Solute carrier family 4, anion exchanger, member 1 (erythrocyte membrane protein band 3, Diego blood group)
Atomic microscope image of Band 3
Available structures: 1bh7, 1bzk, 1hyn
Identifiers
Symbol(s)	SLC4A1; WD; AE1; BND3; CD233; DI; EMPB3; EPB3; FR; MGC116750; MGC116753; MGC126619; MGC126623; RTA1A; SW; WD1; WR
External IDs	OMIM: 109270 MGI: 109393 HomoloGene: 37290
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	6521	20533
Ensembl	ENSG00000004939	ENSMUSG00000006574
Uniprot	P02730	Q3TA19
Refseq	NM_000342 (mRNA) NP_000333 (protein)	NM_011403 (mRNA) NP_035533 (protein)
Location	Chr 17: 39.68 - 39.7 Mb	Chr 11: 102.16 - 102.18 Mb
Pubmed search	[1]	[2]

solute carrier family 4 (anion exchanger), member 1, adaptor protein
Identifiers
Symbol	SLC4A1AP
Entrez	22950
HUGO	13813
OMIM	602655
RefSeq	NM_018158
UniProt	Q9BWU0
Other data
Locus	Chr. 2 p23.3

Anion Exchanger 1 (AE1) or Band 3 is a phylogenetically preserved transport protein responsible for mediating the electroneutral exchange of chloride (Cl-) for bicarbonate (HCO3-) across a plasma membrane. The Diego Antigen (or Blood Group System comprises 21 rare blood factors any of which is carried on the band 3 protein, coded for by the gene SLC4A1 ( Solute The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mouse Genome Informatics (MGI website is run by The Jackson Laboratory. HomoloGene, a tool of the National Center for Biotechnology Information (NCBI is a system for automated detection of homologs (similarity attributable to descent The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences Ensembl is a joint scientific project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, which was launched in 1999 in response to the imminent UniProt is the uni versal prot ein resource a central repository of Protein data created by combining Swiss-Prot, TrEMBL PubMed is a free search engine for accessing the MEDLINE database of citations and abstracts of biomedical research articles The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The National Center for Biotechnology Information ( NCBI) is part of the United States National Library of Medicine (NLM a branch of the National Institutes Swiss-Prot is a manually curated Biological database of Protein sequences In the fields of Genetics and Evolutionary computation, a locus (plural loci) is a fixed position on a Chromosome such as the position of a Chromosome 2 is one of the 23 pairs of Chromosomes in Humans People normally have two copies of this chromosome The chloride Ion is formed when the element Chlorine picks up one Electron to form an Anion (negatively-charged ion Cl&minus In Inorganic chemistry, bicarbonate ( IUPAC -recommended nomenclature hydrogencarbonate) is an intermediate form in the Deprotonation The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer

It is ubiquitous throughout the vertebrates. Vertebrates are members of the Subphylum Vertebrata, Chordates with backbones or spinal columns The grouping sometimes includes 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. Human beings, humans or man (Origin 1590–1600 L homō man OL hemō the earthly one (see Humus Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood The collecting duct system of the Kidney consists of a series of tubules and ducts that connect the Nephrons to the Ureter. The collecting duct system of the Kidney consists of a series of tubules and ducts that connect the Nephrons to the Ureter. The kidneys are complicated organs that have numerous biological roles

The erythrocyte and kidney forms are different isoforms of the same protein. A protein isoform is a version of a Protein with only small differences to another isoform of the same protein Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl

Discovery

AE1 was discovered following SDS-PAGE gel electrophoresis of erythrocyte cell membrane. SDS-PAGE, Sodium dodecyl sulfate Polyacrylamide gel Electrophoresis, is a technique widely used in Biochemistry, forensics The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer 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. "Ion pump" redirects here For pumps that reduce pressure see Ion pump (physics. Nor is it strictly an enzyme. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins It is protein counter-transporter, known as band III. Active transport is the mediated process of moving particles across Biological membrane against the concentration gradient ^[1]

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 carbonic anhydrases (or carbonate dehydratases) form a family of Enzymes that catalyze the rapid conversion of Carbon dioxide to Bicarbonate The proton ( Greek πρῶτον / proton "first" is a Subatomic particle with an Electric charge of one positive In Inorganic chemistry, bicarbonate ( IUPAC -recommended nomenclature hydrogencarbonate) is an intermediate form in the Deprotonation 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). Ankyrins are a family of adaptor proteins that mediate the attachment of Integral membrane proteins to the Spectrin - Actin based membrane skeleton Erythrocyte membrane protein band 42, also known as EPB42, is a human Gene. 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. The Diego Antigen (or Blood Group System comprises 21 rare blood factors any of which is carried on the band 3 protein, coded for by the gene SLC4A1 ( Solute A blood type (also called a blood group) is a classification of Blood based on the presence or absence of inherited Antigenic substances on the

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 ^[2] and Southeast Asian Ovalocytosis ^[3]

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. Hereditary spherocytosis is a genetically-transmitted form of Spherocytosis, an auto- hemolytic Anemia characterized by the production of red blood cells 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' Ovalocytosis is an inherited condition in which a person's Red blood cells which are supposed to be round instead have a slightly Oval or elliptical The collecting duct system of the Kidney consists of a series of tubules and ducts that connect the Nephrons to the Ureter.

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. Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 The carbonic anhydrases (or carbonate dehydratases) form a family of Enzymes that catalyze the rapid conversion of Carbon dioxide to Bicarbonate

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. This article is about proton pumps in general For the proton P-type ATPase see Proton ATPase. Urine is a liquid waste product of the body secreted by the Kidneys by a process of filtration from Blood and Excreted through the Urethra.

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. Renal tubular acidosis ( RTA) is a medical condition that involves an accumulation of acid in the body due to a failure of the kidneys to appropriately acidify In Computer science, ACID ( Atomicity Consistency Isolation Durability) is a set of properties that guarantee that Database transactions are 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.

See also

• Cluster of differentiation

References

1. ^ Hunter M (1977). The cluster of differentiation (often abbreviated as CD) is a protocol used for the identification and investigation of Cell surface molecules present on Leukocytes "Human erythrocyte anion permeabilities measured under conditions of net charge transfer. ". J Physiol 268 (1): 35–49. PMID 874904.  
2. ^ LJ Bruce (Nov 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.  
3. ^ Jarolim p (1991). "Deletion in Erythrocyte Band 3 Gene in Malaria-Resistant Southeast Asian Ovalocytosis". PNAS 88: 11022–11026.  .

External links

• Diego blood group system at BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH
• MeSH Band+3+Protein
• MeSH Chloride-Bicarbonate+Antiporters

Further reading