CFTR_HUMAN
ID CFTR_HUMAN Reviewed; 1480 AA.
AC P13569; Q20BG8; Q20BH2; Q2I0A1; Q2I102;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 3.
DT 03-AUG-2022, entry version 267.
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:0000269|PubMed:11524016, ECO:0000269|PubMed:15284228, ECO:0000269|PubMed:26627831, ECO:0000269|PubMed:8910473};
DE AltName: Full=cAMP-dependent chloride channel;
GN Name=CFTR; Synonyms=ABCC7;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT MET-470.
RX PubMed=2475911; DOI=10.1126/science.2475911;
RA Riordan J.R., Rommens J.M., Kerem B., Alon N., Rozmahel R., Grzelczak Z.,
RA Zielenski J., Lok S., Plavsic N., Chou J.-L., Drumm M.L., Iannuzzi M.C.,
RA Collins F.S., Tsui L.-C.;
RT "Identification of the cystic fibrosis gene: cloning and characterization
RT of complementary DNA.";
RL Science 245:1066-1073(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT MET-470.
RX PubMed=1710598; DOI=10.1016/0888-7543(91)90503-7;
RA Zielenski J., Rozmahel R., Bozon D., Kerem B., Grzelczak Z., Riordan J.R.,
RA Rommens J., Tsui L.-C.;
RT "Genomic DNA sequence of the cystic fibrosis transmembrane conductance
RT regulator (CFTR) gene.";
RL Genomics 10:214-228(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS MET-470 AND TRP-1453.
RA Stacy R., Subramanian S., Deodato C., Burkhardt P., Song Y., Paddock M.,
RA Chang J., Zhou Y., Haugen E., Waring D., Chapman P., Hayden H., Levy R.,
RA Wu Z., Rouse G., James R., Phelps K., Olson M.V., Kaul R.;
RL Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [6]
RP PHOSPHORYLATION AT SER-660; SER-686; SER-700; SER-737; SER-768; SER-790;
RP SER-795 AND SER-813.
RX PubMed=1377674; DOI=10.1016/s0021-9258(18)42339-3;
RA Picciotto M.R., Cohn J.A., Bertuzzi G., Greenguard P., Nairn A.C.;
RT "Phosphorylation of the cystic fibrosis transmembrane conductance
RT regulator.";
RL J. Biol. Chem. 267:12742-12752(1992).
RN [7]
RP GLYCOSYLATION AT ASN-894 AND ASN-900, AND TOPOLOGY.
RX PubMed=7518437; DOI=10.1016/s0021-9258(17)32347-5;
RA Chang X.-B., Hou Y.-X., Jensen T.J., Riordan J.R.;
RT "Mapping of cystic fibrosis transmembrane conductance regulator membrane
RT topology by glycosylation site insertion.";
RL J. Biol. Chem. 269:18572-18575(1994).
RN [8]
RP PHOSPHORYLATION AT SER-660; SER-700; SER-712; SER-737; SER-753; SER-768;
RP SER-795 AND SER-813.
RX PubMed=9385646; DOI=10.1002/pro.5560061117;
RA Neville D.C.A., Rozanas C.R., Rice E.M., Gruis D.B., Verkman A.S.,
RA Townsend R.R.;
RT "Evidence for phosphorylation of serine 753 in CFTR using a novel metal-ion
RT affinity resin and matrix-assisted laser desorption mass spectrometry.";
RL Protein Sci. 6:2436-2445(1997).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORM 2).
RX PubMed=10766763; DOI=10.1074/jbc.m910165199;
RA Pagani F., Buratti E., Stuani C., Romano M., Zuccato E., Niksic M.,
RA Giglio L., Faraguna D., Baralle F.E.;
RT "Splicing factors induce cystic fibrosis transmembrane regulator exon 9
RT skipping through a nonevolutionary conserved intronic element.";
RL J. Biol. Chem. 275:21041-21047(2000).
RN [10]
RP DOMAIN, FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=10792060; DOI=10.1073/pnas.100588797;
RA Ostedgaard L.S., Baldursson O., Vermeer D.W., Welsh M.J., Robertson A.D.;
RT "A functional R domain from cystic fibrosis transmembrane conductance
RT regulator is predominantly unstructured in solution.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:5657-5662(2000).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=11524016; DOI=10.1021/bi0108195;
RA Ramjeesingh M., Li C., Kogan I., Wang Y., Huan L.J., Bear C.E.;
RT "A monomer is the minimum functional unit required for channel and ATPase
RT activity of the cystic fibrosis transmembrane conductance regulator.";
RL Biochemistry 40:10700-10706(2001).
RN [12]
RP INTERACTION WITH GOPC, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11707463; DOI=10.1074/jbc.m110177200;
RA Cheng J., Moyer B.D., Milewski M., Loffing J., Ikeda M., Mickle J.E.,
RA Cutting G.R., Li M., Stanton B.A., Guggino W.B.;
RT "A Golgi-associated PDZ domain protein modulates cystic fibrosis
RT transmembrane regulator plasma membrane expression.";
RL J. Biol. Chem. 277:3520-3529(2002).
RN [13]
RP INTERACTION WITH SLC4A7 AND SLC9A3R1, AND FUNCTION.
RX PubMed=12403779; DOI=10.1074/jbc.m201862200;
RA Park M., Ko S.B.H., Choi J.Y., Muallem G., Thomas P.J., Pushkin A.,
RA Lee M.-S., Kim J.Y., Lee M.G., Muallem S., Kurtz I.;
RT "The cystic fibrosis transmembrane conductance regulator interacts with and
RT regulates the activity of the HCO3- salvage transporter human Na+-HCO3-
RT cotransport isoform 3.";
RL J. Biol. Chem. 277:50503-50509(2002).
RN [14]
RP PHOSPHORYLATION BY AMPK, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12519745; DOI=10.1152/ajpcell.00227.2002;
RA Hallows K.R., Kobinger G.P., Wilson J.M., Witters L.A., Foskett J.K.;
RT "Physiological modulation of CFTR activity by AMP-activated protein kinase
RT in polarized T84 cells.";
RL Am. J. Physiol. 284:C1297-C1308(2003).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=15010471; DOI=10.1074/jbc.m313323200;
RA Shcheynikov N., Kim K.H., Kim K.M., Dorwart M.R., Ko S.B., Goto H.,
RA Naruse S., Thomas P.J., Muallem S.;
RT "Dynamic control of cystic fibrosis transmembrane conductance regulator
RT Cl(-)/HCO3(-) selectivity by external Cl(-).";
RL J. Biol. Chem. 279:21857-21865(2004).
RN [16]
RP INTERACTION WITH MYO6, AND SUBCELLULAR LOCATION.
RX PubMed=15247260; DOI=10.1074/jbc.m403141200;
RA Swiatecka-Urban A., Boyd C., Coutermarsh B., Karlson K.H., Barnaby R.,
RA Aschenbrenner L., Langford G.M., Hasson T., Stanton B.A.;
RT "Myosin VI regulates endocytosis of the cystic fibrosis transmembrane
RT conductance regulator.";
RL J. Biol. Chem. 279:38025-38031(2004).
RN [17]
RP REVIEW.
RX PubMed=1378801; DOI=10.1096/fasebj.6.10.1378801;
RA McIntosh I., Cutting G.R.;
RT "Cystic fibrosis transmembrane conductance regulator and the etiology and
RT pathogenesis of cystic fibrosis.";
RL FASEB J. 6:2775-2782(1992).
RN [18]
RP ALTERNATIVE SPLICING (ISOFORM 3).
RX PubMed=12913074; DOI=10.1093/hmg/ddg215;
RA Aznarez I., Chan E.M., Zielenski J., Blencowe B.J., Tsui L.-C.;
RT "Characterization of disease-associated mutations affecting an exonic
RT splicing enhancer and two cryptic splice sites in exon 13 of the cystic
RT fibrosis transmembrane conductance regulator gene.";
RL Hum. Mol. Genet. 12:2031-2040(2003).
RN [19]
RP CHANNEL GATING REGULATION, PHOSPHORYLATION, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12588899; DOI=10.1113/jphysiol.2002.035790;
RA Chappe V., Hinkson D.A., Zhu T., Chang X.B., Riordan J.R., Hanrahan J.W.;
RT "Phosphorylation of protein kinase C sites in NBD1 and the R domain control
RT CFTR channel activation by PKA.";
RL J. Physiol. (Lond.) 548:39-52(2003).
RN [20]
RP FUNCTION.
RX PubMed=14668433; DOI=10.1073/pnas.2634339100;
RA Coakley R.D., Grubb B.R., Paradiso A.M., Gatzy J.T., Johnson L.G.,
RA Kreda S.M., O'Neal W.K., Boucher R.C.;
RT "Abnormal surface liquid pH regulation by cultured cystic fibrosis
RT bronchial epithelium.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:16083-16088(2003).
RN [21]
RP CATALYTIC ACTIVITY, AND DOMAIN.
RX PubMed=15284228; DOI=10.1074/jbc.m407666200;
RA Kidd J.F., Ramjeesingh M., Stratford F., Huan L.J., Bear C.E.;
RT "A heteromeric complex of the two nucleotide binding domains of cystic
RT fibrosis transmembrane conductance regulator (CFTR) mediates ATPase
RT activity.";
RL J. Biol. Chem. 279:41664-41669(2004).
RN [22]
RP FUNCTION.
RX PubMed=16645176; DOI=10.1164/rccm.200506-987oc;
RA Blouquit S., Regnier A., Dannhoffer L., Fermanian C., Naline E.,
RA Boucher R., Chinet T.;
RT "Ion and fluid transport properties of small airways in cystic fibrosis.";
RL Am. J. Respir. Crit. Care Med. 174:299-305(2006).
RN [23]
RP DOMAIN, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=17036051; DOI=10.1038/sj.emboj.7601373;
RA Mense M., Vergani P., White D.M., Altberg G., Nairn A.C., Gadsby D.C.;
RT "In vivo phosphorylation of CFTR promotes formation of a nucleotide-binding
RT domain heterodimer.";
RL EMBO J. 25:4728-4739(2006).
RN [24]
RP IDENTIFICATION IN A COMPLEX WITH RAB11A AND MYO5B, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17462998; DOI=10.1074/jbc.m608531200;
RA Swiatecka-Urban A., Talebian L., Kanno E., Moreau-Marquis S.,
RA Coutermarsh B., Hansen K., Karlson K.H., Barnaby R., Cheney R.E.,
RA Langford G.M., Fukuda M., Stanton B.A.;
RT "Myosin Vb is required for trafficking of the cystic fibrosis transmembrane
RT conductance regulator in Rab11a-specific apical recycling endosomes in
RT polarized human airway epithelial cells.";
RL J. Biol. Chem. 282:23725-23736(2007).
RN [25]
RP FUNCTION.
RX PubMed=17434346; DOI=10.1016/j.jcf.2007.03.001;
RA Lu C., Jiang C., Pribanic S., Rotin D.;
RT "CFTR stabilizes ENaC at the plasma membrane.";
RL J. Cyst. Fibros. 6:419-422(2007).
RN [26]
RP DOMAIN.
RX PubMed=17660831; DOI=10.1038/nsmb1278;
RA Baker J.M., Hudson R.P., Kanelis V., Choy W.Y., Thibodeau P.H.,
RA Thomas P.J., Forman-Kay J.D.;
RT "CFTR regulatory region interacts with NBD1 predominantly via multiple
RT transient helices.";
RL Nat. Struct. Mol. Biol. 14:738-745(2007).
RN [27]
RP UBIQUITINATION, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=19398555; DOI=10.1074/jbc.m109.001685;
RA Bomberger J.M., Barnaby R.L., Stanton B.A.;
RT "The deubiquitinating enzyme USP10 regulates the post-endocytic sorting of
RT cystic fibrosis transmembrane conductance regulator in airway epithelial
RT cells.";
RL J. Biol. Chem. 284:18778-18789(2009).
RN [28]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19019741; DOI=10.1016/j.jcf.2008.10.004;
RA Tang L., Fatehi M., Linsdell P.;
RT "Mechanism of direct bicarbonate transport by the CFTR anion channel.";
RL J. Cyst. Fibros. 8:115-121(2009).
RN [29]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19621064; DOI=10.1371/journal.pbio.1000155;
RA Zhang L., Button B., Gabriel S.E., Burkett S., Yan Y., Skiadopoulos M.H.,
RA Dang Y.L., Vogel L.N., McKay T., Mengos A., Boucher R.C., Collins P.L.,
RA Pickles R.J.;
RT "CFTR delivery to 25% of surface epithelial cells restores normal rates of
RT mucus transport to human cystic fibrosis airway epithelium.";
RL PLoS Biol. 7:E1000155-E1000155(2009).
RN [30]
RP INTERACTION WITH CSE1L.
RX PubMed=20933420; DOI=10.1016/j.cub.2010.09.012;
RA Bagnat M., Navis A., Herbstreith S., Brand-Arzamendi K., Curado S.,
RA Gabriel S., Mostov K., Huisken J., Stainier D.Y.;
RT "Cse1l is a negative regulator of CFTR-dependent fluid secretion.";
RL Curr. Biol. 20:1840-1845(2010).
RN [31]
RP SUBCELLULAR LOCATION, CHARACTERIZATION OF VARIANT CF PHE-508 DEL,
RP MUTAGENESIS OF ASN-894 AND ASN-900, AND GLYCOSYLATION AT ASN-894 AND
RP ASN-900.
RX PubMed=20008117; DOI=10.1152/ajplung.00016.2009;
RA Cholon D.M., O'Neal W.K., Randell S.H., Riordan J.R., Gentzsch M.;
RT "Modulation of endocytic trafficking and apical stability of CFTR in
RT primary human airway epithelial cultures.";
RL Am. J. Physiol. 298:L304-L314(2010).
RN [32]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19923167; DOI=10.1093/humrep/dep406;
RA Li C.Y., Jiang L.Y., Chen W.Y., Li K., Sheng H.Q., Ni Y., Lu J.X., Xu W.X.,
RA Zhang S.Y., Shi Q.X.;
RT "CFTR is essential for sperm fertilizing capacity and is correlated with
RT sperm quality in humans.";
RL Hum. Reprod. 25:317-327(2010).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-549, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [34]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH ANO1.
RX PubMed=22178883; DOI=10.1159/000335765;
RA Ousingsawat J., Kongsuphol P., Schreiber R., Kunzelmann K.;
RT "CFTR and TMEM16A are separate but functionally related Cl-channels.";
RL Cell. Physiol. Biochem. 28:715-724(2011).
RN [35]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=22207244; DOI=10.1007/s00418-011-0904-1;
RA Enuka Y., Hanukoglu I., Edelheit O., Vaknine H., Hanukoglu A.;
RT "Epithelial sodium channels (ENaC) are uniformly distributed on motile
RT cilia in the oviduct and the respiratory airways.";
RL Histochem. Cell Biol. 137:339-353(2012).
RN [36]
RP INTERACTION WITH SLC26A8.
RX PubMed=22121115; DOI=10.1093/hmg/ddr558;
RA Rode B., Dirami T., Bakouh N., Rizk-Rabin M., Norez C., Lhuillier P.,
RA Lores P., Jollivet M., Melin P., Zvetkova I., Bienvenu T., Becq F.,
RA Planelles G., Edelman A., Gacon G., Toure A.;
RT "The testis anion transporter TAT1 (SLC26A8) physically and functionally
RT interacts with the cystic fibrosis transmembrane conductance regulator
RT channel: a potential role during sperm capacitation.";
RL Hum. Mol. Genet. 21:1287-1298(2012).
RN [37]
RP PHOSPHORYLATION AT SER-660; SER-686; SER-700; SER-712; THR-717; SER-737;
RP SER-795; SER-1444 AND SER-1456, UBIQUITINATION AT LYS-688, PALMITOYLATION
RP AT CYS-524 AND CYS-1395, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=22119790; DOI=10.1093/protein/gzr054;
RA McClure M., Delucas L.J., Wilson L., Ray M., Rowe S.M., Wu X., Dai Q.,
RA Hong J.S., Sorscher E.J., Kappes J.C., Barnes S.;
RT "Purification of CFTR for mass spectrometry analysis: identification of
RT palmitoylation and other post-translational modifications.";
RL Protein Eng. Des. Sel. 25:7-14(2012).
RN [38]
RP UBIQUITINATION BY RNF185.
RX PubMed=24019521; DOI=10.1074/jbc.m113.470500;
RA El Khouri E., Le Pavec G., Toledano M.B., Delaunay-Moisan A.;
RT "RNF185 is a novel E3 ligase of endoplasmic reticulum-associated
RT degradation (ERAD) that targets cystic fibrosis transmembrane conductance
RT regulator (CFTR).";
RL J. Biol. Chem. 288:31177-31191(2013).
RN [39]
RP INTERACTION WITH MARCHF2, UBIQUITINATION, AND MUTAGENESIS OF PHE-508 AND
RP 1478-TYR--LEU-1480.
RX PubMed=23818989; DOI=10.1371/journal.pone.0068001;
RA Cheng J., Guggino W.;
RT "Ubiquitination and degradation of CFTR by the E3 ubiquitin ligase MARCH2
RT through its association with adaptor proteins CAL and STX6.";
RL PLoS ONE 8:e68001-e68001(2013).
RN [40]
RP FUNCTION, CHARACTERIZATION OF CF VARIANT PHE-508 DEL, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION AT SER-660; SER-670; SER-700; SER-712; SER-737; SER-753;
RP SER-768; SER-795 AND SER-813, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=25330774; DOI=10.1002/pmic.201400218;
RA Pasyk S., Molinski S., Ahmadi S., Ramjeesingh M., Huan L.J., Chin S.,
RA Du K., Yeger H., Taylor P., Moran M.F., Bear C.E.;
RT "The major cystic fibrosis causing mutation exhibits defective propensity
RT for phosphorylation.";
RL Proteomics 15:447-461(2015).
RN [41]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=26627831; DOI=10.1074/jbc.m115.704809;
RA Ehrhardt A., Chung W.J., Pyle L.C., Wang W., Nowotarski K., Mulvihill C.M.,
RA Ramjeesingh M., Hong J., Velu S.E., Lewis H.A., Atwell S., Aller S.,
RA Bear C.E., Lukacs G.L., Kirk K.L., Sorscher E.J.;
RT "Channel gating regulation by the cystic fibrosis transmembrane conductance
RT regulator (CFTR) first cytosolic loop.";
RL J. Biol. Chem. 291:1854-1865(2016).
RN [42]
RP FUNCTION.
RX PubMed=26823428; DOI=10.1126/science.aad5589;
RA Shah V.S., Meyerholz D.K., Tang X.X., Reznikov L., Abou Alaiwa M.,
RA Ernst S.E., Karp P.H., Wohlford-Lenane C.L., Heilmann K.P., Leidinger M.R.,
RA Allen P.D., Zabner J., McCray P.B. Jr., Ostedgaard L.S., Stoltz D.A.,
RA Randak C.O., Welsh M.J.;
RT "Airway acidification initiates host defense abnormalities in cystic
RT fibrosis mice.";
RL Science 351:503-507(2016).
RN [43]
RP FUNCTION.
RX PubMed=27941075; DOI=10.1152/ajplung.00375.2016;
RA Rauh R., Hoerner C., Korbmacher C.;
RT "deltabetagamma-ENaC is inhibited by CFTR but stimulated by cAMP in Xenopus
RT laevis oocytes.";
RL Am. J. Physiol. 312:L277-L287(2017).
RN [44]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=28130590; DOI=10.1007/s00418-016-1535-3;
RA Hanukoglu I., Boggula V.R., Vaknine H., Sharma S., Kleyman T.,
RA Hanukoglu A.;
RT "Expression of epithelial sodium channel (ENaC) and CFTR in the human
RT epidermis and epidermal appendages.";
RL Histochem. Cell Biol. 147:733-748(2017).
RN [45]
RP FUNCTION.
RX PubMed=27714810; DOI=10.1002/jcp.25634;
RA Puga Molina L.C., Pinto N.A., Torres Rodriguez P., Romarowski A.,
RA Vicens Sanchez A., Visconti P.E., Darszon A., Trevino C.L., Buffone M.G.;
RT "Essential role of CFTR in PKA-dependent phosphorylation, alkalinization,
RT and hyperpolarization during human sperm capacitation.";
RL J. Cell. Physiol. 232:1404-1414(2017).
RN [46]
RP 3D-STRUCTURE MODELING OF 425-638.
RX PubMed=9517543;
RX DOI=10.1002/(sici)1097-0134(19980215)30:3<275::aid-prot7>3.0.co;2-j;
RA Hoedemaeker F.J., Davidson A.R., Rose D.R.;
RT "A model for the nucleotide-binding domains of ABC transporters based on
RT the large domain of aspartate aminotransferase.";
RL Proteins 30:275-286(1998).
RN [47]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1476-1480 IN COMPLEX WITH
RP SLC9A3R1.
RX PubMed=11304524; DOI=10.1074/jbc.c100154200;
RA Karthikeyan S., Leung T., Ladias J.A.A.;
RT "Structural basis of the Na+/H+ exchanger regulatory factor PDZ1
RT interaction with the carboxyl-terminal region of the cystic fibrosis
RT transmembrane conductance regulator.";
RL J. Biol. Chem. 276:19683-19686(2001).
RN [48] {ECO:0007744|PDB:2LOB}
RP STRUCTURE BY NMR OF 1473-1480 IN COMPLEX WITH GOPC.
RX PubMed=16331976; DOI=10.1021/bi0516475;
RA Piserchio A., Fellows A., Madden D.R., Mierke D.F.;
RT "Association of the cystic fibrosis transmembrane regulator with CAL:
RT structural features and molecular dynamics.";
RL Biochemistry 44:16158-16166(2005).
RN [49] {ECO:0007744|PDB:1XMI, ECO:0007744|PDB:1XMJ}
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 389-678 OF WILD-TYPE AND VARIANT
RP CF PHE-508 DEL IN COMPLEX WITH ATP, AND CHARACTERIZATION OF VARIANT CF
RP PHE-508 DEL.
RX PubMed=15528182; DOI=10.1074/jbc.m410968200;
RA Lewis H.A., Zhao X., Wang C., Sauder J.M., Rooney I., Noland B.W.,
RA Lorimer D., Kearins M.C., Conners K., Condon B., Maloney P.C.,
RA Guggino W.B., Hunt J.F., Emtage S.;
RT "Impact of the deltaF508 mutation in first nucleotide-binding domain of
RT human cystic fibrosis transmembrane conductance regulator on domain folding
RT and structure.";
RL J. Biol. Chem. 280:1346-1353(2005).
RN [50] {ECO:0007744|PDB:3GD7}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 1193-1435 AND 1458-1470 IN
RP COMPLEX WITH ATP ANALOG.
RA Atwell S., Antonysamy S., Guggino W.B., Conners K., Emtage S., Gheyi T.,
RA Hunt J.F., Lewis H.A., Lu F., Sauder J.M., Weber P.C., Wetmore D., Zhao X.;
RT "Crystal structure of human NBD2 complexed with N6-phenylethyl-ATP (P-
RT ATP).";
RL Submitted (FEB-2009) to the PDB data bank.
RN [51] {ECO:0007744|PDB:2BBO, ECO:0007744|PDB:2BBS, ECO:0007744|PDB:2BBT}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 389-677 IN COMPLEX WITH ATP.
RX PubMed=19944699; DOI=10.1016/j.jmb.2009.11.051;
RA Lewis H.A., Wang C., Zhao X., Hamuro Y., Conners K., Kearins M.C., Lu F.,
RA Sauder J.M., Molnar K.S., Coales S.J., Maloney P.C., Guggino W.B.,
RA Wetmore D.R., Weber P.C., Hunt J.F.;
RT "Structure and dynamics of NBD1 from CFTR characterized using
RT crystallography and hydrogen/deuterium exchange mass spectrometry.";
RL J. Mol. Biol. 396:406-430(2010).
RN [52] {ECO:0007744|PDB:2PZE, ECO:0007744|PDB:2PZF, ECO:0007744|PDB:2PZG}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 387-646 IN COMPLEX WITH ATP, AND
RP CHARACTERIZATION OF VARIANT CF PHE-508 DEL.
RX PubMed=20150177; DOI=10.1093/protein/gzq004;
RA Atwell S., Brouillette C.G., Conners K., Emtage S., Gheyi T., Guggino W.B.,
RA Hendle J., Hunt J.F., Lewis H.A., Lu F., Protasevich I.I., Rodgers L.A.,
RA Romero R., Wasserman S.R., Weber P.C., Wetmore D., Zhang F.F., Zhao X.;
RT "Structures of a minimal human CFTR first nucleotide-binding domain as a
RT monomer, head-to-tail homodimer, and pathogenic mutant.";
RL Protein Eng. Des. Sel. 23:375-384(2010).
RN [53]
RP STRUCTURE BY ELECTRON MICROSCOPY (9 ANGSTROMS).
RX PubMed=21931164; DOI=10.1074/jbc.m111.292268;
RA Rosenberg M.F., O'Ryan L.P., Hughes G., Zhao Z., Aleksandrov L.A.,
RA Riordan J.R., Ford R.C.;
RT "The cystic fibrosis transmembrane conductance regulator (CFTR): three-
RT dimensional structure and localization of a channel gate.";
RL J. Biol. Chem. 286:42647-42654(2011).
RN [54] {ECO:0007744|PDB:4WZ6}
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 389-678.
RX PubMed=26444971; DOI=10.1002/pro.2821;
RA Hall J.D., Wang H., Byrnes L.J., Shanker S., Wang K., Efremov I.V.,
RA Chong P.A., Forman-Kay J.D., Aulabaugh A.E.;
RT "Binding screen for cystic fibrosis transmembrane conductance regulator
RT correctors finds new chemical matter and yields insights into cystic
RT fibrosis therapeutic strategy.";
RL Protein Sci. 25:360-373(2016).
RN [55] {ECO:0007744|PDB:5UAK}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.87 ANGSTROMS), AND TOPOLOGY.
RA Liu F., Zhang Z., Chen J.;
RT "Structure of human cystic fibrosis transmembrane conductance regulator
RT (CFTR).";
RL Submitted (DEC-2016) to the PDB data bank.
RN [56]
RP REVIEW ON VARIANTS.
RX PubMed=1284534; DOI=10.1002/humu.1380010304;
RA Tsui L.-C.;
RT "Mutations and sequence variations detected in the cystic fibrosis
RT transmembrane conductance regulator (CFTR) gene: a report from the Cystic
RT Fibrosis Genetic Analysis Consortium.";
RL Hum. Mutat. 1:197-203(1992).
RN [57]
RP CHARACTERIZATION OF VARIANT CF TRP-334; ILE-507 DEL; PHE-508 DEL; ASP-551
RP AND ILE-549, MUTAGENESIS OF LYS-464; PHE-508 AND LYS-1250, AND
RP GLYCOSYLATION.
RX PubMed=1699669; DOI=10.1016/0092-8674(90)90148-8;
RA Cheng S.H., Gregory R.J., Marshall J., Paul S., Souza D.W., White G.A.,
RA O'Riordan C.R., Smith A.E.;
RT "Defective intracellular transport and processing of CFTR is the molecular
RT basis of most cystic fibrosis.";
RL Cell 63:827-834(1990).
RN [58]
RP VARIANTS CF.
RX PubMed=1695717; DOI=10.1038/346366a0;
RA Cutting G.R., Kasch L.M., Rosenstein B.J., Zielenski J., Tsui L.-C.,
RA Antonarakis S.E., Kazazian H.H. Jr.;
RT "A cluster of cystic fibrosis mutations in the first nucleotide-binding
RT fold of the cystic fibrosis conductance regulator protein.";
RL Nature 346:366-369(1990).
RN [59]
RP VARIANTS CF.
RX PubMed=2236053; DOI=10.1073/pnas.87.21.8447;
RA Kerem B.-S., Zielenski J., Markiewicz D., Bozon D., Gazit E., Yahav J.,
RA Kennedy D., Riordan J.R., Collins F.S., Rommens J.M., Tsui L.-C.;
RT "Identification of mutations in regions corresponding to the two putative
RT nucleotide (ATP)-binding folds of the cystic fibrosis gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:8447-8451(1990).
RN [60]
RP VARIANTS CF.
RX PubMed=1710600; DOI=10.1016/0888-7543(91)90510-l;
RA White M.B., Krueger L.J., Holsclaw D.S. Jr., Gerrard B.C., Stewart C.,
RA Quittell L., Dolganov G., Baranov V., Ivaschenko T., Kapronov N.I.,
RA Sebastio G., Castiglione O., Dean M.;
RT "Detection of three rare frameshift mutations in the cystic fibrosis gene
RT in an African-American (CF444delA), an Italian (CF2522insC), and a Soviet
RT (CF3821delT).";
RL Genomics 10:266-269(1991).
RN [61]
RP CHARACTERIZATION OF CF VARIANTS ILE-507 DEL; PHE-508 DEL; ILE-549; ARG-549;
RP ASP-551; THR-559; ASN-572; LYS-1303 AND ASP-1349, FUNCTION, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF PHE-508.
RX PubMed=1712898; DOI=10.1128/mcb.11.8.3886-3893.1991;
RA Gregory R.J., Rich D.P., Cheng S.H., Souza D.W., Paul S., Manavalan P.,
RA Anderson M.P., Welsh M.J., Smith A.E.;
RT "Maturation and function of cystic fibrosis transmembrane conductance
RT regulator variants bearing mutations in putative nucleotide-binding domains
RT 1 and 2.";
RL Mol. Cell. Biol. 11:3886-3893(1991).
RN [62]
RP VARIANTS VAL-44; MET-470; VAL-506; CYS-508; ALA-576; CYS-668; PHE-997;
RP THR-1027 AND LEU-1162, AND VARIANTS CF GLY-44; ARG-178; ARG-225; TRP-334;
RP PHE-508 DEL; 542-GLY--LEU-1480 DEL; ASP-551; ILE-562; ARG-628;
RP 710-LYS--LEU-1480 DEL; 846-TRP--LEU-1480 DEL; CYS-913; 1063-TRP--LEU-1480
RP DEL; CYS-1066; 1092-TYR--LEU-1480 DEL; 1162-ARG--LEU-1480 DEL; GLU-1200;
RP 1282-TRP--LEU-1480 DEL AND LYS-1303.
RX PubMed=1379210; DOI=10.1016/0888-7543(92)90152-i;
RA Fanen P., Ghanem N., Vidaud M., Besmond C., Martin J., Costes B.,
RA Plassa F., Goossens M.;
RT "Molecular characterization of cystic fibrosis: 16 novel mutations
RT identified by analysis of the whole cystic fibrosis conductance
RT transmembrane regulator (CFTR) coding regions and splice site junctions.";
RL Genomics 13:770-776(1992).
RN [63]
RP VARIANTS CF PHE-520 AND HIS-1291.
RX PubMed=1284466; DOI=10.1093/hmg/1.1.11;
RA Jones C.T., McIntosh I., Keston M., Ferguson A., Brock D.J.H.;
RT "Three novel mutations in the cystic fibrosis gene detected by chemical
RT cleavage: analysis of variant splicing and a nonsense mutation.";
RL Hum. Mol. Genet. 1:11-17(1992).
RN [64]
RP VARIANT CF MET-1283.
RX PubMed=1284468; DOI=10.1093/hmg/1.2.123;
RA Cheadle J.P., Meredith A.L., Al-Jader L.N.;
RT "A new missense mutation (R1283M) in exon 20 of the cystic fibrosis
RT transmembrane conductance regulator gene.";
RL Hum. Mol. Genet. 1:123-125(1992).
RN [65]
RP VARIANT CF PRO-1255.
RX PubMed=1284530; DOI=10.1093/hmg/1.6.441;
RA Lissens W., Bonduelle M., Malfroot A., Dab I., Liebaers I.;
RT "A serine to proline substitution (S1255P) in the second nucleotide binding
RT fold of the cystic fibrosis gene.";
RL Hum. Mol. Genet. 1:441-442(1992).
RN [66]
RP VARIANTS CF LYS-92 AND CYS-117.
RX PubMed=1284529; DOI=10.1093/hmg/1.6.439;
RA Shackleton S., Beards F., Harris A.;
RT "Detection of novel and rare mutations in exon 4 of the cystic fibrosis
RT gene by SSCP.";
RL Hum. Mol. Genet. 1:439-440(1992).
RN [67]
RP CHARACTERIZATION OF VARIANT CF PHE-508 DEL AND ASP-551, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=1284548; DOI=10.1038/ng0892-321;
RA Kartner N., Augustinas O., Jensen T.J., Naismith A.L., Riordan J.R.;
RT "Mislocalization of delta F508 CFTR in cystic fibrosis sweat gland.";
RL Nat. Genet. 1:321-327(1992).
RN [68]
RP VARIANT CF LYS-1101.
RX PubMed=7680525;
RA Zielenski J., Fugiwara T.M., Markiewicz D., Paradis A.J., Anacleto A.I.,
RA Richards B., Schwartz R.H., Klinger K.W., Tsui L.-C., Morgan K.;
RT "Identification of the M1101K mutation in the cystic fibrosis transmembrane
RT conductance regulator (CFTR) gene and complete detection of cystic fibrosis
RT mutations in the Hutterite population.";
RL Am. J. Hum. Genet. 52:609-615(1993).
RN [69]
RP VARIANTS CF VAL-1052; ARG-1061; LEU-1066; GLN-1070; ARG-1085 AND ARG-1101.
RX PubMed=7683628; DOI=10.1006/geno.1993.1183;
RA Mercier B., Lissens W., Novelli G., Kalaydjieva L., De Arce M.,
RA Kapranov N., Klain N.C., Lenoir G., Chauveau P., Lenaerts C., Rault G.,
RA Cashman S., Sangiuolo F., Audrezet M.-P., Dallapiccola B., Guillermit H.,
RA Bonduelle M., Liebaers I., Quere I., Verlingue C., Ferec C.;
RT "Identification of eight novel mutations in a collaborative analysis of a
RT part of the second transmembrane domain of the CFTR gene.";
RL Genomics 16:296-297(1993).
RN [70]
RP VARIANT CF LEU-693.
RX PubMed=8406518; DOI=10.1159/000154147;
RA Audrezet M.P., Novelli G., Mercier B., Sangiuolo F., Maceratesi P.,
RA Ferec C., Dallapiccola B.;
RT "Identification of three novel cystic fibrosis mutations in a sample of
RT Italian cystic fibrosis patients.";
RL Hum. Hered. 43:295-300(1993).
RN [71]
RP VARIANT CF LYS-92.
RX PubMed=7683954; DOI=10.1093/hmg/2.1.79;
RA Nunes V., Chillon M., Doerk T., Tuemmler B., Casals T., Estivill X.;
RT "A new missense mutation (E92K) in the first transmembrane domain of the
RT CFTR gene causes a benign cystic fibrosis phenotype.";
RL Hum. Mol. Genet. 2:79-80(1993).
RN [72]
RP VARIANT CF SER-205.
RX PubMed=7505694; DOI=10.1093/hmg/2.10.1741;
RA Chillon M., Casals T., Nunes V., Gimenez J., Ruiz E.P., Estivill X.;
RT "Identification of a new missense mutation (P205S) in the first
RT transmembrane domain of the CFTR gene associated with a mild cystic
RT fibrosis phenotype.";
RL Hum. Mol. Genet. 2:1741-1742(1993).
RN [73]
RP VARIANTS CF.
RX PubMed=7504969; DOI=10.1002/humu.1380020511;
RA Gasparini P., Marigo C., Bisceglia G., Nicolis E., Zelante L., Bombieri C.,
RA Borgo G., Pignatti P.F., Cabrini G.;
RT "Screening of 62 mutations in a cohort of cystic fibrosis patients from
RT north eastern Italy: their incidence and clinical features of defined
RT genotypes.";
RL Hum. Mutat. 2:389-394(1993).
RN [74]
RP VARIANTS CYS-31 AND ILE-1220, AND VARIANTS CF 890-GLN--LEU-1480 DEL;
RP LEU-912; TYR-949; PRO-1065; PRO-1071 AND 1204-TRP--LEU-1480 DEL.
RX PubMed=7522211; DOI=10.1006/geno.1994.1290;
RA Ghanem N., Costes B., Girodon E., Martin J., Fanen P., Goossens M.;
RT "Identification of eight mutations and three sequence variations in the
RT cystic fibrosis transmembrane conductance regulator (CFTR) gene.";
RL Genomics 21:434-436(1994).
RN [75]
RP VARIANT CF PRO-346.
RX PubMed=7513296; DOI=10.1007/bf00202817;
RA Boteva K., Papageorgiou E., Georgiou C., Angastiniotis M., Middleton L.T.,
RA Constantinou-Deltas C.D.;
RT "Novel cystic fibrosis mutation associated with mild disease in Cypriot
RT patients.";
RL Hum. Genet. 93:529-532(1994).
RN [76]
RP VARIANTS CF TYR-199; SER-619; ARG-1005 AND ARG-1291.
RX PubMed=7525450; DOI=10.1007/bf00211022;
RA Doerk T., Mekus F., Schmidt K., Bosshammer J., Fislage R., Heuer T.,
RA Dziadek V., Neumann T., Kaelin N., Wulbrand U., Wulf B., von der Hardt H.,
RA Maass G., Tuemmler B.;
RT "Detection of more than 50 different CFTR mutations in a large group of
RT German cystic fibrosis patients.";
RL Hum. Genet. 94:533-542(1994).
RN [77]
RP VARIANT CF GLU-1249.
RX PubMed=7520022; DOI=10.1159/000154223;
RA Greil I., Wagner K., Rosenkranz W.;
RT "A new missense mutation G1249E in exon 20 of the cystic fibrosis
RT transmembrane conductance regulator (CFTR) gene.";
RL Hum. Hered. 44:238-240(1994).
RN [78]
RP VARIANT CF GLU-1397.
RX PubMed=7524913; DOI=10.1093/hmg/3.6.999;
RA Petreska L., Koceva S., Gordova-Muratovska A., Nestorov R., Efremov G.D.;
RT "Identification of two new mutations (711 +3A-->G and V1397E) in CF
RT chromosomes of Albanian and Macedonian origin.";
RL Hum. Mol. Genet. 3:999-1000(1994).
RN [79]
RP VARIANT CF CYS-109.
RX PubMed=7524909; DOI=10.1093/hmg/3.6.1001;
RA Schaedel C., Kristoffersson A.-C., Kornfaelt R., Holmberg L.;
RT "A novel cystic fibrosis mutation, Y109C, in the first transmembrane domain
RT of CFTR.";
RL Hum. Mol. Genet. 3:1001-1002(1994).
RN [80]
RP VARIANT CF THR-120.
RX PubMed=7517264; DOI=10.1002/humu.1380030308;
RA Chillon M., Casals T., Gimenez J., Nunes V., Estivill X.;
RT "Analysis of the CFTR gene in the Spanish population: SSCP-screening for 60
RT known mutations and identification of four new mutations (Q30X, A120T,
RT 1812-1 G-->A, and 3667del4).";
RL Hum. Mutat. 3:223-230(1994).
RN [81]
RP VARIANT CF LEU-87.
RX PubMed=8081395; DOI=10.1002/humu.1380030412;
RA Bienvenu T., Petitpretz P., Beldjord C., Kaplan J.C.;
RT "A missense mutation (F87L) in exon 3 of the cystic fibrosis transmembrane
RT conductance regulator gene.";
RL Hum. Mutat. 3:395-396(1994).
RN [82]
RP VARIANTS CBAVD ARG-149; LYS-193; GLY-258 AND GLY-800.
RX PubMed=7529962;
RA Mercier B., Verlingue C., Lissens W., Silber S.J., Novelli G.,
RA Bonduelle M., Audrezet M.-P., Ferec C.;
RT "Is congenital bilateral absence of vas deferens a primary form of cystic
RT fibrosis? Analyses of the CFTR gene in 67 patients.";
RL Am. J. Hum. Genet. 56:272-277(1995).
RN [83]
RP VARIANTS CBAVD.
RX PubMed=7539342;
RA Jezequel P., Dorval I., Fergelot P., Chauvel B., Le Treut A.,
RA Le Gall J.-Y., Le Lannou D., Blayau M.;
RT "Structural analysis of CFTR gene in congenital bilateral absence of vas
RT deferens.";
RL Clin. Chem. 41:833-835(1995).
RN [84]
RP VARIANT CF SER-551.
RX PubMed=7606851; DOI=10.1111/j.1399-0004.1995.tb03931.x;
RA Orozco L., Lezana J.L., Villarreal M.T., Chavez M., Carnevale A.;
RT "Mild cystic fibrosis disease in three Mexican delta-F508/G551S compound
RT heterozygous siblings.";
RL Clin. Genet. 47:96-98(1995).
RN [85]
RP VARIANTS CF GLY-57; LYS-193 AND GLY-579.
RX PubMed=7544319; DOI=10.1007/bf00210414;
RA Brancolini V., Cremonesi L., Belloni E., Pappalardo E., Bordoni R.,
RA Seia M., Russo S., Padoan R., Giunta A., Ferrari M.;
RT "Search for mutations in pancreatic sufficient cystic fibrosis Italian
RT patients: detection of 90% of molecular defects and identification of three
RT novel mutations.";
RL Hum. Genet. 96:312-318(1995).
RN [86]
RP VARIANT CF TRP-206.
RX PubMed=8522333; DOI=10.1007/bf00210305;
RA Desgeorges M., Rodier M., Piot M., Demaille J., Claustres M.;
RT "Four adult patients with the missense mutation L206W and a mild cystic
RT fibrosis phenotype.";
RL Hum. Genet. 96:717-720(1995).
RN [87]
RP VARIANTS CF LEU-31 AND ARG-1098.
RX PubMed=7537150; DOI=10.1002/humu.1380050106;
RA Zielenski J., Markiewicz D., Chen H.S., Schappert K.T., Seller A.,
RA Durie P., Corey M., Tsui L.-C.;
RT "Identification of six mutations (R31L, 441delA, 681delC, 1461ins4, W1089R,
RT E1104X) in the cystic fibrosis transmembrane conductance regulator (CFTR)
RT gene.";
RL Hum. Mutat. 5:43-47(1995).
RN [88]
RP VARIANT CF ASN-572.
RX PubMed=7541273; DOI=10.1002/humu.1380050304;
RA Verlingue C., Kapranov N.I., Mercier B., Ginter E.K., Petrova N.V.,
RA Audrezet M.P., Ferec C.;
RT "Complete screening of mutations in the coding sequence of the CFTR gene in
RT a sample of CF patients from Russia: identification of three novel
RT alleles.";
RL Hum. Mutat. 5:205-209(1995).
RN [89]
RP VARIANT CF ARG-98.
RX PubMed=7581407; DOI=10.1002/humu.1380060216;
RA Romey M.-C., Desgeorges M., Ray P., Godard P., Demaille J., Claustres M.;
RT "Novel missense mutation in the first transmembrane segment of the CFTR
RT gene (Q98R) identified in a male adult.";
RL Hum. Mutat. 6:190-191(1995).
RN [90]
RP VARIANT CF ILE-338.
RX PubMed=7543567; DOI=10.1016/s0022-3476(95)70310-1;
RA Leoni G.B., Pitzalis S., Podda R., Zanda M., Silvetti M., Caocci L.,
RA Cao A., Rosatelli M.C.;
RT "A specific cystic fibrosis mutation (T338I) associated with the phenotype
RT of isolated hypotonic dehydration.";
RL J. Pediatr. 127:281-283(1995).
RN [91]
RP VARIANTS CF PHE-42; LEU-117; ARG-139 AND GLU-1006.
RX PubMed=7541510; DOI=10.1016/s0890-8508(95)80038-7;
RA Ferec C., Novelli G., Verlingue C., Quere I., Dallapiccola B.,
RA Audrezet M.P., Mercier B.;
RT "Identification of six novel CFTR mutations in a sample of Italian cystic
RT fibrosis patients.";
RL Mol. Cell. Probes 9:135-137(1995).
RN [92]
RP VARIANT CF SER-665.
RX PubMed=8800923; DOI=10.1159/000472165;
RA Messaoud T., Verlingue C., Denamur E., Pascaud O., Quere I., Fattoum S.,
RA Elion J., Ferec C.;
RT "Distribution of CFTR mutations in cystic fibrosis patients of Tunisian
RT origin: identification of two novel mutations.";
RL Eur. J. Hum. Genet. 4:20-24(1996).
RN [93]
RP VARIANT CF ARG-314.
RX PubMed=8829633;
RX DOI=10.1002/(sici)1098-1004(1996)7:2<151::aid-humu10>3.0.co;2-1;
RA Nasr S.Z., Strong T.V., Mansoura M.K., Dawson D.C., Collins F.S.;
RT "Novel missense mutation (G314R) in a cystic fibrosis patient with hepatic
RT failure.";
RL Hum. Mutat. 7:151-154(1996).
RN [94]
RP VARIANT CF CYS-569.
RX PubMed=8723693; DOI=10.1002/humu.1380070402;
RA Petreska L., Plaseska D., Koseva S., Stavljenic-Rukavina A., Efremov G.D.;
RT "A novel mutation in exon 12 (Y569C) of the CFTR gene identified in a
RT patient of Croatian origin.";
RL Hum. Mutat. 7:374-375(1996).
RN [95]
RP VARIANT CF ARG-1061.
RX PubMed=8723695;
RX DOI=10.1002/(sici)1098-1004(1996)7:4<376::aid-humu18>3.0.co;2-#;
RA Bienvenu T., Chertkoff L., Beldjord C., Segal E., Carniglia L.,
RA Barreiro C., Kaplan J.-C.;
RT "Identification of three novel mutations in the cystic fibrosis
RT transmembrane conductance regulator gene in Argentinian CF patients.";
RL Hum. Mutat. 7:376-377(1996).
RN [96]
RP VARIANT CF LEU-562.
RX PubMed=8956039;
RX DOI=10.1002/(sici)1098-1004(1996)8:4<340::aid-humu7>3.0.co;2-b;
RA Hughes D.J., Hill A.J.M., Macek M. Jr., Redmond A.O., Nevin N.C.,
RA Graham C.A.;
RT "Mutation characterization of CFTR gene in 206 Northern Irish CF families:
RT thirty mutations, including two novel, account for approximately 94% of CF
RT chromosomes.";
RL Hum. Mutat. 8:340-347(1996).
RN [97]
RP CHARACTERIZATION OF VARIANT CF ASP-551, CATALYTIC ACTIVITY, FUNCTION,
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=8910473; DOI=10.1074/jbc.271.45.28463;
RA Li C., Ramjeesingh M., Wang W., Garami E., Hewryk M., Lee D., Rommens J.M.,
RA Galley K., Bear C.E.;
RT "ATPase activity of the cystic fibrosis transmembrane conductance
RT regulator.";
RL J. Biol. Chem. 271:28463-28468(1996).
RN [98]
RP VARIANT CBAVD TYR-50.
RX PubMed=9067761;
RX DOI=10.1002/(sici)1098-1004(1997)9:2<183::aid-humu13>3.0.co;2-z;
RA Zielenski J., Patrizio P., Markiewicz D., Asch R.H., Tsui L.-C.;
RT "Identification of two mutations (S50Y and 4173delC) in the CFTR gene from
RT patients with congenital bilateral absence of vas deferens (CBAVD).";
RL Hum. Mutat. 9:183-184(1997).
RN [99]
RP VARIANT CF MET-1140 DEL.
RX PubMed=9101301;
RX DOI=10.1002/(sici)1098-1004(1997)9:4<368::aid-humu13>3.0.co;2-0;
RA Clavel C., Pennaforte F., Pigeon F., Verlingue C., Birembaut P., Ferec C.;
RT "Identification of four novel mutations in the cystic fibrosis
RT transmembrane conductance regulator gene: E664X, 2113delA, 306delTAGA, and
RT delta M1140.";
RL Hum. Mutat. 9:368-369(1997).
RN [100]
RP VARIANT CF ASP-141.
RX PubMed=9222768;
RX DOI=10.1002/(sici)1098-1004(1997)10:1<86::aid-humu15>3.0.co;2-w;
RA Gouya L., Pascaud O., Munck A., Elion J., Denamur E.;
RT "Novel mutation (A141D) in exon 4 of the CFTR gene identified in an
RT Algerian patient.";
RL Hum. Mutat. 10:86-87(1997).
RN [101]
RP VARIANT CF CYS-1066.
RX PubMed=9375855;
RX DOI=10.1002/(sici)1098-1004(1997)10:5<387::aid-humu9>3.0.co;2-c;
RA Casals T., Pacheco P., Barreto C., Gimenez J., Ramos M.D., Pereira S.,
RA Pinheiro J.A., Cobos N., Curvelo A., Vazquez C., Rocha H., Seculi J.L.,
RA Perez E., Dapena J., Carrilho E., Duarte A., Palacio A.M., Nunes V.,
RA Lavinha J., Estivill X.;
RT "Missense mutation R1066C in the second transmembrane domain of CFTR causes
RT a severe cystic fibrosis phenotype: study of 19 heterozygous and 2
RT homozygous patients.";
RL Hum. Mutat. 10:387-392(1997).
RN [102]
RP VARIANTS CF GLU-85; HIS-117; TYR-287; GLU-455; ASP-551; PRO-1070 AND
RP LYS-1303.
RX PubMed=9401006;
RX DOI=10.1002/(sici)1098-1004(1997)10:6<436::aid-humu4>3.0.co;2-b;
RA Shrimpton A.E., Borowitz D., Swender P.;
RT "Cystic fibrosis mutation frequencies in upstate New York.";
RL Hum. Mutat. 10:436-442(1997).
RN [103]
RP VARIANT CF PHE-311 DEL.
RX PubMed=9443874; DOI=10.1086/301681;
RA Friedman K.J., Leigh M.W., Czarnecki P., Feldman G.L.;
RT "Cystic fibrosis transmembrane-conductance regulator mutations among
RT African Americans.";
RL Am. J. Hum. Genet. 62:195-196(1998).
RN [104]
RP CHARACTERIZATION OF VARIANTS CF VAL-1137; MET-1140 DEL AND HIS-1152,
RP MUTAGENESIS OF MET-1137; ILE-1139 AND ASP-1154, SUBCELLULAR LOCATION, AND
RP FUNCTION.
RX PubMed=9804160; DOI=10.1016/s0014-5793(98)01042-4;
RA Vankeerberghen A., Wei L., Teng H., Jaspers M., Cassiman J.J., Nilius B.,
RA Cuppens H.;
RT "Characterization of mutations located in exon 18 of the CFTR gene.";
RL FEBS Lett. 437:1-4(1998).
RN [105]
RP VARIANTS CF LEU-1013 AND ILE-1028.
RX PubMed=9521595; DOI=10.1007/s004390050683;
RA Onay T., Topaloglu O., Zielenski J., Gokgoz N., Kayserili H., Camcioglu Y.,
RA Cokugras H., Akcakaya N., Apak M., Tsui L.-C., Kirdar B.;
RT "Analysis of the CFTR gene in Turkish cystic fibrosis patients:
RT identification of three novel mutations (3172delAC, P1013L and M1028I).";
RL Hum. Genet. 102:224-230(1998).
RN [106]
RP VARIANTS CF, AND VARIANTS CYS-31; GLN-75; VAL-506 AND CYS-668.
RX PubMed=9921909; DOI=10.1007/s004390050897;
RA Bombieri C., Benetazzo M., Saccomani A., Belpinati F., Gile L.S.,
RA Luisetti M., Pignatti P.F.;
RT "Complete mutational screening of the CFTR gene in 120 patients with
RT pulmonary disease.";
RL Hum. Genet. 103:718-722(1998).
RN [107]
RP CHARACTERIZATION OF VARIANTS CF PHE-601; SER-610; THR-613; GLY-614;
RP THR-618; SER-619; GLN-620; PRO-620; ARG-628; PRO-633 AND SER-665,
RP CHARACTERIZATION OF VARIANTS CBAVD ASP-622; GLY-792 AND GLY-800, AND
RP CHARACTERIZATION OF VARIANT THORACIC SARCOIDOSIS LYS-828.
RX PubMed=9736778; DOI=10.1093/hmg/7.11.1761;
RA Vankeerberghen A., Wei L., Jaspers M., Cassiman J.-J., Nilius B.,
RA Cuppens H.;
RT "Characterization of 19 disease-associated missense mutations in the
RT regulatory domain of the cystic fibrosis transmembrane conductance
RT regulator.";
RL Hum. Mol. Genet. 7:1761-1769(1998).
RN [108]
RP VARIANTS CF SER-560 AND ASP-569.
RX PubMed=9482579;
RX DOI=10.1002/(sici)1098-1004(1998)11:2<152::aid-humu8>3.0.co;2-l;
RA Malone G., Haworth A., Schwarz M.J., Cuppens H., Super M.;
RT "Detection of five novel mutations of the cystic fibrosis transmembrane
RT regulator (CFTR) gene in Pakistani patients with cystic fibrosis: Y569D,
RT Q98X, 296+12(T>C), 1161delC and 621+2(T>C).";
RL Hum. Mutat. 11:152-157(1998).
RN [109]
RP VARIANTS CF PHE-13 AND ILE-338.
RX PubMed=9554753;
RA Leoni G.B., Pitzalis S., Tonelli R., Cao A.;
RT "Identification of a novel mutation (S13F) in the CFTR gene in a CF patient
RT of Sardinian origin.";
RL Hum. Mutat. 11:337-337(1998).
RN [110]
RP VARIANTS CF PRO-117 AND ASP-192 DEL.
RX PubMed=9452048; DOI=10.1002/humu.1380110127;
RA Feldmann D., Sardet A., Cougoureux E., Plouvier E., Fontaine J.-L.,
RA Tournier G., Aymard P.;
RT "Identification of three novel mutations in the CFTR gene, R117P,
RT deltaD192, and 3121+1G-->A in four French patients.";
RL Hum. Mutat. Suppl. 1:S78-S80(1998).
RN [111]
RP VARIANT CF ARG-1065.
RX PubMed=9452054; DOI=10.1002/humu.1380110133;
RA Casals T., Ramos M.D., Gimenez J., Nadal M., Nunes V., Estivill X.;
RT "Paternal origin of a de novo novel CFTR mutation (L1065R) causing cystic
RT fibrosis.";
RL Hum. Mutat. Suppl. 1:S99-S102(1998).
RN [112]
RP VARIANT CF ASN-LYS-370 INS.
RX PubMed=9452073; DOI=10.1002/humu.1380110152;
RA Shackleton S., Harris A.;
RT "A 2-amino acid insertion mutation (1243insACAAAA) in exon 7 of the CFTR
RT gene.";
RL Hum. Mutat. Suppl. 1:S156-S157(1998).
RN [113]
RP VARIANT CBAVD GLY-513, AND VARIANT MET-470.
RX PubMed=10651488;
RA Bienvenu T., Bousquet S., Vidaud D., Hubert D., Francoual C., Beldjord C.,
RA Kaplan J.-C.;
RT "A novel missense mutation D513G in exon 10 of the cystic fibrosis
RT transmembrane conductance regulator (CFTR) gene identified in a French
RT CBAVD patient.";
RL Hum. Mutat. 12:213-214(1998).
RN [114]
RP VARIANTS CBAVD LEU-111; LYS-244; VAL-544 AND VAL-1364.
RA de Meeus A., Guittard C., Desgeorges M., Carles S., Demaille J.,
RA Claustres M.;
RT "Genetic findings in congenital bilateral aplasia of vas deferens patients
RT and identification of six novel mutations.";
RL Hum. Mutat. 12:480-480(1998).
RN [115]
RP VARIANT CF GLY-579.
RX PubMed=10094564;
RX DOI=10.1002/(sici)1098-1004(1999)13:2<173::aid-humu20>3.0.co;2-3;
RA Picci L., Cameran M., Olante P., Zacchello F., Scarpa M.;
RT "Identification of a D579G homozygote cystic fibrosis patient with
RT pancreatic sufficiency and minor lung involvement.";
RL Hum. Mutat. 13:173-173(1999).
RN [116]
RP CHARACTERIZATION OF VARIANTS CF HIS-117; THR-148; ARG-178; LYS-193;
RP ASP-551; SER-551; GLN-620; VAL-648; GLY-800; TYR-949; THR-1067; GLN-1070;
RP GLU-1244; PRO-1255 AND ASP-1349.
RX PubMed=11242048; DOI=10.1038/35065099;
RA Choi J.Y., Muallem D., Kiselyov K., Lee M.G., Thomas P.J., Muallem S.;
RT "Aberrant CFTR-dependent HCO3- transport in mutations associated with
RT cystic fibrosis.";
RL Nature 410:94-97(2001).
RN [117]
RP VARIANTS CF THR-148; PHE-508 DEL; 890-GLN--LEU-1480 DEL; 1023-ILE-VAL-1024
RP DEL AND LYS-1303.
RX PubMed=12394343; DOI=10.1097/00125817-200209000-00001;
RA Rohlfs E.M., Zhou Z., Sugarman E.A., Heim R.A., Pace R.G., Knowles M.R.,
RA Silverman L.M., Allitto B.A.;
RT "The I148T CFTR allele occurs on multiple haplotypes: a complex allele is
RT associated with cystic fibrosis.";
RL Genet. Med. 4:319-323(2002).
RN [118]
RP VARIANT CF LEU-693.
RX PubMed=12167682; DOI=10.1056/nejmoa011899;
RA Groman J.D., Meyer M.E., Wilmott R.W., Zeitlin P.L., Cutting G.R.;
RT "Variant cystic fibrosis phenotypes in the absence of CFTR mutations.";
RL N. Engl. J. Med. 347:401-407(2002).
RN [119]
RP CHARACTERIZATION OF VARIANT CF TYR-287 AND PHE-508 DEL, SUBCELLULAR
RP LOCATION, FUNCTION, AND GLYCOSYLATION.
RX PubMed=12529365; DOI=10.1074/jbc.m212843200;
RA Silvis M.R., Picciano J.A., Bertrand C., Weixel K., Bridges R.J.,
RA Bradbury N.A.;
RT "A mutation in the cystic fibrosis transmembrane conductance regulator
RT generates a novel internalization sequence and enhances endocytic rates.";
RL J. Biol. Chem. 278:11554-11560(2003).
RN [120]
RP CHARACTERIZATION OF VARIANT CF PHE-508 DEL, SUBCELLULAR LOCATION, FUNCTION,
RP AND TISSUE SPECIFICITY.
RX PubMed=15716351; DOI=10.1091/mbc.e04-11-1010;
RA Kreda S.M., Mall M., Mengos A., Rochelle L., Yankaskas J., Riordan J.R.,
RA Boucher R.C.;
RT "Characterization of wild-type and deltaF508 cystic fibrosis transmembrane
RT regulator in human respiratory epithelia.";
RL Mol. Biol. Cell 16:2154-2167(2005).
RN [121]
RP CHARACTERIZATION OF VARIANTS CF PHE-508 DEL; THR-560; GLU-561 AND ILE-562.
RX PubMed=17098864; DOI=10.1073/pnas.0608312103;
RA Roxo-Rosa M., Xu Z., Schmidt A., Neto M., Cai Z., Soares C.M.,
RA Sheppard D.N., Amaral M.D.;
RT "Revertant mutants G550E and 4RK rescue cystic fibrosis mutants in the
RT first nucleotide-binding domain of CFTR by different mechanisms.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:17891-17896(2006).
RN [122]
RP CHARACTERIZATION OF VARIANT CF THR-148.
RX PubMed=16822950; DOI=10.1152/ajpcell.00088.2006;
RA Suaud L., Yan W., Rubenstein R.C.;
RT "Abnormal regulatory interactions of I148T-CFTR and the epithelial Na+
RT channel in Xenopus oocytes.";
RL Am. J. Physiol. 292:C603-C611(2007).
RN [123]
RP CHARACTERIZATION OF VARIANT CF LYS-1303, FUNCTION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=17182731; DOI=10.1152/ajpcell.00064.2006;
RA Suaud L., Yan W., Carattino M.D., Robay A., Kleyman T.R., Rubenstein R.C.;
RT "Regulatory interactions of N1303K-CFTR and ENaC in Xenopus oocytes:
RT evidence that chloride transport is not necessary for inhibition of ENaC.";
RL Am. J. Physiol. 292:C1553-C1561(2007).
RN [124]
RP VARIANTS GLN-75 AND MET-470, AND VARIANTS CBAVD TRP-74; HIS-110; HIS-117;
RP HIS-170; TRP-206; ASP-232; TRP-334; TYR-443; PHE-508 DEL; VAL-556; ILE-562;
RP ALA-576; ASP-622; CYS-668; GLY-938; ILE-952; VAL-959; PHE-977; PHE-997;
RP CYS-1032; ARG-1069; HIS-1152; GLU-1153; ASN-1270; 1282-TRP--LEU-1480 DEL;
RP HIS-1352 AND 1473-GLU--LEU-1480 DEL.
RX PubMed=17329263; DOI=10.1093/humrep/dem024;
RA Ratbi I., Legendre M., Niel F., Martin J., Soufir J.C., Izard V.,
RA Costes B., Costa C., Goossens M., Girodon E.;
RT "Detection of cystic fibrosis transmembrane conductance regulator (CFTR)
RT gene rearrangements enriches the mutation spectrum in congenital bilateral
RT absence of the vas deferens and impacts on genetic counselling.";
RL Hum. Reprod. 22:1285-1291(2007).
RN [125]
RP VARIANT [LARGE SCALE ANALYSIS] MET-470.
RX PubMed=18987736; DOI=10.1038/nature07485;
RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S.,
RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A.,
RA DiPersio J.F., Wilson R.K.;
RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT genome.";
RL Nature 456:66-72(2008).
RN [126]
RP VARIANTS CF 220-GLN--LEU-1480 DEL; MET-470; PHE-508 DEL; ILE-562 AND
RP GLU-1006.
RX PubMed=20691141; DOI=10.25011/cim.v33i4.14226;
RA Tomaiuolo A.C., Alghisi F., Petrocchi S., Surace C., Roberti M.C.,
RA Bella S., Lucidi V., Angioni A.;
RT "Clinical hallmarks and genetic polymorphisms in the CFTR gene contribute
RT to the disclosure of the A1006E mutation.";
RL Clin. Invest. Med. 33:E234-E239(2010).
RN [127]
RP CHARACTERIZATION OF VARIANT CF PHE-508 DEL, INTERACTION WITH GORASP2,
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=21884936; DOI=10.1016/j.cell.2011.07.021;
RA Gee H.Y., Noh S.H., Tang B.L., Kim K.H., Lee M.G.;
RT "Rescue of DeltaF508-CFTR trafficking via a GRASP-dependent unconventional
RT secretion pathway.";
RL Cell 146:746-760(2011).
RN [128]
RP CHARACTERIZATION OF VARIANT CF PHE-508 DEL.
RX PubMed=27241308; DOI=10.1016/j.jmb.2016.05.016;
RA Faure G., Bakouh N., Lourdel S., Odolczyk N., Premchandar A., Servel N.,
RA Hatton A., Ostrowski M.K., Xu H., Saul F.A., Moquereau C., Bitam S.,
RA Pranke I., Planelles G., Teulon J., Herrmann H., Roldan A.,
RA Zielenkiewicz P., Dadlez M., Lukacs G.L., Sermet-Gaudelus I., Ollero M.,
RA Corringer P.J., Edelman A.;
RT "Rattlesnake phospholipase A2 increases CFTR-chloride channel current and
RT corrects DelF508CFTR dysfunction: impact in cystic fibrosis.";
RL J. Mol. Biol. 428:2898-2915(2016).
RN [129]
RP CHARACTERIZATION OF VARIANT CF HIS-117, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26846474; DOI=10.1113/jp271723;
RA Yu Y.C., Sohma Y., Hwang T.C.;
RT "On the mechanism of gating defects caused by the R117H mutation in cystic
RT fibrosis transmembrane conductance regulator.";
RL J. Physiol. (Lond.) 594:3227-3244(2016).
RN [130]
RP CHARACTERIZATION OF VARIANT CF PHE-508 DEL, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ILE-539.
RX PubMed=28001373; DOI=10.1021/acs.biochem.6b00853;
RA Zhang Z., Baksh M.M., Finn M.G., Heidary D.K., Richards C.I.;
RT "Direct measurement of trafficking of the cystic fibrosis transmembrane
RT conductance regulator to the cell surface and binding to a chemical
RT chaperone.";
RL Biochemistry 56:240-249(2017).
RN [131]
RP CHARACTERIZATION OF VARIANTS CF PHE-508 DEL AND ASP-551, SUBCELLULAR
RP LOCATION, AND FUNCTION.
RX PubMed=28087700; DOI=10.1074/jbc.m116.751537;
RA Meng X., Wang Y., Wang X., Wrennall J.A., Rimington T.L., Li H., Cai Z.,
RA Ford R.C., Sheppard D.N.;
RT "Two small molecules restore stability to a sub-population of the cystic
RT fibrosis transmembrane conductance regulator with the predominant disease-
RT causing mutation.";
RL J. Biol. Chem. 292:3706-3719(2017).
RN [132]
RP CHARACTERIZATION OF VARIANT CF PHE-508 DEL, AND SUBCELLULAR LOCATION.
RX PubMed=28067262; DOI=10.1038/srep39887;
RA Piao H., Kim J., Noh S.H., Kweon H.S., Kim J.Y., Lee M.G.;
RT "Sec16A is critical for both conventional and unconventional secretion of
RT CFTR.";
RL Sci. Rep. 7:39887-39887(2017).
CC -!- FUNCTION: Epithelial ion channel that plays an important role in the
CC regulation of epithelial ion and water transport and fluid homeostasis
CC (PubMed:26823428). Mediates the transport of chloride ions across the
CC cell membrane (PubMed:10792060, PubMed:11524016, PubMed:11707463,
CC PubMed:12519745, PubMed:15010471, PubMed:12588899, PubMed:17036051,
CC PubMed:19398555, PubMed:19621064, PubMed:22178883, PubMed:25330774,
CC PubMed:1712898, PubMed:8910473, PubMed:9804160, PubMed:12529365,
CC PubMed:17182731, PubMed:26846474, PubMed:28087700). Channel activity is
CC coupled to ATP hydrolysis (PubMed:8910473). The ion channel is also
CC permeable to HCO(3)(-); selectivity depends on the extracellular
CC chloride concentration (PubMed:15010471, PubMed:19019741). Exerts its
CC function also by modulating the activity of other ion channels and
CC transporters (PubMed:12403779, PubMed:22178883, PubMed:22121115,
CC PubMed:27941075). Plays an important role in airway fluid homeostasis
CC (PubMed:16645176, PubMed:19621064, PubMed:26823428). Contributes to the
CC regulation of the pH and the ion content of the airway surface fluid
CC layer and thereby plays an important role in defense against pathogens
CC (PubMed:14668433, PubMed:16645176, PubMed:26823428). Modulates the
CC activity of the epithelial sodium channel (ENaC) complex, in part by
CC regulating the cell surface expression of the ENaC complex
CC (PubMed:17434346, PubMed:27941075, PubMed:17182731). Inhibits the
CC activity of the ENaC channel containing subunits SCNN1A, SCNN1B and
CC SCNN1G (PubMed:17182731). Inhibits the activity of the ENaC channel
CC containing subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC
CC channel containing subunits SCNN1A, SCNN1B and SCNN1G
CC (PubMed:17182731). Inhibits the activity of the ENaC channel containing
CC subunits SCNN1D, SCNN1B and SCNN1G, but not of the ENaC channel
CC containing subunits SCNN1A, SCNN1B and SCNN1G (PubMed:27941075). May
CC regulate bicarbonate secretion and salvage in epithelial cells by
CC regulating the transporter SLC4A7 (PubMed:12403779). Can inhibit the
CC chloride channel activity of ANO1 (PubMed:22178883). Plays a role in
CC the chloride and bicarbonate homeostasis during sperm epididymal
CC maturation and capacitation (PubMed:19923167, PubMed:27714810).
CC {ECO:0000269|PubMed:10792060, ECO:0000269|PubMed:11524016,
CC ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:12403779,
CC ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:12529365,
CC ECO:0000269|PubMed:12588899, ECO:0000269|PubMed:14668433,
CC ECO:0000269|PubMed:15010471, ECO:0000269|PubMed:16645176,
CC ECO:0000269|PubMed:17036051, ECO:0000269|PubMed:1712898,
CC ECO:0000269|PubMed:17182731, ECO:0000269|PubMed:19019741,
CC ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:19621064,
CC ECO:0000269|PubMed:22178883, ECO:0000269|PubMed:25330774,
CC ECO:0000269|PubMed:26627831, ECO:0000269|PubMed:26823428,
CC ECO:0000269|PubMed:26846474, ECO:0000269|PubMed:27714810,
CC ECO:0000269|PubMed:27941075, ECO:0000269|PubMed:28087700,
CC ECO:0000269|PubMed:8910473, ECO:0000269|PubMed:9804160,
CC ECO:0000305|PubMed:19923167}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + closed Cl(-) channel = ADP + phosphate + open
CC Cl(-) channel.; EC=5.6.1.6; Evidence={ECO:0000269|PubMed:11524016,
CC ECO:0000269|PubMed:15284228, ECO:0000269|PubMed:26627831,
CC ECO:0000269|PubMed:8910473};
CC -!- SUBUNIT: Monomer; does not require oligomerization for channel activity
CC (PubMed:11524016). May form oligomers in the membrane
CC (PubMed:11524016). Interacts with SLC26A3, SLC26A6 and SHANK2 (By
CC similarity). Interacts with SLC9A3R1 and MYO6 (PubMed:12403779,
CC PubMed:15247260, PubMed:11304524). Interacts (via C-terminus) with GOPC
CC (via PDZ domain); this promotes CFTR internalization and thereby
CC decreases channel activity (PubMed:11707463, PubMed:16331976).
CC Interacts with SLC4A7 through SLC9A3R1 (PubMed:12403779). Found in a
CC complex with MYO5B and RAB11A (PubMed:17462998). Interacts with ANO1
CC (PubMed:22178883). Interacts with SLC26A8 (PubMed:22121115). Interacts
CC with AHCYL1; the interaction increases CFTR activity (By similarity).
CC Interacts with CSE1L (PubMed:20933420). The core-glycosylated form
CC interacts with GORASP2 (via PDZ GRASP-type 1 domain) in respone to ER
CC stress (PubMed:21884936). Interacts with MARCHF2; the interaction leads
CC to CFTR ubiqtuitination and degradation (PubMed:23818989).
CC {ECO:0000250|UniProtKB:P26361, ECO:0000250|UniProtKB:P34158,
CC ECO:0000269|PubMed:11304524, ECO:0000269|PubMed:11524016,
CC ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:12403779,
CC ECO:0000269|PubMed:15247260, ECO:0000269|PubMed:16331976,
CC ECO:0000269|PubMed:17462998, ECO:0000269|PubMed:20933420,
CC ECO:0000269|PubMed:21884936, ECO:0000269|PubMed:22121115,
CC ECO:0000269|PubMed:22178883, ECO:0000269|PubMed:23818989}.
CC -!- INTERACTION:
CC P13569; P60709: ACTB; NbExp=5; IntAct=EBI-349854, EBI-353944;
CC P13569; P16615-1: ATP2A2; NbExp=6; IntAct=EBI-349854, EBI-11613988;
CC P13569; P51572: BCAP31; NbExp=3; IntAct=EBI-349854, EBI-77683;
CC P13569; O43852-1: CALU; NbExp=2; IntAct=EBI-349854, EBI-5280679;
CC P13569; P27824: CANX; NbExp=13; IntAct=EBI-349854, EBI-355947;
CC P13569; P07384: CAPN1; NbExp=3; IntAct=EBI-349854, EBI-1542113;
CC P13569; P51790-2: CLCN3; NbExp=2; IntAct=EBI-349854, EBI-25495635;
CC P13569; Q9BUN8: DERL1; NbExp=2; IntAct=EBI-349854, EBI-398977;
CC P13569; Q9HD26: GOPC; NbExp=4; IntAct=EBI-349854, EBI-349832;
CC P13569; Q9H8Y8: GORASP2; NbExp=3; IntAct=EBI-349854, EBI-739467;
CC P13569; O15554: KCNN4; NbExp=5; IntAct=EBI-349854, EBI-2924473;
CC P13569; P05787: KRT8; NbExp=7; IntAct=EBI-349854, EBI-297852;
CC P13569; Q9HBW0: LPAR2; NbExp=4; IntAct=EBI-349854, EBI-765995;
CC P13569; Q5T2W1: PDZK1; NbExp=3; IntAct=EBI-349854, EBI-349819;
CC P13569; Q99942: RNF5; NbExp=3; IntAct=EBI-349854, EBI-348482;
CC P13569; Q96RN1: SLC26A8; NbExp=2; IntAct=EBI-349854, EBI-1792052;
CC P13569; O14745: SLC9A3R1; NbExp=15; IntAct=EBI-349854, EBI-349787;
CC P13569; Q15599: SLC9A3R2; NbExp=14; IntAct=EBI-349854, EBI-1149760;
CC P13569; P19120: HSPA8; Xeno; NbExp=2; IntAct=EBI-349854, EBI-907802;
CC P13569; Q9QX74: Shank2; Xeno; NbExp=2; IntAct=EBI-349854, EBI-397902;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:12519745, ECO:0000269|PubMed:12529365,
CC ECO:0000269|PubMed:1284548, ECO:0000269|PubMed:15247260,
CC ECO:0000269|PubMed:15716351, ECO:0000269|PubMed:17462998,
CC ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:19621064,
CC ECO:0000269|PubMed:20008117, ECO:0000269|PubMed:22207244,
CC ECO:0000269|PubMed:28130590}; Multi-pass membrane protein
CC {ECO:0000269|Ref.55}. Early endosome membrane
CC {ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20008117}; Multi-pass
CC membrane protein {ECO:0000269|Ref.55}. Cell membrane
CC {ECO:0000269|PubMed:10792060, ECO:0000269|PubMed:11524016,
CC ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:12588899,
CC ECO:0000269|PubMed:15010471, ECO:0000269|PubMed:17036051,
CC ECO:0000269|PubMed:1712898, ECO:0000269|PubMed:17182731,
CC ECO:0000269|PubMed:19019741, ECO:0000269|PubMed:19398555,
CC ECO:0000269|PubMed:21884936, ECO:0000269|PubMed:22178883,
CC ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:26846474,
CC ECO:0000269|PubMed:28001373, ECO:0000269|PubMed:28067262,
CC ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:28130590,
CC ECO:0000269|PubMed:9804160, ECO:0000305|PubMed:8910473}; Multi-pass
CC membrane protein {ECO:0000269|Ref.55}. Recycling endosome membrane
CC {ECO:0000305|PubMed:17462998}; Multi-pass membrane protein
CC {ECO:0000269|Ref.55}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:25330774}; Multi-pass
CC membrane protein {ECO:0000269|Ref.55}. Nucleus
CC {ECO:0000250|UniProtKB:P34158}. 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 (PubMed:17462998, PubMed:19398555,
CC PubMed:20008117). In the oviduct and bronchus, detected on the apical
CC side of epithelial cells, but not associated with cilia
CC (PubMed:22207244). In Sertoli cells, a processed product is detected in
CC the nucleus (By similarity). ER stress induces GORASP2-mediated
CC unconventional (ER/Golgi-independent) trafficking of core-glycosylated
CC CFTR to cell membrane (PubMed:21884936). {ECO:0000250|UniProtKB:P34158,
CC ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20008117,
CC ECO:0000269|PubMed:21884936, ECO:0000269|PubMed:22207244,
CC ECO:0000305|PubMed:17462998}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P13569-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P13569-2; Sequence=VSP_022123;
CC Name=3;
CC IsoId=P13569-3; Sequence=VSP_022124, VSP_022125;
CC -!- TISSUE SPECIFICITY: Expressed in the respiratory airway, including
CC bronchial epithelium, and in the female reproductive tract, including
CC oviduct (at protein level) (PubMed:22207244, PubMed:15716351). Detected
CC in pancreatic intercalated ducts in the exocrine tissue, on epithelial
CC cells in intralobular striated ducts in sublingual salivary glands, on
CC apical membranes of crypt cells throughout the small and large
CC intestine, and on the reabsorptive duct in eccrine sweat glands
CC (PubMed:1284548, PubMed:28130590). Detected on the equatorial segment
CC of the sperm head (at protein level) (PubMed:19923167). Detected in
CC nasal and bronchial superficial epithelium (PubMed:15716351). Expressed
CC by the central cells on the sebaceous glands, dermal adipocytes and, at
CC lower levels, by epithelial cells (PubMed:28130590).
CC {ECO:0000269|PubMed:1284548, ECO:0000269|PubMed:15716351,
CC ECO:0000269|PubMed:19923167, ECO:0000269|PubMed:22207244,
CC ECO:0000269|PubMed:28130590}.
CC -!- DOMAIN: Binds and hydrolyzes ATP via the two cytoplasmic ABC
CC transporter nucleotide-binding domains (PubMed:15284228). The two ATP-
CC binding domains interact with each other, forming a head-to-tail dimer
CC (PubMed:17036051). Normal ATPase activity requires interaction between
CC the two domains (PubMed:15284228). The first ABC transporter
CC nucleotide-binding domain has no ATPase activity by itself (By
CC similarity). {ECO:0000250|UniProtKB:P26361,
CC ECO:0000269|PubMed:15284228, ECO:0000269|PubMed:17036051}.
CC -!- DOMAIN: The PDZ-binding motif mediates interactions with GOPC and with
CC the SLC4A7, SLC9A3R1/EBP50 complex. {ECO:0000269|PubMed:11304524,
CC ECO:0000269|PubMed:11707463, ECO:0000269|PubMed:16331976}.
CC -!- DOMAIN: The R region is intrinsically disordered (PubMed:10792060,
CC PubMed:17660831). It mediates channel activation when it is
CC phosphorylated, but not in the absence of phosphorylation
CC (PubMed:10792060). {ECO:0000269|PubMed:10792060,
CC ECO:0000269|PubMed:17660831}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12529365,
CC ECO:0000269|PubMed:1699669, ECO:0000269|PubMed:20008117,
CC ECO:0000269|PubMed:21884936, ECO:0000269|PubMed:28067262}.
CC -!- PTM: Phosphorylated; cAMP treatment promotes phosphorylation and
CC activates the channel (PubMed:12588899, PubMed:17036051,
CC PubMed:8910473). Dephosphorylation decreases the ATPase activity (in
CC vitro) (PubMed:8910473). Phosphorylation at PKA sites activates the
CC channel (PubMed:10792060, PubMed:12519745, PubMed:12588899,
CC PubMed:25330774). Phosphorylation at PKC sites enhances the response to
CC phosphorylation by PKA (PubMed:12588899). Phosphorylated by AMPK; this
CC inhibits channel activity (PubMed:12519745).
CC {ECO:0000269|PubMed:10792060, ECO:0000269|PubMed:12519745,
CC ECO:0000269|PubMed:12588899, ECO:0000269|PubMed:1377674,
CC ECO:0000269|PubMed:17036051, ECO:0000269|PubMed:22119790,
CC ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:8910473,
CC ECO:0000269|PubMed:9385646}.
CC -!- PTM: Ubiquitinated, leading to its degradation in the lysosome
CC (PubMed:19398555, PubMed:23818989). Deubiquitination by USP10 in early
CC endosomes enhances its endocytic recycling to the cell membrane
CC (PubMed:19398555). Ubiquitinated by RNF185 during ER stress
CC (PubMed:24019521). Ubiquitinated by MARCHF2 (PubMed:23818989).
CC {ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:22119790,
CC ECO:0000269|PubMed:23818989, ECO:0000269|PubMed:24019521}.
CC -!- DISEASE: Cystic fibrosis (CF) [MIM:219700]: A common generalized
CC disorder of the exocrine glands which impairs clearance of secretions
CC in a variety of organs. It is characterized by the triad of chronic
CC bronchopulmonary disease (with recurrent respiratory infections),
CC pancreatic insufficiency (which leads to malabsorption and growth
CC retardation) and elevated sweat electrolytes. It is the most common
CC genetic disease in Caucasians, with a prevalence of about 1 in 2'000
CC live births. Inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:10094564, ECO:0000269|PubMed:11242048,
CC ECO:0000269|PubMed:12167682, ECO:0000269|PubMed:12394343,
CC ECO:0000269|PubMed:12529365, ECO:0000269|PubMed:1284466,
CC ECO:0000269|PubMed:1284468, ECO:0000269|PubMed:1284529,
CC ECO:0000269|PubMed:1284530, ECO:0000269|PubMed:1284548,
CC ECO:0000269|PubMed:1379210, ECO:0000269|PubMed:15528182,
CC ECO:0000269|PubMed:15716351, ECO:0000269|PubMed:16822950,
CC ECO:0000269|PubMed:1695717, ECO:0000269|PubMed:1699669,
CC ECO:0000269|PubMed:17098864, ECO:0000269|PubMed:1710600,
CC ECO:0000269|PubMed:1712898, ECO:0000269|PubMed:17182731,
CC ECO:0000269|PubMed:20008117, ECO:0000269|PubMed:20150177,
CC ECO:0000269|PubMed:20691141, ECO:0000269|PubMed:21884936,
CC ECO:0000269|PubMed:2236053, ECO:0000269|PubMed:25330774,
CC ECO:0000269|PubMed:26846474, ECO:0000269|PubMed:27241308,
CC ECO:0000269|PubMed:28001373, ECO:0000269|PubMed:28067262,
CC ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:7504969,
CC ECO:0000269|PubMed:7505694, ECO:0000269|PubMed:7513296,
CC ECO:0000269|PubMed:7517264, ECO:0000269|PubMed:7520022,
CC ECO:0000269|PubMed:7522211, ECO:0000269|PubMed:7524909,
CC ECO:0000269|PubMed:7524913, ECO:0000269|PubMed:7525450,
CC ECO:0000269|PubMed:7537150, ECO:0000269|PubMed:7541273,
CC ECO:0000269|PubMed:7541510, ECO:0000269|PubMed:7543567,
CC ECO:0000269|PubMed:7544319, ECO:0000269|PubMed:7581407,
CC ECO:0000269|PubMed:7606851, ECO:0000269|PubMed:7680525,
CC ECO:0000269|PubMed:7683628, ECO:0000269|PubMed:7683954,
CC ECO:0000269|PubMed:8081395, ECO:0000269|PubMed:8406518,
CC ECO:0000269|PubMed:8522333, ECO:0000269|PubMed:8723693,
CC ECO:0000269|PubMed:8723695, ECO:0000269|PubMed:8800923,
CC ECO:0000269|PubMed:8829633, ECO:0000269|PubMed:8910473,
CC ECO:0000269|PubMed:8956039, ECO:0000269|PubMed:9101301,
CC ECO:0000269|PubMed:9222768, ECO:0000269|PubMed:9375855,
CC ECO:0000269|PubMed:9401006, ECO:0000269|PubMed:9443874,
CC ECO:0000269|PubMed:9452048, ECO:0000269|PubMed:9452054,
CC ECO:0000269|PubMed:9452073, ECO:0000269|PubMed:9482579,
CC ECO:0000269|PubMed:9521595, ECO:0000269|PubMed:9554753,
CC ECO:0000269|PubMed:9736778, ECO:0000269|PubMed:9804160,
CC ECO:0000269|PubMed:9921909}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. There is some evidence
CC that the functional defect caused by the most common variant Phe-508
CC DEL can be corrected by the binding to the snake phospholipase A2
CC crotoxin basic subunit CB. This toxin both disrupts the Phe-508 DEL-
CC cytokeratin 8 complex, allowing for the escape from degradation, and
CC increases the chloride channel current (PubMed:27241308).
CC {ECO:0000269|PubMed:27241308}.
CC -!- DISEASE: Congenital bilateral absence of the vas deferens (CBAVD)
CC [MIM:277180]: An autosomal recessive disease characterized by vas
CC deferens aplasia resulting in azoospermia and male infertility. CBAVD
CC may occur in isolation or as a manifestation of cystic fibrosis.
CC {ECO:0000269|PubMed:10651488, ECO:0000269|PubMed:17329263,
CC ECO:0000269|PubMed:7529962, ECO:0000269|PubMed:7539342,
CC ECO:0000269|PubMed:9067761, ECO:0000269|PubMed:9736778,
CC ECO:0000269|Ref.114}. Note=The disease is caused by variants affecting
CC the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 2]: Exon 9 splicing depends upon 2 polymorphic
CC tracts within intron 8, a T(n) tract and TG(n) tract, where the number
CC of T and/or TG repeats affect the extent of correct splicing of exon 9.
CC Low numbers of T residues and high numbers of TG repeats give rise to
CC less efficient splicing. Transcripts that lack exon 9 sequences fail to
CC mature. Causes congenital bilateral absence of the vas deferens
CC (CBAVD). {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Alternative acceptor site favored by
CC mutation in an exonic splicing enhancer (ESE). Causes cystic fibrosis
CC (CF). {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family.
CC CFTR transporter (TC 3.A.1.202) subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=CFTR entry;
CC URL="https://en.wikipedia.org/wiki/Cystic_fibrosis_transmembrane_conductance_regulator";
CC -!- WEB RESOURCE: Name=ABCMdb; Note=Database for mutations in ABC proteins;
CC URL="http://abcm2.hegelab.org/search";
CC ---------------------------------------------------------------------------
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DR EMBL; M28668; AAA35680.1; -; mRNA.
DR EMBL; M55131; AAC13657.1; -; Genomic_DNA.
DR EMBL; M55106; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55107; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55108; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55110; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55111; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55112; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55113; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55114; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55115; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55116; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55117; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55118; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55119; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55120; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55121; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55122; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55123; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55124; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55125; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55126; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55127; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55128; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55129; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; M55130; AAC13657.1; JOINED; Genomic_DNA.
DR EMBL; DQ354388; ABC79050.1; -; Genomic_DNA.
DR EMBL; DQ354389; ABC79052.1; -; Genomic_DNA.
DR EMBL; DQ354390; ABC79054.1; -; Genomic_DNA.
DR EMBL; DQ354391; ABC79056.1; -; Genomic_DNA.
DR EMBL; DQ356258; ABC87055.1; -; Genomic_DNA.
DR EMBL; DQ356259; ABC87057.1; -; Genomic_DNA.
DR EMBL; DQ356261; ABC87061.1; -; Genomic_DNA.
DR EMBL; DQ356262; ABC87063.1; -; Genomic_DNA.
DR EMBL; DQ356263; ABC87065.1; -; Genomic_DNA.
DR EMBL; DQ356264; ABC87067.1; -; Genomic_DNA.
DR EMBL; DQ388128; ABD72183.1; -; Genomic_DNA.
DR EMBL; DQ388129; ABD72185.1; -; Genomic_DNA.
DR EMBL; DQ388131; ABD72189.1; -; Genomic_DNA.
DR EMBL; DQ388132; ABD72191.1; -; Genomic_DNA.
DR EMBL; DQ388133; ABD72193.1; -; Genomic_DNA.
DR EMBL; DQ388134; ABD72195.1; -; Genomic_DNA.
DR EMBL; DQ388135; ABD72197.1; -; Genomic_DNA.
DR EMBL; DQ388138; ABD72203.1; -; Genomic_DNA.
DR EMBL; DQ388139; ABD72205.1; -; Genomic_DNA.
DR EMBL; DQ388140; ABD72207.1; -; Genomic_DNA.
DR EMBL; DQ388141; ABD72209.1; -; Genomic_DNA.
DR EMBL; DQ388142; ABD72211.1; -; Genomic_DNA.
DR EMBL; DQ388143; ABD72213.1; -; Genomic_DNA.
DR EMBL; DQ388145; ABD72217.1; -; Genomic_DNA.
DR EMBL; AC000061; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC000111; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236947; EAL24353.1; -; Genomic_DNA.
DR EMBL; M65196; AAA51979.1; -; Genomic_DNA.
DR EMBL; M65197; AAA51980.1; -; Genomic_DNA.
DR CCDS; CCDS5773.1; -. [P13569-1]
DR PIR; A39069; DVHUCF.
DR RefSeq; NP_000483.3; NM_000492.3. [P13569-1]
DR PDB; 1XMI; X-ray; 2.25 A; A/B/C/D/E=389-678.
DR PDB; 1XMJ; X-ray; 2.30 A; A=389-677.
DR PDB; 2BBO; X-ray; 2.55 A; A=389-678.
DR PDB; 2BBS; X-ray; 2.05 A; A/B=389-677.
DR PDB; 2BBT; X-ray; 2.30 A; A/B=389-678.
DR PDB; 2LOB; NMR; -; B=1473-1480.
DR PDB; 2PZE; X-ray; 1.70 A; A/B=387-646.
DR PDB; 2PZF; X-ray; 2.00 A; A/B=387-646.
DR PDB; 2PZG; X-ray; 1.80 A; A/B=375-646.
DR PDB; 3GD7; X-ray; 2.70 A; A/B/C/D=1193-1427.
DR PDB; 3ISW; X-ray; 2.80 A; C=5-20.
DR PDB; 4WZ6; X-ray; 2.05 A; A=389-678.
DR PDB; 5D2D; X-ray; 2.10 A; C=747-774.
DR PDB; 5D3E; X-ray; 2.75 A; C/G/K=762-801.
DR PDB; 5D3F; X-ray; 2.74 A; C=747-774.
DR PDB; 5TF7; X-ray; 1.93 A; A=387-646.
DR PDB; 5TF8; X-ray; 1.86 A; A=387-646.
DR PDB; 5TFA; X-ray; 1.87 A; A=387-646.
DR PDB; 5TFB; X-ray; 1.87 A; A=387-646.
DR PDB; 5TFC; X-ray; 1.92 A; A=387-646.
DR PDB; 5TFD; X-ray; 1.89 A; A=387-646.
DR PDB; 5TFF; X-ray; 1.89 A; A=387-646.
DR PDB; 5TFG; X-ray; 1.91 A; A=387-646.
DR PDB; 5TFI; X-ray; 1.89 A; A=387-646.
DR PDB; 5TFJ; X-ray; 1.85 A; A=387-646.
DR PDB; 5TGK; X-ray; 1.91 A; A=387-646.
DR PDB; 5UAK; EM; 3.87 A; A=1-1480.
DR PDB; 6GJQ; X-ray; 2.49 A; A/C/E/G=387-646.
DR PDB; 6GJS; X-ray; 1.95 A; A=387-646.
DR PDB; 6GJU; X-ray; 2.60 A; A=387-646.
DR PDB; 6GK4; X-ray; 2.91 A; A/D=387-646.
DR PDB; 6GKD; X-ray; 2.99 A; A/F/I/L/O/R=387-646.
DR PDB; 6HEP; X-ray; 1.86 A; E/F=747-774.
DR PDB; 6MSM; EM; 3.20 A; A=1-1480.
DR PDB; 6O1V; EM; 3.20 A; A=1-1480.
DR PDB; 6O2P; EM; 3.30 A; A=1-1480.
DR PDB; 6UK1; X-ray; 2.69 A; A/B/C/D=1202-1430.
DR PDB; 6WBS; X-ray; 1.86 A; A/B=388-646.
DR PDB; 6ZE1; X-ray; 2.71 A; A=387-646.
DR PDB; 7SV7; EM; 3.80 A; A=1-1480.
DR PDB; 7SVD; EM; 2.70 A; A=1-1480.
DR PDB; 7SVR; EM; 3.90 A; A=1-1480.
DR PDBsum; 1XMI; -.
DR PDBsum; 1XMJ; -.
DR PDBsum; 2BBO; -.
DR PDBsum; 2BBS; -.
DR PDBsum; 2BBT; -.
DR PDBsum; 2LOB; -.
DR PDBsum; 2PZE; -.
DR PDBsum; 2PZF; -.
DR PDBsum; 2PZG; -.
DR PDBsum; 3GD7; -.
DR PDBsum; 3ISW; -.
DR PDBsum; 4WZ6; -.
DR PDBsum; 5D2D; -.
DR PDBsum; 5D3E; -.
DR PDBsum; 5D3F; -.
DR PDBsum; 5TF7; -.
DR PDBsum; 5TF8; -.
DR PDBsum; 5TFA; -.
DR PDBsum; 5TFB; -.
DR PDBsum; 5TFC; -.
DR PDBsum; 5TFD; -.
DR PDBsum; 5TFF; -.
DR PDBsum; 5TFG; -.
DR PDBsum; 5TFI; -.
DR PDBsum; 5TFJ; -.
DR PDBsum; 5TGK; -.
DR PDBsum; 5UAK; -.
DR PDBsum; 6GJQ; -.
DR PDBsum; 6GJS; -.
DR PDBsum; 6GJU; -.
DR PDBsum; 6GK4; -.
DR PDBsum; 6GKD; -.
DR PDBsum; 6HEP; -.
DR PDBsum; 6MSM; -.
DR PDBsum; 6O1V; -.
DR PDBsum; 6O2P; -.
DR PDBsum; 6UK1; -.
DR PDBsum; 6WBS; -.
DR PDBsum; 6ZE1; -.
DR PDBsum; 7SV7; -.
DR PDBsum; 7SVD; -.
DR PDBsum; 7SVR; -.
DR AlphaFoldDB; P13569; -.
DR BMRB; P13569; -.
DR SMR; P13569; -.
DR BioGRID; 107506; 852.
DR CORUM; P13569; -.
DR DIP; DIP-32788N; -.
DR IntAct; P13569; 855.
DR MINT; P13569; -.
DR STRING; 9606.ENSP00000003084; -.
DR BindingDB; P13569; -.
DR ChEMBL; CHEMBL4051; -.
DR DrugBank; DB00171; ATP.
DR DrugBank; DB00887; Bumetanide.
DR DrugBank; DB02587; Colforsin.
DR DrugBank; DB04941; Crofelemer.
DR DrugBank; DB04522; Dexfosfoserine.
DR DrugBank; DB09213; Dexibuprofen.
DR DrugBank; DB15444; Elexacaftor.
DR DrugBank; DB01016; Glyburide.
DR DrugBank; DB01050; Ibuprofen.
DR DrugBank; DB08820; Ivacaftor.
DR DrugBank; DB06266; Lonidamine.
DR DrugBank; DB09280; Lumacaftor.
DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester.
DR DrugBank; DB11712; Tezacaftor.
DR DrugCentral; P13569; -.
DR GuidetoPHARMACOLOGY; 707; -.
DR MoonProt; P13569; -.
DR TCDB; 3.A.1.202.1; the atp-binding cassette (abc) superfamily.
DR GlyGen; P13569; 2 sites.
DR iPTMnet; P13569; -.
DR PhosphoSitePlus; P13569; -.
DR SwissPalm; P13569; -.
DR BioMuta; CFTR; -.
DR DMDM; 147744553; -.
DR jPOST; P13569; -.
DR MassIVE; P13569; -.
DR PaxDb; P13569; -.
DR PeptideAtlas; P13569; -.
DR PRIDE; P13569; -.
DR ProteomicsDB; 52926; -. [P13569-1]
DR ProteomicsDB; 52927; -. [P13569-2]
DR ProteomicsDB; 52928; -. [P13569-3]
DR ABCD; P13569; 10 sequenced antibodies.
DR Antibodypedia; 4530; 1089 antibodies from 41 providers.
DR DNASU; 1080; -.
DR Ensembl; ENST00000003084.11; ENSP00000003084.6; ENSG00000001626.17. [P13569-1]
DR Ensembl; ENST00000649781.1; ENSP00000497203.1; ENSG00000001626.17. [P13569-2]
DR GeneID; 1080; -.
DR KEGG; hsa:1080; -.
DR MANE-Select; ENST00000003084.11; ENSP00000003084.6; NM_000492.4; NP_000483.3.
DR UCSC; uc003vjd.4; human. [P13569-1]
DR CTD; 1080; -.
DR DisGeNET; 1080; -.
DR GeneCards; CFTR; -.
DR GeneReviews; CFTR; -.
DR HGNC; HGNC:1884; CFTR.
DR HPA; ENSG00000001626; Tissue enhanced (gallbladder, intestine, pancreas).
DR MalaCards; CFTR; -.
DR MIM; 219700; phenotype.
DR MIM; 277180; phenotype.
DR MIM; 602421; gene.
DR neXtProt; NX_P13569; -.
DR OpenTargets; ENSG00000001626; -.
DR Orphanet; 498359; Aquagenic palmoplantar keratoderma.
DR Orphanet; 48; Congenital bilateral absence of vas deferens.
DR Orphanet; 586; Cystic fibrosis.
DR Orphanet; 676; Hereditary chronic pancreatitis.
DR Orphanet; 60033; Idiopathic bronchiectasis.
DR Orphanet; 399805; Male infertility with azoospermia or oligozoospermia due to single gene mutation.
DR PharmGKB; PA109; -.
DR VEuPathDB; HostDB:ENSG00000001626; -.
DR eggNOG; KOG0054; Eukaryota.
DR GeneTree; ENSGT00940000158567; -.
DR InParanoid; P13569; -.
DR OMA; NIRQEEM; -.
DR OrthoDB; 853728at2759; -.
DR PhylomeDB; P13569; -.
DR TreeFam; TF105200; -.
DR BioCyc; MetaCyc:HS00075-MON; -.
DR BRENDA; 2.7.4.3; 2681.
DR BRENDA; 5.6.1.6; 2681.
DR PathwayCommons; P13569; -.
DR Reactome; R-HSA-382556; ABC-family proteins mediated transport.
DR Reactome; R-HSA-5627083; RHO GTPases regulate CFTR trafficking.
DR Reactome; R-HSA-5678895; Defective CFTR causes cystic fibrosis.
DR Reactome; R-HSA-5689880; Ub-specific processing proteases.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-HSA-9013406; RHOQ GTPase cycle.
DR Reactome; R-HSA-9613829; Chaperone Mediated Autophagy.
DR Reactome; R-HSA-9615710; Late endosomal microautophagy.
DR Reactome; R-HSA-9646399; Aggrephagy.
DR SignaLink; P13569; -.
DR SIGNOR; P13569; -.
DR BioGRID-ORCS; 1080; 8 hits in 1072 CRISPR screens.
DR ChiTaRS; CFTR; human.
DR EvolutionaryTrace; P13569; -.
DR GenomeRNAi; 1080; -.
DR Pharos; P13569; Tclin.
DR PRO; PR:P13569; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P13569; protein.
DR Bgee; ENSG00000001626; Expressed in body of pancreas and 116 other tissues.
DR ExpressionAtlas; P13569; baseline and differential.
DR Genevisible; P13569; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0030669; C:clathrin-coated endocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005769; C:early endosome; IDA:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0030660; C:Golgi-associated vesicle membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0055037; C:recycling endosome; IDA: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; TAS:ProtInc.
DR GO; GO:0016887; F:ATP hydrolysis activity; IDA:UniProtKB.
DR GO; GO:0043225; F:ATPase-coupled inorganic anion transmembrane transporter activity; TAS:Reactome.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015106; F:bicarbonate transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; IPI:ARUK-UCL.
DR GO; GO:0005254; F:chloride channel activity; IDA:UniProtKB.
DR GO; GO:0019869; F:chloride channel inhibitor activity; IDA:UniProtKB.
DR GO; GO:0017081; F:chloride channel regulator activity; TAS:Reactome.
DR GO; GO:0015108; F:chloride transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0005260; F:intracellularly ATP-gated chloride channel activity; IMP:UniProtKB.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0030165; F:PDZ domain binding; IDA:UniProtKB.
DR GO; GO:0106138; F:Sec61 translocon complex binding; IDA:UniProtKB.
DR GO; GO:0097186; P:amelogenesis; ISS:ARUK-UCL.
DR GO; GO:0015701; P:bicarbonate transport; IDA:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:1904322; P:cellular response to forskolin; IDA:UniProtKB.
DR GO; GO:1902476; P:chloride transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:Ensembl.
DR GO; GO:0030301; P:cholesterol transport; IEA:Ensembl.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
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; IMP:UniProtKB.
DR GO; GO:1902161; P:positive regulation of cyclic nucleotide-gated ion channel activity; IMP:UniProtKB.
DR GO; GO:0070175; P:positive regulation of enamel mineralization; ISS:ARUK-UCL.
DR GO; GO:0045921; P:positive regulation of exocytosis; IMP:UniProtKB.
DR GO; GO:0035774; P:positive regulation of insulin secretion involved in cellular response to glucose stimulus; IMP:UniProtKB.
DR GO; GO:1902943; P:positive regulation of voltage-gated chloride channel activity; IDA:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0048240; P:sperm capacitation; ISS:UniProtKB.
DR GO; GO:0035377; P:transepithelial water transport; IMP:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; IEA:Ensembl.
DR DisProt; DP00012; -.
DR Gene3D; 1.20.1560.10; -; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR IDEAL; IID00540; -.
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 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Chloride;
KW Chloride channel; Disease variant; Endoplasmic reticulum; Endosome;
KW Glycoprotein; Ion channel; Ion transport; Isomerase; Isopeptide bond;
KW Lipoprotein; Membrane; Nucleotide-binding; Nucleus; Palmitate;
KW Phosphoprotein; Reference proteome; Repeat; Transmembrane;
KW Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..1480
FT /note="Cystic fibrosis transmembrane conductance regulator"
FT /id="PRO_0000093419"
FT TOPO_DOM 1..77
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 78..98
FT /note="Helical; Name=1"
FT /evidence="ECO:0000269|Ref.55"
FT TOPO_DOM 99..122
FT /note="Extracellular"
FT /evidence="ECO:0000269|Ref.55"
FT TRANSMEM 123..146
FT /note="Helical; Name=2"
FT /evidence="ECO:0000269|Ref.55"
FT TOPO_DOM 147..195
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|Ref.55"
FT TRANSMEM 196..216
FT /note="Helical; Name=3"
FT /evidence="ECO:0000269|Ref.55"
FT TOPO_DOM 217..222
FT /note="Extracellular"
FT /evidence="ECO:0000269|Ref.55"
FT TRANSMEM 223..243
FT /note="Helical; Name=4"
FT /evidence="ECO:0000269|Ref.55"
FT TOPO_DOM 244..298
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|Ref.55"
FT TRANSMEM 299..319
FT /note="Helical; Name=5"
FT /evidence="ECO:0000269|Ref.55"
FT TOPO_DOM 320..339
FT /note="Extracellular"
FT /evidence="ECO:0000269|Ref.55"
FT TRANSMEM 340..358
FT /note="Helical; Name=6"
FT /evidence="ECO:0000269|Ref.55"
FT TOPO_DOM 359..858
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|Ref.55"
FT TRANSMEM 859..879
FT /note="Helical; Name=7"
FT /evidence="ECO:0000269|Ref.55"
FT TOPO_DOM 880..918
FT /note="Extracellular"
FT /evidence="ECO:0000269|Ref.55"
FT TRANSMEM 919..939
FT /note="Discontinuously helical; Name=8"
FT /evidence="ECO:0000269|Ref.55"
FT TOPO_DOM 940..990
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|Ref.55"
FT TRANSMEM 991..1011
FT /note="Helical; Name=9"
FT /evidence="ECO:0000269|Ref.55"
FT TOPO_DOM 1012..1013
FT /note="Extracellular"
FT /evidence="ECO:0000269|Ref.55"
FT TRANSMEM 1014..1034
FT /note="Helical; Name=10"
FT /evidence="ECO:0000269|Ref.55"
FT TOPO_DOM 1035..1095
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|Ref.55"
FT TRANSMEM 1096..1116
FT /note="Helical; Name=11"
FT /evidence="ECO:0000269|Ref.55"
FT TOPO_DOM 1117..1130
FT /note="Extracellular"
FT /evidence="ECO:0000269|Ref.55"
FT TRANSMEM 1131..1151
FT /note="Helical; Name=12"
FT /evidence="ECO:0000269|Ref.55"
FT TOPO_DOM 1152..1480
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|Ref.55"
FT DOMAIN 81..365
FT /note="ABC transmembrane type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 423..646
FT /note="ABC transporter 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT DOMAIN 859..1155
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1210..1443
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 654..831
FT /note="Disordered R region"
FT /evidence="ECO:0000269|PubMed:10792060"
FT REGION 1386..1480
FT /note="Interaction with GORASP2"
FT /evidence="ECO:0000269|PubMed:21884936"
FT REGION 1452..1480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1478..1480
FT /note="PDZ-binding"
FT /evidence="ECO:0000269|PubMed:11707463,
FT ECO:0000269|PubMed:16331976"
FT COMPBIAS 1463..1480
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 401
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15528182,
FT ECO:0000269|PubMed:20150177, ECO:0007744|PDB:1XMI,
FT ECO:0007744|PDB:1XMJ, ECO:0007744|PDB:2BBO,
FT ECO:0007744|PDB:2BBS, ECO:0007744|PDB:2BBT,
FT ECO:0007744|PDB:2PZE, ECO:0007744|PDB:2PZF,
FT ECO:0007744|PDB:2PZG"
FT BINDING 434
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:20150177,
FT ECO:0007744|PDB:2PZE, ECO:0007744|PDB:2PZF,
FT ECO:0007744|PDB:2PZG"
FT BINDING 458..465
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434,
FT ECO:0000269|PubMed:15528182, ECO:0007744|PDB:1XMI,
FT ECO:0007744|PDB:1XMJ, ECO:0007744|PDB:2BBO,
FT ECO:0007744|PDB:2BBS, ECO:0007744|PDB:2BBT"
FT BINDING 493
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:15528182,
FT ECO:0007744|PDB:1XMI, ECO:0007744|PDB:2BBO,
FT ECO:0007744|PDB:2BBS"
FT BINDING 1219
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0007744|PDB:3GD7"
FT BINDING 1244..1251
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434,
FT ECO:0007744|PDB:3GD7"
FT MOD_RES 549
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 660
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:1377674,
FT ECO:0000269|PubMed:22119790, ECO:0000269|PubMed:25330774,
FT ECO:0000269|PubMed:9385646"
FT MOD_RES 670
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:25330774"
FT MOD_RES 686
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:1377674,
FT ECO:0000269|PubMed:22119790"
FT MOD_RES 700
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:1377674,
FT ECO:0000269|PubMed:22119790, ECO:0000269|PubMed:25330774,
FT ECO:0000269|PubMed:9385646"
FT MOD_RES 712
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:22119790,
FT ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:9385646"
FT MOD_RES 717
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:22119790"
FT MOD_RES 737
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:1377674,
FT ECO:0000269|PubMed:22119790, ECO:0000269|PubMed:25330774,
FT ECO:0000269|PubMed:9385646"
FT MOD_RES 753
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:25330774,
FT ECO:0000269|PubMed:9385646"
FT MOD_RES 768
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:1377674,
FT ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:9385646"
FT MOD_RES 790
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:1377674"
FT MOD_RES 795
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:1377674,
FT ECO:0000269|PubMed:22119790, ECO:0000269|PubMed:25330774,
FT ECO:0000269|PubMed:9385646"
FT MOD_RES 813
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:1377674,
FT ECO:0000269|PubMed:25330774, ECO:0000269|PubMed:9385646"
FT MOD_RES 1444
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22119790"
FT MOD_RES 1456
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22119790"
FT LIPID 524
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:22119790"
FT LIPID 1395
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:22119790"
FT CARBOHYD 894
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7518437,
FT ECO:0000305|PubMed:20008117"
FT CARBOHYD 900
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:7518437,
FT ECO:0000305|PubMed:20008117"
FT CROSSLNK 688
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:22119790"
FT VAR_SEQ 404..464
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_022123"
FT VAR_SEQ 589..605
FT /note="SCVCKLMANKTRILVTS -> RRRCSCLLDRNKKTIF (in isoform
FT 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_022124"
FT VAR_SEQ 606..1480
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_022125"
FT VARIANT 13
FT /note="S -> F (in CF; dbSNP:rs397508635)"
FT /evidence="ECO:0000269|PubMed:9554753"
FT /id="VAR_000101"
FT VARIANT 31
FT /note="R -> C (in dbSNP:rs1800073)"
FT /evidence="ECO:0000269|PubMed:7522211,
FT ECO:0000269|PubMed:9921909"
FT /id="VAR_000102"
FT VARIANT 31
FT /note="R -> L (in CF; dbSNP:rs149353983)"
FT /evidence="ECO:0000269|PubMed:7537150"
FT /id="VAR_000103"
FT VARIANT 42
FT /note="S -> F (in CF; dbSNP:rs143456784)"
FT /evidence="ECO:0000269|PubMed:7541510"
FT /id="VAR_000104"
FT VARIANT 44
FT /note="D -> G (in CF; unknown pathological significance;
FT dbSNP:rs1800074)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_000105"
FT VARIANT 44
FT /note="D -> V (in dbSNP:rs1800074)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_000106"
FT VARIANT 50
FT /note="S -> Y (in CBAVD; dbSNP:rs397508220)"
FT /evidence="ECO:0000269|PubMed:9067761"
FT /id="VAR_000107"
FT VARIANT 57
FT /note="W -> G (in CF; dbSNP:rs397508272)"
FT /evidence="ECO:0000269|PubMed:7544319"
FT /id="VAR_000108"
FT VARIANT 67
FT /note="P -> L (in CF; dbSNP:rs368505753)"
FT /id="VAR_000109"
FT VARIANT 74
FT /note="R -> W (in CF and CBAVD; dbSNP:rs115545701)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_000110"
FT VARIANT 75
FT /note="R -> Q (in dbSNP:rs1800076)"
FT /evidence="ECO:0000269|PubMed:17329263,
FT ECO:0000269|PubMed:9921909"
FT /id="VAR_000111"
FT VARIANT 85
FT /note="G -> E (in CF; dbSNP:rs75961395)"
FT /evidence="ECO:0000269|PubMed:9401006"
FT /id="VAR_000112"
FT VARIANT 87
FT /note="F -> L (in CF; dbSNP:rs397508403)"
FT /evidence="ECO:0000269|PubMed:8081395"
FT /id="VAR_000113"
FT VARIANT 91
FT /note="G -> R (in CF; dbSNP:rs121908750)"
FT /id="VAR_000114"
FT VARIANT 92
FT /note="E -> K (in CF; dbSNP:rs121908751)"
FT /evidence="ECO:0000269|PubMed:1284529,
FT ECO:0000269|PubMed:7683954"
FT /id="VAR_000115"
FT VARIANT 98
FT /note="Q -> R (in CF; dbSNP:rs397508464)"
FT /evidence="ECO:0000269|PubMed:7581407"
FT /id="VAR_000116"
FT VARIANT 105
FT /note="I -> S (in CF)"
FT /id="VAR_000117"
FT VARIANT 109
FT /note="Y -> C (in CF; dbSNP:rs121909031)"
FT /evidence="ECO:0000269|PubMed:7524909"
FT /id="VAR_000118"
FT VARIANT 110
FT /note="D -> H (in CF and CBAVD; dbSNP:rs113993958)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_000119"
FT VARIANT 111
FT /note="P -> L (in CBAVD; dbSNP:rs140502196)"
FT /evidence="ECO:0000269|Ref.114"
FT /id="VAR_000120"
FT VARIANT 117
FT /note="R -> C (in CF; dbSNP:rs77834169)"
FT /evidence="ECO:0000269|PubMed:1284529"
FT /id="VAR_000121"
FT VARIANT 117
FT /note="R -> H (in CF and CBAVD; strong decrease in single
FT channel conductance; promotes rapid return to the closed
FT state of the channel; decrease in bicarbonate transport;
FT dbSNP:rs78655421)"
FT /evidence="ECO:0000269|PubMed:11242048,
FT ECO:0000269|PubMed:17329263, ECO:0000269|PubMed:26846474,
FT ECO:0000269|PubMed:9401006"
FT /id="VAR_000122"
FT VARIANT 117
FT /note="R -> L (in CF; dbSNP:rs78655421)"
FT /evidence="ECO:0000269|PubMed:7541510"
FT /id="VAR_000123"
FT VARIANT 117
FT /note="R -> P (in CF; dbSNP:rs78655421)"
FT /evidence="ECO:0000269|PubMed:9452048"
FT /id="VAR_000124"
FT VARIANT 120
FT /note="A -> T (in CF; dbSNP:rs201958172)"
FT /evidence="ECO:0000269|PubMed:7517264"
FT /id="VAR_000125"
FT VARIANT 138
FT /note="L -> P (in dbSNP:rs1800078)"
FT /id="VAR_009895"
FT VARIANT 139
FT /note="H -> R (in CF; dbSNP:rs76371115)"
FT /evidence="ECO:0000269|PubMed:7541510"
FT /id="VAR_000126"
FT VARIANT 141
FT /note="A -> D (in CF; dbSNP:rs397508700)"
FT /evidence="ECO:0000269|PubMed:9222768"
FT /id="VAR_000127"
FT VARIANT 148
FT /note="I -> T (in CF; unknown pathological significance;
FT loss of bicarbonate transport; decreased inhibition of
FT epithelial sodium channel (ENaC), when tested in a
FT heterologous system; no effect on protein maturation,
FT subcellular location at the plasma membrane, nor on
FT chloride channel activity; dbSNP:rs35516286)"
FT /evidence="ECO:0000269|PubMed:11242048,
FT ECO:0000269|PubMed:12394343, ECO:0000269|PubMed:16822950"
FT /id="VAR_000128"
FT VARIANT 149
FT /note="G -> R (in CBAVD; dbSNP:rs397508718)"
FT /evidence="ECO:0000269|PubMed:7529962"
FT /id="VAR_000129"
FT VARIANT 170
FT /note="R -> H (in CBAVD; unknown pathological significance;
FT dbSNP:rs1800079)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_009896"
FT VARIANT 178
FT /note="G -> R (in CF; loss of bicarbonate transport; no
FT effect on protein maturation, subcellular location at the
FT plasma membrane, nor on chloride channel activity;
FT dbSNP:rs80282562)"
FT /evidence="ECO:0000269|PubMed:11242048,
FT ECO:0000269|PubMed:1379210"
FT /id="VAR_000130"
FT VARIANT 182
FT /note="S -> G (in dbSNP:rs1800080)"
FT /id="VAR_009897"
FT VARIANT 192
FT /note="Missing (in CF)"
FT /evidence="ECO:0000269|PubMed:9452048"
FT /id="VAR_000131"
FT VARIANT 193
FT /note="E -> K (in CBAVD and CF; decrease in bicarbonate
FT transport; no effect on chloride channel activity;
FT dbSNP:rs397508759)"
FT /evidence="ECO:0000269|PubMed:11242048,
FT ECO:0000269|PubMed:7529962, ECO:0000269|PubMed:7544319"
FT /id="VAR_000132"
FT VARIANT 199
FT /note="H -> Q (in CF; dbSNP:rs397508765)"
FT /id="VAR_000133"
FT VARIANT 199
FT /note="H -> Y (in CF; dbSNP:rs121908802)"
FT /evidence="ECO:0000269|PubMed:7525450"
FT /id="VAR_000134"
FT VARIANT 205
FT /note="P -> S (in CF; dbSNP:rs121908803)"
FT /evidence="ECO:0000269|PubMed:7505694"
FT /id="VAR_000135"
FT VARIANT 206
FT /note="L -> W (in CF and CBAVD; dbSNP:rs121908752)"
FT /evidence="ECO:0000269|PubMed:17329263,
FT ECO:0000269|PubMed:8522333"
FT /id="VAR_000136"
FT VARIANT 220..1480
FT /note="Missing (in CF)"
FT /evidence="ECO:0000269|PubMed:20691141"
FT /id="VAR_080302"
FT VARIANT 225
FT /note="C -> R (in CF; unknown pathological significance;
FT dbSNP:rs397508780)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_000137"
FT VARIANT 232
FT /note="V -> D (in CBAVD; dbSNP:rs397508783)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_080303"
FT VARIANT 244
FT /note="M -> K (in CBAVD; dbSNP:rs397508790)"
FT /evidence="ECO:0000269|Ref.114"
FT /id="VAR_000138"
FT VARIANT 258
FT /note="R -> G (in CBAVD; dbSNP:rs191456345)"
FT /evidence="ECO:0000269|PubMed:7529962"
FT /id="VAR_000139"
FT VARIANT 287
FT /note="N -> Y (in CF; decreased presence at the cell
FT membrane due to increased internalization from the apical
FT cell membrane; no effect on single channel gating and
FT conductance; dbSNP:rs397508804)"
FT /evidence="ECO:0000269|PubMed:12529365,
FT ECO:0000269|PubMed:9401006"
FT /id="VAR_000140"
FT VARIANT 297
FT /note="R -> Q (in CF; dbSNP:rs143486492)"
FT /id="VAR_000141"
FT VARIANT 301
FT /note="Y -> C (in CF; unknown pathological significance;
FT dbSNP:rs150691494)"
FT /id="VAR_000142"
FT VARIANT 307
FT /note="S -> N (in CF; dbSNP:rs397508817)"
FT /id="VAR_000143"
FT VARIANT 311
FT /note="F -> L (in CF; dbSNP:rs121909016)"
FT /id="VAR_000144"
FT VARIANT 311
FT /note="Missing (in CF)"
FT /evidence="ECO:0000269|PubMed:9443874"
FT /id="VAR_000145"
FT VARIANT 314
FT /note="G -> E (in CF; dbSNP:rs75763344)"
FT /id="VAR_000146"
FT VARIANT 314
FT /note="G -> R (in CF; dbSNP:rs397508819)"
FT /evidence="ECO:0000269|PubMed:8829633"
FT /id="VAR_000147"
FT VARIANT 322
FT /note="V -> M (in dbSNP:rs1800085)"
FT /id="VAR_009898"
FT VARIANT 334
FT /note="R -> W (in CF and CBAVD; mild; does not prevent
FT maturation of glycans; dbSNP:rs121909011)"
FT /evidence="ECO:0000269|PubMed:1379210,
FT ECO:0000269|PubMed:1699669, ECO:0000269|PubMed:17329263"
FT /id="VAR_000148"
FT VARIANT 336
FT /note="I -> K (in CF; dbSNP:rs397508139)"
FT /id="VAR_000150"
FT VARIANT 338
FT /note="T -> I (in CF; mild; isolated hypotonic dehydration;
FT dbSNP:rs77409459)"
FT /evidence="ECO:0000269|PubMed:7543567,
FT ECO:0000269|PubMed:9554753"
FT /id="VAR_000151"
FT VARIANT 346
FT /note="L -> P (in CF; dominant mutation but mild phenotype;
FT dbSNP:rs397508146)"
FT /evidence="ECO:0000269|PubMed:7513296"
FT /id="VAR_000152"
FT VARIANT 347
FT /note="R -> H (in CF; dbSNP:rs77932196)"
FT /id="VAR_000153"
FT VARIANT 347
FT /note="R -> L (in CF; dbSNP:rs77932196)"
FT /id="VAR_000154"
FT VARIANT 347
FT /note="R -> P (in CF; MILD; dbSNP:rs77932196)"
FT /id="VAR_000155"
FT VARIANT 351
FT /note="T -> S (in dbSNP:rs1800086)"
FT /id="VAR_009899"
FT VARIANT 352
FT /note="R -> Q (in CF; dbSNP:rs121908753)"
FT /id="VAR_000156"
FT VARIANT 353
FT /note="Q -> H (in dbSNP:rs1800087)"
FT /id="VAR_009900"
FT VARIANT 359..360
FT /note="QT -> KK (in CF; dbSNP:rs397508152)"
FT /id="VAR_000158"
FT VARIANT 359
FT /note="Q -> K (in CF; dbSNP:rs76879328)"
FT /id="VAR_000157"
FT VARIANT 370
FT /note="K -> KNK (in CF)"
FT /evidence="ECO:0000269|PubMed:9452073"
FT /id="VAR_000159"
FT VARIANT 443
FT /note="D -> Y (in CBAVD; unknown pathological significance;
FT dbSNP:rs147422190)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_080304"
FT VARIANT 455
FT /note="A -> E (in CF; dbSNP:rs74551128)"
FT /evidence="ECO:0000269|PubMed:9401006"
FT /id="VAR_000160"
FT VARIANT 456
FT /note="V -> F (in CF; dbSNP:rs397508195)"
FT /id="VAR_000161"
FT VARIANT 458
FT /note="G -> V (in CF; dbSNP:rs121909009)"
FT /id="VAR_000162"
FT VARIANT 467
FT /note="L -> F (in dbSNP:rs1800089)"
FT /id="VAR_000163"
FT VARIANT 470
FT /note="V -> M (in dbSNP:rs213950)"
FT /evidence="ECO:0000269|PubMed:10651488,
FT ECO:0000269|PubMed:1379210, ECO:0000269|PubMed:1710598,
FT ECO:0000269|PubMed:17329263, ECO:0000269|PubMed:18987736,
FT ECO:0000269|PubMed:20691141, ECO:0000269|PubMed:2475911,
FT ECO:0000269|Ref.3"
FT /id="VAR_000164"
FT VARIANT 480
FT /note="G -> C (in CF; dbSNP:rs79282516)"
FT /id="VAR_000165"
FT VARIANT 492
FT /note="S -> F (in CF; dbSNP:rs121909017)"
FT /id="VAR_000166"
FT VARIANT 504
FT /note="E -> Q (in CF; dbSNP:rs397508223)"
FT /id="VAR_000167"
FT VARIANT 506
FT /note="I -> M (in dbSNP:rs1800092)"
FT /id="VAR_009901"
FT VARIANT 506
FT /note="I -> V (in dbSNP:rs1800091)"
FT /evidence="ECO:0000269|PubMed:1379210,
FT ECO:0000269|PubMed:9921909"
FT /id="VAR_000168"
FT VARIANT 507
FT /note="I -> V (in dbSNP:rs1801178)"
FT /id="VAR_000169"
FT VARIANT 507
FT /note="Missing (in CF; impaired maturation of glycan
FT chains; dbSNP:rs121908745)"
FT /evidence="ECO:0000269|PubMed:1699669,
FT ECO:0000269|PubMed:1710600"
FT /id="VAR_000170"
FT VARIANT 508
FT /note="F -> C (in dbSNP:rs74571530)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_000172"
FT VARIANT 508
FT /note="Missing (in CF and CBAVD; most common mutation in
FT Caucasian CF chromosomes; impairs protein folding and
FT stability; causes local changes to the surface that
FT mediates interactions between domains; decreases frequency
FT of channel opening in vitro; binds to the cytokeratin-8 and
FT through this binding is primed for the degradation pathway
FT that ends in the proteasome, thus impairing trafficking;
FT impairs maturation and trafficking to the cell membrane;
FT impairs recycling to the cell membrane after endocytosis;
FT dbSNP:rs121909001)"
FT /evidence="ECO:0000269|PubMed:12394343,
FT ECO:0000269|PubMed:12529365, ECO:0000269|PubMed:1284548,
FT ECO:0000269|PubMed:1379210, ECO:0000269|PubMed:15528182,
FT ECO:0000269|PubMed:15716351, ECO:0000269|PubMed:1699669,
FT ECO:0000269|PubMed:17098864, ECO:0000269|PubMed:1710600,
FT ECO:0000269|PubMed:17329263, ECO:0000269|PubMed:20008117,
FT ECO:0000269|PubMed:20150177, ECO:0000269|PubMed:20691141,
FT ECO:0000269|PubMed:21884936, ECO:0000269|PubMed:25330774,
FT ECO:0000269|PubMed:27241308, ECO:0000269|PubMed:28001373,
FT ECO:0000269|PubMed:28067262, ECO:0000269|PubMed:28087700"
FT /id="VAR_000171"
FT VARIANT 513
FT /note="D -> G (in CBAVD; dbSNP:rs397508225)"
FT /evidence="ECO:0000269|PubMed:10651488"
FT /id="VAR_000173"
FT VARIANT 520
FT /note="V -> F (in CF; dbSNP:rs77646904)"
FT /evidence="ECO:0000269|PubMed:1284466"
FT /id="VAR_000174"
FT VARIANT 532
FT /note="K -> E (in dbSNP:rs35032490)"
FT /id="VAR_048150"
FT VARIANT 542..1480
FT /note="Missing (in CF)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_080305"
FT VARIANT 544
FT /note="G -> V (in CBAVD; dbSNP:rs397508241)"
FT /evidence="ECO:0000269|Ref.114"
FT /id="VAR_000175"
FT VARIANT 549
FT /note="S -> I (in CF; impaired maturation of glycan chains;
FT dbSNP:rs121908755)"
FT /evidence="ECO:0000269|PubMed:1699669,
FT ECO:0000269|PubMed:1712898"
FT /id="VAR_000177"
FT VARIANT 549
FT /note="S -> N (in CF; dbSNP:rs121908755)"
FT /id="VAR_000176"
FT VARIANT 549
FT /note="S -> R (in CF; impaired maturation of glycan chains;
FT dbSNP:rs121909005)"
FT /evidence="ECO:0000269|PubMed:1712898"
FT /id="VAR_000178"
FT VARIANT 551
FT /note="G -> D (in CF; decrease in the frequency of channel
FT opening in vitro; decrease in channel activity and ATPase
FT activity; complete loss of bicarbonate transport; no effect
FT on trafficking to the cell membrane, protein stability, nor
FT on the maturation of glycans; dbSNP:rs75527207)"
FT /evidence="ECO:0000269|PubMed:11242048,
FT ECO:0000269|PubMed:1284548, ECO:0000269|PubMed:1379210,
FT ECO:0000269|PubMed:1699669, ECO:0000269|PubMed:1712898,
FT ECO:0000269|PubMed:28087700, ECO:0000269|PubMed:8910473,
FT ECO:0000269|PubMed:9401006"
FT /id="VAR_000179"
FT VARIANT 551
FT /note="G -> S (in CF; decrease in bicarbonate transport; no
FT effect on chloride channel activity; dbSNP:rs121909013)"
FT /evidence="ECO:0000269|PubMed:7606851"
FT /id="VAR_000180"
FT VARIANT 553
FT /note="R -> Q (in CF; dbSNP:rs121909044)"
FT /id="VAR_000181"
FT VARIANT 556
FT /note="I -> V (in CBAVD; unknown pathological significance;
FT dbSNP:rs75789129)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_080306"
FT VARIANT 558
FT /note="L -> S (in CF; dbSNP:rs193922504)"
FT /id="VAR_000182"
FT VARIANT 559
FT /note="A -> T (in CF; impaired maturation of glycan chains;
FT dbSNP:rs75549581)"
FT /evidence="ECO:0000269|PubMed:1712898"
FT /id="VAR_000183"
FT VARIANT 560
FT /note="R -> K (in CF; dbSNP:rs80055610)"
FT /id="VAR_000184"
FT VARIANT 560
FT /note="R -> S (in CF; dbSNP:rs397508267)"
FT /evidence="ECO:0000269|PubMed:9482579"
FT /id="VAR_000185"
FT VARIANT 560
FT /note="R -> T (in CF; impairs maturation and trafficking to
FT the cell membrane; decrease in channel activity;
FT dbSNP:rs80055610)"
FT /evidence="ECO:0000269|PubMed:17098864"
FT /id="VAR_000186"
FT VARIANT 561
FT /note="A -> E (in CF; impairs maturation and trafficking to
FT the cell membrane; decrease in channel activity;
FT dbSNP:rs121909047)"
FT /evidence="ECO:0000269|PubMed:17098864"
FT /id="VAR_080307"
FT VARIANT 562
FT /note="V -> I (in CBAVD and CF; unknown pathological
FT significance; found in cis of the IVS8 TG11-T5 allele,
FT which affects exon 9 splicing; no effect on protein
FT maturation, trafficking to the cell membrane, nor on
FT channel activity; dbSNP:rs1800097)"
FT /evidence="ECO:0000269|PubMed:1379210,
FT ECO:0000269|PubMed:17098864, ECO:0000269|PubMed:17329263,
FT ECO:0000269|PubMed:20691141"
FT /id="VAR_000187"
FT VARIANT 562
FT /note="V -> L (in CF; dbSNP:rs1800097)"
FT /evidence="ECO:0000269|PubMed:8956039"
FT /id="VAR_000188"
FT VARIANT 563
FT /note="Y -> N (in CF; dbSNP:rs121909006)"
FT /id="VAR_000189"
FT VARIANT 569
FT /note="Y -> C (in CF; dbSNP:rs397508277)"
FT /evidence="ECO:0000269|PubMed:8723693"
FT /id="VAR_000190"
FT VARIANT 569
FT /note="Y -> D (in CF; dbSNP:rs397508276)"
FT /evidence="ECO:0000269|PubMed:9482579"
FT /id="VAR_000191"
FT VARIANT 569
FT /note="Y -> H (in CF; dbSNP:rs397508276)"
FT /id="VAR_000192"
FT VARIANT 571
FT /note="L -> S (in CF; dbSNP:rs397508280)"
FT /id="VAR_000193"
FT VARIANT 572
FT /note="D -> N (in CF; impaired maturation of glycan chains;
FT dbSNP:rs397508282)"
FT /evidence="ECO:0000269|PubMed:1712898,
FT ECO:0000269|PubMed:7541273"
FT /id="VAR_000194"
FT VARIANT 574
FT /note="P -> H (in CF; dbSNP:rs121908758)"
FT /id="VAR_000195"
FT VARIANT 576
FT /note="G -> A (in CBAVD; unknown pathological significance;
FT dbSNP:rs1800098)"
FT /evidence="ECO:0000269|PubMed:1379210,
FT ECO:0000269|PubMed:17329263"
FT /id="VAR_000196"
FT VARIANT 579
FT /note="D -> G (in CF; dbSNP:rs397508288)"
FT /evidence="ECO:0000269|PubMed:10094564,
FT ECO:0000269|PubMed:7544319"
FT /id="VAR_000197"
FT VARIANT 601
FT /note="I -> F (in CF; impaired maturation of glycan chains;
FT dbSNP:rs397508306)"
FT /evidence="ECO:0000269|PubMed:9736778"
FT /id="VAR_000198"
FT VARIANT 605
FT /note="S -> F (in dbSNP:rs766874)"
FT /id="VAR_048151"
FT VARIANT 610
FT /note="L -> S (in CF; impaired maturation of glycan chains;
FT dbSNP:rs397508311)"
FT /evidence="ECO:0000269|PubMed:9736778"
FT /id="VAR_000199"
FT VARIANT 613
FT /note="A -> T (in CF; impaired maturation of glycan chains;
FT dbSNP:rs201978662)"
FT /evidence="ECO:0000269|PubMed:9736778"
FT /id="VAR_000200"
FT VARIANT 614
FT /note="D -> G (in CF; impaired maturation of glycan chains;
FT dbSNP:rs201124247)"
FT /evidence="ECO:0000269|PubMed:9736778"
FT /id="VAR_000201"
FT VARIANT 618
FT /note="I -> T (in CF; impaired maturation of glycan chains;
FT dbSNP:rs139468767)"
FT /evidence="ECO:0000269|PubMed:9736778"
FT /id="VAR_000202"
FT VARIANT 619
FT /note="L -> S (in CF; impaired maturation of glycan chains;
FT dbSNP:rs397508313)"
FT /evidence="ECO:0000269|PubMed:7525450,
FT ECO:0000269|PubMed:9736778"
FT /id="VAR_000203"
FT VARIANT 620
FT /note="H -> P (in CF; impaired maturation of glycan chains;
FT dbSNP:rs397508314)"
FT /evidence="ECO:0000269|PubMed:9736778"
FT /id="VAR_000204"
FT VARIANT 620
FT /note="H -> Q (in CF; strong decrease in bicarbonate
FT transport; increase in chloride channel activity in vitro;
FT no effect on glycan maturation; dbSNP:rs397508315)"
FT /evidence="ECO:0000269|PubMed:9736778"
FT /id="VAR_000205"
FT VARIANT 622
FT /note="G -> D (in CBAVD; decreased channel activity; has no
FT effect on glycan maturation; dbSNP:rs121908759)"
FT /evidence="ECO:0000269|PubMed:17329263,
FT ECO:0000269|PubMed:9736778"
FT /id="VAR_000206"
FT VARIANT 628
FT /note="G -> R (in CF; impaired maturation of glycan chains;
FT dbSNP:rs397508316)"
FT /evidence="ECO:0000269|PubMed:1379210,
FT ECO:0000269|PubMed:9736778"
FT /id="VAR_000207"
FT VARIANT 633
FT /note="L -> P (in CF; impaired maturation of glycan chains;
FT dbSNP:rs397508318)"
FT /evidence="ECO:0000269|PubMed:9736778"
FT /id="VAR_000208"
FT VARIANT 648
FT /note="D -> V (in CF; decrease in bicarbonate transport; no
FT effect chloride channel activity; dbSNP:rs121909033)"
FT /evidence="ECO:0000269|PubMed:11242048"
FT /id="VAR_000209"
FT VARIANT 651
FT /note="D -> N (in CF; dbSNP:rs780526529)"
FT /id="VAR_000210"
FT VARIANT 654
FT /note="S -> G (in dbSNP:rs1800099)"
FT /id="VAR_009902"
FT VARIANT 665
FT /note="T -> S (in CF; no effect on glycan maturation and
FT channel activity; dbSNP:rs1177201180)"
FT /evidence="ECO:0000269|PubMed:8800923,
FT ECO:0000269|PubMed:9736778"
FT /id="VAR_000211"
FT VARIANT 668
FT /note="R -> C (in CBAVD; unknown pathological significance;
FT dbSNP:rs1800100)"
FT /evidence="ECO:0000269|PubMed:1379210,
FT ECO:0000269|PubMed:17329263, ECO:0000269|PubMed:9921909"
FT /id="VAR_000212"
FT VARIANT 693
FT /note="F -> L (in CF; unknown pathological significance;
FT dbSNP:rs145540754 and dbSNP:rs397508338)"
FT /evidence="ECO:0000269|PubMed:12167682,
FT ECO:0000269|PubMed:8406518"
FT /id="VAR_000213"
FT VARIANT 710..1480
FT /note="Missing (in CF)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_080308"
FT VARIANT 754
FT /note="V -> M (in CF; dbSNP:rs150157202)"
FT /id="VAR_000214"
FT VARIANT 766
FT /note="R -> M (in CBAVD; dbSNP:rs397508363)"
FT /id="VAR_000215"
FT VARIANT 792
FT /note="R -> G (in CBAVD; no effect on glycan maturation but
FT decreased channel activity; dbSNP:rs145449046)"
FT /evidence="ECO:0000269|PubMed:9736778"
FT /id="VAR_000216"
FT VARIANT 800
FT /note="A -> G (in CBAVD; small decrease in bicarbonate
FT transport; increase in chloride channel activity in vitro;
FT no effect on glycan maturation; dbSNP:rs397508373)"
FT /evidence="ECO:0000269|PubMed:11242048,
FT ECO:0000269|PubMed:7529962, ECO:0000269|PubMed:9736778"
FT /id="VAR_000217"
FT VARIANT 807
FT /note="I -> M (in CBAVD; dbSNP:rs1800103)"
FT /id="VAR_000218"
FT VARIANT 822
FT /note="E -> K (in CF; dbSNP:rs397508378)"
FT /id="VAR_000219"
FT VARIANT 826
FT /note="E -> K (in thoracic sarcoidosis; no effect on glycan
FT maturation and channel activity; dbSNP:rs397508381)"
FT /evidence="ECO:0000269|PubMed:9736778"
FT /id="VAR_000220"
FT VARIANT 846..1480
FT /note="Missing (in CF)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_080309"
FT VARIANT 866
FT /note="C -> Y (in CF; dbSNP:rs193922506)"
FT /id="VAR_000221"
FT VARIANT 890..1480
FT /note="Missing (in CF)"
FT /evidence="ECO:0000269|PubMed:12394343,
FT ECO:0000269|PubMed:7522211"
FT /id="VAR_080310"
FT VARIANT 903
FT /note="Y -> H (in dbSNP:rs1800106)"
FT /id="VAR_009903"
FT VARIANT 909
FT /note="S -> I (in dbSNP:rs1800107)"
FT /id="VAR_009904"
FT VARIANT 912
FT /note="S -> L (in dbSNP:rs121909034)"
FT /evidence="ECO:0000269|PubMed:7522211"
FT /id="VAR_000222"
FT VARIANT 913
FT /note="Y -> C (in CF; dbSNP:rs121909008)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_000223"
FT VARIANT 917
FT /note="Y -> C (in CF; dbSNP:rs397508428)"
FT /id="VAR_000224"
FT VARIANT 938
FT /note="V -> G (in CBAVD; unknown pathological significance;
FT dbSNP:rs193922511)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_080311"
FT VARIANT 949
FT /note="H -> Y (in CF; decrease in bicarbonate transport; no
FT effect on chloride channel activity; dbSNP:rs121909035)"
FT /evidence="ECO:0000269|PubMed:11242048,
FT ECO:0000269|PubMed:7522211"
FT /id="VAR_000225"
FT VARIANT 952
FT /note="M -> I (in CF and CBAVD; unknown pathological
FT significance; dbSNP:rs151048781)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_000226"
FT VARIANT 959
FT /note="A -> V (in CBAVD; unknown pathological significance;
FT dbSNP:rs397508448)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_080312"
FT VARIANT 967
FT /note="L -> S (in dbSNP:rs1800110)"
FT /id="VAR_009905"
FT VARIANT 977
FT /note="S -> F (in CBAVD; unknown pathological significance;
FT dbSNP:rs141033578)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_080313"
FT VARIANT 997
FT /note="L -> F (in CF and CBAVD; unknown pathological
FT significance; dbSNP:rs1800111)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_000227"
FT VARIANT 1005
FT /note="I -> R (in CF; dbSNP:rs397508479)"
FT /evidence="ECO:0000269|PubMed:7525450"
FT /id="VAR_000228"
FT VARIANT 1006
FT /note="A -> E (in CF; dbSNP:rs397508480)"
FT /evidence="ECO:0000269|PubMed:20691141,
FT ECO:0000269|PubMed:7541510"
FT /id="VAR_000229"
FT VARIANT 1013
FT /note="P -> L (in CF; dbSNP:rs193922516)"
FT /evidence="ECO:0000269|PubMed:9521595"
FT /id="VAR_000230"
FT VARIANT 1023..1024
FT /note="Missing (in CF; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:12394343"
FT /id="VAR_080314"
FT VARIANT 1027
FT /note="I -> T (in dbSNP:rs1800112)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_080315"
FT VARIANT 1028
FT /note="M -> I (in CF; dbSNP:rs200553511)"
FT /evidence="ECO:0000269|PubMed:9521595"
FT /id="VAR_000231"
FT VARIANT 1032
FT /note="Y -> C (in CBAVD; unknown pathological significance;
FT dbSNP:rs144055758)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_080316"
FT VARIANT 1052
FT /note="F -> V (in CF; dbSNP:rs150212784)"
FT /evidence="ECO:0000269|PubMed:7683628"
FT /id="VAR_000232"
FT VARIANT 1061
FT /note="G -> R (in CF; dbSNP:rs142394380)"
FT /evidence="ECO:0000269|PubMed:7683628,
FT ECO:0000269|PubMed:8723695"
FT /id="VAR_000233"
FT VARIANT 1063..1480
FT /note="Missing (in CF)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_080317"
FT VARIANT 1065
FT /note="L -> P (in CF; dbSNP:rs121909036)"
FT /evidence="ECO:0000269|PubMed:7522211"
FT /id="VAR_000234"
FT VARIANT 1065
FT /note="L -> R (in CF; dbSNP:rs121909036)"
FT /evidence="ECO:0000269|PubMed:9452054"
FT /id="VAR_000235"
FT VARIANT 1066
FT /note="R -> C (in CF; dbSNP:rs78194216)"
FT /evidence="ECO:0000269|PubMed:1379210,
FT ECO:0000269|PubMed:9375855"
FT /id="VAR_000236"
FT VARIANT 1066
FT /note="R -> H (in CF; dbSNP:rs121909019)"
FT /id="VAR_000237"
FT VARIANT 1066
FT /note="R -> L (in CF; dbSNP:rs121909019)"
FT /evidence="ECO:0000269|PubMed:7683628"
FT /id="VAR_000238"
FT VARIANT 1067
FT /note="A -> T (in CF; loss of bicarbonate transport; no
FT effect on protein maturation, subcellular location at the
FT plasma membrane, nor on chloride channel activity;
FT dbSNP:rs121909020)"
FT /evidence="ECO:0000269|PubMed:11242048"
FT /id="VAR_000239"
FT VARIANT 1067
FT /note="A -> V (in dbSNP:rs1800114)"
FT /id="VAR_000240"
FT VARIANT 1069
FT /note="G -> R (in CBAVD; unknown pathological significance;
FT dbSNP:rs200321110)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_080318"
FT VARIANT 1070
FT /note="R -> P (in CF; dbSNP:rs78769542)"
FT /evidence="ECO:0000269|PubMed:9401006"
FT /id="VAR_000242"
FT VARIANT 1070
FT /note="R -> Q (in CF; decrease in bicarbonate transport; no
FT effect on chloride channel activity; dbSNP:rs78769542)"
FT /evidence="ECO:0000269|PubMed:11242048,
FT ECO:0000269|PubMed:7683628"
FT /id="VAR_000241"
FT VARIANT 1070
FT /note="R -> W (in CBAVD; dbSNP:rs202179988)"
FT /id="VAR_011564"
FT VARIANT 1071
FT /note="Q -> P (in CF; dbSNP:rs121909037)"
FT /evidence="ECO:0000269|PubMed:7522211"
FT /id="VAR_000243"
FT VARIANT 1072
FT /note="P -> L (in CF)"
FT /id="VAR_000244"
FT VARIANT 1077
FT /note="L -> P (in CF; dbSNP:rs139304906)"
FT /id="VAR_000245"
FT VARIANT 1085
FT /note="H -> R (in CF; dbSNP:rs79635528)"
FT /evidence="ECO:0000269|PubMed:7683628"
FT /id="VAR_000246"
FT VARIANT 1092..1480
FT /note="Missing (in CF)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_080319"
FT VARIANT 1098
FT /note="W -> R (in CF; dbSNP:rs397508531)"
FT /evidence="ECO:0000269|PubMed:7537150"
FT /id="VAR_000247"
FT VARIANT 1101
FT /note="M -> K (in CF; dbSNP:rs36210737)"
FT /evidence="ECO:0000269|PubMed:7680525"
FT /id="VAR_000248"
FT VARIANT 1101
FT /note="M -> R (in CF; dbSNP:rs36210737)"
FT /evidence="ECO:0000269|PubMed:7683628"
FT /id="VAR_011565"
FT VARIANT 1137
FT /note="M -> V (in CF; decreases channel activity; no
FT visible effect on protein maturation; dbSNP:rs397508553)"
FT /evidence="ECO:0000269|PubMed:9804160"
FT /id="VAR_000249"
FT VARIANT 1140
FT /note="Missing (in CF; abolishes channel activity; no
FT visible effect on protein maturation; dbSNP:rs397508557)"
FT /evidence="ECO:0000269|PubMed:9101301,
FT ECO:0000269|PubMed:9804160"
FT /id="VAR_000250"
FT VARIANT 1152
FT /note="D -> H (in CF and CBAVD; decreases channel activity;
FT no visible effect on protein maturation; dbSNP:rs75541969)"
FT /evidence="ECO:0000269|PubMed:17329263,
FT ECO:0000269|PubMed:9804160"
FT /id="VAR_000251"
FT VARIANT 1153
FT /note="V -> E (in CBAVD; unknown pathological significance;
FT dbSNP:rs397508567)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_080320"
FT VARIANT 1162..1480
FT /note="Missing (in CF)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_080321"
FT VARIANT 1162
FT /note="R -> L (in dbSNP:rs1800120)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_000252"
FT VARIANT 1200
FT /note="K -> E (in CF; unknown pathological significance)"
FT /evidence="ECO:0000269|PubMed:1379210"
FT /id="VAR_080322"
FT VARIANT 1204..1480
FT /note="Missing (in CF)"
FT /evidence="ECO:0000269|PubMed:7522211"
FT /id="VAR_080323"
FT VARIANT 1220
FT /note="T -> I (in dbSNP:rs1800123)"
FT /evidence="ECO:0000269|PubMed:7522211"
FT /id="VAR_000253"
FT VARIANT 1234
FT /note="I -> V (in CF; dbSNP:rs75389940)"
FT /id="VAR_000254"
FT VARIANT 1235
FT /note="S -> R (in CF; dbSNP:rs34911792)"
FT /id="VAR_000255"
FT VARIANT 1244
FT /note="G -> E (in CF; loss of bicarbonate transport; no
FT effect on protein maturation, subcellular location at the
FT plasma membrane, nor on chloride channel activity;
FT dbSNP:rs267606723)"
FT /evidence="ECO:0000269|PubMed:11242048"
FT /id="VAR_000256"
FT VARIANT 1249
FT /note="G -> E (in CF; dbSNP:rs121909040)"
FT /evidence="ECO:0000269|PubMed:7520022"
FT /id="VAR_000257"
FT VARIANT 1251
FT /note="S -> N (in CF; dbSNP:rs74503330)"
FT /id="VAR_000258"
FT VARIANT 1255
FT /note="S -> P (in CF; loss of bicarbonate transport; no
FT effect on protein maturation, subcellular location at the
FT plasma membrane, nor on chloride channel activity;
FT dbSNP:rs121909041)"
FT /evidence="ECO:0000269|PubMed:11242048,
FT ECO:0000269|PubMed:1284530"
FT /id="VAR_000259"
FT VARIANT 1270
FT /note="D -> N (in CF and CBAVD; dbSNP:rs11971167)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_000260"
FT VARIANT 1282..1480
FT /note="Missing (in CF and CBAVD)"
FT /evidence="ECO:0000269|PubMed:1379210,
FT ECO:0000269|PubMed:17329263"
FT /id="VAR_080324"
FT VARIANT 1282
FT /note="W -> R (in CF; dbSNP:rs397508616)"
FT /id="VAR_000261"
FT VARIANT 1283
FT /note="R -> M (in CF; dbSNP:rs77902683)"
FT /evidence="ECO:0000269|PubMed:1284468"
FT /id="VAR_000262"
FT VARIANT 1286
FT /note="F -> S (in CF; dbSNP:rs121909028)"
FT /id="VAR_000263"
FT VARIANT 1291
FT /note="Q -> H (in CF; dbSNP:rs121909015)"
FT /evidence="ECO:0000269|PubMed:1284466"
FT /id="VAR_000264"
FT VARIANT 1291
FT /note="Q -> R (in CF; dbSNP:rs397508621)"
FT /evidence="ECO:0000269|PubMed:7525450"
FT /id="VAR_000265"
FT VARIANT 1303
FT /note="N -> H (in CF; dbSNP:rs121909042)"
FT /id="VAR_000266"
FT VARIANT 1303
FT /note="N -> K (in CF; impaired maturation of glycan chains;
FT has low in vitro channel activity at low temperature;
FT dbSNP:rs80034486)"
FT /evidence="ECO:0000269|PubMed:12394343,
FT ECO:0000269|PubMed:1379210, ECO:0000269|PubMed:1712898,
FT ECO:0000269|PubMed:17182731, ECO:0000269|PubMed:9401006"
FT /id="VAR_000267"
FT VARIANT 1349
FT /note="G -> D (in CF; loss of bicarbonate transport; no
FT effect on protein maturation, subcellular location at the
FT plasma membrane, nor on chloride channel activity;
FT dbSNP:rs193922525)"
FT /evidence="ECO:0000269|PubMed:11242048,
FT ECO:0000269|PubMed:1712898"
FT /id="VAR_000268"
FT VARIANT 1352
FT /note="Q -> H (in CBAVD; unknown pathological significance;
FT dbSNP:rs113857788)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_080325"
FT VARIANT 1364
FT /note="A -> V (in CBAVD; dbSNP:rs397508670)"
FT /evidence="ECO:0000269|Ref.114"
FT /id="VAR_000269"
FT VARIANT 1397
FT /note="V -> E (in CF; dbSNP:rs397508691)"
FT /evidence="ECO:0000269|PubMed:7524913"
FT /id="VAR_000270"
FT VARIANT 1453
FT /note="R -> W (in dbSNP:rs4148725)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_048152"
FT VARIANT 1473..1480
FT /note="Missing (in CBAVD; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:17329263"
FT /id="VAR_080326"
FT MUTAGEN 464
FT /note="K->M: Impaired maturation of glycan chains
FT indicating impaired trafficking from the endoplasmic
FT reticulum to the cell membrane."
FT /evidence="ECO:0000269|PubMed:1699669"
FT MUTAGEN 508
FT /note="F->R: Impaired maturation of glycan chains
FT indicating impaired trafficking from the endoplasmic
FT reticulum to the cell membrane."
FT /evidence="ECO:0000269|PubMed:1699669,
FT ECO:0000269|PubMed:1712898"
FT MUTAGEN 508
FT /note="Missing: Abolishes MARCHF2-mediated degradation."
FT /evidence="ECO:0000269|PubMed:23818989"
FT MUTAGEN 539
FT /note="I->T: Enhances trafficking from the endoplasmic
FT reticulum to the cell membrane."
FT /evidence="ECO:0000269|PubMed:28001373"
FT MUTAGEN 894
FT /note="N->D: Abolishes N-glycosylation, enhances
FT endocytosis and impairs subsequent recycling to the cell
FT surface; when associated with D-900."
FT /evidence="ECO:0000269|PubMed:20008117"
FT MUTAGEN 900
FT /note="N->D: Abolishes N-glycosylation, enhances
FT endocytosis and impairs subsequent recycling to the cell
FT surface; when associated with D-894."
FT /evidence="ECO:0000269|PubMed:20008117"
FT MUTAGEN 1137
FT /note="M->R: Abolishes channel activity. Impairs protein
FT maturation, suggesting the protein is retained in the
FT endoplasmic reticulum."
FT /evidence="ECO:0000269|PubMed:9804160"
FT MUTAGEN 1139
FT /note="I->V: Decreases channel activity, no visible effect
FT on protein maturation."
FT /evidence="ECO:0000269|PubMed:9804160"
FT MUTAGEN 1154
FT /note="D->G: Decreases channel activity, no visible effect
FT on protein maturation."
FT /evidence="ECO:0000269|PubMed:9804160"
FT MUTAGEN 1250
FT /note="K->M: No effect on maturation of glycans, suggesting
FT that trafficking to the plasma membrane is not altered."
FT /evidence="ECO:0000269|PubMed:1699669"
FT MUTAGEN 1478..1480
FT /note="Missing: Reduces interaction with MARCHF2 and
FT abolishes subsequent MARCHF2-mediated degradation. No
FT effect on localization to the Golgi."
FT /evidence="ECO:0000269|PubMed:23818989"
FT CONFLICT 620
FT /note="H -> N (in Ref. 1; AAA35680)"
FT /evidence="ECO:0000305"
FT CONFLICT 833
FT /note="F -> L (in Ref. 1; AAA35680)"
FT /evidence="ECO:0000305"
FT HELIX 11..16
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 18..20
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 21..27
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 34..36
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 46..63
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 70..97
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 99..107
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 120..164
FT /evidence="ECO:0007829|PDB:7SVD"
FT TURN 169..173
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 177..185
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 190..193
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 194..196
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 200..216
FT /evidence="ECO:0007829|PDB:7SVD"
FT TURN 220..222
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 223..249
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 252..266
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 269..275
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 278..312
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 314..328
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 333..351
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 354..375
FT /evidence="ECO:0007829|PDB:7SVD"
FT STRAND 390..399
FT /evidence="ECO:0007829|PDB:2PZE"
FT HELIX 403..411
FT /evidence="ECO:0007829|PDB:2BBS"
FT HELIX 414..417
FT /evidence="ECO:0007829|PDB:2BBT"
FT HELIX 433..436
FT /evidence="ECO:0007829|PDB:1XMI"
FT STRAND 440..449
FT /evidence="ECO:0007829|PDB:2PZE"
FT STRAND 450..452
FT /evidence="ECO:0007829|PDB:6MSM"
FT STRAND 453..457
FT /evidence="ECO:0007829|PDB:2PZE"
FT HELIX 460..462
FT /evidence="ECO:0007829|PDB:6ZE1"
FT HELIX 464..471
FT /evidence="ECO:0007829|PDB:2PZE"
FT STRAND 478..484
FT /evidence="ECO:0007829|PDB:2PZE"
FT STRAND 488..491
FT /evidence="ECO:0007829|PDB:2PZE"
FT STRAND 499..501
FT /evidence="ECO:0007829|PDB:2PZG"
FT HELIX 502..507
FT /evidence="ECO:0007829|PDB:2PZE"
FT HELIX 514..523
FT /evidence="ECO:0007829|PDB:2PZE"
FT HELIX 527..530
FT /evidence="ECO:0007829|PDB:2PZE"
FT STRAND 533..535
FT /evidence="ECO:0007829|PDB:2PZF"
FT HELIX 536..538
FT /evidence="ECO:0007829|PDB:2PZE"
FT STRAND 540..545
FT /evidence="ECO:0007829|PDB:5TFJ"
FT HELIX 550..563
FT /evidence="ECO:0007829|PDB:2PZE"
FT STRAND 567..573
FT /evidence="ECO:0007829|PDB:2PZE"
FT TURN 574..577
FT /evidence="ECO:0007829|PDB:2PZE"
FT HELIX 580..589
FT /evidence="ECO:0007829|PDB:2PZE"
FT HELIX 590..594
FT /evidence="ECO:0007829|PDB:2PZE"
FT TURN 595..597
FT /evidence="ECO:0007829|PDB:2PZE"
FT STRAND 598..603
FT /evidence="ECO:0007829|PDB:2PZE"
FT HELIX 607..612
FT /evidence="ECO:0007829|PDB:2PZE"
FT STRAND 614..620
FT /evidence="ECO:0007829|PDB:2PZE"
FT STRAND 623..628
FT /evidence="ECO:0007829|PDB:2PZE"
FT HELIX 630..634
FT /evidence="ECO:0007829|PDB:2PZE"
FT HELIX 640..644
FT /evidence="ECO:0007829|PDB:2PZE"
FT HELIX 650..652
FT /evidence="ECO:0007829|PDB:2BBS"
FT HELIX 655..669
FT /evidence="ECO:0007829|PDB:2BBS"
FT HELIX 849..853
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 857..882
FT /evidence="ECO:0007829|PDB:7SVD"
FT TURN 883..886
FT /evidence="ECO:0007829|PDB:7SVD"
FT STRAND 904..906
FT /evidence="ECO:0007829|PDB:7SVD"
FT TURN 910..913
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 914..926
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 931..956
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 961..965
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 969..1011
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 1015..1046
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 1049..1060
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 1062..1068
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 1071..1121
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 1128..1136
FT /evidence="ECO:0007829|PDB:7SVD"
FT TURN 1137..1139
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 1140..1167
FT /evidence="ECO:0007829|PDB:7SVD"
FT STRAND 1204..1207
FT /evidence="ECO:0007829|PDB:3GD7"
FT STRAND 1210..1220
FT /evidence="ECO:0007829|PDB:6UK1"
FT STRAND 1226..1234
FT /evidence="ECO:0007829|PDB:6UK1"
FT STRAND 1239..1243
FT /evidence="ECO:0007829|PDB:6UK1"
FT HELIX 1250..1257
FT /evidence="ECO:0007829|PDB:6UK1"
FT STRAND 1261..1269
FT /evidence="ECO:0007829|PDB:6UK1"
FT HELIX 1274..1276
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 1279..1283
FT /evidence="ECO:0007829|PDB:6UK1"
FT STRAND 1286..1290
FT /evidence="ECO:0007829|PDB:6UK1"
FT STRAND 1297..1299
FT /evidence="ECO:0007829|PDB:6UK1"
FT HELIX 1300..1304
FT /evidence="ECO:0007829|PDB:6UK1"
FT HELIX 1312..1321
FT /evidence="ECO:0007829|PDB:6UK1"
FT HELIX 1325..1329
FT /evidence="ECO:0007829|PDB:6UK1"
FT STRAND 1331..1333
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 1334..1336
FT /evidence="ECO:0007829|PDB:6UK1"
FT TURN 1341..1345
FT /evidence="ECO:0007829|PDB:6UK1"
FT HELIX 1348..1361
FT /evidence="ECO:0007829|PDB:6UK1"
FT STRAND 1365..1371
FT /evidence="ECO:0007829|PDB:6UK1"
FT HELIX 1372..1375
FT /evidence="ECO:0007829|PDB:6UK1"
FT HELIX 1378..1387
FT /evidence="ECO:0007829|PDB:6UK1"
FT TURN 1388..1394
FT /evidence="ECO:0007829|PDB:6UK1"
FT STRAND 1395..1403
FT /evidence="ECO:0007829|PDB:6UK1"
FT HELIX 1404..1406
FT /evidence="ECO:0007829|PDB:6UK1"
FT STRAND 1411..1415
FT /evidence="ECO:0007829|PDB:6UK1"
FT STRAND 1422..1427
FT /evidence="ECO:0007829|PDB:6UK1"
FT HELIX 1435..1439
FT /evidence="ECO:0007829|PDB:7SVD"
FT HELIX 1443..1449
FT /evidence="ECO:0007829|PDB:7SVD"
FT STRAND 1478..1480
FT /evidence="ECO:0007829|PDB:2LOB"
SQ SEQUENCE 1480 AA; 168142 MW; 8D082AA2E768C065 CRC64;
MQRSPLEKAS VVSKLFFSWT RPILRKGYRQ RLELSDIYQI PSVDSADNLS EKLEREWDRE
LASKKNPKLI NALRRCFFWR FMFYGIFLYL GEVTKAVQPL LLGRIIASYD PDNKEERSIA
IYLGIGLCLL FIVRTLLLHP AIFGLHHIGM QMRIAMFSLI YKKTLKLSSR VLDKISIGQL
VSLLSNNLNK FDEGLALAHF VWIAPLQVAL LMGLIWELLQ ASAFCGLGFL IVLALFQAGL
GRMMMKYRDQ RAGKISERLV ITSEMIENIQ SVKAYCWEEA MEKMIENLRQ TELKLTRKAA
YVRYFNSSAF FFSGFFVVFL SVLPYALIKG IILRKIFTTI SFCIVLRMAV TRQFPWAVQT
WYDSLGAINK IQDFLQKQEY KTLEYNLTTT EVVMENVTAF WEEGFGELFE KAKQNNNNRK
TSNGDDSLFF SNFSLLGTPV LKDINFKIER GQLLAVAGST GAGKTSLLMV IMGELEPSEG
KIKHSGRISF CSQFSWIMPG TIKENIIFGV SYDEYRYRSV IKACQLEEDI SKFAEKDNIV
LGEGGITLSG GQRARISLAR AVYKDADLYL LDSPFGYLDV LTEKEIFESC VCKLMANKTR
ILVTSKMEHL KKADKILILH EGSSYFYGTF SELQNLQPDF SSKLMGCDSF DQFSAERRNS
ILTETLHRFS LEGDAPVSWT ETKKQSFKQT GEFGEKRKNS ILNPINSIRK FSIVQKTPLQ
MNGIEEDSDE PLERRLSLVP DSEQGEAILP RISVISTGPT LQARRRQSVL NLMTHSVNQG
QNIHRKTTAS TRKVSLAPQA NLTELDIYSR RLSQETGLEI SEEINEEDLK ECFFDDMESI
PAVTTWNTYL RYITVHKSLI FVLIWCLVIF LAEVAASLVV LWLLGNTPLQ DKGNSTHSRN
NSYAVIITST SSYYVFYIYV GVADTLLAMG FFRGLPLVHT LITVSKILHH KMLHSVLQAP
MSTLNTLKAG GILNRFSKDI AILDDLLPLT IFDFIQLLLI VIGAIAVVAV LQPYIFVATV
PVIVAFIMLR AYFLQTSQQL KQLESEGRSP IFTHLVTSLK GLWTLRAFGR QPYFETLFHK
ALNLHTANWF LYLSTLRWFQ MRIEMIFVIF FIAVTFISIL TTGEGEGRVG IILTLAMNIM
STLQWAVNSS IDVDSLMRSV SRVFKFIDMP TEGKPTKSTK PYKNGQLSKV MIIENSHVKK
DDIWPSGGQM TVKDLTAKYT EGGNAILENI SFSISPGQRV GLLGRTGSGK STLLSAFLRL
LNTEGEIQID GVSWDSITLQ QWRKAFGVIP QKVFIFSGTF RKNLDPYEQW SDQEIWKVAD
EVGLRSVIEQ FPGKLDFVLV DGGCVLSHGH KQLMCLARSV LSKAKILLLD EPSAHLDPVT
YQIIRRTLKQ AFADCTVILC EHRIEAMLEC QQFLVIEENK VRQYDSIQKL LNERSLFRQA
ISPSDRVKLF PHRNSSKCKS KPQIAALKEE TEEEVQDTRL
