Q07DX5 · CFTR_NOMLE

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 site434ATP 1 (UniProtKB | ChEBI)
Binding site458-465ATP 1 (UniProtKB | ChEBI)
Binding site493ATP 1 (UniProtKB | ChEBI)
Binding site1219ATP 2 (UniProtKB | ChEBI)
Binding site1244-1251ATP 2 (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentchloride channel complex
Cellular Componentcytosol
Cellular Componentearly endosome
Cellular Componentearly endosome membrane
Cellular Componentendoplasmic reticulum membrane
Cellular Componentmembrane
Cellular Componentnucleus
Cellular Componentplasma membrane
Cellular Componentrecycling endosome membrane
Molecular FunctionABC-type transporter activity
Molecular FunctionATP binding
Molecular FunctionATP hydrolysis activity
Molecular Functionbicarbonate transmembrane transporter activity
Molecular Functionchloride channel activity
Molecular Functionchloride channel inhibitor activity
Molecular Functionchloride transmembrane transporter activity
Molecular Functionintracellularly ATP-gated chloride channel activity
Molecular Functionisomerase activity
Biological Processbicarbonate transport
Biological Processcellular response to cAMP
Biological Processcellular response to forskolin
Biological Processchloride transmembrane transport
Biological Processintracellular pH elevation
Biological Processmembrane hyperpolarization
Biological Processmulticellular organismal-level water homeostasis
Biological Processresponse to endoplasmic reticulum stress
Biological Processsperm capacitation
Biological Processtransepithelial water transport

Keywords

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

Accessions

  • Primary accession
    Q07DX5

Proteomes

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. In the oviduct and bronchus, detected on the apical side of epithelial cells, but not associated with cilia. In Sertoli cells, a processed product is detected in the nucleus. ER stress induces GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of core-glycosylated CFTR to cell membrane.

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 domain359-858Cytoplasmic
Transmembrane859-879Helical; Name=7
Topological domain880-918Extracellular
Transmembrane919-939Discontinuously helical; Name=8
Topological domain940-990Cytoplasmic
Transmembrane991-1011Helical; Name=9
Topological domain1012-1013Extracellular
Transmembrane1014-1034Helical; Name=10
Topological domain1035-1095Cytoplasmic
Transmembrane1096-1116Helical; Name=11
Topological domain1117-1130Extracellular
Transmembrane1131-1151Helical; Name=12
Topological domain1152-1480Cytoplasmic

Keywords

PTM/Processing

Features

Showing features for chain, lipidation, modified residue, cross-link, glycosylation.

TypeIDPosition(s)Description
ChainPRO_00002607751-1480Cystic fibrosis transmembrane conductance regulator
Lipidation524S-palmitoyl cysteine
Modified residue549Phosphoserine
Modified residue660Phosphoserine
Modified residue670Phosphoserine; by PKA
Modified residue686Phosphoserine
Cross-link688Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Modified residue700Phosphoserine
Modified residue712Phosphoserine
Modified residue717Phosphothreonine
Modified residue737Phosphoserine
Modified residue753Phosphoserine
Modified residue768Phosphoserine
Modified residue790Phosphoserine
Modified residue795Phosphoserine
Modified residue813Phosphoserine
Glycosylation894N-linked (GlcNAc...) asparagine
Glycosylation900N-linked (GlcNAc...) asparagine
Lipidation1395S-palmitoyl cysteine
Modified residue1444Phosphoserine
Modified residue1456Phosphoserine

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

PTM databases

Interaction

Subunit

Monomer; does not require oligomerization for channel activity. May form oligomers in the membrane (By similarity).
Interacts with SLC26A3, SLC26A6 and NHERF1 (By similarity).
Interacts with SHANK2 (By similarity).
Interacts with MYO6 (By similarity).
Interacts (via C-terminus) with GOPC (via PDZ domain); this promotes CFTR internalization and thereby decreases channel activity. 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

Family & Domains

Features

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

TypeIDPosition(s)Description
Domain81-365ABC transmembrane type-1 1
Domain423-646ABC transporter 1
Region654-831Disordered R region
Domain859-1155ABC transmembrane type-1 2
Domain1210-1443ABC transporter 2
Region1386-1480Interaction with GORASP2
Region1451-1480Disordered
Compositional bias1466-1480Basic and acidic residues
Motif1478-1480PDZ-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
    1,480
  • Mass (Da)
    168,068
  • Last updated
    2006-10-31 v1
  • Checksum
    4C5365853DFF7A74
MQRSPLEKASVVSKLFFSWTRPILRKGYRQRLELSDIYQIPSADSADNLSEKLEREWDRELASKKNPKLINALRRCFFWRFMFYGIFLYLGEVTKAVQPLLLGRIIASYDPDNKEERSIAIYLGIGLCLLFIVRTLLLHPAIFGLHHIGMQMRIAMFSLIYKKTLKLSSRVLDKISIGQLVSLLSNNLNKFDEGLALAHFVWIAPLQVALLMGLIWELLQASAFCGLGFLIVLALFQAGLGRMMMKYRDQRAGKISERLVITSEMIENIQSVKAYCWEEAMEKMIENLRQTELKLTRKAAYVRYFNSSAFFFSGFFVVFLSVLPYALIKGIVLRKIFTTISFCIVLRMAVTRQFPWAVQTWYDSLGAINKIQDFLQKQEYKTLEYNLTTTEVVMENVTAFWEEGFGELFEKAKQNNNNRKTSNGDDSLFFSNFSLLGTPVLKDINFKIERGQLLAVAGSTGAGKTSLLMMIMGELEPSEGKIKHSGRISFCSQFSWIMPGTIKENIIFGVSYDEYRYRSVIKACQLEEDISKFAEKDNIVLGEGGITLSGGQRARISLARAVYKDADLYLLDSPFGYLDVLTEKEIFESCICKLMANKTRILVTSKMEHLKKADKILILHEGSSYFYGTFSELQNLRPDFSSKLMGCDSFDQFSAERRNSILTETLRRFSLEGDAPVSWTETKKQSFKQTGEFGEKRKNSILNPINSIRKFSIVPKTPLQMNGIEEDSDEPLERRLSLVPDSEQGEAILPHISVISTGPTLQARRRQSVLNLMTHSINQGQSIHRKTTASTRKVSLAPQANLTELDIYSRRLSQETGLEISEEINEEDLKECFFDDMESIPAVTTWNTYLRYITVHKSLIFVLIWCLVIFLAEVAASLVVLWLLGNTPLQDKGNSTHSRNNSYAVIITSTSSYYVFYIYVGVADTLLAMGFFRGLPLVHTLITVSKILHHKMLHSVLQAPMSTLNTLKAGGILNRFSKDIAILDDLLPLTIFDFIQLLLIVIGAIAVVAVLQPYIFVATVPVIVAFIMLRAYFLQTSQQLKQLESEGRSPIFTHLVTSLKGLWTLRAFGRQPYFETLFHKALNLHTANWFLYLSTLRWFQMRIEMIFVMFFIAVTFISILTTGEGEGRIGIILTLAMNIMSTLQWAVNSSIDVDSLMRSVSRVFKFIDMPTEGKPTKSTKPYKNGQLSKVMIIENSHVKKDDIWPSGGQMTVKDLSAKYTEGGNAILENISFSISPGQRVGLLGRTGSGKSTLLSALLRLLNTEGEIQIDGVSWDSITLQQWRKAFGVIPQKVFIFSGTFRKNLDPYEQWSDQEIWKVADEVGLRSVIEQFPGKLDFVLVDGGCVLSHGHKQLMCLARSVLSKAKILLLDEPSAHLDPVTYQIIRRTLKQAFADCTVILCEHRIEAMLECQQFLVIEENKVRQYDSIQKLLNERSLFRQAISPSDRVKLFPHRNSSKGKSQPQIAALKEETEEEVQDTRL

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias1466-1480Basic and acidic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
DP000194
EMBL· GenBank· DDBJ
ABJ08867.1
EMBL· GenBank· DDBJ
Genomic DNA

Similar Proteins

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