CFTR_XENLA
ID CFTR_XENLA Reviewed; 1485 AA.
AC P26363;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1992, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Cystic fibrosis transmembrane conductance regulator;
DE Short=CFTR;
DE AltName: Full=ATP-binding cassette sub-family C member 7;
DE AltName: Full=Channel conductance-controlling ATPase;
DE EC=5.6.1.6 {ECO:0000250|UniProtKB:P13569};
DE AltName: Full=cAMP-dependent chloride channel;
GN Name=cftr; Synonyms=abcc7;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1284470; DOI=10.1093/hmg/1.2.77;
RA Tucker S.J., Tannahill D., Higgins C.F.;
RT "Identification and developmental expression of the Xenopus laevis cystic
RT fibrosis transmembrane conductance regulator gene.";
RL Hum. Mol. Genet. 1:77-82(1992).
CC -!- FUNCTION: Epithelial ion channel that plays an important role in the
CC regulation of epithelial ion and water transport and fluid homeostasis.
CC Mediates the transport of chloride ions across the cell membrane (By
CC similarity). Channel activity is coupled to ATP hydrolysis. The ion
CC channel is also permeable to HCO(3)(-); selectivity depends on the
CC extracellular chloride concentration. Exerts its function also by
CC modulating the activity of other ion channels and transporters.
CC Contributes to the regulation of the pH and the ion content of the
CC epithelial fluid layer (By similarity). {ECO:0000250|UniProtKB:P13569,
CC ECO:0000250|UniProtKB:P26361}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + closed Cl(-) channel = ADP + phosphate + open
CC Cl(-) channel.; EC=5.6.1.6; Evidence={ECO:0000250|UniProtKB:P13569};
CC -!- SUBUNIT: Monomer; does not require oligomerization for channel
CC activity. May form oligomers in the membrane (By similarity).
CC {ECO:0000250|UniProtKB:P13569}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000250|UniProtKB:P26361}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P13569}. Early endosome membrane
CC {ECO:0000250|UniProtKB:P13569}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P13569}. Cell membrane
CC {ECO:0000250|UniProtKB:P26361}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P13569}. Recycling endosome membrane
CC {ECO:0000250|UniProtKB:P13569}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P13569}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P13569}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P13569}. Note=The channel is internalized from
CC the cell surface into an endosomal recycling compartment, from where it
CC is recycled to the cell membrane. {ECO:0000250|UniProtKB:P13569}.
CC -!- DOMAIN: Binds and hydrolyzes ATP via the two cytoplasmic ABC
CC transporter nucleotide-binding domains. The two ATP-binding domains
CC interact with each other, forming a head-to-tail dimer. Normal ATPase
CC activity requires interaction between the two domains. The first ABC
CC transporter nucleotide-binding domain has no ATPase activity by itself.
CC {ECO:0000250|UniProtKB:P13569, ECO:0000250|UniProtKB:P26361}.
CC -!- DOMAIN: The disordered R region mediates channel activation when it is
CC phosphorylated, but not in the absence of phosphorylation.
CC {ECO:0000250|UniProtKB:P13569}.
CC -!- PTM: Phosphorylated; cAMP treatment promotes phosphorylation and
CC activates the channel. Dephosphorylation decreases the ATPase activity
CC (in vitro). Phosphorylation at PKA sites activates the channel.
CC Phosphorylation at PKC sites enhances the response to phosphorylation
CC by PKA. {ECO:0000250|UniProtKB:P13569}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family.
CC CFTR transporter (TC 3.A.1.202) subfamily. {ECO:0000305}.
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DR EMBL; X65256; CAA46348.1; -; mRNA.
DR PIR; S23756; S23756.
DR AlphaFoldDB; P26363; -.
DR SMR; P26363; -.
DR PRIDE; P26363; -.
DR Proteomes; UP000186698; Genome assembly.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB.
DR GO; GO:0015106; F:bicarbonate transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005254; F:chloride channel activity; ISS:UniProtKB.
DR GO; GO:0015108; F:chloride transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0005260; F:intracellularly ATP-gated chloride channel activity; ISS:UniProtKB.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0015701; P:bicarbonate transport; ISS:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:1904322; P:cellular response to forskolin; ISS:UniProtKB.
DR GO; GO:1902476; P:chloride transmembrane transport; ISS:UniProtKB.
DR GO; GO:0051454; P:intracellular pH elevation; ISS:UniProtKB.
DR GO; GO:0060081; P:membrane hyperpolarization; ISS:UniProtKB.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; ISS:UniProtKB.
DR GO; GO:0048240; P:sperm capacitation; ISS:UniProtKB.
DR GO; GO:0035377; P:transepithelial water transport; ISS:UniProtKB.
DR Gene3D; 1.20.1560.10; -; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR009147; CFTR/ABCC7.
DR InterPro; IPR025837; CFTR_reg_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR24223:SF19; PTHR24223:SF19; 1.
DR Pfam; PF00664; ABC_membrane; 2.
DR Pfam; PF00005; ABC_tran; 2.
DR Pfam; PF14396; CFTR_R; 1.
DR PRINTS; PR01851; CYSFIBREGLTR.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF90123; SSF90123; 2.
DR TIGRFAMs; TIGR01271; CFTR_protein; 1.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Chloride; Chloride channel;
KW Endoplasmic reticulum; Endosome; Glycoprotein; Ion channel; Ion transport;
KW Isomerase; Membrane; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1485
FT /note="Cystic fibrosis transmembrane conductance regulator"
FT /id="PRO_0000093432"
FT TOPO_DOM 1..78
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 79..99
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 100..123
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 124..147
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 148..196
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 197..217
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 218..223
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 224..244
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 245..299
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 300..320
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 321..340
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 341..359
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 360..860
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 861..881
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 882..923
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 924..944
FT /note="Discontinuously helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 945..995
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 996..1016
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 1017..1018
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 1019..1039
FT /note="Helical; Name=10"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 1040..1100
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 1101..1121
FT /note="Helical; Name=11"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 1122..1135
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 1136..1156
FT /note="Helical; Name=12"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 1157..1485
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT DOMAIN 82..366
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 422..647
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 880..1163
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1213..1446
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 652..833
FT /note="Disordered R region"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT REGION 1458..1485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1483..1485
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT COMPBIAS 703..720
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 746..760
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1468..1485
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 402
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT BINDING 435
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT BINDING 459..466
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT BINDING 494
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P26361"
FT BINDING 1222
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT BINDING 1247..1254
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 894
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 900
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1485 AA; 168896 MW; 2859E9B7DB233B89 CRC64;
MQKTPLEKAS IFSQIFFSWT KPILWKGYRQ RLELSDIYQI HPGDSADNLS ERLEREWDRE
VATSKKNPKL INALKRCFFW KFLFYGILLY LGEVTKAVQP LLLGRIIASY DRDNEHERSI
AYYLAIGLCL LFVVRMLLLH PAIFGLHHIG MQMRIAMFSL IYKKTLKLSS KVLDKISTGQ
LVSLLSNNLN KFDEGLALAH FVWIAPLQVL LLMGLLWDLL QASAFCGLGF LIILSLFQAR
LGRMMMKYKD KRAGKINERL VITSQIIENI QSVKAYCWEN AMEKIIETIR ETELKLTRKA
AYVRYFNSSA FFFSGFFVVF LSIVPHLLLD GISLRKIFTT ISFSIVLRMA VTRQFPWAVQ
TWYDSLGVIN KIQEFLQKEE YKSLEYNLTT TEVAMENVSA SWDEGIGEFF EKAKLEVNGG
NISNEDPSAF FSNFSLHVAP VLRNINFKIE KGQLLAIAGS TGAGKTSLLM MIMGELEPSA
GKIKHSGRIS FSPQVSWIMP GTIKENIVFG VSYDQYRYLS VIKACQLEED ISKFPEKDNT
VLGEGGITLS GGQRARISLA RAVYKDADLY LLDSPFSYLD LFTEKEIFES CVCKLMANKT
RILVTSKVEQ LKKADKVLIL HEGSCYFYGT FSELEDQRPE FSSHLIGFDH FNAERRNSII
TETLRRCSID SDPSAVRNEV KNKSFKQVAD FTEKRKSSII NPRKSSRKFS LMQKSQPQMS
GIEEEDMPAE QGERKLSLVP ESEQGEASLP RSNFLNTGPT FQGRRRQSVL NLMTRTSISQ
GSNAFATRNA SVRKMSVNSY SNSSFDLDIY NRRLSQDSIL EVSEEINEED LKECFLDDTD
SQSPTTTWNT YLRFLTAHKN FIFILVFCLV IFFVEVAASS AWLWIIKRNA PAINMTSNEN
VSEVSDTLSV IVTHTSFYYV FYIYVGVADS LLALGIFRGL PLVHSLISVS KVLHKKMLHA
ILHAPMSTFN TMRAGRILNR FSKDTAILDD ILPLSIFDLT QLVLIVIGAI TVVSLLEPYI
FLATVPVIVA FILLRSYFLH TSQQLKQLES KARSPIFAHL ITSLKGLWTL RAFGRQPYFE
TLFHKALNLH TANWFLYLST LRWFQMTIEM IFVIFFIAVS FISIATSGAG EEKVGIVLTL
AMNIMNTLQW AVNASIDVDS LMRSVSRIFR FIDLPVEELI NENKNKEEQL SEVLIYENDY
VKKTQVWPSG GQMTVKNLSA NYIDGGNTVL ENISFSLSPG QRVGLLGRTG SGKSTLLSAF
LRLLSTQGDI QIDGVSWQTI PLQKWRKAFG VIPQKVFIFS GSIRKNLDPY GKWSDEELLK
VTEEVGLKLI IDQFPGQLDF VLLDGGCVLS HGHKQLVCLA RSVLSKAKIL LLDEPSAHLD
PITFQIIRKT LKHAFADCTV ILSEHRLEAM LECQRFLVIE DNTVRQYDSI QKLVNEKSFF
KQAISHSDRL KLFPLHRRNS SKRKSRPQIS ALQEETEEEV QDTRL
