Cftr

From Anvita Health Wiki

Contents 1 Function 2 Structure 3 Compartment 4 Alternative-splicing 5 Expression 6 Pathology 7 More General Terms 8 Internet Database 9 References

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

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)

• skipping of exon 9 associated with CBAVD
• a high number of TG repeats & a low number of T repeats at the intron 8- exon 9 junction favor exon skipping

More General Terms

• transmembrane 12 protein
• Cl- channel
• ATP-binding cassette sub-family C (ABC transporter-C, ABCC)
• phosphoprotein

Internet Database

Kegg: [1]
OMIM: 219700
OMIM: 277180
OMIM: 602421
Prosite: [2]
Prosite: [3]
Prosite: [4]
UniProt: [5]
Entrez gene: 1080

References

1. UniProt [6]
2. CFTR; Cystic fibrosis mutation db [7]
3. GeneReviews [8]
4. Wikipedia; Note: CFTR entry [9]
5. Miller C Cystic fibrosis. Sickly channels in mild disease. Nature 362:106 1993 PMID: &dopt=Abstract
6. Davis Hospital Practice 27:79 1993)
7. Entrez Gene [10]
8. Egan ME et al, Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 304:600, 2004 PMID: [11]

cystic fibrosis transmembrane conductance regulator; CFTR; cAMP-dependent chloride channel; ATP-binding cassette transporter sub-family C member 7 (CFTR ABCC7)