Multidrug resistance-associated protein 2 (MRP2) and Multidrug resistance-associated protein 4 (MRP4) (MRP2 and MRP4)

Multidrug resistance-associated protein 2 (MRP2, ABCC2) and Multidrug resistance-associated protein 4 (MRP4, ABCC4) are members of the ATP-binding cassette (ABC) transporter superfamily (UniProt P51812; UniProt O15439). MRP2 is primarily localized to the apical membranes of polarized cells, such as the canalicular membrane of hepatocytes and the brush border of renal proximal tubules, where it mediates the efflux of organic anions, including bilirubin glucuronides and various drug conjugates (PubMed: 11159801). MRP4 has a broader tissue distribution and transports a wide range of substrates, including cyclic nucleotides, prostaglandins, and antiviral or chemotherapeutic drugs (PubMed: 12765648). Both transporters are critical determinants of drug disposition and are frequently involved in multidrug resistance (MDR) in cancer by actively pumping therapeutic agents out of malignant cells (PubMed: 15102446). Genetic mutations in ABCC2 lead to Dubin-Johnson syndrome, characterized by conjugated hyperbilirubinemia (NIH: Genetic and Rare Diseases Information Center). Because they share overlapping substrate specificities and roles in drug clearance, they are often studied together in the context of pharmacokinetics and potential drug-drug interactions.

Other names

ABCC2ABCC4Canalicular multispecific organic anion transporter 1cMOATMRP2MRP4Multidrug resistance-associated protein 2Multidrug resistance-associated protein 4

ATP-dependent efflux of endogenous and exogenous organic anions and conjugates across cellular membranes.