A systematic study of the structural and regulatory features of post‐translational modifications of cellular enzymes: a case study based upon information in PhosphoSitePlus™

PhosphoSitePlus (PSP) is an open resource offering comprehensive information about site‐specific protein modification. PSP aggregates all published sites of protein post‐translational modifications, as well as thousands of newly‐discovered modification sites identified using high‐throughput methods at CST and elsewhere. Data that is manually curated includes upstream events that regulate modifications, and downstream consequences of modifications on the protein and more global cellular processes. The vast amount of information in PSP can be mined to build signaling networks to explore novel features of cellular processes. Of >10,000 proteins curated into PSP, about 1,850 are cellular enzymes with >15,000 known modification sites. We have analyzed information in PSP for patterns and interactions that may provide novel insights into the biology and biochemistry of enzymatic systems. These studies include: 1) pathway analysis of regulatory information in PSP; 2) potential associations between specific upstream kinases and classes of modified enzymes, protein domains shared between enzymes, or novel sequence motifs; 3) identification of sites within motifs or domains that are common to related enzymes; and 4) role of modification sites common to sets of enzymes on regulation of downstream processes. www.phosphosite.org Supported by NIH grants R43GM065768, R44AA014848, and 5R44CA126080