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Protein

Cystic fibrosis transmembrane conductance regulator

Gene

CFTR

Organism
Ovis aries (Sheep)
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 bindingi457 – 4648ATP 1PROSITE-ProRule annotation
Nucleotide bindingi1245 – 12528ATP 2PROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

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
OrganismiOvis aries (Sheep)
Taxonomic identifieri9940 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeCaprinaeOvis
Proteomesi
  • UP000002356 Componenti: Chromosome 4

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 – 10121Helical; Name=1PROSITE-ProRule annotationAdd
BLAST
Topological domaini102 – 11716ExtracellularSequence 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 – 3313ExtracellularSequence analysis
Transmembranei332 – 35019Helical; Name=6PROSITE-ProRule annotationAdd
BLAST
Topological domaini351 – 859509CytoplasmicSequence analysisAdd
BLAST
Transmembranei860 – 88021Helical; Name=7PROSITE-ProRule annotationAdd
BLAST
Topological domaini881 – 91131ExtracellularSequence analysisAdd
BLAST
Transmembranei912 – 93221Helical; Name=8PROSITE-ProRule annotationAdd
BLAST
Topological domaini933 – 99058CytoplasmicSequence analysisAdd
BLAST
Transmembranei991 – 101121Helical; Name=9PROSITE-ProRule annotationAdd
BLAST
Topological domaini1012 – 10132ExtracellularSequence analysis
Transmembranei1014 – 103421Helical; Name=10PROSITE-ProRule annotationAdd
BLAST
Topological domaini1035 – 110268CytoplasmicSequence analysisAdd
BLAST
Transmembranei1103 – 112321Helical; Name=11PROSITE-ProRule annotationAdd
BLAST
Topological domaini1124 – 11263ExtracellularSequence analysis
Transmembranei1127 – 114721Helical; Name=12PROSITE-ProRule annotationAdd
BLAST
Topological domaini1148 – 1481334CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 14811481Cystic fibrosis transmembrane conductance regulatorPRO_0000093429Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Lipidationi523 – 5231S-palmitoyl cysteineBy similarity
Modified residuei548 – 5481PhosphoserineBy similarity
Modified residuei659 – 6591PhosphoserineBy similarity
Modified residuei685 – 6851PhosphoserineBy similarity
Cross-linki687 – 687Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei699 – 6991PhosphoserineBy similarity
Modified residuei711 – 7111PhosphoserineBy similarity
Modified residuei716 – 7161PhosphothreonineBy similarity
Modified residuei736 – 7361PhosphoserineBy similarity
Modified residuei767 – 7671PhosphoserineBy similarity
Modified residuei790 – 7901PhosphoserineBy similarity
Modified residuei795 – 7951PhosphoserineBy similarity
Modified residuei813 – 8131PhosphoserineBy similarity
Glycosylationi894 – 8941N-linked (GlcNAc...)Sequence analysis
Glycosylationi898 – 8981N-linked (GlcNAc...)Sequence analysis
Lipidationi1396 – 13961S-palmitoyl cysteineBy similarity
Modified residuei1457 – 14571PhosphoserineBy 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, Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Expressioni

Gene expression databases

ExpressionAtlasiQ00555. baseline.

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

Structurei

Secondary structure

1
1481
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi502 – 5065Combined sources
Helixi508 – 51710Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CKWNMR-A497-522[»]
1CKXNMR-A497-522[»]
1CKYNMR-A497-522[»]
1CKZNMR-A497-522[»]
ProteinModelPortaliQ00555.
SMRiQ00555. Positions 389-670.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ00555.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini81 – 365285ABC transmembrane type-1 1PROSITE-ProRule annotationAdd
BLAST
Domaini421 – 645225ABC transporter 1PROSITE-ProRule annotationAdd
BLAST
Domaini859 – 1155297ABC transmembrane type-1 2PROSITE-ProRule annotationAdd
BLAST
Domaini1211 – 1444234ABC transporter 2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1479 – 14813PDZ-binding

Domaini

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

GeneTreeiENSGT00840000129721.
HOVERGENiHBG004169.
KOiK05031.

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. 2 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.

Q00555-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRSPLEKAS VVSKLFFSWT RPILKKGYRQ RLELSDIYHI SSSDSADNLS
60 70 80 90 100
EKLEREWDRE LASKKNPKLI NALRRCFFWR FMFYGIILYL GEVTKAVQPL
110 120 130 140 150
LLGRIIASYD PDNKVERSIA IYLGIGLCLL FIVRTLLLHP AIFGLHHIGM
160 170 180 190 200
QMRIAMFSLI YKKTLKLSSR VLDKISIGQL VSLLSNNLNK FDEGLALAHF
210 220 230 240 250
VWIAPLQVTL LMGLLWDLLQ AFTFCGLAFL VVLALLQAGL GKMMMKYRDQ
260 270 280 290 300
RAGKINERLV ITSEMIENIQ SVKAYCWEEA MEKIIENLRQ TELKLTRKAA
310 320 330 340 350
YVRYLNSSAF FFSGFFVVFL SVLPYALLKG IILRKIFTTI SFCIVLRMAV
360 370 380 390 400
TRQFPWAVQT WYDSLGAINK IQDFLQKQEY KTLEYNLTTT DVVMENVTAF
410 420 430 440 450
WEEGFSKLFE KAKENNNNRK ISNCDTSLFF SNLLLGTPVL KDISFKIERG
460 470 480 490 500
QLLAVAGSTG AGKTSLLMMI MGELEPSEGK IKHSGRISFC SQYSWIMPGT
510 520 530 540 550
IKDNIIFGVS YDEYRYRSVI KACQLEEDIS KFSEKDNIVL GEGGITLSGG
560 570 580 590 600
QRARISLARA VYKDADLYLL DSPFGYLDVL TEKEIFESCV CKLMANKTRI
610 620 630 640 650
LVTSKMEHLK KADKILILHE GSVYFYGTFS ELQNQRPDFS SKLMGCDTFD
660 670 680 690 700
QFTAERRNSI ITETLRRFSL EGDTSVSWNE TKKPSFKQTG EFGEKRKNSI
710 720 730 740 750
LNSINSIRKF SVVQKTSLQM NGIDGASDEP LERRLSLVPH SEPGEGILPR
760 770 780 790 800
SNAVNSGPTF LGGRRQSVLN LMTCSSVNQG QSIHRKTATS TRKMSLAPQA
810 820 830 840 850
SLAEIDIYSR RLSQDTGLEI SEEINEEDLR DCFFDDVENI PAVTTWNTYL
860 870 880 890 900
RYITVHKSLM FVLIWCLVVF LVEVAASLVV LCLFPKILLQ DKGNSTKNAS
910 920 930 940 950
NSYAVIITST SSYYIFYIYV GVADTLLALG LFRGLPLVHT LITVSKTLHH
960 970 980 990 1000
KMLQSVLQAP MSTLNTLKTG GILNRFSKDI AVLDDLLPLT IFDFIQLLLI
1010 1020 1030 1040 1050
VIGAVVVVSV LQPYIFLATV PVIAAFILLR GYFLHTSQQL KQLESEGRSP
1060 1070 1080 1090 1100
IFTHLVTSLK GLWTLRAFGR QPYFETLFHK ALNLHTANWF LYLSTLRWFQ
1110 1120 1130 1140 1150
MRIEMIFVIF FIAVTFISIL TTGEGEGRVG IILTLAMNIM GTLQWAVNSS
1160 1170 1180 1190 1200
IDVDSLMRSV SRVFKFIDMP TEDGKPNNSF RPSKDSQPSK VMIIENQHVK
1210 1220 1230 1240 1250
KDDIWPSGGQ MTVKDLTAKY IDGGNAILEN ISFSISPGQR VGLLGRTGSG
1260 1270 1280 1290 1300
KSTLLLAFLR LLNTKGEIQI DGVSWDSITL QQWRKAFGVI PQKVFIFSGT
1310 1320 1330 1340 1350
FRKNLDPYEQ WSDQEIWKVA DEVGLRSVIE QFPGKLDFVL VDGGCVLSHG
1360 1370 1380 1390 1400
HKQLMCLARS VLSKAKILLL DEPSAHLDPI TYQIIRRTLK QAFADCTVIL
1410 1420 1430 1440 1450
SEHRIEAMLE CQRFLVIEEN KVRQYDSIQR MLSEKSLFRQ AISPADRLKL
1460 1470 1480
LPHRNSSRQR SRANIAALKE ETEEEVQETK L
Length:1,481
Mass (Da):167,927
Last modified:November 1, 1997 - v2
Checksum:iFCAB69E8205B6E32
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti600 – 6023ILV → TTL in AAA31514 (PubMed:1719001).Curated
Sequence conflicti668 – 6681F → L in AAA31514 (PubMed:1719001).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti297 – 2971R → Q.1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20418 mRNA. Translation: AAA68600.1.
DP000179 Genomic DNA. Translation: ABI75298.1.
M96682 Genomic DNA. Translation: AAA31514.1.
PIRiB39323.
RefSeqiNP_001009781.1. NM_001009781.1.
UniGeneiOar.402.

Genome annotation databases

EnsembliENSOART00000019744; ENSOARP00000019473; ENSOARG00000018133.
GeneIDi443347.
KEGGioas:443347.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U20418 mRNA. Translation: AAA68600.1.
DP000179 Genomic DNA. Translation: ABI75298.1.
M96682 Genomic DNA. Translation: AAA31514.1.
PIRiB39323.
RefSeqiNP_001009781.1. NM_001009781.1.
UniGeneiOar.402.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1CKWNMR-A497-522[»]
1CKXNMR-A497-522[»]
1CKYNMR-A497-522[»]
1CKZNMR-A497-522[»]
ProteinModelPortaliQ00555.
SMRiQ00555. Positions 389-670.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

DNASUi443347.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSOART00000019744; ENSOARP00000019473; ENSOARG00000018133.
GeneIDi443347.
KEGGioas:443347.

Organism-specific databases

CTDi1080.

Phylogenomic databases

GeneTreeiENSGT00840000129721.
HOVERGENiHBG004169.
KOiK05031.

Miscellaneous databases

EvolutionaryTraceiQ00555.

Gene expression databases

ExpressionAtlasiQ00555. baseline.

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. 2 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_SHEEP
AccessioniPrimary (citable) accession number: Q00555
Secondary accession number(s): Q09YI2, Q28544
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: November 1, 1997
Last modified: July 6, 2016
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.