8rq4

Structural highlights

Disease

MRP2_RAT Defects in Abcc2 are a cause of hereditary conjugated hyperbilirubinemia (EHBR).^[1] [REFERENCE:3]

Function

MRP2_RAT ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:8662992, PubMed:10421658, PubMed:10220572, PubMed:11248200). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:10220572, PubMed:8662992). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:11248200). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (By similarity).[UniProtKB:Q92887]^{[2] [3] [4] [5]}

References

1. ↑ Paulusma CC, Bosma PJ, Zaman GJ, Bakker CT, Otter M, Scheffer GL, Scheper RJ, Borst P, Oude Elferink RP. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science. 1996 Feb 23;271(5252):1126-8. PMID:8599091 doi:10.1126/science.271.5252.1126
2. ↑ Cui Y, König J, Buchholz JK, Spring H, Leier I, Keppler D. Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells. Mol Pharmacol. 1999 May;55(5):929-37 PMID:10220572
3. ↑ Kamisako T, Leier I, Cui Y, König J, Buchholz U, Hummel-Eisenbeiss J, Keppler D. Transport of monoglucuronosyl and bisglucuronosyl bilirubin by recombinant human and rat multidrug resistance protein 2. Hepatology. 1999 Aug;30(2):485-90. PMID:10421658 doi:10.1002/hep.510300220
4. ↑ Akita H, Suzuki H, Ito K, Kinoshita S, Sato N, Takikawa H, Sugiyama Y. Characterization of bile acid transport mediated by multidrug resistance associated protein 2 and bile salt export pump. Biochim Biophys Acta. 2001 Mar 9;1511(1):7-16. PMID:11248200 doi:10.1016/s0005-2736(00)00355-2
5. ↑ Büchler M, König J, Brom M, Kartenbeck J, Spring H, Horie T, Keppler D. cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats. J Biol Chem. 1996 Jun 21;271(25):15091-8. PMID:8662992 doi:10.1074/jbc.271.25.15091