational scanning of the multi-domain phosphatase SHP2 reveals mechanisms of regulation and pathogenicity

Fig. 1

a Domain architecture diagram of SHP2. b Cartoon depiction of SHP2 activation by phosphoprotein binding. c Structures of the auto-inhibited (PDB code 4DGP) and active states of SHP2 (PDB code 6CRF). Note that the active state shown is that of the E76K mutant, and other active conformations likely exist in solution. d Positions and frequencies of cancer hotspot mutations (black bars) in SHP2 along its 593-residue sequence, derived from the COSMIC and TCGA databases. Sites of other pathogenic mutations and variants of uncertain significance are labeled as red and gray dots, respectively, derived from the ClinVar database.

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