Figure 4. AKT phosphorylation network: a custom query into PhosphoAtlas.

a. Connectivity of AKT family proteins. Proteins that phosphorylate AKT1/2/3, and proteins that are phosphorylated by AKT1/2/3, are respectively listed above and below AKTs. Each connecting line is a directional vector that symbolizes the top-down flow of phosphorylation from a kinase enzyme to a specific substrate. Color and continuity of connectors depict knowledge of phosphorylatable sites within protein targets. All proteins that can function as kinase enzymes are associated with a red bar containing a number that corresponds to the number of different substrate proteins they phosphorylate. The pie chart insert is an example of how the ensemble of AKT-affiliated proteins ramifies into biological processes with human disease implications. Numbers within color-coded boxes include all residue sites, variants, and upstream kinases per protein, beyond the exclusively AKT-related molecular hub.

b. WebLogo alignment of 85 heptameric biological peptide targets of the AKT1 kinase unravels the most conserved residues surrounding the phosphorylation site.

c. Breakdown of amino acid alterations and affected substrate targets resulting from the occurrence of 91 non-synonymous variants found in the genomic locations overlapping with the HPR’s of AKT1.