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P26361 (CFTR_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Cftr
Synonyms:Abcc7
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1476 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation. Ref.6

Catalytic activity

ATP + H2O = ADP + phosphate.

Subunit structure

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 By similarity. Ref.6

Subcellular location

Early endosome membrane; Multi-pass membrane protein By similarity. Cell membrane By similarity.

Tissue specificity

Isoform 1 is expressed in a variety of epithelial tissues including colon, kidney, lung, small intestine and testis. Isoforms 2 and 3 are expressed only in testis.

Domain

The PDZ-binding motif mediates interactions with GOPC and with the SLC4A7, SLC9A3R1/EBP50 complex By similarity.

Post-translational modification

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.

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.

Sequence similarities

Belongs to the ABC transporter superfamily. ABCC family. CFTR transporter (TC 3.A.1.202) subfamily. [View classification]

Contains 2 ABC transmembrane type-1 domains.

Contains 2 ABC transporter domains.

Ontologies

Keywords
   Biological processIon transport
Transport
   Cellular componentCell membrane
Endosome
Membrane
   Coding sequence diversityAlternative splicing
   DomainRepeat
Transmembrane
Transmembrane helix
   LigandATP-binding
Chloride
Nucleotide-binding
   Molecular functionChloride channel
Hydrolase
Ion channel
   PTMGlycoprotein
Lipoprotein
Palmitate
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to cAMP

Inferred from direct assay Ref.6. Source: UniProtKB

cellular response to hormone stimulus

Inferred from electronic annotation. Source: Ensembl

chloride transmembrane transport

Inferred from mutant phenotype Ref.6. Source: GOC

chloride transport

Inferred from genetic interaction PubMed 19033647. Source: MGI

cholesterol biosynthetic process

Inferred from mutant phenotype PubMed 17085523. Source: MGI

cholesterol transport

Inferred from mutant phenotype PubMed 17085523. Source: MGI

intracellular pH elevation

Inferred from mutant phenotype Ref.6. Source: UniProtKB

iodide transport

Inferred from electronic annotation. Source: Ensembl

lung development

Inferred from electronic annotation. Source: Ensembl

membrane hyperpolarization

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of vasodilation

Inferred from electronic annotation. Source: Ensembl

response to cytokine

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to estrogen

Inferred from electronic annotation. Source: Ensembl

response to peptide hormone

Inferred from electronic annotation. Source: Ensembl

sperm capacitation

Inferred from mutant phenotype Ref.6. Source: UniProtKB

transepithelial chloride transport

Inferred from electronic annotation. Source: Ensembl

vasodilation

Inferred from electronic annotation. Source: Ensembl

water transport

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentapical plasma membrane

Inferred from electronic annotation. Source: Ensembl

basolateral plasma membrane

Inferred from electronic annotation. Source: Ensembl

cell surface

Inferred from electronic annotation. Source: Ensembl

chloride channel complex

Inferred from electronic annotation. Source: UniProtKB-KW

cytoplasmic vesicle membrane

Inferred from electronic annotation. Source: Ensembl

early endosome

Inferred from sequence or structural similarity. Source: UniProtKB

early endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

endoplasmic reticulum Sec complex

Inferred from electronic annotation. Source: Ensembl

microvillus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

bicarbonate transmembrane transporter activity

Inferred from mutant phenotype Ref.6. Source: UniProtKB

channel-conductance-controlling ATPase activity

Inferred from electronic annotation. Source: UniProtKB-EC

chloride channel activity

Inferred from sequence or structural similarity. Source: UniProtKB

chloride channel inhibitor activity

Inferred from sequence or structural similarity. Source: UniProtKB

chloride transmembrane transporter activity

Inferred from mutant phenotype Ref.6. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

HSPA8P191205EBI-6115317,EBI-907802From a different organism.
Slc26a3Q9WVC83EBI-6115317,EBI-6895537
Slc26a6Q8CIW63EBI-6115317,EBI-6895517
Slc9a3r1P704413EBI-6115317,EBI-1184085

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P26361-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P26361-2)

The sequence of this isoform differs from the canonical sequence as follows:
     561-576: AVYKDADLYLLDSPFG → FLICLQTKDKVSLFRN
     577-1476: Missing.
Isoform 3 (identifier: P26361-3)

The sequence of this isoform differs from the canonical sequence as follows:
     561-600: AVYKDADLYL...VCKLMANKTR → QRTRSPYLEI...QYIKMLICTY
     601-1476: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14761476Cystic fibrosis transmembrane conductance regulator
PRO_0000093424

Regions

Topological domain1 – 8080Cytoplasmic Potential
Transmembrane81 – 10323Helical; Name=1; Potential
Topological domain104 – 11714Extracellular Potential
Transmembrane118 – 13821Helical; Name=2; Potential
Topological domain139 – 19456Cytoplasmic Potential
Transmembrane195 – 21521Helical; Name=3; Potential
Topological domain216 – 2205Extracellular Potential
Transmembrane221 – 24121Helical; Name=4; Potential
Topological domain242 – 30766Cytoplasmic Potential
Transmembrane308 – 32821Helical; Name=5; Potential
Topological domain329 – 3302Extracellular Potential
Transmembrane331 – 35020Helical; Name=6; Potential
Topological domain351 – 854504Cytoplasmic Potential
Transmembrane855 – 87521Helical; Name=7; Potential
Topological domain876 – 90631Extracellular Potential
Transmembrane907 – 92721Helical; Name=8; Potential
Topological domain928 – 98558Cytoplasmic Potential
Transmembrane986 – 100621Helical; Name=9; Potential
Topological domain1007 – 10082Extracellular Potential
Transmembrane1009 – 102921Helical; Name=10; Potential
Topological domain1030 – 109768Cytoplasmic Potential
Transmembrane1098 – 111821Helical; Name=11; Potential
Topological domain1119 – 11235Extracellular Potential
Transmembrane1124 – 114421Helical; Name=12; Potential
Topological domain1145 – 1476332Cytoplasmic Potential
Domain81 – 365285ABC transmembrane type-1 1
Domain423 – 646224ABC transporter 1
Domain854 – 1153300ABC transmembrane type-1 2
Domain1208 – 1439232ABC transporter 2
Nucleotide binding458 – 4658ATP 1 Potential
Nucleotide binding1240 – 12478ATP 2 Potential
Motif1474 – 14763PDZ-binding

Amino acid modifications

Modified residue5491Phosphoserine By similarity
Modified residue6601Phosphoserine By similarity
Modified residue6841Phosphoserine By similarity
Modified residue6981Phosphoserine By similarity
Modified residue7101Phosphoserine By similarity
Modified residue7151Phosphothreonine By similarity
Modified residue7321Phosphoserine By similarity
Modified residue7631Phosphoserine By similarity
Modified residue7851Phosphoserine By similarity
Modified residue7901Phosphoserine By similarity
Modified residue8081Phosphoserine By similarity
Modified residue14401Phosphoserine By similarity
Modified residue14521Phosphoserine By similarity
Lipidation5241S-palmitoyl cysteine By similarity
Lipidation13911S-palmitoyl cysteine By similarity
Glycosylation8891N-linked (GlcNAc...) Potential
Glycosylation8951N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence561 – 60040AVYKD…ANKTR → QRTRSPYLEIRIFLCLFLYT RMKVCATTPEQYIKMLICTY in isoform 3.
VSP_000064
Alternative sequence561 – 57616AVYKD…DSPFG → FLICLQTKDKVSLFRN in isoform 2.
VSP_000062
Alternative sequence577 – 1476900Missing in isoform 2.
VSP_000063
Alternative sequence601 – 1476876Missing in isoform 3.
VSP_000065

Experimental info

Sequence conflict20 – 223TTP → STA in AAF30300. Ref.3
Sequence conflict301H → Q in AAF30300. Ref.3
Sequence conflict410 – 4123EKV → QKA in AAA37417. Ref.1
Sequence conflict4621S → L in AAA37417. Ref.1
Sequence conflict6231S → T in AAA37417. Ref.1
Sequence conflict6391D → S in AAA37417. Ref.1

Secondary structure

....................................................... 1476
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 31, 2002. Version 2.
Checksum: 3D1B0BBDD80C1DA8

FASTA1,476167,870
        10         20         30         40         50         60 
MQKSPLEKAS FISKLFFSWT TPILRKGYRH HLELSDIYQA PSADSADHLS EKLEREWDRE 

        70         80         90        100        110        120 
QASKKNPQLI HALRRCFFWR FLFYGILLYL GEVTKAVQPV LLGRIIASYD PENKVERSIA 

       130        140        150        160        170        180 
IYLGIGLCLL FIVRTLLLHP AIFGLHRIGM QMRTAMFSLI YKKTLKLSSR VLDKISIGQL 

       190        200        210        220        230        240 
VSLLSNNLNK FDEGLALAHF IWIAPLQVTL LMGLLWDLLQ FSAFCGLGLL IILVIFQAIL 

       250        260        270        280        290        300 
GKMMVKYRDQ RAAKINERLV ITSEIIDNIY SVKAYCWESA MEKMIENLRE VELKMTRKAA 

       310        320        330        340        350        360 
YMRFFTSSAF FFSGFFVVFL SVLPYTVING IVLRKIFTTI SFCIVLRMSV TRQFPTAVQI 

       370        380        390        400        410        420 
WYDSFGMIRK IQDFLQKQEY KVLEYNLMTT GIIMENVTAF WEEGFGELLE KVQQSNGDRK 

       430        440        450        460        470        480 
HSSDENNVSF SHLCLVGNPV LKNINLNIEK GEMLAITGST GSGKTSLLML ILGELEASEG 

       490        500        510        520        530        540 
IIKHSGRVSF CSQFSWIMPG TIKENIIFGV SYDEYRYKSV VKACQLQQDI TKFAEQDNTV 

       550        560        570        580        590        600 
LGEGGVTLSG GQRARISLAR AVYKDADLYL LDSPFGYLDV FTEEQVFESC VCKLMANKTR 

       610        620        630        640        650        660 
ILVTSKMEHL RKADKILILH QGSSYFYGTF SELQSLRPDF SSKLMGYDTF DQFTEERRSS 

       670        680        690        700        710        720 
ILTETLRRFS VDDSSAPWSK PKQSFRQTGE VGEKRKNSIL NSFSSVRKIS IVQKTPLCID 

       730        740        750        760        770        780 
GESDDLQEKR LSLVPDSEQG EAALPRSNMI ATGPTFPGRR RQSVLDLMTF TPNSGSSNLQ 

       790        800        810        820        830        840 
RTRTSIRKIS LVPQISLNEV DVYSRRLSQD STLNITEEIN EEDLKECFLD DVIKIPPVTT 

       850        860        870        880        890        900 
WNTYLRYFTL HKGLLLVLIW CVLVFLVEVA ASLFVLWLLK NNPVNSGNNG TKISNSSYVV 

       910        920        930        940        950        960 
IITSTSFYYI FYIYVGVADT LLALSLFRGL PLVHTLITAS KILHRKMLHS ILHAPMSTIS 

       970        980        990       1000       1010       1020 
KLKAGGILNR FSKDIAILDD FLPLTIFDFI QLVFIVIGAI IVVSALQPYI FLATVPGLVV 

      1030       1040       1050       1060       1070       1080 
FILLRAYFLH TAQQLKQLES EGRSPIFTHL VTSLKGLWTL RAFRRQTYFE TLFHKALNLH 

      1090       1100       1110       1120       1130       1140 
TANWFMYLAT LRWFQMRIDM IFVLFFIVVT FISILTTGEG EGTAGIILTL AMNIMSTLQW 

      1150       1160       1170       1180       1190       1200 
AVNSSIDTDS LMRSVSRVFK FIDIQTEESM YTQIIKELPR EGSSDVLVIK NEHVKKSDIW 

      1210       1220       1230       1240       1250       1260 
PSGGEMVVKD LTVKYMDDGN AVLENISFSI SPGQRVGLLG RTGSGKSTLL SAFLRMLNIK 

      1270       1280       1290       1300       1310       1320 
GDIEIDGVSW NSVTLQEWRK AFGVITQKVF IFSGTFRQNL DPNGKWKDEE IWKVADEVGL 

      1330       1340       1350       1360       1370       1380 
KSVIEQFPGQ LNFTLVDGGY VLSHGHKQLM CLARSVLSKA KIILLDEPSA HLDPITYQVI 

      1390       1400       1410       1420       1430       1440 
RRVLKQAFAG CTVILCEHRI EAMLDCQRFL VIEESNVWQY DSLQALLSEK SIFQQAISSS 

      1450       1460       1470 
EKMRFFQGRH SSKHKPRTQI TALKEETEEE VQETRL 

« Hide

Isoform 2 [UniParc].

Checksum: 5EED7EC29AD39CFC
Show »

FASTA57665,799
Isoform 3 [UniParc].

Checksum: C8E6AE26516811C4
Show »

FASTA60068,782

References

[1]"Cloning the mouse homolog of the human cystic fibrosis transmembrane conductance regulator gene."
Tata F., Stanier P., Wicking C., Halford S., Kruyer H., Lench N.J., Scambler P.J., Hansen C., Braman J.C., Williamson R., Wainwright B.J.
Genomics 10:301-307(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Molecular cloning and sequence analysis of the murine cDNA for the cystic fibrosis transmembrane conductance regulator."
Yorifuji T., Lemna W.K., Ballard C.F., Rosenbloom C.L., Rozmahel R., Plavsic N., Tsui L.-C., Beaudet A.L.
Genomics 10:547-550(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
[3]"Comparative genomic sequence analysis of the human and mouse cystic fibrosis transmembrane conductance regulator genes."
Ellsworth R.E., Jamison D.C., Touchman J.W., Chissoe S.L., Braden Maduro V.V., Bouffard G.G., Dietrich N.L., Beckstrom-Sternberg S.M., Iyer L.M., Weintraub L.A., Cotton M., Courtney L., Edwards J., Maupin R., Ozersky P., Rohlfing T., Wohldmann P., Miner T. expand/collapse author list , Kemp K., Kramer J., Korf I., Pepin K., Antonacci-Fulton L., Fulton R.S., Minx P., Hillier L.W., Wilson R.K., Waterston R.H., Miller W., Green E.D.
Proc. Natl. Acad. Sci. U.S.A. 97:1172-1177(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"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.
[5]"Cystic fibrosis transmembrane conductance regulator splice variants are not conserved and fail to produce chloride channels."
Delaney S.J., Rich D.P., Thomson S.A., Hargrave M.R., Lovelock P.K., Welsh M.J., Wainwright B.J.
Nat. Genet. 4:426-431(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 549-600, ALTERNATIVE SPLICING.
Tissue: Testis.
[6]"Participation of the Cl-/HCO(3)- exchangers SLC26A3 and SLC26A6, the Cl- channel CFTR, and the regulatory factor SLC9A3R1 in mouse sperm capacitation."
Chavez J.C., Hernandez-Gonzalez E.O., Wertheimer E., Visconti P.E., Darszon A., Trevino C.L.
Biol. Reprod. 86:1-14(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH SLC26A3; SLC26A6 AND SLC9A3R1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M69298 mRNA. Translation: AAA37417.1.
M60493 mRNA. Translation: AAA18903.1.
AF162137 Genomic DNA. Translation: AAF30300.1.
L04873 Genomic DNA. Translation: AAA73562.1.
S65942, S65940, S65941 Genomic DNA. Translation: AAB28393.1.
S65942 Genomic DNA. Translation: AAB28391.1.
S65941, S65940 Genomic DNA. Translation: AAB28392.1.
PIRA39901.
A40303.
I49593.
I58115.
I78527.
RefSeqNP_066388.1. NM_021050.2.
XP_006505040.1. XM_006504977.1.
XP_006505041.1. XM_006504978.1.
UniGeneMm.15621.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1Q3HX-ray2.50A/B/C/D389-673[»]
1R0WX-ray2.20A/B/C/D389-673[»]
1R0XX-ray2.20A/B/C/D389-673[»]
1R0YX-ray2.55A/B/C/D389-673[»]
1R0ZX-ray2.35A/B/C/D389-673[»]
1R10X-ray3.00A/B389-673[»]
1XF9X-ray2.70A/B/C/D389-670[»]
1XFAX-ray3.10A/B389-670[»]
3SI7X-ray2.25A/B/C/D389-673[»]
ProteinModelPortalP26361.
SMRP26361. Positions 87-700, 943-1446.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198687. 2 interactions.
DIPDIP-29618N.
IntActP26361. 9 interactions.
MINTMINT-2841263.

PTM databases

PhosphoSiteP26361.

Proteomic databases

PRIDEP26361.

Protocols and materials databases

DNASU12638.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000045706; ENSMUSP00000049228; ENSMUSG00000041301. [P26361-1]
ENSMUST00000115405; ENSMUSP00000111064; ENSMUSG00000041301. [P26361-3]
ENSMUST00000140407; ENSMUSP00000116957; ENSMUSG00000041301. [P26361-2]
GeneID12638.
KEGGmmu:12638.
UCSCuc009bai.1. mouse. [P26361-1]

Organism-specific databases

CTD1080.
MGIMGI:88388. Cftr.

Phylogenomic databases

eggNOGCOG1132.
GeneTreeENSGT00750000117627.
HOGENOMHOG000185880.
HOVERGENHBG004169.
InParanoidP26361.
KOK05031.
OMATLAMNIM.
OrthoDBEOG7C2R0B.
PhylomeDBP26361.
TreeFamTF105200.

Enzyme and pathway databases

BRENDA3.6.3.49. 3474.

Gene expression databases

ArrayExpressP26361.
BgeeP26361.
GenevestigatorP26361.

Family and domain databases

Gene3D3.40.50.300. 2 hits.
InterProIPR003593. AAA+_ATPase.
IPR011527. ABC1_TM_dom.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR001140. ABC_transptr_TM_dom.
IPR005291. cAMP_cl_channel.
IPR025837. CFTR_reg_dom.
IPR009147. CysFib_conduc_TM.
IPR027417. P-loop_NTPase.
[Graphical view]
PfamPF00664. ABC_membrane. 2 hits.
PF00005. ABC_tran. 2 hits.
PF14396. CFTR_R. 1 hit.
[Graphical view]
PRINTSPR01851. CYSFIBREGLTR.
SMARTSM00382. AAA. 2 hits.
[Graphical view]
SUPFAMSSF52540. SSF52540. 2 hits.
SSF90123. SSF90123. 3 hits.
TIGRFAMsTIGR01271. CFTR_protein. 1 hit.
PROSITEPS50929. ABC_TM1F. 2 hits.
PS00211. ABC_TRANSPORTER_1. 1 hit.
PS50893. ABC_TRANSPORTER_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP26361.
NextBio281830.
PROP26361.
SOURCESearch...

Entry information

Entry nameCFTR_MOUSE
AccessionPrimary (citable) accession number: P26361
Secondary accession number(s): Q63893, Q63894, Q9JKQ6
Entry history
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: January 31, 2002
Last modified: April 16, 2014
This is version 145 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot