Band 3 anion transport protein
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 protein that is encoded by the SLC4A1 gene in humans.
Band 3 anion transport protein is a phylogenetically-preserved transport protein responsible for mediating the exchange of chloride (Cl−) with bicarbonate (HCO3−) across plasma membranes. Functionally similar members of the AE clade are AE2 and AE3.[5]
Function
[edit]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, 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 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.
Distribution
[edit]It is ubiquitous throughout the vertebrates. In mammals, it is present in two specific sites:[citation needed]
- 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.
Gene products
[edit]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.[citation needed]
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.[citation needed]
Clinical significance
[edit]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.[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 the Diego antigen system (blood group).[citation needed]
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]
Interactions
[edit]Band 3 has been shown to interact with CA2[9][10][11][12] and CA4.[13]
Discovery
[edit]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]
See also
[edit]References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000004939 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000006574 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Alper SL (2009). "Molecular physiology and genetics of Na+-independent SLC4 anion exchangers". Journal of Experimental Biology. 212 (11): 1672–1683. doi:10.1242/jeb.029454. PMC 2683012. PMID 19448077.
- ^ Schlüter K, Drenckhahn D (August 1986). "Co-clustering of denatured hemoglobin with band 3: its role in binding of autoantibodies against band 3 to abnormal and aged erythrocytes". Proc. Natl. Acad. Sci. U.S.A. 83 (16): 6137–41. Bibcode:1986PNAS...83.6137S. doi:10.1073/pnas.83.16.6137. PMC 386454. PMID 3461480.
- ^ 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. PMID 16227998. S2CID 23554234.
- ^ Jarolim P, Palek J, Amato D, Hassan K, Sapak P, Nurse GT, et al. (1991). "Deletion in erythrocyte band 3 gene in malaria-resistant Southeast Asian ovalocytosis". Proc. Natl. Acad. Sci. U.S.A. 88 (24): 11022–6. Bibcode:1991PNAS...8811022J. doi:10.1073/pnas.88.24.11022. PMC 53065. PMID 1722314.
- ^ 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. PMID 11606574.
- ^ 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. PMID 9774471.
- ^ 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. PMID 11063570.
- ^ 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. PMID 10820026.
- ^ 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. PMID 11994299.
- ^ Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular Biology of the Cell (Fourth ed.). Garland Science. p. 604. ISBN 0815332181.
Further reading
[edit]- Tanner MJ (1993). "Molecular and cellular biology of the erythrocyte anion exchanger (AE1)". Semin. Hematol. 30 (1): 34–57. PMID 8434259.
- 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. PMID 9765907.
- Inaba M (2002). "[Band 3: expanding knowledge on its functions]". Seikagaku. 73 (12): 1431–5. PMID 11831035.
- Tanner MJ (2002). "Band 3 anion exchanger and its involvement in erythrocyte and kidney disorders". Curr. Opin. Hematol. 9 (2): 133–9. doi:10.1097/00062752-200203000-00009. PMID 11844997. S2CID 30536102.
- 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. PMID 15067510. S2CID 5671983.
External links
[edit]- Diego blood group system at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH
- Band+3+Protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Chloride-Bicarbonate+Antiporters at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Human SLC4A1 genome location and SLC4A1 gene details page in the UCSC Genome Browser.
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