Critical amino acid residues in proteins: a BioMart integration of Reactome protein annotations with PRIDE mass spectrometry data and COSMIC somatic mutations

The reversible phosphorylation of serine, threonine and tyrosine hydroxyl groups is an especially prominent form of post-translational modification (PTM) of proteins. It plays critical roles in the regulation of diverse processes, and mutations that directly or indirectly affect these phosphorylation events have been associated with many cancers and other pathologies. Here, we describe the development of a new BioMart tool that gathers data from three different biological resources to provide the user with an integrated view of phosphorylation events associated with a human protein of interest, the complexes of which the protein (modified or not) is a part, the reactions in which the protein and its complexes participate and the somatic mutations that might be expected to perturb those functions. The three resources used are the Reactome, PRIDE and COSMIC databases. The Reactome knowledgebase contains annotations of phosphorylated human proteins linked to the reactions in which they are phosphorylated and dephosphorylated, to the complexes of which they are parts and to the reactions in which the phosphorylated proteins participate as substrates, catalysts and regulators. The PRIDE database holds extensive mass spectrometry data from which protein phosphorylation patterns can be inferred, and the COSMIC database holds records of somatic mutations found in human cancer cells. This tool supports both flexible, user-specified queries and standard (‘canned’) queries to retrieve frequently used combinations of data for user-specified proteins and reactions. We demonstrate using the Wnt signaling pathway and the human c-SRC protein how the tool can be used to place somatic mutation data into a functional perspective by changing critical residues involved in pathway modulation, and where available, check for mass spectrometry evidence in PRIDE supporting identification of the critical residue. Database URL: http://www.reactome.org/cgi-bin/mart