Product Code Database
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 (secondary active transport) 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. (2025). 9781429234139, W.H. Freeman and Co.. ISBN 9781429234139
Cotransporters can be classified as antiporters and symporters. Both use electric potential, chemical gradients, or both to move protons and ions against a concentration gradient. In plants, the proton is considered a secondary substance, and high proton concentration in the apoplast powers the inward movement of certain ions by symporters. A proton gradient causes ions to be moved into the vacuole by the proton-sodium antiporter or the proton-calcium antiporter. In plants, sucrose transport is distributed throughout the plant by the proton-pump; the pump creates a gradient of protons so that there are many more on one side of the membrane than the other. As the protons diffuse back across the membrane, the free energy liberated by this diffusion is used to co-transport sucrose. In mammals, glucose is transported through sodium-dependent glucose transporters, a process that uses energy. Since both glucose and sodium are transported in the same direction across the membrane, they are classified as symporters. The glucose transporter system was first hypothesized by Robert K. Crane in 1960.
Cotransporters undergo a cycle of conformational changes by linking the movement of an ion with its concentration gradient (downhill movement) to the movement of a cotransported solute against its concentration gradient (uphill movement). In one conformation the protein will have the binding site (or sites in the case of symporters) exposed to one side of the membrane. Upon binding of both the molecule which is to be transported uphill and the molecule to be transported downhill a conformational change will occur. This conformational change will expose the bound substrates to the opposite side of the membrane, where the substrates will disassociate. Both the molecule and the cation must be bound in order for the conformational change to occur. This mechanism was first introduced by Oleg Jardetzky in 1966. This cycle of conformational changes only transports one substrate ion at a time, which results in a fairly slow transport rate (100 to 104 ions or molecules per second) when compared to other transport proteins like . The rate at which this cycle of conformational changes occurs is called the turnover rate (TOR) and is expressed as the average number of complete cycles per second performed by a single cotransporter molecule.
Cells also contain anion antiporters such as the Band 3 (or AE1) anion transport protein. This cotransporter is an important integral protein in mammalian erythrocytes and moves chloride ion and bicarbonate ion in a one-to-one ratio across the plasma membrane based only on the concentration gradient of the two ions. The AE1 antiporter is essential in the removal of carbon dioxide waste that is converted to bicarbonate inside the erythrocyte.
Na+/phosphate cotransporter (NaPi) – Sodium-phosphate cotransporters are from the SLC34 and SLC20 protein families. They are also found across the epithelial cells of renal proximal tubule and of the small intestine. It transfers inorganic phosphate into cells through active transport with the help of a Na+ gradient. Similar to SGTL1, they are classified as electrogenic transporters. NaPi coupled with 3 Na+ ions and 1 divalent Pi, are classified as NaPi IIa and NaPi IIb. NaPi that couples with 2 Na+ and 1 divalent Pi are classified as NaPi IIc.
Na+/I− symporter (NIS) – Sodium-Iodide is a type of symporter that is responsible for transferring iodide in the thyroid gland. NIS is primarily found in cells of the thyroid gland and also in the mammary glands. They are located on the basolateral membrane of thyroid follicular cells where 2 Na+ ions and 1 I− ion is coupled to transfer the iodide. NIS activity helps in the diagnosis and treatment of thyroid disease, including the highly successful treatment of thyroid cancer with radioiodide after thyroidectomy.
Na-K-2Cl symporter – This specific cotransporter regulates the cell volume by controlling the water and electrolyte content within the cell. The Na-K-2Cl Cotransporter is vital in salt secretion in secretory epithelia cells along with renal salt reabsorption. Two variations of the Na-K-2Cl symporter exist and are known as NKCC1 and NKCC2. The NKCC1 cotransport protein is found throughout the body but NKCC2 is found only in the kidney and removes the sodium, potassium, and chloride found in the body's urine, so it can be absorbed into the blood.
GABA transporter – neurotransmitter γ-aminobutyric acid (GABA) transporters are members of the solute carrier family 6 (SLC6) of sodium- and chloride-dependent neurotransmitter receptor transporters that are located in the plasma membrane and regulate the concentration of GABA in the synaptic cleft. The SLC6A1 gene encodes GABA transporters. The transporters are electrogenic and couples 2 Na+, 1 Cl− and 1 GABA for inward translocation.
K+Cl− Symporter – The K+-Cl− cotransporter family consists of four specific symporters known as KCC1, KCC2, KCC3, and KCC4. The KCC2 isoform is specific to neuronal tissue and the other three can be found in various tissues throughout the body. This cotransporter family controls the concentration levels of potassium and chloride within cells through the combined movement of K+/H+ and Cl−/HCO3− exchangers or through combined movement of both ions due to concentration activated channels. The four known KCC proteins team up to form two separate subfamilies with KCC1 and KCC3 pairing together and KCC2 and KCC4 becoming a pair to facilitate ion movement.
| Lysinuric |
| Tangier disease |
| X-linked sideroblastic anemia |
| Stargardt disease, Fundus flavimaculatus |
| elliptocytosis, ovalocytosis, hemolytic anemia, spherocytosis, renal tubular acidosis |
| congenital chloroidorrhea |
| congenital chloroidorrhea |
| Adrenoleukodystrophy |
| ankylosis (calcification); arthritis accompanied by mineral deposition, formation of bony outgrowths, and joint destruction |
| adult-onset type II citrullinemia |
| Neurodegeneration |
| HHH |
| Cystic fibrosis |
| Menkes/Wilsons disease |
| Menkes/Wilsons disease, X-linked hypophosphatemia |
| chondrodysplasias/ Diastrophic dysplasia |
| Neurodegeneration, Amyotrophic lateral sclerosis |
| Neurodegeneration, Dicarboxylic aminoaciduria |
| Neurodegeneration |
| Neurodegeneration |
| Neurodegeneration |
| Progressive familial intrahepatic cholestasis |
| Folate malabsorption/megaloblastic anemia |
| low CNS glucose causing seizures, Fanconi-Bickel syndrome, Glycogen storage disease type Id, Non-insulin-dependent diabetes mellitus, defect in glucose transport across the blood-brain barrier |
| low CNS glucose causing seizures, Fanconi-Bickel syndrome, Glycogen storage disease type Id, Non-insulin-dependent diabetes mellitus (NIDDM) |
| low CNS glucose causing seizures, Fanconi-Bickel syndrome, Glycogen storage disease type Id, Non-insulin-dependent diabetes mellitus (NIDDM) |
| low CNS glucose causing seizures, Fanconi-Bickel syndrome, Glycogen storage disease type Id, Non-insulin-dependent diabetes mellitus (NIDDM) |
| Isolated fructose malabsorption |
| anemia, genetic hemochromatosis |
| anxiety-related traits |
| Lysinuric protein intolerance |
| lysinuric protein intolerance |
| human cancers |
| Familia intrahepatic cholestasis |
| human cancers |
| Down syndrome |
| renal tubular acidosis |
| congenital hypothyroidism |
| Gitelman syndrome |
| Microvillus inclusion disease |
| Microvillus inclusion disease |
| congenital hypothyroidism |
| gitelman syndrome |
| Bartter syndrome |
| DiGeorge syndrome, velocardiofacial syndrome |
| Attention deficit hyperactivity disorder |
| primary bile acid malabsorption (PBAM) |
| systemic carnitine deficiency (progressive cardiomyopathy, skeletal myopathy, hypoglycaemia, hyperammonaemia, sudden infant death syndrome) |
| HHH |
| Graves disease |
| cystinuria |
| Neurodegeneration |
| hypocitraturia |
| various mental disorders |
| renal glucosuria / glucose-galactose malabsorption |
| renal glucosuria |
| anxiety-related traits, depression |
| juvenile onset psoriasis |
| Cystinuria |
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