Conserved Site

Anion exchange, conserved site (IPR018241)

Short name: Anion_exchange_CS


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.

Anion exchange proteins participate in pH and cell volume regulation. They are glycosylated, plasma-membrane transport proteins that exchange hydrogen carbonate (HCO3-) for chloride (Cl-) in a reversible, electroneutral manner [PMID: 2289848, PMID: 2042971]. To date three anion exchanger isoforms have been identified (AE1-3), AE1 being the previously-characterised erythrocyte band 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 abundant membrane protein in mature erythrocytes. It has a molecular mass of ~95kDa and consists of two major domains. The N-terminal 390 residues form a water-soluble, highly elongated domain that serves as an attachment site for the binding of the membrane skeleton and other cytoplasmic proteins. The remainder of the protein is a 55kDa hydrophobic domain that is responsible for catalysing anion exchange. The function of the analogous domains of AE2 and AE3 remains to be determined [PMID: 9491367].

Naturally-occurring mutations have been characterised in the AE1 gene, which give rise to forms of several human diseases: included are spherocytosis, affecting red blood cells, and familial distal renal tubular acidosis, a kidney disease associated with the formation of kidney stones [PMID: 10353704].

GO terms

Biological Process

GO:0006820 anion transport

Molecular Function

GO:0005452 inorganic anion exchanger activity

Cellular Component

GO:0016020 membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PROSITE patterns
PROSITE patterns