Affinage

ABCG2

Broad substrate specificity ATP-binding cassette transporter ABCG2 · UniProt Q9UNQ0

Round 2 corrected
Length
655 aa
Mass
72.3 kDa
Annotated
2026-04-28
130 papers in source corpus 36 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ABCG2 (BCRP/MXR) is a homodimeric ABC half-transporter that couples ATP hydrolysis to the apical efflux of a remarkably broad substrate repertoire—including anticancer drugs, porphyrins, sulfated steroid conjugates, uric acid, phytoestrogens, and statins—at pharmacological barrier tissues such as the intestinal epithelium, liver canaliculi, placental syncytiotrophoblast, kidney proximal tubule, and blood–brain barrier endothelium (PMID:9861027, PMID:11309308, PMID:12438926, PMID:19506252). Substrate specificity is critically governed by residue Arg482 in the third transmembrane segment, where acquired mutations broaden the transported drug spectrum, while the common Q141K polymorphism reduces surface protein levels—without altering intrinsic catalytic activity—leading to impaired urate secretion and clinically significant hyperuricemia and gout (PMID:11559526, PMID:15553238, PMID:20368174). High-resolution cryo-EM structures reveal an inward-facing homodimer with a central hydrophobic multidrug-binding pocket occupied by cholesterol molecules, rationalizing the polyspecific binding mechanism and allosteric inhibition by antibodies and pharmacological agents (PMID:28554189). ABCG2 expression is transcriptionally regulated by HIF-1α under hypoxia, the SIRT1–PGC-1α–PPARγ axis, and E2F1, and the transporter defines the hematopoietic side-population stem cell phenotype through Hoechst 33342 and porphyrin efflux, protecting progenitor cells from phototoxic and oxidative damage (PMID:15044468, PMID:11533706, PMID:12429862, PMID:24276245).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1998 High

    The identification of ABCG2 as a novel half-transporter overexpressed in multidrug-resistant breast cancer cells established it as an ATP-dependent xenobiotic efflux pump, resolving the molecular basis of a mitoxantrone-resistance phenotype that was not attributable to P-gp or MRP1.

    Evidence cDNA cloning from MCF-7/AdrVp cells with drug accumulation/efflux assays and independent cloning from placenta

    PMID:9850061 PMID:9861027

    Open questions at the time
    • No structural information
    • Full substrate range unknown
    • Endogenous physiological substrates not identified
  2. 2001 High

    Mapping of ABCG2 to apical membranes of barrier epithelia (intestine, liver canaliculi, placenta, brain endothelium) and its identification as the molecular determinant of the hematopoietic side-population phenotype established its dual role as a pharmacological gatekeeper and stem cell marker.

    Evidence Immunohistochemistry with two independent antibodies across human tissues; retroviral transduction and transplantation assays in bone marrow cells; Hoechst 33342 efflux in transduced MCF-7 cells

    PMID:11309308 PMID:11533706 PMID:11801536

    Open questions at the time
    • Mechanism linking ABCG2 expression to stemness beyond dye efflux unclear
    • Blood–brain barrier functional significance not quantified in vivo at this stage
  3. 2001 High

    Demonstrating that residue 482 governs substrate specificity resolved why different drug-selected cell lines showed discordant resistance profiles and provided the first structure–function insight into the transmembrane drug-binding site.

    Evidence Sequencing of resistant lines, site-directed mutagenesis, vaccinia virus expression system with drug efflux and cytotoxicity assays

    PMID:11559526

    Open questions at the time
    • No atomic-level explanation for how position 482 alters binding pocket geometry
    • Only a few substrates tested at this point
  4. 2002 High

    Knockout mice revealed essential physiological roles for ABCG2 in porphyrin homeostasis and protection from dietary phototoxins, demonstrating that ABCG2 is not merely a drug-resistance factor but a guardian against endogenous and dietary toxins.

    Evidence Bcrp1−/− mice developed phototoxic lesions and protoporphyria; bone marrow transplant from wild-type donors rescued the phenotype

    PMID:12429862

    Open questions at the time
    • Full spectrum of endogenous substrates beyond porphyrins not yet defined
    • Tissue-specific contributions (erythroid vs. hepatic) incompletely resolved
  5. 2003 High

    Reconstituted vesicle transport assays quantified ATP-dependent transport of methotrexate, sulfated steroids (estrone 3-sulfate, DHEAS), and xenobiotic sulfate conjugates, establishing ABCG2 as a major sulfate conjugate transporter with defined kinetic parameters.

    Evidence Inside-out membrane vesicle assays with radiolabeled substrates, Km determination, and position-482 mutagenesis comparison

    PMID:12682043 PMID:14500392

    Open questions at the time
    • Glucuronide and glutathione conjugate transport appeared minor but was not systematically evaluated
    • In vivo relevance of steroid sulfate transport not yet demonstrated
  6. 2003 High

    Dominant-negative co-injection experiments in Xenopus oocytes proved that ABCG2 functions as a homodimer (or homomultimer), establishing the minimal functional unit required for transport.

    Evidence Co-injection of signature-motif mutant (S187T) cRNA with wild-type cRNA in Xenopus oocytes, dose-dependent suppression of transport

    PMID:14645676

    Open questions at the time
    • No direct cross-linking or analytical ultracentrifugation data at this stage
    • Whether higher-order oligomers exist in native membranes unresolved
  7. 2004 High

    Characterization of the Q141K polymorphism revealed that its functional deficit arises from reduced protein expression and impaired surface trafficking rather than altered catalytic activity, explaining variable drug pharmacokinetics in carriers.

    Evidence Transfection in LLC-PK1 and HEK293 cells with quantitative transport normalized to protein expression, immunofluorescence localization of SNP variants

    PMID:12479221 PMID:15553238

    Open questions at the time
    • Molecular mechanism of Q141K-mediated protein instability (ubiquitination, ER retention) not fully elucidated
    • Population-level pharmacokinetic consequences only partially quantified
  8. 2004 High

    Discovery that HIF-1α transcriptionally upregulates ABCG2 and that ABCG2 binds heme linked the transporter to hypoxia signaling and hematopoietic progenitor survival, explaining why stem cells expressing ABCG2 are protected under low-oxygen conditions.

    Evidence Bcrp1−/− progenitor colony assays under hypoxia, heme biosynthesis blockade rescue, HIF-1 reporter analysis

    PMID:15044468

    Open questions at the time
    • Whether HIF-1α acts on ABCG2 promoter directly or indirectly not fully resolved by ChIP at this stage
    • Relative contribution of porphyrin efflux vs. other substrates to stem cell protection unclear
  9. 2009 High

    Identification of ABCG2 as a renal urate efflux transporter, with Q141K causing 53% reduced transport, established a causal link between ABCG2 dysfunction, hyperuricemia, and gout—attributing ≥10% of gout cases in European-descent populations to this variant.

    Evidence Functional urate transport assay with site-directed mutagenesis, kidney brush-border localization, population genetic association in 14,783 individuals

    PMID:19506252 PMID:20368174

    Open questions at the time
    • Relative contribution of intestinal vs. renal ABCG2 to total urate excretion debated
    • Therapeutic strategies targeting ABCG2-mediated urate transport not developed
  10. 2010 High

    Low-resolution electron crystallography provided the first 3D structural view of ABCG2, revealing an inward-facing homodimer with separated NBDs and substrate-dependent conformational changes, bridging the gap between biochemical data and structural biology.

    Evidence 2D crystallization and cryo-EM projection maps of purified ABCG2 from Pichia pastoris, with and without mitoxantrone

    PMID:20399185 PMID:26249353

    Open questions at the time
    • Resolution too low to identify substrate-binding residues
    • Outward-facing conformation not captured
  11. 2017 High

    The first high-resolution cryo-EM structure of ABCG2 (with 5D3 Fab) identified two cholesterol molecules in the central multidrug-binding pocket, providing an atomic-level framework for understanding polyspecific substrate recognition, allosteric inhibition, and the structural basis of disease-causing SNPs.

    Evidence Cryo-EM of ABCG2–5D3 Fab complex at near-atomic resolution with functional transport validation

    PMID:28554189

    Open questions at the time
    • Structures with diverse drug substrates bound (e.g., urate, methotrexate) not yet reported in this timeline
    • Outward-facing ATP-bound state not captured
    • Mechanism of cholesterol modulation of transport cycle incompletely understood

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the complete conformational cycle of ABCG2 during ATP-driven transport, the structural basis by which residue 482 mutations alter substrate selectivity at atomic resolution, the relative physiological contributions of intestinal versus renal ABCG2 to urate homeostasis, and whether ABCG2's effect on cell cycle progression reflects direct transport of an endogenous signaling substrate.
  • Full transport cycle intermediates not structurally resolved
  • Endogenous signaling substrates linking ABCG2 to cell cycle regulation unidentified
  • Tissue-specific conditional knockouts needed to delineate organ-level contributions

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 7 GO:0140657 ATP-dependent activity 5
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-382551 Transport of small molecules 7 R-HSA-1430728 Metabolism 4 R-HSA-9748784 Drug ADME 3
Partners
E2F1HIF1APPARGPPARGC1ASIRT1
Complex memberships
ABCG2 homodimer

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 ABCG2 (BCRP) was identified as a novel 655-amino acid ABC half-transporter overexpressed in multidrug-resistant MCF-7/AdrVp breast cancer cells; enforced BCRP expression conferred resistance to mitoxantrone, doxorubicin, and daunorubicin, reduced daunorubicin accumulation, and caused ATP-dependent enhancement of rhodamine 123 efflux, establishing ABCG2 as a functional xenobiotic efflux transporter. cDNA cloning, transfection/overexpression, drug accumulation/efflux assays, RNA fingerprinting Proceedings of the National Academy of Sciences of the United States of America High 9861027
1998 ABCG2 (ABCP) was independently cloned as a human placenta-specific ABC transporter; the predicted protein has a single N-terminal ATP-binding domain and a single C-terminal transmembrane domain (half-transporter architecture), closely related to Drosophila white and yeast ADP1, and maps to chromosome 4q22. cDNA cloning, sequence analysis, chromosomal mapping, Northern blot Cancer research High 9850061
1999 MXR/BCRP/ABCG2 was independently cloned from mitoxantrone-resistant cells and shown to have homology to the Drosophila white gene; overexpression correlated with resistance to topotecan, SN-38, and mitoxantrone, and pharmacodynamic analysis showed that 70% of the intracellular topotecan pool was effluxed within 30 seconds in overexpressing cells. Differential hybridization, Northern blot, drug efflux kinetics, partial revertant correlation Cancer research High 10493507 9892175
2001 Amino acid 482 in ABCG2 is a critical determinant of substrate specificity: wild-type arginine at position 482 (R482) transports mitoxantrone but not rhodamine 123 or doxorubicin, whereas acquired mutations R482T or R482G broaden the substrate profile to include rhodamine 123 and anthracyclines, as confirmed by vaccinia virus expression system. Gene sequencing, vaccinia virus expression, drug efflux and cytotoxicity assays, mutagenesis Cancer research High 11559526
2001 Bcrp1/ABCG2 expression is a conserved molecular determinant of the hematopoietic 'side population' (SP) stem cell phenotype; enforced ABCG2 expression directly conferred the SP phenotype to bone marrow cells and caused reduced maturing progeny both in vitro and in transplantation assays, while Bcrp1 mRNA was sharply downregulated upon differentiation. Retroviral transduction, flow cytometry (Hoechst 33342 exclusion), transplantation assay, RT-PCR Nature medicine High 11533706
2001 ABCG2 (MXR) transports mitoxantrone and prazosin (BODIPY-prazosin) but not rhodamine 123 in wild-type-expressing cells; fumitremorgin C (FTC) at 1 µM causes half-maximal inhibition of ABCG2-associated ATPase activity, establishing that ABCG2 is an ATPase whose hydrolytic activity is coupled to substrate transport. Flow cytometry efflux assay, ATPase activity assay, Northern blot Biochimica et biophysica acta High 11406094
2001 ABCG2 is expressed in the SP of hematopoietic stem cells and directly mediates Hoechst 33342 efflux; MCF-7 cells retrovirally transduced with ABCG2 showed lower Hoechst 33342 uptake equivalent to drug-selected resistant cells, establishing Hoechst 33342 as an ABCG2 substrate. Retroviral transduction, flow cytometry, Hoechst 33342 transport assay Clinical cancer research High 11801536
2001 Subcellular localization of BCRP/ABCG2 in normal human tissues was mapped by immunohistochemistry: BCRP localizes prominently to the apical membrane of placental syncytiotrophoblasts, the apical surface of small intestine and colon epithelium, the liver canalicular membrane, and venous/capillary endothelium (but not arterial endothelium); differential glycosylation was observed between drug-selected cell lines. Immunohistochemistry with monoclonal antibodies BXP-21 and BXP-34, immunoprecipitation, Western blot, RT-PCR Cancer research High 11309308
2002 In Abcg2 knockout mice, Bcrp1 is required to protect against the dietary phototoxin pheophorbide a (a chlorophyll catabolite) and against protoporphyria: knockout mice developed severe phototoxic skin lesions upon light exposure and showed 10-fold elevated erythrocyte protoporphyrin IX; bone marrow transplant from wild-type mice cured the protoporphyria, establishing that erythroid ABCG2 controls porphyrin levels. Knockout mouse model, dietary challenge, bone marrow transplantation, erythrocyte porphyrin measurement Proceedings of the National Academy of Sciences of the United States of America High 12429862
2002 The Q141K (C421A) SNP in ABCG2 results in markedly decreased protein expression (similar mRNA but low protein) and low-level drug resistance in transfected cells; in a Japanese population, heterozygous and homozygous carriers express less BCRP protein, indicating reduced efflux capacity. Transfection, Western blot, drug resistance assay, population genotyping Molecular cancer therapeutics High 12479221
2003 Wild-type ABCG2 (Arg482) transports methotrexate (MTX) and its polyglutamate forms (MTX-Glu2, MTX-Glu3) in an ATP-dependent, osmotically sensitive manner as shown by inside-out membrane vesicle transport assays; the mutant Gly482 form does not transport MTX, demonstrating that position 482 also governs MTX transport specificity. Inside-out membrane vesicle transport assay, fumitremorgin C inhibition, competition assay Cancer research High 14500392
2003 ABCG2 transports sulfated conjugates of steroids and xenobiotics (estrone 3-sulfate, DHEAS, 4-methylumbelliferone sulfate, E3040 sulfate) in an ATP-dependent manner in membrane vesicles, with Km values of ~13–27 µM; transport is preferentially for sulfate conjugates over glucuronide and glutathione conjugates, suggesting physiological roles in steroid sulfate homeostasis. Inside-out membrane vesicle transport assay with radiolabeled substrates, inhibition studies The Journal of biological chemistry High 12682043
2003 Functional BCRP expressed in Xenopus laevis oocytes is a homodimer or homomultimer: mutations in the ATP-binding cassette signature motif (S187T or S187A) abolished transport activity despite high expression, and co-injection of dominant-negative S187T with active R482T suppressed transport in a dose-dependent manner; wild-type transported only mitoxantrone and flavopiridol, while R482T additionally transported daunorubicin and rhodamine 123. Xenopus oocyte heterologous expression, cRNA co-injection dominant-negative analysis, accumulation and efflux assays Molecular pharmacology High 14645676
2003 BCRP/ABCG2 was localized at the luminal surface of microvessel endothelium in human brain by immunofluorescence confocal microscopy and RT-PCR/Western blot, closely resembling the localization of P-gp, establishing BCRP as a component of the blood-brain barrier. RT-PCR, Western blotting, immunofluorescence confocal microscopy on human brain tissue Neuroreport High 12438926
2004 ABCG2 binds heme and interacts with porphyrins; under hypoxia, Bcrp1(-/-) progenitor cells have reduced colony-forming ability, and this susceptibility is reversed by blocking heme biosynthesis; BCRP expression is transcriptionally upregulated by the HIF-1 hypoxia-inducible factor complex, positioning ABCG2 as a hypoxia-regulated porphyrin efflux transporter in stem cell survival. Knockout mouse progenitor colony assay, heme biosynthesis inhibition, HIF-1 reporter/ChIP-type analysis, binding assays The Journal of biological chemistry High 15044468
2004 Pheophorbide a (PhA) is an ABCG2-specific substrate; FTC-inhibitable PhA transport in cell lines correlates with ABCG2 surface expression (measured by anti-ABCG2 antibody 5D3), and transport is not observed in cells expressing P-glycoprotein or MRP1 alone, validating PhA as a specific ABCG2 probe. Flow cytometry transport assay, FTC inhibition, antibody 5D3 surface staining correlation Cancer research High 14973080
2004 SNP variants of BCRP/ABCG2 affect protein expression and localization: Q141K and S441N variants show significantly lower protein expression than wild type; S441N causes intracellular (non-apical) localization; the transport activity per unit protein (for E1S, DHEAS, MTX) is unchanged for Q141K, indicating the functional deficit is due to reduced protein expression/surface delivery rather than intrinsic catalytic deficiency. Transfection in LLC-PK1 and HEK293 cells, immunofluorescence localization, membrane vesicle transport assays, Western blot Pharmaceutical research High 15553238
2005 BCRP/ABCG2 mediates biliary excretion of the statin pitavastatin: ATP-dependent uptake was demonstrated in BCRP-expressing membrane vesicles (Km ~5.7 µM for human, ~4.8 µM for mouse), and biliary excretion clearance of pitavastatin in Bcrp1(-/-) mice was reduced to one-tenth of wild type, while MRP2-deficient rats showed no change. Membrane vesicle transport assay, Bcrp1(-/-) mouse in vivo biliary excretion, Eisai hyperbilirubinemic rat comparison, transcellular transport in MDCK double transfectants Molecular pharmacology High 15955871
2007 Bcrp/ABCG2 limits the oral bioavailability and tissue distribution (brain, testis, epididymis, fetus) of phytoestrogens (daidzein, genistein, coumestrol): Bcrp(-/-) mice showed increased plasma levels after oral administration and significantly elevated brain and testis tissue-to-plasma ratios; Bcrp protein was localized to the luminal membrane of endothelial cells in testis and epididymis. Bcrp(-/-) knockout mouse pharmacokinetics, MDCK transfected cell transcellular transport, immunolocalization Molecular pharmacology High 17644650
2009 ABCG2 is a urate efflux transporter located in the brush border membrane of kidney proximal tubule cells: functional assays confirmed ATP-dependent urate transport; the Q141K mutation (rs2231142) caused 53% reduction in urate transport rates; population data showed rs2231142 is causal for elevated serum urate and gout, attributing ≥10% of gout cases in whites to this variant. Site-directed mutagenesis, functional urate transport assay, kidney localization, population-based genetic association (14,783 individuals) Proceedings of the National Academy of Sciences of the United States of America High 19506252
2009 Common dysfunctional ABCG2 variants (Q141K, Q126X) essentially block gut and renal urate excretion, causing gout: urate transport assays confirmed ABCG2 is a high-capacity urate secretion transporter; 10% of gout patients had genotype combinations resulting in >75% reduction of ABCG2 function (OR 25.8). Urate transport assay, gene sequencing of hyperuricemia patients, quantitative trait locus analysis Science translational medicine High 20368174
2010 Structural analysis of purified human BCRP/ABCG2 by 2D electron crystallography at 5 Å resolution revealed an asymmetric ring-shaped transmembrane domain structure; in the absence of mitoxantrone, ABCG2 adopts a more open conformation, while in the presence of mitoxantrone, a more closed/compact conformation is observed, consistent with inward-facing substrate-bound and substrate-free states. Purification from Pichia pastoris, 2D crystallization, cryo-electron microscopy projection maps, homology modeling Structure High 20399185
2010 ABCG2 knockdown (RNAi) in MCF-7/MX and A549 cancer cells significantly inhibited cell proliferation, reduced the S-phase fraction, and caused G0/G1 arrest associated with downregulation of cyclin D3 and upregulation of p21; chemical inhibition by fumitremorgin C produced a similar cell cycle effect, suggesting ABCG2 has a role in cell cycle progression beyond drug transport. RNA interference knockdown, flow cytometry cell cycle analysis, chemical inhibitor FTC, Western blot for cyclins International journal of cancer Medium 19642144
2012 Steroid hormones allosterically inhibit BCRP/ABCG2-mediated transport: estradiol, testosterone, progesterone, and androstenedione inhibited BCRP-mediated estrone sulfate uptake in membrane vesicles with Ki values of 5–217 µM through non-competitive (allosteric) inhibition; Bcrp is localized in the cortex of the adrenal gland and plasma membranes of adipocytes. Membrane vesicle transport assay with Ki determination, immunohistochemistry, quantitative PCR Cell and tissue research Medium 22581381
2013 E2F1 transcription factor directly activates ABCG2 expression and drives chemotherapeutic drug resistance through ABCG2 in vitro and in vivo; E2F1-induced drug efflux was abrogated by ABCG2 inhibition, and a significant correlation between elevated E2F1 and ABCG2 expression was identified in human lung cancers. E2F1 overexpression and knockdown, luciferase reporter assay (direct promoter activation), in vivo xenograft, gene expression correlation in clinical samples Oncogene Medium 24276245
2015 3D electron crystallography of full-length human ABCG2 without nucleotides or substrates revealed a symmetric homodimer in an inward-facing conformation with widely separated nucleotide-binding domains (NBDs), similar to murine ABCB1, and cytoplasmic extensions connecting TMDs to NBDs were resolved; this was the first 3D structure of full-length ABCG2. 2D crystallization, electron crystallography, subtomogram averaging at ~2 nm resolution, homology model refinement Acta crystallographica Section D High 26249353
2016 ABCG2 mediates androgen efflux in prostate stem cells (PSCs), maintaining an undifferentiated state: Ko143-mediated ABCG2 inhibition increased intracellular androgen levels, leading to nuclear AR translocation, upregulation of AR-regulated genes, and luminal differentiation; in vivo, Ko143 reduced tumor growth and increased percentage of differentiated CK8+/AR+ luminal cells. Ko143 pharmacological inhibition, siRNA knockdown, nuclear AR translocation assay, xenograft mouse model, immunohistochemistry Molecular cancer research Medium 27856956
2016 SIRT1 upregulates ABCG2 expression in the ileum through a PGC-1α/PPARγ signaling axis: resveratrol-activated SIRT1 deacetylated PGC-1α, which activated PPARγ to drive ABCG2 transcription; siRNA knockdown of PGC-1α or PPARγ abolished the SIRT1-induced upregulation of ABCG2, reducing serum uric acid in hyperuricemic mice. siRNA knockdown, resveratrol treatment, SIRT1 activation, Western blot, hyperuricemic mouse model Endocrine Medium 27022940
2017 High-resolution cryo-EM structure of human ABCG2 in complex with inhibitory antibody 5D3 Fab fragments was determined: two cholesterol molecules were found bound in the central hydrophobic multidrug-binding pocket within an inward-facing translocation pathway between transmembrane domains; structural data rationalized disease-causing SNPs, explained allosteric inhibition by 5D3 antibody, and revealed a cholesterol recognition mechanism shared with other G-subfamily ABC transporters. Cryo-electron microscopy (high-resolution), complex with 5D3 antibody Fab fragments, functional in vitro transport analyses Nature High 28554189
2017 Placental BCRP/ABCG2 expression is down-regulated by hypoxia: HIF-1α activation (by CoCl2 or 3% O2) reduced BCRP mRNA and protein by 30–75% in BeWo trophoblast cells and impaired substrate efflux activity; women at high altitude (chronic hypoxia) showed reduced BCRP in placental microvillous membranes correlating with elevated HIF-1α target expression. CoCl2 and hypoxia treatment, HIF-1α Western blot/ELISA, qPCR, fluorescent substrate transport assay, human placental tissue analysis Placenta Medium 28292469
2008 Lapatinib directly inhibits ABCG2 transport function: lapatinib stimulated ABCG2 ATPase activity, inhibited photolabeling of ABCG2 with [125I]iodoarylazidoprazosin in a concentration-dependent manner, inhibited ABCG2-mediated methotrexate and E217βG transport, increased mitoxantrone accumulation in ABCG2-overexpressing cells, and enhanced paclitaxel efficacy in ABCB1-overexpressing xenografts, without affecting transporter expression. ATPase stimulation assay, photoaffinity labeling, transport assay, accumulation assay, xenograft in vivo Cancer research High 18829547
2004 Imatinib mesylate (STI571) is a substrate for BCRP/ABCG2: imatinib competes with mitoxantrone for export in BCRP-overexpressing cell lines, and BCRP-mediated efflux is reversed by the fumitremorgin C analog Ko-143; this suggests BCRP can influence gastrointestinal absorption and cellular resistance to imatinib. Drug competition efflux assay, Ko-143 inhibition, multiple BCRP-overexpressing cell lines Blood High 15251980
2007 Pregnancy hormones regulate placental BCRP expression: estriol (E3), human placental lactogen (hPL), and prolactin (hPRL) increased BCRP protein and mRNA ~2–3-fold in BeWo cells; the inductive effect of E3 was abrogated by ER antagonist ICI-182,780; testosterone combined with E2 increased BCRP through E2-mediated upregulation of testosterone receptor (TR) mRNA; hCG had no effect. Hormone treatment in BeWo cells, immunoblotting, qRT-PCR, ER antagonist, siRNA knockdown of ERα, immunofluorescence Pharmaceutical research Medium 17823853
2008 ABCG2 undergoes post-translational modifications including disulfide bond formation, ubiquitination, and ER-associated degradation that regulate its expression and trafficking; these modifications were identified as key determinants of ABCG2 protein stability and surface delivery. Biochemical characterization (disulfide bond analysis, ubiquitination assay, ER degradation experiments) Xenobiotica Medium 18668433
2010 BCRP/Abcg2 plays a dominant role in intestinal genistein sulfate excretion: in Bcrp knockout mice, genistein sulfate excretion was reduced >90% in small intestine and became undetectable in colon; genistein glucuronide excretion also decreased significantly (78%), demonstrating that BCRP drives apical efflux of sulfated and glucuronidated isoflavone conjugates to prevent backward hydrolysis. Bcrp(-/-) knockout mouse intestinal perfusion model, LC/MS metabolite quantification, inhibitor studies The AAPS journal High 20582579

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The ABC transporter Bcrp1/ABCG2 is expressed in a wide variety of stem cells and is a molecular determinant of the side-population phenotype. Nature medicine 1819 11533706
1998 A multidrug resistance transporter from human MCF-7 breast cancer cells. Proceedings of the National Academy of Sciences of the United States of America 1789 9861027
2019 Blood-Brain Barrier: From Physiology to Disease and Back. Physiological reviews 1645 30280653
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 Establishment and Dysfunction of the Blood-Brain Barrier. Cell 1304 26590417
2005 Multidrug resistance proteins: role of P-glycoprotein, MRP1, MRP2, and BCRP (ABCG2) in tissue defense. Toxicology and applied pharmacology 1086 15845415
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2001 Subcellular localization and distribution of the breast cancer resistance protein transporter in normal human tissues. Cancer research 928 11309308
2003 Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene 815 14576842
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2005 Side population is enriched in tumorigenic, stem-like cancer cells, whereas ABCG2+ and ABCG2- cancer cells are similarly tumorigenic. Cancer research 724 16024622
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
1999 Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes. Cancer research 681 9892175
1998 A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance. Cancer research 670 9850061
2012 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nature genetics 657 23263486
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2002 The breast cancer resistance protein protects against a major chlorophyll-derived dietary phototoxin and protoporphyria. Proceedings of the National Academy of Sciences of the United States of America 631 12429862
2001 From MDR to MXR: new understanding of multidrug resistance systems, their properties and clinical significance. Cellular and molecular life sciences : CMLS 566 11497241
2008 Association of three genetic loci with uric acid concentration and risk of gout: a genome-wide association study. Lancet (London, England) 551 18834626
2004 The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. The Journal of biological chemistry 526 15044468
2009 Identification of a urate transporter, ABCG2, with a common functional polymorphism causing gout. Proceedings of the National Academy of Sciences of the United States of America 525 19506252
2009 Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS genetics 506 19503597
2014 Role of the breast cancer resistance protein (BCRP/ABCG2) in drug transport--an update. The AAPS journal 497 25236865
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1999 Overexpression of the BCRP/MXR/ABCP gene in a topotecan-selected ovarian tumor cell line. Cancer research 434 10493507
2010 Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science (New York, N.Y.) 421 20360068
2000 The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). Journal of cell science 418 10806112
2010 Genome-wide association study of hematological and biochemical traits in a Japanese population. Nature genetics 406 20139978
2002 C421A polymorphism in the human breast cancer resistance protein gene is associated with low expression of Q141K protein and low-level drug resistance. Molecular cancer therapeutics 378 12479221
2008 ABCG2: a perspective. Advanced drug delivery reviews 372 19135109
2001 Acquired mutations in the MXR/BCRP/ABCP gene alter substrate specificity in MXR/BCRP/ABCP-overexpressing cells. Cancer research 368 11559526
2009 Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population. Science translational medicine 350 20368174
2008 Lapatinib (Tykerb, GW572016) reverses multidrug resistance in cancer cells by inhibiting the activity of ATP-binding cassette subfamily B member 1 and G member 2. Cancer research 344 18829547
2017 Structure of the human multidrug transporter ABCG2. Nature 340 28554189
2004 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump. Blood 338 15251980
2002 Localisation of breast cancer resistance protein in microvessel endothelium of human brain. Neuroreport 322 12438926
2012 Role of breast cancer resistance protein (BCRP/ABCG2) in cancer drug resistance. Biochemical pharmacology 321 22248732
2009 ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and rosuvastatin. Clinical pharmacology and therapeutics 320 19474787
2002 The multidrug resistance transporter ABCG2 (breast cancer resistance protein 1) effluxes Hoechst 33342 and is overexpressed in hematopoietic stem cells. Clinical cancer research : an official journal of the American Association for Cancer Research 319 11801536
2007 ABCG2: determining its relevance in clinical drug resistance. Cancer metastasis reviews 313 17323127
2001 Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells. Clinical cancer research : an official journal of the American Association for Cancer Research 310 11205902
2011 Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels. Molecular pharmaceutics 308 21707071
2004 Pheophorbide a is a specific probe for ABCG2 function and inhibition. Cancer research 303 14973080
2005 Role of the breast cancer resistance protein (ABCG2) in drug transport. The AAPS journal 294 16146333
2006 Role of ABCG2/BCRP in biology and medicine. Annual review of pharmacology and toxicology 278 16402910
2003 ABCG2 transports sulfated conjugates of steroids and xenobiotics. The Journal of biological chemistry 236 12682043
2001 A functional assay for detection of the mitoxantrone resistance protein, MXR (ABCG2). Biochimica et biophysica acta 223 11406094
1999 Camptothecin resistance: role of the ATP-binding cassette (ABC), mitoxantrone-resistance half-transporter (MXR), and potential for glucuronidation in MXR-expressing cells. Cancer research 223 10606239
2005 Involvement of BCRP (ABCG2) in the biliary excretion of pitavastatin. Molecular pharmacology 212 15955871
2004 Functional analysis of SNPs variants of BCRP/ABCG2. Pharmaceutical research 198 15553238
2006 Pharmacogenetics of ABCG2 and adverse reactions to gefitinib. Journal of the National Cancer Institute 187 17148776
2003 Wild-type breast cancer resistance protein (BCRP/ABCG2) is a methotrexate polyglutamate transporter. Cancer research 182 14500392
2013 Molecular pharmacology of ABCG2 and its role in chemoresistance. Molecular pharmacology 181 24021215
2008 ABCG2: structure, function and role in drug response. Expert opinion on drug metabolism & toxicology 175 18370855
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2007 Modulation of human BCRP (ABCG2) activity by anti-HIV drugs. The Journal of antimicrobial chemotherapy 163 17202245
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2003 Breast cancer resistance protein (BCRP/ABCG2) induces cellular resistance to HIV-1 nucleoside reverse transcriptase inhibitors. Molecular pharmacology 121 12488537
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2000 BCRP/MXR/ABCP expression in topotecan-resistant human breast carcinoma cells. Biochemical pharmacology 109 10930538
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2005 BCRP transports dipyridamole and is inhibited by calcium channel blockers. Pharmaceutical research 97 16247709
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2005 Transport of anthelmintic benzimidazole drugs by breast cancer resistance protein (BCRP/ABCG2). Drug metabolism and disposition: the biological fate of chemicals 92 15703302
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2012 Impact of genetic variation in breast cancer resistance protein (BCRP/ABCG2) on sunitinib pharmacokinetics. Drug metabolism and pharmacokinetics 74 22673043
2002 Expression of the BCRP gene (ABCG2/MXR/ABCP) in childhood acute lymphoblastic leukaemia. British journal of haematology 74 12100141
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2000 Effects of MDR1 and MDR3 P-glycoproteins, MRP1, and BCRP/MXR/ABCP on the transport of (99m)Tc-tetrofosmin. Biochemical pharmacology 70 10856437
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2010 The bioflavonoid kaempferol is an Abcg2 substrate and inhibits Abcg2-mediated quercetin efflux. Drug metabolism and disposition: the biological fate of chemicals 67 21139040
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2004 Regulation of expression of multixenobiotic resistance (MXR) genes by environmental factors in the blue mussel Mytilus edulis. Aquatic toxicology (Amsterdam, Netherlands) 63 15210293
2003 Functional characterization of human breast cancer resistance protein (BCRP, ABCG2) expressed in the oocytes of Xenopus laevis. Molecular pharmacology 63 14645676
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2006 Down-regulation of BCRP/ABCG2 in colorectal and cervical cancer. Biochemical and biophysical research communications 61 16554028
2010 Breast cancer resistance protein (BCRP) and sulfotransferases contribute significantly to the disposition of genistein in mouse intestine. The AAPS journal 60 20582579
2000 Seasonal variation of MXR and stress proteins in the common mussel, Mytilus galloprovincialis. Aquatic toxicology (Amsterdam, Netherlands) 59 10958952
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2007 The emerging pharmacotherapeutic significance of the breast cancer resistance protein (ABCG2). British journal of pharmacology 56 17375082
2008 Pharmacogenomic importance of ABCG2. Pharmacogenomics 52 18681776
2010 Suppression of ABCG2 inhibits cancer cell proliferation. International journal of cancer 51 19642144
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2002 Modulation of the atypical multidrug-resistant phenotype by a hammerhead ribozyme directed against the ABC transporter BCRP/MXR/ABCG2. Cancer gene therapy 48 12082458
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2014 First evidence for toxic defense based on the multixenobiotic resistance (MXR) mechanism in Daphnia magna. Aquatic toxicology (Amsterdam, Netherlands) 46 24486881
2007 Identification and functional assessment of BCRP polymorphisms in a Korean population. Drug metabolism and disposition: the biological fate of chemicals 46 17237154
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2007 Molecular and cellular characterization of ABCG2 in the prostate. BMC urology 44 17425799
2012 Breast cancer resistance protein (BCRP/ABCG2) localises to the nucleus in glioblastoma multiforme cells. Xenobiotica; the fate of foreign compounds in biological systems 43 22401348
2008 Role of breast cancer resistance protein (Bcrp/Abcg2) in fetal protection during gestation in rat. Toxicology letters 42 18450391
2009 Molecular expression and functional evidence of a drug efflux pump (BCRP) in human corneal epithelial cells. Current eye research 41 19172464
2008 Modulation of breast cancer resistance protein (BCRP/ABCG2) by non-basic chalcone analogues. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences 41 18598762
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2013 Dietary polyacetylenes of the falcarinol type are inhibitors of breast cancer resistance protein (BCRP/ABCG2). European journal of pharmacology 35 24269959
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2005 Piperazinobenzopyranones and phenalkylaminobenzopyranones: potent inhibitors of breast cancer resistance protein (ABCG2). Journal of medicinal chemistry 35 16279786
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2008 Human ABC transporters ABCG2 (BCRP) and ABCG4. Xenobiotica; the fate of foreign compounds in biological systems 33 18668433
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2017 Metabolism of KO143, an ABCG2 inhibitor. Drug metabolism and pharmacokinetics 32 28619281
2020 SOX9 enhances sorafenib resistance through upregulating ABCG2 expression in hepatocellular carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 31 32554246
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2015 Three-dimensional structure of the human breast cancer resistance protein (BCRP/ABCG2) in an inward-facing conformation. Acta crystallographica. Section D, Biological crystallography 30 26249353