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Gene Review

ABCC3  -  ATP-binding cassette, sub-family C...

Homo sapiens

Synonyms: ABC31, ATP-binding cassette sub-family C member 3, CMOAT2, Canalicular multispecific organic anion transporter 2, EST90757, ...
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Disease relevance of ABCC3


High impact information on ABCC3

  • Re: Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins [4].
  • MOAT-D is also highly related to cMOAT (about 47% identity) [5].
  • MOAT-C transcripts are widely expressed in human tissues; however, MOAT-D transcript expression is more restricted [5].
  • Double immunofluorescence microscopy using 2 specific antibodies for the respective MRP isoform showed the simultaneous expression of MRP2 in the apical membrane and MRP3 in the basolateral membrane of gallbladder epithelia [6].
  • By using morphine as a model aglycone, we demonstrate that multidrug resistance protein 3 (MRP3/ABCC3), a protein present in the basolateral membrane of polarized cells, transports morphine-3-glucuronide (M3G) and morphine-6-glucuronide in vitro [7].

Chemical compound and disease context of ABCC3


Biological context of ABCC3


Anatomical context of ABCC3

  • Localization of MRP2 and MRP3 may provide an explanation of how the products of phase II conjugation are effluxed from gallbladder epithelia [6].
  • Cell lines were retrovirally transduced with MRP3 cDNA, and new monoclonal antibodies specific for MRP3 were generated [2].
  • The multidrug resistance-associated protein 3 (MRP3) is associated with a poor outcome in childhood ALL and may account for the worse prognosis in male patients and T-cell immunophenotype [3].
  • The ATP-dependent uptake of [(3)H]taurocholate (TC), [(14)C]glycocholate (GC), [(3)H]taurochenodeoxycholate-3-sulfate (TCDC-S), and [(3)H]taurolithocholate-3-sulfate (TLC-S) was markedly stimulated by Mrp3 transfection in LLC-PK1 cells [15].
  • MRP3 mediates the ATP-dependent transport of anionic conjugates, particularly of glucuronides and sulfoconjugates, across the basolateral hepatocyte membrane into sinusoidal blood [1].

Associations of ABCC3 with chemical compounds

  • Neither 2008 cells nor Madin-Darby canine kidney II cells overexpressing MRP3 showed an increase in glutathione export or a decrease in the level of intracellular glutathione, in contrast to cells overexpressing MRP1 or MRP2 [2].
  • In short-term drug exposure experiments, MRP3 also confers high-level resistance to methotrexate [2].
  • Higher levels of MRP3 were found in patients with a poor in vivo response to prednisone, but this could not be confirmed in an independent case-control study (40 patients) for prednisone response [3].
  • In contrast to MRP1, cMOAT, and all other characterized mammalian ABC transporters, however, MRP3 is active in the transport of the monoanionic human bile constituent glycocholate [13].
  • Furthermore, sulphated bile salts were high-affinity competitive inhibitors of etoposide glucuronide transport by MRP3 (IC50 approximately 10 microM) [16].

Physical interactions of ABCC3


Regulatory relationships of ABCC3

  • MRP1 and MRP3 were the most abundantly expressed genes in placenta but only MRP1 was highly expressed in the BeWo cells [18].
  • In summary, KLF6 and HSF4 are stimuli-specific regulatory elements which may be important in the control of the rat mdr1b and mrp3 genes during health and disease [17].

Other interactions of ABCC3


Analytical, diagnostic and therapeutic context of ABCC3


  1. Hepatic secretion of conjugated drugs and endogenous substances. Keppler, D., König, J. Semin. Liver Dis. (2000) [Pubmed]
  2. MRP3, an organic anion transporter able to transport anti-cancer drugs. Kool, M., van der Linden, M., de Haas, M., Scheffer, G.L., de Vree, J.M., Smith, A.J., Jansen, G., Peters, G.J., Ponne, N., Scheper, R.J., Elferink, R.P., Baas, F., Borst, P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  3. The multidrug resistance-associated protein 3 (MRP3) is associated with a poor outcome in childhood ALL and may account for the worse prognosis in male patients and T-cell immunophenotype. Steinbach, D., Wittig, S., Cario, G., Viehmann, S., Mueller, A., Gruhn, B., Haefer, R., Zintl, F., Sauerbrey, A. Blood (2003) [Pubmed]
  4. Re: Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. Cole, S.P. J. Natl. Cancer Inst. (1999) [Pubmed]
  5. Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. Belinsky, M.G., Bain, L.J., Balsara, B.B., Testa, J.R., Kruh, G.D. J. Natl. Cancer Inst. (1998) [Pubmed]
  6. Expression and localization of the multidrug resistance proteins MRP2 and MRP3 in human gallbladder epithelia. Rost, D., König, J., Weiss, G., Klar, E., Stremmel, W., Keppler, D. Gastroenterology (2001) [Pubmed]
  7. Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception. Zelcer, N., van de Wetering, K., Hillebrand, M., Sarton, E., Kuil, A., Wielinga, P.R., Tephly, T., Dahan, A., Beijnen, J.H., Borst, P. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  8. Isolation of a novel human canalicular multispecific organic anion transporter, cMOAT2/MRP3, and its expression in cisplatin-resistant cancer cells with decreased ATP-dependent drug transport. Uchiumi, T., Hinoshita, E., Haga, S., Nakamura, T., Tanaka, T., Toh, S., Furukawa, M., Kawabe, T., Wada, M., Kagotani, K., Okumura, K., Kohno, K., Akiyama, S., Kuwano, M. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  9. The apical conjugate efflux pump ABCC2 (MRP2). Nies, A.T., Keppler, D. Pflugers Arch. (2007) [Pubmed]
  10. Multidrug resistance proteins MRP3, MRP1, and MRP2 in lung cancer: correlation of protein levels with drug response and messenger RNA levels. Young, L.C., Campling, B.G., Cole, S.P., Deeley, R.G., Gerlach, J.H. Clin. Cancer Res. (2001) [Pubmed]
  11. Mice lacking Mrp3 (Abcc3) have normal bile salt transport, but altered hepatic transport of endogenous glucuronides. Zelcer, N., van de Wetering, K., de Waart, R., Scheffer, G.L., Marschall, H.U., Wielinga, P.R., Kuil, A., Kunne, C., Smith, A., van der Valk, M., Wijnholds, J., Elferink, R.O., Borst, P. J. Hepatol. (2006) [Pubmed]
  12. Multidrug resistance protein (MRP) 1 and MRP3 attenuate cytotoxic and transactivating effects of the cyclopentenone prostaglandin, 15-deoxy-Delta(12,14)prostaglandin J2 in MCF7 breast cancer cells. Paumi, C.M., Wright, M., Townsend, A.J., Morrow, C.S. Biochemistry (2003) [Pubmed]
  13. Transport of amphipathic anions by human multidrug resistance protein 3. Zeng, H., Liu, G., Rea, P.A., Kruh, G.D. Cancer Res. (2000) [Pubmed]
  14. Expression of multidrug resistance protein-3 (multispecific organic anion transporter-D) in human embryonic kidney 293 cells confers resistance to anticancer agents. Zeng, H., Bain, L.J., Belinsky, M.G., Kruh, G.D. Cancer Res. (1999) [Pubmed]
  15. ATP-dependent transport of bile salts by rat multidrug resistance-associated protein 3 (Mrp3). Hirohashi, T., Suzuki, H., Takikawa, H., Sugiyama, Y. J. Biol. Chem. (2000) [Pubmed]
  16. Transport of bile acids in multidrug-resistance-protein 3-overexpressing cells co-transfected with the ileal Na+-dependent bile-acid transporter. Zelcer, N., Saeki, T., Bot, I., Kuil, A., Borst, P. Biochem. J. (2003) [Pubmed]
  17. KLF6 and HSF4 transcriptionally regulate multidrug resistance transporters during inflammation. Ho, E.A., Piquette-Miller, M. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  18. Effects of maturation on RNA transcription and protein expression of four MRP genes in human placenta and in BeWo cells. Pascolo, L., Fernetti, C., Pirulli, D., Crovella, S., Amoroso, A., Tiribelli, C. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  19. ATP-binding cassette superfamily transporter gene expression in human soft tissue sarcomas. Oda, Y., Saito, T., Tateishi, N., Ohishi, Y., Tamiya, S., Yamamoto, H., Yokoyama, R., Uchiumi, T., Iwamoto, Y., Kuwano, M., Tsuneyoshi, M. Int. J. Cancer (2005) [Pubmed]
  20. Expression and localization of human multidrug resistance protein (ABCC) family members in pancreatic carcinoma. König, J., Hartel, M., Nies, A.T., Martignoni, M.E., Guo, J., Büchler, M.W., Friess, H., Keppler, D. Int. J. Cancer (2005) [Pubmed]
  21. Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma. Nies, A.T., König, J., Pfannschmidt, M., Klar, E., Hofmann, W.J., Keppler, D. Int. J. Cancer (2001) [Pubmed]
  22. Transport of Glyburide by Placental ABC Transporters: Implications in Fetal Drug Exposure. Gedeon, C., Behravan, J., Koren, G., Piquette-Miller, M. Placenta (2006) [Pubmed]
  23. MRP3, BCRP, and P-glycoprotein activities are prognostic factors in adult acute myeloid leukemia. Benderra, Z., Faussat, A.M., Sayada, L., Perrot, J.Y., Tang, R., Chaoui, D., Morjani, H., Marzac, C., Marie, J.P., Legrand, O. Clin. Cancer Res. (2005) [Pubmed]
  24. Molecular and functional MDR1-Pgp and MRPs expression in human glioblastoma multiforme cell lines. Declèves, X., Fajac, A., Lehmann-Che, J., Tardy, M., Mercier, C., Hurbain, I., Laplanche, J.L., Bernaudin, J.F., Scherrmann, J.M. Int. J. Cancer (2002) [Pubmed]
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