ABCMdb

ABCG2 p.His155Ala

Predicted by SNAP2:	A: N (87%), C: N (72%), D: N (87%), E: N (93%), F: N (53%), G: N (82%), I: N (87%), K: N (97%), L: N (82%), M: N (93%), N: N (93%), P: N (78%), Q: N (97%), R: N (97%), S: N (93%), T: N (93%), V: N (87%), W: N (72%), Y: N (72%),
Predicted by PROVEAN:	A: D, C: D, D: N, E: N, F: D, G: D, I: D, K: N, L: D, M: D, N: N, P: D, Q: N, R: N, S: D, T: D, V: D, W: D, Y: D,

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[hide] ABCG2: the molecular mechanisms of urate secretion... Am J Physiol Renal Physiol. 2015 Sep 15;309(6):F485-8. doi: 10.1152/ajprenal.00242.2015. Epub 2015 Jul 1. Woodward OM
ABCG2: the molecular mechanisms of urate secretion and gout.
Am J Physiol Renal Physiol. 2015 Sep 15;309(6):F485-8. doi: 10.1152/ajprenal.00242.2015. Epub 2015 Jul 1., [PMID:26136557]

Abstract [show]
The human propensity for high levels of serum uric acid (SUA) is a trait that has defied explanation. Is it beneficial? Is it pathogenic? Its role in the human diseases like gout and kidney stones was discovered over a century ago [Richette P, Bardin T. Lancet 375: 318-328, 2010; Rivard C, Thomas J, Lanaspa MA, Johnson RJ. Rheumatology (Oxford) 52: 421-426, 2013], but today emerging new genetic and epidemiological techniques have revived an age-old debate over whether high uric acid levels (hyperuricemia) independently increase risk for diseases like hypertension and chronic kidney disease [Feig DI. J Clin Hypertens (Greenwich) 14: 346-352, 2012; Feig DI, Madero M, Jalal DI, Sanchez-Lozada LG, Johnson RJ. J Pediatr 162: 896-902, 2013; Feig DI, Soletsky B, Johnson RJ. JAMA 300: 924-932, 2008; Wang J, Qin T, Chen J, Li Y, Wang L, Huang H, Li J. PLoS One 9: e114259, 2014; Zhu P, Liu Y, Han L, Xu G, Ran JM. PLoS One 9: e100801, 2014]. Part of the mystery of the role uric acid plays in human health stems from our lack of understanding of how humans regulate uric acid homeostasis, an understanding that could shed light on the historic role of uric acid in human adaptation and its present role in human pathogenesis. This review will highlight the recent work to identify the first important human uric acid secretory transporter, ABCG2, and the identification of a common causal ABCG2 variant, Q141K, for hyperuricemia and gout.

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No. Sentence Comment
51 Q141K Q141K / H155A 0.00 0.25 0.50 Q141K ABCG2 abundance relative to Wt Q141K ABCG2 H155A -- -- H155A GAPDH ABCG2 Wt ABCG2 Q141K H155 2 Q141K + H155A H155A ICL Q141K / Wt NBD B A C D ** Fig. 1. Login to comment
55 C: biochemical confirmation of the model shows the Q141K mutant expression levels can be rescued with the secondary H155A substitution. Login to comment
81 Replacing the histidine with an alanine appeared to resolve the shift and also significantly increased total Q141K (H155A) and mature, glycosylated protein abundance (Fig. 1, B-D) when expressed in HEK293 cells. Login to comment