P34158 · CFTR_RAT

  • Protein
    Cystic fibrosis transmembrane conductance regulator
  • Gene
    Cftr
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis. Mediates the transport of chloride ions across the cell membrane (By similarity).
Possesses an intrinsic ATPase activity and utilizes ATP to gate its channel; the passive flow of anions through the channel is gated by cycles of ATP binding and hydrolysis by the ATP-binding domains (By similarity).
The ion channel is also permeable to HCO3-; selectivity depends on the extracellular chloride concentration. Exerts its function also by modulating the activity of other ion channels and transporters. Contributes to the regulation of the pH and the ion content of the epithelial fluid layer. Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7. Can inhibit the chloride channel activity of ANO1 (By similarity).
Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (By similarity).

Catalytic activity

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site401ATP 1 (UniProtKB | ChEBI)
Binding site458-465ATP 1 (UniProtKB | ChEBI)
Binding site458-465ATP (UniProtKB | ChEBI)
Binding site493ATP 1 (UniProtKB | ChEBI)
Binding site1215ATP 2 (UniProtKB | ChEBI)
Binding site1240-1247ATP 2 (UniProtKB | ChEBI)
Binding site1240-1247ATP (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Cellular Componentcell surface
Cellular Componentchloride channel complex
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentdendrite
Cellular Componentearly endosome
Cellular Componentearly endosome membrane
Cellular Componentendoplasmic reticulum membrane
Cellular Componentmembrane
Cellular Componentmicrovillus
Cellular Componentneuronal cell body
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular Componentprotein-containing complex
Cellular Componentrecycling endosome
Cellular Componentrecycling endosome membrane
Molecular FunctionABC-type transporter activity
Molecular FunctionATP binding
Molecular FunctionATP hydrolysis activity
Molecular FunctionATPase-coupled transmembrane transporter activity
Molecular Functionbicarbonate transmembrane transporter activity
Molecular Functionchloride channel activity
Molecular Functionchloride channel inhibitor activity
Molecular Functionchloride transmembrane transporter activity
Molecular Functionenzyme binding
Molecular Functionintracellularly ATP-gated chloride channel activity
Molecular Functionisomerase activity
Molecular FunctionPDZ domain binding
Molecular Functionprotein-folding chaperone binding
Molecular FunctionSec61 translocon complex binding
Biological Processamelogenesis
Biological Processbicarbonate transport
Biological Processcellular response to anoxia
Biological Processcellular response to cAMP
Biological Processcellular response to forskolin
Biological Processcellular response to heat
Biological Processcellular response to hormone stimulus
Biological Processchloride transmembrane transport
Biological Processchloride transport
Biological Processcholesterol biosynthetic process
Biological Processcholesterol transport
Biological Processenamel mineralization
Biological Processestablishment of localization in cell
Biological Processintracellular pH elevation
Biological Processliver regeneration
Biological Processlung development
Biological Processmembrane hyperpolarization
Biological Processmulticellular organismal-level water homeostasis
Biological Processnegative regulation of type B pancreatic cell development
Biological Processnegative regulation of vascular associated smooth muscle cell apoptotic process
Biological Processpositive regulation of enamel mineralization
Biological Processpositive regulation of establishment of Sertoli cell barrier
Biological Processpositive regulation of exocytosis
Biological Processpositive regulation of insulin secretion involved in cellular response to glucose stimulus
Biological Processpositive regulation of mast cell activation
Biological Processresponse to cytokine
Biological Processresponse to endoplasmic reticulum stress
Biological Processresponse to estrogen
Biological Processresponse to peptide hormone
Biological Processresponse to xenobiotic stimulus
Biological Processsodium ion transmembrane transport
Biological Processsperm capacitation
Biological Processtransepithelial chloride transport
Biological Processtransepithelial water transport
Biological Processvasodilation
Biological Processvesicle docking involved in exocytosis
Biological Processwater transport

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Cystic fibrosis transmembrane conductance regulator
  • Short names
    CFTR
  • Alternative names
    • ATP-binding cassette sub-family C member 7
    • Channel conductance-controlling ATPase (EC:5.6.1.6
      ) . EC:5.6.1.6 (UniProtKB | ENZYME | Rhea)
    • cAMP-dependent chloride channel

Gene names

    • Name
      Cftr
    • Synonyms
      Abcc7

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus

Accessions

  • Primary accession
    P34158
  • Secondary accessions
    • Q2IBD3

Proteomes

Organism-specific databases

Subcellular Location

Apical cell membrane
; Multi-pass membrane protein
Early endosome membrane
; Multi-pass membrane protein
Cell membrane
; Multi-pass membrane protein
Recycling endosome membrane
; Multi-pass membrane protein
Endoplasmic reticulum membrane
; Multi-pass membrane protein
Nucleus
Note: The channel is internalized from the cell surface into an endosomal recycling compartment, from where it is recycled to the cell membrane (By similarity).
In the oviduct and bronchus, detected on the apical side of epithelial cells, but not associated with cilia (By similarity).
In Sertoli cells, a processed product is detected in the nucleus (PubMed:29453757).
ER stress induces GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of core-glycosylated CFTR to cell membrane (By similarity).

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-77Cytoplasmic
Transmembrane78-98Helical; Name=1
Topological domain99-122Extracellular
Transmembrane123-146Helical; Name=2
Topological domain147-195Cytoplasmic
Transmembrane196-216Helical; Name=3
Topological domain217-222Extracellular
Transmembrane223-243Helical; Name=4
Topological domain244-298Cytoplasmic
Transmembrane299-319Helical; Name=5
Topological domain320-339Extracellular
Transmembrane340-358Helical; Name=6
Topological domain359-853Cytoplasmic
Transmembrane854-874Helical; Name=7
Topological domain875-913Extracellular
Transmembrane914-934Discontinuously helical; Name=8
Topological domain935-985Cytoplasmic
Transmembrane986-1006Helical; Name=9
Topological domain1007-1008Extracellular
Transmembrane1009-1029Helical; Name=10
Topological domain1030-1090Cytoplasmic
Transmembrane1091-1111Helical; Name=11
Topological domain1112-1125Extracellular
Transmembrane1126-1146Helical; Name=12
Topological domain1147-1476Cytoplasmic

Keywords

Phenotypes & Variants

PTM/Processing

Features

Showing features for chain, lipidation, modified residue, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00000934281-1476Cystic fibrosis transmembrane conductance regulator
Lipidation524S-palmitoyl cysteine
Modified residue549Phosphoserine
Modified residue660Phosphoserine
Modified residue670Phosphoserine; by PKA
Modified residue684Phosphoserine
Modified residue698Phosphoserine
Modified residue710Phosphoserine
Modified residue715Phosphothreonine
Modified residue732Phosphoserine
Modified residue763Phosphoserine
Modified residue785Phosphoserine
Modified residue790Phosphoserine
Modified residue808Phosphoserine
Glycosylation889N-linked (GlcNAc...) asparagine
Glycosylation895N-linked (GlcNAc...) asparagine
Lipidation1391S-palmitoyl cysteine
Modified residue1440Phosphoserine
Modified residue1452Phosphoserine

Post-translational modification

N-glycosylated.
Phosphorylated; cAMP treatment promotes phosphorylation and activates the channel. Dephosphorylation decreases the ATPase activity (in vitro). Phosphorylation at PKA sites activates the channel. Phosphorylation at PKC sites enhances the response to phosphorylation by PKA. Phosphorylated by AMPK; this inhibits channel activity.
Ubiquitinated, leading to its degradation in the lysosome. Deubiquitination by USP10 in early endosomes enhances its endocytic recycling to the cell membrane. Ubiquitinated by RNF185 during ER stress. Ubiquitinated by MARCHF2 (By similarity).

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Detected in epithelial cells in nasopharynx, submandibular gland, pancreas and ileum (at protein level) (PubMed:12519745).
Expressed in the epididymis (PubMed:30659401).
In the caput section of the epididymis, expressed uniformly on both the luminal and basolateral sides of the ducts and on sperm in the caput lumen (at protein level) (PubMed:30659401).
In the cauda, detected along the luminal border but not continuously and is also expressed on the basolateral surface (PubMed:30659401).
Within the caudal lumen, detected on sperm (PubMed:30659401).

Interaction

Subunit

Monomer; does not require oligomerization for channel activity. May form oligomers in the membrane (By similarity).
Interacts with SLC4A7 through NHERF1 (By similarity).
Interacts with SHANK2 (PubMed:14679199).
Interacts with NHERF1 and MYO6. Interacts (via C-terminus) with GOPC (via PDZ domain); this promotes CFTR internalization and thereby decreases channel activity (PubMed:11707463).
Interacts with SLC4A7 through NHERF1. Found in a complex with MYO5B and RAB11A. Interacts with ANO1. Interacts with SLC26A8 (By similarity).
Interacts with AHCYL1; the interaction increases CFTR activity (By similarity).
Interacts with CSE1L (By similarity).
The core-glycosylated form interacts with GORASP2 (via PDZ GRASP-type 1 domain) in respone to ER stress (By similarity).
Interacts with MARCHF2; the interaction leads to CFTR ubiqtuitination and degradation (By similarity).

Protein-protein interaction databases

Chemistry

Structure

Family & Domains

Features

Showing features for domain, region, compositional bias, motif.

TypeIDPosition(s)Description
Domain81-365ABC transmembrane type-1 1
Domain412-646ABC transporter 1
Region654-826Disordered R region
Domain854-1153ABC transmembrane type-1 2
Domain1208-1439ABC transporter 2
Region1382-1476Interaction with GORASP2
Region1445-1476Disordered
Compositional bias1459-1476Basic and acidic residues
Motif1474-1476PDZ-binding

Domain

Binds and hydrolyzes ATP via the two cytoplasmic ABC transporter nucleotide-binding domains. The two ATP-binding domains interact with each other, forming a head-to-tail dimer. Normal ATPase activity requires interaction between the two domains. The first ABC transporter nucleotide-binding domain has no ATPase activity by itself.
The PDZ-binding motif mediates interactions with GOPC and with the SLC4A7, NHERF1/EBP50 complex.
The disordered R region mediates channel activation when it is phosphorylated, but not in the absence of phosphorylation.

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    1,476
  • Mass (Da)
    167,830
  • Last updated
    2007-06-12 v3
  • Checksum
    B2B2A25EB5107640
MQKSPLEKASFISKLFFSWTTPILRKGYRHHLELSDIYQAPSSDSADHLSEKLEREWDREQASKKKPQLIHALRRCFVWRFVFYGVLLYLGEVTKAVQPVLLGRIIASYDPDNTEERSIAIYLGIGLCLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLSSRVLDKISIGQLISLLSNNLNKFDEGLALAHFIWIAPLQVVLLMGLLWDLLQFSAFCGLGLLIVLVIFQAILGKMMVKYRDKRAAKINERLVITSEVIDNIYSVKAYCWESAMEKIIESLREEELKMTRRSAYMRFFTSSAFFFSGFFVVFLSVLPYTVINGIVLRKIFTTISFCIVLRMSVTRQFPTAVQIWYDSLGMIRKIQDFLQTQEYKVLEYNLMFTGLVMENVTAFWEEGFQELLEKVQLNNDDRKTSNGENHLSFSHLCLVGNPVLKNINLNIKKGEMLAITGSTGAGKTSLLMLILGELEASEGIIKHSGRVSFSSQISWIMPGTIKENIIFGVSYDEYRYKSVVKACQLQEDITKFAEQDNTVLGEGGVTLSGGQRARISLARAVYKDADLYLLDSPFGYLDVLTEEQIFESCVCKLMASKTRILVTSKMEQLKKADKILILHEGSSYFYGTFSELQSLRPDFSSKLMGYDTFDQFTEERRSSILTETLRRFSVDDASTTWNKAKQSFRQTGEFGEKRKNSILSSFSSVKKISIVQKTPLSIEGESDDLQERRLSLVPDSEHGEAALPRSNMITAGPTFPGRRRQSVLDLMTFTPSSVSSSLQRTRASIRKISLAPRISLKEEDIYSRRLSQDSTLNITEEINEEDLKECFFDDMVKIPTVTTWNTYLRYFTLHRGLFAVLIWCVLVFLVEVAASLFVLWLLKNNPVNGGNNGTKIANTSYVVVITSSSFYYIFYIYVGVADTLLALSLFRGLPLVHTLITASKILHRKMLHSILHAPMSTFNKLKAGGILNRFSKDIAILDDFLPLTIFDFIQLLFIVVGAIIVVSALQPYIFLATVPGLAVFILLRAYFLHTSQQLKQLESEGRSPIFTHLVTSLKGLWTLRAFRRQTYFETLFHKALNLHTANWFMYLATLRWFQMRIDMIFVLFFIVVTFISILTTGEGEGTTGIILTLAMNIMSTLQWAVNSSIDTDSLMRSVSRVFKFIDIQTEESICTKIMKELHSEDSPNALVIKNEHVKKCDTWPSGGEMVVKDLTVKYVDDGNAILENISFSISPGQRVGLLGRTGSGKSTLLSAFLRMLNIKGEIQIDGVSWNSMTLQEWRKAFGVITQKVFIFSGTFRQNLDPNGKWRDEEIWKVADQVGLKSVIEQFPGQLNFTLVDGGYVLSHGHKQLMCLARSVLSKAKIILLDEPSANLDPITYQVIRRVLRQAFAGCTVVLCEHRIEAMLDCQRFLVIEQGNVWQYESLQALLSEKSVFQRALSSSEKMKLFHGRHSSKQKPRTQITAVKEETEEEVQETRL

Computationally mapped potential isoform sequences

There are 5 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A8I6AKE9A0A8I6AKE9_RATCftr1662
A0A8I6AKF6A0A8I6AKF6_RATCftr1446
A0A0G2K3B1A0A0G2K3B1_RATCftr1665
A0A8I6AU15A0A8I6AU15_RATCftr530
A0A8I6A376A0A8I6A376_RATCftr1499

Features

Showing features for sequence conflict, compositional bias.

TypeIDPosition(s)Description
Sequence conflict987-988in Ref. 3; AAA40918
Compositional bias1459-1476Basic and acidic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
DP000027
EMBL· GenBank· DDBJ
AAR16315.1
EMBL· GenBank· DDBJ
Genomic DNA
L26098
EMBL· GenBank· DDBJ
AAA73561.1
EMBL· GenBank· DDBJ
Genomic DNA
M89906
EMBL· GenBank· DDBJ
AAA40918.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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