cystic fibrosis transmembrane conductance regulator; CFTR; cAMP-dependent chloride channel; ATP-binding cassette transporter sub-family C member 7 (CFTR ABCC7)
Jump to navigation
Jump to search
Function
- epithelial Cl- channel essential to fluid secretion
- role in transport of chloride ions
- may regulate bicarbonate secretion & salvage in epithelial cells by regulating the SLC4A7 transporter
- interacts with SHANK2 (putative)
- interacts with SLC9A3R1, MYO6 & GOPC
- interacts with SLC4A7 through SLC9A3R1
- phosphorylation activates the channel
- PKC phosphorylation may activate the channel or permit activation by phosphorylation by PKA
Structure
- PDZ-binding motif mediates interactions with GOPC & with the SLC4A7, SLC9A3R1/EBP50 complex
- belongs to the ABC transporter family, CFTR transporter (TC 3.A.1.202) subfamily
- contains 2 ABC transmembrane type-1 domains
- residues 81- 365 & 859-1155
- each encompasses several transmembrane domains
- contains 2 ABC transporter domains
Compartment
membrane
Alternative splicing
named isoforms=3
Expression
- found on the surface of the epithelial cells that line the lungs & other organs
Pathology
- defects in CFTR are the cause of cystic fibrosis
- ~70% of patients carry the same mutation, a deletion of Phe-508 in one of the two ATP-binding domains; this mutation results in a temperature-sensitive defect in protein processing (not in aberrant regulation by ATP); at 27 C, the mutant form of CFTR forms functionally active Cl- channels, but at 37 C, it gets stuck in the maturation pathway & fails to reach plasma membrane, thus giving rise to a very severe disease state in which epithelial Cl- channels are absent
- in the endoplasmic reticulum, CFTR binds to calnexin in the maturation process; with the Phe-508 deletion, calnexin fails to release the mutant CFTR
- skipping of the first 248 nucleotides of exon 13, caused by mutation of the exon splicing exon (ESE) in exon 13 results in cystic fibrosis
- defects in CFTR are the cause of congenital bilateral absence of the vas deferens (CBAVD)
More general terms
- transmembrane 12 protein
- Cl- channel
- ATP-binding cassette sub-family C (ABC transporter-C, ABCC)
- phosphoprotein
References
- ↑ UniProt http://www.uniprot.org/uniprot/P13569.html
- ↑ CFTR; Cystic fibrosis mutation db http://www.genet.sickkids.on.ca/cftr/
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=CFTR
- ↑ Wikipedia; Note: CFTR entry http://en.wikipedia.org/wiki/cystic_fibrosis_transmembrane_conductance_regulator
- ↑ Miller C Cystic fibrosis. Sickly channels in mild disease. Nature 362:106 1993 PMID: https://www.ncbi.nlm.nih.gov/pubmed/7680767
- ↑ Davis Hospital Practice 27:79 1993)
- ↑ Entrez Gene http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1080
- ↑ Egan ME et al, Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 304:600, 2004 PMID: https://www.ncbi.nlm.nih.gov/pubmed/15105504
Database
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:1080
- OMIM: https://mirror.omim.org/entry/219700
- OMIM: https://mirror.omim.org/entry/277180
- OMIM: https://mirror.omim.org/entry/602421
- UniProt: http://www.uniprot.org/uniprot/P13569.html
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=1080