PhosphoPOINT, a comprehensive human kinase interactome and phospho-protein database. PhosphoPOINT integrates 4,195 phospho-proteins, 518 serine/threonine/tyrosine kinases, and their corresponding PPI datasets with the goal of delineating the interactions among kinases, their potential substrates and their interacting (phospho)-proteins (Figure 1). In order to uncover novel substrates for specific kinases, we have incorporated gene expression and gene ontology (GO) datasets allowing annotation of the kinases and their interacting proteins. Moreover, PhosphoPOINT also annotates any amino acids near the phosphorylation sites where a cSNP may cause a phosphorylation site to be lost, and at the same time identifies how such alteration of the phosphorylation site may lead to human disease.
PhosphoPOINT has integrated human protein kinases, phospho-proteins, and PPI datasets with the goal to delineate four kinds of links among kinases. These include their interacting proteins (2,947 links in Category 1), substrates (Category 3), and substrates as well as interacting phospho-proteins (Category 4). Some of these interacting proteins for kinases are phospho-proteins (3,974 links in Category 2), which might have the potential to serve as substrates for the interacting kinases. By calculating the Pearson correlation from the NCI60 and GNF gene expression data or the coverage of these four categories in the same module gene set or meta gene set, and analyzing the similarity of cellular component terms from GO for each pairs (Category 1 to 4), we are able to provide possible functional links for each kinase-substrate pair. Annotation at the residue level includes the addition of PDB information for these phospho-peptides. Integration of cSNPs, which cause amino acid alteration, further reveals whether the reported phosphorylation sites may be lost, which may led to functional alteration.
Figure 2. Annotation and visualization in PhosphoPOINT.
To visualize the human kinase (e.g. AURKA) interacting proteins, we have used various colors to represent the different types of nodes (circle)/edges (line). The different node colors represent the phosphorylation status of each protein (e.g. red stands for this protein containing ser/thr phosphorylation sites). Edges represent the relationship between kinase and its interacting (phospho)-proteins/substrates. (Right) For each kinase and its interacting (phospho)-proteins/substrates pairs, we have calculated the Pearson correlation (solid rectangle) of each pair using the NCI60 and GNF microarray datasets. The red solid rectangle means a highly positive correlation (r>=0.7) between each pairs. The similarity of cellular component from GO for each kinase pairs is also illustrated in the third line with a hollow rectangle.