RT Journal Article
SR Electronic
T1 NAT/NCS2-hound: A Webserver for the detection and evolutionary classification of prokaryotic and eukaryotic nucleobase–cation symporters of the NAT/NCS2 family
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 332452
DO 10.1101/332452
A1 A Chaliotis
A1 P Vlastaridis
A1 C Ntountoumi
A1 M Botou
A1 V Yalelis
A1 P Lazou
A1 E Tatsaki
A1 D Mossialos
A1 S Frillingos
A1 GD Amoutzias
YR 2018
UL http://biorxiv.org/content/early/2018/06/14/332452.abstract
AB 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, β- and γ-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.