Multidrug and toxic compound extrusion protein 2 (MATE2-K) (MATE2-K)

Multidrug and toxic compound extrusion protein 2 (MATE2-K) is a transmembrane protein encoded by the SLC47A2 gene, primarily expressed on the apical membrane of renal proximal tubule cells (UniProt: Q86VL8). It functions as an H+/organic cation antiporter, utilizing the proton gradient to drive the efflux of various cationic drugs and endogenous compounds from the cytoplasm into the tubular lumen for urinary excretion (PubMed: 17908936). MATE2-K is a critical determinant of the renal clearance of several widely used medications, most notably the anti-diabetic drug metformin (PubMed: 23135661). Inhibition of MATE2-K by co-administered drugs, such as cimetidine or dolutegravir, can lead to decreased renal clearance and increased systemic exposure of its substrates, potentially resulting in toxicity or altered therapeutic efficacy (FDA: Drug Development and Drug Interactions). Consequently, MATE2-K is recognized by regulatory agencies as a key transporter to be evaluated during drug development to assess the risk of clinically significant drug-drug interactions. Beyond drug transport, it also handles endogenous metabolites like N1-methylnicotinamide, which serves as a potential biomarker for its in vivo activity (PubMed: 26861979). The protein's activity is essential for maintaining the balance of organic cations in the body and preventing the accumulation of potentially toxic substances in renal cells. Genetic polymorphisms in the SLC47A2 gene have been associated with variations in metformin response and disposition, highlighting its clinical relevance in personalized medicine (PubMed: 21143751).

Other names

SLC47A2Solute carrier family 47 member 2MATE2-KMATE2Multidrug and toxin extrusion protein 2

MATE2-K functions as an H+/organic cation antiporter, facilitating the efflux of cationic drugs and endogenous compounds from renal tubular cells into the urine.