ABCG2 p.Met549Ala

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PMID: 26294421 [PubMed] Haider AJ et al: "Identification of residues in ABCG2 affecting protein trafficking and drug transport, using co-evolutionary analysis of ABCG sequences."
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8 Two other mutations (P485A and M549A) showed distinct effects on transport of ABCG2 substrates reinforcing the role of TM helix 3 in drug recognition and transport and indicating the presence of intracellular coupling regions in ABCG2.
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ABCG2 p.Met549Ala 26294421:8:31
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109 We made individual substitutions of each amino acid to alanine: M131A, S195A, K453A, K473A, P485A, M549A, W564A and I573A.
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ABCG2 p.Met549Ala 26294421:109:99
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154 Secondly, there were a pair of mutant isoforms which showed little or no FTC-mediated inhibition of MX export (i.e. having high accumulation of MX even in the absence of FTC) but normal ABCG2 surface protein expression (P485A and M549A; P485A data shown in Figure 5D).
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ABCG2 p.Met549Ala 26294421:154:230
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156 To investigate further the two TMD mutations with impaired drug transport (M549A and P485A), we generated stable expressing cell lines expressing sfGFP-tagged isoforms.
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ABCG2 p.Met549Ala 26294421:156:75
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172 sfGFP-M549A and the catalytically inactive sfGFP-K86A isoform showed no Ko143-inhibited MX transport.
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ABCG2 p.Met549Ala 26294421:172:6
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173 With PhA, neither sfGFP-K86A nor sfGFP-M549A showed Ko143-inhibitable transport.
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ABCG2 p.Met549Ala 26294421:173:39
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179 Of the eight residues we mutated, two resulted in altered drug export function (P485A and M549A) and a further residue (I573A) perturbs the trafficking and maturation of ABCG2 glycosylation.
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ABCG2 p.Met549Ala 26294421:179:90
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193 Two of the remaining residues we mutated (M549A and P485A) affected drug export and provide some further evidence for a role for TM3 in forming part of a drug-binding site on ABCG2.
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ABCG2 p.Met549Ala 26294421:193:42
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206 9 to determine whether the lack of function of the P485A and M549A isoforms is due to impaired substrate binding (i.e. a direct effect on the drug-binding site) and/or impaired TMD-NBD communication.
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ABCG2 p.Met549Ala 26294421:206:63
status: NEW
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