Family 2.A.28 - The Bile Acid:Na+ Symporter Family       

Family ID: 52627

Functionally characterized members of the BASS family catalyze Na+:bile acid symport. These systems have been identified in intestinal, liver and kidney tissues of animals, and at least three isoforms are present in a single species such as humans. A BASS in the apical membrane of the human ileal intestine catalyzes the electrogenic uptake of bile acids with a stoichiometry of bile acid:Na+ of 1:2. These proteins vary in size from about 340 to 480 amino acyl residues and possess 7 or 9 transmembrane spanners (TMSs). The bile acid binding site appears to be localized to the last TMS (last 60 residues) (Kramer et al., 2001).

These symporters exhibit broad specificity, taking up a variety of non bile organic compounds as well as taurocholate and other bile salts. Homologues are found in plants, yeast, archaea and bacteria. For example, functionally uncharacterized homologues are present in Synechocystis (292 aas; gbD90911) and Bacillus subtilis (283 aas; spP55190; Z99104). The bacterial homologues exhibit 6-10 putative TMSs. Because the family is represented in widely divergent organisms, it is probably ubiquitous. PSI-BLAST results suggest that the BASS family is a constituent of the ion transporter (IT) superfamily (Rabus et al., 1999). The rat liver Na+/taurocholate cotransporter is subject to elaborate regulation in response to cell swelling (Webster et al., 2000). It has two N-terminal, N-linked carbohydrate sites and two Tyr-based basolateral sorting motifs at its carboxyl terminus (YEKI and YKAA). The former target the protein to the apical membrane in the absence of the latter, but the latter override the former, targeting the protein to the basolateral membrane (Sun et al., 2001).