Scop3P: A Comprehensive Resource of Human Phosphosites within Their Full Context

Abstract

Protein phosphorylation is a key post-translational modification (PTM) in many biological processes and is associated to human diseases such as cancer and metabolic disorders. The accurate identification, annotation and functional analysis of phosphosites is therefore crucial to understand their various roles. Phosphosites (P-sites) are mainly analysed through phosphoproteomics, which has led to increasing amounts of publicly available phosphoproteomics data. Several resources have been built around the resulting phosphosite information, but these are usually restricted to protein sequence and basic site metadata. What is often missing from these resources, however, is context, including protein structure mapping, experimental provenance information, and biophysical predictions. We therefore developed Scop3P: a comprehensive database of human phosphosites within their full context. Scop3P integrates sequences (UniProtKB/Swiss-Prot), structures (PDB), and uniformly reprocessed phosphoproteomics data (PRIDE) to annotate all known human phosphosites. Furthermore, these sites are put into biophysical context by annotating each phosphoprotein with perresidue structural propensity, solvent accessibility, disordered probability, and early folding information.Scop3P, available at https://iomics.ugent.be/scop3p, presents a unique resource for visualization and analysis of phosphosites, and for understanding of phosphosite structure-function relationships.

Structural analysis of mammalian protein phosphorylation at a proteome level

“…Similarly, we suggest that the functional relevance of a phosphorylation site can be determined by combining alterations at the protein structure and abundance level. In recent years there have been remarkable efforts made toward integration of protein structure and phosphorylation events (Ramasamy et al, 2020;Ochoa et al, 2020;Tyanova et al, 2013).…”

“…During the cell cycle, dynamic phosphorylation sites are confined to the intrinsically disordered regions, in contrast to the regions with regular secondary structures (Tyanova et al, 2013). Recently there has been an emerging effort to construct databases that integrate phosphorylation information with protein structure (Li et al, 2020;Ramasamy et al, 2020). The structural biology field progresses at a fast pace, at which the number of structures deposited in the PDB still increases exponentially.…”

The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences

“…Proteomics researchers are increasingly reusing public data from PRIDE (and other PX resources) for a broad range of purposes. For instance, recent resources that have been started by reusing mostly PRIDE public datasets include OpenProt ( 43 ), MatrisomeDB ( 44 ), Scop3P ( 45 ) and ProteomeHD ( 46 ). Additionally, as just one among many examples of high-profile data reuse, PRIDE datasets are routinely reanalyzed in the context of the Human Proteome Project ( 47 ).…”

A panoramic perspective on human phosphosites

“…In this work we performed an in-depth computational investigation of human P-sites obtained from the large-scale re-processing of multiple phospho-proteomic projects, as made available through Scop3P 46 . First, we differentiate true P-sites from noise by combining protein abundance, peptide evidence (singly or multi phosphorylated peptides), localization probability, distance between adjacent P-sites, and the frequency of P-sites observed in different phospho proteomic projects.…”