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Protein

Cystic fibrosis transmembrane conductance regulator

Gene

CFTR

Organism
Cavia porcellus (Guinea pig)
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 sitei435ATP 1By similarity1
Binding sitei494ATP 1By similarity1
Binding sitei1220ATP 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi459 – 466ATP 1PROSITE-ProRule annotation8
Nucleotide bindingi1245 – 1252ATP 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

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
OrganismiCavia porcellus (Guinea pig)
Taxonomic identifieri10141 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaHystricomorphaCaviidaeCavia
Proteomesi
  • UP000005447 Componenti: Unassembled WGS sequence

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 – 859CytoplasmicBy similarityAdd BLAST501
Transmembranei860 – 880Helical; Name=7By similarityAdd BLAST21
Topological domaini881 – 919ExtracellularBy similarityAdd BLAST39
Transmembranei920 – 940Discontinuously helical; Name=8By similarityAdd BLAST21
Topological domaini941 – 991CytoplasmicBy similarityAdd BLAST51
Transmembranei992 – 1012Helical; Name=9By similarityAdd BLAST21
Topological domaini1013 – 1014ExtracellularBy similarity2
Transmembranei1015 – 1035Helical; Name=10By similarityAdd BLAST21
Topological domaini1036 – 1096CytoplasmicBy similarityAdd BLAST61
Transmembranei1097 – 1117Helical; Name=11By similarityAdd BLAST21
Topological domaini1118 – 1131ExtracellularBy similarityAdd BLAST14
Transmembranei1132 – 1152Helical; Name=12By similarityAdd BLAST21
Topological domaini1153 – 1481CytoplasmicBy similarityAdd BLAST329

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000934181 – 1481Cystic fibrosis transmembrane conductance regulatorAdd BLAST1481

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi525S-palmitoyl cysteineBy similarity1
Modified residuei550PhosphoserineBy similarity1
Modified residuei661Phosphoserine; by PKABy similarity1
Modified residuei671Phosphoserine; by PKABy similarity1
Modified residuei687Phosphoserine; by PKCBy similarity1
Cross-linki689Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei701Phosphoserine; by PKABy similarity1
Modified residuei713Phosphoserine; by PKABy similarity1
Modified residuei718PhosphothreonineBy similarity1
Modified residuei738Phosphoserine; by PKABy similarity1
Modified residuei769Phosphoserine; by PKABy similarity1
Modified residuei796Phosphoserine; by PKABy similarity1
Modified residuei814Phosphoserine; by PKABy similarity1
Glycosylationi895N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi901N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi1396S-palmitoyl cysteineBy similarity1
Modified residuei1445PhosphoserineBy similarity1
Modified residuei1457PhosphoserineBy 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

Protein-protein interaction databases

STRINGi10141.ENSCPOP00000011488.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini81 – 365ABC transmembrane type-1 1PROSITE-ProRule annotationAdd BLAST285
Domaini424 – 647ABC transporter 1PROSITE-ProRule annotationAdd BLAST224
Domaini860 – 1156ABC transmembrane type-1 2PROSITE-ProRule annotationAdd BLAST297
Domaini1211 – 1444ABC transporter 2PROSITE-ProRule annotationAdd BLAST234

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni655 – 832Intrinsically disordered R regionBy similarityAdd BLAST178

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1479 – 1481PDZ-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

eggNOGiKOG0054. Eukaryota.
COG1132. LUCA.
HOVERGENiHBG004169.
InParanoidiQ00552.

Family and domain databases

Gene3Di1.20.1560.10. 2 hits.
InterProiView protein in InterPro
IPR003593. AAA+_ATPase.
IPR011527. ABC1_TM_dom.
IPR036640. ABC1_TM_sf.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR009147. CFTR/ABCC7.
IPR025837. CFTR_reg_dom.
IPR027417. P-loop_NTPase.
PANTHERiPTHR24223:SF19. PTHR24223:SF19. 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.

Q00552-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQKSPLVKAS VISKLFFSWT RPILKKGYRK RLEVSDIYQV PSADSADNLS
60 70 80 90 100
EELEREWDRE LASKKNPKLI NALRRCFLWR FIFYGILLYL GEVTKAVQPL
110 120 130 140 150
LLGRIIASYD PDNKEERSIA IYLAIGLCLL FIVRTLLLHP AIFGLQHIGM
160 170 180 190 200
QMRIAMFSLI YKKTLKLSSR VLDKISIGQL VSLLSNNLNK FDEGLALAHF
210 220 230 240 250
VWIAPLQVTL LMGLLWDLLQ ASAFCGLAVL IVLALFQAWL GKMMMKYRDQ
260 270 280 290 300
RAGKINERLV ITSEMIENIQ SVKAYCWEEA MEKMIENLRQ TELKLTRKAA
310 320 330 340 350
YMRYFNSAAF FFSGFFVVFL SVLPYAFLQG IILRKIFTTI SFCIVLRMAI
360 370 380 390 400
TRQFPGAVQT WYDSLGAINK IQDFLQKQEY KTLEYNLTTT EVVMENVTAF
410 420 430 440 450
WEEQGFGELL EKAKLNNNNR KISNGDNKLF FSNFSLLGSP VLKDINFKIE
460 470 480 490 500
KGQLLAVAGS TGAGKTSLLM MILGELEPSE GKIKHSGRVS FCSQFSWIMP
510 520 530 540 550
GTIKENIIFG VSYDEYRYRS VIKACQLEED ISKFAEKDNI VLGEGGITLS
560 570 580 590 600
GGQRARISLA RAVYKDADLY LLDSPFGYLD VLTEKQIFES CVCKLMANKT
610 620 630 640 650
RILVTSKMEH LKKADKILIL HEGSSYFYGT FSELQNLRPD FSSKLMGYDS
660 670 680 690 700
FDQFSAERRN SILTETLRRF SLEGDPSVSF NETKKQSFKQ TGEFGEKRKN
710 720 730 740 750
SILNSINSIR KFSIVPKTPL QISGIEEDSD DPVERRLSLV PDSEQSDGLL
760 770 780 790 800
LRSNVIHTGP TFQGSRRQSV LNLITHSVNQ GQSFRRTTTA PSRKMSLAPQ
810 820 830 840 850
ASLTEMDIYS RRLSQDSSLE INEEINEEDL KECFFDDVEN IPTVTTWNTY
860 870 880 890 900
LRYITVHKSL ILVLIWCLII FLAEVAASLV VLWLLKNNTP QQEMNSTQSG
910 920 930 940 950
NRSYPVIITN TSFYYIFYIY VGVADTLLAL GLFRGLPLVH TLITVSKILH
960 970 980 990 1000
HKMLRSVLQA PMSTLNALKA GGILNRFSKD IAILDDLLPL TIFDFIQLLL
1010 1020 1030 1040 1050
IVIGAIAVVS VLQPYIFLAT VPVIAAFIML RAYFLHTSQQ LKQLESEGRS
1060 1070 1080 1090 1100
PIFTHLVTSL KGLWTLRAFG RQPYFETLFH KALNLHTANW FLYLSTLRWF
1110 1120 1130 1140 1150
QMRIEMIFVI FFIAVTFISI LTTGEGQGSV GIILTLAMNI MSTLQWAVNS
1160 1170 1180 1190 1200
SIDVDSLMRS VSRVFKFIDM PEEGAPVKSI KPSRDDQLSK VMIIENQHVK
1210 1220 1230 1240 1250
KDDIWPSGGQ MIVKDLTAKY VDGGIAILEN ISFSISPGQR VGLLGRTGSG
1260 1270 1280 1290 1300
KSTLLSAFLR LLNTEGEIQI DGVSWDSTPL QQWRKAFGVI PQKVFIFSGT
1310 1320 1330 1340 1350
FRKNLDPFGQ WSDQEIWKVA DEVGLRSVIE QFPGKLDFVL VDGGYVLSHG
1360 1370 1380 1390 1400
HKQLMCLARS VLSKAKILLL DEPSAHLDPI TYQIIRRTIK QAFADCTVIL
1410 1420 1430 1440 1450
CEHRIEAMLE CQRFLVIEEN KVRQYDSIQK LLSEKSLFRQ AISSSDRLKL
1460 1470 1480
FPHRNSSKHK SRSQITALKE ETEEEVQETR L
Length:1,481
Mass (Da):168,274
Last modified:January 25, 2012 - v2
Checksum:i27364539F003D3D1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti404Missing in ABI93671 (Ref. 2) Curated1
Sequence conflicti597 – 599ANK → TSG in AAA37033 (PubMed:1719001).Curated3
Sequence conflicti705 – 706SI → QF in AAA37033 (PubMed:1719001).Curated2
Sequence conflicti710R → T in AAA37033 (PubMed:1719001).Curated1
Sequence conflicti749Missing in AAA37033 (PubMed:1719001).Curated1
Sequence conflicti753 – 754SN → KH in AAA37033 (PubMed:1719001).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB618655 mRNA. Translation: BAK78871.1.
DP000184 Genomic DNA. Translation: ABI93671.1.
M96679 Genomic DNA. Translation: AAA37033.1.
PIRiD39323.
RefSeqiNP_001265686.1. NM_001278757.1.

Genome annotation databases

GeneIDi100719898.

Similar proteinsi

Entry informationi

Entry nameiCFTR_CAVPO
AccessioniPrimary (citable) accession number: Q00552
Secondary accession number(s): G1UHC1, Q07E05
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: January 25, 2012
Last modified: October 25, 2017
This is version 112 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families