This is present in the principal acid secreting cell of the kidney, which generates hydrogen ions and bicarbonate ions from carbon dioxide and water-a reaction catalysed by Carbonic anhydrase. The hydrogen ions are pumped into the collecting duct tubule by vacuolar H+ ATPase, the apical proton pump, which thus excretes acid into the urine. kAE1 exchanges bicarbonate for chloride on the basolateral surface, essentially returning bicarbonate to the blood. Here it performs two functions:
Electroneutral chloride and bicarbonate exchange across the plasma membrane on a one-for-one basis.This is crucial for CO2 uptake by the red cell and conversion (by hydration catalysed by carbonic anhydrase) into a proton and a bicarbonate ion. The bicarbonate is then extruded (in exchange for a chloride) from the cell by the band 3 molecule.
Physical linkage of the plasma membrane to the underlying membrane skeleton (via binding with ankyrin and protein 4.2). This appears to be to prevent membrane surface loss, rather than being to do with membrane skeleton assembly.
AE1 is an important structural component of the erythrocyte cell membrane, making up to 25% of the cell membrane surface. Each red cell contains approximately one million copies of AE1.
A different isoform of AE1, known as kAE1 (which is 65 amino acids shorter than erythroid AE1) is found in the basolateral surface of the alpha-intercalated cell in the cortical collecting duct of the kidney.
Mutations of kidney AE1 cause distal (type1) renal tubular acidosis, which is an inability to acidify the urine, even if the blood is too acidic. These mutations are disease causing as they cause mistargetting of the mutant band 3 proteins so that they are retained within the cell or occasionally addressed to the wrong (i.e. apical) surface.
Mutations of erythroid AE1 affecting the extracellular domains of the molecule may cause alterations in the individual's blood group, as band 3 determines the Diegoblood group.
AE1 was discovered following SDS-PAGEgel electrophoresis of erythrocyte cell membrane. The large 'third' band on the electrophoresis gel represented AE1, which was thus initially termed 'Band 3'. The chloride-bicarbonate exchanger in the red cell membrane is not a pump, which would use metabolic energy. Nor is it strictly an enzyme. It is protein counter-transporter, known as band III.
^Bruce LJ, Robinson HC, Guizouarn H, Borgese F, Harrison P, King MJ, Goede JS, Coles SE, Gore DM, Lutz HU, Ficarella R, Layton DM, Iolascon A, Ellory JC, Stewart GW (2005). "Monovalent cation leaks in human red cells caused by single amino-acid substitutions in the transport domain of the band 3 chloride-bicarbonate exchanger, AE1". Nat. Genet.37 (11): 1258–63. doi:10.1038/ng1656. PMID16227998.
^Sterling D, Reithmeier RA, Casey JR (Dec 2001). "A transport metabolon. Functional interaction of carbonic anhydrase II and chloride/bicarbonate exchangers". J. Biol. Chem.276 (51): 47886–94. doi:10.1074/jbc.M105959200 (inactive 2014-02-04). PMID11606574.
^Vince JW, Reithmeier RA (October 1998). "Carbonic anhydrase II binds to the carboxyl terminus of human band 3, the erythrocyte C1-/HCO3- exchanger". J. Biol. Chem.273 (43): 28430–7. doi:10.1074/jbc.273.43.28430. PMID9774471.
^Vince JW, Carlsson U, Reithmeier RA (November 2000). "Localization of the Cl-/HCO3- anion exchanger binding site to the amino-terminal region of carbonic anhydrase II". Biochemistry39 (44): 13344–9. doi:10.1021/bi0015111. PMID11063570.
^Vince JW, Reithmeier RA (May 2000). "Identification of the carbonic anhydrase II binding site in the Cl(-)/HCO(3)(-) anion exchanger AE1". Biochemistry39 (18): 5527–33. doi:10.1021/bi992564p. PMID10820026.
^Sterling D, Alvarez BV, Casey JR (July 2002). "The extracellular component of a transport metabolon. Extracellular loop 4 of the human AE1 Cl-/HCO3- exchanger binds carbonic anhydrase IV". J. Biol. Chem.277 (28): 25239–46. doi:10.1074/jbc.M202562200. PMID11994299.
Tanner MJ (1993). "Molecular and cellular biology of the erythrocyte anion exchanger (AE1)". Semin. Hematol.30 (1): 34–57. PMID8434259.
Chambers EJ, Askin D, Bloomberg GB et al. (1998). "Studies on the structure of a transmembrane region and a cytoplasmic loop of the human red cell anion exchanger (band 3, AE1)". Biochem. Soc. Trans.26 (3): 516–20. PMID9765907.
Inaba M (2002). "[Band 3: expanding knowledge on its functions]". Seikagaku73 (12): 1431–5. PMID11831035.