View source for Band 3

{{for|the radio frequency range|Band III}}
{{Infobox_gene}}
{{infobox protein
| Name = solute carrier family 4 (anion exchanger), member 1, adapter protein
| caption =
| image = Alpha_Intercalated_Cell_Cartoon.svg
| width = 250px
| HGNCid = 13813
| Symbol = SLC4A1AP
| AltSymbols =
| EntrezGene = 22950
| OMIM = 602655
| RefSeq = NM_018158
| UniProt = P02730
| PDB =
| ECnumber =
| Chromosome = 2
| Arm = p
| Band = 23.3
| LocusSupplementaryData =
}}

'''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 [[Membrane transport protein|transport protein]] responsible for mediating the [[Active transport#Antiport|exchange]] of [[chloride]] (Cl<sup>−</sup>) with [[bicarbonate]] (HCO<sub>3</sub><sup>−</sup>) across [[plasma membrane]]s. Functionally similar members of the AE clade are [[SLC4A2|AE2]] and [[SLC4A3|AE3]].<ref>{{cite journal | vauthors = Alper SL | title = Molecular physiology and genetics of Na+-independent SLC4 anion exchangers | journal = Journal of Experimental Biology | volume = 212 | issue = 11 | pages = 1672–1683 | year = 2009 | pmid = 19448077 | pmc = 2683012 | doi = 10.1242/jeb.029454 }}</ref>

== Function ==
Band 3 is present in the basolateral face of the [[Collecting duct system|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 [[V-ATPase|vacuolar H<sup>+</sup> 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 CO<sub>2</sub> 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 ==
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]].

== Gene products ==
The erythrocyte and kidney forms are different [[isoforms]] of the same [[protein]].<ref name="pmid3461480">{{cite journal | vauthors = Schlüter K, Drenckhahn D | title = Co-clustering of denatured hemoglobin with band 3: its role in binding of autoantibodies against band 3 to abnormal and aged erythrocytes | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 83 | issue = 16 | pages = 6137–41 | date = August 1986 | pmid = 3461480 | pmc = 386454 | doi = 10.1073/pnas.83.16.6137 | bibcode = 1986PNAS...83.6137S }}</ref>

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.

== 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.

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|Diego]] [[Human blood group systems|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]]<ref name="pmid16227998">{{cite journal | vauthors = 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 | title = 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 | journal = Nat. Genet. | volume = 37 | issue = 11 | pages = 1258–63 | year = 2005 | pmid = 16227998 | doi = 10.1038/ng1656 }}</ref> and Southeast Asian [[Ovalocytosis]]<ref name="pmid1722314">{{cite journal | vauthors = Jarolim P, Palek J, Amato D, Hassan K, Sapak P, Nurse GT, Rubin HL, Zhai S, Sahr KE, Liu SC | title = Deletion in erythrocyte band 3 gene in malaria-resistant Southeast Asian ovalocytosis | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 88 | issue = 24 | pages = 11022–6 | year = 1991 | pmid = 1722314 | pmc = 53065 | doi = 10.1073/pnas.88.24.11022 | bibcode = 1991PNAS...8811022J }}</ref>

== Interactions ==
Band 3 has been shown to [[Protein-protein interaction|interact]] with [[Carbonic anhydrase II|CA2]]<ref name = pmid11606574>{{cite journal | vauthors = Sterling D, Reithmeier RA, Casey JR | title = A transport metabolon. Functional interaction of carbonic anhydrase II and chloride/bicarbonate exchangers | journal = J. Biol. Chem. | volume = 276 | issue = 51 | pages = 47886–94 | date = Dec 2001 | pmid = 11606574 | doi = 10.1074/jbc.M105959200 }}</ref><ref name = pmid9774471>{{cite journal | vauthors = Vince JW, Reithmeier RA | title = Carbonic anhydrase II binds to the carboxyl terminus of human band 3, the erythrocyte C1-/HCO3- exchanger | journal = J. Biol. Chem. | volume = 273 | issue = 43 | pages = 28430–7 | date = October 1998 | pmid = 9774471 | doi = 10.1074/jbc.273.43.28430 }}</ref><ref name = pmid11063570>{{cite journal | vauthors = Vince JW, Carlsson U, Reithmeier RA | title = Localization of the Cl-/HCO3- anion exchanger binding site to the amino-terminal region of carbonic anhydrase II | journal = Biochemistry | volume = 39 | issue = 44 | pages = 13344–9 | date = November 2000 | pmid = 11063570 | doi = 10.1021/bi0015111 }}</ref><ref name = pmid10820026>{{cite journal | vauthors = Vince JW, Reithmeier RA | title = Identification of the carbonic anhydrase II binding site in the Cl(-)/HCO(3)(-) anion exchanger AE1 | journal = Biochemistry | volume = 39 | issue = 18 | pages = 5527–33 | date = May 2000 | pmid = 10820026 | doi = 10.1021/bi992564p }}</ref> and [[Carbonic anhydrase 4|CA4]].<ref name = pmid11994299>{{cite journal | vauthors = Sterling D, Alvarez BV, Casey JR | title = The extracellular component of a transport metabolon. Extracellular loop 4 of the human AE1 Cl-/HCO3- exchanger binds carbonic anhydrase IV | journal = J. Biol. Chem. | volume = 277 | issue = 28 | pages = 25239–46 | date = July 2002 | pmid = 11994299 | doi = 10.1074/jbc.M202562200 }}</ref>

== Discovery ==
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'.

== See also ==
* [[Cluster of differentiation]]
* [[Anion exchanger family]]

== References ==
{{reflist|30em}}

== Further reading ==
{{Refbegin | 2}}
* {{cite journal | vauthors = Tanner MJ | title = Molecular and cellular biology of the erythrocyte anion exchanger (AE1) | journal = Semin. Hematol. | volume = 30 | issue = 1 | pages = 34–57 | year = 1993 | pmid = 8434259 | doi =  }}
* {{cite journal | vauthors = Chambers EJ, Askin D, Bloomberg GB, Ring SM, Tanner MJ | title = Studies on the structure of a transmembrane region and a cytoplasmic loop of the human red cell anion exchanger (band 3, AE1) | journal = Biochem. Soc. Trans. | volume = 26 | issue = 3 | pages = 516–20 | year = 1998 | pmid = 9765907 | doi = }}
* {{cite journal | vauthors = Inaba M | title = [Band 3: expanding knowledge on its functions] | journal = Seikagaku | volume = 73 | issue = 12 | pages = 1431–5 | year = 2002 | pmid = 11831035 | doi =  }}
* {{cite journal | vauthors = Tanner MJ | title = Band 3 anion exchanger and its involvement in erythrocyte and kidney disorders | journal = Curr. Opin. Hematol. | volume = 9 | issue = 2 | pages = 133–9 | year = 2002 | pmid = 11844997 | doi = 10.1097/00062752-200203000-00009 }}
* {{cite journal | vauthors = Shayakul C, Alper SL | title = Defects in processing and trafficking of the AE1 Cl<sup>−</sup>/HCO<sub>3</sub><sup>−</sup> exchanger associated with inherited distal renal tubular acidosis | journal = Clin. Exp. Nephrol. | volume = 8 | issue = 1 | pages = 1–11 | year = 2004 | pmid = 15067510 | doi = 10.1007/s10157-003-0271-x }}
{{Refend}}

== External links ==
* [https://www.ncbi.nlm.nih.gov/projects/mhc/xslcgi.fcgi?cmd=bgmut/systems_info&system=diego Diego blood group system] at [[BGMUT]] Blood Group Antigen Gene Mutation Database at [[National Center for Biotechnology Information|NCBI]], [[NIH]]
* {{MeshName|Band+3+Protein}}
* {{MeshName|Chloride-Bicarbonate+Antiporters}}
* {{UCSC gene info|SLC4A1}}

{{PDB Gallery|geneid=6521}}

{{Clusters of differentiation}}
{{Ion pumps}}
{{Solute carrier family|bg|bg0}}

[[Category:Blood proteins]]
[[Category:Blood antigen systems]]
[[Category:Enzymes]]
[[Category:Clusters of differentiation]]
[[Category:Solute carrier family]]
[[Category:Transfusion medicine]]