Affinage

Showing ABCC2 — MRP2 is a alias.

ABCC2

ATP-binding cassette sub-family C member 2 · UniProt Q92887

Length
1545 aa
Mass
174.2 kDa
Annotated
2026-06-09
100 papers in source corpus 24 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ABCC2 (MRP2/cMOAT) is an ATP-binding cassette transporter that functions as a primary-active export pump at the apical/canalicular membrane of polarized epithelia, driving unidirectional efflux of glutathione, glucuronate, and sulfate conjugates—including bilirubin glucuronosides, leukotriene C4, and a broad range of drug conjugates—from hepatocytes, renal tubule, and intestinal cells (PMID:8662992, PMID:9525973, PMID:16847695). Its canalicular function was established by its absence in transport-deficient hyperbilirubinemic mutant rats and by reconstituted apical conjugate transport in polarized MDCK cells, which also revealed that a polarized cellular context is required for correct plasma-membrane routing (PMID:8662992, PMID:9525973, PMID:9892468). In vivo loss-of-function studies define ABCC2 as the principal route for biliary elimination of conjugated and cytotoxic compounds—glutathionyl-cyclophosphamide, methotrexate and 7-hydroxymethotrexate, and etoposide—where its absence is buffered by basolateral ABCC3, which redirects substrates back to the circulation (PMID:19088030, PMID:20028753, PMID:14617693). Apical residence is dynamically controlled by ezrin: PKC-driven phosphorylation of ezrin at Thr567 governs MRP2 membrane insertion versus internalization, with internalized protein degraded via the E3 ligase GP78, a pathway activated in cholestasis (PMID:24091598, PMID:26212029). Transcription is induced by the nuclear receptors PXR, CAR, and FXR through a shared upstream ER-8 element and by Nrf2 through proximal antioxidant response elements, while post-transcriptional control operates through alternative polyadenylation/miR-379 and through ISGylation of hnRNPA2B1 that suppresses ABCC2 translation (PMID:11706036, PMID:16426233, PMID:31926942, PMID:31757862). Loss-of-function mutations clustering in the cytoplasmic ATP-binding cassette region cause Dubin-Johnson syndrome by impairing protein maturation, apical targeting, and transport activity (PMID:9425227, PMID:10053008, PMID:12388192).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1996 High

    Established the molecular identity of the canalicular conjugate export pump by cloning ABCC2 and tying it to the defect in hyperbilirubinemic mutant rats, answering what protein mediates ATP-dependent biliary excretion of conjugates.

    Evidence cDNA cloning, immunoblotting, confocal immunofluorescence, and comparison with two transport-deficient mutant rat strains

    PMID:8662992

    Open questions at the time
    • Substrate range defined only for glutathione/glucuronate conjugates
    • Transport mechanism not reconstituted in a defined system
  2. 1996 Medium

    Linked ABCC2 overexpression to cisplatin resistance and mapped the locus, introducing a role in cancer drug efflux.

    Evidence RT-PCR/Northern blot and FISH comparing cisplatin-resistant vs sensitive cancer cell lines

    PMID:8797578

    Open questions at the time
    • No direct transport reconstitution for cisplatin
    • Correlation does not establish causal efflux
  3. 1998 High

    Demonstrated that ABCC2 requires a polarized cellular context for apical membrane routing and directly transports glutathione conjugates and vinblastine, answering where it acts and what it carries.

    Evidence cDNA transfection in polarized MDCK cells with transbilayer transport assays, immunofluorescence, and inhibitor controls

    PMID:9525973 PMID:9892468

    Open questions at the time
    • Trafficking determinants for polarized routing not identified
    • MDCK is a heterologous epithelial model
  4. 1998 High

    Identified ABCC2 loss-of-function mutations as the molecular cause of Dubin-Johnson syndrome, connecting the transporter to human disease.

    Evidence Sequencing of genomic DNA from DJS patients identifying deletions and a missense mutation in the ABC signature region

    PMID:9425227

    Open questions at the time
    • Mechanism by which mutations abolish function not yet defined in this study
  5. 1999 Medium

    Defined gene structure and showed DJS mutations cluster in the cytoplasmic ATP-binding cassette region, localizing the functionally critical domain.

    Evidence Genomic exon-intron determination and mutation mapping in DJS patients

    PMID:10053008

    Open questions at the time
    • No structural model of the ATP-binding domain
    • Single lab characterization
  6. 1999 Low

    Proposed a scaffolding interaction by detecting PDZK1 binding to the ABCC2 C-terminus.

    Evidence Yeast two-hybrid assay

    PMID:10496535

    Open questions at the time
    • Single yeast two-hybrid without Co-IP or pulldown validation
    • Functional consequence of the interaction untested
  7. 2001 High

    Established nuclear-receptor transcriptional control of ABCC2 via a shared ER-8 element, explaining drug- and bile-acid-mediated induction.

    Evidence Luciferase reporters, EMSA/supershift, promoter mutagenesis, primary hepatocytes, and PXR-null mice

    PMID:11706036

    Open questions at the time
    • Relative contribution of PXR/CAR/FXR in vivo not partitioned
    • Coactivator requirements unaddressed
  8. 2002 High

    Defined the cellular mechanism of a DJS mutation, showing I1173F causes ER retention, proteasomal degradation, and loss of apical targeting and transport.

    Evidence Stable transfection, vesicular transport assays, glycosylation analysis, proteasome inhibition, and HepG2 localization

    PMID:12388192

    Open questions at the time
    • Generality across other DJS mutations not tested here
    • Chaperone/quality-control machinery not identified
  9. 2003 High

    Demonstrated ABCC2 is required for biliary elimination of a glutathione-conjugated chemotherapeutic, extending its substrate scope to cyclophosphamide metabolites.

    Evidence Biliary and tissue pharmacokinetics in ABCC2-deficient TR- vs wild-type rats

    PMID:14617693

    Open questions at the time
    • Kinetic parameters of transport not determined
  10. 2004 High

    Showed ABCC2 canalicular density is acutely regulated by exocytic insertion, establishing trafficking as a control point for bile formation.

    Evidence Rat infusion, biliary secretion, canalicular membrane vesicle uptake, immunoelectron microscopy, with Mrp2-deficient controls

    PMID:14752835

    Open questions at the time
    • Signaling pathway driving genipin-induced exocytosis not defined
  11. 2005 Medium

    Linked an ABCC2 variant to impaired drug elimination, connecting genetic variation to pharmacokinetics.

    Evidence Patient sequencing, transfected CHO functional assay, and methotrexate pharmacokinetics

    PMID:15864128

    Open questions at the time
    • Single variant, single lab
    • Mechanism of activity loss not resolved
  12. 2006 High

    Established Nrf2/ARE-driven transcriptional induction of ABCC2, linking it to the oxidative stress response.

    Evidence EMSA, promoter deletion, CAT reporters, Nrf2 siRNA, and dominant-negative experiments in mice and hepatoma cells

    PMID:16426233

    Open questions at the time
    • Interplay between Nrf2 and nuclear-receptor inputs not addressed
  13. 2006 Medium

    Consolidated the apical-exclusive localization across tissues and the compensatory ABCC3 upregulation in deficiency.

    Evidence Review synthesizing immunolocalization, transport, mutant-animal, and patient data

    PMID:16847695

    Open questions at the time
    • No new primary data
    • Compensation mechanism not mechanistically dissected
  14. 2007 Medium

    Showed substrate handling is regioselective using quercetin glucuronides, refining substrate recognition.

    Evidence In silico homology modeling validated by competition assays in Sf9 vesicles and inhibition in Caco-2 cells

    PMID:17478601

    Open questions at the time
    • Binding-site model not experimentally confirmed structurally
  15. 2008 High

    Defined ABCC2/ABCC3 epistasis in methotrexate disposition, showing ABCC3 reroutes substrate to circulation when ABCC2 is lost.

    Evidence Pharmacokinetics in Abcc2 and Abcc2;Abcc3 double-knockout mice

    PMID:19088030

    Open questions at the time
    • Human relevance of compensation magnitude not quantified
  16. 2009 High

    Extended the ABCC2/ABCC3 alternative-elimination model to etoposide and its glucuronide.

    Evidence Pharmacokinetics across single, double, and triple knockout mouse strains

    PMID:20028753

    Open questions at the time
    • Tissue-specific contributions beyond liver not parsed
  17. 2011 Medium

    Connected ABCC2 biliary excretion to downstream drug metabolism, showing deficiency raises hepatic exposure and metabolism of erythromycin.

    Evidence Abcc2 knockout mice with Cyp3a controls and human cohort genotyping with breath test

    PMID:21451505

    Open questions at the time
    • Indirect mechanism inferred
    • Human variant effect modest
  18. 2013 Medium

    Identified ezrin phosphorylation as a determinant of MRP2 membrane localization, linking cytoskeletal adaptors to apical residence.

    Evidence Ezrin T567A mutant expression in Caco-2 cells with immunofluorescence/Western and in vivo rat tissue profiling

    PMID:24091598

    Open questions at the time
    • Direct ezrin-MRP2 binding not shown in this study
    • PKC isoform specificity unresolved here
  19. 2015 High

    Established the cholestasis-driven internalization-degradation axis, showing PKC-phospho-Ezrin Thr567 drives MRP2 internalization and GP78 mediates its proteasomal degradation.

    Evidence Reciprocal Co-IP, PKC overexpression/inhibition in HepG2, and cholestatic vs control human liver biopsies

    PMID:26212029

    Open questions at the time
    • Order of phosphorylation, internalization, and ubiquitination not kinetically resolved
  20. 2017 High

    Resolved functional consequences of multiple coding SNPs, distinguishing surface-expression defects from intrinsic transport changes.

    Evidence Site-directed mutagenesis, stable HEK293 expression, flow cytometry, substrate accumulation, and vesicle transport assays

    PMID:28405913

    Open questions at the time
    • In vivo pharmacologic impact of each variant untested
    • Single lab
  21. 2019 Medium

    Revealed 3'-UTR alternative polyadenylation as a post-transcriptional switch via loss of miR-379 regulation.

    Evidence 3'-RACE, luciferase reporter assays, and tissue expression analysis

    PMID:31757862

    Open questions at the time
    • Physiological triggers of APA choice unknown
    • Reporter-based, single lab
  22. 2020 Medium

    Defined a translational repression mechanism in which ISGylation of hnRNPA2B1 blocks ABCC2 5'UTR binding, linking ABCC2 levels to cisplatin sensitivity.

    Evidence WT/mutant ISG15 overexpression, RNA-IP, Western blot, viability assays, and ABCC2 overexpression rescue

    PMID:31926942

    Open questions at the time
    • Generality beyond ovarian cancer cells untested
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How transcriptional, post-transcriptional, and trafficking control are integrated to set apical ABCC2 levels in different tissues, and the high-resolution structural basis of substrate recognition, remain unresolved.
  • No experimental atomic structure of human ABCC2 in the corpus
  • Cross-talk among PXR/CAR/FXR, Nrf2, miR-379, and ISGylation pathways not integrated
  • Mechanism of polarized apical sorting not molecularly defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 4 GO:0140657 ATP-dependent activity 3
Localization
GO:0005886 plasma membrane 3 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-9748784 Drug ADME 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
EZRGP78HNRNPA2B1PDZK1

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 ABCC2 (cMrp) was cloned from rat liver as a canalicular membrane glycoprotein of ~190 kDa that mediates ATP-dependent transport of glutathione and glucuronate conjugates from hepatocytes into bile; it was absent from the canalicular membrane of two hyperbilirubinemic mutant rat strains (Eisai hyperbilirubinemic rat and GY/TR-), which are deficient in ATP-dependent conjugate transport across the canalicular membrane. cDNA cloning, immunoblotting, double immunofluorescence and confocal laser scanning microscopy, comparison with transport-deficient mutant rats The Journal of biological chemistry High 8662992
1996 Human cMOAT (ABCC2) was overexpressed in cisplatin-resistant cancer cell lines and was associated with decreased drug accumulation, identifying ABCC2 as a potential cisplatin efflux transporter; its chromosomal locus was mapped to 10q24 by FISH. RT-PCR/Northern blot, FISH, comparison of cisplatin-resistant vs. sensitive cell lines Cancer research Medium 8797578
1998 ABCC2 (cMOAT) expressed in polarized MDCK cells localizes to the apical plasma membrane and mediates ATP-dependent transport of glutathione conjugates (S-(2,4-dinitrophenyl)-glutathione, glutathione conjugate of ethacrynic acid, S-(PGA1)-glutathione) and the anticancer drug vinblastine to the apical side; in non-polarized cells cMOAT was predominantly intracellular, indicating that a polarized cellular context is required for correct plasma membrane routing. cDNA transfection in polarized MDCK cells, transport assays across cell monolayers, immunofluorescence localization The Journal of clinical investigation High 9525973
1998 Mutations (two deletions and a missense mutation in the ATP-binding-cassette/active transport signature region) in the cMOAT gene were identified in patients with Dubin-Johnson syndrome, demonstrating that loss-of-function mutations in ABCC2 are the molecular basis of this hereditary conjugated hyperbilirubinemia. Mutation analysis of genomic DNA from DJS patients, sequencing Human molecular genetics High 9425227
1999 The human MRP2/cMOAT gene contains 32 exons with a structure conserved with other ABC genes; all DJS-causing mutations identified cluster in the cytoplasmic domain containing the two ATP-binding cassettes and linker region, with particular concentration in the first ATP-binding cassette domain, indicating this region is critical for transport function. Genomic sequencing, exon-intron structure determination, mutation characterization in DJS patients American journal of human genetics Medium 10053008
1999 PDZK1, a PDZ domain-containing protein, interacts with the carboxy-terminal portion of ABCC2 (cMOAT), as demonstrated by yeast two-hybrid assay, suggesting a scaffolding/clustering role for ABCC2 at the membrane. Yeast two-hybrid assay Laboratory investigation Low 10496535
2001 ABCC2 (MRP2) transcription is regulated by the nuclear receptors PXR, CAR, and FXR, which bind as heterodimers with RXRα to an everted repeat (ER-8) element 440 bp upstream of the transcription start site; mutation of this element abolished nuclear receptor responsiveness, and induction by PXR agonists was absent in PXR-null mice. Luciferase reporter assays, gel-shift and supershift assays, primary hepatocyte treatments, PXR-null mouse experiments The Journal of biological chemistry High 11706036
2002 The Dubin-Johnson syndrome mutation I1173F in ABCC2 causes the mutant protein to be retained predominantly in the endoplasmic reticulum as a core-glycosylated form, degraded by proteasomes, and unable to mediate ATP-dependent transport of leukotriene C4; in polarized HepG2 cells, GFP-tagged MRP2-I1173F was found at the apical membrane in only 5% of cells compared with 80% for wild-type MRP2. Stable transfection in HEK-293 cells, vesicular transport assays, immunofluorescence in HepG2 cells, Western blotting (glycosylation), proteasome inhibitor experiments American journal of physiology. Gastrointestinal and liver physiology High 12388192
2004 Genipin enhances ABCC2 (Mrp2)-mediated bile formation by stimulating exocytosis and insertion of Mrp2 protein into the canalicular membrane, increasing protein density in the canalicular membrane without altering mRNA levels; this was absent in Mrp2-deficient rats, confirming Mrp2 dependence. Rat infusion experiments, biliary secretion assays, ATP-dependent uptake in canalicular membrane vesicles, immunoelectron microscopy, Western blotting, compared in Mrp2-deficient rats Hepatology High 14752835
2005 A heterozygous ABCC2 mutation (R412G) in the cytoplasmic part of the second membrane-spanning domain was associated with impaired methotrexate elimination; functional analysis in transiently transfected CHO cells showed loss of transport activity for the G412 MRP2 mutant protein. Patient sequencing, functional analysis in transiently transfected CHO cells, pharmacokinetic measurement of methotrexate Pharmacogenetics and genomics Medium 15864128
2006 Nrf2 regulates ABCC2 (Mrp2) gene expression through binding to antioxidant response elements (ARE) in the Mrp2 promoter, preferentially the proximal ARE-1 element (-95 to -85); Nrf2 knockdown by siRNA suppressed tBHQ-induced ABCC2 mRNA induction, and Nrf2 overexpression increased ARE-1-mediated reporter activity, whereas dominant-negative Nrf2 repressed it. Gel-shift and supershift assays, promoter deletion analysis, CAT reporter assays, siRNA knockdown, BHA treatment of mice and hepatoma cells The Biochemical journal High 16426233
2006 ABCC2 is exclusively localized to the apical membrane domain of polarized cells (hepatocytes, renal proximal tubule epithelia, intestinal epithelia) and mediates unidirectional efflux of glutathione, glucuronate, and sulfate conjugates including leukotriene C4 and bilirubin glucuronosides; hereditary deficiency (Dubin-Johnson syndrome) results in compensatory upregulation of basolateral ABCC3. Review synthesizing prior experimental data (immunolocalization, transport assays, knockout/mutant animals, patient studies) Pflugers Archiv Medium 16847695
2007 ABCC2 (MRP2) transports quercetin glucuronides in a position-dependent manner; computational 3D modeling predicted that the 4'-O-β-D-glucuronide interacts most strongly and 3-O-β-D-glucuronide most weakly with ABCC2, which was confirmed experimentally using binding and competition assays on ABCC2-overexpressing Sf9 cells; MK571 and cyclosporin A inhibited export of quercetin glucuronides from Caco-2 cells. In silico 3D homology modeling, competition assays with ABCC2-overexpressing Sf9 membrane vesicles, transport inhibition assays in Caco-2 cells Drug metabolism and disposition Medium 17478601
2008 Abcc2 is the primary transporter responsible for biliary excretion of methotrexate (MTX) and its toxic metabolite 7-hydroxymethotrexate (7OH-MTX); in Abcc2-knockout mice, biliary excretion of MTX was 3.7-fold reduced, and in the absence of Abcc2, Abcc3 compensates by transporting MTX/7OH-MTX back into the circulation from the liver, leading to increased plasma levels and urinary excretion. Abcc2(-/-) and Abcc2;Abcc3(-/-) double knockout mouse pharmacokinetic studies, plasma AUC, biliary and urinary excretion measurements Clinical cancer research High 19088030
2009 Abcc2 is responsible for almost all hepatobiliary excretion of etoposide; in Abcc2-deficient mice, loss of biliary etoposide excretion is compensated by increased hepatic formation of etoposide glucuronide secreted via Abcc3 into blood; Abcc2;Abcc3 double-knockout mice showed high hepatic accumulation of etoposide glucuronide, demonstrating that Abcc2 and Abcc3 provide alternative pathways for hepatic elimination of etoposide glucuronide. Abcb1a/1b(-/-), Abcc2(-/-), Abcc3(-/-), double/triple knockout mouse pharmacokinetic studies Clinical cancer research High 20028753
2011 Abcc2 deficiency in mice was associated with a significant increase in erythromycin metabolism (without changes in Cyp3a expression or activity), indicating that impaired ABCC2 biliary excretion enhances hepatic exposure and thus metabolism of erythromycin; homozygosity for the reduced-function ABCC2 variant rs717620 in humans was also linked to increased erythromycin metabolism. Abcc2 knockout mouse studies, Cyp3a activity assays, human cohort genotyping and erythromycin breath test Clinical pharmacology and therapeutics Medium 21451505
2013 Ezrin phosphorylation status regulates MRP2/ABCC2 membrane localization along the intestinal tract; expression of a dephosphorylated ezrin mutant (T567A) in Caco-2 cells decreased both membrane surface-localized and total MRP2/ABCC2 expression, while conventional PKC isoforms regulate ezrin phosphorylation; phosphorylated ezrin co-distributes with Mrp2 along the rat gastrointestinal tract. Wild-type and T567A ezrin mutant expression in Caco-2 cells, immunofluorescence, Western blotting, in vivo rat tissue expression profiling American journal of physiology. Gastrointestinal and liver physiology Medium 24091598
2015 In human obstructive cholestasis, PKCα, δ, and ε are upregulated and stimulate phosphorylation of Ezrin at Thr567 (not Radixin), which drives MRP2 internalization from the canalicular membrane; ubiquitin ligase E3 GP78 mediates subsequent proteasomal degradation of internalized MRP2; Ezrin (not Radixin) co-immunoprecipitates with MRP2 in human livers, and increased phospho-Ezrin Thr567 correlates with increased co-precipitated MRP2 in cholestatic livers. Immunoprecipitation, Western blotting, Co-IP, PKC overexpression/inhibition in HepG2 cells, liver biopsies from cholestatic patients (n=30) vs. controls (n=23) Journal of hepatology High 26212029
2017 In vitro functional analysis of seven ABCC2 SNPs expressed in Flp-In HEK293 cells showed that the C2366T variant reduced MRP2 cell surface expression by 40-50% and reduced vesicular CDCF transport by 50%; the G1249A variant had decreased vesicular CDCF transport without altered surface expression; G3542T, T3563A, C3972T, and G4544A variants enhanced calcein AM efflux despite similar surface expression compared to wild type. Site-directed mutagenesis, stable expression in HEK293 cells, flow cytometry of surface expression, substrate accumulation assays, inverted membrane vesicle transport assays Pharmaceutical research High 28405913
2020 ISG15 suppresses ABCC2 protein expression in cisplatin-resistant ovarian cancer cells by ISGylating hnRNPA2B1, which normally binds the 5'UTR of ABCC2 mRNA to promote its translation; ISGylation blocks hnRNPA2B1 recruitment to ABCC2 mRNA, thereby suppressing ABCC2 translation; overexpression of wild-type (but not ISGylation-deficient) ISG15 reduced ABCC2 protein and sensitized cells to cisplatin, while ABCC2 overexpression blocked this sensitization. Overexpression of WT and mutant ISG15, RNA immunoprecipitation, Western blotting, cell viability assays, ABCC2 overexpression rescue experiments Biochimica et biophysica acta. Molecular cell research Medium 31926942
2003 ABCC2 (TR- rat model) mediates biliary transport of 4-glutathionylcyclophosphamide (GSCY); in ABCC2-deficient TR- rats, GSCY was absent from bile, and liver exposure to HCY and its metabolites was significantly increased, demonstrating that ABCC2 is required for biliary elimination of this glutathione conjugate of cyclophosphamide. Comparison of ABCC2-deficient TR- rats and wild-type Wistar rats after CY administration, biliary collection and quantification of GSCY, liver and plasma AUC measurements The Journal of pharmacology and experimental therapeutics High 14617693
2006 In freshly isolated rat hepatocytes, Mrp2 is confined to junctions between adjacent cells, intracellular compartments, and 'legacy' canalicular structures, not the basolateral membrane; functional accumulation of the Mrp2 substrate CDF in cellular compartments was sensitive to the MRP inhibitor MK571 and absent in hepatocytes from Mrp2-deficient rats, confirming functional Mrp2 activity in isolated hepatocytes despite loss of macroscopic canalicular polarity. Immunostaining and confocal microscopy of isolated rat hepatocytes, functional CDF accumulation assay, MK571 inhibition, Mrp2-deficient rat controls Drug metabolism and disposition Medium 17954525
1998 Rat cMOAT (ABCC2) expressed in polarized MDCK cells is functionally localized to the apical membrane and mediates preferential apical export of glutathione S-bimane (GS-B); this preferential apical export was inhibited by cyclosporin A. cDNA transfection in MDCK cells, GS-B export measurement from apical and basal compartments, cyclosporin A inhibition Pharmaceutical research Medium 9892468
2019 Alternative polyadenylation of ABCC2 mRNA produces 3'-UTR length variants; short ABCC2 3'-UTR variants lack the miR-379 binding site, and expression of these short variants in luciferase reporter assays leads to loss of miR-379/ABCC2 interaction and significant upregulation of ABCC2 expression, representing a posttranscriptional regulatory mechanism. 3'-RACE, luciferase reporter gene assays in vitro, tissue expression analysis Molecular pharmacology Medium 31757862

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer research 792 9270026
2001 Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor. The Journal of biological chemistry 727 11706036
1996 cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats. The Journal of biological chemistry 533 8662992
1996 A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. Cancer research 437 8797578
1998 Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA. The Journal of clinical investigation 423 9525973
2006 The apical conjugate efflux pump ABCC2 (MRP2). Pflugers Archiv : European journal of physiology 270 16847695
1997 A canalicular multispecific organic anion transporter (cMOAT) antisense cDNA enhances drug sensitivity in human hepatic cancer cells. Cancer research 236 9407953
1997 Hepatic canalicular membrane 5: Expression and localization of the conjugate export pump encoded by the MRP2 (cMRP/cMOAT) gene in liver. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 216 9212074
1998 Mutations in the canilicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome. Human molecular genetics 206 9425227
2006 Role of Nrf2 in the regulation of the Mrp2 (ABCC2) gene. The Biochemical journal 190 16426233
1999 Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/cMOAT) and mutations in the ATP-binding-cassette region in Dubin-Johnson syndrome. American journal of human genetics 187 10053008
2006 Structure and function of the MRP2 (ABCC2) protein and its role in drug disposition. Expert opinion on drug metabolism & toxicology 183 16863439
2002 Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ABCC2): its impact on drug disposition. Advanced drug delivery reviews 183 12406647
2006 Association between ABCC2 gene haplotypes and tenofovir-induced proximal tubulopathy. The Journal of infectious diseases 177 17083032
2007 Associations of ABCB1, ABCC2, and ABCG2 polymorphisms with irinotecan-pharmacokinetics and clinical outcome in patients with advanced non-small cell lung cancer. Cancer 169 17534875
1998 Characterization of MOAT-C and MOAT-D, new members of the MRP/cMOAT subfamily of transporter proteins. Journal of the National Cancer Institute 132 9827529
2014 Mis-splicing of the ABCC2 gene linked with Bt toxin resistance in Helicoverpa armigera. Scientific reports 130 25154974
1998 Excretion of GSSG and glutathione conjugates mediated by MRP1 and cMOAT/MRP2. Seminars in liver disease 126 9875554
1999 PDZK1, a novel PDZ domain-containing protein up-regulated in carcinomas and mapped to chromosome 1q21, interacts with cMOAT (MRP2), the multidrug resistance-associated protein. Laboratory investigation; a journal of technical methods and pathology 123 10496535
2005 Variable expression of MRP2 (ABCC2) in human placenta: influence of gestational age and cellular differentiation. Drug metabolism and disposition: the biological fate of chemicals 116 15821043
2014 Polymorphisms of the drug transporters ABCB1, ABCG2, ABCC2 and ABCC3 and their impact on drug bioavailability and clinical relevance. Expert opinion on drug metabolism & toxicology 113 25162314
2005 A mutation in the drug transporter gene ABCC2 associated with impaired methotrexate elimination. Pharmacogenetics and genomics 113 15864128
2006 Inhibition of MRP1/ABCC1, MRP2/ABCC2, and MRP3/ABCC3 by nucleoside, nucleotide, and non-nucleoside reverse transcriptase inhibitors. Drug metabolism and disposition: the biological fate of chemicals 109 17172311
2003 Overexpression of cMOAT (MRP2/ABCC2) is associated with decreased formation of platinum-DNA adducts and decreased G2-arrest in melanoma cells resistant to cisplatin. The Journal of investigative dermatology 109 12839578
2004 Genipin enhances Mrp2 (Abcc2)-mediated bile formation and organic anion transport in rat liver. Hepatology (Baltimore, Md.) 95 14752835
2002 Intestinal transport of irinotecan in Caco-2 cells and MDCK II cells overexpressing efflux transporters Pgp, cMOAT, and MRP1. Drug metabolism and disposition: the biological fate of chemicals 94 12065434
2002 A common Dubin-Johnson syndrome mutation impairs protein maturation and transport activity of MRP2 (ABCC2). American journal of physiology. Gastrointestinal and liver physiology 91 12388192
2006 Intestinal expression of P-glycoprotein (ABCB1), multidrug resistance associated protein 2 (ABCC2), and uridine diphosphate-glucuronosyltransferase 1A1 predicts the disposition and modulates the effects of the cholesterol absorption inhibitor ezetimibe in humans. Clinical pharmacology and therapeutics 89 16513445
2007 Localization of P-gp (Abcb1) and Mrp2 (Abcc2) in freshly isolated rat hepatocytes. Drug metabolism and disposition: the biological fate of chemicals 85 17954525
2006 ABCC2 (MRP2, cMOAT) can be localized in the nuclear membrane of ovarian carcinomas and correlates with resistance to cisplatin and clinical outcome. Clinical cancer research : an official journal of the American Association for Cancer Research 82 17145840
2008 Influence of genetic polymorphisms on intestinal expression and rifampicin-type induction of ABCC2 and on bioavailability of talinolol. Pharmacogenetics and genomics 80 18334920
2007 Nrf2-dependent and -independent induction of ABC transporters ABCC1, ABCC2, and ABCG2 in HepG2 cells under oxidative stress. Journal of experimental therapeutics & oncology 80 18038766
2009 P-glycoprotein (P-gp/Abcb1), Abcc2, and Abcc3 determine the pharmacokinetics of etoposide. Clinical cancer research : an official journal of the American Association for Cancer Research 77 20028753
2007 Association of the multidrug-resistance-associated protein gene (ABCC2) variants with intrahepatic cholestasis of pregnancy. Journal of hepatology 76 17997497
2002 Delineating the contribution of secretory transporters in the efflux of etoposide using Madin-Darby canine kidney (MDCK) cells overexpressing P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP1), and canalicular multispecific organic anion transporter (cMOAT). Drug metabolism and disposition: the biological fate of chemicals 73 11901101
1997 Do cMOAT (MRP2), other MRP homologues, and LRP play a role in MDR? Seminars in cancer biology 72 9441949
2007 Interaction of positional isomers of quercetin glucuronides with the transporter ABCC2 (cMOAT, MRP2). Drug metabolism and disposition: the biological fate of chemicals 71 17478601
2010 Impact of ABCC2 haplotypes on transcriptional and posttranscriptional gene regulation and function. The pharmacogenomics journal 69 20351751
1997 The canalicular multidrug resistance protein, cMRP/MRP2, a novel conjugate export pump expressed in the apical membrane of hepatocytes. Advances in enzyme regulation 67 9381978
2011 Common variants in ABCB1, ABCC2 and ABCG2 genes and clinical outcomes among women with advanced stage ovarian cancer treated with platinum and taxane-based chemotherapy: a Gynecologic Oncology Group study. Gynecologic oncology 64 22112610
1999 Overexpression of multidrug resistance genes MDR1 and cMOAT in human hepatocellular carcinoma and hepatoblastoma cell lines. International journal of oncology 63 10427140
2021 ABCB1, ABCG2, ABCC1, ABCC2, and ABCC3 drug transporter polymorphisms and their impact on drug bioavailability: what is our current understanding? Expert opinion on drug metabolism & toxicology 59 33459081
2011 Molecular characterization and functions of zebrafish ABCC2 in cellular efflux of heavy metals. Comparative biochemistry and physiology. Toxicology & pharmacology : CBP 59 21266201
1998 Expression of gamma-glutamylcysteine synthetase (gamma-GCS) and multidrug resistance-associated protein (MRP), but not human canalicular multispecific organic anion transporter (cMOAT), genes correlates with exposure of human lung cancers to platinum drugs. British journal of cancer 58 9569044
2008 Cloning and molecular characterization of apical efflux transporters (ABCB1, ABCB11 and ABCC2) in rainbow trout (Oncorhynchus mykiss) hepatocytes. Aquatic toxicology (Amsterdam, Netherlands) 56 19008001
2005 MRP2 (ABCC2) and cisplatin sensitivity in hepatocytes and human ovarian carcinoma. Gynecologic oncology 56 16213010
2008 Impact of Abcc2 (Mrp2) and Abcc3 (Mrp3) on the in vivo elimination of methotrexate and its main toxic metabolite 7-hydroxymethotrexate. Clinical cancer research : an official journal of the American Association for Cancer Research 54 19088030
2015 Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis. Journal of hepatology 51 26212029
2003 Brain access and anticonvulsant efficacy of carbamazepine, lamotrigine, and felbamate in ABCC2/MRP2-deficient TR- rats. Epilepsia 51 14636316
2014 New insights in the biology of ABC transporters ABCC2 and ABCC3: impact on drug disposition. Expert opinion on drug metabolism & toxicology 50 25380746
2008 Polymorphisms of MRP2 (ABCC2) are associated with susceptibility to nonalcoholic fatty liver disease. The Journal of nutritional biochemistry 50 18926681
2019 MicroRNA-998-3p contributes to Cry1Ac-resistance by targeting ABCC2 in lepidopteran insects. Insect biochemistry and molecular biology 48 31759051
2017 ABCC2 is associated with Bacillus thuringiensis Cry1Ac toxin oligomerization and membrane insertion in diamondback moth. Scientific reports 48 28539590
2015 Novel understanding of ABC transporters ABCB1/MDR/P-glycoprotein, ABCC2/MRP2, and ABCG2/BCRP in colorectal pathophysiology. World journal of gastroenterology 48 26557010
2006 RNA interference-triggered reversal of ABCC2-dependent cisplatin resistance in human cancer cells. Biochemical and biophysical research communications 47 16876126
2011 Impact of abcc2 [multidrug resistance-associated protein (MRP) 2], abcc3 (MRP3), and abcg2 (breast cancer resistance protein) on the oral pharmacokinetics of methotrexate and its main metabolite 7-hydroxymethotrexate. Drug metabolism and disposition: the biological fate of chemicals 46 21566011
2020 CRISPR-Mediated Knockout of the ABCC2 Gene in Ostrinia furnacalis Confers High-Level Resistance to the Bacillus thuringiensis Cry1Fa Toxin. Toxins 45 32290427
2006 Altered hepatobiliary disposition of 5 (and 6)-carboxy-2',7'-dichlorofluorescein in Abcg2 (Bcrp1) and Abcc2 (Mrp2) knockout mice. Drug metabolism and disposition: the biological fate of chemicals 45 16434545
2006 Molecular evidence and functional expression of a novel drug efflux pump (ABCC2) in human corneal epithelium and rabbit cornea and its role in ocular drug efflux. International journal of pharmaceutics 45 17156953
2016 Expressing a moth abcc2 gene in transgenic Drosophila causes susceptibility to Bt Cry1Ac without requiring a cadherin-like protein receptor. Insect biochemistry and molecular biology 44 27914919
2010 Association of ABCC2 polymorphisms with platinum-based chemotherapy response and severe toxicity in non-small cell lung cancer patients. Lung cancer (Amsterdam, Netherlands) 44 20943283
2020 Increased ABCC2 expression predicts cisplatin resistance in non-small cell lung cancer. Cell biochemistry and function 43 32815556
1997 Human canalicular multispecific organic anion transporter (cMOAT) is expressed in human lung, gastric, and colorectal cancer cells. Biochemical and biophysical research communications 43 9398612
1999 Induction of the multispecific organic anion transporter (cMoat/mrp2) gene and biliary glutathione secretion by the herbicide 2,4,5-trichlorophenoxyacetic acid in the mouse liver. The Biochemical journal 42 10377250
2014 Association of SCN1A, SCN2A and ABCC2 gene polymorphisms with the response to antiepileptic drugs in Chinese Han patients with epilepsy. Pharmacogenomics 40 25155934
2011 Gene-wide tagging study of the association between ABCC2, ABCC5 and ABCG2 genetic polymorphisms and multidrug resistance in epilepsy. Pharmacogenomics 39 21449672
2015 SCN1A, ABCC2 and UGT2B7 gene polymorphisms in association with individualized oxcarbazepine therapy. Pharmacogenomics 38 25823783
2017 FOXA transcriptional factor modulates insect susceptibility to Bacillus thuringiensis Cry1Ac toxin by regulating the expression of toxin-receptor ABCC2 and ABCC3 genes. Insect biochemistry and molecular biology 37 28736301
2011 Strain- and sex-dependent circadian changes in abcc2 transporter expression: implications for irinotecan chronotolerance in mouse ileum. PloS one 37 21674030
2015 Influence of ABCC2 and ABCC4 polymorphisms on tenofovir plasma concentrations in Thai HIV-infected patients. Antimicrobial agents and chemotherapy 36 25801567
1996 The function of the multidrug resistance proteins (MRP and cMRP) in drug conjugate transport and hepatobiliary excretion. Advances in enzyme regulation 36 8869738
2016 Associations of genetic polymorphisms of the transporters organic cation transporter 2 (OCT2), multidrug and toxin extrusion 1 (MATE1), and ATP-binding cassette subfamily C member 2 (ABCC2) with platinum-based chemotherapy response and toxicity in non-small cell lung cancer patients. Chinese journal of cancer 35 27590272
2012 Functional characterization of ABCC2 promoter polymorphisms and allele-specific expression. The pharmacogenomics journal 35 22664480
2011 ABCC2 (MRP2, cMOAT) localized in the nuclear envelope of breast carcinoma cells correlates with poor clinical outcome. Pathology oncology research : POR 35 21986666
2006 Simvastatin does not influence the intestinal P-glycoprotein and MPR2, and the disposition of talinolol after chronic medication in healthy subjects genotyped for the ABCB1, ABCC2 and SLCO1B1 polymorphisms. British journal of clinical pharmacology 33 16542205
2020 ISG15 suppresses translation of ABCC2 via ISGylation of hnRNPA2B1 and enhances drug sensitivity in cisplatin resistant ovarian cancer cells. Biochimica et biophysica acta. Molecular cell research 32 31926942
2019 Genetic contribution of ABCC2 to Dubin-Johnson syndrome and inherited cholestatic disorders. Liver international : official journal of the International Association for the Study of the Liver 32 31544333
2011 Genetic variation in the ABCC2 gene is associated with dose decreases or switches to other cholesterol-lowering drugs during simvastatin and atorvastatin therapy. The pharmacogenomics journal 31 22186618
2015 ABCB1, ABCC2, SCN1A, SCN2A, GABRA1 gene polymorphisms and drug resistant epilepsy in the Chinese Han population. Die Pharmazie 30 26189305
2012 Lack of association between ABCC2 gene variants and treatment response in epilepsy. Pharmacogenomics 29 22256867
2011 Effect of ABCC2 (MRP2) transport function on erythromycin metabolism. Clinical pharmacology and therapeutics 29 21451505
2017 In Vitro Assessment of the Effect of Antiepileptic Drugs on Expression and Function of ABC Transporters and Their Interactions with ABCC2. Molecules (Basel, Switzerland) 28 28961159
2016 The ABCC2 c.-24C>T polymorphism increases the risk of resistance to antiepileptic drugs: A meta-analysis. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia 28 27816260
2012 Associations between ABCC2 polymorphisms and cisplatin disposition and efficacy. Clinical pharmacology and therapeutics 28 22534871
2005 Single nucleotide polymorphisms in ABCC2 and ABCB1 genes and their clinical impact in physiology and drug response. Cancer letters 26 16377077
2021 Genomic Insights Into the Antifungal Activity and Plant Growth-Promoting Ability in Bacillus velezensis CMRP 4490. Frontiers in microbiology 25 33519779
2017 The human RNA surveillance factor Up-frameshift 1 inhibits hepatic cancer progression by targeting MRP2/ABCC2. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 25 28554132
2019 Effects of MTHFR and ABCC2 gene polymorphisms on antiepileptic drug responsiveness in Jordanian epileptic patients. Pharmacogenomics and personalized medicine 24 31354331
2019 Association of ABCC2 with levels and toxicity of methotrexate in Malaysian Childhood Acute Lymphoblastic Leukemia (ALL). Pediatric hematology and oncology 24 31870219
2016 Role of ABCB1, ABCG2, ABCC2 and ABCC5 transporters in placental passage of zidovudine. Biopharmaceutics & drug disposition 24 26390406
2013 The effects of ABCC2 G1249A polymorphism on the risk of resistance to antiepileptic drugs: a meta-analysis of the literature. Genetic testing and molecular biomarkers 24 24325761
2003 ABCC2-mediated biliary transport of 4-glutathionylcyclophosphamide and its contribution to elimination of 4-hydroxycyclophosphamide in rat. The Journal of pharmacology and experimental therapeutics 24 14617693
1998 Transfected rat cMOAT is functionally expressed on the apical membrane in Madin-Darby canine kidney (MDCK) cells. Pharmaceutical research 24 9892468
2022 Sec24C mediates a Golgi-independent trafficking pathway that is required for tonoplast localisation of ABCC1 and ABCC2. The New phytologist 23 35510797
2019 Alternative Polyadenylation of ABC Transporters of the C-Family (ABCC1, ABCC2, ABCC3) and Implications on Posttranscriptional Micro-RNA Regulation. Molecular pharmacology 19 31757862
2018 Mutation analysis of the ABCC2 gene in Chinese patients with Dubin-Johnson syndrome. Experimental and therapeutic medicine 19 30344695
2013 Effect of the drug transporters ABCG2, Abcg2, ABCB1 and ABCC2 on the disposition, brain accumulation and myelotoxicity of the aurora kinase B inhibitor barasertib and its more active form barasertib-hydroxy-QPA. Investigational new drugs 19 23315030
2013 Ezrin regulates the expression of Mrp2/Abcc2 and Mdr1/Abcb1 along the rat small intestinal tract. American journal of physiology. Gastrointestinal and liver physiology 19 24091598
2021 Clinical Relevance of ABCB1, ABCG2, and ABCC2 Gene Polymorphisms in Chronic Myeloid Leukemia Patients Treated With Nilotinib. Frontiers in oncology 18 34055641
2017 In Vitro Transport Activity and Trafficking of MRP2/ABCC2 Polymorphic Variants. Pharmaceutical research 18 28405913

Missed literature

Know a paper Affinage missed for ABCC2? Flag it for the maintainers and the community.

No submissions yet.