Analysis of the Protein Phosphotome of Entamoeba histolytica Reveals an Intricate Phosphorylation Network

Abstract

Phosphorylation is the most common mechanism for the propagation of intracellular signals. Protein phosphatases and protein kinases play a dynamic antagonistic role in protein phosphorylation. Protein phosphatases make up a significant fraction of eukaryotic proteome. In this article, we report the identification and analysis of protein phosphatases in the intracellular parasite Entamoeba histolytica. Based on an in silico analysis, we classified 250 non-redundant protein phosphatases in E. histolytica. The phosphotome of E. histolytica is 3.1% of its proteome and 1.3 times of the human phosphotome. In this extensive study, we identified 42 new putative phosphatases (39 hypothetical proteins and 3 pseudophosphatases). The presence of pseudophosphatases may have an important role in virulence of E. histolytica. A comprehensive phosphotome analysis of E. histolytica shows spectacular low similarity to human phosphatases, making them potent candidates for drug target.

Deep Insight into the Phosphatomes of Parasitic Protozoa and a Web Resource ProtozPhosDB

“…The phosphatomes vary in size between genera from 482 phosphatases in Tv to 35 in Ec . The phosphatome of Eh consists of 250 phosphatases that were reported in our earlier analysis [5, 6]. There was a huge variation in phosphatome of the genera Trypanosoma .…”

“…Eh has the highest percentage of phosphatases followed by Lm and Cp . The percentage of phosphatome in Hs is 0.6% of its proteome (Fig 1) [5, 28], which is much less than the selected parasites phosphatomes, indicating that vertebrates have various other mechanisms for the regulation of proteins but in protozoan parasites phosphorylation is an integral mechanism for protein regulation.…”

“…Highest percentage of uncharacterized proteins that were assigned to different families of phosphatases belongs to Tp (51.0%), followed by Lm , Tc and Tbb (Fig 4). For the sake of comparison we have taken the Eh phosphatome data that was analyzed in our previous work [5, 6]. A list of number of uncharacterized phosphatases classified as phosphatases in each genome is shown in Table B in S1 File.…”

“…Phosphatases are classified based on catalytic signature motifs and structural domains, a deeper classification of phosphatases is mentioned in our previous work on E . histolytica and others [5–7]. …”

Bioinformatics Analysis and Functional Prediction of Transmembrane Proteins in Entamoeba histolytica

“…It was demonstrated that the plasma membranes of Leishmania donovani , a protozoan parasite, were enriched in acid phosphatase activity, indicating the integral role of phosphatases in parasitism [ 58 ]. In our previous study, it was suggested that several phosphatases are involved in cation TM transport activity and ion channel activity [ 59 , 60 , 61 ]. Cell signaling has been found to regulate lipid phosphate phosphatases (LPPs) by adjusting the concentrations of lipid phosphates against their dephosphorylated products [ 62 ].…”