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Gene Review

ABCC5  -  ATP-binding cassette, sub-family C...

Homo sapiens

Synonyms: ABC33, ATP-binding cassette sub-family C member 5, EST277145, MOAT-C, MOATC, ...
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Disease relevance of ABCC5

  • ABCC4 and ABCC5 proteins were the major ABCC subfamily members in gliomas, localized both at the luminal side of the endothelial cells and in the glioma cells of astrocytic tumors and in the astrocytic portions of oligoastrocytomas [1].
  • These results indicate that expression of ABCC4 and ABCC5 is associated with an astrocytic phenotype, in accordance with their expression in astrocytes and with the higher chemoresistance of astrocytic tumors as compared with oligodendrogliomas [1].
  • These data suggest that MRP3 and MRP5 are involved in drug resistance of pancreatic tumors and that quantitative analysis of their expression may contribute to predict the benefit of chemotherapy in patients with pancreatic cancer [2].
  • The MRP5 mRNA levels in tumors from lung cancer patients treated with platinum regimen were significantly higher than in tumors from patients treated with non-platinum regimens, and the MRP5 expression levels were correlate with the GCS expression levels that is the rate-limiting step enzyme in glutathione biosynthesis [3].
  • We speculate that MRP5 might play a role in some cases of unexplained resistance to thiopurines in acute lymphoblastic leukemia and/or to antiretroviral nucleoside analogs in HIV-infected patients [4].

Psychiatry related information on ABCC5


High impact information on ABCC5

  • MOAT-C transcripts are widely expressed in human tissues; however, MOAT-D transcript expression is more restricted [6].
  • This resistance is due to an increased extrusion of PMEA and 6-thioinosine monophosphate from the cells that overproduce MRP5 [4].
  • In polarized Madin-Darby canine kidney II (MDCKII) cells transfected with an MRP5 cDNA construct, MRP5 is routed to the basolateral membrane and these cells transport S-(2,4-dinitrophenyl)glutathione and glutathione preferentially toward the basal compartment [4].
  • The cellular efflux of AZT probably involves MRP4 or MRP5 [7].
  • RESULTS: Levels of MDR1, mrp4 and mrp5 mRNA were high following AZT treatment [7].

Chemical compound and disease context of ABCC5


Biological context of ABCC5

  • The MOAT-C and MOAT-D genes are located at chromosomes 3q27 and 17q21.3, respectively [6].
  • Multidrug resistance protein-5 (MRP5, ABCC5) is a member of the ATP-binding cassette transporter superfamily that effluxes a broad range of natural and xenobiotic compounds such as cyclic GMP, antiviral compounds, and cancer chemotherapeutic agents including nucleoside-based drugs, antifolate agents and platinum compounds [12].
  • Immunoprecipitation of MRP5 from CHAPS-solubilized extract reduced active transport and specific binding by about 45% and 40%, respectively [13].
  • Comparison of kinetic parameters with drug substrates such as methotrexate (MTX), pemetrexed (Alimta), and the metabolite of 5-fluorouracil, 5-fluorodeoxyuridine monophosphate (5-FdUMP) (Km values of 0.3-1.3 mM) indicated that MRP5 has a 25-100-fold higher affinity for CDCF than for these drugs and that they share a common transport binding site [12].
  • Expression, localization, and function of MRP5 (ABCC5), a transporter for cyclic nucleotides, in human placenta and cultured human trophoblasts: effects of gestational age and cellular differentiation [14].

Anatomical context of ABCC5


Associations of ABCC5 with chemical compounds

  • While the mechanism of cellular retention of (anti)folates is mediated via (anti)folylpolyglutamylation, certain efflux transporters including MRP5 (ABCC5) and BCRP were shown to transport both mono-, di- as well as triglutamate derivatives of MTX and folic acid [19].
  • In addition, the potency of MRP5 inhibitors such as probenecid, MK571, and the phosphodiesterase 5 inhibitors correlated well between the uptake of CDCF and MTX [12].
  • The ABCC5 transporter is a ubiquitously expressed ATP-dependent efflux pump that exports nucleotide analogues, including thiopurine anticancer drugs and antiviral drugs [20].
  • Overexpression of pABC11 resulted in reduced labeling with the fluorochromes 5-chloromethylfluorescein diacetate, fluorescein diacetate, and 2',7'-bis-(2-carboxyethyl)-5 (and-6)-carboxyfluorescein acetoxymethyl ester but not with calcein or rhodamine derivatives, consistent with pABC11 being an anion transporter [17].
  • MRP4 and MRP5 resemble each other more closely than they resemble MRPs 1-3 and confer resistance to purine and nucleotide analogs which are either inherently anionic, as in the case of the anti-AIDS drug PMEA, or are phosphorylated and converted to anionic amphiphiles in the cell, as in the case of 6-MP [21].
  • Because cGMP is a physiological substrate of MRP5, the intracellular concentrations of cGMP were modulated by the drugs 3-isobutyl-1-methylxanthin, propentofyllin, L-NAME, zaprinast, and bromo-cGMP, and the effects on hyaluronan export were analyzed [22].

Other interactions of ABCC5

  • MRP4 is expressed only at very low levels in a few tissues, and MRP5, like MRP1, is expressed in almost every tissue tested [23].
  • Phylogenetic analysis determined that ABCC11 and ABCC12 are derived by duplication, and are most closely related to the ABCC5 gene [24].
  • The human MRP4, MRP5 and MRP6 have only partially been characterized [25].
  • Preliminary studies have shown that levels of mRNAs encoding MRP2, MRP3, and MRP5, are increased in some drug-selected cell lines, but the correlation of MRP2-5 mRNA levels with drug resistance has not been examined [26].
  • A novel member of this gene family, designated pABC11, has been identified using degenerate polymerase chain reaction [17].

Analytical, diagnostic and therapeutic context of ABCC5


  1. ABCC drug efflux pumps and organic anion uptake transporters in human gliomas and the blood-tumor barrier. Bronger, H., König, J., Kopplow, K., Steiner, H.H., Ahmadi, R., Herold-Mende, C., Keppler, D., Nies, A.T. Cancer Res. (2005) [Pubmed]
  2. 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]
  3. The MRP family and anticancer drug metabolism. Suzuki, T., Nishio, K., Tanabe, S. Curr. Drug Metab. (2001) [Pubmed]
  4. Multidrug-resistance protein 5 is a multispecific organic anion transporter able to transport nucleotide analogs. Wijnholds, J., Mol, C.A., van Deemter, L., de Haas, M., Scheffer, G.L., Baas, F., Beijnen, J.H., Scheper, R.J., Hatse, S., De Clercq, E., Balzarini, J., Borst, P. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  5. Immunolocalization of multidrug resistance protein 5 in the human genitourinary system. Nies, A.T., Spring, H., Thon, W.F., Keppler, D., Jedlitschky, G. J. Urol. (2002) [Pubmed]
  6. 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]
  7. ATP binding cassette multidrug transporters limit the anti-HIV activity of zidovudine and indinavir in infected human macrophages. Jorajuria, S., Dereuddre-Bosquet, N., Becher, F., Martin, S., Porcheray, F., Garrigues, A., Mabondzo, A., Benech, H., Grassi, J., Orlowski, S., Dormont, D., Clayette, P. Antivir. Ther. (Lond.) (2004) [Pubmed]
  8. The determinants of sensitivity and acquired resistance to gemcitabine differ in non-small cell lung cancer: a role of ABCC5 in gemcitabine sensitivity. Oguri, T., Achiwa, H., Sato, S., Bessho, Y., Takano, Y., Miyazaki, M., Muramatsu, H., Maeda, H., Niimi, T., Ueda, R. Mol. Cancer Ther. (2006) [Pubmed]
  9. Induction of MRP5 and SMRP mRNA by adriamycin exposure and its overexpression in human lung cancer cells resistant to adriamycin. Yoshida, M., Suzuki, T., Komiya, T., Hatashita, E., Nishio, K., Kazuhiko, N., Fukuoka, M. Int. J. Cancer (2001) [Pubmed]
  10. Increased expression of the MRP5 gene is associated with exposure to platinum drugs in lung cancer. Oguri, T., Isobe, T., Suzuki, T., Nishio, K., Fujiwara, Y., Katoh, O., Yamakido, M. Int. J. Cancer (2000) [Pubmed]
  11. Role of MRP4 and MRP5 in biology and chemotherapy. Sampath, J., Adachi, M., Hatse, S., Naesens, L., Balzarini, J., Flatley, R.M., Matherly, L.H., Schuetz, J.D. AAPS PharmSci (2002) [Pubmed]
  12. Kinetic validation of the use of carboxydichlorofluorescein as a drug surrogate for MRP5-mediated transport. Pratt, S., Chen, V., Perry, W.I., Starling, J.J., Dantzig, A.H. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. (2006) [Pubmed]
  13. Reconstitution of ATP-dependent cGMP transport into proteoliposomes by membrane proteins from human erythrocytes. Boadu, E., Sager, G. Scand. J. Clin. Lab. Invest. (2004) [Pubmed]
  14. Expression, localization, and function of MRP5 (ABCC5), a transporter for cyclic nucleotides, in human placenta and cultured human trophoblasts: effects of gestational age and cellular differentiation. Meyer Zu Schwabedissen, H.E., Grube, M., Heydrich, B., Linnemann, K., Fusch, C., Kroemer, H.K., Jedlitschky, G. Am. J. Pathol. (2005) [Pubmed]
  15. cGMP transport by vesicles from human and mouse erythrocytes. de Wolf, C.J., Yamaguchi, H., van der Heijden, I., Wielinga, P.R., Hundscheid, S.L., Ono, N., Scheffer, G.L., de Haas, M., Schuetz, J.D., Wijnholds, J., Borst, P. FEBS J. (2007) [Pubmed]
  16. Multidrug resistance protein (MRP) 4- and MRP 5-mediated efflux of 9-(2-phosphonylmethoxyethyl)adenine by microglia. Dallas, S., Schlichter, L., Bendayan, R. J. Pharmacol. Exp. Ther. (2004) [Pubmed]
  17. pABC11 (also known as MOAT-C and MRP5), a member of the ABC family of proteins, has anion transporter activity but does not confer multidrug resistance when overexpressed in human embryonic kidney 293 cells. McAleer, M.A., Breen, M.A., White, N.L., Matthews, N. J. Biol. Chem. (1999) [Pubmed]
  18. Immuno-histochemical detection of MRPs in human lung cells in culture. Torky, A.R., Stehfest, E., Viehweger, K., Taege, C., Foth, H. Toxicology (2005) [Pubmed]
  19. The role of multidrug resistance efflux transporters in antifolate resistance and folate homeostasis. Assaraf, Y.G. Drug Resist. Updat. (2006) [Pubmed]
  20. Strong linkage disequilibrium at the nucleotide analogue transporter ABCC5 gene locus. Gwee, P.C., Tang, K., Sew, P.H., Lee, E.J., Chong, S.S., Lee, C.G. Pharmacogenet. Genomics (2005) [Pubmed]
  21. MRP subfamily transporters and resistance to anticancer agents. Kruh, G.D., Zeng, H., Rea, P.A., Liu, G., Chen, Z.S., Lee, K., Belinsky, M.G. J. Bioenerg. Biomembr. (2001) [Pubmed]
  22. Hyaluronan export by the ABC transporter MRP5 and its modulation by intracellular cGMP. Schulz, T., Schumacher, U., Prehm, P. J. Biol. Chem. (2007) [Pubmed]
  23. Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Kool, M., de Haas, M., Scheffer, G.L., Scheper, R.J., van Eijk, M.J., Juijn, J.A., Baas, F., Borst, P. Cancer Res. (1997) [Pubmed]
  24. Two new genes from the human ATP-binding cassette transporter superfamily, ABCC11 and ABCC12, tandemly duplicated on chromosome 16q12. Tammur, J., Prades, C., Arnould, I., Rzhetsky, A., Hutchinson, A., Adachi, M., Schuetz, J.D., Swoboda, K.J., Ptácek, L.J., Rosier, M., Dean, M., Allikmets, R. Gene (2001) [Pubmed]
  25. Multidrug resistance-associated proteins: Export pumps for conjugates with glutathione, glucuronate or sulfate. Homolya, L., Váradi, A., Sarkadi, B. Biofactors (2003) [Pubmed]
  26. Expression of multidrug resistance protein-related genes in lung cancer: correlation with drug response. Young, L.C., Campling, B.G., Voskoglou-Nomikos, T., Cole, S.P., Deeley, R.G., Gerlach, J.H. Clin. Cancer Res. (1999) [Pubmed]
  27. Expression and localization of the multidrug resistance protein 5 (MRP5/ABCC5), a cellular export pump for cyclic nucleotides, in human heart. Dazert, P., Meissner, K., Vogelgesang, S., Heydrich, B., Eckel, L., Böhm, M., Warzok, R., Kerb, R., Brinkmann, U., Schaeffeler, E., Schwab, M., Cascorbi, I., Jedlitschky, G., Kroemer, H.K. Am. J. Pathol. (2003) [Pubmed]
  28. Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5. Reid, G., Wielinga, P., Zelcer, N., De Haas, M., Van Deemter, L., Wijnholds, J., Balzarini, J., Borst, P. Mol. Pharmacol. (2003) [Pubmed]
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