Band 3 anion transport protein: Difference between revisions
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{{Ion pumps}} |
{{Ion pumps}} |
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{{Membrane transport proteins}} |
{{Membrane transport proteins}} |
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[[Category:Blood]] |
[[Category:Blood]] |
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[[Category:Blood antigen systems]] |
[[Category:Blood antigen systems]] |
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[[Category:Solute carrier family]] |
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Revision as of 22:40, 19 January 2008
| solute carrier family 4 (anion exchanger), member 1, adaptor protein | |||||||
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| Identifiers | |||||||
| Symbol | SLC4A1AP | ||||||
| NCBI gene | 22950 | ||||||
| HGNC | 13813 | ||||||
| OMIM | 602655 | ||||||
| RefSeq | NM_018158 | ||||||
| UniProt | Q9BWU0 | ||||||
| Other data | |||||||
| Locus | Chr. 2 p23.3 | ||||||
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Anion Exchanger 1 (AE1) or Band 3 is a phylogenetically preserved transport protein responsible for catalysing the electroneutral exchange of chloride (Cl-) for bicarbonate (HCO3-) across a plasma membrane.
It is ubiquitous throughout the vertebrates. In humans 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.
The erythrocyte and kidney forms are different isoforms of the same protein.
Discovery
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. [5]
AE1 in Red Cells
AE1 is an important structural component of the erythrocyte cell membrane, making up to 25% of the cell membrane surface, indeed each red cell contains approximately one million copies of AE1.
Function
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 cell and conversion (by hydration catalysed by carbonic anhydrase) into a proton and a bicarbonate ion. The bicarbonate is then extruded 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.
Pathology
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 between 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 [6] and Southeast Asian Ovalocytosis [7]
AE1 in Alpha-Intercalated cells
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.
Function
This is 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.
Pathology
Mutations of kidney AE1 cause distal (type1) renal tubular acidosis, which is an inability to acidify the urine, even if the blood is too acid. 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 (ie apical) surface.
References
- ^ 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.
- ^ Hunter M (1977). "Human erythrocyte anion permeabilities measured under conditions of net charge transfer". J Physiol. 268 (1): 35–49. PMID 874904.
- ^ LJ Bruce (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". Nature Genetics. 37 (11): 1258–63.
{{cite journal}}: Cite has empty unknown parameter:|quotes=(help); Unknown parameter|month=ignored (help) - ^ Jarolim p (1991). "Deletion in Erythrocyte Band 3 Gene in Malaria-Resistant Southeast Asian Ovalocytosis". PNAS. 88: 11022–11026.
{{cite journal}}: Cite has empty unknown parameters:|quotes=and|month=(help).
External links
- Diego blood group system at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH
- Band+3+Protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Chloride-Bicarbonate+Antiporters at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Further reading