Tclin CFTR 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

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

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: 8818.85   (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: 8818.85   (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: 366

Tclin

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

Active Drugs: 7

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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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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Approved Drugs (7)

Explore Approved Drugs

1 – 7 of 7

felodipine

CFTRTclin IC

BLOCKER :

glibenclamide

CFTRTclin IC

BLOCKER pKd : 9.52

crofelemer

CFTRTclin IC

INHIBITOR pIC50 : 5.19

ivacaftor

CFTRTclin IC

POSITIVE MODULATOR pEC50 : 8.52

lumacaftor

CFTRTclin IC

PHARMACOLOGICAL CHAPERONE pEC50 : 6.46

tezacaftor

CFTRTclin IC

PHARMACOLOGICAL CHAPERONE pEC50 : 6.57

elexacaftor

CFTRTclin IC

pEC50 : 7.15

Active Ligands (366)

Explore Active Ligands

1 – 10 of 366

Apigenin

CFTRTclin IC

pKi : 7.19

aloisine A

CFTRTclin IC

pEC50 : 6.96

crofelemer

CFTRTclin IC

pIC50 : 5.19

CHEMBL4558190

CFTRTclin IC

pEC50 : 9.3

CHEMBL3357142

CFTRTclin IC

pEC50 : 8.7

CHEMBL3357143

CFTRTclin IC

pEC50 : 8.52

CHEMBL3357141

CFTRTclin IC

pEC50 : 8.52

CHEMBL191928

CFTRTclin IC

pEC50 : 8.46

CHEMBL2386374

CFTRTclin IC

pIC50 : 8.4

CHEMBL1779949

CFTRTclin IC

pIC50 : 8.3

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

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (26)

Reactome (18)

KEGG (8)

ABC transporter disorders (R-HSA-5619084)

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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

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (54)

Functions (14)

Components (20)

Processes (20)

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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

Disease Associations (null)

No disease associations found

GWAS Traits (8)

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GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
BMI-adjusted waist-hip ratio	EFO_0007788	4	5	6		87.3
waist-hip ratio	EFO_0004343	3	4	5		86.6
Dupuytren Contracture	EFO_0004229	2	2	0	1.2	77
esophageal adenocarcinoma	EFO_0000478	2	2	0	1.2	52.3
Barrett's esophagus	EFO_0000280	1	1	0	1.2	38.8

• Explore on Target Illumination GWAS Analytics (TIGA)

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GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
BMI-adjusted waist-hip ratio	EFO_0007788	6		87.3
waist-hip ratio	EFO_0004343	5		86.6
Dupuytren Contracture	EFO_0004229	0	1.2	77
esophageal adenocarcinoma	EFO_0000478	0	1.2	52.3
Barrett's esophagus	EFO_0000280	0	1.2	38.8

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
ATP-binding
Cell membrane
Chloride
Chloride channel
Complete proteome
Disease mutation
Endoplasmic reticulum
Endosome

GWAS Trait Find Similar Targets

No Header	No Header
Barrett's esophagus
BMI-adjusted waist-hip ratio
coronary artery disease
Dupuytren Contracture
esophageal adenocarcinoma
inflammatory bowel disease
tonsillectomy risk measurement
waist-hip ratio

MGI Phenotype Find Similar Targets

No Header	No Header
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

IDG Resources

No IDG generated resources found

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

Publication Statistics

PubMed Score 8818.85

PubMed score by year

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PubTator Score 6138.35

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Patents

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Related Publications

Text Mined References (1526)

GeneRif Annotations (1206)

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PMID	Year	Title