Multidrug and toxin extrusion protein 1 and 2-K (MATE1 and MATE2-K) (MATE1/2-K)

Multidrug and toxin extrusion protein 1 (MATE1) and 2-K (MATE2-K) are essential membrane transporters belonging to the SLC47 family that mediate the efflux of organic cations and xenobiotics from cells [1, 3]. Encoded by the SLC47A1 and SLC47A2 genes, these proteins function as H+/organic cation antiporters, utilizing an oppositely directed proton gradient to drive the secretion of substrates into the urine and bile [5, 8]. MATE1 is widely expressed in the kidney, liver, and other tissues, while MATE2-K is primarily localized to the apical membrane of renal proximal tubule cells [2, 11]. They play a pivotal role in the elimination of numerous drugs, most notably the first-line type 2 diabetes medication metformin, as well as various toxins and endogenous metabolites like creatinine [4, 15]. Because many clinically used drugs are substrates or inhibitors of MATE transporters, they are frequent sites of significant drug-drug interactions that can alter systemic drug exposure and increase the risk of adverse effects, such as metformin-associated lactic acidosis or enhanced cisplatin-induced nephrotoxicity [6, 12]. Consequently, MATE1 and MATE2-K are critical targets for pharmacokinetic evaluation during drug development to ensure therapeutic safety and efficacy [13, 14].

Other names

SLC47A1 [1, 11]SLC47A2 [2, 11]Solute carrier family 47 member 1 [1, 11]Solute carrier family 47 member 2 [2, 11]MATE1 [1, 11]MATE2-K [2, 11]H+/organic cation antiporter [5, 11]

H+/organic cation antiport; Inhibition of transport activity; Substrate for efflux transport [1, 5, 11]