The cystic fibrosis transmembrane conductance regulator (CFTR) is a 12-transmembrane ATP-binding cassette (ABC) transporter that functions as a cAMP-dependent chloride channel. It is localized to the apical membrane of epithelial cells within the lungs, liver, pancreas, digestive tract, reproductive tract and skin, where it is involved in fluid transport.
CFTR is composed of five domains: two membrane-spanning domains (MSD1, MSD2) that function as a chloride channel; two nucleotide-binding domains (NBD1, NBD2) that possess ATPase activity; and a regulatory domain that contains a protein kinase A phosphorylation site, which controls channel opening. The CFTR may also regulate other channels including the epithelial sodium channel (ENaC) and the calcium-activated chloride channel (CaCC).
Mutations in the CFTR gene result in a number of diseases including cystic fibrosis (CF). The most common mutation detected in CF patients is a deletion of a phenylalanine residue within the NBD1 domain, and is known as the ΔF508 mutation. This results in a misfolded protein that is not trafficked to the apical membrane, but is instead retained in the endoplasmic reticulum where it undergoes proteasomal degradation. Absence of the CFTR at the apical membrane leads to an imbalance in intracellular chloride ion concentration, as well as the removal of the inhibitory actions of CFTR on ENaC function. This results in an increase in sodium ion conductance, inducing impaired transcellular water transport and abnormal lung secretions that promote bacterial infection.View all products for CFTR »
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