Human Gene CFTR (ENST00000649781.1) from GENCODE V38
  Description: Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. (from UniProt P13569)
RefSeq Summary (NM_000492): 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].
Gencode Transcript: ENST00000649781.1
Gencode Gene: ENSG00000001626.16
Transcript (Including UTRs)
   Position: hg38 chr7:117,480,095-117,667,108 Size: 187,014 Total Exon Count: 26 Strand: +
Coding Region
   Position: hg38 chr7:117,480,095-117,667,108 Size: 187,014 Coding Exon Count: 26 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionProtein StructureOther SpeciesGO AnnotationsmRNA DescriptionsPathways
Other NamesGeneReviewsMethods
Data last updated at UCSC: 2021-09-27 09:51:20

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr7:117,480,095-117,667,108)mRNA (may differ from genome)Protein (1419 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
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UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: CFTR_HUMAN
DESCRIPTION: RecName: Full=Cystic fibrosis transmembrane conductance regulator; Short=CFTR; AltName: Full=ATP-binding cassette sub-family C member 7; AltName: Full=Channel conductance-controlling ATPase; EC=3.6.3.49; AltName: Full=cAMP-dependent chloride channel;
FUNCTION: Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter.
CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.
SUBUNIT: Interacts with SHANK2 (By similarity). Interacts with SLC9A3R1, MYO6 and GOPC. Interacts with SLC4A7 through SLC9A3R1. Found in a complex with MYO5B and RAB11A.
INTERACTION: P51572:BCAP31; NbExp=3; IntAct=EBI-349854, EBI-77683; Q9BUN8:DERL1; NbExp=2; IntAct=EBI-349854, EBI-398977; Q9H8Y8:GORASP2; NbExp=3; IntAct=EBI-349854, EBI-739467; Q9HBW0:LPAR2; NbExp=4; IntAct=EBI-349854, EBI-765995; Q5T2W1:PDZK1; NbExp=2; IntAct=EBI-349854, EBI-349819; Q99942:RNF5; NbExp=3; IntAct=EBI-349854, EBI-348482; Q96RN1:SLC26A8; NbExp=2; IntAct=EBI-349854, EBI-1792052; O14745:SLC9A3R1; NbExp=2; IntAct=EBI-349854, EBI-349787; Q15599:SLC9A3R2; NbExp=4; IntAct=EBI-349854, EBI-1149760;
SUBCELLULAR LOCATION: Early endosome membrane; Multi-pass membrane protein.
TISSUE SPECIFICITY: Found on the surface of the epithelial cells that line the lungs and other organs.
DOMAIN: The PDZ-binding motif mediates interactions with GOPC and with the SLC4A7, SLC9A3R1/EBP50 complex.
PTM: Phosphorylated; activates the channel. It is not clear whether PKC phosphorylation itself activates the channel or permits activation by phosphorylation at PKA sites. Phosphorylated by AMPK.
PTM: Ubiquitinated, leading to its degradation in the lysosome. Deubiquitination by USP10 in early endosomes, enhances its endocytic recycling.
DISEASE: Defects in CFTR are the cause of cystic fibrosis (CF) [MIM:219700]; also known as mucoviscidosis. CF is the most common genetic disease in the Caucasian population, with a prevalence of about 1 in 2'000 live births. Inheritance is autosomal recessive. CF is a common generalized disorder of exocrine gland function which impairs clearance of secretions in a variety of organs. It is characterized by the triad of chronic bronchopulmonary disease (with recurrent respiratory infections), pancreatic insufficiency (which leads to malabsorption and growth retardation) and elevated sweat electrolytes.
DISEASE: Defects in CFTR are the cause of congenital bilateral absence of the vas deferens (CBAVD) [MIM:277180]. CBAVD is an important cause of sterility in men and could represent an incomplete form of cystic fibrosis, as the majority of men suffering from cystic fibrosis lack the vas deferens.
SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family. CFTR transporter (TC 3.A.1.202) subfamily.
SIMILARITY: Contains 2 ABC transmembrane type-1 domains.
SIMILARITY: Contains 2 ABC transporter domains.
WEB RESOURCE: Name=CFTR; Note=Cystic fibrosis mutation db; URL="http://www.genet.sickkids.on.ca/cftr/app";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/CFTR";
WEB RESOURCE: Name=Wikipedia; Note=CFTR entry; URL="http://en.wikipedia.org/wiki/Cystic_fibrosis_transmembrane_conductance_regulator";
WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins; URL="http://abcmutations.hegelab.org/proteinDetails?uniprot_id=P13569";

-  MalaCards Disease Associations
  MalaCards Gene Search: CFTR
Diseases sorted by gene-association score: cystic fibrosis* (1803), congenital bilateral absence of vas deferens* (1606), bronchiectasis with or without elevated sweat chloride 1* (689), pancreatitis, hereditary* (514), idiopathic bronchiectasis* (350), congenital absence of the vas deferens* (119), cftr-related disorders* (119), cftr-related hereditary pancreatitis* (100), cholangitis, primary sclerosing (23), autosomal genetic disease (21), bronchiectasis (20), allergic bronchopulmonary aspergillosis (18), mite infestation (18), young syndrome (17), alcoholic pancreatitis (17), lung disease (16), recurrent acute pancreatitis (15), intussusception (15), secretory diarrhea (14), autosomal dominant polycystic kidney disease (14), nontuberculous mycobacterial lung disease (13), meconium ileus (13), autoimmune pancreatitis (12), rectal prolapse (12), cholera (12), cholangitis (11), pancreatitis (11), liddle syndrome (11), male infertility (10), mycobacterium abscessus (10), oligospermia (10), intestinal obstruction (10), bronchitis (10), pancreatic agenesis 1 (9), azoospermia (8), exocrine pancreatic insufficiency (8), miliaria rubra (8), sclerosing cholangitis (8), sinusitis (7), alpha 1-antitrypsin deficiency (7), johanson-blizzard syndrome (7), steatorrhea (7), renal hypodysplasia/aplasia 1 (6), aspergillosis (6), hyperuricemia, pulmonary hypertension, renal failure, and alkalosis (6), typhoid fever (6), miliaria (6), mammary paget's disease (6), pulmonary edema (6), pseudoxanthoma elasticum (5), specific language impairment (5), male reproductive system disease (5), gallbladder disease (5), asthma (2), autosomal recessive disease (2), primary ciliary dyskinesia (2), respiratory system disease (1), reproductive system disease (1), kartagener syndrome (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 45.29 RPKM in Pancreas
Total median expression: 76.20 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003593 - AAA+_ATPase
IPR003439 - ABC_transporter-like
IPR017871 - ABC_transporter_CS
IPR017940 - ABC_transporter_type1
IPR001140 - ABC_transptr_TM_dom
IPR011527 - ABC_transptrTM_dom_typ1
IPR005291 - cAMP_cl_channel
IPR025837 - CFTR_reg_dom
IPR009147 - CysFib_conduc_TM

Pfam Domains:
PF00664 - ABC transporter transmembrane region
PF00005 - ABC transporter
PF14396 - Cystic fibrosis TM conductance regulator (CFTR), regulator domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1NBD
- Model

1XMI
- X-ray MuPIT

1XMJ
- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
2BBO - X-ray MuPIT 2BBS - X-ray MuPIT 2BBT - X-ray MuPIT
2LOB - NMR MuPIT 2PZE - X-ray MuPIT 2PZF - X-ray MuPIT
2PZG - X-ray MuPIT 3GD7 - X-ray MuPIT 3ISW - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P13569
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0005254 chloride channel activity
GO:0005260 channel-conductance-controlling ATPase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0015106 bicarbonate transmembrane transporter activity
GO:0015108 chloride transmembrane transporter activity
GO:0016787 hydrolase activity
GO:0016887 ATPase activity
GO:0017081 chloride channel regulator activity
GO:0019869 chloride channel inhibitor activity
GO:0019899 enzyme binding
GO:0030165 PDZ domain binding
GO:0042626 ATPase activity, coupled to transmembrane movement of substances
GO:0043225 ATPase-coupled anion transmembrane transporter activity
GO:0051087 chaperone binding

Biological Process:
GO:0006695 cholesterol biosynthetic process
GO:0006811 ion transport
GO:0006821 chloride transport
GO:0006904 vesicle docking involved in exocytosis
GO:0015701 bicarbonate transport
GO:0016579 protein deubiquitination
GO:0030301 cholesterol transport
GO:0035377 transepithelial water transport
GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0045921 positive regulation of exocytosis
GO:0048240 sperm capacitation
GO:0050891 multicellular organismal water homeostasis
GO:0051454 intracellular pH elevation
GO:0055085 transmembrane transport
GO:0060081 membrane hyperpolarization
GO:0061024 membrane organization
GO:0071320 cellular response to cAMP
GO:0099133 ATP hydrolysis coupled anion transmembrane transport
GO:1902161 positive regulation of cyclic nucleotide-gated ion channel activity
GO:1902476 chloride transmembrane transport
GO:1902943 positive regulation of voltage-gated chloride channel activity
GO:1904322 cellular response to forskolin

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005765 lysosomal membrane
GO:0005768 endosome
GO:0005769 early endosome
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016324 apical plasma membrane
GO:0030660 Golgi-associated vesicle membrane
GO:0030665 clathrin-coated vesicle membrane
GO:0031901 early endosome membrane
GO:0032991 macromolecular complex
GO:0034707 chloride channel complex
GO:0055037 recycling endosome
GO:0055038 recycling endosome membrane
GO:0031205 endoplasmic reticulum Sec complex


-  Descriptions from all associated GenBank mRNAs
  M28668 - Human cystic fibrosis mRNA, encoding a presumed transmembrane conductance regulator (CFTR).
JC612186 - Sequence 1 from Patent WO2014045283.
JC612196 - Sequence 11 from Patent WO2014045283.
JC612197 - Sequence 12 from Patent WO2014045283.
BC143713 - Homo sapiens cDNA clone IMAGE:9052227, containing frame-shift errors.
BC156254 - Synthetic construct Homo sapiens clone IMAGE:100061681, MGC:190072 cystic fibrosis transmembrane conductance regulator (ATP-binding cassette sub-family C, member 7) (CFTR) mRNA, encodes complete protein.
LF636471 - JP 2016517437-A/1: CFTR MRNA COMPOSITIONS AND RELATED METHODS AND USES.
LG162859 - KR 1020160010398-A/2: CFTR MRNA COMPOSITIONS AND RELATED METHODS AND USES.
LP043843 - Sequence 2 from Patent WO2014153052.
MP152080 - Sequence 2 from Patent EP3446712.
MB442950 - JP 2018100307-A/1: CFTR MRNA COMPOSITIONS AND RELATED METHODS AND USES.
MP455657 - Sequence 1 from Patent EP3591052.
MP455667 - Sequence 11 from Patent EP3591052.
MP455668 - Sequence 12 from Patent EP3591052.
DQ656054 - Homo sapiens clone UGLsupplH, mRNA sequence.
LP986380 - Sequence 18 from Patent EP3201339.
MA014040 - JP 2017536338-A/18: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986382 - Sequence 20 from Patent EP3201339.
MA014042 - JP 2017536338-A/20: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986384 - Sequence 22 from Patent EP3201339.
MA014044 - JP 2017536338-A/22: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986386 - Sequence 24 from Patent EP3201339.
MA014046 - JP 2017536338-A/24: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986388 - Sequence 26 from Patent EP3201339.
MA014048 - JP 2017536338-A/26: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986390 - Sequence 28 from Patent EP3201339.
MA014050 - JP 2017536338-A/28: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986392 - Sequence 30 from Patent EP3201339.
MA014052 - JP 2017536338-A/30: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986394 - Sequence 32 from Patent EP3201339.
MA014054 - JP 2017536338-A/32: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986396 - Sequence 34 from Patent EP3201339.
MA014056 - JP 2017536338-A/34: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986400 - Sequence 38 from Patent EP3201339.
MA014060 - JP 2017536338-A/38: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
X73053 - H.sapiens CFTR mutation mRNA.
LP986402 - Sequence 40 from Patent EP3201339.
MA014062 - JP 2017536338-A/40: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986404 - Sequence 42 from Patent EP3201339.
MA014064 - JP 2017536338-A/42: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986406 - Sequence 44 from Patent EP3201339.
MA014066 - JP 2017536338-A/44: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
S82430 - TNR-CFTR=cystic fibrosis transmembrane conductance regulator isoform {alternatively spliced} [human, kidney, renal medulla, mRNA Partial, 209 nt].
LP986408 - Sequence 46 from Patent EP3201339.
MA014068 - JP 2017536338-A/46: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986410 - Sequence 48 from Patent EP3201339.
MA014070 - JP 2017536338-A/48: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986412 - Sequence 50 from Patent EP3201339.
MA014072 - JP 2017536338-A/50: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986414 - Sequence 52 from Patent EP3201339.
MA014074 - JP 2017536338-A/52: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986416 - Sequence 54 from Patent EP3201339.
MA014076 - JP 2017536338-A/54: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986418 - Sequence 56 from Patent EP3201339.
MA014078 - JP 2017536338-A/56: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986420 - Sequence 58 from Patent EP3201339.
MA014080 - JP 2017536338-A/58: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986422 - Sequence 60 from Patent EP3201339.
MA014082 - JP 2017536338-A/60: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986424 - Sequence 62 from Patent EP3201339.
MA014084 - JP 2017536338-A/62: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986426 - Sequence 64 from Patent EP3201339.
MA014086 - JP 2017536338-A/64: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986428 - Sequence 66 from Patent EP3201339.
MA014088 - JP 2017536338-A/66: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986430 - Sequence 68 from Patent EP3201339.
MA014090 - JP 2017536338-A/68: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.
LP986432 - Sequence 70 from Patent EP3201339.
MA014092 - JP 2017536338-A/70: TARGETED AUGMENTATION OF NUCLEAR GENE OUTPUT.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa02010 - ABC transporters
hsa05110 - Vibrio cholerae infection

BioCarta from NCI Cancer Genome Anatomy Project
h_cftrPathway - Cystic fibrosis transmembrane conductance regulator (CFTR) and beta 2 adrenergic receptor (b2AR) pathway

Reactome (by CSHL, EBI, and GO)

Protein P13569 (Reactome details) participates in the following event(s):

R-HSA-5679000 Ivacaftor binds CFTR G551D
R-HSA-8866857 CFTR F508del binds components of the ERAD machinery for ubiquitination and degradation
R-HSA-8866551 CFTR binds components of the ERAD machinery for ubiquitination and degradation
R-HSA-383190 HCO3- transport through ion channel
R-HSA-5678863 CFTR transports Cl- from cytosol to extracellular region
R-HSA-8866856 RNF5 and RNF185 ubiquitinate CFTR F508del
R-HSA-8866854 VCP-catalyzed ATP hydrolysis promotes the translocation of CFTR F508del into the cytosol
R-HSA-8866542 VCP-catalyzed ATP hydrolysis promotes the translocation of misfolded CFTR into the cytosol
R-HSA-8866546 RNF5 and RNF185 ubiquitinate misfolded CFTR
R-HSA-1454916 The ABCC family mediates organic anion transport
R-HSA-5627072 RHOQ binds GOPC:CFTR
R-HSA-5627275 GOPC promotes translocation of CFTR to lysosomes
R-HSA-5678992 Ivacaftor:CFTR G551D transports Cl- from cytosol to extracellular region
R-HSA-6782106 USP10 deubiquitinates SNX3, CFTR
R-HSA-8866277 AP-2 directly binds some endocytic cargo
R-HSA-5627071 RHOQ positively regulates trafficking of GOPC:CFTR to the plasma membrane
R-HSA-8867756 CLASP proteins and cargo are recruited to the nascent clathrin-coated pit
R-HSA-8868071 Clathrin recruits PIK3C2A
R-HSA-8868661 Dynamin-mediated GTP hydrolysis promotes vesicle scission
R-HSA-8868648 SYNJ hydrolyze PI(4,5)P2 to PI(4)P
R-HSA-8871194 RAB5 and GAPVD1 bind AP-2
R-HSA-8868658 HSPA8-mediated ATP hydrolysis promotes vesicle uncoating
R-HSA-8868659 Clathrin recruits auxilins to the clathrin-coated vesicle
R-HSA-8868660 Auxilin recruits HSPA8:ATP to the clathrin-coated vesicle
R-HSA-8867754 F- and N- BAR domain proteins bind the clathrin-coated pit
R-HSA-8868230 SNX9 recruits components of the actin polymerizing machinery
R-HSA-8868072 Clathrin-associated PIK3C2A phosphorylates PI(4)P to PI(3,4)P2
R-HSA-8868236 BAR domain proteins recruit dynamin
R-HSA-8868651 Endophilins recruit synaptojanins to the clathrin-coated pit
R-HSA-382556 ABC-family proteins mediated transport
R-HSA-5678895 Defective CFTR causes cystic fibrosis
R-HSA-382551 Transport of small molecules
R-HSA-5619084 ABC transporter disorders
R-HSA-5627083 RHO GTPases regulate CFTR trafficking
R-HSA-5619115 Disorders of transmembrane transporters
R-HSA-5689880 Ub-specific processing proteases
R-HSA-8856825 Cargo recognition for clathrin-mediated endocytosis
R-HSA-195258 RHO GTPase Effectors
R-HSA-1643685 Disease
R-HSA-5688426 Deubiquitination
R-HSA-8856828 Clathrin-mediated endocytosis
R-HSA-194315 Signaling by Rho GTPases
R-HSA-597592 Post-translational protein modification
R-HSA-199991 Membrane Trafficking
R-HSA-162582 Signal Transduction
R-HSA-392499 Metabolism of proteins
R-HSA-5653656 Vesicle-mediated transport

-  Other Names for This Gene
  Alternate Gene Symbols: ABCC7, CFTR_HUMAN, JC612197, P13569, Q20BG8, Q20BH2, Q2I0A1, Q2I102, uc285zxp.1
UCSC ID: ENST00000649781.1
RefSeq Accession: NM_000492
Protein: P13569 (aka CFTR_HUMAN)
CCDS: CCDS5773.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene CFTR:
pancreatitis-ov (Pancreatitis Overview)
cf (Cystic Fibrosis and Congenital Absence of the Vas Deferens)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.