Multidrug and toxin extrusion protein 2K (MATE2-K)

Multidrug and toxin extrusion protein 2K (MATE2-K), encoded by the SLC47A2 gene, is a critical membrane transporter primarily located on the apical membrane of renal proximal tubule cells [1, 2]. As a proton-coupled organic cation antiporter, it utilizes the inwardly directed proton gradient to facilitate the extrusion of organic cations and various xenobiotics from the intracellular compartment into the tubular lumen for urinary excretion [2, 3]. MATE2-K serves as the final gateway for the renal elimination of many clinically significant drugs, most notably the first-line anti-diabetic medication metformin [4, 5]. Because it handles a wide array of cationic substrates, it is a major site for clinically relevant drug-drug interactions (DDIs) [6]. Inhibition of MATE2-K by common medications such as cimetidine or dolutegravir can significantly decrease the renal clearance of co-administered substrates, leading to elevated plasma concentrations and increased risk of adverse effects like lactic acidosis [5, 7]. Consequently, regulatory agencies such as the FDA and EMA require the evaluation of MATE2-K interaction potential during the development of new drug candidates to ensure safety and predictable pharmacokinetics [6, 8]. Sources: [1] UniProt Consortium. (2023). SLC47A2 - Multidrug and toxin extrusion protein 2. [2] Masuda, S., et al. (2006). Molecular cloning and characterization of human MATE2-K. Journal of the American Society of Nephrology. [3] Otsuka, M., et al. (2005). A human transporter in the MATE family. PNAS. [4] DrugBank Online. (2024). Metformin (DB00331). [5] Nies, A. T., et al. (2011). Expression of drug transporters in human kidney: impact of MATE1 and MATE2-K. Pflugers Archiv. [6] FDA. (2020). In Vitro Drug Interaction Studies - Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance for Industry. [7] Tsuda, M., et al. (2009). Involvement of human multidrug and toxin extrusion (MATE) transporters in the efflux and renal secretion of organic cations. J Pharmacol Exp Ther. [8] Hillgren, K. M., et al. (2013). Emerging transporters of clinical importance: an ITC white paper. Clinical Pharmacology & Therapeutics.

Other names

Solute carrier family 47 member 2SLC47A2H(+)/organic cation antiporter 2MATE2MATE-2K

Drugs typically act as competitive inhibitors of the MATE2-K transporter, reducing the efflux of substrate drugs from renal proximal tubule cells into the tubular lumen, thereby increasing systemic drug exposure and potentially leading to toxicity.