ABCG2 p.Tyr645Ser

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PMID: 25445676 [PubMed] Gal Z et al: "Mutations of the central tyrosines of putative cholesterol recognition amino acid consensus (CRAC) sequences modify folding, activity, and sterol-sensing of the human ABCG2 multidrug transporter."
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5 We found that mutation in Y459 prevented protein expression; the Y469S and Y645S mutants lost their activity; while the Y570S, Y469F, and Y645F mutants retained function as well as cholesterol and bile acid sensitivity.
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ABCG2 p.Tyr645Ser 25445676:5:75
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113 In order to test if the inactivity of the Y469S and Y645S mutants was due to a specific loss of Tyr at this position, we also mutated these tyrosines to phenylalanines.
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ABCG2 p.Tyr645Ser 25445676:113:52
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226 The Y469S and Y645S mutants could be expressed in comparable amounts to the wild-type protein, however, they were found to be non-functional (Fig. 2).
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ABCG2 p.Tyr645Ser 25445676:226:14
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231 Our experiments, in which we tested the conformation of the ABCG2 mutants by labeling them with the conformation sensitive anti-ABCG2 5D3 antibody, revealed that the Y469S and Y645S mutants have decreased 5D3 binding capacity (Supplementary Fig. S4).
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ABCG2 p.Tyr645Ser 25445676:231:176
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232 Therefore the loss of the activity of the Y469S and Y645S mutants is most probably due to their improper conformation and not by their altered cholesterol-sensing.
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ABCG2 p.Tyr645Ser 25445676:232:52
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