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Protein

Cystic fibrosis transmembrane conductance regulator

Gene

CFTR

Organism
Squalus acanthias (Spiny dogfish)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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 (By similarity).By similarity

Catalytic activityi

ATP + H2O = ADP + phosphate.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei402ATP 1By similarity1
Binding sitei435ATP 1By similarity1
Binding sitei494ATP 1By similarity1
Binding sitei1229ATP 2By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi459 – 466ATP 1PROSITE-ProRule annotation8
Nucleotide bindingi1254 – 1261ATP 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)
Dogfish transmembrane conductance regulator
cAMP-dependent chloride channel
Gene namesi
Name:CFTR
Synonyms:ABCC7, DFTR
OrganismiSqualus acanthias (Spiny dogfish)
Taxonomic identifieri7797 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataChondrichthyesElasmobranchiiSqualimorphiiSqualiformesSqualidaeSqualus

Subcellular locationi

  • Apical cell membrane 1 Publication; Multi-pass membrane protein By similarity
  • Early endosome membrane By similarity; Multi-pass membrane protein By similarity
  • Cell membrane By similarity; Multi-pass membrane protein By similarity
  • Recycling endosome membrane By similarity; Multi-pass membrane protein By similarity
  • Endoplasmic reticulum membrane By similarity; Multi-pass membrane protein By similarity

  • Note: The channel is internalized from the cell surface into an endosomal recycling compartment, from where it is recycled to the cell membrane.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 78CytoplasmicBy similarityAdd BLAST78
Transmembranei79 – 99Helical; Name=1By similarityAdd BLAST21
Topological domaini100 – 123ExtracellularBy similarityAdd BLAST24
Transmembranei124 – 147Helical; Name=2By similarityAdd BLAST24
Topological domaini148 – 196CytoplasmicBy similarityAdd BLAST49
Transmembranei197 – 217Helical; Name=3By similarityAdd BLAST21
Topological domaini218 – 223ExtracellularBy similarity6
Transmembranei224 – 244Helical; Name=4By similarityAdd BLAST21
Topological domaini245 – 299CytoplasmicBy similarityAdd BLAST55
Transmembranei300 – 320Helical; Name=5By similarityAdd BLAST21
Topological domaini321 – 340ExtracellularBy similarityAdd BLAST20
Transmembranei341 – 359Helical; Name=6By similarityAdd BLAST19
Topological domaini360 – 867CytoplasmicBy similarityAdd BLAST508
Transmembranei868 – 888Helical; Name=7By similarityAdd BLAST21
Topological domaini889 – 932ExtracellularBy similarityAdd BLAST44
Transmembranei933 – 953Discontinuously helical; Name=8By similarityAdd BLAST21
Topological domaini954 – 1004CytoplasmicBy similarityAdd BLAST51
Transmembranei1005 – 1025Helical; Name=9By similarityAdd BLAST21
Topological domaini1026 – 1027ExtracellularBy similarity2
Transmembranei1028 – 1048Helical; Name=10By similarityAdd BLAST21
Topological domaini1049 – 1109CytoplasmicBy similarityAdd BLAST61
Transmembranei1110 – 1130Helical; Name=11By similarityAdd BLAST21
Topological domaini1131 – 1144ExtracellularBy similarityAdd BLAST14
Transmembranei1145 – 1165Helical; Name=12By similarityAdd BLAST21
Topological domaini1166 – 1492CytoplasmicBy similarityAdd BLAST327

GO - Cellular componenti

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Endosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000934311 – 1492Cystic fibrosis transmembrane conductance regulatorAdd BLAST1492

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi905N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi923N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

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.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiP26362.

Expressioni

Tissue specificityi

Expressed in the rectal gland (at protein level).1 Publication

Interactioni

Subunit structurei

Monomer; does not require oligomerization for channel activity. May form oligomers in the membrane (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliP26362.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini82 – 366ABC transmembrane type-1 1PROSITE-ProRule annotationAdd BLAST285
Domaini424 – 647ABC transporter 1PROSITE-ProRule annotationAdd BLAST224
Domaini868 – 1169ABC transmembrane type-1 2PROSITE-ProRule annotationAdd BLAST302
Domaini1220 – 1453ABC transporter 2PROSITE-ProRule annotationAdd BLAST234

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni655 – 840Intrinsically disordered R regionBy similarityAdd BLAST186

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1483 – 1485PDZ-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 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

HOVERGENiHBG004169.

Family and domain databases

InterProiView protein in InterPro
IPR003593. 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.
PANTHERiPTHR24223:SF273. PTHR24223:SF273. 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. 3 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.

P26362-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRSPIEKAN AFSKLFFRWP RPILKKGYRQ KLELSDIYQI PSSDSADELS
60 70 80 90 100
EMLEREWDRE LATSKKNPKL VNALRRCFFW RFLFYGILLY FVEFTKAVQP
110 120 130 140 150
LCLGRIIASY NAKNTYEREI AYYLALGLCL LFVVRTLFLH PAVFGLQHLG
160 170 180 190 200
MQMRIALFSL IYKKILKMSS RVLDKIDTGQ LVSLLSNNLN KFDEGVAVAH
210 220 230 240 250
FVWIAPVQVV LLMGLIWNEL TEFVFCGLGF LIMLALFQAW LGKKMMQYRD
260 270 280 290 300
KRAGKINERL AITSEIIDNI QSVKVYCWED AMEKIIDDIR QVELKLTRKV
310 320 330 340 350
AYCRYFSSSA FFFSGFFVVF LSVVPYAFIH TIKLRRIFTT ISYNIVLRMT
360 370 380 390 400
VTRQFPSAIQ TWYDSLGAIR KIQDFLHKDE HKTVEYNLTT KEVEMVNVTA
410 420 430 440 450
SWDEGIGELF EKVKQNDSER KMANGDDGLF FSNFSLHVTP VLKNISFKLE
460 470 480 490 500
KGELLAIAGS TGSGKSSLLM MIMGELEPSD GKIKHSGRIS YSPQVPWIMP
510 520 530 540 550
GTIKDNIIFG LSYDEYRYTS VVNACQLEED ITVFPNKDKT VLGDGGITLS
560 570 580 590 600
GGQRARISLA RALYKDADLY LLDSPFSHLD VTTEKDIFES CLCKLMVNKT
610 620 630 640 650
RILVTSKLEH LKKADKILLL HEGHCYFYGT FSELQGEKPD FSSQLLGSVH
660 670 680 690 700
FDSFSAERRN SILTETFRRC SVSSGDGAGL GSYSETRKAS FKQPPPEFNE
710 720 730 740 750
KRKSSLIVNP ITSNKKFSLV QTAMSYPQTN GMEDATSEPG ERHFSLIPEN
760 770 780 790 800
ELGEPTKPRS NIFKSELPFQ AHRRQSVLAL MTHSSTSPNK IHARRSAVRK
810 820 830 840 850
MSMLSQTNFA SSEIDIYSRR LSEDGSFEIS EEINEEDLKE CFADEEEIQN
860 870 880 890 900
VTTTWSTYLR YVTTNRNLVF VLILCLVIFL AEVAASLAGL WIISGLAINT
910 920 930 940 950
GSQTNDTSTD LSHLSVFSKF ITNGSHYYIF YIYVGLADSF LALGVIRGLP
960 970 980 990 1000
LVHTLVTVSK DLHKQMLHSV LQGPMTAFNK MKAGRILNRF IKDTAIIDDM
1010 1020 1030 1040 1050
LPLTVFDFVQ LILIVVGAIC VVSVLQPYTL LAAIPVAVIF IMLRAYFLRT
1060 1070 1080 1090 1100
SQQLKQLESE ARSPIFSHLI TSLRGLWTVR AFGRQSYFET LFHKALNLHT
1110 1120 1130 1140 1150
ANWFLYLSTL RWFQMRIDIV FVLFFIAVTF IAIATHDVGE GQVGIILTLA
1160 1170 1180 1190 1200
MNITSTLQWA VNSSIDVDGL MRSVSRVFKY IDIPPEGSET KNRHNANNPS
1210 1220 1230 1240 1250
DVLVIENKHL TKEWPSGGQM MVNNLTAKYT SDGRAVLQDL SFSVNAGQRV
1260 1270 1280 1290 1300
GLLGRTGAGK STLLSALLRL LSTEGEIQID GISWNSVSLQ KWRKAFGVIP
1310 1320 1330 1340 1350
QKVFVFSGTF RKNLDPYEQW SDEEIWKVTE EVGLKSMIEQ FPDKLNFVLV
1360 1370 1380 1390 1400
DGGYILSNGH KQLMCLARSI LSKAKILLLD EPTAHLDPVT FQIIRKTLKH
1410 1420 1430 1440 1450
TFSNCTVILS EHRVEALLEC QQFLVIEGCS VKQFDALQKL LTEASLFKQV
1460 1470 1480 1490
FGHLDRAKLF TAHRRNSSKR KTRPKISALQ EEAEEDLQET RL
Length:1,492
Mass (Da):169,385
Last modified:May 1, 1992 - v1
Checksum:i0E49CA89968FC2F9
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M83785 mRNA. Translation: AAA49616.1.
PIRiA39322.

Similar proteinsi

Entry informationi

Entry nameiCFTR_SQUAC
AccessioniPrimary (citable) accession number: P26362
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: May 1, 1992
Last modified: May 10, 2017
This is version 111 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Documents

  1. SIMILARITY comments
    Index of protein domains and families