Abcc2

Summary

Gene Symbol: Abcc2
Description: ATP-binding cassette, sub-family C (CFTR/MRP), member 2
Alias: AI173996, Abc30, Cmoat, Mrp2, cMRP, canalicular multispecific organic anion transporter 1, ATP-binding cassette sub-family C member 2, multidrug resistance protein 2
Species: mouse
Products:     Abcc2

Top Publications

  1. Carew M, Leslie E. Selenium-dependent and -independent transport of arsenic by the human multidrug resistance protein 2 (MRP2/ABCC2): implications for the mutual detoxification of arsenic and selenium. Carcinogenesis. 2010;31:1450-5 pubmed publisher
    ..The multidrug resistance protein 2 (MRP2/ABCC2) is an adenosine triphosphate (ATP)-binding cassette transporter expressed at the ..
  2. Franke R, Lancaster C, Peer C, Gibson A, Kosloske A, Orwick S, et al. Effect of ABCC2 (MRP2) transport function on erythromycin metabolism. Clin Pharmacol Ther. 2011;89:693-701 pubmed publisher
    ..By means of a transporter screen, erythromycin was identified as a substrate for the transporter ABCC2 (MRP2) and its murine ortholog, Abcc2...
  3. Chu X, Strauss J, Mariano M, Li J, Newton D, Cai X, et al. Characterization of mice lacking the multidrug resistance protein MRP2 (ABCC2). J Pharmacol Exp Ther. 2006;317:579-89 pubmed
    The multidrug resistance protein Mrp2 is an ATP-binding cassette (ABC) transporter mainly expressed in liver, kidney, and intestine...
  4. Maher J, Slitt A, Cherrington N, Cheng X, Klaassen C. Tissue distribution and hepatic and renal ontogeny of the multidrug resistance-associated protein (Mrp) family in mice. Drug Metab Dispos. 2005;33:947-55 pubmed
    ..Highest expression of the Mrp family members is as follows: Mrp1 in testes, ovary, and placenta; Mrp2 in intestine, followed by liver and kidney; Mrp3 in large intestine; Mrp4 in kidney; Mrp5 in brain, followed by ..
  5. Cherrington N, Estrada T, Frisk H, Canet M, Hardwick R, Dvorak B, et al. The hepatic bile acid transporters Ntcp and Mrp2 are downregulated in experimental necrotizing enterocolitis. Am J Physiol Gastrointest Liver Physiol. 2013;304:G48-56 pubmed publisher
    ..rat and mouse models of NEC, levels of Cyp7a1, Cyp27a1, and the hepatic BA transporters Bsep, Ntcp, Oatp2, Oatp4, Mrp2, and Mrp3 were investigated...
  6. Vlaming M, Pala Z, van Esch A, Wagenaar E, van Tellingen O, de Waart D, et al. Impact of Abcc2 (Mrp2) and Abcc3 (Mrp3) on the in vivo elimination of methotrexate and its main toxic metabolite 7-hydroxymethotrexate. Clin Cancer Res. 2008;14:8152-60 pubmed publisher
    ATP-binding cassette sub-family C member 2 [ABCC2; multidrug resistance-associated protein 2 (MRP2)] and ABCC3 (MRP3) mediate the elimination of toxic compounds, such as drugs and carcinogens, and have a large overlap in substrate ..
  7. Vlaming M, Mohrmann K, Wagenaar E, de Waart D, Elferink R, Lagas J, et al. Carcinogen and anticancer drug transport by Mrp2 in vivo: studies using Mrp2 (Abcc2) knockout mice. J Pharmacol Exp Ther. 2006;318:319-27 pubmed
    The ATP-binding-cassette (ABC) transporter multidrug resistance protein (MRP) 2 (ABCC2) forms a natural barrier and efflux system for various (conjugates of) drugs, other xenotoxins, and endogenous compounds...
  8. Bridges C, Joshee L, van den Heuvel J, Russel F, Zalups R. Glutathione status and the renal elimination of inorganic mercury in the Mrp2(-/-) mouse. PLoS ONE. 2013;8:e73559 pubmed publisher
    ..b>MRP2 has also been implicated in the renal and hepatic elimination of mercury...
  9. Shih D, Bussen M, Sehayek E, Ananthanarayanan M, Shneider B, Suchy F, et al. Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism. Nat Genet. 2001;27:375-82 pubmed
    ..Our studies demonstrate that Tcf1, in addition to being an important regulator of insulin secretion, is an essential transcriptional regulator of bile acid and HDL-cholesterol metabolism. ..

More Information

Publications54

  1. Scheer N, Balimane P, Hayward M, Buechel S, Kauselmann G, Wolf C. Generation and characterization of a novel multidrug resistance protein 2 humanized mouse line. Drug Metab Dispos. 2012;40:2212-8 pubmed publisher
    ..Mrp knockout [Mrp2(-/-)] mice have been used recently to study the role of MRP2 in drug disposition...
  2. Zimmermann C, van de Wetering K, van de Steeg E, Wagenaar E, Vens C, Schinkel A. Species-dependent transport and modulation properties of human and mouse multidrug resistance protein 2 (MRP2/Mrp2, ABCC2/Abcc2). Drug Metab Dispos. 2008;36:631-40 pubmed publisher
    b>Multidrug resistance protein 2 (MRP2/Mrp2) is a transporter that can influence the absorption, distribution, and elimination of many drugs...
  3. van de Steeg E, Stránecký V, Hartmannova H, Noskova L, Hrebicek M, Wagenaar E, et al. Complete OATP1B1 and OATP1B3 deficiency causes human Rotor syndrome by interrupting conjugated bilirubin reuptake into the liver. J Clin Invest. 2012;122:519-28 pubmed publisher
    ..Moreover, OATP1B1 and OATP1B3 null mutations may confer substantial drug toxicity risks. ..
  4. Zalups R, Joshee L, Bridges C. Novel Hg2+-induced nephropathy in rats and mice lacking Mrp2: evidence of axial heterogeneity in the handling of Hg2+ along the proximal tubule. Toxicol Sci. 2014;142:250-60 pubmed publisher
    The role of the multi-resistance protein 2 (Mrp2) in the nephropathy induced by inorganic mercuric mercury (Hg(2+)) was studied in rats (TR(-)) and mice (Mrp2(-/-)), which lack functional Mrp2, and control animals...
  5. Konig J, Nies A, Cui Y, Leier I, Keppler D. Conjugate export pumps of the multidrug resistance protein (MRP) family: localization, substrate specificity, and MRP2-mediated drug resistance. Biochim Biophys Acta. 1999;1461:377-94 pubmed
    ..Studies in mutant rats lacking the apical isoform MRP2 (symbol ABCC2) indicate that anionic conjugates of endogenous and exogenous substances cannot exit from cells at a sufficient ..
  6. Fritz F, Chen J, Hayes P, Sirotnak F. Molecular cloning of the murine cMOAT ATPase. Biochim Biophys Acta. 2000;1492:531-6 pubmed
    b>cMOAT encodes an ATPase within the family of cMOAT/MRP ATPases that functions as an ATP dependent, multispecific anion transporter within the canalicular surface of hepatocytes that has pharmacologic significance...
  7. Tanaka Y, Yoshikawa M, Kobayashi Y, Kuroda M, Kaito M, Shiroi A, et al. Expressions of hepatobiliary organic anion transporters and bilirubin-conjugating enzyme in differentiating embryonic stem cells. Biochem Biophys Res Commun. 2003;309:324-30 pubmed
    ..expression of organic anion transporting polypeptide 1 (oatp1), multidrug resistance-associated protein 1 (mrp1), mrp2, mrp3, and ugt1a1 was not seen in the undifferentiated HNF-3beta-ES cells by RT-PCR, whereas all were expressed in ..
  8. Qu W, Pi J, Waalkes M. Metallothionein blocks oxidative DNA damage in vitro. Arch Toxicol. 2013;87:311-21 pubmed publisher
    ..Cd or H(2)O(2) exposure increased the expression of key transport genes, Mrp1 and Mrp2, in WT cells but not in MT-null cells...
  9. Vlaming M, Teunissen S, van de Steeg E, van Esch A, Wagenaar E, Brunsveld L, et al. Bcrp1;Mdr1a/b;Mrp2 combination knockout mice: altered disposition of the dietary carcinogen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) and its genotoxic metabolites. Mol Pharmacol. 2014;85:520-30 pubmed publisher
    ..food-derived carcinogen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) is transported by BCRP, MDR1, and MRP2. To investigate the overlapping functions of Bcrp1, Mdr1a/b, and Mrp2 in vivo, we generated Bcrp1;Mdr1a/b;Mrp2(-/-) ..
  10. Zamek Gliszczynski M, Nezasa K, Tian X, Kalvass J, Patel N, Raub T, et al. The important role of Bcrp (Abcg2) in the biliary excretion of sulfate and glucuronide metabolites of acetaminophen, 4-methylumbelliferone, and harmol in mice. Mol Pharmacol. 2006;70:2127-33 pubmed
    ..sulfate (4MUS) and glucuronide (4MUG), and harmol sulfate (HS) and glucuronide (HG) was studied in Abcc2(-/-), Abcg2(-/-), and Abcb1a(-/-)/Abcb1b(-/-) mouse livers perfused with the respective parent compounds using a ..
  11. Simon F, Iwahashi M, Hu L, Qadri I, Arias I, Ortiz D, et al. Hormonal regulation of hepatic multidrug resistance-associated protein 2 (Abcc2) primarily involves the pattern of growth hormone secretion. Am J Physiol Gastrointest Liver Physiol. 2006;290:G595-608 pubmed
    ..Multidrug resistance-associated protein 2 (Mrp2, Abcc2) is the major transporter for conjugated endo- and xenobiotic-conjugated compounds into bile...
  12. Suriyapperuma S, Lozovatsky L, Ciciotte S, Peters L, Gilligan D. The mouse adducin gene family: alternative splicing and chromosomal localization. Mamm Genome. 2000;11:16-23 pubmed
    ..We also report here the localization of the gene encoding gamma adducin (Add3) to murine Chr 19, in a region that shows conserved synteny with human Chr 10. ..
  13. Schriml L, Dean M. Identification of 18 mouse ABC genes and characterization of the ABC superfamily in Mus musculus. Genomics. 2000;64:24-31 pubmed
    ..The mouse ABC genes could be grouped into the seven previously described human ABC subfamilies. Three mouse ABC genes mapped to regions implicated in cholesterol gallstone susceptibility...
  14. Geier A, Mertens P, Gerloff T, Dietrich C, En Nia A, Kullak Ublick G, et al. Constitutive rat multidrug-resistance protein 2 gene transcription is down-regulated by Y-box protein 1. Biochem Biophys Res Commun. 2003;309:612-8 pubmed
    Molecular mechanisms underlying transcriptional rat multidrug-resistance protein 2 (Mrp2, Abcc2) gene regulation are mostly unclear...
  15. Borst P, Evers R, Kool M, Wijnholds J. A family of drug transporters: the multidrug resistance-associated proteins. J Natl Cancer Inst. 2000;92:1295-302 pubmed
    ..However, MRP1, MRP2, and MRP3 can also cause resistance to neutral organic drugs that are not known to be conjugated to acidic ligands ..
  16. Borst P, Evers R, Kool M, Wijnholds J. The multidrug resistance protein family. Biochim Biophys Acta. 1999;1461:347-57 pubmed
    ..MRP1, the godfather of the family and well known as the multidrug resistance protein, and five homologs, called MRP2-6...
  17. Pfister S, Jones V, Power M, Truisi G, Khoo P, Steiner K, et al. Sox17-dependent gene expression and early heart and gut development in Sox17-deficient mouse embryos. Int J Dev Biol. 2011;55:45-58 pubmed publisher
    ..This is associated with the defective development of the heart in the mutant embryos, which is accompanied by localised loss of Myocd-expressing cardiogenic progenitors and the malformation of the anterior intestinal portal. ..
  18. Kikuchi S, Hata M, Fukumoto K, Yamane Y, Matsui T, Tamura A, et al. Radixin deficiency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes. Nat Genet. 2002;31:320-5 pubmed
    ..to human conjugated hyperbilirubinemia in Dubin-Johnson syndrome, which is caused by mutations in the multidrug resistance protein 2 (MRP2, gene symbol ABCC2), although this syndrome is not associated with overt liver injury...
  19. de Waart D, Vlaming M, Kunne C, Schinkel A, Oude Elferink R. Complex pharmacokinetic behavior of ezetimibe depends on abcc2, abcc3, and abcg2. Drug Metab Dispos. 2009;37:1698-702 pubmed publisher
    ..Presently, it is not clear which mechanisms are responsible for this efficient enterohepatic circulation. Abcc2, Abcc3, and Abcg2 are ATP-binding cassette (ABC) transporters that are expressed in both liver and intestine and ..
  20. Krumpochova P, Sapthu S, Brouwers J, de Haas M, de Vos R, Borst P, et al. Transportomics: screening for substrates of ABC transporters in body fluids using vesicular transport assays. FASEB J. 2012;26:738-47 pubmed publisher
    ..We illustrate the power of this simple "transportomics" approach using ABCC2, a protein present at sites of uptake and elimination. We identified many new substrates of ABCC2 in urine...
  21. Cantore M, Reinehr R, Sommerfeld A, Becker M, Haussinger D. The Src family kinase Fyn mediates hyperosmolarity-induced Mrp2 and Bsep retrieval from canalicular membrane. J Biol Chem. 2011;286:45014-29 pubmed publisher
    In perfused rat liver, hyperosmolarity induces Mrp2- (Kubitz, R., D'urso, D., Keppler, D., and Häussinger, D. (1997) Gastroenterology 113, 1438-1442) and Bsep retrieval (Schmitt, M., Kubitz, R., Lizun, S., Wettstein, M...
  22. Kruh G, Belinsky M, Gallo J, Lee K. Physiological and pharmacological functions of Mrp2, Mrp3 and Mrp4 as determined from recent studies on gene-disrupted mice. Cancer Metastasis Rev. 2007;26:5-14 pubmed
    ..Recently, mice with gene disruptions in Mrp2, Mrp3 and Mrp4 have been developed...
  23. Bauer B, Hartz A, Lucking J, Yang X, Pollack G, Miller D. Coordinated nuclear receptor regulation of the efflux transporter, Mrp2, and the phase-II metabolizing enzyme, GSTpi, at the blood-brain barrier. J Cereb Blood Flow Metab. 2008;28:1222-34 pubmed publisher
    ..expression and transport activity of another efflux pump, multidrug resistance-associated protein isoform 2 (Mrp2), in rat brain capillaries after in vitro and in vivo exposure to PCN and dexamethasone...
  24. Li M, Soroka C, Harry K, Boyer J. CFTR-associated ligand is a negative regulator of Mrp2 expression. Am J Physiol Cell Physiol. 2017;312:C40-C46 pubmed publisher
    The multidrug resistance-associated protein 2 (Mrp2) is an ATP-binding cassette transporter that transports a wide variety of organic anions across the apical membrane of epithelial cells...
  25. Soontornmalai A, Vlaming M, Fritschy J. Differential, strain-specific cellular and subcellular distribution of multidrug transporters in murine choroid plexus and blood-brain barrier. Neuroscience. 2006;138:159-69 pubmed
    ..We report that four ATP-binding cassette transporters, Mdr1, Mrp1, Mrp2 and Mrp5 can be detected in brain endothelial cells, forming three distinct layers, with Mdr1 and Mrp5 being ..
  26. Paigen B, Schork N, Svenson K, Cheah Y, Mu J, Lammert F, et al. Quantitative trait loci mapping for cholesterol gallstones in AKR/J and C57L/J strains of mice. Physiol Genomics. 2000;4:59-65 pubmed
    ..L-Lith2(s). Other suggestive, but not statistically significant, loci mapped to chromosomes 6, 7, 8, 10, and X. The identification of these Lith genes will elucidate the pathophysiology of cholesterol gallstone formation...
  27. Ji W, Herron B, Jones J, Jenkins N, Gilbert D, Copeland N, et al. Identification of genes within the Krd deletion on mouse chromosome 19. Mamm Genome. 1999;10:399-401 pubmed
  28. Vlaming M, van Esch A, Pala Z, Wagenaar E, van de Wetering K, van Tellingen O, et al. Abcc2 (Mrp2), Abcc3 (Mrp3), and Abcg2 (Bcrp1) are the main determinants for rapid elimination of methotrexate and its toxic metabolite 7-hydroxymethotrexate in vivo. Mol Cancer Ther. 2009;8:3350-9 pubmed publisher
    The multidrug transporters ABCC2, ABCC3, and ABCG2 can eliminate potentially toxic compounds from the body and have overlapping substrate specificities...
  29. Tsirulnikov K, Abuladze N, Koag M, Newman D, Scholz K, Bondar G, et al. Transport of N-acetyl-S-(1,2-dichlorovinyl)-L-cysteine, a metabolite of trichloroethylene, by mouse multidrug resistance associated protein 2 (Mrp2). Toxicol Appl Pharmacol. 2010;244:218-25 pubmed publisher
    ..apical transport of Ac-DCVC and/or DCVC may be mediated by the multidrug resistance associated protein 2 (Mrp2, ABCC2), which is known to mediate proximal tubular apical ATP-dependent transport of glutathione and numerous ..
  30. Pazos M, Siccardi D, Mumy K, Bien J, Louie S, Shi H, et al. Multidrug resistance-associated transporter 2 regulates mucosal inflammation by facilitating the synthesis of hepoxilin A3. J Immunol. 2008;181:8044-52 pubmed
    ..is a substrate for the apical efflux ATP-binding protein transporter multidrug resistance-associated protein 2 (MRP2)...
  31. Gavrilova O, Geyer J, Petzinger E. In vivo relevance of Mrp2-mediated biliary excretion of the Amanita mushroom toxin demethylphalloin. Biochim Biophys Acta. 2007;1768:2070-7 pubmed
    ..elimination, hepatobiliary [(3)H]-demethylphalloin (DMP) excretion was studied in normal Wistar rats and in Mrp2 deficient TR(-) Wistar rats as well as in normal wild-type FVB mice, Mdr1a,b(-/-) knockout mice, and Bcrp1(-/-) ..
  32. Wang Z, Zhou Q, Kruh G, Gallo J. Dose-dependent disposition of methotrexate in Abcc2 and Abcc3 gene knockout murine models. Drug Metab Dispos. 2011;39:2155-61 pubmed publisher
    ..To investigate the effects of two transporters-ABC subfamily C member 2 (Abcc2; multidrug resistance protein 2) and ABC subfamily C member 3 (Abcc3; multidrug resistance protein 3)-involved in MTX hepatobiliary ..
  33. Elamiri A, Perwaiz S, Tuchweber B, Yousef I. Effect of mdr2 mutation with combined tandem disruption of canalicular glycoprotein transporters by cyclosporine A on bile formation in mice. Pharmacol Res. 2003;48:467-72 pubmed
  34. Wen X, Buckley B, McCandlish E, Goedken M, Syed S, PELIS R, et al. Transgenic expression of the human MRP2 transporter reduces cisplatin accumulation and nephrotoxicity in Mrp2-null mice. Am J Pathol. 2014;184:1299-308 pubmed publisher
    ..Previous studies suggest that the multidrug resistance-associated protein 2 (Mrp2) transporter may efflux cisplatin conjugates from cells...
  35. Oh J, Lee J, Han D, Cho S, Lee Y. Circadian Clock Is Involved in Regulation of Hepatobiliary Transport Mediated by Multidrug Resistance-Associated Protein 2. J Pharm Sci. 2017;106:2491-2498 pubmed publisher
    ..we investigated circadian rhythm in the expression and function of multidrug resistance-associated protein 2 (Mrp2) in mouse liver and involvement of circadian clock in their regulations by using the circadian clock genes (period ..
  36. Vasilyeva A, Durmus S, Li L, Wagenaar E, Hu S, Gibson A, et al. Hepatocellular Shuttling and Recirculation of Sorafenib-Glucuronide Is Dependent on Abcc2, Abcc3, and Oatp1a/1b. Cancer Res. 2015;75:2729-36 pubmed publisher
    ..mouse models, we show here that sorafenib-glucuronide can be extruded from hepatocytes into the bile by Abcc2 or back into the systemic circulation by Abcc3, and that it can be taken up efficiently again into neighboring ..
  37. Ito K, Suzuki H, Hirohashi T, Kume K, Shimizu T, Sugiyama Y. Functional analysis of a canalicular multispecific organic anion transporter cloned from rat liver. J Biol Chem. 1998;273:1684-8 pubmed
    ..across the bile canalicular membrane is mediated by the canalicular multispecific organic anion transporter (cMOAT). Previously, we cloned cDNA that may encode cMOAT from Sprague-Dawley rat liver (Ito, K., Suzuki, H...
  38. Okyar A, Piccolo E, Ahowesso C, Filipski E, Hossard V, Guettier C, et al. Strain- and sex-dependent circadian changes in abcc2 transporter expression: implications for irinotecan chronotolerance in mouse ileum. PLoS ONE. 2011;6:e20393 pubmed publisher
    ATP-binding cassette transporter abcc2 is involved in the cellular efflux of irinotecan. The drug is toxic for mouse ileum, where abcc2 is highly expressed...
  39. Li M, Wang W, Soroka C, Mennone A, Harry K, Weinman E, et al. NHERF-1 binds to Mrp2 and regulates hepatic Mrp2 expression and function. J Biol Chem. 2010;285:19299-307 pubmed publisher
    Multidrug resistance-associated protein 2 (Mrp2, Abcc2) is an ATP-binding cassette transporter localized at the canalicular membrane of hepatocytes that plays an important role in bile formation and detoxification...
  40. Paulusma C, de Waart D, Kunne C, Mok K, Elferink R. Activity of the bile salt export pump (ABCB11) is critically dependent on canalicular membrane cholesterol content. J Biol Chem. 2009;284:9947-54 pubmed publisher
    ..Using single pass liver perfusions, we show that not only ABCB11-mediated transport but also Abcc2-mediated transport were reduced at least 4-fold in Atp8b1 deficiency...
  41. van de Wetering K, Zelcer N, Kuil A, Feddema W, Hillebrand M, Vlaming M, et al. Multidrug resistance proteins 2 and 3 provide alternative routes for hepatic excretion of morphine-glucuronides. Mol Pharmacol. 2007;72:387-94 pubmed
    ..demonstrate that morphine-3-glucuronide (M3G), the predominant metabolite, is transported in vitro by human MRP2 (ABCC2), a protein present in the apical membrane of hepatocytes...
  42. Sekine T, Miyazaki H, Endou H. Molecular physiology of renal organic anion transporters. Am J Physiol Renal Physiol. 2006;290:F251-61 pubmed
    ..We will also discuss the physiological roles of each organic anion transporter in the light of the transepithelial transport of organic anions in the kidneys...
  43. Lammert F, Cohen D, Paigen B, Carey M, Beier D. The gene encoding the multispecific organic anion transporter (Cmoat) of the hepatocyte canalicular membrane maps to mouse chromosome 19. Mamm Genome. 1998;9:87-8 pubmed
  44. Vollrath V, Wielandt A, Iruretagoyena M, Chianale J. Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene. Biochem J. 2006;395:599-609 pubmed
    ..The Mrp2 (multidrug-resistance protein 2) pump mediates the excretion of GSH and GSSG excretion as well as endo- and xeno-..