A bioinformatics pipeline to search functional motifs within whole-proteome data: a case study of poxviruses

Haitham Sobhy

doi:10.1007/s11262-016-1416-9

Abstract

Proteins harbor domains or short linear motifs, which facilitate their functions and interactions. Finding functional motifs in protein sequences could predict the putative cellular roles or characteristics of hypothetical proteins. In this study, we present Shetti-Motif, which is an interactive tool to (i) map UniProt and PROSITE flat files, (ii) search for multiple pre-defined consensus patterns or experimentally validated functional motifs in large datasets protein sequences (proteome-wide), (iii) search for motifs containing repeated residues (low-complexity regions, e.g., Leu-, SR-, PEST-rich motifs, etc.). As proof of principle, using this comparative proteomics pipeline, eleven proteomes encoded by member of Poxviridae family were searched against about 100 experimentally validated functional motifs. The closely related viruses and viruses infect the same host cells (e.g. vaccinia and variola viruses) show similar motif-containing proteins profile. The motifs encoded by these viruses are correlated, which explains why poxviruses are able to interact with wide range of host cells. In conclusion, this in silico analysis is useful to establish a dataset(s) or potential proteins for further investigation or compare between species.

Highlights

Protein functions and interactions are facilitated by amino acid sequences, so-called functional motifs, or domains, which participate in various processes, including protein interactions, trafficking, pre- or post-translational regulation, or recruiting enzyme [1,2,3,4,5]
All the sequences were downloaded from UniProt, GeneBank and PROSITE websites during October 2015
Shetti-Motif provides two built-in databases; the first obtained from PROSITE database, while the second obtained from literature, which are validated experimentally, Fig. S3, Tables 1, S1–S3

Summary

Introduction

Protein functions and interactions are facilitated by amino acid (aa) sequences, so-called functional motifs, or domains, which participate in various processes, including protein interactions, trafficking, pre- or post-translational regulation, or recruiting enzyme [1,2,3,4,5] They are either short linear motifs (SLiM), 3–11 residues (e.g., RGD), or long domain, [30 residues (e.g., Zinc finger, ankyrin or tetratricopeptide repeats (TPR)). QSLiMFinder, SLiMSearch, 3of, MotifHound, and DoReMi tools can be used to predict motif(s), pattern(s), or shared consensus within input sequence(s) [9,10,11,12,13,14] Another approach uses hidden Markov model (phylo-HMM) to search for evolutionarily conserved functional motifs [15]. It visualizes UniProt and PROSITE flat files and maps them in a human-readable table

Method

Results and discussion

Compliance with ethical standards