Sandbox Reserved 1353

Composed of 1480 amino acids in 5 domains, each connected by a nucleotide binding domain. There are 6 alpha helices and 2 trans-membrane domains. It has 27 exons, 26 introns, and it is a glycoprotein. The gene is 189 kb long.

Function

The protein regulates transport of bicarbonate and chloride ions. Important for fluid and osmotic homeostasis. The Chloride channel only opens when the R domain is phosphorylated. It also protects against pathogens by regulation the pH of airway surfaces. It also involved in production of sweat, digestive fluids, and mucus.

Disease

When the protein isn't functional it causes Cystic Fibrosis (CF). Mutation at the sites below can dis-regulate fluid transport in lungs and pancreas. The gene is autosomal recessive. CF prevents successful excretion of wastes in many organs. Less functional proteins may result in sterility in males. Dysfunction also thickens mucus which can cause the chronic cough of CF. CF can be diagnosed through a sweat test or genetic testing.

Relevance

The protein is crucial for chlorine and thiocyanate ion circulation in epithelial cells, with lack of function leading to serious disease. Gene that encodes this protein is used to explore phylogeny of major mammal groups.

Structural highlights

There are 300 mutations in CFTR that are linked to cystic fibrosis. The main one is F508. The nbd1 domain is altered in CF patients, due to deletion of three nucleotides, the Phenylalaline amino acid is lost on the residue 508 position which results in a severe loss of function and leads to cystic fibrosis. Mutations at any of the below sites confers resistance to salmonella to the cell. These mutations also prevent diarrhea from Cholera in mice. Males that have a mild mutation in one copy of the CFTR gene and a cystic fibrosis causing mutation in the other copy also have a congenital bilateral absence of the vas deferens.

References

Araújo FG, Novaes FC, Santos NP, Martins VC, Souza SM, Santos SE, Ribeiro-dos-Santos AK (January 2005). "Prevalence of deltaF508, G551D, G542X, and R553X mutations among cystic fibrosis patients in the North of Brazil". Braz. J. Med. Biol. Res. 38 (1): 11–5. doi:10.1590/S0100-879X2005000100003. PMID 15665983.
Kavic SM, Frehm EJ, Segal AS (1999). "Case studies in cholera: lessons in medical history and science". Yale J Biol Med. 72 (6): 393–408. PMC 2579035 Freely accessible. PMID 11138935.

Cystic Fibrosis Mutation Database. "Genomic DNA sequence".