PROSITE documentation PDOC00192

Anion exchangers family signatures

Anion exchange is a cellular transport function which contributes to the regulation of cell pH and volume. Anion exchangers are a family of functionally related proteins that contributes to these properties by maintaining the intracellular level of the two principal anions: chloride and HCO3-.

The best characterized anion exchanger is the band 3 protein [1], which is an erythrocyte anion exchange membrane glycoprotein. Band 3 is a protein of about 900 amino acids which consists of a cytoplasmic N-terminal domain of about 400 residues and an hydrophobic C-terminal section of about 500 residues that contains at least ten transmembrane regions. The cytoplasmic domain provides binding sites for cytoskeletal proteins, while the integral membrane domain is responsible for anion transport.

Band 3 protein is specific to erythroid cells, at least two other proteins [2] structurally and functionally related to band 3, are found in nonerythroid tissues:

• AE2 (or B3 related protein; B3RP), a protein of 1200 residues, which seems to be present in a variety of cell types including lymphoid, kidney, and choroid plexus.
• AE3, a protein of 1200 residues, which is specific to neurons.

Structurally AE2 and AE3 are very similar to band 3, the main difference being an extension of some 300 residues of the N-terminal domain in AE2 and AE3.

We developed two signature patterns for these proteins. The first pattern is based on a conserved stretch of sequence that contains four clustered positive charged residues and which is located at the C-terminal extremity of the cytoplasmic domain, just before the first transmembrane segment from the integral domain. The second pattern is based on the perfectly conserved sequence of the fifth transmembrane segment; this segment contains a lysine, which is the covalent binding site for the isothiocyanate group of DIDS, an inhibitor of anion exchange.