CK2 contribution to the generation of the human phosphoproteome

Recent advances in mass spectrometry technology in combination with the development of innovative experimental strategies have allowed the highly confident characterization of protein phosphorylation on a truly global scale. However, to date, the vast majority of phosphorylation events are still functionally uncharacterized and the link between the phosphorylation site and the kinase(s) responsible for its generation is generally missing. Primary sequence analysis surrounding the phosphoacceptor site suggests that the main role in the generation of the human phosphoproteome should be accounted to proline-directed protein kinases, found in several sub-branches of the kinome and sharing the essential requirement for a proline at n+1 position; basophilic kinases, very numerous in the human kinome; and acidophilic Ser/Thr protein kinases, a small minority within the kinome and among which protein kinase CK2 play a prominent role. Here we analyze the potential contribution of CK2 considering the entire human phosphoproteome and sub-phosphoproteomes of different functional classes of proteins and sub-cellular compartments. Our analysis suggests that the currently identified CK2 phosphoproteome, consisting in 522 phosphosites, might represent only the tip of the iceberg as it doesn’t reach get the 4% of the potential CK2 phosphosites.