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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

Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO1. 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.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi458 – 465ATPPROSITE-ProRule annotation8
Nucleotide bindingi1240 – 1247ATPPROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

  • bicarbonate transport Source: RGD
  • body fluid secretion Source: RGD
  • cellular response to cAMP Source: UniProtKB
  • cellular response to hormone stimulus Source: RGD
  • chloride transport Source: RGD
  • intracellular pH elevation Source: UniProtKB
  • iodide transport Source: RGD
  • lung development Source: RGD
  • membrane hyperpolarization Source: UniProtKB
  • positive regulation of vasodilation 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
Complete GO annotation...

Keywords - Molecular functioni

Chloride channel, Hydrolase, Ion channel

Keywords - Biological processi

Ion transport, Transport

Keywords - Ligandi

ATP-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:3.6.3.49)
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

  • Early endosome membrane By similarity; Multi-pass membrane protein Sequence analysis
  • Cell membrane By similarity; Multi-pass membrane protein Sequence analysis

  • Note: In epithelial cells, detected on the apical side, but not associated with cilia.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 80CytoplasmicSequence analysisAdd BLAST80
Transmembranei81 – 103Helical; Name=1PROSITE-ProRule annotationAdd BLAST23
Topological domaini104 – 117ExtracellularSequence analysisAdd BLAST14
Transmembranei118 – 138Helical; Name=2PROSITE-ProRule annotationAdd BLAST21
Topological domaini139 – 194CytoplasmicSequence analysisAdd BLAST56
Transmembranei195 – 215Helical; Name=3PROSITE-ProRule annotationAdd BLAST21
Topological domaini216 – 220ExtracellularSequence analysis5
Transmembranei221 – 241Helical; Name=4PROSITE-ProRule annotationAdd BLAST21
Topological domaini242 – 307CytoplasmicSequence analysisAdd BLAST66
Transmembranei308 – 328Helical; Name=5PROSITE-ProRule annotationAdd BLAST21
Topological domaini329 – 330ExtracellularSequence analysis2
Transmembranei331 – 350Helical; Name=6PROSITE-ProRule annotationAdd BLAST20
Topological domaini351 – 854CytoplasmicSequence analysisAdd BLAST504
Transmembranei855 – 875Helical; Name=7PROSITE-ProRule annotationAdd BLAST21
Topological domaini876 – 906ExtracellularSequence analysisAdd BLAST31
Transmembranei907 – 927Helical; Name=8PROSITE-ProRule annotationAdd BLAST21
Topological domaini928 – 985CytoplasmicSequence analysisAdd BLAST58
Transmembranei986 – 1006Helical; Name=9PROSITE-ProRule annotationAdd BLAST21
Topological domaini1007 – 1008ExtracellularSequence analysis2
Transmembranei1009 – 1029Helical; Name=10PROSITE-ProRule annotationAdd BLAST21
Topological domaini1030 – 1097CytoplasmicSequence analysisAdd BLAST68
Transmembranei1098 – 1118Helical; Name=11PROSITE-ProRule annotationAdd BLAST21
Topological domaini1119 – 1123ExtracellularSequence analysis5
Transmembranei1124 – 1144Helical; Name=12PROSITE-ProRule annotationAdd BLAST21
Topological domaini1145 – 1476CytoplasmicSequence analysisAdd BLAST332

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
  • early endosome Source: UniProtKB
  • early endosome membrane Source: UniProtKB-SubCell
  • microvillus Source: RGD
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, 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 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

Ubiquitinated, leading to its degradation in the lysosome. Deubiquitination by USP10 in early endosomes, enhances its endocytic recycling. Ubiquitinated by RNF185 during ER stress (By similarity).By similarity
Phosphorylated; activates the channel. It is not clear whether PKC phosphorylation itself activates the channel or permits activation by phosphorylation at PKA sites. Phosphorylated by AMPK (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP34158.
PRIDEiP34158.

PTM databases

iPTMnetiP34158.
PhosphoSitePlusiP34158.

Expressioni

Gene expression databases

BgeeiENSRNOG00000008284.

Interactioni

Subunit structurei

Interacts with MYO6 and GOPC. Interacts with SLC4A7 through SLC9A3R1. Interacts with SHANK2 (By similarity). Found in a complex with MYO5B and RAB11A (By similarity). Interacts with ANO1 (By similarity). Interacts with SLC26A3, SLC26A6 and SLC9A3R1. Interacts with SLC26A8. Interacts with AHCYL1; the interaction increases CFTR activity (By similarity).By similarity

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

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1474 – 1476PDZ-bindingBy similarity3

Sequence similaritiesi

Contains 2 ABC transmembrane type-1 domains.PROSITE-ProRule annotation
Contains 2 ABC transporter domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR003593. 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.
[Graphical view]
PANTHERiPTHR24223:SF19. PTHR24223:SF19. 3 hits.
PfamiPF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
PF14396. CFTR_R. 1 hit.
[Graphical view]
PRINTSiPR01851. CYSFIBREGLTR.
SMARTiSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 3 hits.
TIGRFAMsiTIGR01271. CFTR_protein. 1 hit.
PROSITEiPS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 1 hit.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view]

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

PROiP34158.

Gene expression databases

BgeeiENSRNOG00000008284.

Family and domain databases

Gene3Di3.40.50.300. 2 hits.
InterProiIPR003593. 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.
[Graphical view]
PANTHERiPTHR24223:SF19. PTHR24223:SF19. 3 hits.
PfamiPF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
PF14396. CFTR_R. 1 hit.
[Graphical view]
PRINTSiPR01851. CYSFIBREGLTR.
SMARTiSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMiSSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 3 hits.
TIGRFAMsiTIGR01271. CFTR_protein. 1 hit.
PROSITEiPS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 1 hit.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCFTR_RAT
AccessioniPrimary (citable) accession number: P34158
Secondary accession number(s): Q2IBD3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: June 12, 2007
Last modified: November 2, 2016
This is version 157 of the entry and version 3 of the sequence. [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.