ABCC1 p.Gly756Ser
| Predicted by SNAP2: | A: D (59%), C: D (63%), D: D (75%), E: D (75%), F: D (80%), H: D (63%), I: D (75%), K: D (71%), L: D (75%), M: D (75%), N: D (63%), P: D (71%), Q: D (66%), R: N (66%), S: D (53%), T: D (71%), V: D (71%), W: D (85%), Y: D (80%), |
| Predicted by PROVEAN: | A: D, C: D, D: D, E: D, F: D, H: D, I: D, K: D, L: D, M: D, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D, |
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[hide] Mutational analysis of the Saccharomyces cerevisia... Mol Microbiol. 1997 Aug;25(4):683-94. Wemmie JA, Moye-Rowley WS
Mutational analysis of the Saccharomyces cerevisiae ATP-binding cassette transporter protein Ycf1p.
Mol Microbiol. 1997 Aug;25(4):683-94., [PMID:9379898]
Abstract [show]
Ycf1p is a member of the ATP-binding cassette transporter family of membrane proteins. Strong sequence similarity has been observed between Ycf1p, the cystic fibrosis transmembrane conductance regulator (CFTR) and multidrug resistance protein (MRP). In this work, we have examined the functional significance of several of the conserved amino acid residues and the genetic requirements for Ycf1p subcellular localization. Biochemical fractionation experiments have established that Ycf1p, expressed at single-copy gene levels, co-fractionates with the vacuolar membrane and that this co-fractionation is independent of vps15, vps34 or end3 gene function. Several cystic fibrosis-associated alleles of the CFTR were introduced into Ycf1p and found to elicit defects analogous to those seen in the CFTR. An amino-terminal extension shared between Ycf1p and MRP, but absent from CFTR, was found to be required for Ycf1p function, but not its subcellular localization. Mutant forms of Ycf1p were also identified that exhibited enhanced biological function relative to the wild-type protein. These studies indicate that Ycf1p will provide a simple, genetically tractable model system for the study of the trafficking and function of ATP-binding cassette transporter proteins, such as the CFTR and MRP.
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No. Sentence Comment
133 These mutants corresponded to CFTR alterations known to be associated with cystic fibrosis (G551D and G551S in CFTR, G756D and G756S in Ycf1p) as well as lesions that either disturb normal function (K464M in CFTR, K669M in Ycf1p) or act to suppress the phenotype of ⌬F508 CFTR (R553Q and R553M in CFTR, K758Q and K758M in CFTR).
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ABCC1 p.Gly756Ser 9379898:133:127
status: NEW135 K669M, G756S and G756D were unable to complement the cadmium hypersensitivity of the ⌬ycf1 strain. Western blot analysis of these mutant Ycf1p derivatives indicated that all these proteins were produced at the same level in the cell.
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ABCC1 p.Gly756Ser 9379898:135:7
status: NEW237 The three mutant Ycf1p derivatives (⌬F713, G756D and G756S) that correspond to known CF-causing alleles of CFTR (⌬F508, G551D and G551S) all produce a Ycf1p mutant that exhibits a defect analogous to its CFTR counterpart.
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ABCC1 p.Gly756Ser 9379898:237:60
status: NEW281 The 2 m plasmids carrying the indicated mutant forms of YCF1 and the relevant mutagenic PCR primers are listed below: pJAW100 (G756S), 5Ј-ATC TCC TTA TCT GGA TCC CAA AAA GCT CGT TTG-3Ј; pJAW88 (G756D), 5Ј-ATC TCC TTA TCT GGA GAC CAA AAA GCT CGT TTG-3Ј; pJAW86 (K669M), 5Ј- AAA GTT GGC AGT GGT ATG ACA GCT CTA TT-3Ј; pJAW98 (K758R), 5Ј-TTA TCT GGA GGA CAA CGG GCC CGT TTG TCT TTA-3Ј; pJAW108 (K758M), 5Ј-AGA CAA ACG AGC CAT TTG TCC TCC AGA TAA GGA TAT CCC TTT C-3Ј; pJAW109 (K758Q), 5Ј-AGA CAA ACG AGC TTG TTG TCC TCC AGA TAA GCT TAT CCC TTT C-3Ј.
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ABCC1 p.Gly756Ser 9379898:281:135
status: NEW