NAT/NCS2-hound: A webserver for the detection and evolutionary classification of prokaryotic and eukaryotic nucleobase-cation symporters of the NAT/NCS2 family.

Created on 28th May 2018

Paper submitted to journal GigaScience

Last updated on 20th August 2018

Anargyros Chaliotis; Panayotis Vlastaridis; Chrysoula Ntountoumi; Maria Botou; Vasilis Yalelis; Panayota Lazou; Korina Tatsaki; Dimitris Mossialos; Stathis Frillingos; Grigorios Amoutzias;

Nucleobase transporters are important for supplying the cell with purines and/or pyrimidines, for controlling the intracellular pool of nucleotides and for obtaining exogenous nitrogen/carbon sources for the metabolism. Nucleobase transporters are also evaluated as potential targets for antimicrobial therapies, since several pathogenic microorganisms rely on purine/pyrimidine salvage from their hosts. The majority of known nucleobase transporters belong to the evolutionarily conserved and ubiquitous NAT/NCS2 protein family. Based on a large-scale phylogenetic analysis that we performed on thousands of prokaryotic proteomes, we have developed a webserver that can detect and distinguish this family of transporters from other homologous families that recognize different substrates. We can further categorize these transporters to certain evolutionary groups with distinct substrate preferences. The webserver scans whole proteomes and graphically displays which proteins are identified as NAT/NCS2, to which evolutionary groups and subgroups they belong to and which conserved motifs they have. For key subgroups and motifs, the server displays annotated information from published crystal-structures and mutational studies pointing to key functional amino acids that may help experts assess the transport capability of the target sequences. The server is 100% accurate in detecting NAT/NCS2 family members. We also used the server to analyze 9109 prokaryotic proteomes and identified Clostridia, Bacilli, beta- and gamma-Proteobacteria, Actinobacteria and Fusobacteria as the taxa with the largest number of NAT/NCS2 transporters per proteome. An analysis of 120 representative eukaryotic proteomes also demonstrates the server's capability of correctly analyzing this major lineage, with plants emerging as the group with the highest number of NAT/NCS2 members per proteome.

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Review Summary

# Status Date
Hong Qu Completed 1 Jul 2018 View review
Yurong Wen Completed 19 Jul 2018 View review