ABCG2 p.Arg193Lys
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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).
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ABCG2 p.Arg193Lys 23493553:71:148
status: NEWX
ABCG2 p.Arg193Lys 23493553:71:500
status: NEW107 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.
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ABCG2 p.Arg193Lys 23493553:107:239
status: NEWX
ABCG2 p.Arg193Lys 23493553:107:320
status: NEW159 Interestingly, the R193K mutation, homologous to the suppressor mutation R555K in CFTR, didn`t increase Q141K ABCG2 expression; but did appear to decrease the insoluble fraction of Q141K protein (Fig. S6D).
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ABCG2 p.Arg193Lys 23493553:159:19
status: NEW161 It may be that R193K could not rescue mature protein but actually enhanced the degradation of misfolded protein by preventing the formation of the large insoluble aggresomes as reportedly seen by other groups (17).
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ABCG2 p.Arg193Lys 23493553:161:15
status: NEW
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
113
Therefore all these three mutations were introduced into the corresponding regions of the ABCG2 DF142 construct (3R: G188E, R191Q, and R193K).
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ABCG2 p.Arg193Lys 23800412:113:135
status: NEW