Band 3
Encyclopedia
Anion Exchanger 1 or Band 3 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
.
It is ubiquitous throughout the vertebrates. In humans it is present in two specific sites:
The erythrocyte and kidney forms are different isoforms of the same protein
.
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.
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
and Southeast Asian Ovalocytosis
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.
, 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 (i.e. apical) surface.
with Carbonic anhydrase II
and CA4.
Chloride
The chloride ion is formed when the element chlorine, a halogen, picks up one electron to form an anion Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. The chloride ion, and its salts such as sodium chloride, are very soluble in water...
(Cl-) for bicarbonate
Bicarbonate
In inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
(HCO3-) across a plasma membrane. Functionally similar members of the AE clade are AE2
SLC4A2
Anion exchange protein 2 is a membrane transport protein that in humans is encoded by the SLC4A2 gene. AE2 is functionally similar to the Band 3 Cl-/HCO3- exchange protein....
and AE3
SLC4A3
Anion exchange protein 3 is a membrane transport protein that in humans is encoded by the SLC4A3 gene. AE3 is functionally similar to the Band 3 Cl-/HCO3- exchange protein but it is expressed primarily in brain neurons and in the heart. Like AE2 its activity is sensitive to pH. AE3 mutations have...
.
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 kidneyKidneyThe kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
.
The erythrocyte and kidney forms are different isoforms of the same protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
.
Discovery
AE1 was discovered following SDS-PAGESDS-PAGE
SDS-PAGE, sodium dodecyl sulfate polyacrylamide gel electrophoresis, describes a collection of related techniques widely used in biochemistry, forensics, genetics and molecular biology to separate proteins according to their electrophoretic mobility...
gel electrophoresis
Gel electrophoresis
Gel electrophoresis is a method used in clinical chemistry to separate proteins by charge and or size and in biochemistry and molecular biology to separate a mixed population of DNA and RNA fragments by length, to estimate the size of DNA and RNA fragments or to separate proteins by charge...
of erythrocyte cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
. 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
Ion pump (biology)
In biology, an ion transporter, also called an ion pump, is a transmembrane protein that moves ions across a plasma membrane against their concentration gradient, in contrast to ion channels, where ions go through passive transport...
, which would use metabolic energy. Nor is it strictly an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
. It is protein counter-transporter, known as band III.
AE1 in Red Cells
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.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 anhydraseCarbonic anhydraseThe carbonic anhydrases form a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons , a reversible reaction that occurs rather slowly in the absence of a catalyst...
) into a protonProtonThe proton is a subatomic particle with the symbol or and a positive electric charge of 1 elementary charge. One or more protons are present in the nucleus of each atom, along with neutrons. The number of protons in each atom is its atomic number....
and a bicarbonateBicarbonateIn inorganic chemistry, bicarbonate is an intermediate form in the deprotonation of carbonic acid...
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 ankyrinAnkyrinAnkyrins are a family of adaptor proteins that mediate the attachment of integral membrane proteins to the spectrin-actin based membrane skeleton. Ankyrins have binding sites for the beta subunit of spectrin and at least 12 families of integral membrane proteins...
and protein 4.2Protein 4.2Erythrocyte membrane protein band 4.2 is a protein that in humans is encoded by the EPB42 gene.Protein 4.2 is a cytoskeleton protein found in red blood cells.-External links:...
). 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 DiegoDiego antigen system
The Diego Antigen System comprises 21 rare blood factors, any of which is carried on the band 3 protein, coded for by the gene SLC4A1 , located on human chromosome 17. The band 3 protein functions in the transport of chlorine ions and carbonate...
blood group
Human blood group systems
The International Society of Blood Transfusion currently recognises 30 major blood group systems . Thus, in addition to the ABO antigens and Rhesus antigens, many other antigens are expressed on the red blood cell surface membrane...
.
More importantly erythroid AE1 mutations cause between 15-25% of cases of Hereditary spherocytosis
Hereditary spherocytosis
Hereditary spherocytosis is a genetically-transmitted form of spherocytosis, an auto-hemolytic anemia characterized by the production of red blood cells that are sphere-shaped rather than bi-concave disk shaped , and therefore more prone to hemolysis.-Symptoms:As in non-hereditary spherocytosis,...
(a disorder associated with progressive red cell membrane loss), and also cause the hereditary conditions of Hereditary stomatocytosis
Hereditary stomatocytosis
Hereditary stomatocytosis describes a number of inherited autosomal dominant human conditions which affect the red blood cell, in which the membrane or outer coating of the cell 'leaks' sodium and potassium ions.-Pathophysiology:...
and Southeast Asian Ovalocytosis
Ovalocytosis
Southeast Asian ovalocytosis is a form of hereditary elliptocytosis common in some communities in Malaysia and Papua New Guinea, as it confers some resistance to cerebral Falciparum Malaria.-Southeast Asian ovalocytosis:...
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 hydrogenHydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...
ions and bicarbonate ions from carbon dioxide and water-a reaction catalysed by Carbonic anhydrase
Carbonic anhydrase
The carbonic anhydrases form a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons , a reversible reaction that occurs rather slowly in the absence of a catalyst...
.
The hydrogen ions are pumped into the collecting duct tubule by vacuolar H+ATPase, the apical proton pump
Proton pump
A proton pump is an integral membrane protein that is capable of moving protons across a cell membrane, mitochondrion, or other organelle. Mechanisms are based on conformational changes of the protein structure or on the Q cycle.-Function:...
,which thus excretes acid into the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
.
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 acidosisRenal tubular acidosis
Renal tubular acidosis is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify the urine. When blood is filtered by the kidney, the filtrate passes through the tubules of the nephron, allowing for exchange of salts, acid...
, which is an inability to acidify the urine, even if the blood is too acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
.
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.
Interactions
Band 3 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Carbonic anhydrase II
Carbonic anhydrase II
Carbonic anhydrase II , is one of fourteen forms of human α carbonic anhydrases. Carbonic anhydrase catalyzes reversible hydration of carbon dioxide...
and CA4.
External links
- Diego blood group system at BGMUTBGMUTThe BGMUT Database documents allelic variations in the genes encoding for human blood group systems. It was set up in 1999 through an initiative of the Human Genome Variation Society . Since 2006, it has been a part of the dbRBC resource of NCBI at the NIH...
Blood Group Antigen Gene Mutation Database at NCBINational Center for Biotechnology InformationThe National Center for Biotechnology Information is part of the United States National Library of Medicine , a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper...
, NIH