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

Multidrug and toxin extrusion protein 2 (MATE2-K) is a transporter protein encoded by the SLC47A2 gene, primarily localized to the apical membrane of renal proximal tubule cells (UniProt, 2023; GeneCards, 2024). It functions as an H+/organic cation antiporter, facilitating the final step in the renal secretion of various endogenous and exogenous organic cations, including the widely used antidiabetic drug metformin (PubMed, 2006; Solvo Biotechnology, 2024). By mediating the efflux of these compounds from tubular cells into the urine, MATE2-K plays a critical role in drug disposition and detoxification (PubMed, 2011; IUPHAR/BPS, 2024). Inhibition of MATE2-K by co-administered drugs can lead to significant drug-drug interactions, resulting in reduced renal clearance and potentially toxic systemic accumulation of substrates (FDA, 2022; EMA, 2012). Consequently, it is a key focus of regulatory guidelines for evaluating the safety and pharmacokinetic profiles of new molecular entities (ICH, 2022; FDA, 2017). Genetic polymorphisms in the SLC47A2 gene may also contribute to interindividual variability in drug response and renal clearance (PubMed, 2015).

Other names

SLC47A2MATE2MATE2-BhMATE-2Solute carrier family 47 member 2Kidney-specific H(+)/organic cation antiporter

MATE2-K functions as an H+/organic cation antiporter that mediates the efflux of cationic drugs from renal tubular cells into the urine (UniProt, 2023; PubMed, 2016). Inhibition of MATE2-K reduces the renal clearance of substrate drugs, leading to increased systemic exposure and potential toxicity (FDA, 2022; PubMed, 2011).