On July 29, the authors of KinoPlex published a map of sites in human proteins where kinases may attach phosphate groups

On July 29, the authors of KinoPlex published a map of sites in human proteins where kinases may attach phosphate groups

In their paper, the researchers combined AlphaFold predicted structures of nearly 20 thousand proteins with motifs, which are short sequence regions recognized by kinases. The map therefore identifies positions where a suitable motif is accessible within the protein's three-dimensional structure.

A kinase attaches a phosphate group to a protein and changes its function. Cells use these switches to respond to nutrients, stress, and growth signals. When researchers look for a kinase target, they usually examine several amino acids surrounding the proposed site. Together, these amino acids form a motif that the enzyme can recognize.

However, a protein folds into a three-dimensional structure. The same suitable motif may be exposed on the protein surface or buried inside it. KinoPlex assesses the structural location of each position. The motif indicates chemical compatibility with the kinase, while the structure indicates whether the kinase can reach that site in the protein.

The authors applied the map to 1,8 million serine, threonine, and tyrosine residues, the amino acids to which phosphate groups are usually attached. It identified about 567 thousand positions as accessible for phosphorylation. Matching these positions against motifs recognized by individual kinases produced about 250 thousand kinase to position pairs that satisfied both conditions.

The authors tested the predictions using deep phosphoproteomic profiling of K562 cells, a method that measures protein sites carrying attached phosphate groups at scale. In these measurements, the KinoPlex candidates matched phosphorylation sites that were observed experimentally. The map narrows the search from millions of possible sites to specific pairs that can be tested in cellular experiments.

The authors released the data atlas, code, and search portal. Researchers can use these resources to select accessible switches in stress, repair, or growth pathways and test experimentally how phosphorylation changes cellular function.