Tclin CFTR Cystic fibrosis transmembrane conductance regulator

Protein Classes

PANTHER Classes

Protein / Transporter / Atp-binding Cassette (Abc) Transporter / Cystic Fibrosis Transmembrane Conductance Regulator

DTO Classes

Protein / Ion Channel / Abcc Family / Cftr Transporter Subfamily / Cystic Fibrosis Transmembrane Conductance Regulator

Protein Summary

Description

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). This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]

Uniprot Accession IDs

• P13569
• Q20BG8
• Q20BH2
• Q2I0A1
• Q2I102
• CFTR

Gene Name

• CFTR

Ensembl ID

• ENST00000003084
• ENSP00000003084
• ENSG00000001626
• ENST00000649781
• ENSP00000497203

Symbol

• ABCC7
• CF
• MRP7
• ABC35
• ABCC7
• CFTR/MRP
• TNR-CFTR
• dJ760C5.1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
chemical	1
molecular function	1
kinase perturbation	0.95
biological process	0.94
hub protein	0.94

Related Tools

Target Illumination GWAS Analytics (TIGA)

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GENEVA

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GlyGen

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 8576.14   (req: < 5)

Gene RIFs: 1206   (req: <= 3)

Antibodies: 999   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 8576.14   (req: >= 5)

Gene RIFs: 1206   (req: > 3)

Antibodies: 999   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 34

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 185

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 7

Approved Drugs (7)

Explore Approved Drugs

1 – 7 of 7

felodipine

CFTRTclin IC

Ki : 8.4

glibenclamide

CFTRTclin IC

Ki : 4.66

crofelemer

CFTRTclin IC

INHIBITOR IC50 : 5.15490198

tezacaftor

CFTRTclin IC

PHARMACOLOGICAL CHAPERONE :

ivacaftor

CFTRTclin IC

POSITIVE MODULATOR EC50 : 8.52

lumacaftor

CFTRTclin IC

PHARMACOLOGICAL CHAPERONE EC50 : 6.45593214

elexacaftor

CFTRTclin IC

:

Active Ligands (185)

Explore Active Ligands

1 – 10 of 185

CHEMBL28

CFTRTclin IC

EC50 : 5.05

CHEMBL75680

CFTRTclin IC

EC50 : 6.96

crofelemer

CFTRTclin IC

IC50 : 5.1500001

CHEMBL3597884

CFTRTclin IC

EC50 : 5.02

CHEMBL3323404

CFTRTclin IC

IC50 : 5.04

CHEMBL3323399

CFTRTclin IC

IC50 : 5.05

CHEMBL451804

CFTRTclin IC

IC50 : 5.05

CHEMBL3323402

CFTRTclin IC

IC50 : 5.06

CHEMBL3323407

CFTRTclin IC

IC50 : 5.06

CHEMBL513068

CFTRTclin IC

IC50 : 5.06

GWAS Traits (5)

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5

1 – 5 of 5

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
BMI-adjusted waist-hip ratio	EFO_0007788	2	1	2		92.5
waist-hip ratio	EFO_0004343	2	1	2		90.9
esophageal adenocarcinoma	EFO_0000478	2	2	0	1.2	63.4
Barrett's esophagus	EFO_0000280	1	1	0	1.2	43.3
coronary artery disease	EFO_0001645	2	2	2		25.1

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
BMI-adjusted waist-hip ratio	EFO_0007788	2		92.5
waist-hip ratio	EFO_0004343	2		90.9
esophageal adenocarcinoma	EFO_0000478	0	1.2	63.4
Barrett's esophagus	EFO_0000280	0	1.2	43.3
coronary artery disease	EFO_0001645	2		25.1

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Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cystic fibrosis transmembrane conductance regulator		463674
Macaque	cystic fibrosis transmembrane conductance regulator		574346
Mouse	cystic fibrosis transmembrane conductance regulator	MGI:88388	12638
Rat	cystic fibrosis transmembrane conductance regulator	RGD:2332	24255
Dog	cystic fibrosis transmembrane conductance regulator	VGNC:39180	492302

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cystic fibrosis transmembrane conductance regulator
Macaque	cystic fibrosis transmembrane conductance regulator
Mouse	cystic fibrosis transmembrane conductance regulator
Rat	cystic fibrosis transmembrane conductance regulator
Dog	cystic fibrosis transmembrane conductance regulator

Protein Structure (29 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P13569-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 29

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (26)

Reactome (18)

KEGG (8)

ABC transporter disorders (R-HSA-5619084)

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Find Similar Targets

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1 – 5 of 18

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	ABC transporter disorders	78 targets	R-HSA-5619084
Reactome	ABC-family proteins mediated transport	104 targets	R-HSA-382556
Reactome	Cargo recognition for clathrin-mediated endocytosis	105 targets	R-HSA-8856825
Reactome	Clathrin-mediated endocytosis	143 targets	R-HSA-8856828
Reactome	Defective CFTR causes cystic fibrosis	62 targets	R-HSA-5678895

Name	Explore in Pharos	Explore in Source
ABC transporter disorders	78 targets	R-HSA-5619084
ABC-family proteins mediated transport	104 targets	R-HSA-382556
Cargo recognition for clathrin-mediated endocytosis	105 targets	R-HSA-8856825
Clathrin-mediated endocytosis	143 targets	R-HSA-8856828
Defective CFTR causes cystic fibrosis	62 targets	R-HSA-5678895

Gene Ontology Terms (54)

Functions (14)

Components (20)

Processes (20)

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Items per page:

10

1 – 10 of 14

GO Term	Evidence	Assigned by
ATPase activity	Inferred from Direct Assay (IDA)	UniProtKB
bicarbonate transmembrane transporter activity	Inferred from Direct Assay (IDA)	UniProtKB
chloride channel activity	Inferred from Direct Assay (IDA)	UniProtKB
chloride channel inhibitor activity	Inferred from Direct Assay (IDA)	UniProtKB
PDZ domain binding	Inferred from Direct Assay (IDA)	UniProtKB
Sec61 translocon complex binding	Inferred from Direct Assay (IDA)	UniProtKB
chaperone binding	Inferred from Physical Interaction (IPI)	ARUK-UCL
enzyme binding	Inferred from Physical Interaction (IPI)	UniProtKB
intracellularly ATP-gated chloride channel activity	Inferred from Mutant Phenotype (IMP)	UniProtKB
ATPase activity, coupled to transmembrane movement of substances	Inferred from Biological aspect of Ancestor (IBA)	GO_Central

Protein-Protein Interactions (502)

Explore Interacting Targets

1 – 10 of 502

• See Interactions on String-DB

SLC9A3R1

Tbio

Family: Transporter

Novelty: 0.00357766

Score: 0.984

Data Source: STRINGDB

GOPC

Tbio

Novelty: 0.01110168

Score: 0.983

Data Source: Reactome,STRINGDB

USP10

Tchem

Family: Enzyme

Novelty: 0.05830541

Score: 0.973

Data Source: Reactome,STRINGDB

HSPA8

Tchem

Novelty: 0.00081014

Score: 0.972

Data Source: Reactome,STRINGDB

FLNA

Tbio

Novelty: 0.00156479

Score: 0.971

Data Source: STRINGDB

RNF5

Tbio

Family: Enzyme

Novelty: 0.03015609

Score: 0.97

Data Source: STRINGDB

EZR

Tbio

Novelty: 0.00115353

Score: 0.97

Data Source: STRINGDB

DERL1

Tbio

Novelty: 0.01382722

Score: 0.969

Data Source: STRINGDB

RAB5A

Tbio

Family: Enzyme

Novelty: 0.00111347

Score: 0.966

Data Source: STRINGDB

VCP

Tchem

Family: Enzyme

Novelty: 0.00103317

Score: 0.965

Data Source: STRINGDB

Publication Statistics

PubMed Score  8576.14

PubMed score by year

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PubTator Score  6138.35

PubTator score by year

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Patents

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Amino Acid Sequence

Residue Counts

Protein Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Alternative splicing
ATP-binding
Cell membrane
Chloride
Chloride channel
Complete proteome
Disease mutation
Endoplasmic reticulum
Endosome

GWAS Trait Find Similar Targets

Barrett's esophagus
BMI-adjusted waist-hip ratio
coronary artery disease
esophageal adenocarcinoma
waist-hip ratio

MGI Phenotype Find Similar Targets

behavior/neurological phenotype
cellular phenotype
craniofacial phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
liver/biliary system phenotype