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

Completed on 1 Jul 2018 by Hong Qu.

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Comments to author

In this manuscript, the authors constructed a webserver for the evolutionary classification of transporters in the NAT/NCS2 family. However, I have a few concerns as below:

1. Since these transporters have long sequences and high sequence similarity, they should be easily identified from proteomes.

2. Moreover, these transporters have similar transmembrane structures, so the structural similarity is high. Only some of the residues on the transmembrane channel (active center) determine the specificity of the substrate and the conservation of evolution. According to these structural information, these transporters should be easily divided into subgroups. Therefore, the innovative significance of the work is discounted.

3. In addition, on the webpages, the substrate specificity information is not clearly reflected.