ABCMdb

PMID: 18370855

Polgar O, Robey RW, Bates SE
ABCG2: structure, function and role in drug response.
Expert Opin Drug Metab Toxicol. 2008 Jan;4(1):1-15., [PubMed]

Sentences

No. Mutations Sentence Comment

82 ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCG2 p.Ile206Leu ABCG2 p.Asn590Tyr Some of these are in the coding region of ABCG2 and alter the protein sequence, such as V12M, Q141K, I206L and N590Y. Login to comment 83 ABCG2 p.Gln141Lys Of these, Q141K, the substitution of glutamine with lysine at amino acid 141 in the NBD region is by far the most extensively studied. Login to comment 84 ABCG2 p.Gln141Lys The Q141K SNP has an especially high incidence rate in the Asian population (~ 30%) and is also frequently found in Caucasians (~ 10%) [68]. Login to comment 86 ABCG2 p.Gln141Lys Some investigators have also reported reduced surface expression for the Q141K SNP [71,72]. Login to comment 87 ABCG2 p.Gln141Lys In the authors` hands, the Q141K mutant when transfected into human embryonic kidney (HEK) cells was clearly detected on the cell surface by flow cytometry with the 5D3 antibody and in immunofluorescence studied with the BXP-21 antibody, although some intracellular staining was also observed [69]. Login to comment 88 ABCG2 p.Gln141Lys Recently, studies aimed at evaluating the clinical relevance of the Q141K SNP in patients undergoing chemotherapy and in healthy volunteers have also been reported: elevated plasma concentrations of gefitinib [73] and diflomotecan [74] and increased bioavailability of oral topotecan [75] were found. Login to comment 89 ABCG2 p.Gln141Lys In one study a higher incidence of diarrhea in patients carrying the Q141K SNP was observed following treatment with gefitinib [76]. Login to comment 155 ABCG2 p.Gly553Leu When expressed in HEK cells, the glycine to leucine mutation at this position (G553L) results in significantly reduced protein expression levels, altered glycosylation, and retention in the ER, even when coexpressed with the wild-type protein. Login to comment 156 ABCG2 p.Gly553Leu Yet, the G553L mutant can be chemically crosslinked. Login to comment 158 ABCG2 p.Gly553Leu Indeed, the GFP-tagged G553L mutant was pulled down with the His-tagged wild-type ABCG2 in co-immunoprecipitation experiments following coexpression in Sf9 cells (Figure 2). Login to comment 161 ABCG2 p.Gly553Leu Coimmunoprecipitation of the G553L mutant with the wild-type protein in Sf9 insect cells. Login to comment 162 ABCG2 p.Gly553Leu Sf9 insect cells were coinfected with bacculovirus carrying His-tagged wt ABCG2 and GFP-tagged G553L mutant followed by membrane preparation. Login to comment 171 ABCG2 p.Gly553Leu wt-His/wt-GFP 1 2 3 4 5 6 7 8 wt-His/G553L-GFP Figure 1. Login to comment 175 ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCG2 p.Ile206Leu ABCG2 p.Asn590Tyr Membrane Out In 200 100 300 400 500 600 ATP site N-terminus C-terminus V12M Q141K I206L GXXXG, G406/G410 R482 G553 C603 N596 N590Y protein synthesis. Login to comment 344 ABCG2 p.Gln141Lys Pharm Res 2004;21(10):1895-903 72. Imai Y, Nakane M, Kage K, et al. C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low-level drug resistance. Login to comment 348 ABCG2 p.Gln141Lys Cancer Biol Ther 2007;6(3):432-8 • Potential relevance of the Q141K SNP in the pharmacokinetics of ABCG2 substrates. Login to comment 350 ABCG2 p.Gln141Lys Clin Pharmacol Ther 2004;76(1):38-44 • Potential relevance of the Q141K SNP in the pharmacokinetics of ABCG2 substrates. Login to comment 352 ABCG2 p.Gln141Lys Cancer Biol Ther 2005;4(6):650-8 • Potential relevance of the Q141K SNP in the pharmacokinetics of ABCG2 substrates. Login to comment 355 ABCG2 p.Gln141Lys J Natl Cancer Inst 2006;98(23):1739-42 • Potential relevance of the Q141K SNP in the pharmacokinetics of ABCG2 substrates. Login to comment 378 ABCG2 p.Lys86Met Effect of Walker A mutation (K86M) on oligomerization and surface targeting of the multidrug resistance transporter ABCG2. Login to comment