ABCMdb

PMID: 21188243

Ishikawa T, Nakagawa H, Hagiya Y, Nonoguchi N, Miyatake S, Kuroiwa T
Key Role of Human ABC Transporter ABCG2 in Photodynamic Therapy and Photodynamic Diagnosis.
Adv Pharmacol Sci. 2010;2010:587306. Epub 2010 Jul 8., [PubMed]

Sentences

No. Mutations Sentence Comment

158 ABCG2 p.Gln141Lys The most extensively studied among those SNPs with potential clinical relevance is 421 C > A resulting in a glutamine to lysine substitution (Q141K) in the ABCG2 protein. Login to comment 159 ABCG2 p.Gln141Lys The Q141K SNP has been identified with varying frequencies in different ethnic groups and was found to be the most relevant in Japanese and Chinese populations (approximately 30% in the allele frequency). Login to comment 161 ABCG2 p.Gln141Lys Q141K has been associated with lower levels of protein expression and impaired transport in vitro [79-84]. Login to comment 163 ABCG2 p.Gln141Lys Furthermore, the Q141K SNP was reportedly associated with a higher incidence of diarrhea in nonsmall cell lung cancer patients treated with gefitinib [88]. Login to comment 164 ABCG2 p.Gln141Lys It has been demonstrated that the reduced expression levels of the Q141K variant may be due to its ubiquitin-mediated proteasomal degradation [89]. Login to comment 167 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCG2 p.Ile206Leu ABCG2 p.Asn590Tyr ABCG2 p.Gln166Glu ABCG2 p.Phe208Ser ABCG2 p.Asp620Asn ABCG2 p.Thr153Met ABCG2 p.Ser441Asn ABCG2 p.Phe489Leu ABCG2 p.Phe431Leu ABCG2 p.Gly51Cys ABCG2 p.Ser248Pro ABCG2 p.Phe571Ile ABCG2 p.Gln126* ABCG2 p.Glu334* Based on the currently available data on SNPs and acquired mutations, we have created a total of 18 variant forms of ABCG2 (V12M, G51C, Q126stop, Q141K, T153M, Q166E, I206L, F208S, S248P, E334stop, F431L, S441N, R482G, R482T, F489L, F571I, N590Y, and D620N) by site-directed mutagenesis and expressed them in insect cells [41, 90]. Login to comment 168 ABCG2 p.Phe208Ser ABCG2 p.Ser441Asn ABCG2 p.Ser248Pro ABCG2 p.Gln126* ABCG2 p.Glu334* The variants Q126stop, F208S, S248P, E334stop, and S441N are defective in the transport of hematoporphyrin (Figure 4(b)). Login to comment 169 ABCG2 p.Phe489Leu The F489L variant showed impaired transport activity (Figure 4(b)). Login to comment 170 ABCG2 p.Phe208Ser ABCG2 p.Ser441Asn ABCG2 p.Phe489Leu ABCG2 p.Ser248Pro Flp-In-293 cells expressing the F208S, S248P, S441N, and F489L variants were sensitive to light when cells were treated with pheophorbide a. Login to comment 177 ABCG2 p.Arg482Thr ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly ABCG2 p.Arg482Gly ABCG2 p.Gln141Lys ABCG2 p.Gln141Lys ABCG2 p.Val12Met ABCG2 p.Val12Met ABCG2 p.Ile206Leu ABCG2 p.Ile206Leu ABCG2 p.Asn590Tyr ABCG2 p.Asn590Tyr ABCG2 p.Gln166Glu ABCG2 p.Gln166Glu ABCG2 p.Phe208Ser ABCG2 p.Phe208Ser ABCG2 p.Asp620Asn ABCG2 p.Asp620Asn ABCG2 p.Thr153Met ABCG2 p.Thr153Met ABCG2 p.Ser441Asn ABCG2 p.Ser441Asn ABCG2 p.Phe489Leu ABCG2 p.Phe489Leu ABCG2 p.Pro269Ser ABCG2 p.Phe431Leu ABCG2 p.Phe431Leu ABCG2 p.Arg160Gln ABCG2 p.Gly51Cys ABCG2 p.Gly51Cys ABCG2 p.Ser248Pro ABCG2 p.Ser248Pro ABCG2 p.Phe571Ile ABCG2 p.Phe571Ile ABCG2 p.Gln126* ABCG2 p.Gln126* ABCG2 p.Asp296His ABCG2 p.Ala528Thr ABCG2 p.Thr542Ala ABCG2 p.Arg575* ABCG2 p.Glu334* ABCG2 p.Glu334* Gefitinib and imatinib are new anticancer drugs Outside Plasma membrane Inside H2N COOH V12M G51C Q126stop Q141K T153M R160Q Q166E I206L F208S S248P E334stop F431L F489L S441N R482G R482T F571I R575stop N590Y D620N T542A A528T D296H P269S ATP-binding cassette (a) 0 0.1 0.3 0.4 0.2 0.5 Mock WT V12M G51C Q126stop Q141K T153M Q166E I206L F208S S248P E334stop F431L S441N F489L F571I N590Y D620N R482G R482T ATP-dependenthematoporphyrin transport(nmol/min/mgprotein) (b) Figure 4: (a) Schematic illustration of human ABCG2 and its nonsynonymous polymorphisms. Login to comment 179 ABCG2 p.Arg482Thr ABCG2 p.Arg482Gly The variants R482G and R482T are acquired mutations. Login to comment