Sodium bicarbonate cotransporter
IPR003024
Definition
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.
5 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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