title: Protein structure as a means to triage proposed PTM sites.
abstract: PTMs such as phosphorylation are often important actors in protein regulation and recognition. These functions require both visibility and accessibility to other proteins; that the modification is located at the surface of the protein. Currently, many repositories provide information on PTMs but structural information is often lacking. This study, which focuses on phosphorylation sites available in UniProtKB/Swiss-Prot, illustrates that most phosphorylation sites are indeed found at the surface of the protein, but that some sites are found buried in the core of the protein. Several of these identified buried phosphorylation sites can easily become accessible upon small conformational changes while others would require the whole protein to unfold and are hence most unlikely modification sites. Subsequent analysis of phosphorylation sites available in PRIDE demonstrates that taking the structure of the protein into account would be a good guide in the identification of the actual phosphorylated positions in phophoproteomics experiments. This analysis illustrates that care must be taken when simply accepting the position of a PTM without first analyzing its position within the protein structure if the latter is available.
authors.affiliation: Department of Medical Protein Research, VIB, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium.
authors.forename: Elien
authors.initials: E
authors.lastname: Vandermarliere
authors.forename: Lennart
authors.initials: L
authors.lastname: Martens
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D030562:Databases, Protein; D006801:Humans; D058977:Molecular Sequence Annotation / Q000379:methods; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000737:chemistry* / Q000378:metabolism
chemical_list: D020543:Proteome