Band 3

Band 3 anion transport protein also known as anion exchanger 1 (AE1) or band 3 or solute carrier family 4 member 1 (SLC4A1) is a is_associated_with::protein that in humans is encoded by the SLC4A1 is_associated_with::gene.

Band 3 anion transport protein is a is_associated_with::phylogenetically preserved transport protein responsible for mediating the exchange of is_associated_with::chloride (Cl−) for is_associated_with::bicarbonate (HCO3−) across a is_associated_with::plasma membrane. Functionally similar members of the AE clade are AE2 and AE3.

Function
This is present in the principal acid secreting cell of the kidney, which generates is_associated_with::hydrogen ions and bicarbonate ions from carbon dioxide and water - a reaction catalysed by is_associated_with::Carbonic anhydrase. The hydrogen ions are pumped into the collecting duct tubule by vacuolar H+ ATPase, the apical is_associated_with::proton pump, which thus excretes acid into the is_associated_with::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 blood cell and conversion (by hydration catalysed by is_associated_with::carbonic anhydrase) into a is_associated_with::proton and a is_associated_with::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 is_associated_with::ankyrin and is_associated_with::protein 4.2). This appears to be to prevent membrane surface loss, rather than being to do with membrane skeleton assembly.

Species distribution
It is ubiquitous throughout the is_associated_with::vertebrates. In is_associated_with::humans it is present in two specific sites:
 * the is_associated_with::erythrocyte (red blood cell) cell membrane and
 * the is_associated_with::basolateral surface of the alpha-is_associated_with::intercalated cell (the acid secreting cell type) in the is_associated_with::collecting duct of the is_associated_with::kidney.

Tissue distribution
The erythrocyte and kidney forms are different is_associated_with::isoforms of the same is_associated_with::protein.

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 is_associated_with::basolateral surface of the alpha-intercalated cell in the is_associated_with::cortical collecting duct of the kidney.

Clinical significance
Mutations of kidney AE1 cause distal (type1) is_associated_with::renal tubular acidosis, which is an inability to acidify the urine, even if the blood is too is_associated_with::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 Diego blood group.

More importantly erythroid AE1 mutations cause 15–25% of cases of is_associated_with::Hereditary spherocytosis (a disorder associated with progressive red cell membrane loss), and also cause the hereditary conditions of is_associated_with::Hereditary stomatocytosis and Southeast Asian is_associated_with::Ovalocytosis

Interactions
Band 3 has been shown to interact with CA2   and CA4.

Discovery
AE1 was discovered following is_associated_with::SDS-PAGE is_associated_with::gel electrophoresis of erythrocyte is_associated_with::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 is_associated_with::enzyme. It is protein is_associated_with::counter-transporter, known as band III.

External link

 * Diego blood group system at is_associated_with::BGMUT Blood Group Antigen Gene Mutation Database at NCBI, is_associated_with::NIH