Kinase motif decomposition based on phosphorylation variability and structural preferences.

<p>The preferences of various kinases for sites with specific structural background and phosphorylation variation were calculated by the 2D Annotation Enrichment technique (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002842#s4" target="_blank">Methods</a>). In general four classes can be distinguished: (i) tyrosine kinases (black squares), (ii) proline-directed kinases (red circles), (iii) non-proline directed kinases with charged residues in their substrate recognition motif (green and blue triangles corresponding to acidophilic and basophilic kinases respectively) and (iv) proline-oriented kinases, which contain a proline residue in their motif at position different from +1 relative to the modification site (red triangles and pentagons). The vertical axis separates the kinases according to their structural preferences. Tyrosine kinases favor sites within ordered regions with small phosphorylation variability. Serine/threonine kinases prefer more disordered regions, but span a larger space of phosphorylation variation. There is a tendency towards increasing disorderedness with higher phosphorylation variation, which clearly separates non proline-directed, proline-oriented and proline-directed kinases, the latter being characterized by the largest variation in phosphorylation. Examples for each class are shown and the data of all kinases can be found in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002842#pcbi-1002842-t002" target="_blank">Table 2</a>.