Tools for protein posttranslational modifications analysis: FAK, a case study.

Recent advances in mass spectrometry have resulted in an exponential increase in annotation of posttranslational modifications (PTMs). Just in the Swiss-Prot Knowledgebase, there are 89,931 of a total of 27 characterized PTM types reported experimentally. A single protein can be dynamically modified during its lifetime for regulation of its function. Considering a PTM can occur at different levels and the number of different PTMs described, the number of possibilities for a single protein is unthinkable. Narrowing the study to a single PTM can be rather unmerited considering that most proteins are heavily modified. Currently crosstalk between PTMs is plentifully reported in the literature. The example of amino acids serine and threonine on one hand and lysine on the other hand, as targets of different modifications, demand a more global analysis approach of a protein. Besides the direct competition for the same amino acid, a PTM can directly or indirectly influence other PTMs in the same protein molecule by for example steric hindrance due to close proximity between the modifications or creation of a binding site such as an SH2 binding domain for protein recruitment and further modifications. Given the complexity of PTMs a number of tools have been developed to archive, analyze, and visualize modifications. VISUALPROT is presented here to demonstrate the usefulness of visualizing all annotated protein features such as amino acid content, domains, amino acid modification sites and single amino acid polymorphisms in a single image. VISUALPROT application is demonstrated for the protein focal adhesion kinase (FAK) as an example. FAK is a highly phosphorylated cytoplasmatic tyrosine kinase comprising different domains and regions. FAK is crucial for integrating signals from integrins and receptor tyrosine kinases in processes such as cell survival, proliferation, and motility.