UC San Diego

The Transporter Classification Database (TCDB) provides literature-curated, functional and evolutionary information on transporters, as well as descriptions of their families and superfamilies across all domains of life. This project aims to test the hypothesis that the Ligand-gated Ion Channel (LIC) family is a member of the Voltage-gated Ion Channels (VIC) superfamily. The topological similarities between the Glutamate-gated Ion Channel (GIC) family, an established member of the VIC superfamily, and the LIC family provided the initial clue of the relationship. To test our hypothesis, multiple bioinformatic approaches were applied to explore the similarities between the LIC family and existing members of the VIC superfamily. These included (1) sequence similarity, (2) compatibility of topology and hydropathy profiles, (3) shared domains, (4) conserved motifs, and (5) similarity of sequence profiles at the family level. Our results showed that two families from the VIC superfamily, the Glutamate-gated Ion Channel (GIC) Family of Neurotransmitter Receptors and the Voltage-gated Proton Channel (VPC) Family, generated reliable signals and satisfied at least five of our six criteria, thus supporting the conclusion that the LIC family is a distant member of the VIC superfamily.