EKPD: a hierarchical database of eukaryotic protein kinases and protein phosphatases

Abstract

We present here EKPD (http://ekpd.biocuckoo.org), a hierarchical database of eukaryotic protein kinases (PKs) and protein phosphatases (PPs), the key molecules responsible for the reversible phosphorylation of proteins that are involved in almost all aspects of biological processes. As extensive experimental and computational efforts have been carried out to identify PKs and PPs, an integrative resource with detailed classification and annotation information would be of great value for both experimentalists and computational biologists. In this work, we first collected 1855 PKs and 347 PPs from the scientific literature and various public databases. Based on previously established rationales, we classified all of the known PKs and PPs into a hierarchical structure with three levels, i.e. group, family and individual PK/PP. There are 10 groups with 149 families for the PKs and 10 groups with 33 families for the PPs. We constructed 139 and 27 Hidden Markov Model profiles for PK and PP families, respectively. Then we systematically characterized ∼50,000 PKs and >10,000 PPs in eukaryotes. In addition, >500 PKs and >400 PPs were computationally identified by ortholog search. Finally, the online service of the EKPD database was implemented in PHP + MySQL + JavaScript.

Figure 1.

The cutoff values of the 139 and 27 HMM profiles for the PK and PP families. The hmmsearch calculates both the E-values and log-odds likelihood scores for given sequences (17). Because the E-values depend on the database size and generate inconsistent results when the database is updated, we used realistic constant log-odds likelihood scores as the threshold values.

Figure 2.

The heatmap of the classifications and the numbers of proteins for several major groups. Nine major groups of the PKs shown. For the PPs, the groups of PSPs and PTPs were visualized. The numbers of the PKs or PPs is commonly different across species. For example, RGC kinases have been exclusively detected in animals and not plants. Also, TKL kinases are only present in a small proportion of the animal PKs (8.2%), but are widely represented in plants (60.4%).

Figure 3.

The browse option of EKPD. We provided two approaches for browsing the database: (A) By species. (B) By classifications. (C) For a PK or PP family, a brief description and the associated members are shown. (D) Detailed information on human AKT1.

Figure 4.

The kinase-phosphatase relations via common substrates. (A) A human kinase-phosphatase network was reconstructed with 62 PKs (pink), 50 PPs (blue) and 87 common substrates (green). (B) Cases of site-specific kinase-phosphatase relations. For example, the phosphorylation and dephosphorylation of T577 regulates the kinase activity of RPS6KA3 (Supplementary Table S7).