ABCMdb

ABCG2 p.Met131Ala

Predicted by SNAP2:	A: D (71%), C: D (63%), D: D (85%), E: D (85%), F: D (59%), G: D (85%), H: D (71%), I: D (59%), K: D (85%), L: N (61%), N: D (80%), P: D (85%), Q: D (75%), R: D (85%), S: D (75%), T: D (53%), V: D (63%), W: D (71%), Y: D (59%),
Predicted by PROVEAN:	A: D, C: D, D: D, E: D, F: D, G: D, H: D, I: D, K: D, L: N, N: D, P: D, Q: D, R: D, S: D, T: D, V: D, W: D, Y: D,

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Publications
[hide] Identification of residues in ABCG2 affecting prot... Biosci Rep. 2015 Jul 17;35(4). pii: e00241. doi: 10.1042/BSR20150150. Haider AJ, Cox MH, Jones N, Goode AJ, Bridge KS, Wong K, Briggs D, Kerr ID
Identification of residues in ABCG2 affecting protein trafficking and drug transport, using co-evolutionary analysis of ABCG sequences.
Biosci Rep. 2015 Jul 17;35(4). pii: e00241. doi: 10.1042/BSR20150150., [PMID:26294421]

Abstract [show]
ABCG2 is an ABC (ATP-binding cassette) transporter with a physiological role in urate transport in the kidney and is also implicated in multi-drug efflux from a number of organs in the body. The trafficking of the protein and the mechanism by which it recognizes and transports diverse drugs are important areas of research. In the current study, we have made a series of single amino acid mutations in ABCG2 on the basis of sequence analysis. Mutant isoforms were characterized for cell surface expression and function. One mutant (I573A) showed disrupted glycosylation and reduced trafficking kinetics. In contrast with many ABC transporter folding mutations which appear to be 'rescued' by chemical chaperones or low temperature incubation, the I573A mutation was not enriched at the cell surface by either treatment, with the majority of the protein being retained in the endoplasmic reticulum (ER). 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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Sentences [show]
No. Sentence Comment
109 We made individual substitutions of each amino acid to alanine: M131A, S195A, K453A, K473A, P485A, M549A, W564A and I573A. Login to comment
128 Transfection reagent only (PEI) served as negative control, WT His12-ABCG2 and His12-M131A serve as positive controls. Login to comment
135 WT and a representative other mutant (His12-M131A) are fully glycosylated at both 24 and 48 h post transfection. Login to comment
153 Firstly, there was a group of five mutants which showed FTC-inhibited MX export comparable to WT protein (e.g. M131A, S195A, K453A, K473A, W564A; M131A data shown in Figure 3C). Login to comment
165 Data are representative of at least four independent transfections and reflect negative control data (empty vector, A), positive control data (WT ABCG2 expression, B), a mutant with normal MX transport function (M131A, C) and a mutant with abrogated function but normal surface expression (P485A, D). Login to comment