The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

ABCC4  -  ATP-binding cassette, sub-family C...

Homo sapiens

Synonyms: ATP-binding cassette sub-family C member 4, EST170205, MOAT-B, MOATB, MRP/cMOAT-related ABC transporter, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ABCC4


High impact information on ABCC4

  • The MRPs can be further divided into two subfamilies "long" (MRP1, -2, -3, -6, and -7) and "short" (MRP4, -5, -8, -9, and -10) [6].
  • Overexpression of MRP4 mRNA and MRP4 protein severely impaired the antiviral efficacy of PMEA, azidothymidine and other nucleoside analogs [7].
  • In our study of alternative or additional mechanisms of resistance operating during antiviral therapy, overexpression and amplification of the MRP4 gene correlated with ATP-dependent efflux of PMEA (9-(2-phosphonylmethoxyethyl)adenine) and azidothymidine monophosphate from cells and, thus, with resistance to these drugs [7].
  • Increased resistance to PMEA and amplification of the MRP4 gene correlated with enhanced drug efflux; transfer of chromosome 13 containing the amplified MRP4 gene conferred resistance to PMEA [7].
  • CONCLUSIONS: These results indicate that MRP4 confers resistance to short-term methotrexate and continuous PMEA treatment [8].

Chemical compound and disease context of ABCC4


Biological context of ABCC4


Anatomical context of ABCC4

  • Protein synthesis inhibition selectively stabilized PTC containing ABCC4 transcripts in human, monkey and rodent cell lines [12].
  • In cholestatic conditions, ABCC4 may become a key pathway for efflux of bile acids from hepatocytes into blood [14].
  • RESULTS: MRP4 was detected as a 170-kd protein that was localized in the plasma membrane and cytoplasm of transfected cells [8].
  • Furthermore, we found that MRP4 transports dehydroepiandrosterone 3-sulphate (DHEAS), the most abundant circulating steroid in humans, which is made in the adrenal gland [16].
  • Indirect evidence suggests that ABCC4 and ABCC5 contribute to cGMP transport by erythrocytes [17].

Associations of ABCC4 with chemical compounds


Regulatory relationships of ABCC4

  • MRP4 is a novel PAH transporter that has higher affinity for PAH and is expressed more highly in kidney than MRP2, and may therefore be more important in renal PAH excretion [21].

Other interactions of ABCC4


Analytical, diagnostic and therapeutic context of ABCC4


  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 of multidrug transporter MRP4/ABCC4 is a marker of poor prognosis in neuroblastoma and confers resistance to irinotecan in vitro. Norris, M.D., Smith, J., Tanabe, K., Tobin, P., Flemming, C., Scheffer, G.L., Wielinga, P., Cohn, S.L., London, W.B., Marshall, G.M., Allen, J.D., Haber, M. Mol. Cancer Ther. (2005) [Pubmed]
  3. Human multidrug resistance associated protein 4 confers resistance to camptothecins. Tian, Q., Zhang, J., Tan, T.M., Chan, E., Duan, W., Chan, S.Y., Boelsterli, U.A., Ho, P.C., Yang, H., Bian, J.S., Huang, M., Zhu, Y.Z., Xiong, W., Li, X., Zhou, S. Pharm. Res. (2005) [Pubmed]
  4. Cotransport of reduced glutathione with bile salts by MRP4 (ABCC4) localized to the basolateral hepatocyte membrane. Rius, M., Nies, A.T., Hummel-Eisenbeiss, J., Jedlitschky, G., Keppler, D. Hepatology (2003) [Pubmed]
  5. Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine. Chen, Z.S., Lee, K., Kruh, G.D. J. Biol. Chem. (2001) [Pubmed]
  6. Transmembrane transport of endo- and xenobiotics by mammalian ATP-binding cassette multidrug resistance proteins. Deeley, R.G., Westlake, C., Cole, S.P. Physiol. Rev. (2006) [Pubmed]
  7. MRP4: A previously unidentified factor in resistance to nucleoside-based antiviral drugs. Schuetz, J.D., Connelly, M.C., Sun, D., Paibir, S.G., Flynn, P.M., Srinivas, R.V., Kumar, A., Fridland, A. Nat. Med. (1999) [Pubmed]
  8. Analysis of the MRP4 drug resistance profile in transfected NIH3T3 cells. Lee, K., Klein-Szanto, A.J., Kruh, G.D. J. Natl. Cancer Inst. (2000) [Pubmed]
  9. Association between expression of the MRP3 gene and exposure to platinum drugs in lung cancer. Oguri, T., Isobe, T., Fujitaka, K., Ishikawa, N., Kohno, N. Int. J. Cancer (2001) [Pubmed]
  10. Overexpression of mutated MRP4 in cisplatin resistant small cell lung cancer cell line: collateral sensitivity to azidothymidine. Savaraj, N., Wu, C., Wangpaichitr, M., Kuo, M.T., Lampidis, T., Robles, C., Furst, A.J., Feun, L. Int. J. Oncol. (2003) [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. Nonsense mediated decay downregulates conserved alternatively spliced ABCC4 transcripts bearing nonsense codons. Lamba, J.K., Adachi, M., Sun, D., Tammur, J., Schuetz, E.G., Allikmets, R., Schuetz, J.D. Hum. Mol. Genet. (2003) [Pubmed]
  13. The molecular basis of the action of disulfiram as a modulator of the multidrug resistance-linked ATP binding cassette transporters MDR1 (ABCB1) and MRP1 (ABCC1). Sauna, Z.E., Peng, X.H., Nandigama, K., Tekle, S., Ambudkar, S.V. Mol. Pharmacol. (2004) [Pubmed]
  14. Substrate specificity of human ABCC4 (MRP4)-mediated cotransport of bile acids and reduced glutathione. Rius, M., Hummel-Eisenbeiss, J., Hofmann, A.F., Keppler, D. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  15. Multidrug resistance protein 4 (MRP4/ABCC4) mediates efflux of bimane-glutathione. Bai, J., Lai, L., Yeo, H.C., Goh, B.C., Tan, T.M. Int. J. Biochem. Cell Biol. (2004) [Pubmed]
  16. Steroid and bile acid conjugates are substrates of human multidrug-resistance protein (MRP) 4 (ATP-binding cassette C4). Zelcer, N., Reid, G., Wielinga, P., Kuil, A., van der Heijden, I., Schuetz, J.D., Borst, P. Biochem. J. (2003) [Pubmed]
  17. 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]
  18. Functional involvement of multidrug resistance-associated protein 4 (MRP4/ABCC4) in the renal elimination of the antiviral drugs adefovir and tenofovir. Imaoka, T., Kusuhara, H., Adachi, M., Schuetz, J.D., Takeuchi, K., Sugiyama, Y. Mol. Pharmacol. (2007) [Pubmed]
  19. Role of glutathione in the multidrug resistance protein 4 (MRP4/ABCC4)-mediated efflux of cAMP and resistance to purine analogues. Lai, L., Tan, T.M. Biochem. J. (2002) [Pubmed]
  20. Multidrug resistance-associated protein 4 regulates cAMP-dependent signaling pathways and controls human and rat SMC proliferation. Sassi, Y., Lipskaia, L., Vandecasteele, G., Nikolaev, V.O., Hatem, S.N., Cohen Aubart, F., Russel, F.G., Mougenot, N., Vrignaud, C., Lechat, P., Lompré, A.M., Hulot, J.S. J. Clin. Invest. (2008) [Pubmed]
  21. Contribution of multidrug resistance protein 2 (MRP2/ABCC2) to the renal excretion of p-aminohippurate (PAH) and identification of MRP4 (ABCC4) as a novel PAH transporter. Smeets, P.H., van Aubel, R.A., Wouterse, A.C., van den Heuvel, J.J., Russel, F.G. J. Am. Soc. Nephrol. (2004) [Pubmed]
  22. 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]
  23. Immunohistochemical detection of multidrug-resistant protein expression in retinoblastoma treated by primary enucleation. Wilson, M.W., Fraga, C.H., Fuller, C.E., Rodriguez-Galindo, C., Mancini, J., Hagedorn, N., Leggas, M.L., Stewart, C.F. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  24. Isolation of MOAT-B, a widely expressed multidrug resistance-associated protein/canalicular multispecific organic anion transporter-related transporter. Lee, K., Belinsky, M.G., Bell, D.W., Testa, J.R., Kruh, G.D. Cancer Res. (1998) [Pubmed]
  25. Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6 (ABCC1-ABCC6), in human brain. Nies, A.T., Jedlitschky, G., König, J., Herold-Mende, C., Steiner, H.H., Schmitt, H.P., Keppler, D. Neuroscience (2004) [Pubmed]
  26. Topotecan is a substrate for multidrug resistance associated protein 4. Tian, Q., Zhang, J., Chan, S.Y., Tan, T.M., Duan, W., Huang, M., Zhu, Y.Z., Chan, E., Yu, Q., Nie, Y.Q., Ho, P.C., Li, Q., Ng, K.Y., Yang, H.Y., Wei, H., Bian, J.S., Zhou, S.F. Curr. Drug Metab. (2006) [Pubmed]
WikiGenes - Universities