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.

For the radio frequency range, see Band III.

SLC4A1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1BH7, 1BNX, 1BTQ, 1BTR, 1BTS, 1BTT, 1BZK, 1HYN, 3BTB, 2BTA, 2BTB, 4KY9, 4YZF
Identifiers
Aliases	SLC4A1, 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 IDs	OMIM: 109270 MGI: 109393 HomoloGene: 133556 GeneCards: SLC4A1
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q21.31 Start 44,248,390 bp[1] End 44,268,141 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11 66.29 cM|11 D Start 102,348,824 bp[2] End 102,366,203 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • protein homodimerization activity • protein membrane anchor • chloride transmembrane transporter activity • transporter activity • anion transmembrane transporter activity • anion:anion antiporter activity • bicarbonate transmembrane transporter activity • GO:0001948 protein binding • ankyrin binding • inorganic anion exchanger activity • sodium:bicarbonate symporter activity • hemoglobin binding Cellular component • integral component of membrane • blood microparticle • membrane • cortical cytoskeleton • cell membrane • integral component of plasma membrane • basolateral plasma membrane • extracellular exosome • Z disc • cytoplasmic side of plasma membrane Biological process • anion 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 • phospholipid scrambling • negative regulation of urine volume • pH elevation • erythrocyte development • protein localization to plasma membrane Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6521	20533
Ensembl	ENSG00000004939	ENSMUSG00000006574
UniProt	P02730	P04919
RefSeq (mRNA)	NM_000342	NM_011403
RefSeq (protein)	NP_000333	NP_035533
Location (UCSC)	Chr 17: 44.25 – 44.27 Mb	Chr 11: 102.35 – 102.37 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

solute carrier family 4 (anion exchanger), member 1, adapter protein
Identifiers
Symbol	SLC4A1AP
NCBI gene	22950
HGNC	13813
OMIM	602655
RefSeq	NM_018158
UniProt	P02730
Other data
Locus	Chr. 2 p23.3

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

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:

• 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

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.[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.

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 (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[7] and Southeast Asian ovalocytosis.[8]

Interactions

Band 3 has been shown to interact with CA2[9][10][11][12] and CA4.[13]

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'.[14]

See also

• Cluster of differentiation
• Anion exchanger family

References

1. GRCh38: Ensembl release 89: ENSG00000004939 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000006574 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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

• 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. doi:10.1097/00062752-200203000-00009. PMID 11844997.
• 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.

External links

• Diego 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.