The CFTR gene and its protein

The CFTR gene is large, extending over 250 kb of
genomic DNA, and is organized into 27 exons
(24 are shown in the diagram) encoding a 6.5 kb
transcript with several alternatively spliced
forms of mRNA. The CFTR protein has 1480
amino acids. It is a membrane-bound chloride
ion channel regulator with several functional
domains: two nucleotide-binding domains (encoded
by exons 9–12 and 19–23), a regulatory
domain (exons 12–14a), and two transmembrane-
spanning domains (exons 3–7 and 14b–
18). Each of the two transmembrane regions
consists of six transmembrane segments. The
nucleotide-binding domain 1 (NBD1) confers
cAMP-regulated chloride channel activity. The
most common mutation (occurring in 66% of
patients), a deletion of a phenylalanine codon in
position 508 (!F508), is located here. The protein
is a member of the ATP-binding cassette
(ABC) family of transporters. The R domain contains
putative sites for protein kinase A and protein
kinase C phosphorylation. CFTR is widely
expressed in epithelial cells.