ABCMdb

ABCG2 p.Gly188Glu

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Publications

PMID: 23493553 [PubMed] Woodward OM et al: "Gout-causing Q141K mutation in ABCG2 leads to instability of the nucleotide-binding domain and can be corrected with small molecules."

No. Sentence Comment

71 We separately mutated two residues in the Q141K background-a Gly to Glu substitution at position 188 (G188E) and an Arg to Lys substitution at 193 (R193K) (homologous to the Gly-550 and Arg-555 residues of CFTR, shown in Fig. 3A)-and found that the G188E mutation acted as a suppressor mutation, significantly increased the amount of the Q141K total protein (Fig. 3 B-E and Fig. S4 E and G), and increased the dimer protein (Fig. 3 C and E and Fig. S4 F and H) and the surface protein (Fig. 3F); the R193K mutation did not act as a suppressor (P < 0.41; n = 10). Login to comment
80 G188E mutation introduced into the wild-type protein produced no change in expression (Fig. 3G) and did not recue the ƊF142 mutation (Fig. S2 E and F), supporting the hypothesis that the F142 deletion disrupts both stability and interdomain interactions. Login to comment
107 ABCG2 WT 141K 188E -- -- 188E 76k ABCG2 GAPDH surface ABCG2 Na/K atpase WT 141K 188E 193K -- WT 141K 188E 193K -- 76k ABCG2 GAPDH ABCG2 monomer ABCG2 dimer 140k WT 141K 188E 193K -- A B C 0.0 0.5 1.0 Normalized ABCG2 protein WT 141K G188E R193K -- ** 0.0 0.5 1.0 1.5 2.0 2.5 Normalized ABCG2 dimer protein WT 141K G188E R193K -- * E F G D CFTR Fig. 3. Login to comment
114 (F) Surface expression of biotinylated ABCG2 and Q141K variants and Na+ /K+ ATPase, demonstrating strong rescue with the Q141K G188E mutation (n = 6). Login to comment
115 (G) The G188E mutation does not affect WT ABCG2 protein expression (n = 3). Login to comment
121 Interestingly, we found that 4-PBA was also able to increase the amount of Q141K/G188E protein (Fig. 5 A-C), demonstrating that the G188E suppressor mutation is not a full rescue and that some protein is still targeted for degradation. Login to comment
158 Here we tested homologous NBD mutations in Q141K ABCG2 and found the G188E mutation rescued Q141K expression, suggesting the Q141K mutation results in increased ABCG2 NBD instability. Login to comment

PMID: 23800412 [PubMed] Saranko H et al: "Effects of the gout-causing Q141K polymorphism and a CFTR DeltaF508 mimicking mutation on the processing and stability of the ABCG2 protein."

No. Sentence Comment

20 http://dx.doi.org/10.1016/j.bbrc.2013.06.054 Abbreviations: CFTR, cystic fibrosis transmembrane conductance regulator, ABCC7; HEK, human embryonic kidney 293 cells; NBD, nucleotide binding domain; MBP, maltose binding protein; TMD, transmembrane domain; PBA, 4-phenylbutyrate; Sf9, Spodoptera frugiperda cells; SNP, single nucleotide polymorphism; 3R, G188E, R191Q, and R193K rescue mutations in ABCG2-NBD. Login to comment
113 Therefore all these three mutations were introduced into the corresponding regions of the ABCG2 DF142 construct (3R: G188E, R191Q, and R193K). Login to comment
120 Interestingly, one of the rescue mutations, G188E has been reported to promote Q141K maturation [11]. Login to comment
122 While this G188E mutation does not increase the maturation of WT ABCG2 [11], the analogous G550E mutation promotes the maturation of WT CFTR [21] that again suggest fundamental differences between the NBDs of the two proteins. Login to comment

PMID: 26136557 [PubMed] Woodward OM et al: "ABCG2: the molecular mechanisms of urate secretion and gout."

No. Sentence Comment

74 Using either small molecules like the drug VRT-325 (11), or by using the suppressor mutation G188E to enhance NBD sandwich formation (25), we were able to rescue expression, trafficking, and function (32). Login to comment