UC San Diego

The sequence diverse and ubiquitous 4-toluene sulfonate uptake permease (TSUP) family contains few characterized members and is believed to catalyze the transport of sulfur-based compounds. Our analyses revealed that prokaryotic members of the TSUP family outnumber the eukaryotic members substantially and that extensive lateral gene transfer occurred during the evolution of the TSUP family. Despite unequal representation, both taxonomic domains share well-conserved motifs. We show that the prototypical eight TMS topology arose from an intragenic duplication of a four TMS unit. Sequence similarity and homology between TSUP and known secondary carrier families (1) supports a secondary active transport mechanism for the TSUP family, (2) necessitates the creation of the novel Microbial Rhodopsin (MR) superfamily and (3) suggests a common primordial 2 [alpha]-helical hairpin structure for multiple families and superfamilies, similarly to what has been suggested for outer membrane [beta]-barrels. The MR superfamily consists of six currently recognized families. Our suggestion of a Super- superfamily may, in the future, group many superfamilies together, generating a new TC hyperlink. Finally, genome context analyses confirm the proposal of a sulfur-based compound transport role for many TSUP homologues, but functional outliers appear to be prevalent as well