PTMcode v2: a resource for functional associations of post-translational modifications within and between proteins.
Bottom Line: These two processes are interdependent and together are responsible for the function of the protein in a particular cell state.Several databases focus on the prediction and compilation of protein-protein interactions (PPIs) and no less on the collection and analysis of protein post-translational modifications (PTMs), however, there are no resources that concentrate on describing the regulatory role of PTMs in PPIs.In total, we report 8 million associations of PTMs regulating single proteins and over 9.4 million interplays tuning PPIs.
Affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.Show MeSH
Mentions: PTMcode v2 provides a highly curated data set of PTMs collected from six public databases: UniProt (20), PHOSIDA (21), PhosphoSite (22), PhosphoELM (23), dbPTM (24) and HPRD (25) and from nine high-throughput experiments reported in papers (11,26–33). Our input data set has tripled the previous release numbers and now consists of 316 546 experimentally verified PTMs of 69 different types spread over 45 361 proteins from 19 eukaryotes (Figure 1A). Modified residues were mapped into reference protein sequences from the eggNOG 4.0 database and each source validated for every protein requiring all its PTMs matching the correct amino acid. Besides the extensive exercise of PTM compilation, the value of our data set relies on the framework built for its collection, mapping, annotation and finally its visualization and data retrieval. PTMcode uses the same protein repertoire and synonyms dictionary as the databases eggNOG (13) and STRING (34), a powerful tool that allows us to easily include orthologs and network neighborhood information. We use the protein orthologous groups provided by eggNOG 4.0 to calculate our rRCS (12, Methods Summary), that evaluates every PTM conservation. For a user tip, a rRCS >95 means that the modified residue is more conserved than the 95% of the same type of amino acids in the same type of region of the protein, still some caution must be taken when filtering the most conserved PTMs in a protein since fast-evolving PTMs may also have functional roles as shown in phosphorylation sites (35).
Affiliation: European Molecular Biology Laboratory (EMBL), Meyerhofstrasse 1, 69117 Heidelberg, Germany.