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Protein

Cystic fibrosis transmembrane conductance regulator

Gene

CFTR

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 sitei492ATP 1By similarity1
Binding sitei1220ATP 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi457 – 464ATP 1PROSITE-ProRule annotation8
Nucleotide bindingi1245 – 1252ATP 2PROSITE-ProRule annotation8

GO - Molecular functioni

GO - Biological processi

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
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 – 858CytoplasmicBy similarityAdd BLAST500
Transmembranei859 – 879Helical; Name=7By similarityAdd BLAST21
Topological domaini880 – 918ExtracellularBy similarityAdd BLAST39
Transmembranei919 – 939Discontinuously helical; Name=8By similarityAdd BLAST21
Topological domaini940 – 990CytoplasmicBy similarityAdd BLAST51
Transmembranei991 – 1011Helical; Name=9By similarityAdd BLAST21
Topological domaini1012 – 1013ExtracellularBy similarity2
Transmembranei1014 – 1034Helical; Name=10By similarityAdd BLAST21
Topological domaini1035 – 1095CytoplasmicBy similarityAdd BLAST61
Transmembranei1096 – 1116Helical; Name=11By similarityAdd BLAST21
Topological domaini1117 – 1130ExtracellularBy similarityAdd BLAST14
Transmembranei1131 – 1151Helical; Name=12By similarityAdd BLAST21
Topological domaini1152 – 1481CytoplasmicBy similarityAdd BLAST330

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000934161 – 1481Cystic fibrosis transmembrane conductance regulatorAdd BLAST1481

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi523S-palmitoyl cysteineBy similarity1
Modified residuei548PhosphoserineBy similarity1
Modified residuei659Phosphoserine; by PKABy similarity1
Modified residuei669Phosphoserine; by PKABy similarity1
Modified residuei685Phosphoserine; by PKCBy similarity1
Cross-linki687Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei699Phosphoserine; by PKABy similarity1
Modified residuei711PhosphoserineBy similarity1
Modified residuei716PhosphothreonineBy similarity1
Modified residuei736Phosphoserine; by PKABy similarity1
Modified residuei767Phosphoserine; by PKABy similarity1
Modified residuei790Phosphoserine; by PKCBy similarity1
Modified residuei795Phosphoserine; by PKABy similarity1
Modified residuei813Phosphoserine; by PKABy similarity1
Glycosylationi894N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi900N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi1396S-palmitoyl cysteineBy similarity1
Modified residuei1457PhosphoserineBy 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, Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP35071.
PRIDEiP35071.

Interactioni

Subunit structurei

Monomer; does not require oligomerization for channel activity. May form oligomers in the membrane (By similarity). Interacts with SLC26A3, SLC26A6 and SLC9A3R1 (By similarity). Interacts with SHANK2 (By similarity). Interacts with MYO6 (By similarity). Interacts (via C-terminus) with GOPC (via PDZ domain); this promotes CFTR internalization and thereby decreases channel activity. 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 similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000049907.

Structurei

3D structure databases

ProteinModelPortaliP35071.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini81 – 365ABC transmembrane type-1 1PROSITE-ProRule annotationAdd BLAST285
Domaini423 – 645ABC transporter 1PROSITE-ProRule annotationAdd BLAST223
Domaini859 – 1155ABC transmembrane type-1 2PROSITE-ProRule annotationAdd BLAST297
Domaini1211 – 1444ABC transporter 2PROSITE-ProRule annotationAdd BLAST234

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni653 – 831Intrinsically disordered R regionBy similarityAdd BLAST179

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1479 – 1481PDZ-bindingBy similarity3

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.
InParanoidiP35071.
KOiK05031.

Family and domain databases

Gene3Di1.20.1560.10. 2 hits.
InterProiView protein in InterPro
IPR003593. AAA+_ATPase.
IPR011527. ABC1_TM_dom.
IPR036640. ABC1_TM_sf.
IPR003439. ABC_transporter-like.
IPR017871. ABC_transporter_CS.
IPR009147. CFTR/ABCC7.
IPR025837. CFTR_reg_dom.
IPR027417. P-loop_NTPase.
PANTHERiPTHR24223:SF19. PTHR24223:SF19. 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. 2 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.

P35071-1 [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 LMGLLWELLQ AFTFCGLAFL IVLALLQAGL 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 KAKENNNSRK ISNGDNSLFF SNLLLGTPVL KDISFKIERG
460 470 480 490 500
QLLAVAGSTG AGKTSLLMMI MGELEPSEGK IKHSGRISFC SQYSWIMPGT
510 520 530 540 550
IKDNIIFGVS YDEYRYRSVI KACQLEEDIS KFAEKDNVVL GEGGITLSGG
560 570 580 590 600
QRARISLARA VYKDADLYLL DSPFGYLDVL TEKEIFESCI CKLMANKTRI
610 620 630 640 650
LVTSKMEHLK KADKILILHE GSIYFYGTFS ELQNQRPDFS SKLMGCDTFD
660 670 680 690 700
QFTAERRNSI ITETLRRFSL EGDTSVSWNE TKKPSFKQTG EFGEKRKNSI
710 720 730 740 750
LSSINSIRKF SVVQKTSLQM NGIEGAADAP LERRLSLVPH SEPGEGILPR
760 770 780 790 800
SNAVNSGPTF LGGRRQSVLN LMTGSSVNQG QSIHRKTATS TRKMSLAPQA
810 820 830 840 850
SLAEIDIYSR RLSQDTGLEI SEEINEEDLR DCFFDDVENI PAVTTWNTYL
860 870 880 890 900
RYITVHKSLM FVLIWCLVVF LVEVAASLVV LCLFPKIFFQ DKGNSTKSAN
910 920 930 940 950
NSYAVIITST SSYYIFYIYV GVADTLLALG LFRGLPLVHT LITVSKTLHH
960 970 980 990 1000
KMLQSVLQAP MSTLNTLKTG GILNRFSKDI AVLDDLLPLT IFDFVQLLLI
1010 1020 1030 1040 1050
VIGAVVVVSV LQPYIFLATV PVIAAFILLR AYFLHTSQQL 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 TDGGNAILEN ISFSISPGQR VGLLGRTGSG
1260 1270 1280 1290 1300
KSTLLLAFLR LLNTKGEIQI DGVSWDSITL QQWRKAFGVI PQKVFIFSGT
1310 1320 1330 1340 1350
FRKNLDPYGQ WSDQEIWKVA DEVGLRSVIE QFPGKLDFVL VDGGCVLSHG
1360 1370 1380 1390 1400
HKQLMCLARS VLSKAKILLL DEPSAHLDPI TYQIIRRTLK QAFANCTVIL
1410 1420 1430 1440 1450
SEHRIEAMLE CQRFLVIEEN KVRQYDSIQR MLSEKSLFRQ AISPADRLKL
1460 1470 1480
LPHRNSSRQR SRSNIAALKE ETEEEVQETK L
Length:1,481
Mass (Da):167,758
Last modified:May 1, 2007 - v2
Checksum:i8368B627796D2D4B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti15L → V in AAA30772 (PubMed:1719001).Curated1
Sequence conflicti179Q → R in AAA30772 (PubMed:1719001).Curated1
Sequence conflicti259L → V in AAA30772 (PubMed:1719001).Curated1
Sequence conflicti395E → D in AAA30772 (PubMed:1719001).Curated1
Sequence conflicti418S → N in AAA30772 (PubMed:1719001).Curated1
Sequence conflicti468M → L in AAA30772 (PubMed:1719001).Curated1
Sequence conflicti476P → A in AAA30772 (PubMed:1719001).Curated1
Sequence conflicti1068 – 1069FG → LD in AAA30772 (PubMed:1719001).Curated2
Sequence conflicti1237P → S in AAA30772 (PubMed:1719001).Curated1
Sequence conflicti1327S → A in AAA30772 (PubMed:1719001).Curated1
Sequence conflicti1415L → F in AAA30772 (PubMed:1719001).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M76128 mRNA. Translation: AAA30772.1.
DP000008 Genomic DNA. Translation: AAR16263.1.
PIRiA39323.
RefSeqiNP_776443.1. NM_174018.2.
UniGeneiBt.111372.

Genome annotation databases

GeneIDi281067.
KEGGibta:281067.

Similar proteinsi

Entry informationi

Entry nameiCFTR_BOVIN
AccessioniPrimary (citable) accession number: P35071
Secondary accession number(s): A4D7S2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: May 1, 2007
Last modified: October 25, 2017
This is version 138 of the entry and version 2 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