Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Cystic fibrosis transmembrane conductance regulator

Gene

Cftr

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 sitei493ATP 1By similarity1
Binding sitei1215ATP 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi458 – 465ATPPROSITE-ProRule annotation8
Nucleotide bindingi458 – 465ATP 1PROSITE-ProRule annotationBy similarity8
Nucleotide bindingi1240 – 1247ATPPROSITE-ProRule annotation8
Nucleotide bindingi1240 – 1247ATP 2PROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

  • aging Source: RGD
  • bicarbonate transport Source: RGD
  • cellular response to anoxia Source: RGD
  • cellular response to cAMP Source: UniProtKB
  • cellular response to heat Source: RGD
  • cellular response to hormone stimulus Source: RGD
  • chloride transmembrane transport Source: UniProtKB
  • chloride transport Source: RGD
  • intracellular pH elevation Source: UniProtKB
  • iodide transport Source: RGD
  • liver regeneration Source: RGD
  • lung development Source: RGD
  • membrane hyperpolarization Source: UniProtKB
  • negative regulation of type B pancreatic cell development Source: RGD
  • negative regulation of vascular associated smooth muscle cell apoptotic process Source: RGD
  • positive regulation of establishment of Sertoli cell barrier Source: RGD
  • positive regulation of mast cell activation Source: RGD
  • response to cytokine Source: RGD
  • response to drug Source: RGD
  • response to estrogen Source: RGD
  • response to peptide hormone Source: RGD
  • sperm capacitation Source: UniProtKB
  • transepithelial chloride transport Source: RGD
  • vasodilation Source: RGD
  • water transport Source: RGD

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi2332. Cftr.

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 – 853CytoplasmicBy similarityAdd BLAST495
Transmembranei854 – 874Helical; Name=7By similarityAdd BLAST21
Topological domaini875 – 913ExtracellularBy similarityAdd BLAST39
Transmembranei914 – 934Discontinuously helical; Name=8By similarityAdd BLAST21
Topological domaini935 – 985CytoplasmicBy similarityAdd BLAST51
Transmembranei986 – 1006Helical; Name=9By similarityAdd BLAST21
Topological domaini1007 – 1008ExtracellularBy similarity2
Transmembranei1009 – 1029Helical; Name=10By similarityAdd BLAST21
Topological domaini1030 – 1090CytoplasmicBy similarityAdd BLAST61
Transmembranei1091 – 1111Helical; Name=11By similarityAdd BLAST21
Topological domaini1112 – 1125ExtracellularBy similarityAdd BLAST14
Transmembranei1126 – 1146Helical; Name=12By similarityAdd BLAST21
Topological domaini1147 – 1476CytoplasmicBy similarityAdd BLAST330

GO - Cellular componenti

  • apical plasma membrane Source: RGD
  • basolateral plasma membrane Source: RGD
  • chloride channel complex Source: UniProtKB-KW
  • cytoplasm Source: RGD
  • cytoplasmic vesicle membrane Source: RGD
  • cytosol Source: GO_Central
  • dendrite Source: RGD
  • early endosome Source: UniProtKB
  • early endosome membrane Source: UniProtKB-SubCell
  • endoplasmic reticulum membrane Source: UniProtKB
  • integral component of membrane Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • microvillus Source: RGD
  • neuronal cell body Source: RGD
  • plasma membrane Source: UniProtKB

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3992.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000934281 – 1476Cystic fibrosis transmembrane conductance regulatorAdd BLAST1476

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi524S-palmitoyl cysteineBy similarity1
Modified residuei549PhosphoserineBy similarity1
Modified residuei660PhosphoserineBy similarity1
Modified residuei670Phosphoserine; by PKABy similarity1
Modified residuei684PhosphoserineBy similarity1
Modified residuei698PhosphoserineBy similarity1
Modified residuei710PhosphoserineBy similarity1
Modified residuei715PhosphothreonineBy similarity1
Modified residuei732PhosphoserineBy similarity1
Modified residuei763PhosphoserineBy similarity1
Modified residuei785PhosphoserineBy similarity1
Modified residuei790PhosphoserineBy similarity1
Modified residuei808PhosphoserineCombined sources1
Glycosylationi889N-linked (GlcNAc...)Sequence analysis1
Glycosylationi895N-linked (GlcNAc...)Sequence analysis1
Lipidationi1391S-palmitoyl cysteineBy similarity1
Modified residuei1440PhosphoserineBy similarity1
Modified residuei1452PhosphoserineBy 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, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP34158.
PRIDEiP34158.

PTM databases

iPTMnetiP34158.
PhosphoSitePlusiP34158.

Expressioni

Tissue specificityi

Detected in epithelial cells in nasopharynx, submandibular gland, pancreas and ileum (at protein level).1 Publication

Gene expression databases

BgeeiENSRNOG00000008284.

Interactioni

Subunit structurei

Monomer; does not require oligomerization for channel activity. May form oligomers in the membrane (By similarity). Interacts with SLC4A7 through SLC9A3R1 (By similarity). Interacts with SHANK2 (PubMed:14679199). Interacts with SLC9A3R1 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 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 similarity2 Publications

Protein-protein interaction databases

BioGridi246440. 3 interactors.
STRINGi10116.ENSRNOP00000010981.

Chemistry databases

BindingDBiP34158.

Structurei

3D structure databases

ProteinModelPortaliP34158.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini81 – 365ABC transmembrane type-1 1PROSITE-ProRule annotationAdd BLAST285
Domaini412 – 646ABC transporter 1PROSITE-ProRule annotationAdd BLAST235
Domaini854 – 1153ABC transmembrane type-1 2PROSITE-ProRule annotationAdd BLAST300
Domaini1208 – 1439ABC transporter 2PROSITE-ProRule annotationAdd BLAST232

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni654 – 826Intrinsically disordered R regionBy similarityAdd BLAST173

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1474 – 1476PDZ-binding1 Publication3

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.
InParanoidiP34158.
KOiK05031.
PhylomeDBiP34158.
TreeFamiTF105200.

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. 3 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.

P34158-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQKSPLEKAS FISKLFFSWT TPILRKGYRH HLELSDIYQA PSSDSADHLS
60 70 80 90 100
EKLEREWDRE QASKKKPQLI HALRRCFVWR FVFYGVLLYL GEVTKAVQPV
110 120 130 140 150
LLGRIIASYD PDNTEERSIA IYLGIGLCLL FIVRTLLLHP AIFGLHHIGM
160 170 180 190 200
QMRIAMFSLI YKKTLKLSSR VLDKISIGQL ISLLSNNLNK FDEGLALAHF
210 220 230 240 250
IWIAPLQVVL LMGLLWDLLQ FSAFCGLGLL IVLVIFQAIL GKMMVKYRDK
260 270 280 290 300
RAAKINERLV ITSEVIDNIY SVKAYCWESA MEKIIESLRE EELKMTRRSA
310 320 330 340 350
YMRFFTSSAF FFSGFFVVFL SVLPYTVING IVLRKIFTTI SFCIVLRMSV
360 370 380 390 400
TRQFPTAVQI WYDSLGMIRK IQDFLQTQEY KVLEYNLMFT GLVMENVTAF
410 420 430 440 450
WEEGFQELLE KVQLNNDDRK TSNGENHLSF SHLCLVGNPV LKNINLNIKK
460 470 480 490 500
GEMLAITGST GAGKTSLLML ILGELEASEG IIKHSGRVSF SSQISWIMPG
510 520 530 540 550
TIKENIIFGV SYDEYRYKSV VKACQLQEDI TKFAEQDNTV LGEGGVTLSG
560 570 580 590 600
GQRARISLAR AVYKDADLYL LDSPFGYLDV LTEEQIFESC VCKLMASKTR
610 620 630 640 650
ILVTSKMEQL KKADKILILH EGSSYFYGTF SELQSLRPDF SSKLMGYDTF
660 670 680 690 700
DQFTEERRSS ILTETLRRFS VDDASTTWNK AKQSFRQTGE FGEKRKNSIL
710 720 730 740 750
SSFSSVKKIS IVQKTPLSIE GESDDLQERR LSLVPDSEHG EAALPRSNMI
760 770 780 790 800
TAGPTFPGRR RQSVLDLMTF TPSSVSSSLQ RTRASIRKIS LAPRISLKEE
810 820 830 840 850
DIYSRRLSQD STLNITEEIN EEDLKECFFD DMVKIPTVTT WNTYLRYFTL
860 870 880 890 900
HRGLFAVLIW CVLVFLVEVA ASLFVLWLLK NNPVNGGNNG TKIANTSYVV
910 920 930 940 950
VITSSSFYYI FYIYVGVADT LLALSLFRGL PLVHTLITAS KILHRKMLHS
960 970 980 990 1000
ILHAPMSTFN KLKAGGILNR FSKDIAILDD FLPLTIFDFI QLLFIVVGAI
1010 1020 1030 1040 1050
IVVSALQPYI FLATVPGLAV FILLRAYFLH TSQQLKQLES EGRSPIFTHL
1060 1070 1080 1090 1100
VTSLKGLWTL RAFRRQTYFE TLFHKALNLH TANWFMYLAT LRWFQMRIDM
1110 1120 1130 1140 1150
IFVLFFIVVT FISILTTGEG EGTTGIILTL AMNIMSTLQW AVNSSIDTDS
1160 1170 1180 1190 1200
LMRSVSRVFK FIDIQTEESI CTKIMKELHS EDSPNALVIK NEHVKKCDTW
1210 1220 1230 1240 1250
PSGGEMVVKD LTVKYVDDGN AILENISFSI SPGQRVGLLG RTGSGKSTLL
1260 1270 1280 1290 1300
SAFLRMLNIK GEIQIDGVSW NSMTLQEWRK AFGVITQKVF IFSGTFRQNL
1310 1320 1330 1340 1350
DPNGKWRDEE IWKVADQVGL KSVIEQFPGQ LNFTLVDGGY VLSHGHKQLM
1360 1370 1380 1390 1400
CLARSVLSKA KIILLDEPSA NLDPITYQVI RRVLRQAFAG CTVVLCEHRI
1410 1420 1430 1440 1450
EAMLDCQRFL VIEQGNVWQY ESLQALLSEK SVFQRALSSS EKMKLFHGRH
1460 1470
SSKQKPRTQI TAVKEETEEE VQETRL
Length:1,476
Mass (Da):167,830
Last modified:June 12, 2007 - v3
Checksum:iB2B2A25EB5107640
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti987 – 988FD → LT in AAA40918 (PubMed:1282491).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DP000027 Genomic DNA. Translation: AAR16315.1.
L26098 Genomic DNA. Translation: AAA73561.1.
M89906 mRNA. Translation: AAA40918.1.
PIRiI84733.
RefSeqiNP_113694.1. NM_031506.1.
UniGeneiRn.124539.

Genome annotation databases

GeneIDi24255.
KEGGirno:24255.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DP000027 Genomic DNA. Translation: AAR16315.1.
L26098 Genomic DNA. Translation: AAA73561.1.
M89906 mRNA. Translation: AAA40918.1.
PIRiI84733.
RefSeqiNP_113694.1. NM_031506.1.
UniGeneiRn.124539.

3D structure databases

ProteinModelPortaliP34158.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246440. 3 interactors.
STRINGi10116.ENSRNOP00000010981.

Chemistry databases

BindingDBiP34158.
ChEMBLiCHEMBL3992.

PTM databases

iPTMnetiP34158.
PhosphoSitePlusiP34158.

Proteomic databases

PaxDbiP34158.
PRIDEiP34158.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi24255.
KEGGirno:24255.

Organism-specific databases

CTDi1080.
RGDi2332. Cftr.

Phylogenomic databases

eggNOGiKOG0054. Eukaryota.
COG1132. LUCA.
HOVERGENiHBG004169.
InParanoidiP34158.
KOiK05031.
PhylomeDBiP34158.
TreeFamiTF105200.

Miscellaneous databases

PROiPR:P34158.

Gene expression databases

BgeeiENSRNOG00000008284.

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. 3 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.
ProtoNetiSearch...

Entry informationi

Entry nameiCFTR_RAT
AccessioniPrimary (citable) accession number: P34158
Secondary accession number(s): Q2IBD3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: June 12, 2007
Last modified: April 12, 2017
This is version 160 of the entry and version 3 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.