The human DEPhOsphorylation Database DEPOD: 2019 update

Abstract

The human Dephosphorylation Database (DEPOD) is a manually curated resource that harbors human phosphatases, their protein and non-protein substrates, dephosphorylation sites and the associated signaling pathways. We report here an update to DEPOD by integrating and/or linking to annotations from 69 other open access databases including disease associations, phosphorylating kinases, protein interactions, and also genome browsers. We also provide tools to visualize protein interactions, protein structures, phosphorylation networks, evolutionary conservation of proteins, dephosphorylation sites, and short linear motifs within various proteins. The updated version of DEPOD contains 254 human phosphatases, 336 protein and 83 non-protein substrates, and 1215 manually curated phosphatase-substrate relationships. In addition, we have improved the data access as all the data in DEPOD can now be easily downloaded in a user-friendly format. With multiple significant improvements, DEPOD continues serving as a key resource for research on phosphatase-kinase networks. Database URL: www.depod.org.

Figure 1

Schematic organization of DEPOD. DEPOD is organized in the following three modules: compilation, annotations and data access and visualization. Details on each are described in text. Red font indicates new additions or improvements in the current version over earlier versions.

Figure 2

A typical protein entry in DEPOD. Various annotation fields are depicted and newly added annotations are highlighted separately. Phosphatase entries have a ‘Substrates’ tab that harbors information about its protein and non-protein substrates. Substrate entries have a ‘Phosphatases’ tab that includes information about phosphatases that dephosphorylate them.

Figure 3

Kinase-substrate-phosphatase relationships (PSKRs) of TP53 in DEPOD. DEPOD imports the information about the protein kinases (purple squares) experimentally demonstrated to phosphorylate a gene (TP53 shown as blue triangle in this case) from PhosphoSitePlus, PhosphoELM and HPRD. The information about phosphatases (orange spheres) that dephosphorylate this gene is manually curated in DEPOD. PSKRs in DEPOD inform about bidirectional phosphoregulation of a gene of interest. At present, DEPOD distinguishes dephosphorylation of a substrate by different isoforms of a phosphatase only in cases where literature evidence specifically exists for that isoform. In the absence of any such evidence, all isoforms of that phosphatase are considered to dephosphorylate a given substrate (here for example PPP2CA and PPP2CB). The figure was created using Cytoscape (45).