These proton:organic cation exchangers are predicted to have 13 TM segments [10] and are suggested to be responsible for excretion of many drugs in the liver and kidneys.

DAPI has been used to allow quantification of MATE1 and MATE2-mediated transport activity [9]. MATE2 and MATE2-B are inactive splice variants of MATE2-K [3].

* 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]

* 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]

1. Chen Y, Zhang S, Sorani M, Giacomini KM. (2007) Transport of paraquat by human organic cation transporters and multidrug and toxic compound extrusion family. J. Pharmacol. Exp. Ther., 322 (2): 695-700. [PMID:17495125]

2. Ito S, Kusuhara H, Kuroiwa Y, Wu C, Moriyama Y, Inoue K, Kondo T, Yuasa H, Nakayama H, Horita S et al.. (2010) Potent and specific inhibition of mMate1-mediated efflux of type I organic cations in the liver and kidney by pyrimethamine. J. Pharmacol. Exp. Ther., 333 (1): 341-50. [PMID:20065018]

3. 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]

4. 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]

5. 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. U.S.A., 102 (50): 17923-8. [PMID:16330770]

6. 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]

7. 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]

8. 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]

9. 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]

10. Zhang X, Wright SH. (2009) MATE1 has an external COOH terminus, consistent with a 13-helix topology. Am. J. Physiol. Renal Physiol., 297 (2): F263-71. [PMID:19515813]

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