ID A0A1S2ZW56_ERIEU Unreviewed; 1617 AA.
AC A0A1S2ZW56;
DT 12-APR-2017, integrated into UniProtKB/TrEMBL.
DT 12-APR-2017, sequence version 1.
DT 27-MAR-2024, entry version 37.
DE RecName: Full=Cystic fibrosis transmembrane conductance regulator {ECO:0000256|ARBA:ARBA00016668, ECO:0000256|RuleBase:RU362037};
DE EC=5.6.1.6 {ECO:0000256|ARBA:ARBA00012195, ECO:0000256|RuleBase:RU362037};
DE AltName: Full=ATP-binding cassette sub-family C member 7 {ECO:0000256|ARBA:ARBA00029720, ECO:0000256|RuleBase:RU362037};
DE AltName: Full=Channel conductance-controlling ATPase {ECO:0000256|ARBA:ARBA00031358, ECO:0000256|RuleBase:RU362037};
DE AltName: Full=cAMP-dependent chloride channel {ECO:0000256|ARBA:ARBA00033163, ECO:0000256|RuleBase:RU362037};
GN Name=CFTR {ECO:0000313|RefSeq:XP_007525509.1};
OS Erinaceus europaeus (Western European hedgehog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Eulipotyphla; Erinaceidae; Erinaceinae;
OC Erinaceus.
OX NCBI_TaxID=9365 {ECO:0000313|Proteomes:UP000079721, ECO:0000313|RefSeq:XP_007525509.1};
RN [1] {ECO:0000313|RefSeq:XP_007525509.1}
RP IDENTIFICATION.
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
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.
CC Channel activity is coupled to ATP hydrolysis. The ion channel is also
CC permeable to HCO(3-); selectivity depends on the extracellular chloride
CC concentration. Exerts its function also by modulating the activity of
CC other ion channels and transporters. Contributes to the regulation of
CC the pH and the ion content of the epithelial fluid layer.
CC {ECO:0000256|RuleBase:RU362037}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + closed Cl(-) channel = ADP + phosphate + open
CC Cl(-) channel.; EC=5.6.1.6; Evidence={ECO:0000256|ARBA:ARBA00034073,
CC ECO:0000256|RuleBase:RU362037};
CC -!- SUBUNIT: Monomer; does not require oligomerization for channel
CC activity. May form oligomers in the membrane (By similarity). Interacts
CC with SLC26A3, SLC26A6 and NHERF1 (By similarity). Interacts with SHANK2
CC (By similarity). Interacts with MYO6 (By similarity). Interacts (via C-
CC terminus) with GOPC (via PDZ domain); this promotes CFTR
CC internalization and thereby decreases channel activity. Interacts with
CC SLC4A7 through NHERF1. Found in a complex with MYO5B and RAB11A.
CC Interacts with ANO1. Interacts with SLC26A8 (By similarity). Interacts
CC with AHCYL1; the interaction increases CFTR activity (By similarity).
CC Interacts with CSE1L (By similarity). The core-glycosylated form
CC interacts with GORASP2 (via PDZ GRASP-type 1 domain) in respone to ER
CC stress (By similarity). Interacts with MARCHF2; the interaction leads
CC to CFTR ubiqtuitination and degradation.
CC {ECO:0000256|ARBA:ARBA00034805}.
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000256|ARBA:ARBA00004424}; Multi-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004424}. Cell membrane
CC {ECO:0000256|ARBA:ARBA00004651, ECO:0000256|RuleBase:RU362037}; Multi-
CC pass membrane protein {ECO:0000256|ARBA:ARBA00004651,
CC ECO:0000256|RuleBase:RU362037}. Early endosome membrane
CC {ECO:0000256|ARBA:ARBA00004520}; Multi-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004520}. Endoplasmic reticulum membrane
CC {ECO:0000256|ARBA:ARBA00004477}; Multi-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004477}. Endosome membrane
CC {ECO:0000256|ARBA:ARBA00004337}; Multi-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004337}. Membrane
CC {ECO:0000256|ARBA:ARBA00004141}; Multi-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004141}. Nucleus
CC {ECO:0000256|ARBA:ARBA00004123}. Recycling endosome membrane
CC {ECO:0000256|ARBA:ARBA00004195}; Multi-pass membrane protein
CC {ECO:0000256|ARBA:ARBA00004195}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family.
CC CFTR transporter (TC 3.A.1.202) subfamily.
CC {ECO:0000256|ARBA:ARBA00009118, ECO:0000256|RuleBase:RU362037}.
CC -!- CAUTION: Lacks conserved residue(s) required for the propagation of
CC feature annotation. {ECO:0000256|RuleBase:RU362037}.
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DR RefSeq; XP_007525509.1; XM_007525447.2.
DR STRING; 9365.ENSEEUP00000006000; -.
DR CTD; 1080; -.
DR eggNOG; KOG0054; Eukaryota.
DR InParanoid; A0A1S2ZW56; -.
DR OrthoDB; 3384185at2759; -.
DR Proteomes; UP000079721; Unplaced.
DR GO; GO:0016324; C:apical plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-UniRule.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; IEA:InterPro.
DR GO; GO:0005260; F:intracellularly ATP-gated chloride channel activity; IEA:UniProtKB-EC.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR CDD; cd18594; ABC_6TM_CFTR_D1; 1.
DR CDD; cd18600; ABC_6TM_CFTR_D2; 1.
DR CDD; cd03291; ABCC_CFTR1; 1.
DR CDD; cd03289; ABCC_CFTR2; 1.
DR Gene3D; 1.20.1560.10; ABC transporter type 1, transmembrane domain; 2.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 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; IPR047082; CFTR1_ATP-bd_dom1.
DR InterPro; IPR025837; CFTR_reg_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR NCBIfam; TIGR01271; CFTR_protein; 1.
DR PANTHER; PTHR24223; ATP-BINDING CASSETTE SUB-FAMILY C; 1.
DR PANTHER; PTHR24223:SF19; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; 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; SSF90123; ABC transporter transmembrane region; 2.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 2.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 3: Inferred from homology;
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|RuleBase:RU362037};
KW Chloride {ECO:0000256|ARBA:ARBA00023214, ECO:0000256|RuleBase:RU362037};
KW Chloride channel {ECO:0000256|ARBA:ARBA00023173,
KW ECO:0000256|RuleBase:RU362037};
KW Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824};
KW Endosome {ECO:0000256|ARBA:ARBA00022753};
KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW Ion channel {ECO:0000256|ARBA:ARBA00023303, ECO:0000256|RuleBase:RU362037};
KW Ion transport {ECO:0000256|ARBA:ARBA00023065,
KW ECO:0000256|RuleBase:RU362037}; Isomerase {ECO:0000256|ARBA:ARBA00023235};
KW Isopeptide bond {ECO:0000256|ARBA:ARBA00022499};
KW Lipoprotein {ECO:0000256|ARBA:ARBA00023288};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU362037};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741,
KW ECO:0000256|RuleBase:RU362037}; Palmitate {ECO:0000256|ARBA:ARBA00023139};
KW Phosphoprotein {ECO:0000256|ARBA:ARBA00022553,
KW ECO:0000256|RuleBase:RU362037};
KW Reference proteome {ECO:0000313|Proteomes:UP000079721};
KW Repeat {ECO:0000256|ARBA:ARBA00022737};
KW Transmembrane {ECO:0000256|ARBA:ARBA00022692,
KW ECO:0000256|RuleBase:RU362037};
KW Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW ECO:0000256|RuleBase:RU362037};
KW Transport {ECO:0000256|ARBA:ARBA00022448, ECO:0000256|RuleBase:RU362037};
KW Ubl conjugation {ECO:0000256|ARBA:ARBA00022843}.
FT TRANSMEM 253..277
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU362037"
FT TRANSMEM 329..349
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU362037"
FT TRANSMEM 355..375
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU362037"
FT TRANSMEM 438..460
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU362037"
FT TRANSMEM 994..1019
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU362037"
FT TRANSMEM 1122..1144
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU362037"
FT TRANSMEM 1150..1169
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU362037"
FT TRANSMEM 1241..1259
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU362037"
FT TRANSMEM 1265..1283
FT /note="Helical"
FT /evidence="ECO:0000256|RuleBase:RU362037"
FT DOMAIN 220..457
FT /note="ABC transmembrane type-1"
FT /evidence="ECO:0000259|PROSITE:PS50929"
FT DOMAIN 557..780
FT /note="ABC transporter"
FT /evidence="ECO:0000259|PROSITE:PS50893"
FT DOMAIN 995..1294
FT /note="ABC transmembrane type-1"
FT /evidence="ECO:0000259|PROSITE:PS50929"
FT DOMAIN 1347..1580
FT /note="ABC transporter"
FT /evidence="ECO:0000259|PROSITE:PS50893"
FT REGION 1..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1589..1617
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 56..73
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1599..1617
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1617 AA; 182839 MW; C8133F09FD629481 CRC64;
MSDIIAGQRK RGERHARRRV GSLELGTGAQ PAPAGTPAPS SDHAEVASGK GQRHLQTFFQ
KEKKKKQEKS PGSCWRRRAP GGGELRVPRN QARCSGADSA PATALLISSS GALYLESNRD
CPHLQAGLGL SEECHRLHQI NIYTCLSCLY FSWTRPILRK GYRQRLELSD IYQIPSTDSA
DNLSEKLEGE WDRELASKKN PKLINALRRC FFWKFMFYGI LLYLGEVTKA VQPLLLGRII
ASYDPDNKVE RSIAIYLGIG LCLLFVVRTL LLHPAIFGLH HIGMQMRIAM FSLIYKKTLK
LSSRVLDKIS IGQLVSLLSN NLNKFDEGLA LAHFVWIVPL QVTLLMGLLW ELLQASAFCG
LAFLIIVAFY QAGLGRMMMK YRDKRGGKIN ERLVITSEMI ENIQSVKAYC WEEAMEKMIE
NLRQTELKLT RKAAYVRYCN SSAFFFSGFF VVFLSVLPYA LMKGIILRKI FTTISFCIVL
RMAVTRQFPW AVQTWYDSLG AINKIQDFLQ KQEYKTLEYN LTTTEVVMEN ATAYWEEGFG
GLFEKAKQNN NNRKISNGDN SLFFSNFSLL GTPVLKDINF KIERGQLLAV AGSTGAGKTS
LLMMIMGELE PSAGKIKHSG RISFCSQFSW IMPGTIKENI IFGISYDEYR YRSVIKACQL
EEDISKFTEK DNIVLGEGGI TLSGGQRARI SLARAVYKDA DLYLLDSPFG YLDVLTEKEI
FESCVCKLMA NKTRILVTSK MEHLKKADKI LILHEGSTYF YGTFSELQNL RPDFSSKLMG
YDSFDQFSAE RRNSILTETL RRFSLEGDGA VSWNETKKQS FKQTGEFGEK RKNSILNPMN
SARKFSIVQK TTLQMNGIEA NSEEPLERRL SLVPDSELGE TILPRSNVIN TGPTLQGRRR
QSVLNLMTGS SGNQGQGIHR KAAASTRKMS LAPTTNFTEM DIYSRRLSQD SGLEISEEIN
EEDLKECFFD DVENIPAVTT WNTYLRYITV HKSLIFVLIW CLIIFLAEVA ISLVFLLLFE
KSPRQDTGNV TKSSNNSSYG VIITNTSSYY IIYIYVGVAD TLLALGLLRG LPLVHTLITA
SKILHHKMLH SVLQAPMSTL NTLKAGGILN RFSKDIAILD DLLPLTIFDF IQLILIVIGA
VIVVSVLEPY IFLATVPVII AFVMLRAYFL HTSQQLKQLE SEGRSPIFTH LVTSLKGLWT
LRAFGRQPYF ETLFHKALNL HTANWFLYLS TLRWFQMRIE MIFVIFFIAV TFISILTTGD
GEGRVGIILT LAMNIMNTLQ WAVNSSIDVD SLMRSVSRVF KFIDMPTEEI KPSKPVKPSK
EGPLSKVMII ENEHVKKDDI WPSGGQMTVK DLTAKYIESG NAILENISFS ISPGQRVGLL
GRTGSGKSTL LSAFLRLLNT EGEIQIDGVS WDSITLQQWR KAFGVIPQKV FIFSGTFRKN
LDPYEQWNDQ EIWKVADEVG LRSVIEQFPG KLDFVLVDGG YVLSHGHKQL MCLARSVLSK
AKILLLDEPS AHLDPITYQI IRRTIKQAFA DCTVILCEHR IEAMLECQRF LVIEENKVRQ
YDSIQKLLSE KSLFRQAISN SDRLKLFPHR NSSKHKSRSK IAALKEETEE EVQETRL
//
