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 11-NOV-2015, entry version 209. 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=3.6.3.49; DE AltName: Full=cAMP-dependent chloride channel; GN Name=CFTR; Synonyms=ABCC7; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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., RA Grzelczak Z., Zielenski J., Lok S., Plavsic N., Chou J.-L., RA Drumm M.L., Iannuzzi M.C., Collins F.S., Tsui L.-C.; RT "Identification of the cystic fibrosis gene: cloning and RT characterization 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., RA Riordan J.R., 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., RA Paddock M., Chang J., Zhou Y., Haugen E., Waring D., Chapman P., RA Hayden H., Levy R., Wu Z., Rouse G., James R., Phelps K., Olson M.V., RA 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., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA 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., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., 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., RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., RA 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., RA Mural R.J., 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; RP SER-790; SER-795 AND SER-813. RX PubMed=1377674; 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; RA Chang X.-B., Hou Y.-X., Jensen T.J., Riordan J.R.; RT "Mapping of cystic fibrosis transmembrane conductance regulator RT membrane 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; RP SER-768; 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 RT metal-ion affinity resin and matrix-assisted laser desorption mass RT 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 RT 9 skipping through a nonevolutionary conserved intronic element."; RL J. Biol. Chem. 275:21041-21047(2000). RN [10] RP INTERACTION WITH GOPC. 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 [11] RP INTERACTION WITH SC4A7 AND SLC9A3R1. 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 RT with and regulates the activity of the HCO3- salvage transporter human RT Na+-HCO3-cotransport isoform 3."; RL J. Biol. Chem. 277:50503-50509(2002). RN [12] RP PHOSPHORYLATION BY AMPK. 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 RT kinase in polarized T84 cells."; RL Am. J. Physiol. 284:C1297-C1308(2003). RN [13] RP INTERACTION WITH MYO6. 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 [14] RP REVIEW. RX PubMed=1378801; RA McIntosh I., Cutting G.R.; RT "Cystic fibrosis transmembrane conductance regulator and the etiology RT and pathogenesis of cystic fibrosis."; RL FASEB J. 6:2775-2782(1992). RN [15] 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 RT cystic fibrosis transmembrane conductance regulator gene."; RL Hum. Mol. Genet. 12:2031-2040(2003). RN [16] RP CHANNEL GATING REGULATION, AND PHOSPHORYLATION. RX PubMed=12588899; DOI=10.1113/jphysiol.2002.035790; RA Chappe V., Hinkson D.A., Zhu T., Chang X.B., Riordan J.R., RA Hanrahan J.W.; RT "Phosphorylation of protein kinase C sites in NBD1 and the R domain RT control CFTR channel activation by PKA."; RL J. Physiol. (Lond.) 548:39-52(2003). RN [17] RP IDENTIFICATION IN A COMPLEX WITH RAB11A AND MYO5B. 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 RT transmembrane conductance regulator in Rab11a-specific apical RT recycling endosomes in polarized human airway epithelial cells."; RL J. Biol. Chem. 282:23725-23736(2007). RN [18] RP UBIQUITINATION, AND SUBCELLULAR LOCATION. 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 RT sorting of cystic fibrosis transmembrane conductance regulator in RT airway epithelial cells."; RL J. Biol. Chem. 284:18778-18789(2009). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-549, AND IDENTIFICATION RP BY 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [20] 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 [21] 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 [22] 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 RT functionally interacts with the cystic fibrosis transmembrane RT conductance regulator channel: a potential role during sperm RT capacitation."; RL Hum. Mol. Genet. 21:1287-1298(2012). RN [23] RP PHOSPHORYLATION AT SER-660; SER-686; SER-700; SER-712; THR-717; RP SER-737; SER-795; SER-1444 AND SER-1456, UBIQUITINATION AT LYS-688, RP PALMITOYLATION AT CYS-524 AND CYS-1395, AND IDENTIFICATION BY MASS RP 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 RT of palmitoylation and other post-translational modifications."; RL Protein Eng. Des. Sel. 25:7-14(2012). RN [24] 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 RT conductance regulator (CFTR)."; RL J. Biol. Chem. 288:31177-31191(2013). RN [25] RP 3D-STRUCTURE MODELING OF 425-638. RX PubMed=9517543; RX DOI=10.1002/(SICI)1097-0134(19980215)30:3<275::AID-PROT7>3.3.CO;2-L; RA Hoedemaeker F.J., Davidson A.R., Rose D.R.; RT "A model for the nucleotide-binding domains of ABC transporters based RT on the large domain of aspartate aminotransferase."; RL Proteins 30:275-286(1998). RN [26] 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 [27] 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 RT Cystic Fibrosis Genetic Analysis Consortium."; RL Hum. Mutat. 1:197-203(1992). RN [28] 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- RT binding fold of the cystic fibrosis conductance regulator protein."; RL Nature 346:366-369(1990). RN [29] 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., RA Yahav J., Kennedy D., Riordan J.R., Collins F.S., Rommens J.M., RA Tsui L.-C.; RT "Identification of mutations in regions corresponding to the two RT putative nucleotide (ATP)-binding folds of the cystic fibrosis gene."; RL Proc. Natl. Acad. Sci. U.S.A. 87:8447-8451(1990). RN [30] 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 RT gene in an African-American (CF444delA), an Italian (CF2522insC), and RT a Soviet (CF3821delT)."; RL Genomics 10:266-269(1991). RN [31] 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 RT chemical cleavage: analysis of variant splicing and a nonsense RT mutation."; RL Hum. Mol. Genet. 1:11-17(1992). RN [32] 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 [33] 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 RT binding fold of the cystic fibrosis gene."; RL Hum. Mol. Genet. 1:441-442(1992). RN [34] 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 RT fibrosis gene by SSCP."; RL Hum. Mol. Genet. 1:439-440(1992). RN [35] RP VARIANT CF LYS-1101. RX PubMed=7680525; RA Zielenski J., Fugiwara T.M., Markiewicz D., Paradis A.J., RA Anacleto A.I., Richards B., Schwartz R.H., Klinger K.W., Tsui L.-C., RA Morgan K.; RT "Identification of the M1101K mutation in the cystic fibrosis RT transmembrane conductance regulator (CFTR) gene and complete detection RT of cystic fibrosis mutations in the Hutterite population."; RL Am. J. Hum. Genet. 52:609-615(1993). RN [36] RP VARIANTS CF VAL-1052; ARG-1061; LEU-1066; GLN-1070; ARG-1085 AND RP 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., RA Rault G., Cashman S., Sangiuolo F., Audrezet M.-P., Dallapiccola B., RA Guillermit H., Bonduelle M., Liebaers I., Quere I., Verlingue C., RA Ferec C.; RT "Identification of eight novel mutations in a collaborative analysis RT of a part of the second transmembrane domain of the CFTR gene."; RL Genomics 16:296-297(1993). RN [37] 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 RT the CFTR gene causes a benign cystic fibrosis phenotype."; RL Hum. Mol. Genet. 2:79-80(1993). RN [38] 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 [39] RP VARIANTS CF. RX PubMed=7504969; DOI=10.1002/humu.1380020511; RA Gasparini P., Marigo C., Bisceglia G., Nicolis E., Zelante L., RA Bombieri C., Borgo G., Pignatti P.F., Cabrini G.; RT "Screening of 62 mutations in a cohort of cystic fibrosis patients RT from north eastern Italy: their incidence and clinical features of RT defined genotypes."; RL Hum. Mutat. 2:389-394(1993). RN [40] RP VARIANTS CYS-31 AND ILE-1220, AND VARIANTS CF LEU-912; TYR-949; RP PRO-1065 AND PRO-1071. RX PubMed=7522211; DOI=10.1006/geno.1994.1290; RA Ghaneb N., Costes B., Girodon E., Martin J., Fanen P., Goossens M.; RT "Identification of eight mutations and three sequence variations in RT the cystic fibrosis transmembrane conductance regulator (CFTR) gene."; RL Genomics 21:434-436(1994). RN [41] RP VARIANT CF PRO-346. RX PubMed=7513296; DOI=10.1007/BF00202817; RA Boteva K., Papageorgiou E., Georgiou C., Angastiniotis M., RA Middleton L.T., Constantinou-Deltas C.D.; RT "Novel cystic fibrosis mutation associated with mild disease in RT Cypriot patients."; RL Hum. Genet. 93:529-532(1994). RN [42] 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., RA von der Hardt H., Maass G., Tuemmler B.; RT "Detection of more than 50 different CFTR mutations in a large group RT of German cystic fibrosis patients."; RL Hum. Genet. 94:533-542(1994). RN [43] RP VARIANT CF GLU-1249. RX PubMed=7520022; 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 [44] 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., RA 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 [45] 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 RT domain of CFTR."; RL Hum. Mol. Genet. 3:1001-1002(1994). RN [46] 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 RT for 60 known mutations and identification of four new mutations (Q30X, RT A120T, 1812-1 G-->A, and 3667del4)."; RL Hum. Mutat. 3:223-230(1994). RN [47] 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 RT transmembrane conductance regulator gene."; RL Hum. Mutat. 3:395-396(1994). RN [48] 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 RT cystic fibrosis? Analyses of the CFTR gene in 67 patients."; RL Am. J. Hum. Genet. 56:272-277(1995). RN [49] 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 RT vas deferens."; RL Clin. Chem. 41:833-835(1995). RN [50] 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 RT three novel mutations."; RL Hum. Genet. 96:312-318(1995). RN [51] 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 RT cystic fibrosis phenotype."; RL Hum. Genet. 96:717-720(1995). RN [52] 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, RT W1089R, E1104X) in the cystic fibrosis transmembrane conductance RT regulator (CFTR) gene."; RL Hum. Mutat. 5:43-47(1995). RN [53] 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 RT gene in a sample of CF patients from Russia: identification of three RT novel alleles."; RL Hum. Mutat. 5:205-209(1995). RN [54] 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., RA Claustres M.; RT "Novel missense mutation in the first transmembrane segment of the RT CFTR gene (Q98R) identified in a male adult."; RL Hum. Mutat. 6:190-191(1995). RN [55] 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 RT phenotype of isolated hypotonic dehydration."; RL J. Pediatr. 127:281-283(1995). RN [56] 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 RT cystic fibrosis patients."; RL Mol. Cell. Probes 9:135-137(1995). RN [57] RP VARIANT CF SER-665. RX PubMed=8800923; RA Messaoud T., Verlingue C., Denamur E., Pascaud O., Quere I., RA Fattoum S., Elion J., Ferec C.; RT "Distribution of CFTR mutations in cystic fibrosis patients of RT Tunisian origin: identification of two novel mutations."; RL Eur. J. Hum. Genet. 4:20-24(1996). RN [58] 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 RT hepatic failure."; RL Hum. Mutat. 7:151-154(1996). RN [59] RP VARIANT CF CYS-569. RX PubMed=8723693; RX DOI=10.1002/(SICI)1098-1004(1996)7:4<375::AID-HUMU17>3.3.CO;2-K; RA Petreska L., Plaseska D., Koseva S., Stavljenic-Rukavina A., RA 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 [60] RP VARIANT CF ARG-1061. RX PubMed=8723695; RX DOI=10.1002/(SICI)1098-1004(1996)7:4<376::AID-HUMU18>3.3.CO;2-E; 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 [61] RP VARIANT CF LEU-562. RX PubMed=8956039; RX DOI=10.1002/(SICI)1098-1004(1996)8:4<340::AID-HUMU7>3.3.CO;2-K; 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 RT families: thirty mutations, including two novel, account for RT approximately 94% of CF chromosomes."; RL Hum. Mutat. 8:340-347(1996). RN [62] 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 RT from patients with congenital bilateral absence of vas deferens RT (CBAVD)."; RL Hum. Mutat. 9:183-184(1997). RN [63] RP VARIANT CF MET-1140 DEL. RX PubMed=9101301; RX DOI=10.1002/(SICI)1098-1004(1997)9:4<368::AID-HUMU13>3.3.CO;2-F; RA Clavel C., Pennaforte F., Pigeon F., Verlingue C., Birembaut P., RA Ferec C.; RT "Identification of four novel mutations in the cystic fibrosis RT transmembrane conductance regulator gene: E664X, 2113delA, 306delTAGA, RT and delta M1140."; RL Hum. Mutat. 9:368-369(1997). RN [64] 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 [65] RP VARIANT CF CYS-1066. RX PubMed=9375855; RX DOI=10.1002/(SICI)1098-1004(1997)10:5<387::AID-HUMU9>3.3.CO;2-V; 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., RA Seculi J.L., Perez E., Dapena J., Carrilho E., Duarte A., RA Palacio A.M., Nunes V., Lavinha J., Estivill X.; RT "Missense mutation R1066C in the second transmembrane domain of CFTR RT causes a severe cystic fibrosis phenotype: study of 19 heterozygous RT and 2 homozygous patients."; RL Hum. Mutat. 10:387-392(1997). RN [66] 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 [67] 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 [68] 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., RA Camcioglu Y., Cokugras H., Akcakaya N., Apak M., Tsui L.-C., RA Kirdar B.; RT "Analysis of the CFTR gene in Turkish cystic fibrosis patients: RT identification of three novel mutations (3172delAC, P1013L and RT M1028I)."; RL Hum. Genet. 102:224-230(1998). RN [69] RP VARIANTS CF. 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 [70] RP VARIANTS CF. 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 [71] 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 RT transmembrane regulator (CFTR) gene in Pakistani patients with cystic RT fibrosis: Y569D, Q98X, 296+12(T>C), 1161delC and 621+2(T>C)."; RL Hum. Mutat. 11:152-157(1998). RN [72] 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 RT patient of Sardinian origin."; RL Hum. Mutat. 11:337-337(1998). RN [73] RP VARIANTS CF PRO-117 AND ASP-192 DEL. RX PubMed=9452048; 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 [74] RP VARIANT CF ARG-1065. RX PubMed=9452054; 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 RT cystic fibrosis."; RL Hum. Mutat. Suppl. 1:S99-S102(1998). RN [75] RP VARIANT CF ASN-LYS-370 INS. RX PubMed=9452073; RA Shackleton S., Harris A.; RT "A 2-amino acid insertion mutation (1243insACAAAA) in exon 7 of the RT CFTR gene."; RL Hum. Mutat. Suppl. 1:S156-S157(1998). RN [76] RP VARIANT CBAVD GLY-513, AND VARIANT MET-470. RX PubMed=10651488; RA Bienvenu T., Bousquet S., Vidaud D., Hubert D., Francoual C., RA Beldjord C., 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 [77] 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 RT patients and identification of six novel mutations."; RL Hum. Mutat. 12:480-480(1998). RN [78] 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 [79] 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., RA Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., RA Graubert T.A., DiPersio J.F., Wilson R.K.; RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia RT genome."; RL Nature 456:66-72(2008). CC -!- FUNCTION: Involved in the transport of chloride ions. May regulate CC bicarbonate secretion and salvage in epithelial cells by CC regulating the SLC4A7 transporter. Can inhibit the chloride CC channel activity of ANO1. Plays a role in the chloride and CC bicarbonate homeostasis during sperm epididymal maturation and CC capacitation. {ECO:0000269|PubMed:22178883}. CC -!- CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate. CC -!- SUBUNIT: Interacts with SLC26A3, SLC26A6 and SHANK2 (By CC similarity). Interacts with SLC9A3R1, MYO6 and GOPC. Interacts CC with SLC4A7 through SLC9A3R1. Found in a complex with MYO5B and CC RAB11A. Interacts with ANO1. Interacts with SLC26A8. Interacts CC with AHCYL1; the interaction increases CFTR activity (By CC similarity). {ECO:0000250|UniProtKB:P26361, CC ECO:0000269|PubMed:11304524, ECO:0000269|PubMed:11707463, CC ECO:0000269|PubMed:12403779, ECO:0000269|PubMed:15247260, CC ECO:0000269|PubMed:17462998, ECO:0000269|PubMed:22121115, CC ECO:0000269|PubMed:22178883}. CC -!- INTERACTION: CC P51572:BCAP31; NbExp=3; IntAct=EBI-349854, EBI-77683; CC P27824:CANX; NbExp=3; IntAct=EBI-349854, EBI-355947; CC Q9BUN8:DERL1; NbExp=2; IntAct=EBI-349854, EBI-398977; CC Q9H8Y8:GORASP2; NbExp=3; IntAct=EBI-349854, EBI-739467; CC P19120:HSPA8 (xeno); NbExp=2; IntAct=EBI-349854, EBI-907802; CC P05787:KRT8; NbExp=7; IntAct=EBI-349854, EBI-297852; CC Q9HBW0:LPAR2; NbExp=4; IntAct=EBI-349854, EBI-765995; CC Q5T2W1:PDZK1; NbExp=2; IntAct=EBI-349854, EBI-349819; CC Q99942:RNF5; NbExp=3; IntAct=EBI-349854, EBI-348482; CC Q9QX74:Shank2 (xeno); NbExp=2; IntAct=EBI-349854, EBI-397902; CC Q96RN1:SLC26A8; NbExp=2; IntAct=EBI-349854, EBI-1792052; CC O14745:SLC9A3R1; NbExp=5; IntAct=EBI-349854, EBI-349787; CC Q15599:SLC9A3R2; NbExp=7; IntAct=EBI-349854, EBI-1149760; CC -!- SUBCELLULAR LOCATION: Early endosome membrane; Multi-pass membrane CC protein. Cell membrane. Note=In the oviduct and bronchus, detected CC on the apical side of epithelial cells, but not associated with CC cilia. {ECO:0000269|PubMed:22207244}. 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 Note=Exon skipping favored by a high number of TG repeats and a CC low number of T repeats at the intron-exon boundary. Causes CC congenital bilateral absence of the vas deferens (CBAVD).; CC Name=3; CC IsoId=P13569-3; Sequence=VSP_022124, VSP_022125; CC Note=Alternative acceptor site favored by mutation in an exonic CC splicing enhancer (ESE). Causes cystic fibrosis (CF).; CC -!- TISSUE SPECIFICITY: Expressed in the respiratory airway, including CC bronchial epithelium, and in the female reproductive tract, CC including oviduct (at protein level). CC {ECO:0000269|PubMed:22207244}. CC -!- DOMAIN: The PDZ-binding motif mediates interactions with GOPC and CC with the SLC4A7, SLC9A3R1/EBP50 complex. CC -!- PTM: Phosphorylated; activates the channel. It is not clear CC whether PKC phosphorylation itself activates the channel or CC permits activation by phosphorylation at PKA sites. Phosphorylated CC by AMPK. {ECO:0000269|PubMed:12519745, CC ECO:0000269|PubMed:12588899, ECO:0000269|PubMed:1377674, CC ECO:0000269|PubMed:22119790, ECO:0000269|PubMed:9385646}. CC -!- PTM: Ubiquitinated, leading to its degradation in the lysosome. CC Deubiquitination by USP10 in early endosomes, enhances its CC endocytic recycling. Ubiquitinated by RNF185 during ER stress. CC {ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:22119790, CC ECO:0000269|PubMed:24019521}. CC -!- DISEASE: Cystic fibrosis (CF) [MIM:219700]: A common generalized CC disorder of the exocrine glands which impairs clearance of CC secretions in a variety of organs. It is characterized by the CC triad of chronic bronchopulmonary disease (with recurrent CC respiratory infections), pancreatic insufficiency (which leads to CC malabsorption and growth retardation) and elevated sweat CC electrolytes. It is the most common genetic disease in Caucasians, CC with a prevalence of about 1 in 2'000 live births. Inheritance is CC autosomal recessive. {ECO:0000269|PubMed:10094564, CC ECO:0000269|PubMed:1284466, ECO:0000269|PubMed:1284468, CC ECO:0000269|PubMed:1284529, ECO:0000269|PubMed:1284530, CC ECO:0000269|PubMed:1695717, ECO:0000269|PubMed:1710600, CC ECO:0000269|PubMed:2236053, 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:7680525, ECO:0000269|PubMed:7683628, CC ECO:0000269|PubMed:7683954, ECO:0000269|PubMed:8081395, 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:8956039, CC ECO:0000269|PubMed:9101301, ECO:0000269|PubMed:9222768, CC ECO:0000269|PubMed:9375855, ECO:0000269|PubMed:9401006, CC ECO:0000269|PubMed:9443874, ECO:0000269|PubMed:9452048, CC ECO:0000269|PubMed:9452054, ECO:0000269|PubMed:9452073, CC ECO:0000269|PubMed:9482579, ECO:0000269|PubMed:9521595, CC ECO:0000269|PubMed:9554753, ECO:0000269|PubMed:9736778, CC ECO:0000269|PubMed:9921909}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Congenital bilateral absence of the vas deferens (CBAVD) CC [MIM:277180]: Important cause of sterility in men and could CC represent an incomplete form of cystic fibrosis, as the majority CC of men suffering from cystic fibrosis lack the vas deferens. CC {ECO:0000269|PubMed:10651488, ECO:0000269|PubMed:7529962, CC ECO:0000269|PubMed:7539342, ECO:0000269|PubMed:9067761, CC ECO:0000269|Ref.77}. Note=The disease is caused by mutations CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC CC family. CFTR transporter (TC 3.A.1.202) subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 2 ABC transmembrane type-1 domains. CC {ECO:0000255|PROSITE-ProRule:PRU00441}. CC -!- SIMILARITY: Contains 2 ABC transporter domains. CC {ECO:0000255|PROSITE-ProRule:PRU00434}. CC -!- WEB RESOURCE: Name=CFTR; Note=Cystic fibrosis mutation db; CC URL="http://www.genet.sickkids.on.ca/cftr/app"; 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 CC proteins; CC URL="http://abcmutations.hegelab.org/proteinDetails?uniprot_id=P13569"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 UniGene; Hs.489786; -. DR UniGene; Hs.621460; -. DR UniGene; Hs.661104; -. DR PDB; 1NBD; Model; -; A=425-638. 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 PDBsum; 1NBD; -. 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 DisProt; DP00012; -. DR ProteinModelPortal; P13569; -. DR SMR; P13569; 87-738, 860-1470. DR BioGrid; 107506; 270. DR DIP; DIP-32788N; -. DR IntAct; P13569; 138. DR MINT; MINT-148539; -. DR STRING; 9606.ENSP00000003084; -. DR BindingDB; P13569; -. DR ChEMBL; CHEMBL4051; -. DR DrugBank; DB00887; Bumetanide. DR DrugBank; DB04941; Crofelemer. DR DrugBank; DB01016; Glyburide. DR DrugBank; DB01050; Ibuprofen. DR DrugBank; DB08820; Ivacaftor. DR GuidetoPHARMACOLOGY; 707; -. DR MoonProt; P13569; -. DR TCDB; 3.A.1.202.1; the atp-binding cassette (abc) superfamily. DR PhosphoSite; P13569; -. DR BioMuta; CFTR; -. DR DMDM; 147744553; -. DR PaxDb; P13569; -. DR PRIDE; P13569; -. DR DNASU; 1080; -. DR Ensembl; ENST00000003084; ENSP00000003084; ENSG00000001626. [P13569-1] DR GeneID; 1080; -. DR KEGG; hsa:1080; -. DR UCSC; uc003vjd.3; human. [P13569-1] DR CTD; 1080; -. DR GeneCards; CFTR; -. DR GeneReviews; CFTR; -. DR HGNC; HGNC:1884; CFTR. DR HPA; CAB001951; -. DR HPA; HPA021939; -. DR MIM; 219700; phenotype. DR MIM; 277180; phenotype. DR MIM; 602421; gene. DR neXtProt; NX_P13569; -. 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 eggNOG; KOG0054; Eukaryota. DR eggNOG; COG1132; LUCA. DR GeneTree; ENSGT00770000120479; -. DR HOVERGEN; HBG004169; -. DR InParanoid; P13569; -. DR KO; K05031; -. DR OMA; NALRRCF; -. DR OrthoDB; EOG7C2R0B; -. DR PhylomeDB; P13569; -. DR TreeFam; TF105200; -. DR BioCyc; MetaCyc:HS00075-MONOMER; -. DR BRENDA; 3.6.3.49; 2681. 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 EvolutionaryTrace; P13569; -. DR GenomeRNAi; 1080; -. DR NextBio; 4500; -. DR PRO; PR:P13569; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; P13569; -. DR CleanEx; HS_CFTR; -. DR ExpressionAtlas; P13569; baseline and differential. DR Genevisible; P13569; HS. DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB. DR GO; GO:0016323; C:basolateral plasma membrane; NAS:UniProtKB. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW. 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:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0030660; C:Golgi-associated vesicle membrane; TAS:Reactome. DR GO; GO:0005765; C:lysosomal membrane; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0043234; C:protein complex; IDA:UniProtKB. DR GO; GO:0055037; C:recycling endosome; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; TAS:ProtInc. DR GO; GO:0005224; F:ATP-binding and phosphorylation-dependent chloride channel activity; TAS:ProtInc. DR GO; GO:0015106; F:bicarbonate transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0005260; F:channel-conductance-controlling ATPase activity; NAS:UniProtKB. DR GO; GO:0005254; F:chloride channel activity; IDA:UniProtKB. DR GO; GO:0019869; F:chloride channel inhibitor activity; IDA:UniProtKB. DR GO; GO:0015108; F:chloride transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0030165; F:PDZ domain binding; IDA:UniProtKB. DR GO; GO:0015701; P:bicarbonate transport; ISS:GOC. DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB. DR GO; GO:1902476; P:chloride transmembrane transport; IMP:UniProtKB. DR GO; GO:0006695; P:cholesterol biosynthetic process; IEA:Ensembl. DR GO; GO:0030301; P:cholesterol transport; IEA:Ensembl. DR GO; GO:0051454; P:intracellular pH elevation; ISS:UniProtKB. DR GO; GO:0060081; P:membrane hyperpolarization; ISS:UniProtKB. DR GO; GO:1902161; P:positive regulation of cyclic nucleotide-gated ion channel activity; IMP:UniProtKB. 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:0007585; P:respiratory gaseous exchange; TAS:ProtInc. DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0048240; P:sperm capacitation; ISS:UniProtKB. DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome. DR GO; GO:0006810; P:transport; TAS:ProtInc. DR GO; GO:0006904; P:vesicle docking involved in exocytosis; IEA:Ensembl. DR Gene3D; 3.40.50.300; -; 2. DR InterPro; IPR003593; AAA+_ATPase. DR InterPro; IPR011527; ABC1_TM_dom. DR InterPro; IPR003439; ABC_transporter-like. DR InterPro; IPR017871; ABC_transporter_CS. DR InterPro; IPR009147; CFTR/ABCC7. DR InterPro; IPR025837; CFTR_reg_dom. DR InterPro; IPR027417; P-loop_NTPase. DR PANTHER; PTHR24223:SF19; PTHR24223:SF19; 3. 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; KW Chloride; Chloride channel; Complete proteome; Disease mutation; KW Endosome; Glycoprotein; Hydrolase; Ion channel; Ion transport; KW Isopeptide bond; Lipoprotein; Membrane; Nucleotide-binding; Palmitate; KW Phosphoprotein; Polymorphism; Reference proteome; Repeat; KW Transmembrane; Transmembrane helix; Transport; Ubl conjugation. FT CHAIN 1 1480 Cystic fibrosis transmembrane conductance FT regulator. FT /FTId=PRO_0000093419. FT TOPO_DOM 1 80 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 81 103 Helical; Name=1. {ECO:0000255|PROSITE- FT ProRule:PRU00441}. FT TOPO_DOM 104 117 Extracellular. {ECO:0000255}. FT TRANSMEM 118 138 Helical; Name=2. {ECO:0000255|PROSITE- FT ProRule:PRU00441}. FT TOPO_DOM 139 194 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 195 215 Helical; Name=3. {ECO:0000255|PROSITE- FT ProRule:PRU00441}. FT TOPO_DOM 216 220 Extracellular. {ECO:0000255}. FT TRANSMEM 221 241 Helical; Name=4. {ECO:0000255|PROSITE- FT ProRule:PRU00441}. FT TOPO_DOM 242 307 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 308 328 Helical; Name=5. {ECO:0000255|PROSITE- FT ProRule:PRU00441}. FT TOPO_DOM 329 330 Extracellular. {ECO:0000255}. FT TRANSMEM 331 350 Helical; Name=6. {ECO:0000255|PROSITE- FT ProRule:PRU00441}. FT TOPO_DOM 351 859 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 860 880 Helical; Name=7. {ECO:0000255|PROSITE- FT ProRule:PRU00441}. FT TOPO_DOM 881 911 Extracellular. {ECO:0000255}. FT TRANSMEM 912 932 Helical; Name=8. {ECO:0000255|PROSITE- FT ProRule:PRU00441}. FT TOPO_DOM 933 990 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 991 1011 Helical; Name=9. {ECO:0000255|PROSITE- FT ProRule:PRU00441}. FT TOPO_DOM 1012 1013 Extracellular. {ECO:0000255}. FT TRANSMEM 1014 1034 Helical; Name=10. {ECO:0000255|PROSITE- FT ProRule:PRU00441}. FT TOPO_DOM 1035 1102 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 1103 1123 Helical; Name=11. {ECO:0000255|PROSITE- FT ProRule:PRU00441}. FT TOPO_DOM 1124 1128 Extracellular. {ECO:0000255}. FT TRANSMEM 1129 1149 Helical; Name=12. {ECO:0000255|PROSITE- FT ProRule:PRU00441}. FT TOPO_DOM 1150 1480 Cytoplasmic. {ECO:0000255}. FT DOMAIN 81 365 ABC transmembrane type-1 1. FT {ECO:0000255|PROSITE-ProRule:PRU00441}. FT DOMAIN 423 646 ABC transporter 1. {ECO:0000255|PROSITE- FT ProRule:PRU00434}. FT DOMAIN 859 1155 ABC transmembrane type-1 2. FT {ECO:0000255|PROSITE-ProRule:PRU00441}. FT DOMAIN 1210 1443 ABC transporter 2. {ECO:0000255|PROSITE- FT ProRule:PRU00434}. FT NP_BIND 458 465 ATP 1. {ECO:0000255|PROSITE- FT ProRule:PRU00434}. FT NP_BIND 1244 1251 ATP 2. {ECO:0000255|PROSITE- FT ProRule:PRU00434}. FT MOTIF 1478 1480 PDZ-binding. FT MOD_RES 549 549 Phosphoserine. FT {ECO:0000244|PubMed:20068231}. FT MOD_RES 660 660 Phosphoserine; by PKA. FT {ECO:0000269|PubMed:1377674, FT ECO:0000269|PubMed:22119790, FT ECO:0000269|PubMed:9385646}. FT MOD_RES 686 686 Phosphoserine; by PKC. FT {ECO:0000269|PubMed:1377674, FT ECO:0000269|PubMed:22119790}. FT MOD_RES 700 700 Phosphoserine; by PKA. FT {ECO:0000269|PubMed:1377674, FT ECO:0000269|PubMed:22119790, FT ECO:0000269|PubMed:9385646}. FT MOD_RES 712 712 Phosphoserine; by PKA. FT {ECO:0000269|PubMed:22119790, FT ECO:0000269|PubMed:9385646}. FT MOD_RES 717 717 Phosphothreonine. FT {ECO:0000269|PubMed:22119790}. FT MOD_RES 737 737 Phosphoserine; by PKA. FT {ECO:0000269|PubMed:1377674, FT ECO:0000269|PubMed:22119790, FT ECO:0000269|PubMed:9385646}. FT MOD_RES 753 753 Phosphoserine; by PKA. FT {ECO:0000269|PubMed:9385646}. FT MOD_RES 768 768 Phosphoserine; by PKA. FT {ECO:0000269|PubMed:1377674, FT ECO:0000269|PubMed:9385646}. FT MOD_RES 790 790 Phosphoserine; by PKC. FT {ECO:0000269|PubMed:1377674}. FT MOD_RES 795 795 Phosphoserine; by PKA. FT {ECO:0000269|PubMed:1377674, FT ECO:0000269|PubMed:22119790, FT ECO:0000269|PubMed:9385646}. FT MOD_RES 813 813 Phosphoserine; by PKA. FT {ECO:0000269|PubMed:1377674, FT ECO:0000269|PubMed:9385646}. FT MOD_RES 1444 1444 Phosphoserine. FT {ECO:0000269|PubMed:22119790}. FT MOD_RES 1456 1456 Phosphoserine. FT {ECO:0000269|PubMed:22119790}. FT LIPID 524 524 S-palmitoyl cysteine. FT {ECO:0000269|PubMed:22119790}. FT LIPID 1395 1395 S-palmitoyl cysteine. FT {ECO:0000269|PubMed:22119790}. FT CARBOHYD 894 894 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:7518437}. FT CARBOHYD 900 900 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:7518437}. FT CROSSLNK 688 688 Glycyl lysine isopeptide (Lys-Gly) FT (interchain with G-Cter in ubiquitin). FT {ECO:0000269|PubMed:22119790}. FT VAR_SEQ 404 464 Missing (in isoform 2). {ECO:0000305}. FT /FTId=VSP_022123. FT VAR_SEQ 589 605 SCVCKLMANKTRILVTS -> RRRCSCLLDRNKKTIF (in FT isoform 3). {ECO:0000305}. FT /FTId=VSP_022124. FT VAR_SEQ 606 1480 Missing (in isoform 3). {ECO:0000305}. FT /FTId=VSP_022125. FT VARIANT 13 13 S -> F (in CF). FT {ECO:0000269|PubMed:9554753}. FT /FTId=VAR_000101. FT VARIANT 31 31 R -> C (in dbSNP:rs1800073). FT {ECO:0000269|PubMed:7522211}. FT /FTId=VAR_000102. FT VARIANT 31 31 R -> L (in CF). FT {ECO:0000269|PubMed:7537150}. FT /FTId=VAR_000103. FT VARIANT 42 42 S -> F (in CF). FT {ECO:0000269|PubMed:7541510}. FT /FTId=VAR_000104. FT VARIANT 44 44 D -> G (in CF). FT /FTId=VAR_000105. FT VARIANT 44 44 D -> V (in dbSNP:rs1800074). FT /FTId=VAR_000106. FT VARIANT 50 50 S -> Y (in CBAVD). FT {ECO:0000269|PubMed:9067761}. FT /FTId=VAR_000107. FT VARIANT 57 57 W -> G (in CF). FT {ECO:0000269|PubMed:7544319}. FT /FTId=VAR_000108. FT VARIANT 67 67 P -> L (in CF). FT /FTId=VAR_000109. FT VARIANT 74 74 R -> W (in CF; dbSNP:rs115545701). FT /FTId=VAR_000110. FT VARIANT 75 75 R -> Q (in dbSNP:rs1800076). FT /FTId=VAR_000111. FT VARIANT 85 85 G -> E (in CF). FT {ECO:0000269|PubMed:9401006}. FT /FTId=VAR_000112. FT VARIANT 87 87 F -> L (in CF). FT {ECO:0000269|PubMed:8081395}. FT /FTId=VAR_000113. FT VARIANT 91 91 G -> R (in CF). FT /FTId=VAR_000114. FT VARIANT 92 92 E -> K (in CF). FT {ECO:0000269|PubMed:1284529, FT ECO:0000269|PubMed:7683954}. FT /FTId=VAR_000115. FT VARIANT 98 98 Q -> R (in CF). FT {ECO:0000269|PubMed:7581407}. FT /FTId=VAR_000116. FT VARIANT 105 105 I -> S (in CF). FT /FTId=VAR_000117. FT VARIANT 109 109 Y -> C (in CF). FT {ECO:0000269|PubMed:7524909}. FT /FTId=VAR_000118. FT VARIANT 110 110 D -> H (in CF). FT /FTId=VAR_000119. FT VARIANT 111 111 P -> L (in CBAVD). {ECO:0000269|Ref.77}. FT /FTId=VAR_000120. FT VARIANT 117 117 R -> C (in CF). FT {ECO:0000269|PubMed:1284529}. FT /FTId=VAR_000121. FT VARIANT 117 117 R -> H (in CF and CBAVD). FT {ECO:0000269|PubMed:9401006}. FT /FTId=VAR_000122. FT VARIANT 117 117 R -> L (in CF). FT {ECO:0000269|PubMed:7541510}. FT /FTId=VAR_000123. FT VARIANT 117 117 R -> P (in CF). FT {ECO:0000269|PubMed:9452048}. FT /FTId=VAR_000124. FT VARIANT 120 120 A -> T (in CF). FT {ECO:0000269|PubMed:7517264}. FT /FTId=VAR_000125. FT VARIANT 138 138 L -> P (in dbSNP:rs1800078). FT /FTId=VAR_009895. FT VARIANT 139 139 H -> R (in CF). FT {ECO:0000269|PubMed:7541510}. FT /FTId=VAR_000126. FT VARIANT 141 141 A -> D (in CF). FT {ECO:0000269|PubMed:9222768}. FT /FTId=VAR_000127. FT VARIANT 148 148 I -> T (in CF; dbSNP:rs35516286). FT /FTId=VAR_000128. FT VARIANT 149 149 G -> R (in CBAVD). FT {ECO:0000269|PubMed:7529962}. FT /FTId=VAR_000129. FT VARIANT 170 170 R -> H (in dbSNP:rs1800079). FT /FTId=VAR_009896. FT VARIANT 178 178 G -> R (in CF). FT /FTId=VAR_000130. FT VARIANT 182 182 S -> G (in dbSNP:rs1800080). FT /FTId=VAR_009897. FT VARIANT 192 192 Missing (in CF). FT {ECO:0000269|PubMed:9452048}. FT /FTId=VAR_000131. FT VARIANT 193 193 E -> K (in CBAVD and CF). FT {ECO:0000269|PubMed:7529962, FT ECO:0000269|PubMed:7544319}. FT /FTId=VAR_000132. FT VARIANT 199 199 H -> Q (in CF). FT /FTId=VAR_000133. FT VARIANT 199 199 H -> Y (in CF). FT {ECO:0000269|PubMed:7525450}. FT /FTId=VAR_000134. FT VARIANT 205 205 P -> S (in CF). FT {ECO:0000269|PubMed:7505694}. FT /FTId=VAR_000135. FT VARIANT 206 206 L -> W (in CF). FT {ECO:0000269|PubMed:8522333}. FT /FTId=VAR_000136. FT VARIANT 225 225 C -> R (in CF). FT /FTId=VAR_000137. FT VARIANT 244 244 M -> K (in CBAVD). {ECO:0000269|Ref.77}. FT /FTId=VAR_000138. FT VARIANT 258 258 R -> G (in CBAVD; dbSNP:rs191456345). FT {ECO:0000269|PubMed:7529962}. FT /FTId=VAR_000139. FT VARIANT 287 287 N -> Y (in CF). FT {ECO:0000269|PubMed:9401006}. FT /FTId=VAR_000140. FT VARIANT 297 297 R -> Q (in CF). FT /FTId=VAR_000141. FT VARIANT 301 301 Y -> C (in CF; dbSNP:rs150691494). FT /FTId=VAR_000142. FT VARIANT 307 307 S -> N (in CF). FT /FTId=VAR_000143. FT VARIANT 311 311 F -> L (in CF). FT /FTId=VAR_000144. FT VARIANT 311 311 Missing (in CF). FT {ECO:0000269|PubMed:9443874}. FT /FTId=VAR_000145. FT VARIANT 314 314 G -> E (in CF). FT /FTId=VAR_000146. FT VARIANT 314 314 G -> R (in CF). FT {ECO:0000269|PubMed:8829633}. FT /FTId=VAR_000147. FT VARIANT 322 322 V -> M (in dbSNP:rs1800085). FT /FTId=VAR_009898. FT VARIANT 334 334 R -> W (in CF; mild; dbSNP:rs121909011). FT /FTId=VAR_000148. FT VARIANT 336 336 I -> K (in CF). FT /FTId=VAR_000150. FT VARIANT 338 338 T -> I (in CF; mild; isolated hypotonic FT dehydration). FT {ECO:0000269|PubMed:7543567, FT ECO:0000269|PubMed:9554753}. FT /FTId=VAR_000151. FT VARIANT 346 346 L -> P (in CF; dominant mutation but mild FT phenotype). {ECO:0000269|PubMed:7513296}. FT /FTId=VAR_000152. FT VARIANT 347 347 R -> H (in CF). FT /FTId=VAR_000153. FT VARIANT 347 347 R -> L (in CF). FT /FTId=VAR_000154. FT VARIANT 347 347 R -> P (in CF; MILD). FT /FTId=VAR_000155. FT VARIANT 351 351 T -> S (in dbSNP:rs1800086). FT /FTId=VAR_009899. FT VARIANT 352 352 R -> Q (in CF). FT /FTId=VAR_000156. FT VARIANT 353 353 Q -> H (in dbSNP:rs1800087). FT /FTId=VAR_009900. FT VARIANT 359 360 QT -> KK (in CF). FT /FTId=VAR_000158. FT VARIANT 359 359 Q -> K (in CF). FT /FTId=VAR_000157. FT VARIANT 370 370 K -> KNK (in CF). FT {ECO:0000269|PubMed:9452073}. FT /FTId=VAR_000159. FT VARIANT 455 455 A -> E (in CF). FT {ECO:0000269|PubMed:9401006}. FT /FTId=VAR_000160. FT VARIANT 456 456 V -> F (in CF). FT /FTId=VAR_000161. FT VARIANT 458 458 G -> V (in CF). FT /FTId=VAR_000162. FT VARIANT 467 467 L -> F (in dbSNP:rs1800089). FT /FTId=VAR_000163. FT VARIANT 470 470 V -> M (in dbSNP:rs213950). FT {ECO:0000269|PubMed:10651488, FT ECO:0000269|PubMed:1710598, FT ECO:0000269|PubMed:18987736, FT ECO:0000269|PubMed:2475911, FT ECO:0000269|Ref.3}. FT /FTId=VAR_000164. FT VARIANT 480 480 G -> C (in CF). FT /FTId=VAR_000165. FT VARIANT 492 492 S -> F (in CF). FT /FTId=VAR_000166. FT VARIANT 504 504 E -> Q (in CF). FT /FTId=VAR_000167. FT VARIANT 506 506 I -> M (in dbSNP:rs1800092). FT /FTId=VAR_009901. FT VARIANT 506 506 I -> V. FT /FTId=VAR_000168. FT VARIANT 507 507 I -> V (in dbSNP:rs1800091). FT /FTId=VAR_000169. FT VARIANT 507 507 Missing (in CF). FT /FTId=VAR_000170. FT VARIANT 508 508 F -> C (in dbSNP:rs1800093). FT /FTId=VAR_000172. FT VARIANT 508 508 Missing (in CF and CBAVD; most common FT mutation; 72% of the population; CFTR FT fails to be properly delivered to plasma FT membrane). FT /FTId=VAR_000171. FT VARIANT 513 513 D -> G (in CBAVD). FT {ECO:0000269|PubMed:10651488}. FT /FTId=VAR_000173. FT VARIANT 520 520 V -> F (in CF; dbSNP:rs77646904). FT {ECO:0000269|PubMed:1284466}. FT /FTId=VAR_000174. FT VARIANT 532 532 K -> E (in dbSNP:rs35032490). FT /FTId=VAR_048150. FT VARIANT 544 544 G -> V (in CBAVD). {ECO:0000269|Ref.77}. FT /FTId=VAR_000175. FT VARIANT 549 549 S -> I (in CF). FT /FTId=VAR_000177. FT VARIANT 549 549 S -> N (in CF). FT /FTId=VAR_000176. FT VARIANT 549 549 S -> R (in CF). FT /FTId=VAR_000178. FT VARIANT 551 551 G -> D (in CF). FT {ECO:0000269|PubMed:9401006}. FT /FTId=VAR_000179. FT VARIANT 551 551 G -> S (in CF). FT /FTId=VAR_000180. FT VARIANT 553 553 R -> Q (in CF). FT /FTId=VAR_000181. FT VARIANT 558 558 L -> S (in CF). FT /FTId=VAR_000182. FT VARIANT 559 559 A -> T (in CF). FT /FTId=VAR_000183. FT VARIANT 560 560 R -> K (in CF). FT /FTId=VAR_000184. FT VARIANT 560 560 R -> S (in CF). FT {ECO:0000269|PubMed:9482579}. FT /FTId=VAR_000185. FT VARIANT 560 560 R -> T (in CF). FT /FTId=VAR_000186. FT VARIANT 562 562 V -> I (in dbSNP:rs1800097). FT /FTId=VAR_000187. FT VARIANT 562 562 V -> L (in CF; dbSNP:rs1800097). FT {ECO:0000269|PubMed:8956039}. FT /FTId=VAR_000188. FT VARIANT 563 563 Y -> N (in CF). FT /FTId=VAR_000189. FT VARIANT 569 569 Y -> C (in CF). FT {ECO:0000269|PubMed:8723693}. FT /FTId=VAR_000190. FT VARIANT 569 569 Y -> D (in CF). FT {ECO:0000269|PubMed:9482579}. FT /FTId=VAR_000191. FT VARIANT 569 569 Y -> H (in CF). FT /FTId=VAR_000192. FT VARIANT 571 571 L -> S (in CF). FT /FTId=VAR_000193. FT VARIANT 572 572 D -> N (in CF). FT {ECO:0000269|PubMed:7541273}. FT /FTId=VAR_000194. FT VARIANT 574 574 P -> H (in CF). FT /FTId=VAR_000195. FT VARIANT 576 576 G -> A (in dbSNP:rs1800098). FT /FTId=VAR_000196. FT VARIANT 579 579 D -> G (in CF). FT {ECO:0000269|PubMed:10094564, FT ECO:0000269|PubMed:7544319}. FT /FTId=VAR_000197. FT VARIANT 601 601 I -> F (in CF). FT /FTId=VAR_000198. FT VARIANT 605 605 S -> F (in dbSNP:rs766874). FT /FTId=VAR_048151. FT VARIANT 610 610 L -> S (in CF). FT /FTId=VAR_000199. FT VARIANT 613 613 A -> T (in CF; dbSNP:rs201978662). FT /FTId=VAR_000200. FT VARIANT 614 614 D -> G (in CF; dbSNP:rs201124247). FT /FTId=VAR_000201. FT VARIANT 618 618 I -> T (in CF). FT /FTId=VAR_000202. FT VARIANT 619 619 L -> S (in CF). FT {ECO:0000269|PubMed:7525450}. FT /FTId=VAR_000203. FT VARIANT 620 620 H -> P (in CF). FT /FTId=VAR_000204. FT VARIANT 620 620 H -> Q (in CF). FT /FTId=VAR_000205. FT VARIANT 622 622 G -> D (in oligospermia). FT /FTId=VAR_000206. FT VARIANT 628 628 G -> R (in CF). FT /FTId=VAR_000207. FT VARIANT 633 633 L -> P (in CF). FT /FTId=VAR_000208. FT VARIANT 648 648 D -> V (in CF). FT /FTId=VAR_000209. FT VARIANT 651 651 D -> N (in CF). FT /FTId=VAR_000210. FT VARIANT 654 654 S -> G (in dbSNP:rs1800099). FT /FTId=VAR_009902. FT VARIANT 665 665 T -> S (in CF). FT {ECO:0000269|PubMed:8800923}. FT /FTId=VAR_000211. FT VARIANT 668 668 R -> C (in dbSNP:rs1800100). FT /FTId=VAR_000212. FT VARIANT 693 693 F -> L (in dbSNP:rs1800101). FT /FTId=VAR_000213. FT VARIANT 754 754 V -> M (in CF; dbSNP:rs150157202). FT /FTId=VAR_000214. FT VARIANT 766 766 R -> M (in CBAVD). FT /FTId=VAR_000215. FT VARIANT 792 792 R -> G (in CBAVD). FT /FTId=VAR_000216. FT VARIANT 800 800 A -> G (in CBAVD). FT {ECO:0000269|PubMed:7529962}. FT /FTId=VAR_000217. FT VARIANT 807 807 I -> M (in CBAVD; dbSNP:rs1800103). FT /FTId=VAR_000218. FT VARIANT 822 822 E -> K (in CF). FT /FTId=VAR_000219. FT VARIANT 826 826 E -> K (in thoracic sarcoidosis). FT /FTId=VAR_000220. FT VARIANT 866 866 C -> Y (in CF). FT /FTId=VAR_000221. FT VARIANT 903 903 Y -> H (in dbSNP:rs1800106). FT /FTId=VAR_009903. FT VARIANT 909 909 S -> I (in dbSNP:rs1800107). FT /FTId=VAR_009904. FT VARIANT 912 912 S -> L (in dbSNP:rs121909034). FT {ECO:0000269|PubMed:7522211}. FT /FTId=VAR_000222. FT VARIANT 913 913 Y -> C (in CF). FT /FTId=VAR_000223. FT VARIANT 917 917 Y -> C (in CF). FT /FTId=VAR_000224. FT VARIANT 949 949 H -> Y (in CF). FT {ECO:0000269|PubMed:7522211}. FT /FTId=VAR_000225. FT VARIANT 952 952 M -> I (in CF). FT /FTId=VAR_000226. FT VARIANT 967 967 L -> S (in dbSNP:rs1800110). FT /FTId=VAR_009905. FT VARIANT 997 997 L -> F (in CF; dbSNP:rs1800111). FT /FTId=VAR_000227. FT VARIANT 1005 1005 I -> R (in CF). FT {ECO:0000269|PubMed:7525450}. FT /FTId=VAR_000228. FT VARIANT 1006 1006 A -> E (in CF). FT {ECO:0000269|PubMed:7541510}. FT /FTId=VAR_000229. FT VARIANT 1013 1013 P -> L (in CF). FT {ECO:0000269|PubMed:9521595}. FT /FTId=VAR_000230. FT VARIANT 1028 1028 M -> I (in CF). FT {ECO:0000269|PubMed:9521595}. FT /FTId=VAR_000231. FT VARIANT 1052 1052 F -> V (in CF). FT {ECO:0000269|PubMed:7683628}. FT /FTId=VAR_000232. FT VARIANT 1061 1061 G -> R (in CF; dbSNP:rs142394380). FT {ECO:0000269|PubMed:7683628, FT ECO:0000269|PubMed:8723695}. FT /FTId=VAR_000233. FT VARIANT 1065 1065 L -> P (in CF). FT {ECO:0000269|PubMed:7522211}. FT /FTId=VAR_000234. FT VARIANT 1065 1065 L -> R (in CF). FT {ECO:0000269|PubMed:9452054}. FT /FTId=VAR_000235. FT VARIANT 1066 1066 R -> C (in CF). FT {ECO:0000269|PubMed:9375855}. FT /FTId=VAR_000236. FT VARIANT 1066 1066 R -> H (in CF). FT /FTId=VAR_000237. FT VARIANT 1066 1066 R -> L (in CF). FT {ECO:0000269|PubMed:7683628}. FT /FTId=VAR_000238. FT VARIANT 1067 1067 A -> T (in CF). FT /FTId=VAR_000239. FT VARIANT 1067 1067 A -> V (in dbSNP:rs1800114). FT /FTId=VAR_000240. FT VARIANT 1070 1070 R -> P (in CF). FT {ECO:0000269|PubMed:9401006}. FT /FTId=VAR_000242. FT VARIANT 1070 1070 R -> Q (in CF). FT {ECO:0000269|PubMed:7683628}. FT /FTId=VAR_000241. FT VARIANT 1070 1070 R -> W (in CBAVD; dbSNP:rs202179988). FT /FTId=VAR_011564. FT VARIANT 1071 1071 Q -> P (in CF). FT {ECO:0000269|PubMed:7522211}. FT /FTId=VAR_000243. FT VARIANT 1072 1072 P -> L (in CF). FT /FTId=VAR_000244. FT VARIANT 1077 1077 L -> P (in CF). FT /FTId=VAR_000245. FT VARIANT 1085 1085 H -> R (in CF). FT {ECO:0000269|PubMed:7683628}. FT /FTId=VAR_000246. FT VARIANT 1098 1098 W -> R (in CF). FT {ECO:0000269|PubMed:7537150}. FT /FTId=VAR_000247. FT VARIANT 1101 1101 M -> K (in CF; dbSNP:rs36210737). FT {ECO:0000269|PubMed:7680525}. FT /FTId=VAR_000248. FT VARIANT 1101 1101 M -> R (in CF). FT {ECO:0000269|PubMed:7683628}. FT /FTId=VAR_011565. FT VARIANT 1137 1137 M -> V (in CF). FT /FTId=VAR_000249. FT VARIANT 1140 1140 Missing (in CF). FT {ECO:0000269|PubMed:9101301}. FT /FTId=VAR_000250. FT VARIANT 1152 1152 D -> H (in CF). FT /FTId=VAR_000251. FT VARIANT 1162 1162 R -> L (in dbSNP:rs1800120). FT /FTId=VAR_000252. FT VARIANT 1220 1220 T -> I (in dbSNP:rs1800123). FT {ECO:0000269|PubMed:7522211}. FT /FTId=VAR_000253. FT VARIANT 1234 1234 I -> V (in CF). FT /FTId=VAR_000254. FT VARIANT 1235 1235 S -> R (in CF; dbSNP:rs34911792). FT /FTId=VAR_000255. FT VARIANT 1244 1244 G -> E (in CF). FT /FTId=VAR_000256. FT VARIANT 1249 1249 G -> E (in CF). FT {ECO:0000269|PubMed:7520022}. FT /FTId=VAR_000257. FT VARIANT 1251 1251 S -> N (in CF). FT /FTId=VAR_000258. FT VARIANT 1255 1255 S -> P (in CF). FT {ECO:0000269|PubMed:1284530}. FT /FTId=VAR_000259. FT VARIANT 1270 1270 D -> N (in CF; dbSNP:rs11971167). FT /FTId=VAR_000260. FT VARIANT 1282 1282 W -> R (in CF). FT /FTId=VAR_000261. FT VARIANT 1283 1283 R -> M (in CF). FT {ECO:0000269|PubMed:1284468}. FT /FTId=VAR_000262. FT VARIANT 1286 1286 F -> S (in CF). FT /FTId=VAR_000263. FT VARIANT 1291 1291 Q -> H (in CF). FT {ECO:0000269|PubMed:1284466}. FT /FTId=VAR_000264. FT VARIANT 1291 1291 Q -> R (in CF). FT {ECO:0000269|PubMed:7525450}. FT /FTId=VAR_000265. FT VARIANT 1303 1303 N -> H (in CF). FT /FTId=VAR_000266. FT VARIANT 1303 1303 N -> K (in CF; dbSNP:rs80034486). FT {ECO:0000269|PubMed:9401006}. FT /FTId=VAR_000267. FT VARIANT 1349 1349 G -> D (in CF). FT /FTId=VAR_000268. FT VARIANT 1364 1364 A -> V (in CBAVD). {ECO:0000269|Ref.77}. FT /FTId=VAR_000269. FT VARIANT 1397 1397 V -> E (in CF). FT {ECO:0000269|PubMed:7524913}. FT /FTId=VAR_000270. FT VARIANT 1453 1453 R -> W (in dbSNP:rs4148725). FT {ECO:0000269|Ref.3}. FT /FTId=VAR_048152. FT CONFLICT 620 620 H -> N (in Ref. 1; AAA35680). FT {ECO:0000305}. FT CONFLICT 833 833 F -> L (in Ref. 1; AAA35680). FT {ECO:0000305}. FT STRAND 11 19 {ECO:0000244|PDB:3ISW}. FT STRAND 390 399 {ECO:0000244|PDB:2PZE}. FT HELIX 403 411 {ECO:0000244|PDB:2BBS}. FT HELIX 414 417 {ECO:0000244|PDB:2BBT}. FT HELIX 433 436 {ECO:0000244|PDB:1XMI}. FT STRAND 440 449 {ECO:0000244|PDB:2PZE}. FT STRAND 453 457 {ECO:0000244|PDB:2PZE}. FT HELIX 464 471 {ECO:0000244|PDB:2PZE}. FT STRAND 478 484 {ECO:0000244|PDB:2PZE}. FT STRAND 488 491 {ECO:0000244|PDB:2PZE}. FT STRAND 499 501 {ECO:0000244|PDB:2PZG}. FT HELIX 502 507 {ECO:0000244|PDB:2PZE}. FT HELIX 514 523 {ECO:0000244|PDB:2PZE}. FT HELIX 527 530 {ECO:0000244|PDB:2PZE}. FT STRAND 533 535 {ECO:0000244|PDB:2PZF}. FT HELIX 536 538 {ECO:0000244|PDB:2PZE}. FT STRAND 540 542 {ECO:0000244|PDB:1XMJ}. FT HELIX 550 563 {ECO:0000244|PDB:2PZE}. FT STRAND 567 573 {ECO:0000244|PDB:2PZE}. FT TURN 574 577 {ECO:0000244|PDB:2PZE}. FT HELIX 580 589 {ECO:0000244|PDB:2PZE}. FT HELIX 590 594 {ECO:0000244|PDB:2PZE}. FT TURN 595 597 {ECO:0000244|PDB:2PZE}. FT STRAND 598 603 {ECO:0000244|PDB:2PZE}. FT HELIX 607 612 {ECO:0000244|PDB:2PZE}. FT STRAND 614 620 {ECO:0000244|PDB:2PZE}. FT STRAND 623 628 {ECO:0000244|PDB:2PZE}. FT HELIX 630 634 {ECO:0000244|PDB:2PZE}. FT HELIX 640 644 {ECO:0000244|PDB:2PZE}. FT HELIX 650 652 {ECO:0000244|PDB:2BBS}. FT HELIX 655 669 {ECO:0000244|PDB:2BBS}. FT STRAND 1204 1207 {ECO:0000244|PDB:3GD7}. FT STRAND 1210 1223 {ECO:0000244|PDB:3GD7}. FT STRAND 1226 1234 {ECO:0000244|PDB:3GD7}. FT STRAND 1239 1245 {ECO:0000244|PDB:3GD7}. FT HELIX 1250 1258 {ECO:0000244|PDB:3GD7}. FT STRAND 1261 1271 {ECO:0000244|PDB:3GD7}. FT HELIX 1279 1284 {ECO:0000244|PDB:3GD7}. FT STRAND 1286 1290 {ECO:0000244|PDB:3GD7}. FT STRAND 1297 1299 {ECO:0000244|PDB:3GD7}. FT HELIX 1300 1304 {ECO:0000244|PDB:3GD7}. FT HELIX 1312 1321 {ECO:0000244|PDB:3GD7}. FT HELIX 1325 1328 {ECO:0000244|PDB:3GD7}. FT HELIX 1334 1336 {ECO:0000244|PDB:3GD7}. FT TURN 1341 1345 {ECO:0000244|PDB:3GD7}. FT HELIX 1348 1361 {ECO:0000244|PDB:3GD7}. FT STRAND 1366 1371 {ECO:0000244|PDB:3GD7}. FT HELIX 1372 1375 {ECO:0000244|PDB:3GD7}. FT HELIX 1378 1389 {ECO:0000244|PDB:3GD7}. FT TURN 1390 1394 {ECO:0000244|PDB:3GD7}. FT STRAND 1397 1400 {ECO:0000244|PDB:3GD7}. FT STRAND 1402 1404 {ECO:0000244|PDB:3GD7}. FT HELIX 1405 1407 {ECO:0000244|PDB:3GD7}. FT STRAND 1411 1417 {ECO:0000244|PDB:3GD7}. FT STRAND 1420 1426 {ECO:0000244|PDB:3GD7}. FT HELIX 1427 1432 {ECO:0000244|PDB:3GD7}. FT HELIX 1436 1441 {ECO:0000244|PDB:3GD7}. FT STRAND 1442 1445 {ECO:0000244|PDB:3GD7}. FT STRAND 1448 1457 {ECO:0000244|PDB:3GD7}. FT STRAND 1462 1465 {ECO:0000244|PDB:3GD7}. FT STRAND 1478 1480 {ECO:0000244|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 //