A functional superfamily of sodium/solute symporters

Eleven families of sodium/solute symporters are defined based on their degrees of sequence similarities, and the protein members of these families are characterized in terms of their solute and cation specificities, their sizes, their topological features, their evolutionary relationships, and their relative degrees and regions of sequence conservation. In some cases, particularly where site-specific mutagenesis analyses have provided functional information about specific proteins, multiple alignments of members of the relevant families are presented, and the degrees of conservation of the mutated residues are evaluated. Signature sequences for several of the eleven families are presented to facilitate identification of new members of these families as they become sequenced. Phylogenetic tree construction reveals the evolutionary relationships between members of each family. One of these families is shown to belong to the previously defined major facilitator superfamily. The other ten families do not show sufficient sequence similarity with each other or with other identified transport protein families to establish homology between them. This study serves to clarify structural, functional and evolutionary relationships among eleven distinct families of functionally related transport proteins.