| Primary Identifier | IPR002978 | Type | Family |
| Short Name | Anion_exchange_2 |
| description | 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 []. Na+/HCO3-co-transport proteins mediate the coupled movement of Na+and HCO3-across plasma membranes, often in an electrogenic manner []. 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 []. 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.Anion exchange proteins participate in pH and cell volumeregulation. They are glycosylated, plasma-membrane transport proteins thatexchange hydrogen carbonate (HCO3-) for chloride (Cl-) in a reversible,electroneutral manner [, ]. To date three anion exchanger isoforms havebeen identified (AE1-3), AE1 being the previously-characterised erythrocyteband 3 protein. They share a predicted topology of 12-14 transmembrane (TM)domains, but have differing distribution patterns and cellular localisation.The best characterised isoform, AE1, is known to be the most abundantmembrane protein in mature erythrocytes. It has a molecular mass of ~95kDaand consists of two major domains. The N-terminal 390 residues form a water-soluble, highly elongated domain that serves as an attachment site for thebinding of the membrane skeleton and other cytoplasmic proteins. Theremainder of the protein is a 55kDa hydrophobic domain that is responsiblefor catalysing anion exchange. The function of the analogous domains of AE2and AE3 remains to be determined [].AE2 (~1240 amino acids) is a non-erythroid anion exchanger. It was cloned from choroid plexus but has been detected in many organs including the gastrointestinal tract and kidney. It is expressed in both epithelial and non-epithelial cells, and may be present in the Golgi apparatus in addition to the cell membrane []. Three AE2 N-terminal variants have been described, arising due to the presence of alternative promoter sites within the gene. They are referred to as AE2a-c and have differing distribution patterns: AE2a is expressed in all tissues; AE2b exhibits a more restricted distribution, with highest levels in the stomach; and AE2c is expressed only in the stomach []. |
