Skip to main content

Advertisement

SpringerLink
Log in

ABCG transporters: structure, substrate specificities and physiological roles

A Brief Overview

  • Transport ATPases: Structure, Mechanism and Relevance to Multiple Diseases
  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

Abstract

The ATP-binding cassette (ABC) transporter superfamily is one of the largest protein families with representatives in all kingdoms of life. Members of this superfamily are involved in a wide variety of transport processes with substrates ranging from small ions to relatively large polypeptides and polysaccharides. The G subfamily of ABC transporters consists of half-transporters, which oligomerise to form the functional transporter. While ABCG1, ABCG4 and ABCG5/8 are involved in the ATP-dependent translocation of steroids and, possibly, other lipids, ABCG2 (also termed the breast cancer resistance protein) has been identified as a multidrug transporter that confers resistance on tumor cells. Evidence will be summarized suggesting that ABCG2 can also mediate the binding/transport of non-drug substrates, including free and conjugated steroids. The characterization of the substrate specificities of ABCG proteins at a molecular level might provide further clues about their potential physiological role(s), and create new opportunities for the modulation of their activities in relation to human disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Albrecht C, Elliott JI, Sardini A, Litman T, Stieger B, Meier PJ, Higgins CF (2002) Biochim Biophys Acta 1567:133–142

    Article  CAS  Google Scholar 

  • Allen JD, Jackson SC, Schinkel AH (2002) Cancer Res 62:2294–2299

    CAS  Google Scholar 

  • Allikmets R, Schriml LM, Hutchinson A, Romano-Spica V, Dean M (1998) Cancer Res 58:5337–5339

    CAS  Google Scholar 

  • Ando T, Kusuhara H, Merino G, Alvarez AI, Schinkel AH, Sugiyama Y (2007) Drug Metab Dispos 35:1873–1879

    Google Scholar 

  • Annilo T, Tammur J, Hutchinson A, Rzhetsky A, Dean M, Allikmets R (2001) Cytogenet Cell Genet 94:196–201

    Article  CAS  Google Scholar 

  • Berge KE, Tian H, Graf GA, Yu L, Grishin NV, Schultz J, Kwiterovich P, Shan B, Barnes R, Hobbs HH (2000) Science 290:1771–1775

    Article  CAS  Google Scholar 

  • Borst P, Oude Elferink R (2002) Annu Rev Biochem 71:537–592

    Article  CAS  Google Scholar 

  • Buchmann J, Meyer C, Neschen S, Augustin R, Schmolz K, Kluge R, Al-Hasani H, Jurgens H, Eulenberg K, Wehr R, Dohrmann C, Joost H-G, Schurmann A (2007) Endocrinology 148:1561–1573

    Article  CAS  Google Scholar 

  • Chen ZS, Robey RW, Belinsky MG, Shchaveleva I, Ren XQ, Sugimoto Y, Ross DD, Bates SE, Kruh GD (2003) Cancer Res 63:4048–4054

    CAS  Google Scholar 

  • Chen H, Rossier C, Lalioti MD, Lynn A, Chakravarti A, Perrin G, Antonarakis SE (1996) Am J Hum Genet 59:66–75

    CAS  Google Scholar 

  • Cooray HC, Blackmore CG, Maskell L, Barrand MA (2002) Neuroreport 13:2059–2063

    Article  CAS  Google Scholar 

  • Cooray HC, Shahi S, Cahn AP, van Veen HW, Hladky SB, Barrand MA (2006) Eur J Pharmacol 531:25–33

    Article  CAS  Google Scholar 

  • Croop JM, Tiller GE, Fletcher JA, Lux ML, Raab E, Goldenson D, Son D, Arciniegas S, Wu RL (1997) Gene 185:77–85

    Article  CAS  Google Scholar 

  • Cserepes J, Szentpetery Z, Seres L, Ozvegy-Laczka C, Langmann T, Schmitz G, Glavinas H, Klein I, Homolya L, Varadi A, Sarkadi B, Elkind NB (2004) Biochem Biophys Res Commun 320:860–867

    Article  CAS  Google Scholar 

  • Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD (1998) Proc Natl Acad Sci U S A 95:15665–15670

    Article  CAS  Google Scholar 

  • Dressen TD, Johnson DH, Heinkoff S (1998) Mol Cell Biol 8:5206–5215

    Google Scholar 

  • Ee PL, He X, Ross DD, Beck WT (2004) Mol Cancer Ther 3:1577–1583

    CAS  Google Scholar 

  • Engel T, Lorkowski S, Lueken A, Rust S, Schluter B, Berger G, Cullen P, Assmann G (2001) Biochem Biophys Res Commun 288:483–488

    Article  CAS  Google Scholar 

  • Ejendal KFK, Diop NK, Schweiger LC, Hrycyna CA (2006) Protein Sci 15:1597–1607

    Article  CAS  Google Scholar 

  • Enokizono J, Kusuhara H, Sugiyama Y (2007) Mol Pharmacol 72:967–975

    Google Scholar 

  • Garrigues A, Escargueil AE, Orlowski S (2002) Proc Natl Acad Sci U S A 99:10347–10352

    Article  CAS  Google Scholar 

  • Gottesman MM (2002) Annu Rev Med 53:615–627

    Article  CAS  Google Scholar 

  • Graf GA, Yu L, Li WP, Gerard R, Tuma PL, Cohen JC, Hobbs HH (2003) J Biol Chem 278:48275–48282

    Article  CAS  Google Scholar 

  • Hardwick LJ, Velamakanni S, van Veen HW (2007) Br J Pharmacol 151:163–174

    Article  CAS  Google Scholar 

  • Higgins CF (1992) Annu Rev Cell Biol (1992) 8:67–113

    CAS  Google Scholar 

  • Higgins CF, Callaghan R, Linton KJ, Rosenberg MF, Ford RC (1997) Semin Cancer Biol 8:135–142

    Article  CAS  Google Scholar 

  • Honjo Y, Hrycyna CA, Yan QW, Medina-Perez WY, Robey RW, van de Laar A, Litman T, Dean M, Bates SE (2001) Cancer Res 61:6635–6639

    CAS  Google Scholar 

  • Huss WJ, Gray DR, Greenberg NM, Mohler JL, Smith GJ (2005) Cancer Res 65:6640–6650

    Article  CAS  Google Scholar 

  • Imai Y, Asada S, Tsukahara S, Ishikawa E, Tsuruo T, Sugimoto Y (2003) Mol Pharmacol 64:610–618

    Article  CAS  Google Scholar 

  • Janvilisri T, Shahi S, Venter H, Balakrishnan L, van Veen HW (2005) Biochem J 385:419–426

    Article  CAS  Google Scholar 

  • Janvilisri T, Venter H, Shahi S, Reuter G, Balakrishnan L, van Veen HW (2003) J Biol Chem 278:20645–20651

    Article  CAS  Google Scholar 

  • Jonker JW, Buitelaar M, Wagenaar E, van der Valk MA, Scheffer GL, Scheper RJ, Plosch T, Kuipers F, Elferink RP, Rosing H, Beijnen JH, Schinkel AH (2002) Proc Natl Acad Sci U S A 99:15649–15654

    Article  CAS  Google Scholar 

  • Jonker JW, Smit JW, Brinkhuis RF, Maliepaard M, Beijnen JH, Schellens JH, Schinkel AH (2000) J Natl Cancer Inst 92:1651–1656

    Article  CAS  Google Scholar 

  • Kage K, Tsukahara S, Sugiyama T, Asada S, Ishikawa E, Tsuruo T, Sugimoto Y (2002) Int J Cancer 97:626–630

    Article  CAS  Google Scholar 

  • Kim M, Turnquist H, Jackson J, Sgagias M, Yan Y, Gong M, Dean M, Sharp JG, Cowan K (2002) Clin Cancer Res 8:22–28

    CAS  Google Scholar 

  • Klucken J, Buechler C, Orso E, Kaminski WE, Porsch-Ozcurumez M, Liebisch G, Kapinsky M, Diederich W, Drobnik W, Dean M, Allikmets R, Schmitz G (2000) Proc Natl Acad Sci U S A 97:817–822

    Article  CAS  Google Scholar 

  • Kobayashi A, Takanezawa Y, Hirata T, Shimizu Y, Misasa K, Kioka N, Arai H, Ueda K, Matsuo M (2006) J Lipid Res 17:1791–1802

    Article  Google Scholar 

  • Langheim S, Yu L, von Bergmann K, Lutjohann D, Xu F, Hobbs HH, Cohen JC (2005) J Lipid Res 46:1732–1738

    Article  CAS  Google Scholar 

  • Lee MH, Lu K, Patel SB (2001) Curr Opin Lipidol 12:141–149

    Article  CAS  Google Scholar 

  • Leslie EM, Deeley RG, Cole SPC (2005) Tox Appl Pharmacol 204:216–237

    Article  CAS  Google Scholar 

  • Litman T, Brangi M, Hudson E, Fetsch P, Abati A, Ross DD, Miyake K, Resau JH, Bates SE (2000) J Cell Sci 113(Pt 11):2011–2021

    CAS  Google Scholar 

  • Lorkowski S, Rust S, Engel T, Jung E, Tegelkamp K, Galinski EA, Assmann G, Cullen P (2001a) Biochem Biophys Res Commun 280:121–131

  • Lorkowski S, Kratz M, Wenner C, Schmidt R, Weitkamp B, Fobker M, Reinhardt J, Rauterberg J, Galinski EA, Cullen P (2001b) Biochem Biophys Res Commun 283:821–830

  • Maliepaard M, van Gastelen MA, Tohgo A, Hausheer FH, van Waardenburg RC, de Jong LA, Pluim D, Beijnen JH, Schellens JH (2001) Clin Cancer Res 7:935–941

    CAS  Google Scholar 

  • Maliepaard M, Scheffer GL, Faneyte IF, van Gastelen MA, Pijnenborg AC, Schinkel AH, van de Vijver MJ, Scheper RJ, Schellens JH (2001) Cancer Res 61:3458–3464

    CAS  Google Scholar 

  • Mao Q, Conseil G, Gupta A, Cole SP, Unadkat JD (2004) Biochem Biophys Res Commun 320:730–737

    Article  CAS  Google Scholar 

  • Margolles A, Putman M, van Veen HW, Konings WN (1999) Biochemistry 38:16298–16306

    Article  CAS  Google Scholar 

  • McDevitt CA, Collins RF, Conway M, Modok S, Storm J, Kerr ID, Ford RC, Callaghan R (2006) Structure 14:1623–1632

    Article  CAS  Google Scholar 

  • Merino G, Jonker JW, Wagenaar E, van Herwaarden AE, Schinkel AH (2005) Mol Pharmacol 67:1758–1764

    Article  CAS  Google Scholar 

  • Mitomo H, Kato R, Ito A, Kasamatsu S, Ikegami Y, Kii I, Kudo A, Kobatake E, Sumino Y, Ishikawa T (2003) Biochem J 373:767–774

    Article  CAS  Google Scholar 

  • Nakamura Y, Oka M, Soda H, Shiozawa K, Yoshikawa M, Itoh A, Ikegami Y, Tsurutani J, Nakatomi K, Kitazaki T, Doi S, Yoshida H, Kohno S (2005) Cancer Res 65:1541–1546

    Article  CAS  Google Scholar 

  • Nakanishi T, Doyle LA, Hassel B, Wei Y, Bauer KS, Wu S, Pumplin DW, Fang HB, Ross DD (2003) Mol Pharmacol 64:1452–1462

    Article  CAS  Google Scholar 

  • Oldfield S, Lowry C, Ruddick J, Lightman S (2002) Biochim Biophys Acta 1591:175–179

    Article  CAS  Google Scholar 

  • Oram JF, Lawn RM (2001) J Lipid Res 42:73–1179

    Google Scholar 

  • Otsu CT, daSilva I, de Molfetta JB, da Silva LR, de Almeida-Engler J, Engler G, Torraca PC, Goldman GH, Goldman MH (2004) J Exp Bot 55:1643–1654

    Article  CAS  Google Scholar 

  • Ozvegy C, Litman T, Szakacs G, Nagy Z, Bates S, Varadi A, Sarkadi B (2001) Biochem Biophys Res Commun 285:111–117

    Article  CAS  Google Scholar 

  • Pal A, Mehn D, Molnar E, Gedey S, Meszaros P, Nagy T, Glavinas H, Janaky T, von Richter O, Bathori G, Szente L, Krajcsi P (2007) J Pharmacol Exp Ther 321:1085–1094

    Article  CAS  Google Scholar 

  • Pavek P, Merino G, Wagenaar E, Bolscher E, Novotna M, Jonker JW, Schinkel AH (2005) J Pharmacol Exp Ther 312:144–152

    Article  CAS  Google Scholar 

  • Pozza A, Perez-Victoria JM, Sardo A, Ahmed-Belkacem A, Di Pietro A (2006) Cell Mol Life Sci 63:1912–1922

    Article  CAS  Google Scholar 

  • Rabindran SK, Ross DD, Doyle LA, Yang W, Greenberger LM (2000) Cancer Res 60:47–50

    CAS  Google Scholar 

  • Repa JJ, Dietschy JM, Turley SD (2002) J Lipid Res 43:1864–1874

    Article  CAS  Google Scholar 

  • Rebbeor JF, Senior AE (1998) Biochim Biophys Acta 1369:85–93

    Article  CAS  Google Scholar 

  • Reuter G, Janvilisri T, Venter H, Shahi S, Balakrishnan L, van Veen HW (2003) J Biol Chem 278:35193–35198

    Article  CAS  Google Scholar 

  • Robey RW, Honjo Y, van de Laar A, Miyake K, Regis JT, Litman T, Bates SE (2001) Biochim Biophys Acta 1512:171–182

    Article  CAS  Google Scholar 

  • Romsicki Y, Sharom FJ (1999) Biochemistry 38:6887–6896

    Article  CAS  Google Scholar 

  • Rothnie A, Theron D, Soceneantu L, Martin C, Traikia M, Berridge G, Higgins CF, Devaux PF, Callaghan R (2001) Eur Biophys J 30:430–442

    Article  CAS  Google Scholar 

  • Ruetz S, Gros P (1994) Cell 77:1071–1081

    Article  CAS  Google Scholar 

  • Sabol SL, Brewer HB Jr, Santamarina-Fojo S (2005) J Lipid Res 46:2151–2167

    Google Scholar 

  • Sano O, Kobayashi A, Nagao K, Kumagai K, Kioka N, Hanada K, Ueda K, Matsuo M (2007) J Lipid Res 48:2377–2384

    Google Scholar 

  • Savary S, Denizot F, Luciani M, Mattei M, Chimini G (1996) Mamm Genome 7:673–676

    Article  CAS  Google Scholar 

  • Scharenberg CW, Harkey MA, Torok-Storb B (2002) Blood 99:507–512

    Article  CAS  Google Scholar 

  • Schmitz G, Langmann T, Heimerl S (2001) J Lipid Res 42:1513–1520

    CAS  Google Scholar 

  • Smith AJ, Timmermans-Hereijgers JL, Roelofsen B, Wirtz KW, van Blitterswijk WJ, Smit JJ, Schinkel AH, Borst P (1994) FEBS Lett 354:263–266

    Google Scholar 

  • Storch CH, Ehehalt R, Haefeli WE, Weiss J (2007) J Pharmacol Exp Ther 323:257–264

    Google Scholar 

  • Suzuki M, Suzuki H, Sugimoto Y, Sugiyama Y (2003) J Biol Chem 278:22644–22649

    Article  CAS  Google Scholar 

  • Telbisz A, Muller M, Ozvegy-Laczka C, Homolya L, Szente L, Varadi A, Sarkadi B (2007) Biochim Biophys Acta (in press). DOI 10.1016/j.bbamem.2007.06.026

  • Tusnady GE, Sarkadi B, Simon I, Varadi A (2006) FEBS Lett 580:1017–1022

    Article  CAS  Google Scholar 

  • van Helvoort A, Smith AJ, Sprong H et al (1996) Cell 87:507–517

    Article  Google Scholar 

  • van Helvoort A, Giudici ML, Thielman M, van Meer G (1997) J Cell Sci 110(Pt 1):75–83

    Google Scholar 

  • van Herwaarden AE, Jonker JW, Wagenaar E, Brinkhuis RF, Schellens JH, Beijnen JH, Schinkel AH (2003) Cancer Res 63:6447–6452

    Google Scholar 

  • van Herwaarden AE, Wagenaar E, Karnekamp B, Merino G, Jonker JW, Schinkel AH (2006) Carcinogenesis 27:123–130

    Article  Google Scholar 

  • van Veen HW, Callaghan R, Soceneantu L, Sardini A, Konings WN, Higgins CF (1998) Nature 391:291–295

    Google Scholar 

  • van Veen HW, Margolles A, Muller M, Higgins CF, Konings WN (2000) EMBO J 19:2503–2514

    Google Scholar 

  • Vaughan AM, Oram JF (2005) J Biol Chem 280:30150–30157

    Article  CAS  Google Scholar 

  • Venkateswaran A, Repa JJ, Lobaccaro JM, Bronson A, Mangelsdorf DJ, Edwards PA (2000) J Biol Chem 275:14700–14707

    Article  CAS  Google Scholar 

  • Volk EL, Farley KM, Wu Y, Li F, Robey RW, Schneider E (2002) Cancer Res 62:5035–5040

    CAS  Google Scholar 

  • Vrins C, Vink E, Vandenberghe KE, Frijters R, Seppen J, Groen AK (2007) FEBS Lett 581:4616–4620

    Google Scholar 

  • Wanders RJ, Visser WF, van Roermund CW, Kemp S, Waterham HR (2007) Pflugers Arch 453:719–734

    Article  CAS  Google Scholar 

  • Wang N, Lan D, Chen W, Matsuura F, Tall AR (2004) Proc Natl Acad Sci U S A 101:9774–9779

    Article  CAS  Google Scholar 

  • Woehlecke H, Pohl A, Alder-Baerens N, Lage H, Herrmann A (2003) Biochem J 376:489–495

    Article  CAS  Google Scholar 

  • Xu J, Liu Y, Yang Y, Bates S, Zhang JT (2004) J Biol Chem 279:19781–19789

    Article  CAS  Google Scholar 

  • Yanase K, Tsukahara S, Asada S, Ishikawa E, Imai Y, Sugimoto Y (2004) Mol Cancer Ther 3:1119–1125

    CAS  Google Scholar 

  • Yu L, Hammer RE, Li-Hawkins J, Von Bergmann K, Lutjohann D, Cohen JC, Hobbs HH (2002) Proc Natl Acad Sci USA 99:16237–16242

    Article  CAS  Google Scholar 

  • Zhou S, Morris JJ, Barnes Y, Lan L, Schuetz JD, Sorrentino BP (2002) Proc Natl Acad Sci U S A 99:12339–12344

    Article  CAS  Google Scholar 

  • Zhou S, Schuetz JD, Bunting KD, Colapietro AM, Sampath J, Morris JJ, Lagutina I, Grosveld GC, Osawa M, Nakauchi H, Sorrentino BP (2001) Nat Med 7:1028–1034

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1PD, UK

    Saroj Velamakanni, Shen L. Wei, Tavan Janvilisri & Hendrik W. van Veen

Authors
  1. Saroj Velamakanni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shen L. Wei
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tavan Janvilisri
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hendrik W. van Veen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hendrik W. van Veen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Velamakanni, S., Wei, S.L., Janvilisri, T. et al. ABCG transporters: structure, substrate specificities and physiological roles. J Bioenerg Biomembr 39, 465–471 (2007). https://doi.org/10.1007/s10863-007-9122-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10863-007-9122-x

Keywords

Search

Navigation