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 SLC4A1gene in humans.
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:[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.
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
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]
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]
^ abcGRCh38: Ensembl release 89: ENSG00000004939 - Ensembl, May 2017
^ abcGRCm38: 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. PMC2683012. 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. PMC386454. PMID 3461480.
^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. PMID 16227998. S2CID 23554234.
^Jarolim P, Palek J, Amato D, Hassan K, Sapak P, Nurse GT, Rubin HL, Zhai S, Sahr KE, Liu SC (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. PMC53065. 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, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. Molecular Biology of the Cell (Fourth ed.). Garland Science. p. 604. ISBN0815332181.
Further reading
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
Diego blood group system at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH
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.
March 13, 2023
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For the radio frequency range see Band III 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 SLC4A1Available structuresPDBOrtholog search PDBe RCSBList of PDB id codes1BH7 1BNX 1BTQ 1BTR 1BTS 1BTT 1BZK 1HYN 3BTB 2BTA 2BTB 4KY9 4YZFIdentifiersAliasesSLC4A1 solute carrier family 4 anion exchanger member 1 Diego blood group AE1 BND3 CD233 DI EMPB3 EPB3 FR RTA1A SW WD WD1 WR CHC SAO SPH4 solute carrier family 4 member 1 Diego blood group External IDsOMIM 109270 MGI 109393 HomoloGene 133556 GeneCards SLC4A1Gene location Human Chr Chromosome 17 human 1 Band17q21 31Start44 248 390 bp 1 End44 268 141 bp 1 Gene location Mouse Chr Chromosome 11 mouse 2 Band11 66 29 cM 11 DStart102 239 650 bp 2 End102 257 029 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed incancellous bonebone marrowbone marrow cellsrenal medullabloodkidneymonocytekidney tubulevena cavaglomerulusTop expressed inbloodinternal carotid arterybody of femurexternal carotid arteryyolk sacendocardial cushionspleenbelly cordfossaatriumMore reference expression dataBioGPSMore reference expression dataGene ontologyMolecular functionprotein homodimerization activity protein membrane adaptor activity chloride transmembrane transporter activity transporter activity anion transmembrane transporter activity bicarbonate transmembrane transporter activity protein binding ankyrin binding inorganic anion exchanger activity sodium bicarbonate symporter activity hemoglobin bindingCellular componentintegral component of membrane blood microparticle membrane cortical cytoskeleton plasma membrane integral component of plasma membrane basolateral plasma membrane extracellular exosome Z disc cytoplasmic side of plasma membraneBiological processanion transport bicarbonate transport cellular ion homeostasis chloride transport ion transport regulation of intracellular pH anion transmembrane transport chloride transmembrane transport sodium ion transmembrane transport transport glycolytic process blood coagulation plasma membrane phospholipid scrambling negative regulation of urine volume pH elevation erythrocyte development protein localization to plasma membraneSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez652120533EnsemblENSG00000004939ENSMUSG00000006574UniProtP02730P04919RefSeq mRNA NM 000342NM 011403RefSeq protein NP 000333NP 035533Location UCSC Chr 17 44 25 44 27 MbChr 11 102 24 102 26 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mousesolute carrier family 4 anion exchanger member 1 adapter proteinIdentifiersSymbolSLC4A1APNCBI gene22950HGNC13813OMIM602655RefSeqNM 018158UniProtP02730Other dataLocusChr 2 p23 3Search forStructuresSwiss modelDomainsInterProBand 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 Contents 1 Function 2 Distribution 3 Gene products 4 Clinical significance 5 Interactions 6 Discovery 7 See also 8 References 9 Further reading 10 External linksFunction EditBand 3 is present in the basolateral face of the a 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 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 EditIt 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 EditThe 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 EditMutations 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 EditBand 3 has been shown to interact with CA2 9 10 11 12 and CA4 13 Discovery EditAE1 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 EditCluster of differentiation Anion exchanger familyReferences 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 Schluter 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 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 PMID 16227998 S2CID 23554234 Jarolim P Palek J Amato D Hassan K Sapak P Nurse GT Rubin HL Zhai S Sahr KE Liu SC 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 Bruce Johnson Alexander Lewis Julian Raff Martin Roberts Keith Walter Peter Molecular Biology of the Cell Fourth ed Garland Science p 604 ISBN 0815332181 Further reading EditTanner 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 EditDiego 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 Retrieved from https en wikipedia org w index php title Band 3 anion transport protein amp oldid 1137443356, wikipedia, wiki, book, books, library,
