CFTR

Target id: 707

Nomenclature: CFTR

Family: CFTR

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1480 7q31-q32 CFTR cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7)
Mouse - 1476 6 A3 Cftr cystic fibrosis transmembrane conductance regulator
Rat - 1476 4q21 Cftr cystic fibrosis transmembrane conductance regulator
Previous and Unofficial Names
ABCC7
ABC35
CFTR/MRP
MRP7
TNR-CFTR
ATP-binding cassette sub-family C member 7
cAMP-dependent chloride channel
Database Links
DrugBank Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
Orphanet Gene
PhosphoSitePlus
TreeFam
UniProtKB
Functional Characteristics
γ = 6-10 pS; permeability sequence = Br- ≥ Cl- > I- > F-, (PI/PCl = 0.1–0.85); slight outward rectification; phosphorylation necessary for activation by ATP binding at binding nucleotide binding domains (NBD)1 and 2; positively regulated by PKC and PKGII (tissue specific); regulated by several interacting proteins including syntaxin 1A, Munc18 and PDZ domain proteins such as NHERF (EBP50) and CAP70
Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
felodipine Hs Potentiation 8.4 pKi - no 1
pKi 8.4 (Ki 4x10-9 M) [1]
Not voltage dependent
phenylglycine-01 Hs Potentiation - - - no

Not voltage dependent
UCCF-029 Hs Potentiation - - - no

Not voltage dependent
capsaicin Hs Potentiation - - - no

Not voltage dependent
nimodipine Hs Potentiation - - - no

Not voltage dependent
NS004 Hs Potentiation - - - no

Not voltage dependent
ivacaftor Hs Potentiation - - - no

Not voltage dependent
sulfonamide-01 Hs Potentiation - - - no

Not voltage dependent
UCCF-339 Hs Potentiation - - - no

Not voltage dependent
CBIQ Hs Potentiation - - - no

Not voltage dependent
UCCF-853 Hs Potentiation - - - no

Not voltage dependent
apigenin Hs Potentiation - - - no

Not voltage dependent
genistein Hs Potentiation - - - no

Not voltage dependent
Activator Comments
UCCF-339, UCCF-029, apigenin and genistein are examples of flavones. UCCF-853 and NS004 are examples of benzimidazolones. CBIQ is an example of a benzoquinoline. felodipine and nimodipine are examples of 1,4-dihydropyridines. Phenylglycine-01 is an example of a phenylglycine. SF-01 is an example of a sulfonamide.
Inhibitors
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
crofelemer Hs Inhibition 5.15 pIC50 - no 3
pIC50 5.15 (IC50 7x10-6 M) [3]
Not voltage dependent
Channel Blockers
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Voltage-dependent (mV) Reference
glibenclamide Hs - 4.66 pKi - no 2
pKi 4.66 (Ki 2.18x10-5 M) [2]
Not voltage dependent
GaTx1 Hs - - - - no

Not voltage dependent
intracellular CFTRinh-172 Hs - - - - no
intracellular application prolongs mean closed time
Not voltage dependent
extracellular GlyH-101 Hs - - - - no

Not voltage dependent
Channel Blocker Comments
Malonic acid hydrazide conjugates are also CFTR channel blockers (see Verkman and Galietta, 2009 [4]).
Clinically-Relevant Mutations and Pathophysiology
Disease:  Bronchiectasis with or without elevated sweat chloride 1, modifier of
OMIM:  211400
Orphanet:  60033
Disease:  Congenital bilateral absence of vas deferens
OMIM:  277180
Orphanet:  48
Disease:  Cystic fibrosis
OMIM:  219700
Orphanet:  586
Disease:  Hereditary pancreatitis
OMIM:  167800
Orphanet:  676
Disease:  Male infertility with normal virilization due to meiosis defect
Orphanet:  217034

References

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1. Pedemonte N, Boido D, Moran O, Giampieri M, Mazzei M, Ravazzolo R, Galietta LJ. (2007) Structure-activity relationship of 1,4-dihydropyridines as potentiators of the cystic fibrosis transmembrane conductance regulator chloride channel. Mol. Pharmacol.72 (1): 197-207. [PMID:17452495]

2. Sheppard DN, Welsh MJ. (1992) Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents. J. Gen. Physiol.100 (4): 573-91. [PMID:1281220]

3. Tradtrantip L, Namkung W, Verkman AS. (2010) Crofelemer, an antisecretory antidiarrheal proanthocyanidin oligomer extracted from Croton lechleri, targets two distinct intestinal chloride channels. Mol. Pharmacol.77 (1): 69-78. [PMID:19808995]

4. Verkman AS, Galietta LJ. (2009) Chloride channels as drug targets. Nat Rev Drug Discov8 (2): 153-71. [PMID:19153558]

How to cite this page

CFTR: CFTR. Last modified on 19/08/2014. Accessed on 21/12/2014. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=707.