ABCMdb

ABCG2 p.Tyr469Ser

None has been submitted yet.

Publications

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."

No. Sentence Comment

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. Login to comment
112 We found that mutation of Tyr to Ser at position 469 or 645 resulted in the loss of ATP hydrolysis (even if the activity is corrected for the lower expression level of the Y469S mutant); while mutations in the other two positions apparently did not alter ABCG2 functionality, as both the Y413S and Y570S mutants showed a high level of ATPase activity, which could be inhibited by a general ATPase inhibitor vanadate or the specific ABCG2 inhibitor Ko143 (Fig. 2B). Login to comment
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. Login to comment
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). Login to comment
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). Login to comment
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. Login to comment