UC San Diego

The Transporter Classification Database (TCDB) provides curated functional, evolutionary, and familial classification information on physiologically relevant transporter proteins across all domains of life. The Voltage-gated Ion Channel (VIC) Superfamily is comprised of 7 family members, and while the Ligand-gated Ion Channel (LIC) Family is not currently a member, topological similarities between the LIC family and the Glutamate-gated Ion Channel (GIC) Family, a member of the VIC superfamily, suggested that the LIC family is a member of the VIC superfamily. To test this hypothesis that the LIC family is a member of the VIC superfamily, we used a series of bioinformatic approaches to search for similarities between the LIC family and members of the VIC superfamily. These included 1) sequence similarity, 2) compatibility of topology and hydropathy profiles, 3) shared domains, 4) conserved motifs, 5) similarity of HMM-based sequence profiles at the family level, 6) 3D structural similarities, and 7) protein clustering analysis of all families. Our results showed that two families from the VIC superfamily, the Glutamate-gated Ion Channel (GIC) Family and the Voltage-gated Proton Channel (VPC) Family, generated reliable signals of homology with the LIC family. These findings support the conclusion that the LIC family is a distant member of the VIC superfamily. Since classification of transporters into families and superfamilies enables better understanding of transporters and their mechanisms of action, classification of the LIC family as a member of the VIC superfamily should be useful for further research into the biology and evolution of this superfamily.