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

Multidrug and toxin extrusion protein 2-K (MATE2-K) is a human kidney-specific efflux transporter, encoded by the SLC47A2 gene, and is primarily localized to the apical membrane of renal proximal tubule epithelial cells[1][2][3]. It functions as a H+/organic cation antiporter, mediating the export of diverse endogenous and exogenous organic cations, including major drugs like metformin[1][3][4]. MATE2-K operates in tandem with basolateral organic cation transporter OCT2 to enable the active, vectorial secretion of organic cations from blood into urine[1][3]. It displays broad substrate specificity and is an important modulator of drug pharmacokinetics and drug–drug interactions, given its overlapping recognition for drugs and inhibitors with other cation transporters such as MATE1 and OCT2[4][6]. Human MATE2-K has a major clinical significance due to its essential role in the renal elimination of drugs and other cations; genetic polymorphisms can significantly impact drug response and toxicity, particularly for drugs with a narrow therapeutic index such as metformin[1][3]. MATE2-K is considered a key therapeutic target for modulating renal drug excretion and is increasingly recognized as a critical determinant in drug safety and efficacy in pharmacogenomic and clinical pharmacology settings[3][4][5].

Other names

MATE2-KMATE2KMATE2-B (less commonly, but note that functional activity for MATE2-B has not been demonstrated in humans)hMATE-2KSolute carrier family 47 member 2 (kidney isoform)SLC47A2 (gene name)

Substrate transport: mediates efflux (transport out of cells) of cationic drugs from renal tubular epithelial cells to urine, using a proton gradient as a driving force Drug–drug interaction: MATE2-K can be inhibited by drugs that are also substrates or inhibitors of organic cation transporters (OCTs), resulting in altered pharmacokinetics