Figure 1

Phylogenetic tree of the complete NSS family. The tree is composed of six major distinct subfamilies, four of which are specifically associated with a specific chemical class of substrates (osmolytes, biogenic amines, and two distinct classes of amino acids). Only 7 of the 24 sequences within the subfamily generically annotated as Renal system (light purple) have been experimentally characterized. The dark purple subfamily lacks any experimental annotation; however, we include it within the Renal system subfamily based on the location of the branch point. The sixth subfamily (generically annotated as prokaryotic) is much more divergent. In fact, it appears that the prokaryotic subfamily could be further split, indicated by the light and dark shades of blue. However, we do not do so due to the lack of functional annotation discriminating between the two. Triple asterisks indicate leaves of experimentally annotated homologs; the other highlighted leaf (<<<) corresponds to the sequence of the LeuT_Aa structure.