Pendrin | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | IPR030285 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | GeneCards: | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Pendrin is an anion exchange protein that in humans is encoded by the SLC26A4 gene (solute carrier family 26, member 4). [1] [2] Pendrin was initially identified as a sodium-independent chloride-iodide exchanger [3] with subsequent studies showing that it also accepts formate and bicarbonate as substrates. [4] [5] Pendrin is similar to the Band 3 transport protein found in red blood cells. Pendrin is the protein which is mutated in Pendred syndrome, which is an autosomal recessive disorder characterized by sensorineural hearing loss, goiter and a partial organification problem detectable by a positive perchlorate test. [6]
Pendrin is responsible for mediating the electroneutral exchange of chloride (Cl−) for bicarbonate (HCO3−) across a plasma membrane in the chloride cells of freshwater fish.
By phylogenetic analysis, pendrin has been found to be a close relative of prestin present on the hair cells or organ of corti in the inner ear. Prestin is primarily an electromechanical transducer but pendrin is an ion transporter.
Pendrin is an ion exchanger found in many types of cells in the body. High levels of pendrin expression have been identified in the inner ear and thyroid. In the thyroid, pendrin mediates a component of the efflux of iodide across the apical membrane of the thyrocyte, which is critical for the formation of thyroid hormone. [7] The exact function of pendrin in the inner ear remains unclear; however, pendrin may play a role in acid-base balance as a chloride-bicarbonate exchanger, regulate volume homeostasis through its ability to function as a chloride-formate exchanger [8] [9] or indirectly modulate the calcium concentration of the endolymph. [10] Pendrin is also expressed in the kidney, and has been localized to the apical membrane of a population of intercalated cells in the cortical collecting duct where it is involved in bicarbonate secretion. [11] [12]
Mutations in this gene are associated with Pendred syndrome, the most common form of syndromic deafness, an autosomal-recessive disease. Pendred syndrome is characterized by thyroid goiter and enlargement of the vestibular aqueduct resulting in deafness; however, despite being expressed in the kidney, individuals with Pendred syndrome do not show any kidney-related acid-base, or volume abnormalities under basal conditions. This is probably the result of other bicarbonate or chloride transporters in the kidney compensating for any loss of pendrin function. Only under extreme situations of salt depletion or metabolic alkalosis, or with inactivation of the sodium-chloride cotransporter, are fluid and electrolyte disorders manifested in these patients. [13] SLC26A4 is highly homologous to the SLC26A3 gene; they have similar genomic structures and this gene is located 3' of the SLC26A3 gene. The encoded protein has homology to sulfate transporters. [1]
Another little-understood role of pendrin is in airway hyperreactivity and inflammation, as during asthma attacks and allergic reactions. Expression of pendrin in the lung increases in response to allergens and high concentrations of IL-13, [14] [15] and overexpression of pendrin results in airway inflammation, hyperreactivity, and increased mucus production. [16] [17] These symptoms could result from pendrin's effects on ion concentration in the airway surface liquid, possibly causing the liquid to be less hydrated. [18]
Cotransporters are a subcategory of membrane transport proteins (transporters) that couple the favorable movement of one molecule with its concentration gradient and unfavorable movement of another molecule against its concentration gradient. They enable coupled or cotransport and include antiporters and symporters. In general, cotransporters consist of two out of the three classes of integral membrane proteins known as transporters that move molecules and ions across biomembranes. Uniporters are also transporters but move only one type of molecule down its concentration gradient and are not classified as cotransporters.
Pendred syndrome is a genetic disorder leading to congenital bilateral sensorineural hearing loss and goitre with euthyroid or mild hypothyroidism. There is no specific treatment, other than supportive measures for the hearing loss and thyroid hormone supplementation in case of hypothyroidism. It is named after Vaughan Pendred (1869–1946), the British doctor who first described the condition in an Irish family living in Durham in 1896. It accounts for 7.5% to 15% of all cases of congenital deafness.
Prestin is a protein that is critical to sensitive hearing in mammals. It is encoded by the SLC26A5 gene.
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.
The Na-K-Cl cotransporter (NKCC) is a protein that aids in the secondary active transport of sodium, potassium, and chloride into cells. In humans there are two isoforms of this membrane transport protein, NKCC1 and NKCC2, encoded by two different genes. Two isoforms of the NKCC1/Slc12a2 gene result from keeping or skipping exon 21 in the final gene product.
The sodium-chloride symporter (also known as Na+-Cl− cotransporter, NCC or NCCT, or as the thiazide-sensitive Na+-Cl− cotransporter or TSC) is a cotransporter in the kidney which has the function of reabsorbing sodium and chloride ions from the tubular fluid into the cells of the distal convoluted tubule of the nephron. It is a member of the SLC12 cotransporter family of electroneutral cation-coupled chloride cotransporters. In humans, it is encoded by the SLC12A3 gene (solute carrier family 12 member 3) located in 16q13.
Thiamine transporter 1, also known as thiamine carrier 1 (TC1) or solute carrier family 19 member 2 (SLC19A2) is a protein that in humans is encoded by the SLC19A2 gene. SLC19A2 is a thiamine transporter. Mutations in this gene cause thiamine-responsive megaloblastic anemia syndrome (TRMA), which is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anemia and sensorineural deafness.
The sulfate transporter is a solute carrier family protein that in humans is encoded by the SLC26A2 gene. SLC26A2 is also called the diastrophic dysplasia sulfate transporter (DTDST), and was first described by Hästbacka et al. in 1994. A defect in sulfate activation described by Superti-Furga in achondrogenesis type 1B was subsequently also found to be caused by genetic variants in the sulfate transporter gene. This sulfate (SO42−) transporter also accepts chloride, hydroxyl ions (OH−), and oxalate as substrates. SLC26A2 is expressed at high levels in developing and mature cartilage, as well as being expressed in lung, placenta, colon, kidney, pancreas and testis.
Cadherin-23 is a protein that in humans is encoded by the CDH23 gene.
The major facilitator superfamily (MFS) is a superfamily of membrane transport proteins that facilitate movement of small solutes across cell membranes in response to chemiosmotic gradients.
Chloride anion exchanger, also known as down-regulated in adenoma, is a protein that in humans is encoded by the SLC26A3 gene.
Monocarboxylate transporter 8 (MCT8) is an active transporter protein that in humans is encoded by the SLC16A2 gene.
Membrane-associated transporter protein (MATP), also known as solute carrier family 45 member 2 (SLC45A2) or melanoma antigen AIM1, is a protein that in humans is encoded by the SLC45A2 gene.
Sodium bicarbonate transporter-like protein 11 is a protein that in humans is encoded by the SLC4A11 gene.
Solute carrier family 26 member 6 is a protein that in humans is encoded by the SLC26A6 gene. It is an anion-exchanger expressed in the apical membrane of the kidney proximal tubule, the apical membranes of the duct cells in the pancreas, and the villi of the duodenum.
The Cl−-formate exchanger, otherwise known as Pendrin encoded by the SLC26A4 gene, is a transport protein present in the kidney, where it functions in the renal chloride reabsorption. It is also present in vascular smooth muscle and cardiac muscle.
Otoferlin is a protein that in humans is encoded by the OTOF gene.
Anion exchange transporter is a protein that in humans is encoded by the SLC26A7 gene.
Congenital chloride diarrhea is a genetic disorder due to an autosomal recessive mutation on chromosome 7. The mutation is in downregulated-in-adenoma (DRA), a gene that encodes a membrane protein of intestinal cells. The protein belongs to the solute carrier 26 family of membrane transport proteins. More than 20 mutations in the gene are known to date. A rare disease, CCD occurs in all parts of the world but is more common in some populations with genetic founder effects, most notably in Finland.
The anion exchanger family is a member of the large APC superfamily of secondary carriers. Members of the AE family are generally responsible for the transport of anions across cellular barriers, although their functions may vary. All of them exchange bicarbonate. Characterized protein members of the AE family are found in plants, animals, insects and yeast. Uncharacterized AE homologues may be present in bacteria. Animal AE proteins consist of homodimeric complexes of integral membrane proteins that vary in size from about 900 amino acyl residues to about 1250 residues. Their N-terminal hydrophilic domains may interact with cytoskeletal proteins and therefore play a cell structural role. Some of the currently characterized members of the AE family can be found in the Transporter Classification Database.