Protein Domain : Sodium bicarbonate cotransporter IPR003024

Type	Family
Description	Bicarbonate (HCO 3-) transport mechanisms are the principal regulators of pH in animal cells. Such transport also plays a vital role in acid-base movements in the stomach, pancreas, intestine, kidney, reproductive organs and the central nervous system. Functional studies have suggested four different HCO 3-transport modes. Anion exchanger proteins exchange HCO 3-for Cl -in a reversible, electroneutral manner [ ]. Na+/HCO 3-co-transport proteins mediate the coupled movement of Na +and HCO 3-across plasma membranes, often in an electrogenic manner [ ]. Na+driven Cl -/HCO 3-exchange and K +/HCO 3-exchange activities have also been detected in certain cell types, although the molecular identities of the proteins responsible remain to be determined. Sequence analysis of the two families of HCO 3-transporters that have been cloned to date (the anion exchangers and Na +/HCO 3-co-transporters) reveals that they are homologous. This is not entirely unexpected, given that they both transport HCO 3-and are inhibited by a class of pharmacological agents called disulphonic stilbenes [ ]. They share around ~25-30% sequence identity, which is distributed along their entire sequence length, and have similar predicted membrane topologies, suggesting they have ~10 transmembrane (TM) domains.Na +/HCO 3-co-transport proteins are involved in cellular HCO 3-absorption and secretion, and also with intracellular pH regulation. They mediate thecoupled movement of Na +and HCO 3-across plasma membranes in most of the cell types so far investigated. A single HCO3-is transported together with one to three Na+; this transport mode is therefore often electrogenic. In the kidney, an electrogenic Na+/HCO 3-co-transporter is the principal HCO3-transporter of the renal proximal tubule, and is responsible forreabsorption of more than 85% of the filtered load of HCO 3-[ ]. Untilrecently, the molecular nature of these Na +/HCO 3-co-transporters had remained undiscovered, as initial attempts to clone them based on presumedhomology to Cl -/HCO 3-(anion) exchangers had proved unsuccessful. Instead, an expression cloning strategy was successfully utilised to identify theNa +/HCO 3-co-transporter from salamander kidney, an organ previously found to possess electrogenic Na+/HCO 3-co-transport activity [ ]. At least 3 mammalian Na+/HCO 3-co-transporters have since been cloned, with similar primary sequence lengths and putative membrance topologies. One ofthese has been found to be a kidney-specific isoform [ ], which isnear-identical (except for a varying N-terminal region) to a more widely-distributed co-transporter cloned from pancreatic tissue [].
Short Name	Na/HCO3_transpt