Band 3 anion transport protein, also known asanion exchanger 1 (AE1) orband 3 orsolute carrier family 4 member 1 (SLC4A1), is aprotein that is encoded by theSLC4A1gene in humans.
Band 3 is present in the basolateral face of theα-intercalated cells of the collecting ducts of thenephron, which are the main acid-secreting cells of the kidney. They generatehydrogen ions and bicarbonate ions from carbon dioxide and water – a reaction catalysed bycarbonic anhydrase. The hydrogen ions are pumped into the collecting duct tubule byvacuolar H+ ATPase, the apicalproton pump, which thus excretes acid into theurine. kAE1, the kidney isoform of AE1, exchanges bicarbonate for chloride on the basolateral surface, essentially returning bicarbonate to the blood. Here it performs two functions:[citation needed]
Electroneutral chloride and bicarbonate exchange across the plasma membrane on a one-for-one basis. This is crucial for CO2 uptake by the red blood cell and conversion (by hydration catalysed bycarbonic anhydrase) into aproton and abicarbonate ion. The bicarbonate is then excreted (in exchange for a chloride) from the cell by band 3.
Physical linkage of the plasma membrane to the underlying membrane skeleton (via binding withankyrin andprotein 4.2). This appears to be to prevent membrane surface loss, rather than having to do with membrane skeleton assembly.
The erythrocyte and kidney forms are differentisoforms of the sameprotein.[6]
The erythrocyte isoform of AE1, known as eAE1, is composed of 911 amino acids. eAE1 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 eAE1.[citation needed]
The kidney isoform of AE1, known as kAE1 (which is 65 amino acids shorter than erythroid AE1) is found in thebasolateral membrane of alpha-intercalated cells in thecortical collecting duct of the kidney.[citation needed]
Mutations of kidney AE1 cause distal (type 1)renal tubular acidosis, which is an inability to acidify the urine, even if the blood is tooacidic. 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.[citation needed]
Mutations of erythroid AE1 affecting the extracellular domains of the molecule may cause alterations in the individual's blood group, as band 3 determines theDiego antigen system (blood group).[citation needed]
AE1 was discovered followingSDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) of erythrocytecell membrane. The large 'third' band on the electrophoresis gel represented AE1, which was thus initially termed 'Band 3'.[14]
^Bruce LJ, Robinson HC, Guizouarn H, Borgese F, Harrison P, King MJ, et al. (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.S2CID23554234.
^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".Biochemistry.39 (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".Biochemistry.39 (18):5527–33.doi:10.1021/bi992564p.PMID10820026.
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, Ring SM, Tanner MJ (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.doi:10.1042/bst0260516.PMID9765907.
Inaba M (2002). "[Band 3: expanding knowledge on its functions]".Seikagaku.73 (12):1431–5.PMID11831035.
Shayakul C, Alper SL (2004). "Defects in processing and trafficking of the AE1 Cl−/HCO3− exchanger associated with inherited distal renal tubular acidosis".Clin. Exp. Nephrol.8 (1):1–11.doi:10.1007/s10157-003-0271-x.PMID15067510.S2CID5671983.
