The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Evolutionary conservation predicts function of variants of the human organic cation transporter, OCT1
Open accessAbstract
The organic cation transporter, OCT1, is a major hepatic transporter that mediates the uptake of many organic cations from the blood into the liver where the compounds may be metabolized or secreted into the bile. Because OCT1 interacts with a variety of structurally diverse organic cations, including clinically used drugs as well as toxic substances (e.g., N -methylpyridinium, MPP + ), it is an important determinant of systemic exposure to many xenobiotics. To understand the genetic basis of extensive interindividual differences in xenobiotic disposition, we functionally characterized 15 protein-altering variants of the human liver organic cation transporter, OCT1, in Xenopus oocytes. All variants that reduced or eliminated function (OCT1-R61C, OCT1-P341L, OCT1-G220V, OCT1-G401S, and OCT1-G465R) altered evolutionarily conserved amino acid residues. In general, variants with decreased function had amino acid substitutions that resulted in more radical chemical changes (higher Grantham values) and were less evolutionarily favorable (lower blosum 62 values) than variants that maintained function. A variant with increased function (OCT1-S14F) changed an amino acid residue such that the human protein matched the consensus of the OCT1 mammalian orthologs. Our results indicate that changes at evolutionarily conserved positions of OCT1 are strong predictors of decreased function and suggest that a combination of evolutionary conservation and chemical change might be a stronger predictor of function.
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Cites
A New Statistical Method for Haplotype Reconstruction from Population Data
Stephens, M., Smith, N. J., & Donnelly, P. (2001) · The American Journal of Human Genetics · doi:10.1086/319501 · Cited by 7,493
Amino acid substitution matrices from protein blocks.
Henikoff, S., & Henikoff, J. G. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.10915 · Cited by 6,218
Chronic Parkinsonism in Humans Due to a Product of Meperidine-Analog Synthesis
Langston, J. W., Ballard, P., Tetrud, J. W., & Irwin, I. (1983) · Science · doi:10.1126/science.6823561 · Cited by 4,914
Pharmacogenomics: Translating Functional Genomics into Rational Therapeutics
Evans, W. E., & Relling, M. V. (1999) · Science · doi:10.1126/science.286.5439.487 · Cited by 2,475
Predicting Deleterious Amino Acid Substitutions
Ng, P. C., & Henikoff, S. (2001) · Genome Research · doi:10.1101/gr.176601 · Cited by 2,368
Amino Acid Difference Formula to Help Explain Protein Evolution
Grantham, R. (1974) · Science · doi:10.1126/science.185.4154.862 · Cited by 2,363
Characterization of single-nucleotide polymorphisms in coding regions of human genes
Cargill, M., Altshuler, D., Ireland, J., Sklar, P., Ardlie, K., Patil, N., Lane, C. R., Lim, E. P., Kalyanaraman, N., Nemesh, J., et al. (1999) · Nature Genetics · doi:10.1038/10290 · Cited by 1,547
Strautnieks, S. S., Bull, L. N., Knisely, A. S., Kocoshis, S. A., Dahl, N., Arnell, H., Sokal, E., Dahan, K., Childs, S., Ling, V., et al. (1998) · Nature Genetics · doi:10.1038/3034 · Cited by 995
A gene encoding a P-type ATPase mutated in two forms of hereditary cholestasis
Bull, L. N., van Eijk, M. J. T., Pawlikowska, L., DeYoung, J. A., Juijn, J. A., Liao, M., Klomp, L. W. J., Lomri, N., Berger, R., Scharschmidt, B. R., et al. (1998) · Nature Genetics · doi:10.1038/ng0398-219 · Cited by 736
Self-citationCloning and Characterization of Two Human Polyspecific Organic Cation Transporters
GORBOULEV, V., ULZHEIMER, J. C., AKHOUNDOVA, A., ULZHEIMER-TEUBER, I., KARBACH, U., QUESTER, S., BAUMANN, C., LANG, F., BUSCH, A. E., & KOEPSELL, H. (1997) · DNA and Cell Biology · doi:10.1089/dna.1997.16.871 · Cited by 638
Cited by
Koepsell, H., Lips, K., & Volk, C. (2007) · Pharmaceutical Research · doi:10.1007/s11095-007-9254-z · Cited by 988
Transporters and drug therapy: Implications for drug disposition and disease
HO, R., & KIM, R. (2005) · Clinical Pharmacology & Therapeutics · doi:10.1016/j.clpt.2005.05.011 · Cited by 502
Nies, A. T., Koepsell, H., Damme, K., & Schwab, M. (2011) · Handbook of Experimental Pharmacology · doi:10.1007/978-3-642-14541-4_3 · Cited by 375
Sex‐Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans
Blöcher, J. A., Meyer‐Tönnies, M. J., Morof, F., Rönnpagel, V., Bethmann, J., Vollmer, M., Engeli, S., & Tzvetkov, M. V. (2025) · Clinical Pharmacology & Therapeutics · doi:10.1002/cpt.3454 · Cited by 16
Metadata
- Authors
- Shu, Y., Leabman, M. K., Feng, B., Mangravite, L. M., Huang, C. C., Stryke, D., Kawamoto, M., Johns, S. J., DeYoung, J., Carlson, E., Ferrin, T. E., Herskowitz, I., Giacomini, K. M., & Pharmacogenetics of Membrane Transporters Investigators‡‡
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2003-04-28
- Volume
- 100
- Issue
- 10
- Pages
- 5902-5907
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2147839361
- Cited by
- 285
- References
- 23
- FWCI
- 6.23
- Type
- journal article
- Language
- en
- Open access
- green
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- Shu, Y., Leabman, M. K., Feng, B., Mangravite, L. M., Huang, C. C., Stryke, D., Kawamoto, M., Johns, S. J., DeYoung, J., Carlson, E., Ferrin, T. E., Herskowitz, I., Giacomini, K. M., & Pharmacogenetics of Membrane Transporters Investigators‡‡. (2003). Evolutionary conservation predicts function of variants of the human organic cation transporter, OCT1. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0730858100
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