Linear motif atlas for phosphorylation-dependent signaling.
Miller ML., Jensen LJ., Diella F., Jørgensen C., Tinti M., Li L., Hsiung M., Parker SA., Bordeaux J., Sicheritz-Ponten T., Olhovsky M., Pasculescu A., Alexander J., Knapp S., Blom N., Bork P., Li S., Cesareni G., Pawson T., Turk BE., Yaffe MB., Brunak S., Linding R.
Systematic and quantitative analysis of protein phosphorylation is revealing dynamic regulatory networks underlying cellular responses to environmental cues. However, matching these sites to the kinases that phosphorylate them and the phosphorylation-dependent binding domains that may subsequently bind to them remains a challenge. NetPhorest is an atlas of consensus sequence motifs that covers 179 kinases and 104 phosphorylation-dependent binding domains [Src homology 2 (SH2), phosphotyrosine binding (PTB), BRCA1 C-terminal (BRCT), WW, and 14-3-3]. The atlas reveals new aspects of signaling systems, including the observation that tyrosine kinases mutated in cancer have lower specificity than their non-oncogenic relatives. The resource is maintained by an automated pipeline, which uses phylogenetic trees to structure the currently available in vivo and in vitro data to derive probabilistic sequence models of linear motifs. The atlas is available as a community resource (http://netphorest.info).