ABCG2
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| Location (UCSC) | Chr 4: 88.09 – 88.23 Mb | Chr 6: 58.56 – 58.67 Mb | |||||||
| PubMed search | [4] | [5] | |||||||
| View/Edit Human | View/Edit Mouse |
ATP-binding cassette super-family G member 2 is a protein that in humans is encoded by the ABCG2 gene.[6][7] ABCG2 has also been designated as CDw338 (cluster of differentiation w338). ABCG2 is a translocation protein used to actively pump drugs and other compounds against their concentration gradient using the bonding and hydrolysis of ATP as the energy source.[1]
ABCG2 forms into a homodimer to assume its active transport conformation. The dimer weighs approximately 144 kDa. The expression of this transport protein is highly conserved throughout the animal kingdom, pointing to its importance.[8]
Substrate binding with compounds occurs in the large central cavity. ABCG2 can bind to a broad range of compounds but binds strongest to flat, polycyclic chemicals with lots of hydrophobic character.[1]
Function
The membrane-associated protein encoded by this gene is included in the superfamily of
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 (BCRP), this protein functions as a xenobiotic transporter which may play a role in multi-drug resistance to chemotherapeutic agents including mitoxantrone and camptothecin analogues.[8] 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,[9] and it has been shown to have a role in protecting the fetus from xenobiotics in the maternal circulation.[10]
The transporter has been shown to play protective roles in blocking absorption at the
The protein also carries the Jr(a) antigen, which defines the Junior blood group system.[11]
Interactive pathway map
| Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
Fluorouracil (5-FU) Activity edit
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Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Irinotecan Pathway edit
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Inhibition
It is inhibited by some calcium channel blockers such as amlodipine, felodipine and nifedipine.[12] The fungal toxin fumitremorgin C (FTC) inhibits the protein but has neurotoxic side effects. A synthetic tetracyclic analog of FTC called Ko-143 inhibits ABCG2.[13]
See also
- ATP-binding cassette transporter
References
- ^ S2CID 4461745.
- ^ a b c GRCh38: Ensembl release 89: ENSG00000118777 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000029802 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 8894702.
- PMID 9861027.
- ^ PMID 19135109.
- ^ "Entrez Gene: ABCG2 ATP-binding cassette, sub-family G (WHITE), member 2".
- ^ PMID 19118589.
- ^ Kniffin CL (2013). "OMIM entry # 614490 – BLOOD GROUP, JUNIOR SYSTEM; JR". Online Mendelian Inheritance in Man. Retrieved 1 September 2019.
- PMID 19742263.
- S2CID 4617388.
Further reading
- Hazai E, Bikádi Z (April 2008). "Homology modeling of breast cancer resistance protein (ABCG2)". Journal of Structural Biology. 162 (1): 63–74. PMID 18249138.
- Abbott BL (January 2006). "ABCG2 (BCRP): a cytoprotectant in normal and malignant stem cells". Clinical Advances in Hematology & Oncology. 4 (1): 63–72. PMID 16562373.
- Schmitz G, Langmann T, Heimerl S (October 2001). "Role of ABCG1 and other ABCG family members in lipid metabolism". Journal of Lipid Research. 42 (10): 1513–1520. PMID 11590207.
- Ejendal KF, Hrycyna CA (October 2002). "Multidrug resistance and cancer: the role of the human ABC transporter ABCG2". Current Protein & Peptide Science. 3 (5): 503–511. PMID 12369998.
- Doyle L, Ross DD (October 2003). "Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2)". Oncogene. 22 (47): 7340–7358. S2CID 9648841.
- Sugimoto Y, Tsukahara S, Ishikawa E, Mitsuhashi J (August 2005). "Breast cancer resistance protein: molecular target for anticancer drug resistance and pharmacokinetics/pharmacodynamics". Cancer Science. 96 (8): 457–465. S2CID 20734576.
- Ishikawa T, Tamura A, Saito H, Wakabayashi K, Nakagawa H (October 2005). "Pharmacogenomics of the human ABC transporter ABCG2: from functional evaluation to drug molecular design". Die Naturwissenschaften. 92 (10): 451–463. S2CID 22151149.
- Krishnamurthy P, Schuetz JD (2006). "Role of ABCG2/BCRP in biology and medicine". Annual Review of Pharmacology and Toxicology. 46: 381–410. PMID 16402910.
- Robey RW, Polgar O, Deeken J, To KW, Bates SE (March 2007). "ABCG2: determining its relevance in clinical drug resistance". Cancer and Metastasis Reviews. 26 (1): 39–57. S2CID 11293439.
External links
- ABCG2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Human ABCG2 genome location and ABCG2 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: Q9UNQ0 (Broad substrate specificity ATP-binding cassette transporter ABCG2) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.