Cystic fibrosis transmembrane conductance regulator
Also known as: ABCC7, CFTR
Function
Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis. Mediates the transport of chloride ions across the cell membrane. Possesses an intrinsic ATPase activity and utilizes ATP to gate its channel; the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains. The ion channel is also permeable to HCO(3)(-); selectivity depends on the extracellular chloride concentration. In vitro, mediates ATP-dependent glutathione flux. Exerts its function also by modulating the activity of other ion channels and transporters. Plays an important role in airway fluid homeostasis. Contributes to the regulation of the pH and the ion content of the airway surface fluid layer and thereby plays an important role in defense against pathogens. Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex. Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G. Inhibits the activity of the ENaC channel containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7. Can inhibit the chloride channel activity of ANO1. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation.
Classification
- Family (Pfam)
- PF00664 ABC_membrane, PF00005 ABC_tran, PF14396 CFTR_R
- InterPro
- AAA+_ATPase, ABC1_TM_dom, ABC1_TM_sf, ABC_transporter-like_ATP-bd, ABC_transporter-like_CS, ABC_transporter_C-like, CFTR/ABCC7, CFTR1_ATP-bd_dom1, CFTR_reg_dom, P-loop_NTPase
- Functional cluster
- Serine/Threonine Protein Kinases
Experimental structures · PDB · 58
- 1XMI X-ray 2.25A
- 1XMJ X-ray 2.30A
- 2BBO X-ray 2.55A
- 2BBS X-ray 2.05A
- 2BBT X-ray 2.30A
- 2LOB NMR
- 2PZE X-ray 1.70A
- 2PZF X-ray 2.00A
- 2PZG X-ray 1.80A
- 3GD7 X-ray 2.70A
- 3ISW X-ray 2.80A
- 4WZ6 X-ray 2.05A
- … and 46 more
A predicted model is available from AlphaFold.
Gene Ontology · 49
- GO:0016324 apical plasma membrane
- GO:0016323 basolateral plasma membrane
- GO:0009986 cell surface
- GO:0034707 chloride channel complex
- GO:0030669 clathrin-coated endocytic vesicle membrane
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005769 early endosome
- GO:0031901 early endosome membrane
- GO:0005789 endoplasmic reticulum membrane
- GO:0010008 endosome membrane
- GO:0030660 Golgi-associated vesicle membrane
- GO:0005765 lysosomal membrane
- GO:0016020 membrane
- GO:0005634 nucleus
- GO:0005886 plasma membrane
- GO:0032991 protein-containing complex
- GO:0055037 recycling endosome
- GO:0055038 recycling endosome membrane
- GO:0071889 14-3-3 protein binding
- GO:0140359 ABC-type transporter activity
- GO:0005524 ATP binding
- GO:0016887 ATP hydrolysis activity
- GO:0042626 ATPase-coupled transmembrane transporter activity
- GO:0015106 bicarbonate transmembrane transporter activity
- GO:0005254 chloride channel activity
- GO:0019869 chloride channel inhibitor activity
- GO:0017081 chloride channel regulator activity
- GO:0015108 chloride transmembrane transporter activity
- GO:0019899 enzyme binding
- GO:0042802 identical protein binding
- GO:0005260 intracellularly ATP-gated chloride channel activity
- GO:0030165 PDZ domain binding
- GO:0051087 protein-folding chaperone binding
- GO:0106138 Sec61 translocon complex binding
- GO:0097186 amelogenesis
- GO:0015701 bicarbonate transport
- GO:0071320 cellular response to cAMP
- GO:1904322 cellular response to forskolin
- GO:1902476 chloride transmembrane transport
- GO:0051454 intracellular pH elevation
- GO:0060081 membrane hyperpolarization
- GO:0050891 multicellular organismal-level water homeostasis
- GO:0070175 positive regulation of enamel mineralization
- GO:0034976 response to endoplasmic reticulum stress
- GO:0048240 sperm capacitation
- GO:0035377 transepithelial water transport
- GO:0055085 transmembrane transport
- GO:0006833 water transport
Disease associations
- cystic fibrosis MONDO:0009061
- congenital bilateral aplasia of vas deferens from CFTR mutation MONDO:0010178
Drugs targeting this protein · 12
- IVACAFTOR positive modulator
- LUMACAFTOR stabiliser
- TEZACAFTOR positive modulator
- GALICAFTOR positive modulator
- IOWH-032 inhibitor
- DEUTIVACAFTOR activator
- OLACAFTOR positive modulator
- BAMOCAFTOR positive modulator
- ELEXACAFTOR positive modulator
- ICENTICAFTOR activator
- NAVOCAFTOR positive modulator
- VANZACAFTOR positive modulator
Related proteins · sequence + function similarity
- Cystic fibrosis transmembrane conductance regulator 1.00
- Cystic fibrosis transmembrane conductance regulator 1.00
- Cystic fibrosis transmembrane conductance regulator 1.00
- Cystic fibrosis transmembrane conductance regulator 1.00
- Cystic fibrosis transmembrane conductance regulator 1.00
- Cystic fibrosis transmembrane conductance regulator 1.00
- Cystic fibrosis transmembrane conductance regulator 1.00
- Cystic fibrosis transmembrane conductance regulator 1.00
- Cystic fibrosis transmembrane conductance regulator 1.00
- Cystic fibrosis transmembrane conductance regulator 1.00
- Cystic fibrosis transmembrane conductance regulator 1.00
- Cystic fibrosis transmembrane conductance regulator 1.00
Co-cited proteins · studied together in the literature
- E3 ubiquitin-protein ligase RNF185 1 shared papers
- Cystic fibrosis transmembrane conductance regulator 1 shared papers
- Adhesion G protein-coupled receptor G2 1 shared papers
- Unconventional myosin-VI 1 shared papers
- Testis anion transporter 1 1 shared papers
- Cystic fibrosis transmembrane conductance regulator 2 shared papers
- Exportin-2 1 shared papers
- Cystic fibrosis transmembrane conductance regulator 2 shared papers
- Epithelial sodium channel subunit alpha 2 shared papers
- Na(+)/H(+) exchange regulatory cofactor NHE-RF1 2 shared papers
- Testis anion transporter 1 1 shared papers
- Golgi-associated PDZ and coiled-coil motif-containing protein 2 shared papers
Literature · 138 cited papers
- Current Status of Genetic Diagnosis Laboratories and Frequency of Genetic Variants Associated with Cystic Fibrosis through a Newborn-Screening Program in Turkey. Genes (Basel) · 2021
- Genotype patterns for mutations of the cystic fibrosis transmembrane conductance regulator gene: a retrospective descriptive study from Saudi Arabia. Ann. Saudi Med. · 2020
- Gq activity- and beta-arrestin-1 scaffolding-mediated ADGRG2/CFTR coupling are required for male fertility. Elife · 2018
- Expression of epithelial sodium channel (ENaC) and CFTR in the human epidermis and epidermal appendages. Histochem. Cell Biol. · 2017
- Two small molecules restore stability to a sub-population of the cystic fibrosis transmembrane conductance regulator with the predominant disease-causing mutation. J. Biol. Chem. · 2017
- Sec16A is critical for both conventional and unconventional secretion of CFTR. Sci. Rep. · 2017
- Direct measurement of trafficking of the cystic fibrosis transmembrane conductance regulator to the cell surface and binding to a chemical chaperone. Biochemistry · 2017
- deltabetagamma-ENaC is inhibited by CFTR but stimulated by cAMP in Xenopus laevis oocytes. Am. J. Physiol. · 2017
- Essential role of CFTR in PKA-dependent phosphorylation, alkalinization, and hyperpolarization during human sperm capacitation. J. Cell. Physiol. · 2017
- Rattlesnake phospholipase A2 increases CFTR-chloride channel current and corrects DelF508CFTR dysfunction: impact in cystic fibrosis. J. Mol. Biol. · 2016
- On the mechanism of gating defects caused by the R117H mutation in cystic fibrosis transmembrane conductance regulator. J. Physiol. (Lond.) · 2016
- Airway acidification initiates host defense abnormalities in cystic fibrosis mice. Science · 2016
- … and 126 more in the literature graph