Sodium bicarbonate cotransporter (IPR003024)
Short name: Na/HCO3_transpt
Overlapping homologous superfamilies
- Bicarbonate transporter, eukaryotic (IPR003020)
- Sodium bicarbonate cotransporter (IPR003024)
Bicarbonate (HCO3-) 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 HCO3- transport modes. Anion exchanger proteins exchange HCO3- for Cl- in a reversible, electroneutral manner [PMID: 2289848]. Na+/HCO3- co-transport proteins mediate the coupled movement of Na+ and HCO3- across plasma membranes, often in an electrogenic manner [PMID: 9261985]. Na- driven Cl-/HCO3- exchange and K+/HCO3- 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 HCO3- transporters that have been cloned to date (the anion exchangers and Na+/HCO3- co-transporters) reveals that they are homologous. This is not entirely unexpected, given that they both transport HCO3- and are inhibited by a class of pharmacological agents called disulphonic stilbenes [PMID: 9235899]. 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+/HCO3- co-transport proteins are involved in cellular HCO3- absorption and secretion, and also with intracellular pH regulation. They mediate the coupled movement of Na+ and HCO3- 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+/HCO3- co-transporter is the principal HCO3- transporter of the renal proximal tubule, and is responsible for reabsorption of more than 85% of the filtered load of HCO3- [PMID: 9261985]. Until recently, the molecular nature of these Na+/HCO3- co-transporters had remained undiscovered, as initial attempts to clone them based on presumed homology to Cl-/HCO3- (anion) exchangers had proved unsuccessful. Instead, an expression cloning strategy was successfully utilised to identify the Na+/HCO3- co-transporter from salamander kidney, an organ previously found to possess electrogenic Na+/HCO3- co-transport activity [PMID: 9163427]. At least 3 mammalian Na+/HCO3- co-transporters have since been cloned, with similar primary sequence lengths and putative membrance topologies. One of these has been found to be a kidney-specific isoform [PMID: 9235899], which is near-identical (except for a varying N-terminal region) to a more widely-distributed co-transporter cloned from pancreatic tissue [PMID: 9651366].
- PR01232 (NAHCO3TRSPRT)