Open Access Articles- Top Results for Band 3

Band 3

For the radio frequency range, see Band III.
SymbolsSLC4A1 ; AE1; BND3; CD233; DI; EMPB3; EPB3; FR; RTA1A; SW; WD; WD1; WR
External IDsOMIM109270 MGI109393 HomoloGene133556 IUPHAR: 904 GeneCards: SLC4A1 Gene
RNA expression pattern
File:PBB GE SLC4A1 205592 at tn.png
More reference expression data
RefSeq (mRNA)NM_000342NM_011403
RefSeq (protein)NP_000333NP_035533
Location (UCSC)Chr 17:
42.33 – 42.35 Mb
Chr 11:
102.35 – 102.37 Mb
PubMed search[1][2]
solute carrier family 4 (anion exchanger), member 1, adapter protein
Symbol SLC4A1AP
Entrez 22950
HUGO 13813
OMIM 602655
RefSeq NM_018158
UniProt P02730
Other data
Locus Chr. 2 p23.3

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 protein that in humans is encoded by the SLC4A1 gene.

Band 3 anion transport protein is a phylogenetically preserved transport protein responsible for mediating the exchange of chloride (Cl) for bicarbonate (HCO3) across a plasma membrane. Functionally similar members of the AE clade are AE2 and AE3.[1]


This is present in the principal acid secreting cell of the kidney, which generates 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 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 ankyrin and 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 vertebrates. In humans it is present in two specific sites:

Tissue distribution

The erythrocyte and kidney forms are different isoforms of the same protein.[2]

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

Clinical significance

Mutations of kidney AE1 cause distal (type1) 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 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[3] and Southeast Asian Ovalocytosis[4]


Band 3 has been shown to interact with CA2[5][6][7][8] and CA4.[9]


AE1 was discovered following SDS-PAGE gel electrophoresis of erythrocyte 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 enzyme. It is protein counter-transporter, known as band III.[10]

See also


  1. ^ Alper SL (2009). "Molecular physiology and genetics of Na+-independent SLC4 anion exchangers". Journal of Experimental Biology 212 (11): 1672–1683. PMC 2683012. PMID 19448077. doi:10.1242/jeb.029454. 
  2. ^ 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. PMC 386454. PMID 3461480. doi:10.1073/pnas.83.16.6137. 
  3. ^ 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. PMID 16227998. doi:10.1038/ng1656. 
  4. ^ 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. PMC 53065. PMID 1722314. doi:10.1073/pnas.88.24.11022. 
  5. ^ 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. PMID 11606574. doi:10.1074/jbc.M105959200 (inactive 2015-01-10). 
  6. ^ 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. PMID 9774471. doi:10.1074/jbc.273.43.28430. 
  7. ^ 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. PMID 11063570. doi:10.1021/bi0015111. 
  8. ^ 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. PMID 10820026. doi:10.1021/bi992564p. 
  9. ^ 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. PMID 11994299. doi:10.1074/jbc.M202562200. 
  10. ^ Hunter MJ (1977). "Human erythrocyte anion permeabilities measured under conditions of net charge transfer". J Physiol 268 (1): 35–49. PMC 1283651. PMID 874904. doi:10.1113/jphysiol.1977.sp011845. 

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. 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. PMID 11844997. doi:10.1097/00062752-200203000-00009. 
  • 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. PMID 15067510. doi:10.1007/s10157-003-0271-x. 

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