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Tuesday, April 19, 2022

04-19-2022-0459 - ATP-binding cassette transporters (ABC transporters)

The ATP-binding cassette transporters (ABC transporters) are a transport system superfamily that is one of the largest and possibly one of the oldest gene families. It is represented in all extant phyla, from prokaryotes to humans.[1][2][3]

ABC transporters often consist of multiple subunits, one or two of which are transmembrane proteins and one or two of which are membrane-associated AAA ATPases. The ATPase subunits utilize the energy of adenosine triphosphate (ATP) binding and hydrolysis to provide the energy needed for the translocation of substrates across membranes, either for uptake or for export of the substrate.

Most of the uptake systems also have an extracytoplasmic receptor, a solute binding protein. Some homologous ATPases function in non-transport-related processes such as translation of RNA and DNA repair.[4][5] ABC transporters are considered to be an ABC superfamily based on the similarities of the sequence and organization of their ATP-binding cassette (ABC) domains, even though the integral membrane proteins appear to have evolved independently several times, and thus comprise different protein families.[6] Like the ABC exporters, it is possible that the integral membrane proteins of ABC uptake systems also evolved at least 3 times independently, based on their high resolution 3-dimensional structures.[7] ABC uptake porters take up a large variety of nutrients, biosynthetic precursors, trace metals and vitamins, while exporters transport lipidssterolsdrugs, and a large variety of primary and secondary metabolites. Some of these exporters in humans are involved in tumor resistance, cystic fibrosis and a range of other inherited human diseases. High level expression of the genes encoding some of these exporters in both prokaryotic and eukaryotic organisms (including human) result in the development of resistance to multiple drugs such as antibiotics and anti-cancer agents.

Hundreds of ABC transporters have been characterized from both prokaryotes and eukaryotes.[8] ABC genes are essential for many processes in the cell, and mutations in human genes cause or contribute to several human genetic diseases.[9] Forty eight ABC genes have been reported in humans. Among these, many have been characterized and shown to be causally related to diseases present in humans such as cystic fibrosis, adrenoleukodystrophy, Stargardt disease, drug-resistant tumors, Dubin–Johnson syndrome, Byler's disease, progressive familiar intrahepatic cholestasis, X-linked sideroblastic anemia, ataxia, and persistent and hyperinsulimenic hypoglycemia.[8] ABC transporters are also involved in multiple drug resistance, and this is how some of them were first identified. When the ABC transport proteins are overexpressed in cancer cells, they can export anticancer drugs and render tumors resistant.[10] 

https://en.wikipedia.org/wiki/ATP-binding_cassette_transporter


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