ABCMdb

ABCG2 p.Gly406Ala

None has been submitted yet.

Publications

PMID: 15260487 [PubMed] Polgar O et al: "Mutational analysis of ABCG2: role of the GXXXG motif."

No. Sentence Comment

55 The following ABCG2 mutants were generated: G406L, G410L, G406L/G410L, G406A, G410A, and G406A/ G410A. Login to comment
145 Transport studies for the GXXXG alanine mutants using the same ABCG2 substrates were also performed; Figure 3 shows the results obtained with the G406A/G410A mutant. Login to comment
146 Changes in fluorescence when FTC was added were almost identical to the R482G mutant, indicating that alanine is able to replace glycine without interfering with protein function. Flow cytometry also proved that the G406A and G410A mutants had intact transport of these substrates (data not shown). Login to comment
161 Transport capacity for BODIPY-prazosin, rhodamine 123, mitoxantrone, and pheohorbide A in the R482G, G406A/G410A, G406L/G410L, G406L, and G410L transfected cells. Plots: Accumulation without FTC (s) and with FTC (---). Login to comment
164 The G406A/G410A mutants show intact transport capacity for all studied substrates. Login to comment
168 (C) Dimerization is suggested in both G406A and G410L mutants by high molecular weight bands detected following either exposure to DSP or harvesting under nonreducing conditions. Login to comment
174 Identical results were obtained with all the leucine and alanine mutants (Figure 4C showing results for the G406A and G410L mutants and Figure 4D for G406L and G410A; similar data not shown for the G406L/G410L and G406A/G410A mutants), implying that even if dimerization is impaired in these mutants, it has not prevented their close association on the cell surface. Login to comment

PMID: 17027309 [PubMed] Li YF et al: "Towards understanding the mechanism of action of the multidrug resistance-linked half-ABC transporter ABCG2: a molecular modeling study."

No. Sentence Comment

177 Exhibit reduced transport of mitoxantrone, pheophorbide and basal ATPase activity [17] G406A, G410A, G406A/G410A TM1 Fully functional b E446A,D,G,H,K,R,S TM2 Loss of drug resistance [21] R482G,T,M,S, N,D,K,Y TM3 T or G change produces gain of function mutant. Login to comment

PMID: 25036722 [PubMed] Szafraniec MJ et al: "Determinants of the activity and substrate recognition of breast cancer resistance protein (ABCG2)."

No. Sentence Comment

209 Position Type of mutation Effect on the transporter References NBD Lys 86 Met (i) No stimulation of the ATPase activity by prazosin; (ii) no influence on the transport of mitoxantrone Henriksen et al. (2005b) Glu 126 stop, Phe 208 Ser, Ser 248 Phe, Glu 334 stop Inability to transport hematoporphyrin Tamura et al. (2006) Glu 211 Gln Complete abolishment of the ATPase activity and methotrexate transport Hou et al. (2009) Pro 392 Ala Significant reduction in the efflux activity of mitoxantrone, BODIPY-prazosin and Hoechst 33342 Ni et al. (2011) TM1 Gly 406 Ala Gly 410 Ala No influence on the activity of the transporter Polgar et al. (2004) Gly 406 Leu Gly 410 Leu (i) Loss of the ability to transport rhodamine123; (ii) impaired transport of mitoxantrone, Pheide and BODIPY-prazosin Polgar et al. (2004) Extracellular loop 1 Phe 431 Leu (i) Loss of the ability to transport methotrexate; (ii) 10% level of hematoporphyrin transport compared to the WT protein Tamura et al. (2006) Ser 441 Asn Inability to transport hematoporphyrin Tamura et al. (2006) Ser 441 Asn Loss of the ability to transport methotrexate Tamura et al. (2006) TM2 Lys 452 Ala His 457 Ala Increase in transport of mitoxantrone, BODIPY-prazosin and Hoechst 33342 Cai et al. (2010) Lys 453 Ala Arg 465 Ala Decrease in transport of mitoxantrone, BODIPY-prazosin, Hoechst 33342, doxorubicin, SN-38 and rhodamine 123 Cai et al. (2010) TM3 Arg 482 Gly Arg 482 Thr (i) No change in the inhibitory activity of lapatinib; (ii) about two times greater inhibition by ritonavir, saquinavir and nalfinavir than in the WT variant; (iii) gaining the ability to transport rhodamine123 and doxorubicin; (iv) no influence on the transport of mitoxantrone; (v) loss of the ability to transport methotrexate Dai et al. (2008), Gupta et al. (2004), Honjo et al. (2001), Mitomo et al. (2003) Arg 482 Thr (i) Lower IC 50 of cyclosporine A for mutant than for WT variant; (ii) lower elacridar inhibition potency Xia et al. (2007) Arg 482 Lys Complete loss of transport activity Ejendal et al. (2006) Phe 489 Leu Impaired transport of porphyrins, no transport of methotrexate Tamura et al. (2006) Extracellular loop 3 Asn 590 Tyr Over twice reduced transport of mitoxantrone, topotecan, daunorubicin and rhodamine 123 Vethanayagam et al. (2005) Cys 592 Ala/Cys 608 Ala (i) Transport of mitoxantrone almost unchanged; (ii) transport of BODIPY-prazosin significantly impaired Henriksen et al. (2005a) Extracellular loop 3 Cys 603 Ser Cys 592 Ser/Cys 608 Ser Cys 592 Ser/Cys 603 Ser/Cys 608 Ser Diminished susceptibility to the inhibitory activity of fumitremorgin C Shigeta et al. (2010) Cys-less Arg 482 Gly-BCRP Complete loss of the ability to efflux mitoxantrone Liu et al. (2008b) The positions of the amino acid residues refer to the topological model of BCRP proposed by Wang et al. (2009). Login to comment