Journal of Bioenergetics and Biomembranes

, Volume 33, Issue 6, pp 453–458 | Cite as

Overview: ABC Transporters and Human Disease

  • Michael M. Gottesman
  • Suresh V. Ambudkar


ABC transporters are found in all known organisms, and approximately 1,100 different transporters belonging to this family have been described in the literature. The family is defined by homology within the ATP-binding cassette (ABC) region, which extends outside of the more typical Walker motifs found in all ATP-binding proteins. Most family members also contain transmembrane domains involved in recognition of substrates, which are transported across, into, and out of cell membranes, but some members utilize ABCs as engines to regulate ion channels. There are approximately 50 known ABC transporters in the human, and there are currently 13 genetic diseases associated with defects in 14 of these transporters. The most common genetic disease conditions include cystic fibrosis, Stargardt disease, age-related macular degeneration, adrenoleukodystrophy, Tangier disease, Dubin–Johnson syndrome and progressive familial intrahepatic cholestasis. At least 8 members of this family are involved in the transport of a variety of amphipathic compounds, including anticancer drugs, and some appear to contribute to the resistance of cancer cells to chemotherapy.

ATP hydrolysis diseases multidrug resistance nucleotide-binding domains transmembrane domains transport proteins substrates structure 


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  1. Allen, J. D., Brinkhuis, R. F., van Deemter, L., Wijnholds, J., and Schinkel, A. H. (2000). Cancer Res. 60, 5761–5766.Google Scholar
  2. Allikmets, R., Raskind, W. H., Hutchinson, A., Schueck, N. D., Dean, M., and Koeller, D. M. (1999). Hum. Mol. Genet. 8, 743–749.Google Scholar
  3. Allikmets, R., Schriml, L. M., Hutchinson, A., Romano-Spica, V., and Dean, M. (1998). Cancer Res. 58, 5337–5339.Google Scholar
  4. Allikmets, R., Singh, N., Sun, H., Shroyer, N. F., Hutchinson, A., Chidambaram, A., Gerrard, B., Baird, L., Stauffer, D., Peiffer, A., Rattner, A., Smallwood, P., Li, Y., Anderson, K. L., Lewis, R. A., Nathans, J., Leppert, M., Dean, M., and Lupski, J. R. (1997). Nat. Genet. 15, 236–246.Google Scholar
  5. Ambudkar, S. V., Dey, S., Hrycyna, C. A., Ramachandra, M., Pastan, I., and Gottesman, M. M. (1999). Annu. Rev. Pharmacol. Toxicol. 39, 361–398.Google Scholar
  6. Ambudkar, S. V., and Gottesman, M. M. (1998). Eds. Methods Enzymol. 292, 1–787.Google Scholar
  7. Belfield, G. P., Ross-Smith, N. J., and Tuite, M. F. (1995). J. Mol. Evol. 41, 376–387.Google Scholar
  8. Berge, K. E., Tian, H., Graf, G. A., Yu, H., Grishin, N. V., Schultz, J., Kwiterovich, P., Shan, B., Barnes, R., and Hobbs, H. H. (2000). Science 290, 1771–1775.Google Scholar
  9. Brooks-Wilson, A., Marcil, M., Clee, S. M., Zhang, L.-H., Roomp, C., van Dam, M., Yu, L., Brewer, C., Collins, J. A., Molhuizen, H. O. F., Loubser, O., Ouelette, F. B. F., Ficher, K., Ashbourne-Excoffon, K. J. D., Sensen, C. W., Scherer, S., Mott, S., Denis. M., Martindale, D., Frohlich, J., Morgan, K., Koop, B., Pimston, S., Kastelein, J. J. P., Genest, J., and Hayden, M. R. (1999). Nat. Genet. 22, 336–345.Google Scholar
  10. Bryan, J., and Aguilar-Bryan, L. (1999). Biochim. Biophys. Acta. 1461, 285–303.Google Scholar
  11. Chen, C.-J., Chin, J. E., Ueda, K., Clark, D. P., Pastan, I., Gottesman, M. M., and Roninson, I. (1986). Cell 47, 381–389.Google Scholar
  12. Cole, S. P., Bhardwaj, G., Gerlach, J. H., Mackie, J. E., Grant, C. E., Almquist, K. C., Stewart, A. J., Kurz, E. U., Duncan, A. M., and Deeley, R. G. (1992). Science 258, 1650–1654.Google Scholar
  13. de Vree, J. M., Jacquemin, E., Sturm, E., Cresteil, D., Bosma, P. J., Aten, J., Deleuze, J. F., Desrochers, M., Burdelski, M., Bernard, O., Oude Elferink, R. P., and Hadchouel, M. (1998). Proc. Natl. Acad. Sci. U.S.A. 95, 282–287.Google Scholar
  14. Diederichs, K., Diez, J., Greller, G., Muller, C., Breed, J., Schnell, C., Vonrhein, C., Boos, W., and Welte, W. (2000). EMBO J. 19, 5951–5961.Google Scholar
  15. Dixon, P. H., Weerasekera, N., Linton, K. J., Donaldson, O., Chambers, J., Egginton, E., Weaver, J., Nelson-Piercy, C., de Swiet, M., Warnes, G., Elias, E., Higgins, C. F., Johnston, D. G., McCarthy, M. I., and Williamson, C. (2000). Hum. Mol. Genet. 9, 1209–1217.Google Scholar
  16. Doyle, L. A., Yang, W., Abruzzo, L. V., Krogmann, T., Gao, Y., Rishi, A. K., and Ross, D. D. (1998). Proc. Natl. Acad. Sci. U.S.A. 95, 5665–5670. This article has been corrected. See Proc. Natl. Acad. Sci. U.S.A. 96(5), 2569d, March 2, 1999.Google Scholar
  17. Gottesman, M. M. (in press). Annu. Rev. Med. Google Scholar
  18. Gottesman, M. M., and Pastan, I. (1993). Annu. Rev. Biochem. 62, 385–427.Google Scholar
  19. Higgins, C. F. (1992). Annu. Rev. Cell Biol. 8, 67–113.Google Scholar
  20. Hoffmeyer, S., Burk, O., von Richter, O., Arnold, H. P., Brockmoller, J., Johne, A., Cascorbi, I., Gerloff, T., Eichelbaum, M., and Brinkman, U. (2000). Proc. Natl. Acad. Sci. U.S.A. 97, 3473–3478.Google Scholar
  21. Hung, L. W., Wang, I. X., Nikaido, K., Liu, P. Q., Ames, G. F.-L., and Kim, S. H. (1998). Nature 396, 703–707.Google Scholar
  22. Johnson, D. R., Finch, R., Lin, P., Zeiss, C. J., and Sartorelli, A. C. (2001). Cancer Res. 61, 1469–1470.Google Scholar
  23. Karpowich, N., Martsinkevich, O., Millen, L., Yuan, Y.-R., Dai, P., MacVey, K., Thomas, P. J., and Hunt, J. F. (2001). Structure 9, 571–586.Google Scholar
  24. Lamers, M. H., Perrakis, A., Enzlin, J. H., Winterwerp, H. H., de Wind, N., and Sixma, T. K. (2000). Nature 407, 711–717.Google Scholar
  25. Lee, M.-H., Lu, K., and Patel, S. B. (2001). Curr. Opin. Lipidol. 12, 141–149.Google Scholar
  26. Miyake, K., Mickley, L., Litman, T., Zhan, Z., Robey, R., Cristensen, B., Brangi, M., Greenberger, L., Dean, M., Fojo, T., and Bates, S. E. (1998). Cancer Res. 59, 8–13.Google Scholar
  27. Momburg, F., Roelse, J., Howard, J. C., Butcher, G. W., Hammerling, G. J., and Neefjes, J. J. (1994). Nature 367, 648–651.Google Scholar
  28. Obmolova, G., Ban, C., Hsieh, P., and Yang, W. (2000). Nature 407, 703–710.Google Scholar
  29. Paulusma, C. C., Bosma, P. J., Zaman, G. J. R., Bakker, C. T. M., Otter, M., Scheffer, G. L., Scheper, R. J., Borst, P., and Oude Elferink, R. P. J. (1996). Science 271, 1126–1128.Google Scholar
  30. Powis, S. J., Towsend, A. R. M., Deverson, E. V., Bastin, J., Butcher, G. W., and Howard, J. C. (1991). Nature 354, 528–531.Google Scholar
  31. Ringpfeil, F., Lebwohl, M. G., Christiano, A. M., and Uitto, J. (2000). Proc. Natl. Acad. Sci. U.S.A. 97, 6001–6006.Google Scholar
  32. Riordan, J. R., Rommens, J. M., Kerem, B., Alon, N., Rozmahel, R., Grzelczak, Z., Zielenski, J., Lok, S., Plavsic, N., Chou, J. L., Drumm, M. L., Iannuzzi, M. C., Collins, F. S., and Tsui, L.-C. (1989). Science 270, 1066–1073.Google Scholar
  33. Rust, S., Rosier, M., Funke, H., Real, J., Amoura, Z., Piette, J.-C., Deleuze, J.-F., Brewer, H. B., Duverger, N., Denelfe, P., and Assmann, G. (1999). Nat. Genet. 22, 352–355.Google Scholar
  34. Sauna, Z. E., and Ambudkar, S. V. (2000). Proc. Natl. Acad. Sci. U.S.A. 97, 2515–2520.Google Scholar
  35. Sauna, Z. E., and Ambudkar, S. V. (2001). J. Biol. Chem. 276, 11653–11661.Google Scholar
  36. Schinkel, A. H., Mayer, U., Wagenaar, E., Mol, C. A., van Deemter, L., Smit, J. J. M., van der Valk, M. A., Voodouw, A. C., Spits, H., van Tellingen, O., Zijlmans, J. M., Fibbe, W. E., and Borst, P. (1997). Proc. Natl. Acad. Sci. U.S.A. 94, 4028–4033.Google Scholar
  37. Shani, N., and Valle, D. (1998). Methods Enzymol. 298, 753–776.Google Scholar
  38. Strautnieks, S., Bull, L. N., Knisley, A. S., Kocoshis, S. A., Dahl, N., Arnell, H., Sokal, E., Dahan, K., Childs, S., Ling, V., Tanner, M. S., Kagalwalla, A. F., Nemeth, A., Pawlowska, J., Baker, A., Mieli-Vergani, G., Freimer, N. B., Gardiner, R. M., and Thompson, R. J. (1998). Nat. Genet. 20, 233–238.Google Scholar
  39. Sun, H., Molday, R. S., and Nathans, J. (1999). J. Biol. Chem. 274, 8269–8281.Google Scholar
  40. Tanabe, M., Ieiri, I., Nagata, N., Inoue, K., Ito, S., Kanamori, Y., Takahashi, M., Kurata, Y., Kigawa, J., Higuchi, S., Terakawa, N., and Otsubo, K. (2001). J. Pharmacol. Exp. Therapeut. 297, 1137–1143.Google Scholar
  41. Thomas, P. M., Cote, G. J., Wohllk, N., Haddad, B., Mathew, P. M., Rabl, W., Aguilar-Bryan, L., Gagel, R. F., and Bryan, J. (1995). Science 268, 426–429.Google Scholar
  42. Wada, M., Toh, S., Taniguchi, K., Nakamura, T., Uchiumi, T., Kohno, K., Yoshida, I., Kimura, A., Sakisaka, S., Adachi, Y., and Kuwano, M. (1998). Hum. Mol. Genet. 7, 203–207.Google Scholar
  43. Zhang, F., Sheps, J. A., and Ling, V. (1998). Methods Enzymol. 292, 51–66.Google Scholar
  44. Zhou, T., Radaev, S., Rosen, B. P., and Gatti, D. L. (2000). EMBO J. 19, 4838–4845.Google Scholar

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Michael M. Gottesman
  • Suresh V. Ambudkar

There are no affiliations available

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