In the Schis toDB it is possible to encounter, for each ePK, the devel opment expression stages by EST evidence, information about orthologs, Gene Onthology function, meta bolic pathways, structural information, PDB selleck Tofacitinib structures, and links to external databases such as the TDR database. The TDR database contains additional information for S. mansoni genes like antigenicity, essentiality, pheno types and associated compounds. As shown in Figure 2, S. mansoni proteins have repre sentatives in the main ePK groups. ePKs that do not fall into these groups are categorized as Other in which multiple families have been defined. The S. mansoni lar gest ePK group is CMGC, a feature unique to this para site, and the smallest group is RGC, a common feature shared with many of the analyzed organisms.

Of the 252 ePKs identified in S. mansoni proteome, only 16 were experimentally studied as highlighted in the supplementary material and the others 236 ePKs were previously annotated only by automatic methods based on sequence similarity searches. S. mansoni ePKs were examined for the presence of the 12 smaller subdomains present in the catalytic domain and also for the presence of a lysine in subdomain II and aspartic acids residues in subdomain VIb and VII, which are known to play essential roles in the kinase function. According to our analysis, 12 proteins are pre dicted to be catalytically inactive ePKs, as they lack one or more of the three essential amino acid residues in the catalytic domain, including all mem bers of S. mansoni RGC group. Approximately 2% of the S.

mansoni ePK remain unclassified once they do not have similarity to any known PK family. All these proteins have a truncated catalytic domain probably because of an incorrect pro tein prediction. The unclassified ePKs from C. elegans, D. melanogaster, H. sapiens and S. cerevisiae range from 19% to about 38% their kinomes. Serine Threonine kinases AGC group Around 13 families have been classified as part of the AGC group in eukaryotic organisms. In S. mansoni, most AGC proteins belong to PKA, DMPK, PKC and PKG families. Other S. mansoni proteins have only one representative in the remaining AGC families. According to our phylogenetic analysis, S. man soni has no homolog of the YANK family.

The most significant difference between PKA and PKG family members is that in PKA, the regulatory and cataly tic activities are performed by separate gene products known as PKA R and PKA C, respectively, whereas in PKG the cNMP binding and catalytic domains are usually present in the same polypeptide. The inactive conformation of PKA is a heterotetramer of two PKA R and two PKA C subu nits, while PKG exists as a homodimer. S. mansoni processes five homologs of the PKA C subunit, and six predicted of PKC R subunit allowing for a variety of different holoen GSK-3 zymes to be formed in this parasite.