PTPN11 and neoplasm: Our identification of SHP2 pY62 as one of the most frequently detected phosphosites in the human phosphoproteome, along with its evolutionary conservation and selective retention across orthologs and SH2 domains, and its high frequency in RTK-driven patient tumor types suggests that Y62 phosphorylation may exert distinct conformational or functional effects that contribute to RTK-driven oncogenesis.