Multidrug resistance-associated protein 2
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RefSeq (protein) | |||||||||
Location (UCSC) | Chr 10: 99.78 – 99.85 Mb | Chr 19: 43.77 – 43.83 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Multidrug resistance-associated protein 2 (MRP2) also called canalicular multispecific organic anion transporter 1 (cMOAT) or ATP-binding cassette sub-family C member 2 (ABCC2) is a protein that in humans is encoded by the ABCC2 gene.[5][6][7]
Function
MRP2 is a member of the superfamily of
MRP2 is also expressed in the
MRP2 inhibitors
Drug | Class | Indications | Source | Structure |
---|---|---|---|---|
probenecid | uricosuric | gout hyperuricemia |
[9] | |
furosemide | loop diuretic | heart failure edema |
[9] | |
ritonavir | protease inhibitor | antiretroviral
|
[10] | |
saquinavir | protease inhibitor | antiretroviral
|
[11] | |
lamivudine | Nucleoside analog
|
antiviral | [12] | |
abacavir | Nucleoside analog
|
antiretroviral
|
[12] | |
emtricitabine | Nucleoside analog
|
antiviral | [12] | |
efavirenz | NNRTI
|
antiretroviral
|
[12] | |
delavirdine | NNRTI
|
antiretroviral
|
[12] | |
nevirapine | NNRTI
|
antiretroviral
|
[12] | |
cidofovir | nucleoside phosphonate | antiviral | [13] | |
adefovir | nucleoside phosphonate | antiviral | [11] | |
tenofovir
|
nucleoside phosphonate | antiviral | [12] |
Clinical significance
Dubin–Johnson syndrome
Several different mutations in this gene have been observed in patients with Dubin–Johnson syndrome (DJS), an autosomal recessive disorder characterized by conjugated hyperbilirubinemia.[7][14]
Iatrogenic Fanconi syndrome
Many negatively charged metabolic waste products are eliminated from the body by the kidneys. These
Drugs that inhibit the MRP2 transporter can cause a buildup of organic anions inside renal proximal tubule cells. If some of these organic anions inhibit mitochondrial DNA synthesis, it may cause
are also nucleoside phosphonates that inhibit MRP2 and have been associated with Fanconi syndrome.Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- ^ The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP229".
See also
- ATP-binding cassette transporter
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000023839 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000025194 - 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 8797578.
- S2CID 46739365.
- ^ a b "Entrez Gene: ABCC2 ATP-binding cassette, sub-family C (CFTR/MRP), member 2".
- PMID 16403838.
- ^ PMID 10727523.
- PMID 15076241.
- ^ S2CID 6030800.
- ^ S2CID 46141353.
- PMID 11602668.
- PMID 27406372.
- PMID 12606735.
- PMID 19334329.
- PMID 9257778.
Further reading
- Keppler D, König J (2001). "Hepatic secretion of conjugated drugs and endogenous substances". Semin. Liver Dis. 20 (3): 265–72. S2CID 25626705.
- Gerk PM, Vore M (2002). "Regulation of expression of the multidrug resistance-associated protein 2 (MRP2) and its role in drug disposition". J. Pharmacol. Exp. Ther. 302 (2): 407–15. S2CID 873234.
- Mayer R, Kartenbeck J, Büchler M, et al. (1995). "Expression of the MRP gene-encoded conjugate export pump in liver and its selective absence from the canalicular membrane in transport-deficient mutant hepatocytes". J. Cell Biol. 131 (1): 137–50. PMID 7559771.
- Büchler M, König J, Brom M, et al. (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". J. Biol. Chem. 271 (25): 15091–8. PMID 8662992.
- Paulusma CC, Kool M, Bosma PJ, et al. (1997). "A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin-Johnson syndrome" (PDF). Hepatology. 25 (6): 1539–42. S2CID 22635775.
- Wada M, Toh S, Taniguchi K, et al. (1998). "Mutations in the canilicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia II/Dubin-Johnson syndrome". Hum. Mol. Genet. 7 (2): 203–7. PMID 9425227.
- Evers R, Kool M, van Deemter L, et al. (1998). "Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA". J. Clin. Invest. 101 (7): 1310–9. PMID 9525973.
- Kajihara S, Hisatomi A, Mizuta T, et al. (1999). "A splice mutation in the human canalicular multispecific organic anion transporter gene causes Dubin-Johnson syndrome". Biochem. Biophys. Res. Commun. 253 (2): 454–7. PMID 9878557.
- Toh S, Wada M, Uchiumi T, et al. (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". Am. J. Hum. Genet. 64 (3): 739–46. PMID 10053008.
- Schaub TP, Kartenbeck J, König J, et al. (1999). "Expression of the MRP2 gene-encoded conjugate export pump in human kidney proximal tubules and in renal cell carcinoma". J. Am. Soc. Nephrol. 10 (6): 1159–69. PMID 10361853.
- Tsujii H, König J, Rost D, et al. (1999). "Exon-intron organization of the human multidrug-resistance protein 2 (MRP2) gene mutated in Dubin-Johnson syndrome". Gastroenterology. 117 (3): 653–60. PMID 10464142.
- Kocher O, Comella N, Gilchrist A, et al. (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". Lab. Invest. 79 (9): 1161–70. PMID 10496535.
- Tanaka T, Uchiumi T, Hinoshita E, et al. (1999). "The human multidrug resistance protein 2 gene: functional characterization of the 5'-flanking region and expression in hepatic cells". Hepatology. 30 (6): 1507–12. S2CID 22514353.
- St-Pierre MV, Serrano MA, Macias RI, et al. (2000). "Expression of members of the multidrug resistance protein family in human term placenta". Am. J. Physiol. Regul. Integr. Comp. Physiol. 279 (4): R1495–503. S2CID 36043361.
- Keitel V, Kartenbeck J, Nies AT, et al. (2001). "Impaired protein maturation of the conjugate export pump multidrug resistance protein 2 as a consequence of a deletion mutation in Dubin-Johnson syndrome". Hepatology. 32 (6): 1317–28. S2CID 20920288.
- Ito S, Ieiri I, Tanabe M, et al. (2001). "Polymorphism of the ABC transporter genes, MDR1, MRP1 and MRP2/cMOAT, in healthy Japanese subjects". Pharmacogenetics. 11 (2): 175–84. PMID 11266082.
- Mor-Cohen R, Zivelin A, Rosenberg N, et al. (2001). "Identification and functional analysis of two novel mutations in the multidrug resistance protein 2 gene in Israeli patients with Dubin-Johnson syndrome". J. Biol. Chem. 276 (40): 36923–30. PMID 11477083.
- Mallants R, Van Oosterwyck K, Van Vaeck L, Mols R, De Clercq E, Augustijns P (2005). "Multidrug resistance-associated protein 2 (MRP2) affects hepatobiliary elimination but not the intestinal disposition of tenofovir disoproxil fumarate and its metabolites". S2CID 6888528.
External links
- ABCC2+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.