ATP-binding cassette sub-family G member 2 is a protein that in humans is encoded by the ABCG2gene.[1][2] ABCG2 has also been designated as CDw338 (cluster of differentiation w338).
The membrane-associated protein encoded by this gene is included in the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the White subfamily. Alternatively referred to as the Breast Cancer Resistance Protein, this protein functions as a xenobiotic transporter which may play a role in multi-drug resistance to chemotherapeutic agents including mitoxantrone and camptothecin analogues. Early observations of significant ABCG2-mediated resistance to anthracyclines were subsequently attributed mutations encountered in vitro but not in nature or the clinic. Significant expression of this protein has been observed in the placenta,[3] and it has been shown to have a role in protecting the fetus from xenobiotics in the maternal circulation.[4]
The transporter has also been shown to play protective roles in blocking absorption at the apical membrane of the intestine, and at the blood-testis barrier,[4] the blood–brain barrier,[4] and the membranes of hematopoietic progenitor and other stem cells. At the apical membranes of the liver and kidney, it enhances excretion of xenobiotics. In the lactating mammary gland, it has a role on excreting vitamins such as riboflavin and biotin into milk.[4] In the kidney and gastrointestinal tract, it has a role in urate excretion.
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
↑Allikmets R, Gerrard B, Hutchinson A, Dean M (Feb 1997). "Characterization of the human ABC superfamily: isolation and mapping of 21 new genes using the expressed sequence tags database". Hum Mol Genet. 5 (10): 1649–55. doi:10.1093/hmg/5.10.1649. PMID8894702.
↑ 4.04.14.24.3Vlaming ML, Lagas JS, Schinkel AH (January 2009). "Physiological and pharmacological roles of ABCG2 (BCRP): recent findings in Abcg2 knockout mice". Adv. Drug Deliv. Rev. 61 (1): 14–25. doi:10.1016/j.addr.2008.08.007. PMID19118589.
Further reading
Hazai E, Bikadi Z (2008). "Homology modeling of breast cancer resistance protein (ABCG2)". J Struct Biol. 162 (1): 63–74. doi:10.1016/j.jsb.2007.12.001. PMID18249138.
Abbott BL (2006). "ABCG2 (BCRP): a cytoprotectant in normal and malignant stem cells". Clin Adv Hematol Oncol. 4 (1): 63–72. PMID16562373.
Schmitz G, Langmann T, Heimerl S (2002). "Role of ABCG1 and other ABCG family members in lipid metabolism". J. Lipid Res. 42 (10): 1513–20. PMID11590207.
Ejendal KF, Hrycyna CA (2003). "Multidrug resistance and cancer: the role of the human ABC transporter ABCG2". Curr. Protein Pept. Sci. 3 (5): 503–11. doi:10.2174/1389203023380521. PMID12369998.
Doyle LA, Ross DD (2003). "Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2)". Oncogene. 22 (47): 7340–58. doi:10.1038/sj.onc.1206938. PMID14576842.
Sugimoto Y, Tsukahara S, Ishikawa E, Mitsuhashi J (2005). "Breast cancer resistance protein: molecular target for anticancer drug resistance and pharmacokinetics/pharmacodynamics". Cancer Sci. 96 (8): 457–65. doi:10.1111/j.1349-7006.2005.00081.x. PMID16108826.
Ishikawa T, Tamura A, Saito H, et al. (2006). "Pharmacogenomics of the human ABC transporter ABCG2: from functional evaluation to drug molecular design". Naturwissenschaften. 92 (10): 451–63. doi:10.1007/s00114-005-0019-4. PMID16160819.
Robey RW, Polgar O, Deeken J, et al. (2007). "ABCG2: determining its relevance in clinical drug resistance". Cancer Metastasis Rev. 26 (1): 39–57. doi:10.1007/s10555-007-9042-6. PMID17323127.
