CFTR_MOUSE
ID CFTR_MOUSE Reviewed; 1476 AA.
AC P26361; Q63893; Q63894; Q9JKQ6;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Cystic fibrosis transmembrane conductance regulator;
DE Short=CFTR;
DE AltName: Full=ATP-binding cassette sub-family C member 7;
DE AltName: Full=Channel conductance-controlling ATPase;
DE EC=5.6.1.6 {ECO:0000250|UniProtKB:P13569};
DE AltName: Full=cAMP-dependent chloride channel;
GN Name=Cftr; Synonyms=Abcc7;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1712752; DOI=10.1016/0888-7543(91)90312-3;
RA Tata F., Stanier P., Wicking C., Halford S., Kruyer H., Lench N.J.,
RA Scambler P.J., Hansen C., Braman J.C., Williamson R., Wainwright B.J.;
RT "Cloning the mouse homolog of the human cystic fibrosis transmembrane
RT conductance regulator gene.";
RL Genomics 10:301-307(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=1716243; DOI=10.1016/0888-7543(91)90434-g;
RA Yorifuji T., Lemna W.K., Ballard C.F., Rosenbloom C.L., Rozmahel R.,
RA Plavsic N., Tsui L.-C., Beaudet A.L.;
RT "Molecular cloning and sequence analysis of the murine cDNA for the cystic
RT fibrosis transmembrane conductance regulator.";
RL Genomics 10:547-550(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10655503; DOI=10.1073/pnas.97.3.1172;
RA Ellsworth R.E., Jamison D.C., Touchman J.W., Chissoe S.L.,
RA Braden Maduro V.V., Bouffard G.G., Dietrich N.L., Beckstrom-Sternberg S.M.,
RA Iyer L.M., Weintraub L.A., Cotton M., Courtney L., Edwards J., Maupin R.,
RA Ozersky P., Rohlfing T., Wohldmann P., Miner T., Kemp K., Kramer J.,
RA Korf I., Pepin K., Antonacci-Fulton L., Fulton R.S., Minx P., Hillier L.W.,
RA Wilson R.K., Waterston R.H., Miller W., Green E.D.;
RT "Comparative genomic sequence analysis of the human and mouse cystic
RT fibrosis transmembrane conductance regulator genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:1172-1177(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-17.
RX PubMed=7526924; DOI=10.1093/hmg/3.7.1089;
RA Denamur E., Chehab F.F.;
RT "Analysis of the mouse and rat CFTR promoter regions.";
RL Hum. Mol. Genet. 3:1089-1094(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 549-600, ALTERNATIVE SPLICING, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Testis;
RX PubMed=7691356; DOI=10.1038/ng0893-426;
RA Delaney S.J., Rich D.P., Thomson S.A., Hargrave M.R., Lovelock P.K.,
RA Welsh M.J., Wainwright B.J.;
RT "Cystic fibrosis transmembrane conductance regulator splice variants are
RT not conserved and fail to produce chloride channels.";
RL Nat. Genet. 4:426-431(1993).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=7685652; DOI=10.1038/ng0593-35;
RA Ratcliff R., Evans M.J., Cuthbert A.W., MacVinish L.J., Foster D.,
RA Anderson J.R., Colledge W.H.;
RT "Production of a severe cystic fibrosis mutation in mice by gene
RT targeting.";
RL Nat. Genet. 4:35-41(1993).
RN [7]
RP FUNCTION, AND INTERACTION WITH AHCYL1.
RX PubMed=19033647; DOI=10.1172/jci36983;
RA Yang D., Shcheynikov N., Zeng W., Ohana E., So I., Ando H., Mizutani A.,
RA Mikoshiba K., Muallem S.;
RT "IRBIT coordinates epithelial fluid and HCO3- secretion by stimulating the
RT transporters pNBC1 and CFTR in the murine pancreatic duct.";
RL J. Clin. Invest. 119:193-202(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-698 AND SER-790, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP FUNCTION, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=20231442; DOI=10.1073/pnas.0902661107;
RA Lu M., Dong K., Egan M.E., Giebisch G.H., Boulpaep E.L., Hebert S.C.;
RT "Mouse cystic fibrosis transmembrane conductance regulator forms cAMP-PKA-
RT regulated apical chloride channels in cortical collecting duct.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:6082-6087(2010).
RN [10]
RP FUNCTION, AND INTERACTION WITH SLC26A3; SLC26A6 AND SLC9A3R1.
RX PubMed=21976599; DOI=10.1095/biolreprod.111.094037;
RA Chavez J.C., Hernandez-Gonzalez E.O., Wertheimer E., Visconti P.E.,
RA Darszon A., Trevino C.L.;
RT "Participation of the Cl-/HCO(3)- exchangers SLC26A3 and SLC26A6, the
RT Cl- channel CFTR, and the regulatory factor SLC9A3R1 in mouse sperm
RT capacitation.";
RL Biol. Reprod. 86:1-14(2012).
RN [11]
RP INTERACTION WITH AHCYL1.
RX PubMed=23542070; DOI=10.1053/j.gastro.2013.03.047;
RA Park S., Shcheynikov N., Hong J.H., Zheng C., Suh S.H., Kawaai K., Ando H.,
RA Mizutani A., Abe T., Kiyonari H., Seki G., Yule D., Mikoshiba K.,
RA Muallem S.;
RT "Irbit mediates synergy between ca(2+) and cAMP signaling pathways during
RT epithelial transport in mice.";
RL Gastroenterology 145:232-241(2013).
RN [12]
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 [13]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF PHE-508.
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 [14]
RP TISSUE SPECIFICITY.
RX PubMed=30659401; DOI=10.1007/s10735-019-09813-3;
RA Sharma S., Hanukoglu I.;
RT "Mapping the sites of localization of epithelial sodium channel (ENaC) and
RT CFTR in segments of the mammalian epididymis.";
RL J. Mol. Histol. 50:141-154(2019).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 389-673 IN COMPLEXES WITH ATP AND
RP ATP ANALOGS, AND DOMAIN.
RX PubMed=14685259; DOI=10.1038/sj.emboj.7600040;
RA Lewis H.A., Buchanan S.G., Burley S.K., Conners K., Dickey M., Dorwart M.,
RA Fowler R., Gao X., Guggino W.B., Hendrickson W.A., Hunt J.F., Kearins M.C.,
RA Lorimer D., Maloney P.C., Post K.W., Rajashankar K.R., Rutter M.E.,
RA Sauder J.M., Shriver S., Thibodeau P.H., Thomas P.J., Zhang M., Zhao X.,
RA Emtage S.;
RT "Structure of nucleotide-binding domain 1 of the cystic fibrosis
RT transmembrane conductance regulator.";
RL EMBO J. 23:282-293(2004).
RN [16] {ECO:0007744|PDB:1XF9, ECO:0007744|PDB:1XFA}
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 389-670 IN COMPLEX WITH ATP,
RP DOMAIN, AND MUTAGENESIS OF PHE-508.
RX PubMed=15619636; DOI=10.1038/nsmb881;
RA Thibodeau P.H., Brautigam C.A., Machius M., Thomas P.J.;
RT "Side chain and backbone contributions of Phe508 to CFTR folding.";
RL Nat. Struct. Mol. Biol. 12:10-16(2005).
RN [17] {ECO:0007744|PDB:3SI7}
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 389-673 IN COMPLEX WITH ATP AND
RP MAGNESIUM, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF PHE-508.
RX PubMed=22265409; DOI=10.1016/j.cell.2011.11.023;
RA Mendoza J.L., Schmidt A., Li Q., Nuvaga E., Barrett T., Bridges R.J.,
RA Feranchak A.P., Brautigam C.A., Thomas P.J.;
RT "Requirements for efficient correction of F508 CFTR revealed by analyses of
RT evolved sequences.";
RL Cell 148:164-174(2012).
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:20231442, PubMed:22265409). Channel activity is
CC coupled to ATP hydrolysis. The ion channel is also permeable to
CC HCO(3)(-); selectivity depends on the extracellular chloride
CC concentration. Exerts its function also by modulating the activity of
CC other ion channels and transporters. Contributes to the regulation of
CC the pH and the ion content of the epithelial fluid layer. Modulates the
CC activity of the epithelial sodium channel (ENaC) complex, in part by
CC regulating the cell surface expression of the ENaC complex. May
CC regulate bicarbonate secretion and salvage in epithelial cells by
CC regulating the transporter SLC4A7. Can inhibit the chloride channel
CC activity of ANO1 (By similarity). Plays a role in the chloride and
CC bicarbonate homeostasis during sperm epididymal maturation and
CC capacitation (PubMed:21976599). {ECO:0000250|UniProtKB:P13569,
CC ECO:0000269|PubMed:19033647, ECO:0000269|PubMed:20231442,
CC ECO:0000269|PubMed:21976599, ECO:0000269|PubMed:22265409,
CC ECO:0000269|PubMed:26823428}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O + closed Cl(-) channel = ADP + phosphate + open
CC Cl(-) channel.; EC=5.6.1.6; Evidence={ECO:0000250|UniProtKB:P13569};
CC -!- SUBUNIT: Monomer; does not require oligomerization for channel
CC activity. May form oligomers in the membrane (By similarity). Interacts
CC with SLC26A3, SLC26A6 and SLC9A3R1 (PubMed:21976599). Interacts with
CC SHANK2 (By similarity). Interacts with MYO6 (By similarity). Interacts
CC (via C-terminus) with GOPC (via PDZ domain); this promotes CFTR
CC internalization and thereby decreases channel activity. Interacts with
CC SLC4A7 through SLC9A3R1. Found in a complex with MYO5B and RAB11A.
CC Interacts with ANO1. Interacts with SLC26A8 (By similarity). Interacts
CC with AHCYL1; the interaction increases CFTR activity (PubMed:19033647,
CC PubMed:23542070). Interacts with CSE1L (By similarity). The core-
CC glycosylated form interacts with GORASP2 (via PDZ GRASP-type 1 domain)
CC in respone to ER stress (By similarity). Interacts with MARCHF2; the
CC interaction leads to CFTR ubiqtuitination and degradation (By
CC similarity). {ECO:0000250|UniProtKB:P13569,
CC ECO:0000250|UniProtKB:P34158, ECO:0000269|PubMed:19033647,
CC ECO:0000269|PubMed:21976599, ECO:0000269|PubMed:23542070}.
CC -!- INTERACTION:
CC P26361; Q9WVC8: Slc26a3; NbExp=3; IntAct=EBI-6115317, EBI-6895537;
CC P26361; Q8CIW6: Slc26a6; NbExp=3; IntAct=EBI-6115317, EBI-6895517;
CC P26361; P70441: Slc9a3r1; NbExp=3; IntAct=EBI-6115317, EBI-1184085;
CC P26361; P19120: HSPA8; Xeno; NbExp=5; IntAct=EBI-6115317, EBI-907802;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:20231442, ECO:0000269|PubMed:21884936}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P13569}. Early endosome
CC membrane {ECO:0000250|UniProtKB:P13569}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P13569}. Cell membrane
CC {ECO:0000269|PubMed:20231442, ECO:0000269|PubMed:22265409}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:P13569}. Recycling endosome
CC membrane {ECO:0000250|UniProtKB:P13569}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P13569}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P13569}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P13569}. Nucleus {ECO:0000250|UniProtKB:P34158}.
CC Note=The channel is internalized from the cell surface into an
CC endosomal recycling compartment, from where it is recycled to the cell
CC membrane. In the oviduct and bronchus, detected on the apical side of
CC epithelial cells, but not associated with cilia. In Sertoli cells, a
CC processed product is detected in the nucleus. ER stress induces
CC GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of
CC core-glycosylated CFTR to cell membrane (PubMed:21884936).
CC {ECO:0000250|UniProtKB:P13569, ECO:0000250|UniProtKB:P34158,
CC ECO:0000269|PubMed:21884936}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P26361-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P26361-2; Sequence=VSP_000062, VSP_000063;
CC Name=3;
CC IsoId=P26361-3; Sequence=VSP_000064, VSP_000065;
CC -!- TISSUE SPECIFICITY: Expressed in the epididymis (at protein level)
CC (PubMed:30659401). In the initial segment of the epididymis, detected
CC on both the luminal and basolateral sides of the ducts where it is
CC expressed in the duct columnar cells as well as in the interstitial
CC smooth muscle cells (PubMed:30659401). Expressed in sperm in the caput
CC (PubMed:30659401). In the cauda, detected along the luminal border but
CC not continuously and is also expressed on the basolateral surface
CC (PubMed:30659401). Within the caudal lumen, detected on sperm
CC (PubMed:30659401). Isoform 1: Expressed in a variety of epithelial
CC tissues including colon, kidney, lung, small intestine, pancreatic duct
CC and testis (PubMed:7691356). Isoform 2: Expressed only in testis
CC (PubMed:7691356). Isoform 3: Expressed only in testis (PubMed:7691356).
CC {ECO:0000269|PubMed:30659401, ECO:0000269|PubMed:7691356}.
CC -!- DOMAIN: Binds and hydrolyzes ATP via the two cytoplasmic ABC
CC transporter nucleotide-binding domains. The two ATP-binding domains
CC interact with each other, forming a head-to-tail dimer. Normal ATPase
CC activity requires interaction between the two domains (By similarity).
CC The first ABC transporter nucleotide-binding domain has no ATPase
CC activity by itself (PubMed:14685259, PubMed:15619636).
CC {ECO:0000250|UniProtKB:P13569, ECO:0000269|PubMed:14685259,
CC ECO:0000269|PubMed:15619636}.
CC -!- DOMAIN: The PDZ-binding motif mediates interactions with GOPC and with
CC the SLC4A7, SLC9A3R1/EBP50 complex. {ECO:0000250|UniProtKB:P13569}.
CC -!- DOMAIN: The disordered R region mediates channel activation when it is
CC phosphorylated, but not in the absence of phosphorylation.
CC {ECO:0000250|UniProtKB:P13569}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P13569}.
CC -!- PTM: Phosphorylated; cAMP treatment promotes phosphorylation and
CC activates the channel. Dephosphorylation decreases the ATPase activity
CC (in vitro). Phosphorylation at PKA sites activates the channel.
CC Phosphorylation at PKC sites enhances the response to phosphorylation
CC by PKA. Phosphorylated by AMPK; this inhibits channel activity.
CC {ECO:0000250|UniProtKB:P13569}.
CC -!- PTM: Ubiquitinated, leading to its degradation in the lysosome.
CC Deubiquitination by USP10 in early endosomes enhances its endocytic
CC recycling to the cell membrane. Ubiquitinated by RNF185 during ER
CC stress. Ubiquitinated by MARCHF2 (By similarity).
CC {ECO:0000250|UniProtKB:P13569}.
CC -!- DISRUPTION PHENOTYPE: Mice are born at the expected Mendelian rate, but
CC about 80% die within two to five days after birth due to peritonitis
CC (PubMed:7685652). Those that survive fail to thrive, appear runted and
CC weigh about half as much as wild-type littermates (PubMed:7685652).
CC Many of the surviving pups die when they start ingesting solid food,
CC due to intestinal blockage caused by excessive mucus accumulation
CC (PubMed:7685652). None survive for more than about 45 days after birth
CC (PubMed:7685652). Intestinal crypts in the jejunum and ileum are filled
CC with excessive mucus (PubMed:7685652). Excessive accumulation of mucus
CC is also seen in colon (PubMed:7685652). In contrast, their lungs do not
CC present pathological mucus accumulation (PubMed:7685652). Likewise,
CC only five out of ten animals show dilatation and blockage of several
CC small pancreatic ducts (PubMed:7685652). Besides, mutant mice present
CC defects in their lacrimal glands that make them more susceptible to
CC develop eye infections (PubMed:7685652). In caecum epithelium,
CC forskolin-sensitive ion transport is nearly abolished (PubMed:7685652).
CC {ECO:0000269|PubMed:7685652}.
CC -!- SIMILARITY: Belongs to the ABC transporter superfamily. ABCC family.
CC CFTR transporter (TC 3.A.1.202) subfamily. {ECO:0000305}.
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DR EMBL; M69298; AAA37417.1; -; mRNA.
DR EMBL; M60493; AAA18903.1; -; mRNA.
DR EMBL; AF162137; AAF30300.1; -; Genomic_DNA.
DR EMBL; L04873; AAA73562.1; -; Genomic_DNA.
DR EMBL; S65942; AAB28393.1; -; Genomic_DNA.
DR EMBL; S65940; AAB28393.1; JOINED; Genomic_DNA.
DR EMBL; S65941; AAB28393.1; JOINED; Genomic_DNA.
DR EMBL; S65942; AAB28391.1; -; Genomic_DNA.
DR EMBL; S65941; AAB28392.1; -; Genomic_DNA.
DR EMBL; S65940; AAB28392.1; JOINED; Genomic_DNA.
DR CCDS; CCDS19930.1; -. [P26361-1]
DR PIR; A39901; A39901.
DR PIR; A40303; A40303.
DR PIR; I49593; I49593.
DR PIR; I58115; I58115.
DR PIR; I78527; I78527.
DR RefSeq; NP_066388.1; NM_021050.2. [P26361-1]
DR RefSeq; XP_006505040.1; XM_006504977.1.
DR RefSeq; XP_006505041.1; XM_006504978.1.
DR PDB; 1Q3H; X-ray; 2.50 A; A/B/C/D=389-673.
DR PDB; 1R0W; X-ray; 2.20 A; A/B/C/D=389-673.
DR PDB; 1R0X; X-ray; 2.20 A; A/B/C/D=389-673.
DR PDB; 1R0Y; X-ray; 2.55 A; A/B/C/D=389-673.
DR PDB; 1R0Z; X-ray; 2.35 A; A/B/C/D=389-673.
DR PDB; 1R10; X-ray; 3.00 A; A/B=389-673.
DR PDB; 1XF9; X-ray; 2.70 A; A/B/C/D=389-670.
DR PDB; 1XFA; X-ray; 3.10 A; A/B=389-670.
DR PDB; 3SI7; X-ray; 2.25 A; A/B/C/D=389-673.
DR PDBsum; 1Q3H; -.
DR PDBsum; 1R0W; -.
DR PDBsum; 1R0X; -.
DR PDBsum; 1R0Y; -.
DR PDBsum; 1R0Z; -.
DR PDBsum; 1R10; -.
DR PDBsum; 1XF9; -.
DR PDBsum; 1XFA; -.
DR PDBsum; 3SI7; -.
DR AlphaFoldDB; P26361; -.
DR SMR; P26361; -.
DR BioGRID; 198687; 12.
DR DIP; DIP-29618N; -.
DR IntAct; P26361; 10.
DR MINT; P26361; -.
DR STRING; 10090.ENSMUSP00000049228; -.
DR GlyGen; P26361; 2 sites.
DR iPTMnet; P26361; -.
DR PhosphoSitePlus; P26361; -.
DR MaxQB; P26361; -.
DR PaxDb; P26361; -.
DR PeptideAtlas; P26361; -.
DR PRIDE; P26361; -.
DR ProteomicsDB; 281397; -. [P26361-1]
DR ProteomicsDB; 281398; -. [P26361-2]
DR ProteomicsDB; 281399; -. [P26361-3]
DR Antibodypedia; 4530; 1089 antibodies from 41 providers.
DR DNASU; 12638; -.
DR Ensembl; ENSMUST00000045706; ENSMUSP00000049228; ENSMUSG00000041301. [P26361-1]
DR Ensembl; ENSMUST00000115405; ENSMUSP00000111064; ENSMUSG00000041301. [P26361-3]
DR Ensembl; ENSMUST00000140407; ENSMUSP00000116957; ENSMUSG00000041301. [P26361-2]
DR GeneID; 12638; -.
DR KEGG; mmu:12638; -.
DR UCSC; uc009bai.1; mouse. [P26361-1]
DR CTD; 1080; -.
DR MGI; MGI:88388; Cftr.
DR VEuPathDB; HostDB:ENSMUSG00000041301; -.
DR eggNOG; KOG0054; Eukaryota.
DR GeneTree; ENSGT00940000158567; -.
DR HOGENOM; CLU_000604_27_14_1; -.
DR InParanoid; P26361; -.
DR OMA; NIRQEEM; -.
DR OrthoDB; 138195at2759; -.
DR PhylomeDB; P26361; -.
DR TreeFam; TF105200; -.
DR BRENDA; 2.7.4.3; 3474.
DR BRENDA; 5.6.1.6; 3474.
DR Reactome; R-MMU-382556; ABC-family proteins mediated transport.
DR Reactome; R-MMU-5627083; RHO GTPases regulate CFTR trafficking.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8856828; Clathrin-mediated endocytosis.
DR Reactome; R-MMU-9013406; RHOQ GTPase cycle.
DR Reactome; R-MMU-9646399; Aggrephagy.
DR BioGRID-ORCS; 12638; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Cftr; mouse.
DR EvolutionaryTrace; P26361; -.
DR PRO; PR:P26361; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P26361; protein.
DR Bgee; ENSMUSG00000041301; Expressed in paneth cell and 106 other tissues.
DR ExpressionAtlas; P26361; baseline and differential.
DR Genevisible; P26361; MM.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0034707; C:chloride channel complex; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISO:MGI.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0031901; C:early endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005902; C:microvillus; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0055037; C:recycling endosome; ISO:MGI.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0140359; F:ABC-type transporter activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISS:UniProtKB.
DR GO; GO:0042626; F:ATPase-coupled transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0015106; F:bicarbonate transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0005254; F:chloride channel activity; IDA:UniProtKB.
DR GO; GO:0019869; F:chloride channel inhibitor activity; ISS:UniProtKB.
DR GO; GO:0015108; F:chloride transmembrane transporter activity; IMP:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0005260; F:intracellularly ATP-gated chloride channel activity; ISS:UniProtKB.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
DR GO; GO:0030165; F:PDZ domain binding; ISO:MGI.
DR GO; GO:0106138; F:Sec61 translocon complex binding; ISO:MGI.
DR GO; GO:0097186; P:amelogenesis; IDA:ARUK-UCL.
DR GO; GO:0015701; P:bicarbonate transport; ISS:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB.
DR GO; GO:1904322; P:cellular response to forskolin; ISS:UniProtKB.
DR GO; GO:1902476; P:chloride transmembrane transport; IDA:UniProtKB.
DR GO; GO:0006821; P:chloride transport; IGI:MGI.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IMP:MGI.
DR GO; GO:0030301; P:cholesterol transport; IMP:MGI.
DR GO; GO:0070166; P:enamel mineralization; ISO:MGI.
DR GO; GO:0051649; P:establishment of localization in cell; IGI:MGI.
DR GO; GO:0051454; P:intracellular pH elevation; IMP:UniProtKB.
DR GO; GO:0030324; P:lung development; ISO:MGI.
DR GO; GO:0060081; P:membrane hyperpolarization; IMP:UniProtKB.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; ISS:UniProtKB.
DR GO; GO:2000077; P:negative regulation of type B pancreatic cell development; ISO:MGI.
DR GO; GO:1905460; P:negative regulation of vascular associated smooth muscle cell apoptotic process; ISO:MGI.
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; IDA:ARUK-UCL.
DR GO; GO:1904446; P:positive regulation of establishment of Sertoli cell barrier; ISO:MGI.
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:0033005; P:positive regulation of mast cell activation; ISO:MGI.
DR GO; GO:1902943; P:positive regulation of voltage-gated chloride channel activity; ISO:MGI.
DR GO; GO:0036253; P:response to amiloride; ISO:MGI.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; ISO:MGI.
DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:MGI.
DR GO; GO:0048240; P:sperm capacitation; IMP:UniProtKB.
DR GO; GO:0030321; P:transepithelial chloride transport; ISO:MGI.
DR GO; GO:0035377; P:transepithelial water transport; ISS:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR GO; GO:0042311; P:vasodilation; ISO:MGI.
DR GO; GO:0006904; P:vesicle docking involved in exocytosis; IMP:UniProtKB.
DR GO; GO:0006833; P:water transport; ISO:MGI.
DR Gene3D; 1.20.1560.10; -; 2.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR011527; ABC1_TM_dom.
DR InterPro; IPR036640; ABC1_TM_sf.
DR InterPro; IPR003439; ABC_transporter-like_ATP-bd.
DR InterPro; IPR017871; ABC_transporter-like_CS.
DR InterPro; IPR009147; CFTR/ABCC7.
DR InterPro; IPR025837; CFTR_reg_dom.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR24223:SF19; PTHR24223:SF19; 1.
DR Pfam; PF00664; ABC_membrane; 2.
DR Pfam; PF00005; ABC_tran; 2.
DR Pfam; PF14396; CFTR_R; 1.
DR PRINTS; PR01851; CYSFIBREGLTR.
DR SMART; SM00382; AAA; 2.
DR SUPFAM; SSF52540; SSF52540; 2.
DR SUPFAM; SSF90123; SSF90123; 2.
DR TIGRFAMs; TIGR01271; CFTR_protein; 1.
DR PROSITE; PS50929; ABC_TM1F; 2.
DR PROSITE; PS00211; ABC_TRANSPORTER_1; 1.
DR PROSITE; PS50893; ABC_TRANSPORTER_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; Chloride;
KW Chloride channel; Endoplasmic reticulum; Endosome; Glycoprotein;
KW Ion channel; Ion transport; Isomerase; Lipoprotein; Membrane;
KW Nucleotide-binding; Nucleus; Palmitate; Phosphoprotein; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport; Ubl conjugation.
FT CHAIN 1..1476
FT /note="Cystic fibrosis transmembrane conductance regulator"
FT /id="PRO_0000093424"
FT TOPO_DOM 1..77
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 78..98
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 99..122
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 123..146
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 147..195
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 196..216
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 217..222
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 223..243
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 244..298
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 299..319
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 320..339
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 340..358
FT /note="Helical; Name=6"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 359..853
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 854..874
FT /note="Helical; Name=7"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 875..913
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 914..934
FT /note="Discontinuously helical; Name=8"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 935..985
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 986..1006
FT /note="Helical; Name=9"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 1007..1008
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 1009..1029
FT /note="Helical; Name=10"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 1030..1090
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 1091..1111
FT /note="Helical; Name=11"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 1112..1125
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TRANSMEM 1126..1146
FT /note="Helical; Name=12"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT TOPO_DOM 1147..1476
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13569"
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 854..1153
FT /note="ABC transmembrane type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00441"
FT DOMAIN 1208..1439
FT /note="ABC transporter 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT REGION 654..826
FT /note="Disordered R region"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT REGION 1382..1476
FT /note="Interaction with GORASP2"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT REGION 1446..1476
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1474..1476
FT /note="PDZ-binding"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT COMPBIAS 1458..1476
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:0000250|UniProtKB:P13569"
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:0007744|PDB:1Q3H, ECO:0007744|PDB:1R0X,
FT ECO:0007744|PDB:1R0Z, ECO:0007744|PDB:1R10,
FT ECO:0007744|PDB:1XF9, ECO:0007744|PDB:1XFA,
FT ECO:0007744|PDB:3SI7"
FT BINDING 493
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="1"
FT /evidence="ECO:0007744|PDB:1Q3H, ECO:0007744|PDB:1R0X,
FT ECO:0007744|PDB:1R0Z, ECO:0007744|PDB:1XFA"
FT BINDING 1215
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT BINDING 1240..1247
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00434"
FT MOD_RES 549
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT MOD_RES 660
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT MOD_RES 670
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT MOD_RES 684
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT MOD_RES 698
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 710
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT MOD_RES 715
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT MOD_RES 732
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT MOD_RES 763
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT MOD_RES 785
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT MOD_RES 790
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT MOD_RES 1440
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT MOD_RES 1452
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT LIPID 524
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT LIPID 1391
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:P13569"
FT CARBOHYD 889
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 895
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 561..600
FT /note="AVYKDADLYLLDSPFGYLDVFTEEQVFESCVCKLMANKTR -> QRTRSPYL
FT EIRIFLCLFLYTRMKVCATTPEQYIKMLICTY (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_000064"
FT VAR_SEQ 561..576
FT /note="AVYKDADLYLLDSPFG -> FLICLQTKDKVSLFRN (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_000062"
FT VAR_SEQ 577..1476
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_000063"
FT VAR_SEQ 601..1476
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_000065"
FT MUTAGEN 508
FT /note="F->A,L,Q: Mildly impairs protein maturation."
FT /evidence="ECO:0000269|PubMed:15619636"
FT MUTAGEN 508
FT /note="F->C,M: No effect on protein maturation."
FT /evidence="ECO:0000269|PubMed:15619636"
FT MUTAGEN 508
FT /note="F->E,D,G,H,I,K,P,R,Y: Abolishes normal maturation."
FT /evidence="ECO:0000269|PubMed:15619636"
FT MUTAGEN 508
FT /note="F->N,S,V: Nearly abolishes normal maturation."
FT /evidence="ECO:0000269|PubMed:15619636"
FT MUTAGEN 508
FT /note="Missing: Impairs protein folding, due to small local
FT changes that probably disrupt crucial interactions with the
FT transmembrane domain. Abolishes normal maturation. Impairs
FT trafficking to the apical cell membrane."
FT /evidence="ECO:0000269|PubMed:15619636,
FT ECO:0000269|PubMed:21884936, ECO:0000269|PubMed:22265409"
FT CONFLICT 20..22
FT /note="TTP -> STA (in Ref. 3; AAF30300)"
FT /evidence="ECO:0000305"
FT CONFLICT 30
FT /note="H -> Q (in Ref. 3; AAF30300)"
FT /evidence="ECO:0000305"
FT CONFLICT 410..412
FT /note="EKV -> QKA (in Ref. 1; AAA37417)"
FT /evidence="ECO:0000305"
FT CONFLICT 462
FT /note="S -> L (in Ref. 1; AAA37417)"
FT /evidence="ECO:0000305"
FT CONFLICT 623
FT /note="S -> T (in Ref. 1; AAA37417)"
FT /evidence="ECO:0000305"
FT CONFLICT 639
FT /note="D -> S (in Ref. 1; AAA37417)"
FT /evidence="ECO:0000305"
FT STRAND 392..400
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 405..412
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 423..425
FT /evidence="ECO:0007829|PDB:1R0Z"
FT HELIX 430..435
FT /evidence="ECO:0007829|PDB:1R0W"
FT STRAND 439..448
FT /evidence="ECO:0007829|PDB:1R0W"
FT STRAND 453..459
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 464..471
FT /evidence="ECO:0007829|PDB:1R0W"
FT STRAND 478..483
FT /evidence="ECO:0007829|PDB:1R0W"
FT STRAND 488..491
FT /evidence="ECO:0007829|PDB:1R0W"
FT STRAND 499..501
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 502..506
FT /evidence="ECO:0007829|PDB:1R0W"
FT TURN 507..509
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 514..523
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 527..530
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 536..538
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 543..545
FT /evidence="ECO:0007829|PDB:1R0X"
FT HELIX 550..563
FT /evidence="ECO:0007829|PDB:1R0W"
FT STRAND 567..573
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 580..589
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 590..594
FT /evidence="ECO:0007829|PDB:1R0W"
FT TURN 595..597
FT /evidence="ECO:0007829|PDB:1R0W"
FT STRAND 598..603
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 607..611
FT /evidence="ECO:0007829|PDB:1R0W"
FT STRAND 614..620
FT /evidence="ECO:0007829|PDB:1R0W"
FT STRAND 623..628
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 630..636
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 638..645
FT /evidence="ECO:0007829|PDB:1R0W"
FT STRAND 647..649
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 650..652
FT /evidence="ECO:0007829|PDB:1R0W"
FT HELIX 655..668
FT /evidence="ECO:0007829|PDB:1R0W"
SQ SEQUENCE 1476 AA; 167870 MW; 3D1B0BBDD80C1DA8 CRC64;
MQKSPLEKAS FISKLFFSWT TPILRKGYRH HLELSDIYQA PSADSADHLS EKLEREWDRE
QASKKNPQLI HALRRCFFWR FLFYGILLYL GEVTKAVQPV LLGRIIASYD PENKVERSIA
IYLGIGLCLL FIVRTLLLHP AIFGLHRIGM QMRTAMFSLI YKKTLKLSSR VLDKISIGQL
VSLLSNNLNK FDEGLALAHF IWIAPLQVTL LMGLLWDLLQ FSAFCGLGLL IILVIFQAIL
GKMMVKYRDQ RAAKINERLV ITSEIIDNIY SVKAYCWESA MEKMIENLRE VELKMTRKAA
YMRFFTSSAF FFSGFFVVFL SVLPYTVING IVLRKIFTTI SFCIVLRMSV TRQFPTAVQI
WYDSFGMIRK IQDFLQKQEY KVLEYNLMTT GIIMENVTAF WEEGFGELLE KVQQSNGDRK
HSSDENNVSF SHLCLVGNPV LKNINLNIEK GEMLAITGST GSGKTSLLML ILGELEASEG
IIKHSGRVSF CSQFSWIMPG TIKENIIFGV SYDEYRYKSV VKACQLQQDI TKFAEQDNTV
LGEGGVTLSG GQRARISLAR AVYKDADLYL LDSPFGYLDV FTEEQVFESC VCKLMANKTR
ILVTSKMEHL RKADKILILH QGSSYFYGTF SELQSLRPDF SSKLMGYDTF DQFTEERRSS
ILTETLRRFS VDDSSAPWSK PKQSFRQTGE VGEKRKNSIL NSFSSVRKIS IVQKTPLCID
GESDDLQEKR LSLVPDSEQG EAALPRSNMI ATGPTFPGRR RQSVLDLMTF TPNSGSSNLQ
RTRTSIRKIS LVPQISLNEV DVYSRRLSQD STLNITEEIN EEDLKECFLD DVIKIPPVTT
WNTYLRYFTL HKGLLLVLIW CVLVFLVEVA ASLFVLWLLK NNPVNSGNNG TKISNSSYVV
IITSTSFYYI FYIYVGVADT LLALSLFRGL PLVHTLITAS KILHRKMLHS ILHAPMSTIS
KLKAGGILNR FSKDIAILDD FLPLTIFDFI QLVFIVIGAI IVVSALQPYI FLATVPGLVV
FILLRAYFLH TAQQLKQLES EGRSPIFTHL VTSLKGLWTL RAFRRQTYFE TLFHKALNLH
TANWFMYLAT LRWFQMRIDM IFVLFFIVVT FISILTTGEG EGTAGIILTL AMNIMSTLQW
AVNSSIDTDS LMRSVSRVFK FIDIQTEESM YTQIIKELPR EGSSDVLVIK NEHVKKSDIW
PSGGEMVVKD LTVKYMDDGN AVLENISFSI SPGQRVGLLG RTGSGKSTLL SAFLRMLNIK
GDIEIDGVSW NSVTLQEWRK AFGVITQKVF IFSGTFRQNL DPNGKWKDEE IWKVADEVGL
KSVIEQFPGQ LNFTLVDGGY VLSHGHKQLM CLARSVLSKA KIILLDEPSA HLDPITYQVI
RRVLKQAFAG CTVILCEHRI EAMLDCQRFL VIEESNVWQY DSLQALLSEK SIFQQAISSS
EKMRFFQGRH SSKHKPRTQI TALKEETEEE VQETRL
