Identification of Enriched PTM Crosstalk Motifs from Large-Scale Experimental Data Sets

Post-translational modifications
(PTMs) play an important role
in the regulation of protein function. Mass spectrometry based proteomics
experiments nowadays identify tens of thousands of PTMs in a single
experiment. A wealth of data has therefore become publically available.
Evidently the biological function of each PTM is the key question
to be addressed; however, such analyses focus primarily on single
PTM events. This ignores the fact that PTMs may act in concert in
the regulation of protein function, a process termed PTM crosstalk.
Relatively little is known on the frequency and functional relevance
of crosstalk between PTM sites. In a bioinformatics approach, we extracted
PTMs occurring in proximity in the protein sequence from publically
available databases. These PTMs and their flanking sequences were
subjected to stringent motif searches, including a scoring for evolutionary
conservation. Our unprejudiced approach was able to detect a respectable
set of motifs, of which about half were described previously. Among
these we could add many new proteins harboring these motifs. We extracted
also several novel motifs, which through their widespread appearance
and high conservation may pinpoint at previously nonannotated concerted
PTM actions. By employing network analyses on these proteins, we propose
putative functional roles for these novel motifs with two PTM sites
in close proximity.