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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

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 bindingi457 – 464ATP 1PROSITE-ProRule annotation8
Nucleotide bindingi1245 – 1252ATP 2PROSITE-ProRule annotation8

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

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 – 859CytoplasmicSequence analysisAdd BLAST509
Transmembranei860 – 880Helical; Name=7PROSITE-ProRule annotationAdd BLAST21
Topological domaini881 – 911ExtracellularSequence analysisAdd BLAST31
Transmembranei912 – 932Helical; Name=8PROSITE-ProRule annotationAdd BLAST21
Topological domaini933 – 990CytoplasmicSequence analysisAdd BLAST58
Transmembranei991 – 1011Helical; Name=9PROSITE-ProRule annotationAdd BLAST21
Topological domaini1012 – 1013ExtracellularSequence analysis2
Transmembranei1014 – 1034Helical; Name=10PROSITE-ProRule annotationAdd BLAST21
Topological domaini1035 – 1102CytoplasmicSequence analysisAdd BLAST68
Transmembranei1103 – 1123Helical; Name=11PROSITE-ProRule annotationAdd BLAST21
Topological domaini1124 – 1128ExtracellularSequence analysis5
Transmembranei1129 – 1149Helical; Name=12PROSITE-ProRule annotationAdd BLAST21
Topological domaini1150 – 1481CytoplasmicSequence analysisAdd BLAST332

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, 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 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...)Sequence analysis1
Glycosylationi900N-linked (GlcNAc...)Sequence analysis1
Lipidationi1396S-palmitoyl cysteineBy similarity1
Modified residuei1457PhosphoserineBy 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, Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP35071.
PRIDEiP35071.

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

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

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1479 – 1481PDZ-binding3

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

eggNOGiKOG0054. Eukaryota.
COG1132. LUCA.
HOVERGENiHBG004169.
InParanoidiP35071.
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.

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliP35071.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000049907.

Proteomic databases

PaxDbiP35071.
PRIDEiP35071.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi281067.
KEGGibta:281067.

Organism-specific databases

CTDi1080.

Phylogenomic databases

eggNOGiKOG0054. Eukaryota.
COG1132. LUCA.
HOVERGENiHBG004169.
InParanoidiP35071.
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]
ProtoNetiSearch...

Entry informationi

Entry nameiCFTR_BOVIN
AccessioniPrimary (citable) accession number: P35071
Secondary accession number(s): A4D7S2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: May 1, 2007
Last modified: October 5, 2016
This is version 132 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

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.