ABCC7 p.Lys335Ile
| Predicted by SNAP2: | A: D (66%), C: D (80%), D: D (91%), E: D (75%), F: D (91%), G: D (80%), H: D (80%), I: D (80%), L: D (80%), M: D (80%), N: D (80%), P: D (91%), Q: N (53%), R: N (87%), S: D (66%), T: D (75%), V: D (80%), W: D (91%), Y: D (85%), |
| Predicted by PROVEAN: | A: N, C: D, D: N, E: N, F: D, G: N, H: N, I: N, L: N, M: N, N: N, P: N, Q: N, R: N, S: N, T: N, V: N, W: D, Y: D, |
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[hide] An unstable transmembrane segment in the cystic fi... EMBO J. 1999 Nov 15;18(22):6290-8. Tector M, Hartl FU
An unstable transmembrane segment in the cystic fibrosis transmembrane conductance regulator.
EMBO J. 1999 Nov 15;18(22):6290-8., 1999-11-15 [PMID:10562541]
Abstract [show]
The cystic fibrosis transmembrane conductance regulator (CFTR), a chloride channel with 12 membrane-spanning sequences, undergoes inefficient maturation in the endoplasmic reticulum (ER). Potentially charged residues in transmembrane segments may contribute to this defect in biogenesis. We demonstrate that transmembrane segment 6 of CFTR, which contains three basic amino acids, is extremely unstable in the lipid bilayer upon membrane insertion in vitro and in vivo. However, two distinct mechanisms counteract this anchoring deficiency: (i) the ribosome and the ER translocon co-operate to prevent transmembrane segment 6 from passing through the membrane co- translationally; and (ii) cytosolic domains of the ion channel post-translationally maintain this segment of CFTR in a membrane-spanning topology. Although these mechanisms are essential for successful completion of CFTR biogenesis, inefficiencies in their function retard the maturation of the protein. It seems possible that some of the disease-causing mutations in CFTR may reduce the efficiency of proper membrane anchoring of the protein.
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No. Sentence Comment
80 (C) Translation and translocation into microsomes of constructs containing wild-type or doubly mutated, R334L and K335I, Tm6 were analysed by immunoprecipitation with anti-myc antibody (lanes 1, 2, 5 and 6) or a non-relevant control antibody (NRA) (lanes 3 and 7) from TX-100 extracts of the isolated microsomes.
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ABCC7 p.Lys335Ile 10562541:80:114
status: NEW95 Arginine 334 was changed to leucine and lysine 335 to isoleucine, generating construct Tm5-6(RK-LI)-Inv (Figure 3A).
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ABCC7 p.Lys335Ile 10562541:95:40
status: NEW203 These mutations enabled the production of proteins containing leucine in place of arginine 334 and isoleucine in place of lysine 335 in Tm6 of CFTR.
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ABCC7 p.Lys335Ile 10562541:203:99
status: NEW