Identification of multidrug and toxin extrusion (MATE1 and MATE2-K) variants with complete loss of transport activity
| العنوان: | Identification of multidrug and toxin extrusion (MATE1 and MATE2-K) variants with complete loss of transport activity |
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| المؤلفون: | Moto Kajiwara, Ken-ichi Inui, Ken Ogasawara, Junko Iwano, Toshio Doi, Toshiya Katsura, Tomohiro Terada, Atsushi Fukatsu |
| المصدر: | Journal of Human Genetics. 54:40-46 |
| بيانات النشر: | Springer Science and Business Media LLC, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | SLC47A1, Organic Cation Transport Proteins, Blotting, Western, Molecular Sequence Data, Cell, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Cell Line, Exon, Genetics, medicine, Humans, Biotinylation, Amino Acid Sequence, Gene, Peptide sequence, Genetics (clinical), Cell Membrane, Wild type, Tetraethylammonium, Biological Transport, Molecular biology, Metformin, Kinetics, medicine.anatomical_structure, biology.protein, Mutant Proteins |
| الوصف: | H(+)/organic cation antiporters (multidrug and toxin extrusion: MATE1 and MATE2-K) play important roles in the renal tubular secretion of cationic drugs. We have recently identified a regulatory single nucleotide polymorphism (SNP) of the MATE1 gene (-32G>A). There is no other information about SNPs of the MATE gene. In this study, we evaluated the functional significance of genetic polymorphisms in MATE1 and MATE2-K. We sequenced all exons of MATE1 and MATE2-K genes in 89 Japanese subjects and identified coding SNPs (cSNPs) encoding MATE1 (V10L, G64D, A310V, D328A and N474S) and MATE2-K (K64N and G211V). All the variants except for MATE1 V10L showed significant decrease in transport activity. In particular, MATE1 G64D and MATE2-K G211V variants completely lost transport activities. When membrane expression level was evaluated by cell surface biotinylation, those of MATE1 (G64D and D328A) and MATE2-K (K64N and G211V) were significantly decreased compared with that of wild type. These findings suggested that the loss of transport activities of the MATE1 G64D and MATE2-K G211V variants were due to the alteration of protein expression in cell surface membranes. This is the first demonstration of functional impairment of the MATE family induced by cSNPs. |
| تدمد: | 1435-232X 1434-5161 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::77b1854823915e0207e564108bc721fe https://doi.org/10.1038/jhg.2008.1 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....77b1854823915e0207e564108bc721fe |
| قاعدة البيانات: | OpenAIRE |
Find this article in full text from Springer Verlag. | تدمد: | 1435232X 14345161 |
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