Figure 6

Occurrence of missense cancer mutations in PIK3CA gene relative to orthologous and paralogous PI3K kinases. PIK3CA sequences are from human (hs_PIK3CA), mouse (mus_PIK3CA), and dog (dog_PIK3CA) and cow (cow_PIK3CA) as well as the human paralogs PIK3CB (hs_PIK3CB), PIK3CD (hs_PIK3CD), and PIK3CG (hs_PIK3CG). Also included is a composite cancer mutant human PI3KCA (hs_PI3KCAm in red) with amino acid substitutions (mutations) mapped as reported by Samuels et al. [8] and the Sanger COSMIC database [27]. Regions of the alignments are shown where a cancer missense mutation is identical to an amino acid occurring in normal human paralogs. Numbers indicate coordinates in normal human PI3KCA. Arrows at the bottom of the alignment point to those specific changes across paralogues. Note for H1047, three different amino acid substitutions have been observed and font size of label indicates the relative high (large font) to low (small font) oncogenic potency of each type [28]. Structural domains were taken from the alignment of PI3K kinases to the PI3K C-γ structure reported by Walker et al. [47] and are not drawn to scale.