Contents

Search

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

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 a) residues 81- 365 & 859-1155 b) 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 a) ~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 b) in the endoplasmic reticulum, CFTR binds to calnexin in the maturation process; with the Phe-508 deletion, calnexin fails to release the mutant CFTR c) 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) a) skipping of exon 9 associated with CBAVD b) a high number of TG repeats & a low number of T repeats at the intron 8-exon 9 junction favor exon skipping

Related

CFTR gene mutation

General

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

Properties

SIZE: entity length = 1480 aa MW = 168 kD COMPARTMENT: plasma membrane MOTIF: cytoplasmic domain {1-80} transmembrane domain {81-103} exoplasmic loop {104-117} transmembrane domain {118-138} cytoplasmic loop {139-194} transmembrane domain {195-215} exoplasmic loop {216-220} transmembrane domain {221-241} cytoplasmic loop {242-307} transmembrane domain {308-328} exoplasmic loop {329-330} transmembrane domain {331-350} cytoplasmic loop {351-859} MOTIF: ABC transporter 1 {423-646} ATP-binding site NAME: ATP-binding site SITE: 458-465 Tyr phosphorylation site {Y515} Ser phosphorylation site {S660} Ser phosphorylation site {S686} Ser phosphorylation site {S700} Ser phosphorylation site {S712} Ser phosphorylation site {S737} Ser phosphorylation site {S753} Ser phosphorylation site {S768} Ser phosphorylation site {S790} Ser phosphorylation site {S795} Ser phosphorylation site {S813} transmembrane domain {860-880} exoplasmic loop {881-911} N-glycosylation site {N894} N-glycosylation site {N900} transmembrane domain {912-932} cytoplasmic loop {933-990} transmembrane domain {991-1011} exoplasmic loop {1012-1013} transmembrane domain {1014-1034} cytoplasmic loop {1035-1102} transmembrane domain {1103-1123} exoplasmic loop {1124-1128} transmembrane domain {1129-1149} cytoplasmic domain {1150-1480} MOTIF: ABC transporter 2 {1210-1443} ATP-binding site NAME: ATP-binding site SITE: 1244-1251 PDZ recognition motif NAME: PDZ recognition motif SITE: 1478-1480 FOR-BINDING-VIA: PDZ domain ION-PERMEABILITY: Cl-

Database Correlations

OMIM correlations MORBIDMAP 602421 UniProt P13569 PFAM correlations Entrez Gene 1080 Kegg hsa:1080

References

  1. UniProt :accession P13569
  2. CFTR; Cystic fibrosis mutation db http://www.genet.sickkids.on.ca/cftr/
  3. GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=CFTR
  4. Wikipedia; Note: CFTR entry http://en.wikipedia.org/wiki/cystic_fibrosis_transmembrane_conductance_regulator
  5. Miller C Cystic fibrosis. Sickly channels in mild disease. Nature 362:106 1993 PMID: 7680767
  6. Davis Hospital Practice 27:79 1993)
  7. Entrez Gene :accession 1080
  8. Egan ME et al, Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects. Science 304:600, 2004 PMID: 15105504