Fig. 5.

Protein kinase A mutational themes. (A) Lollipop plots of PRKACA pathogenic mutations in genetic diseases (ClinVar database) (Landrum et al., 2020). The frequency of residue mutation in cancer (residues representing >1% of all PRKACA mutations) is depicted below (COSMIC database) (Tate et al., 2019). Darker blue represents that a greater proportion of PRKACA mutations occur at that residue. (B) Structure of Cα in complex with RIα (protein data bank ID: 5JR7). Pathogenic mutations are depicted as red spheres. PRKACA mutations lie at the interface of the catalytic and regulatory subunits, whereas PRKAR1A mutations are distributed throughout the protein. (C) As in (A), lollipop plots of genetic disease mutations in PRKACB and frequency of residue mutation in cancer below. (D) Structure of the R binding domain of AKAP10 in complex with RIα (PDB: 3IM4) [dotted line connects to the same region of RIα as shown in (B)]. Mutations of unknown significance (shown in yellow) reside within the D/D domain that mediates regulatory subunit dimerization and AKAP binding. (E) As in (A) and (C), lollipop plots and cancer residue frequency illustrate that no recurrent mutations occur in PRKAR1A.