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Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)

Activators

The cystic fibrosis transmembrane conductance regulator (CFTR) is the most dominant Cl channel in several epithelial tissues, especially in lung and colon. Remarkably, CFTR is a member of the ATP-binding cassette (ABC) transporter superfamily that uses ATP hydrolyzation as the driving force for the translocation of a wide variety of substrates including sugars, amino acids, proteins and hydrophobic compounds, across cellular membranes. The CFTR is unique among ABC transporters in that it is a cAMP-regulated Cl channel. It shares the superfamily topology of 12 transmembrane domains with two nucleotide-binding domains (NBDs) and a regulatory (R) domain in the large third intracytoplasmic loop that is phosphorylated in multiple sites by PKA. Mutations in the CFTR gene cause channel dysfunction in several ways, ranging from complete loss of surface expression to diminished Cl secretion. Defects in the CFTR gene cause cystic fibrosis (CF), the most common genetic disease among Caucasians, as well as a form of male sterility.

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