A Proteome-wide Domain-centric Perspective on Protein Phosphorylation.
Phosphorylation is a widespread post-translational modification that modulates the function of a large number of proteins. Here we show that a significant proportion of all the domains in the human proteome is significantly enriched or depleted in phosphorylation events. A substantial improvement in phosphosites prediction is achieved by leveraging this observation, which has not been tapped by existing methods. Phosphorylation sites are often not shared between multiple occurrences of the same domain in the proteome, even when the phosphoacceptor residue is conserved. This is partly because of different functional constraints acting on the same domain in different protein contexts. Moreover, by augmenting domain alignments with structural information, we were able to provide direct evidence that phosphosites in protein-protein interfaces need not be positionally conserved, likely because they can modulate interactions simply by sitting in the same general surface area.
From the ‡Centre for Molecular Bioinformatics, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica snc, 00133 Rome, Italy.
Antonio
A
Palmeri
From the ‡Centre for Molecular Bioinformatics, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica snc, 00133 Rome, Italy.
Gabriele
G
Ausiello
From the ‡Centre for Molecular Bioinformatics, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica snc, 00133 Rome, Italy.
Fabrizio
F
Ferrè
From the ‡Centre for Molecular Bioinformatics, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica snc, 00133 Rome, Italy citterich@uniroma2.it.
Manuela
M
Helmer-Citterich
From the ‡Centre for Molecular Bioinformatics, Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica snc, 00133 Rome, Italy.
Pier Federico
PF
Gherardini
D019295:Computational Biology / Q000379:methods; D006801:Humans; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D000072417:Protein Domains; D020543:Proteome / Q000737:chemistry / Q000378:metabolism*
D010750:Phosphoproteins; D020543:Proteome