Band 3 anion transport protein

Band 3 is present in the basolateral face of the α-intercalated cells of the collecting ducts of the nephron, which are the main acid-secreting cells of the kidney. They generate 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 blood cell and conversion (by hydration catalysed by carbonic anhydrase) into a proton and a bicarbonate 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 with ankyrin and protein 4.2). This appears to be to prevent membrane surface loss, rather than having to do with membrane skeleton assembly.

It is ubiquitous throughout the vertebrates. In mammals, it is present in two specific sites:

• the erythrocyte (red blood cell) cell membrane and
• the basolateral surface of the alpha-intercalated cell (the acid secreting cell type) in the collecting duct of the kidney.

The erythrocyte and kidney forms are different isoforms of the same protein.[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.

The kidney isoform of AE1, known as kAE1 (which is 65 amino acids shorter than erythroid AE1) is found in the basolateral membrane of alpha-intercalated cells in the cortical collecting duct of the kidney.

Mutations of kidney AE1 cause distal (type 1) 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 Diego antigen system (blood group).

More importantly erythroid AE1 mutations cause 15–25% of cases of hereditary spherocytosis (a disorder associated with progressive red cell membrane loss), and also cause the hereditary conditions of hereditary stomatocytosis[7] and Southeast Asian ovalocytosis.[8]

Band 3 has been shown to interact with CA2[9][10][11][12] and CA4.[13]

AE1 was discovered following SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) of erythrocyte cell membrane. The large 'third' band on the electrophoresis gel represented AE1, which was thus initially termed 'Band 3'.[14]

• Cluster of differentiation
• Anion exchanger family

• Diego blood group system at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH
• Band+3+Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
• Chloride-Bicarbonate+Antiporters at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human SLC4A1 genome location and SLC4A1 gene details page in the UCSC Genome Browser.