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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)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi458 – 4658ATPPROSITE-ProRule annotation
Nucleotide bindingi1240 – 12478ATPPROSITE-ProRule annotation

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 transmembrane transport Source: GOC
  • 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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8080CytoplasmicSequence analysisAdd
BLAST
Transmembranei81 – 10323Helical; Name=1PROSITE-ProRule annotationAdd
BLAST
Topological domaini104 – 11714ExtracellularSequence analysisAdd
BLAST
Transmembranei118 – 13821Helical; Name=2PROSITE-ProRule annotationAdd
BLAST
Topological domaini139 – 19456CytoplasmicSequence analysisAdd
BLAST
Transmembranei195 – 21521Helical; Name=3PROSITE-ProRule annotationAdd
BLAST
Topological domaini216 – 2205ExtracellularSequence analysis
Transmembranei221 – 24121Helical; Name=4PROSITE-ProRule annotationAdd
BLAST
Topological domaini242 – 30766CytoplasmicSequence analysisAdd
BLAST
Transmembranei308 – 32821Helical; Name=5PROSITE-ProRule annotationAdd
BLAST
Topological domaini329 – 3302ExtracellularSequence analysis
Transmembranei331 – 35020Helical; Name=6PROSITE-ProRule annotationAdd
BLAST
Topological domaini351 – 854504CytoplasmicSequence analysisAdd
BLAST
Transmembranei855 – 87521Helical; Name=7PROSITE-ProRule annotationAdd
BLAST
Topological domaini876 – 90631ExtracellularSequence analysisAdd
BLAST
Transmembranei907 – 92721Helical; Name=8PROSITE-ProRule annotationAdd
BLAST
Topological domaini928 – 98558CytoplasmicSequence analysisAdd
BLAST
Transmembranei986 – 100621Helical; Name=9PROSITE-ProRule annotationAdd
BLAST
Topological domaini1007 – 10082ExtracellularSequence analysis
Transmembranei1009 – 102921Helical; Name=10PROSITE-ProRule annotationAdd
BLAST
Topological domaini1030 – 109768CytoplasmicSequence analysisAdd
BLAST
Transmembranei1098 – 111821Helical; Name=11PROSITE-ProRule annotationAdd
BLAST
Topological domaini1119 – 11235ExtracellularSequence analysis
Transmembranei1124 – 114421Helical; Name=12PROSITE-ProRule annotationAdd
BLAST
Topological domaini1145 – 1476332CytoplasmicSequence analysisAdd
BLAST

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

ChEMBLiCHEMBL3992.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 14761476Cystic fibrosis transmembrane conductance regulatorPRO_0000093428Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi524 – 5241S-palmitoyl cysteineBy similarity
Modified residuei549 – 5491PhosphoserineBy similarity
Modified residuei660 – 6601PhosphoserineBy similarity
Modified residuei684 – 6841PhosphoserineBy similarity
Modified residuei698 – 6981PhosphoserineBy similarity
Modified residuei710 – 7101PhosphoserineBy similarity
Modified residuei715 – 7151PhosphothreonineBy similarity
Modified residuei732 – 7321PhosphoserineBy similarity
Modified residuei763 – 7631PhosphoserineBy similarity
Modified residuei785 – 7851PhosphoserineBy similarity
Modified residuei790 – 7901PhosphoserineBy similarity
Modified residuei808 – 8081PhosphoserineCombined sources
Glycosylationi889 – 8891N-linked (GlcNAc...)Sequence analysis
Glycosylationi895 – 8951N-linked (GlcNAc...)Sequence analysis
Lipidationi1391 – 13911S-palmitoyl cysteineBy similarity
Modified residuei1440 – 14401PhosphoserineBy similarity
Modified residuei1452 – 14521PhosphoserineBy similarity

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.
PhosphoSiteiP34158.

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. 1 interaction.
STRINGi10116.ENSRNOP00000010981.

Chemistry

BindingDBiP34158.

Structurei

3D structure databases

ProteinModelPortaliP34158.
SMRiP34158. Positions 390-670.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini81 – 365285ABC transmembrane type-1 1PROSITE-ProRule annotationAdd
BLAST
Domaini412 – 646235ABC transporter 1PROSITE-ProRule annotationAdd
BLAST
Domaini854 – 1153300ABC transmembrane type-1 2PROSITE-ProRule annotationAdd
BLAST
Domaini1208 – 1439232ABC transporter 2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1474 – 14763PDZ-bindingBy similarity

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.
OMAiNALRRCF.
OrthoDBiEOG7C2R0B.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti987 – 9882FD → LT in AAA40918 (PubMed:1282491).Curated

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.
SMRiP34158. Positions 390-670.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi246440. 1 interaction.
STRINGi10116.ENSRNOP00000010981.

Chemistry

BindingDBiP34158.
ChEMBLiCHEMBL3992.

PTM databases

iPTMnetiP34158.
PhosphoSiteiP34158.

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.
OMAiNALRRCF.
OrthoDBiEOG7C2R0B.
PhylomeDBiP34158.
TreeFamiTF105200.

Miscellaneous databases

NextBioi602781.
PROiP34158.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Comparative analyses of multi-species sequences from targeted genomic regions."
    Thomas J.W., Touchman J.W., Blakesley R.W., Bouffard G.G., Beckstrom-Sternberg S.M., Margulies E.H., Blanchette M., Siepel A.C., Thomas P.J., McDowell J.C., Maskeri B., Hansen N.F., Schwartz M.S., Weber R.J., Kent W.J., Karolchik D., Bruen T.C., Bevan R.
    , Cutler D.J., Schwartz S., Elnitski L., Idol J.R., Prasad A.B., Lee-Lin S.-Q., Maduro V.V.B., Summers T.J., Portnoy M.E., Dietrich N.L., Akhter N., Ayele K., Benjamin B., Cariaga K., Brinkley C.P., Brooks S.Y., Granite S., Guan X., Gupta J., Haghighi P., Ho S.-L., Huang M.C., Karlins E., Laric P.L., Legaspi R., Lim M.J., Maduro Q.L., Masiello C.A., Mastrian S.D., McCloskey J.C., Pearson R., Stantripop S., Tiongson E.E., Tran J.T., Tsurgeon C., Vogt J.L., Walker M.A., Wetherby K.D., Wiggins L.S., Young A.C., Zhang L.-H., Osoegawa K., Zhu B., Zhao B., Shu C.L., De Jong P.J., Lawrence C.E., Smit A.F., Chakravarti A., Haussler D., Green P., Miller W., Green E.D.
    Nature 424:788-793(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "Analysis of the mouse and rat CFTR promoter regions."
    Denamur E., Chehab F.F.
    Hum. Mol. Genet. 3:1089-1094(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-17.
  3. "Localization of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) in the rat to chromosome 4 and implications for the evolution of mammalian chromosomes."
    Trezise A.E., Szpirer C., Buchwald M.
    Genomics 14:869-874(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 482-988.
  4. "Inhibitory regulation of cystic fibrosis transmembrane conductance regulator anion-transporting activities by Shank2."
    Kim J.Y., Han W., Namkung W., Lee J.H., Kim K.H., Shin H., Kim E., Lee M.G.
    J. Biol. Chem. 279:10389-10396(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SHANK2.
  5. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-808, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

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: February 17, 2016
This is version 152 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.