Human multidrug and toxin extrusion MATE1 and MATE2-K are H⁺/organic cation antiporters [1]. They are predominantly expressed in the kidney and play a role in renal tubular secretion of cationic drugs.

DAPI has been used to allow quantification of MATE1 and MATE2-mediated transport activity [10]. MATE2 and MATE2-B are inactive splice variants of MATE2-K [4].

* Key recommended reading is highlighted with an asterisk

* Damme K, Nies AT, Schaeffeler E, Schwab M. (2011) Mammalian MATE (SLC47A) transport proteins: impact on efflux of endogenous substrates and xenobiotics. Drug Metab Rev, 43 (4): 499-523. [PMID:21923552]

* Koepsell H. (2020) Organic Cation Transporters in Health and Disease. Pharmacol Rev, 72 (1): 253-319. [PMID:31852803]

* Krishnan S, Ramsden D, Ferguson D, Stahl SH, Wang J, McGinnity DF, Hariparsad N. (2022) Challenges and Opportunities for Improved Drug-Drug Interaction Predictions for Renal OCT2 and MATE1/2-K Transporters. Clin Pharmacol Ther, 112 (3): 562-572. [PMID:35598119]

* Motohashi H, Inui K. (2013) Multidrug and toxin extrusion family SLC47: physiological, pharmacokinetic and toxicokinetic importance of MATE1 and MATE2-K. Mol Aspects Med, 34 (2-3): 661-8. [PMID:23506899]

Nies AT, Damme K, Kruck S, Schaeffeler E, Schwab M. (2016) Structure and function of multidrug and toxin extrusion proteins (MATEs) and their relevance to drug therapy and personalized medicine. Arch Toxicol, 90 (7): 1555-84. [PMID:27165417]

Terada T, Inui K. (2008) Physiological and pharmacokinetic roles of H+/organic cation antiporters (MATE/SLC47A). Biochem Pharmacol, 75 (9): 1689-96. [PMID:18262170]

Wagner DJ, Hu T, Wang J. (2016) Polyspecific organic cation transporters and their impact on drug intracellular levels and pharmacodynamics. Pharmacol Res, 111: 237-246. [PMID:27317943]

* Yonezawa A, Inui K. (2011) Importance of the multidrug and toxin extrusion MATE/SLC47A family to pharmacokinetics, pharmacodynamics/toxicodynamics and pharmacogenomics. Br J Pharmacol, 164 (7): 1817-25. [PMID:21457222]

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4. Masuda S, Terada T, Yonezawa A, Tanihara Y, Kishimoto K, Katsura T, Ogawa O, Inui K. (2006) Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2. J Am Soc Nephrol, 17 (8): 2127-35. [PMID:16807400]

5. Ohta KY, Inoue K, Hayashi Y, Yuasa H. (2006) Molecular identification and functional characterization of rat multidrug and toxin extrusion type transporter 1 as an organic cation/H+ antiporter in the kidney. Drug Metab Dispos, 34 (11): 1868-74. [PMID:16928787]

6. Otsuka M, Matsumoto T, Morimoto R, Arioka S, Omote H, Moriyama Y. (2005) A human transporter protein that mediates the final excretion step for toxic organic cations. Proc Natl Acad Sci USA, 102 (50): 17923-8. [PMID:16330770]

7. Tanihara Y, Masuda S, Sato T, Katsura T, Ogawa O, Inui K. (2007) Substrate specificity of MATE1 and MATE2-K, human multidrug and toxin extrusions/H(+)-organic cation antiporters. Biochem Pharmacol, 74 (2): 359-71. [PMID:17509534]

8. Terada T, Masuda S, Asaka J, Tsuda M, Katsura T, Inui K. (2006) Molecular cloning, functional characterization and tissue distribution of rat H+/organic cation antiporter MATE1. Pharm Res, 23 (8): 1696-701. [PMID:16850272]

9. Tsuda M, Terada T, Ueba M, Sato T, Masuda S, Katsura T, Inui K. (2009) Involvement of human multidrug and toxin extrusion 1 in the drug interaction between cimetidine and metformin in renal epithelial cells. J Pharmacol Exp Ther, 329 (1): 185-91. [PMID:19164462]

10. Yasujima T, Ohta KY, Inoue K, Ishimaru M, Yuasa H. (2010) Evaluation of 4',6-diamidino-2-phenylindole as a fluorescent probe substrate for rapid assays of the functionality of human multidrug and toxin extrusion proteins. Drug Metab Dispos, 38 (4): 715-21. [PMID:20047987]

Ken-ichi Inui Kyoto Pharmaceutical University Yamashina-ku Kyoto 607-8414, Japan