Menu
Home
People
Places
Arts
History
Plants & Animals
Science
Life & Culture
Technology
Reference.org
Band 3 anion transport protein
open-in-new
<h2 id="function">Function</h2> <p>Band 3 is present in the basolateral face of the <a href="/facts/Collecting_duct_system/MmpNcpLA">α-intercalated cells</a> of the collecting ducts of the <a href="/facts/Nephron/ss24U1zW">nephron</a>, which are the main acid-secreting cells of the kidney. They generate <a href="/facts/Hydrogen/BoYHjl0J">hydrogen</a> ions and bicarbonate ions from carbon dioxide and water – a reaction catalysed by <a href="/facts/Carbonic_anhydrase/je7bk6fk">carbonic anhydrase</a>. The hydrogen ions are pumped into the collecting duct tubule by <a href="/facts/V-ATPase/K1Lh2P3j">vacuolar H+ ATPase</a>, the apical <a href="/facts/Proton_pump/mMzXv8P3">proton pump</a>, which thus excretes acid into the <a href="/facts/Urine/oNUYVtvX">urine</a>. 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: </p> <ul><li>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 <a href="/facts/Carbonic_anhydrase/je7bk6fk">carbonic anhydrase</a>) into a <a href="/facts/Proton/clCjepXP">proton</a> and a <a href="/facts/Bicarbonate/zzSVVAl1">bicarbonate</a> ion. The bicarbonate is then excreted (in exchange for a chloride) from the cell by band 3.</li> <li>Physical linkage of the plasma membrane to the underlying membrane skeleton (via binding with <a href="/facts/Ankyrin/zWFJv5xg">ankyrin</a> and <a href="/facts/Protein_4.2/aQL5H2xJ">protein 4.2</a>). This appears to be to prevent membrane surface loss, rather than having to do with membrane skeleton assembly.</li></ul> <h2 id="distribution">Distribution</h2> <p>It is ubiquitous throughout the <a href="/facts/Vertebrates/tT54FSTT">vertebrates</a>. In <a href="/facts/Mammals/phSwTzBo">mammals</a>, it is present in two specific sites: </p> <ul><li>the <a href="/facts/Erythrocyte/Kggpq8Jh">erythrocyte</a> (red blood cell) cell membrane and</li> <li>the <a href="/facts/Basolateral/vAXSD0DT">basolateral</a> surface of the alpha-<a href="/facts/Intercalated_cell/MmpNcpLA">intercalated cell</a> (the acid secreting cell type) in the <a href="/facts/Collecting_duct/MmpNcpLA">collecting duct</a> of the <a href="/facts/Kidney/HBspPrv9">kidney</a>.</li></ul> <h2 id="gene-products">Gene products</h2> <p>The erythrocyte and kidney forms are different <a href="/facts/Isoforms/oWmzfg4l">isoforms</a> of the same <a href="/facts/Protein/Jxmagu3E">protein</a>.<a class="footnote-ref" id="fnref:2" href="#fn:2"><sup>2</sup></a> </p><p>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. </p><p>The kidney isoform of AE1, known as kAE1 (which is 65 amino acids shorter than erythroid AE1) is found in the <a href="/facts/Basolateral/vAXSD0DT">basolateral</a> membrane of alpha-intercalated cells in the <a href="/facts/Cortical_collecting_duct/MmpNcpLA">cortical collecting duct</a> of the kidney. </p> <h2 id="clinical-significance">Clinical significance</h2> <p>Mutations of kidney AE1 cause distal (type 1) <a href="/facts/Renal_tubular_acidosis/PcrVnYW5">renal tubular acidosis</a>, which is an inability to acidify the urine, even if the blood is too <a href="/facts/Acidic/FySU18n1">acidic</a>. 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. </p><p>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 <a href="/facts/Diego_antigen_system/WAhnzEkM">Diego antigen system</a> (<a href="/facts/Human_blood_group_systems/FqIKE4DK">blood group</a>). </p><p>More importantly erythroid AE1 mutations cause 15–25% of cases of <a href="/facts/Hereditary_spherocytosis/e3WwHaAn">hereditary spherocytosis</a> (a disorder associated with progressive red cell membrane loss), and also cause the hereditary conditions of <a href="/facts/Hereditary_stomatocytosis/R7W05dP2">hereditary stomatocytosis</a><a class="footnote-ref" id="fnref:3" href="#fn:3"><sup>3</sup></a> and Southeast Asian <a href="/facts/Ovalocytosis/wEXuehpm">ovalocytosis</a>.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p> <h2 id="interactions">Interactions</h2> <p>Band 3 has been shown to <a href="/facts/Protein-protein_interaction/etvm9Wmg">interact</a> with <a href="/facts/Carbonic_anhydrase_II/9TsLk2a6">CA2</a><a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a><a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a><a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a><a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> and <a href="/facts/Carbonic_anhydrase_4/N9VgKgoR">CA4</a>.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> </p> <h2 id="discovery">Discovery</h2> <p>AE1 was discovered following <a href="/facts/SDS-PAGE/4QMXcY2o">SDS-PAGE</a> (sodium dodecyl sulfate polyacrylamide gel electrophoresis) of erythrocyte <a href="/facts/Cell_membrane/vAXSD0DT">cell membrane</a>. The large 'third' band on the electrophoresis gel represented AE1, which was thus initially termed 'Band 3'.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> </p> <h2 id="see-also">See also</h2> <ul><li><a href="/facts/Cluster_of_differentiation/cLEuDQId">Cluster of differentiation</a></li> <li><a href="/facts/Anion_exchanger_family/awa2BovD">Anion exchanger family</a></li></ul> <h2 id="further-reading">Further reading</h2> <ul><li>Tanner MJ (1993). "Molecular and cellular biology of the erythrocyte anion exchanger (AE1)". <i>Semin. Hematol</i>. 30 (1): 34–57. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8434259">8434259</a>.</li> <li>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)". <i>Biochem. Soc. Trans</i>. 26 (3): 516–20. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1042%2Fbst0260516">10.1042/bst0260516</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9765907">9765907</a>.</li> <li>Inaba M (2002). "[Band 3: expanding knowledge on its functions]". <i>Seikagaku</i>. 73 (12): 1431–5. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11831035">11831035</a>.</li> <li>Tanner MJ (2002). "Band 3 anion exchanger and its involvement in erythrocyte and kidney disorders". <i>Curr. Opin. Hematol</i>. 9 (2): 133–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1097%2F00062752-200203000-00009">10.1097/00062752-200203000-00009</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11844997">11844997</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:30536102">30536102</a>.</li> <li>Shayakul C, Alper SL (2004). "Defects in processing and trafficking of the AE1 Cl−/HCO3− exchanger associated with inherited distal renal tubular acidosis". <i>Clin. Exp. Nephrol</i>. 8 (1): 1–11. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1007%2Fs10157-003-0271-x">10.1007/s10157-003-0271-x</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/15067510">15067510</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:5671983">5671983</a>.</li></ul> <h2 id="external-links">External links</h2> <ul><li><a href="https://www.ncbi.nlm.nih.gov/projects/mhc/xslcgi.fcgi?cmd=bgmut/systems_info&system=diego">Diego blood group system</a> at <a href="/facts/BGMUT/sf9Jjm6m">BGMUT</a> Blood Group Antigen Gene Mutation Database at <a href="/facts/National_Center_for_Biotechnology_Information/6Xj5wCbu">NCBI</a>, <a href="/facts/NIH/G3Eytfcc">NIH</a></li> <li><a href="https://meshb.nlm.nih.gov/record/ui?name=Band+3+Protein">Band+3+Protein</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li> <li><a href="https://meshb.nlm.nih.gov/record/ui?name=Chloride-Bicarbonate+Antiporters">Chloride-Bicarbonate+Antiporters</a> at the U.S. National Library of Medicine <a href="/facts/Medical_Subject_Headings/C57g2JuF">Medical Subject Headings</a> (MeSH)</li> <li>Human <a href="https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg38&singleSearch=knownCanonical&position=SLC4A1"><i>SLC4A1</i></a> genome location and <a href="https://genome.ucsc.edu/cgi-bin/hgGene?db=hg38&hgg_type=knownGene&hgg_gene=SLC4A1"><i>SLC4A1</i></a> gene details page in the <a href="/facts/UCSC_Genome_Browser/kwumPyLb">UCSC Genome Browser</a>.</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683012" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2683012</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC386454" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC386454</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>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. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC53065" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC53065</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>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. <a href="https://doi.org/10.1074%2Fjbc.M105959200" target="_blank">https://doi.org/10.1074%2Fjbc.M105959200</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>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. <a href="https://doi.org/10.1074%2Fjbc.273.43.28430" target="_blank">https://doi.org/10.1074%2Fjbc.273.43.28430</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>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. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>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. <a href="https://doi.org/10.1074%2Fjbc.M202562200" target="_blank">https://doi.org/10.1074%2Fjbc.M202562200</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>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. <a href="0815332181" target="_blank">0815332181</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> </ol>