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Protein

Cystic fibrosis transmembrane conductance regulator

Gene

CFTR

Organism
Trichosurus vulpecula (Brush-tailed possum)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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). Channel activity is coupled to ATP hydrolysis. 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).By similarity

Catalytic activityi

ATP + H2O = ADP + phosphate.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei401ATP 1By similarity1
Binding sitei434ATP 1By similarity1
Binding sitei493ATP 1By similarity1
Binding sitei1217ATP 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi458 – 465ATP 1PROSITE-ProRule annotation8
Nucleotide bindingi1242 – 1249ATP 2PROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChloride channel, Hydrolase, Ion channel
Biological processIon transport, Transport
LigandATP-binding, Chloride, Nucleotide-binding

Enzyme and pathway databases

BRENDAi3.6.3.49. 6475.

Names & Taxonomyi

Protein namesi
Recommended name:
Cystic fibrosis transmembrane conductance regulator
Short name:
CFTR
Alternative name(s):
ATP-binding cassette sub-family C member 7
Channel conductance-controlling ATPase (EC:3.6.3.49By similarity)
cAMP-dependent chloride channel
Gene namesi
Name:CFTR
Synonyms:ABCC7
OrganismiTrichosurus vulpecula (Brush-tailed possum)
Taxonomic identifieri9337 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaMetatheriaDiprotodontiaPhalangeridaeTrichosurus

Subcellular locationi

  • Apical cell membrane By similarity; Multi-pass membrane protein By similarity
  • Early endosome membrane By similarity; Multi-pass membrane protein By similarity
  • Cell membrane By similarity; Multi-pass membrane protein By similarity
  • Recycling endosome membrane By similarity; Multi-pass membrane protein By similarity
  • Endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity

  • 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.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 77CytoplasmicBy similarityAdd BLAST77
Transmembranei78 – 98Helical; Name=1By similarityAdd BLAST21
Topological domaini99 – 122ExtracellularBy similarityAdd BLAST24
Transmembranei123 – 146Helical; Name=2By similarityAdd BLAST24
Topological domaini147 – 195CytoplasmicBy similarityAdd BLAST49
Transmembranei196 – 216Helical; Name=3By similarityAdd BLAST21
Topological domaini217 – 222ExtracellularBy similarity6
Transmembranei223 – 243Helical; Name=4By similarityAdd BLAST21
Topological domaini244 – 298CytoplasmicBy similarityAdd BLAST55
Transmembranei299 – 319Helical; Name=5By similarityAdd BLAST21
Topological domaini320 – 339ExtracellularBy similarityAdd BLAST20
Transmembranei340 – 358Helical; Name=6By similarityAdd BLAST19
Topological domaini359 – 860CytoplasmicBy similarityAdd BLAST502
Transmembranei861 – 881Helical; Name=7By similarityAdd BLAST21
Topological domaini882 – 917ExtracellularBy similarityAdd BLAST36
Transmembranei918 – 938Discontinuously helical; Name=8By similarityAdd BLAST21
Topological domaini939 – 989CytoplasmicBy similarityAdd BLAST51
Transmembranei990 – 1010Helical; Name=9By similarityAdd BLAST21
Topological domaini1011 – 1012ExtracellularBy similarity2
Transmembranei1013 – 1033Helical; Name=10By similarityAdd BLAST21
Topological domaini1034 – 1094CytoplasmicBy similarityAdd BLAST61
Transmembranei1095 – 1115Helical; Name=11By similarityAdd BLAST21
Topological domaini1116 – 1129ExtracellularBy similarityAdd BLAST14
Transmembranei1130 – 1150Helical; Name=12By similarityAdd BLAST21
Topological domaini1151 – 1478CytoplasmicBy similarityAdd BLAST328

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000934301 – 1478Cystic fibrosis transmembrane conductance regulatorAdd BLAST1478

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi524S-palmitoyl cysteineBy similarity1
Modified residuei549PhosphoserineBy similarity1
Modified residuei660PhosphoserineBy similarity1
Modified residuei670Phosphoserine; by PKABy similarity1
Modified residuei686PhosphoserineBy similarity1
Cross-linki688Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei700PhosphoserineBy similarity1
Modified residuei712PhosphoserineBy similarity1
Modified residuei737PhosphoserineBy similarity1
Modified residuei769PhosphoserineBy similarity1
Modified residuei797PhosphoserineBy similarity1
Modified residuei815PhosphoserineBy similarity1
Glycosylationi896N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi899N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi908N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi1393S-palmitoyl cysteineBy similarity1
Modified residuei1442PhosphoserineBy similarity1
Modified residuei1454PhosphoserineBy similarity1

Post-translational modificationi

N-glycosylated.By similarity
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.By similarity
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.By similarity

Keywords - PTMi

Glycoprotein, Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Interactioni

Subunit structurei

Monomer; does not require oligomerization for channel activity. May form oligomers in the membrane (By similarity). Interacts with SLC26A3, SLC26A6 and SLC9A3R1 (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 SLC9A3R1. 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).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ5D1Z7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini81 – 365ABC transmembrane type-1 1PROSITE-ProRule annotationAdd BLAST285
Domaini423 – 646ABC transporter 1PROSITE-ProRule annotationAdd BLAST224
Domaini861 – 1154ABC transmembrane type-1 2PROSITE-ProRule annotationAdd BLAST294
Domaini1208 – 1441ABC transporter 2PROSITE-ProRule annotationAdd BLAST234

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni654 – 833Intrinsically disordered R regionBy similarityAdd BLAST180

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1476 – 1478PDZ-bindingBy similarity3

Domaini

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.By similarity
The PDZ-binding motif mediates interactions with GOPC and with the SLC4A7, SLC9A3R1/EBP50 complex.By similarity
The R region is intrinsically disordered. It mediates channel activation when it is phosphorylated, but not in the absence of phosphorylation.By similarity

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

HOVERGENiHBG004169.

Family and domain databases

InterProiView protein in InterPro
IPR003593. AAA+_ATPase.
IPR011527. ABC1_TM_dom.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR009147. CFTR/ABCC7.
IPR025837. CFTR_reg_dom.
IPR027417. P-loop_NTPase.
PANTHERiPTHR24223:SF273. PTHR24223:SF273. 1 hit.
PfamiView protein in Pfam
PF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
PF14396. CFTR_R. 1 hit.
PRINTSiPR01851. CYSFIBREGLTR.
SMARTiView protein in SMART
SM00382. AAA. 2 hits.
SUPFAMiSSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 2 hits.
TIGRFAMsiTIGR01271. CFTR_protein. 1 hit.
PROSITEiView protein in PROSITE
PS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 1 hit.
PS50893. ABC_TRANSPORTER_2. 2 hits.

Sequencei

Sequence statusi: Complete.

Q5D1Z7-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRSPLEKAN VFSKLFFSWT RPILKKGFRR RLELSDIYQI PSCNSADHLS
60 70 80 90 100
EKLEREWDRE LASKKKPKLI NALRRCFFWR FVFHGIILYL GEVTKAVQPL
110 120 130 140 150
LLGRIIASYD PDNKAERSIA IYLGIGLCLL FIVRTLLLHP AIFGLHHMGM
160 170 180 190 200
QMRIALFSLI YKKTLKLSSR VLDKISTGQL ISLLSNNLNK FDEGLALAHF
210 220 230 240 250
VWIAPLQVVL LMGLLWDLLQ ASAFCGLAFL VVLALFQAWL GQMMMKYRER
260 270 280 290 300
RAGKINERLV ITSEMIDNIQ SVKAYCWEEA METMIENLRQ TELKLTRKTA
310 320 330 340 350
YVRYFNSSAF FFSGFFVVFL AVLPYALIKG IILRKIFTTI SFCIVLRMAV
360 370 380 390 400
TRQFPWAVQT WYDSLGAINK IQDFLQKEEY KTLEYNLTTT DVMMENITAF
410 420 430 440 450
WDEGFGDLFI KVKQSNSDGK IPNGDHGLFF SNFSLLGTPV LKNISFKIEK
460 470 480 490 500
GQLLAVAGST GAGKTSLLML IMGELEPSEG KIKHSGRISF CSQFSWIMPG
510 520 530 540 550
TIKENIIFGV SYDEYRYRSV IKACQLEEEI SKFAEKDNTI LGEGGITLSG
560 570 580 590 600
GQRARISLAR AIYKDADLYL LDSPFGYLDV LTEKEIFESC VCKLMANKTR
610 620 630 640 650
ILITSKMEHL KKADKILILH EGSCYFYGAF SELQSLRPDF SSKLMGFDSF
660 670 680 690 700
DQFSADRRSS ILTETLRRFS IEGDAAVSWN EGKMQSFKQT GDFGERRKNS
710 720 730 740 750
VLSPLNSNRK FSVVQKGQQQ MNGIEENDDE PLERRLSLVP DSEQGEAILP
760 770 780 790 800
RSNMINTGPT FQGRNRRQSV LNLMTRPSVH QGQGMYRTGN AAVRKMSMVP
810 820 830 840 850
QSQLSEIDIY SRRLSRDSGM DISDEINEED LKEWFFDDVE NIPAVTTWNT
860 870 880 890 900
YLRYITVHKS LIFVLIWCLV IFLVEVGASL VGLWVLKETS LKDKANTTNN
910 920 930 940 950
TYAVIITNTS KYYLFYIYVG VADTFFALGL LRGLPLVHTL ISVSKILHHK
960 970 980 990 1000
MLCSVLKAPM STFSTLKAGG ILNRFSKDIA ILDDLLPLTI FDFVQLILIV
1010 1020 1030 1040 1050
VGALIVVSVL QPYIFLATVP VIIAFIMLRA YFLQTSQQLK QLESEARTPI
1060 1070 1080 1090 1100
FTHLVTSLKG LWTLRAFGRQ PYFETLFHKA LNLHTANWFL YMSTLRWFQM
1110 1120 1130 1140 1150
RIEIIFVTFF CIVTFISILT TGDGEGRVGI LLTLAMNIMS TLQWAVNSSI
1160 1170 1180 1190 1200
DVDSLMRSVS RVFKFIDMPS EEPLPPKPTK SKKNQLSQVL IIENEHVKKE
1210 1220 1230 1240 1250
NWPSGGQMTV KDLTAKYIDG GNAVLENISF SISSGQRVGL LGRTGSGKST
1260 1270 1280 1290 1300
LLAAFLRLLN TQGDIQIDGV SWDSVPLQQW RKAFGVIPQK VFIFSGTFRK
1310 1320 1330 1340 1350
NLDPYGQWSD HELWKVADEV GLKSVIEQFP GKLDFVLVDA GCVLSHGHKQ
1360 1370 1380 1390 1400
LICLARSVLS KAKILLLDEP SAHLDPITYQ IIRRALKNAF ADCTVILSEH
1410 1420 1430 1440 1450
RIEAMLECQR FLVIEESKVR QYESIQKLVT EKRLYGQAIS HSDRMKLFPH
1460 1470
RNSSRHKSRA KITALKEETE EEVQETRL
Length:1,478
Mass (Da):168,170
Last modified:March 29, 2005 - v1
Checksum:i86DCDEF74F6F6504
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY916796 mRNA. Translation: AAX13970.1.

Similar proteinsi

Entry informationi

Entry nameiCFTR_TRIVU
AccessioniPrimary (citable) accession number: Q5D1Z7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: March 29, 2005
Last modified: May 10, 2017
This is version 76 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families