title: Identifying human kinase-specific protein phosphorylation sites by integrating heterogeneous information from various sources.
abstract: Phosphorylation is an important type of protein post-translational modification. Identification of possible phosphorylation sites of a protein is important for understanding its functions. Unbiased screening for phosphorylation sites by in vitro or in vivo experiments is time consuming and expensive; in silico prediction can provide functional candidates and help narrow down the experimental efforts. Most of the existing prediction algorithms take only the polypeptide sequence around the phosphorylation sites into consideration. However, protein phosphorylation is a very complex biological process in vivo. The polypeptide sequences around the potential sites are not sufficient to determine the phosphorylation status of those residues. In the current work, we integrated various data sources such as protein functional domains, protein subcellular location and protein-protein interactions, along with the polypeptide sequences to predict protein phosphorylation sites. The heterogeneous information significantly boosted the prediction accuracy for some kinase families. To demonstrate potential application of our method, we scanned a set of human proteins and predicted putative phosphorylation sites for Cyclin-dependent kinases, Casein kinase 2, Glycogen synthase kinase 3, Mitogen-activated protein kinases, protein kinase A, and protein kinase C families (available at http://cmbi.bjmu.edu.cn/huphospho). The predicted phosphorylation sites can serve as candidates for further experimental validation. Our strategy may also be applicable for the in silico identification of other post-translational modification substrates.
authors.affiliation: Department of Biomedical Informatics, Peking University Health Science Center, Beijing, China. litt@hsc.pku.edu.cn
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.forename: Pufeng
authors.initials: P
authors.lastname: Du
authors.forename: Nanfang
authors.initials: N
authors.lastname: Xu
mesh_terms: D000465:Algorithms; D001665:Binding Sites; D047390:Casein Kinase II / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D030562:Databases, Protein; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D011494:Protein Kinases; D047390:Casein Kinase II; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D018844:Cyclin-Dependent Kinases; D020928:Mitogen-Activated Protein Kinases