CFTR_SQUAC
ID CFTR_SQUAC Reviewed; 1492 AA.
AC P26362;
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=Dogfish transmembrane conductance regulator;
DE AltName: Full=cAMP-dependent chloride channel;
GN Name=CFTR; Synonyms=ABCC7, DFTR;
OS Squalus acanthias (Spiny dogfish).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Chondrichthyes;
OC Elasmobranchii; Squalomorphii; Squaliformes; Squalidae; Squalus.
OX NCBI_TaxID=7797;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Rectal gland;
RX PubMed=1718999; DOI=10.1016/s0021-9258(18)54631-7;
RA Marshall J., Martin K.A., Picciotto M., Hockfield S., Nairn A.C.,
RA Kaczmarek L.K.;
RT "Identification and localization of a dogfish homolog of human cystic
RT fibrosis transmembrane conductance regulator.";
RL J. Biol. Chem. 266:22749-22754(1991).
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:0000269|PubMed:1718999}; 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 -!- TISSUE SPECIFICITY: Expressed in the rectal gland (at protein level).
CC {ECO:0000269|PubMed:1718999}.
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; M83785; AAA49616.1; -; mRNA.
DR PIR; A39322; A39322.
DR AlphaFoldDB; P26362; -.
DR SMR; P26362; -.
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 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Chloride; Chloride channel;
KW Endoplasmic reticulum; Endosome; Glycoprotein; Ion channel; Ion transport;
KW Isomerase; Membrane; Nucleotide-binding; Phosphoprotein; Repeat;
KW Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..1492
FT /note="Cystic fibrosis transmembrane conductance regulator"
FT /id="PRO_0000093431"
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..867
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 868..888
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 889..932
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 933..953
FT /note="Discontinuously helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 954..1004
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 1005..1025
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 1026..1027
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 1028..1048
FT /note="Helical; Name=10"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 1049..1109
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 1110..1130
FT /note="Helical; Name=11"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 1131..1144
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 1145..1165
FT /note="Helical; Name=12"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 1166..1492
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 424..647
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 868..1169
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1220..1453
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 655..840
FT /note="Disordered R region"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT REGION 1465..1492
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 1474..1492
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 1229
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT BINDING 1254..1261
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT CARBOHYD 905
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 923
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1492 AA; 169385 MW; 0E49CA89968FC2F9 CRC64;
MQRSPIEKAN AFSKLFFRWP RPILKKGYRQ KLELSDIYQI PSSDSADELS EMLEREWDRE
LATSKKNPKL VNALRRCFFW RFLFYGILLY FVEFTKAVQP LCLGRIIASY NAKNTYEREI
AYYLALGLCL LFVVRTLFLH PAVFGLQHLG MQMRIALFSL IYKKILKMSS RVLDKIDTGQ
LVSLLSNNLN KFDEGVAVAH FVWIAPVQVV LLMGLIWNEL TEFVFCGLGF LIMLALFQAW
LGKKMMQYRD KRAGKINERL AITSEIIDNI QSVKVYCWED AMEKIIDDIR QVELKLTRKV
AYCRYFSSSA FFFSGFFVVF LSVVPYAFIH TIKLRRIFTT ISYNIVLRMT VTRQFPSAIQ
TWYDSLGAIR KIQDFLHKDE HKTVEYNLTT KEVEMVNVTA SWDEGIGELF EKVKQNDSER
KMANGDDGLF FSNFSLHVTP VLKNISFKLE KGELLAIAGS TGSGKSSLLM MIMGELEPSD
GKIKHSGRIS YSPQVPWIMP GTIKDNIIFG LSYDEYRYTS VVNACQLEED ITVFPNKDKT
VLGDGGITLS GGQRARISLA RALYKDADLY LLDSPFSHLD VTTEKDIFES CLCKLMVNKT
RILVTSKLEH LKKADKILLL HEGHCYFYGT FSELQGEKPD FSSQLLGSVH FDSFSAERRN
SILTETFRRC SVSSGDGAGL GSYSETRKAS FKQPPPEFNE KRKSSLIVNP ITSNKKFSLV
QTAMSYPQTN GMEDATSEPG ERHFSLIPEN ELGEPTKPRS NIFKSELPFQ AHRRQSVLAL
MTHSSTSPNK IHARRSAVRK MSMLSQTNFA SSEIDIYSRR LSEDGSFEIS EEINEEDLKE
CFADEEEIQN VTTTWSTYLR YVTTNRNLVF VLILCLVIFL AEVAASLAGL WIISGLAINT
GSQTNDTSTD LSHLSVFSKF ITNGSHYYIF YIYVGLADSF LALGVIRGLP LVHTLVTVSK
DLHKQMLHSV LQGPMTAFNK MKAGRILNRF IKDTAIIDDM LPLTVFDFVQ LILIVVGAIC
VVSVLQPYTL LAAIPVAVIF IMLRAYFLRT SQQLKQLESE ARSPIFSHLI TSLRGLWTVR
AFGRQSYFET LFHKALNLHT ANWFLYLSTL RWFQMRIDIV FVLFFIAVTF IAIATHDVGE
GQVGIILTLA MNITSTLQWA VNSSIDVDGL MRSVSRVFKY IDIPPEGSET KNRHNANNPS
DVLVIENKHL TKEWPSGGQM MVNNLTAKYT SDGRAVLQDL SFSVNAGQRV GLLGRTGAGK
STLLSALLRL LSTEGEIQID GISWNSVSLQ KWRKAFGVIP QKVFVFSGTF RKNLDPYEQW
SDEEIWKVTE EVGLKSMIEQ FPDKLNFVLV DGGYILSNGH KQLMCLARSI LSKAKILLLD
EPTAHLDPVT FQIIRKTLKH TFSNCTVILS EHRVEALLEC QQFLVIEGCS VKQFDALQKL
LTEASLFKQV FGHLDRAKLF TAHRRNSSKR KTRPKISALQ EEAEEDLQET RL
