Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

CFTR (P13569) - Overview - Molecular Target Synopsis

Protein


CFTR, Cystic fibrosis transmembrane conductance regulator
Enzyme Classification 5.6.1.6
UniProt P13569

Also Known as CFTR_HUMAN, CFTR, ABCC7

Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:26823428). Mediates the transport of chloride ions across the cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463, PubMed:12519745, PubMed:15010471, PubMed:12588899, PubMed:17036051, PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774, PubMed:1712898, PubMed:8910473, PubMed:9804160, PubMed:12529365, PubMed:17182731, PubMed:26846474, PubMed:28087700). Channel activity is coupled to ATP hydrolysis (PubMed:8910473). The ion channel is also permeable to HCO(3-); selectivity depends on the extracellular chloride concentration (PubMed:15010471, PubMed:19019741). Exerts its function also by modulating the activity of other ion channels and transporters (PubMed:12403779, PubMed:22178883, PubMed:22121115, PubMed:27941075). Plays an important role in airway fluid homeostasis (PubMed:16645176, PubMed:19621064, PubMed:26823428). 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 (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex (PubMed:17434346, PubMed:27941075, PubMed:17182731). Inhibits the activity of the ENaC channel containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:17182731). 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 (PubMed:27941075). May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the chloride channel activity of ANO1 (PubMed:22178883). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (PubMed:19923167, PubMed:27714810). Monomer; does not require oligomerization for channel activity (PubMed:11524016). May form oligomers in the membrane (PubMed:11524016). Interacts with SLC26A3, SLC26A6 and SHANK2 (By similarity). Interacts with SLC9A3R1 and MYO6 (PubMed:12403779, PubMed:15247260, PubMed:11304524). Interacts (via C-terminus) with GOPC (via PDZ domain); this promotes CFTR internalization and thereby decreases channel activity (PubMed:11707463, PubMed:16331976). Interacts with SLC4A7 through SLC9A3R1 (PubMed:12403779). Found in a complex with MYO5B and RAB11A (PubMed:17462998). Interacts with ANO1 (PubMed:22178883). Interacts with SLC26A8 (PubMed:22121115). Interacts with AHCYL1; the interaction increases CFTR activity (By similarity). Interacts with CSE1L (PubMed:20933420). The core-glycosylated form interacts with GORASP2 (via PDZ GRASP-type 1 domain) in respone to ER stress (PubMed:21884936).

6O1V
COMPLEX OF HUMAN CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR (CFTR) AND GLPG1837
RCSB/PDB
Inspect Structure
See all 3D Structures for CFTR

Isoforms / Transcripts (Protein Coding)


Drugs


CFTR is targeted by Approved Drugs Ivacaftor, Lumacaftor. (see details)
Ivacaftor
Lumacaftor

Sub-cellular localization


Gene Copy Number Variation


In COSMIC - Cell Lines Project CFTR has gain in 17 cell-lines, loss in 1 cell-lines and no signal in 987 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: MOLT_4, MCF7, HCC_2998

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HT-115, SUIT-2, Calu-3

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, NHLF, HSMM

(see details)

3D Structures


For CFTR there are:
31 structures (46 chains) solved
24 are solved in complex with at least one small molecule ligand
2 are solved with an approved drug

CFTR is solved in complex with the approved drug(s):

CLR/CHOLESTEROL (6MSM_A, 6O1V_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


CFTR has been screened with 695 compounds (1049 bioactivities), 127 compounds have bioactivities that show binding affinity of <= 500nM (156 bioactivities). (see details)