- 関
- canalicular multispecific organic anion transporter
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/09/07 17:18:58」(JST)
[Wiki en表示]
| ATP-binding cassette, sub-family C (CFTR/MRP), member 2 |
| Identifiers |
| Symbols |
ABCC2; ABC30; CMOAT; DJS; MRP2; cMRP |
| External IDs |
OMIM: 601107 MGI: 1352447 HomoloGene: 68052 ChEMBL: 5748 GeneCards: ABCC2 Gene |
| Gene Ontology |
| Molecular function |
• protein binding
• ATP binding
• organic anion transmembrane transporter activity
• ATPase activity, coupled to transmembrane movement of substances
|
| Cellular component |
• plasma membrane
• integral to plasma membrane
• apical plasma membrane
• intercellular canaliculus
|
| Biological process |
• transport
• organic anion transport
• transmembrane transport
|
| Sources: Amigo / QuickGO |
|
| RNA expression pattern |
|
| More reference expression data |
| Orthologs |
| Species |
Human |
Mouse |
|
| Entrez |
1244 |
12780 |
|
| Ensembl |
ENSG00000023839 |
ENSMUSG00000025194 |
|
| UniProt |
Q92887 |
Q8VI47 |
|
| RefSeq (mRNA) |
NM_000392 |
NM_013806 |
|
| RefSeq (protein) |
NP_000383 |
NP_038834 |
|
| Location (UCSC) |
Chr 10:
101.54 – 101.61 Mb |
Chr 19:
43.78 – 43.84 Mb |
|
| PubMed search |
[1] |
[2] |
|
|
|
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.[1][2][3]
Contents
- 1 Function
- 2 MRP2 inhibitors
- 3 Clinical significance
- 3.1 Dubin-Johnson syndrome
- 3.2 Iatrogenic Fanconi syndrome
- 4 Interactive pathway map
- 5 See also
- 6 References
- 7 Further reading
- 8 External links
Function[edit source | edit]
MRP2 is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). More specifically, this protein is a member of the MRP subfamily, which is involved in multi-drug resistance. This protein is expressed in the canalicular (apical) part of the hepatocyte and functions in biliary transport. Substrates include anticancer drugs such as vinblastine; therefore, this protein appears to contribute to drug resistance in mammalian cells.
MRP2 is also expressed in on the apical membrane of proximal renal tubule endothelial cells where they are involved in the excretion of small organic anions.[4]₳
MRP2 inhibitors[edit source | edit]
| Drug |
Class |
Indications |
Source |
Structure |
| probenecid |
uricosuric |
gout
hyperuricemia |
[5] |
|
| furosemide |
loop diuretic |
heart failure
edema |
[5] |
|
| ritonavir |
protease inhibitor |
antiretroviral |
[6] |
|
| saquinavir |
protease inhibitor |
antiretroviral |
[7] |
|
| lamivudine |
Nucleoside analog |
antiviral |
[8] |
|
| abacavir |
Nucleoside analog |
antiretroviral |
[8] |
|
| emtricitabine |
Nucleoside analog |
antiviral |
[8] |
|
| efavirenz |
NNRTI |
antiretroviral |
[8] |
|
| delavirdine |
NNRTI |
antiretroviral |
[8] |
|
| nevirapine |
NNRTI |
antiretroviral |
[8] |
|
| cidofovir |
nucleoside phosphonate |
antiviral |
[9] |
|
| adefovir |
nucleoside phosphonate |
antiviral |
[7] |
|
| tenofovir |
nucleoside phosphonate |
antiviral |
[8] |
|
Clinical significance[edit source | edit]
Dubin-Johnson syndrome[edit source | edit]
Several different mutations in this gene have been observed in patients with Dubin-Johnson syndrome (DJS), an autosomal recessive disorder characterized by conjugated hyperbilirubinemia.[3]
Iatrogenic Fanconi syndrome[edit source | edit]
Many negatively charged metabolic waste products are eliminated from the body by the kidneys. These organic anions are transported from the blood into the endothelial cells of the renal proximal tubules by the OAT1 transporter. From there, these waste molecules are transported into the lumen of the tubule by the MRP2 transporter. Many drugs are eliminated from the body by this mechanism. Some of these drugs pass through the MRP2 transporter slowly. This may cause a build up of organic anions in the cytoplasm of the cells.
Drugs that inhibit the MRP2 transporter can cause a build up of organic anions inside renal proximal tubule cells. If some of these organic anions inhibit mitochondrial DNA synthesis, it may cause iatrogenic Fanconi syndrome. The nucleoside phosphonate adefovir is a MRP2 inhibitor that has been linked to kidney disease.[10] Tenofovir[11] and cidofovir[12] are also nucleoside phosphonates that inhibit MRP2 and have been associated with Fanconi syndrome.
Interactive pathway map[edit source | edit]
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
- ^ The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP46359".
See also[edit source | edit]
- ATP-binding cassette transporter
References[edit source | edit]
- ^ Taniguchi K, Wada M, Kohno K, Nakamura T, Kawabe T, Kawakami M, Kagotani K, Okumura K, Akiyama S, Kuwano M (Oct 1996). "A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation". Cancer Res 56 (18): 4124–9. PMID 8797578.
- ^ van Kuijck MA, Kool M, Merkx GF, Geurts van Kessel A, Bindels RJ, Deen PM, van Os CH (Sep 1997). "Assignment of the canalicular multispecific organic anion transporter gene (CMOAT) to human chromosome 10q24 and mouse chromosome 19D2 by fluorescent in situ hybridization". Cytogenet Cell Genet 77 (3-4): 285–7. doi:10.1159/000134599. PMID 9284939.
- ^ a b "Entrez Gene: ABCC2 ATP-binding cassette, sub-family C (CFTR/MRP), member 2".
- ^ Sekine T, Miyazaki H, Endou H (February 2006). "Molecular physiology of renal organic anion transporters". Am. J. Physiol. Renal Physiol. 290 (2): F251–61. doi:10.1152/ajprenal.00439.2004. PMID 16403838.
- ^ a b Bakos E, Evers R, Sinkó E, Váradi A, Borst P, Sarkadi B (April 2000). "Interactions of the human multidrug resistance proteins MRP1 and MRP2 with organic anions". Mol. Pharmacol. 57 (4): 760–8. PMID 10727523.
- ^ Peyrière H, Reynes J, Rouanet I, et al. (March 2004). "Renal tubular dysfunction associated with tenofovir therapy: report of 7 cases". J. Acquir. Immune Defic. Syndr. 35 (3): 269–73. PMID 15076241.
- ^ a b Gimenez F, Fernandez C, Mabondzo A (June 2004). "Transport of HIV protease inhibitors through the blood–brain barrier and interactions with the efflux proteins, P-glycoprotein and multidrug resistance proteins". J. Acquir. Immune Defic. Syndr. 36 (2): 649–58. PMID 15167283.
- ^ a b c d e f g Weiss J, Theile D, Ketabi-Kiyanvash N, Lindenmaier H, Haefeli WE (March 2007). "Inhibition of MRP1/ABCC1, MRP2/ABCC2, and MRP3/ABCC3 by nucleoside, nucleotide, and non-nucleoside reverse transcriptase inhibitors". Drug Metab. Dispos. 35 (3): 340–4. doi:10.1124/dmd.106.012765. PMID 17172311.
- ^ Miller DS (November 2001). "Nucleoside phosphonate interactions with multiple organic anion transporters in renal proximal tubule". J. Pharmacol. Exp. Ther. 299 (2): 567–74. PMID 11602668.
- ^ Marcellin P, Chang TT, Lim SG, et al. (February 2003). "Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B". N. Engl. J. Med. 348 (9): 808–16. doi:10.1056/NEJMoa020681. PMID 12606735.
- ^ Atta MG, Fine DM (March 2009). "Editorial comment: tenofovir nephrotoxicity--the disconnect between clinical trials and real-world practice". AIDS Read 19 (3): 118–9. PMID 19334329.
- ^ Vittecoq D, Dumitrescu L, Beaufils H, Deray G (August 1997). "Fanconi syndrome associated with cidofovir therapy". Antimicrob. Agents Chemother. 41 (8): 1846. PMC 164022. PMID 9257778.
Further reading[edit source | edit]
- Keppler D, König J (2001). "Hepatic secretion of conjugated drugs and endogenous substances.". Semin. Liver Dis. 20 (3): 265–72. doi:10.1055/s-2000-9391. PMID 11076395.
- 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. doi:10.1124/jpet.102.035014. PMID 12130697.
- 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. doi:10.1083/jcb.131.1.137. PMC 2120605. 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. doi:10.1074/jbc.271.25.15091. 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.". Hepatology 25 (6): 1539–42. doi:10.1002/hep.510250635. PMID 9185779.
- 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. doi:10.1093/hmg/7.2.203. 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. doi:10.1172/JCI119886. PMC 508708. 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. doi:10.1006/bbrc.1998.9780. 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. doi:10.1086/302292. PMC 1377791. 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. doi:10.1016/S0016-5085(99)70459-2. 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. doi:10.1002/hep.510300617. PMID 10573531.
- 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. PMID 11004020.
- 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. doi:10.1053/jhep.2000.19791. PMID 11093739.
- 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. doi:10.1097/00008571-200103000-00008. 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. doi:10.1074/jbc.M105047200. 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". Xenobiotica 35 (10-11): 1055–66. doi:10.1080/00498250500354493. PMID 16393861.
External links[edit source | edit]
- ABCC2 protein, human at the US 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.
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Membrane proteins, carrier proteins: membrane transport proteins ABC-transporter (TC 3A1)
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| A |
- A1
- A2
- A3
- A4
- A7
- A8
- A12
- A13
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| B |
- B1
- B2-3 (B2
- B3)
- B4
- B5
- B6
- B7
- B9
- B11
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|
| C |
- C1
- C2
- C3
- C4
- C5
- C6
- C7
- C8-9 (C8, C9)
- C10
- C11
- C13
|
|
| D |
|
|
| E |
|
|
| F |
|
|
| G |
- G1
- G2
- G4
- Sterolin (G5, G8)
|
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|
see also ABC transporter disorders
B memb: cead, trns (1A, 1C, 1F, 2A, 3A1, 3A2-3, 3D), othr
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UpToDate Contents
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English Journal
- Canalicular membrane MRP2/ABCC2 internalization is determined by Ezrin Thr567 phosphorylation in human obstructive cholestasis.
- Chai J1, Cai SY2, Liu X1, Lian W1, Chen S3, Zhang L1, Feng X1, Cheng Y1, He X4, He Y5, Chen L1, Wang R1, Wang H6, Boyer JL2, Chen W7.
- Journal of hepatology.J Hepatol.2015 Dec;63(6):1440-8. doi: 10.1016/j.jhep.2015.07.016. Epub 2015 Jul 23.
- BACKGROUND & AIMS: Multidrug resistance-associated protein 2 (MRP2) excretes conjugated organic anions including bilirubin and bile acids. Malfunction of MRP2 leads to jaundice in patients. Studies in rodents indicate that Radixin plays a critical role in determining Mrp2 canalicular membrane ex
- PMID 26212029
- Enhancement effect of resveratrol on the intestinal absorption of bestatin by regulating PEPT1, MDR1 and MRP2 in vivo and in vitro.
- Jia Y1, Liu Z2, Huo X3, Wang C4, Meng Q5, Liu Q6, Sun H7, Sun P8, Yang X9, Shu X10, Liu K11.
- International journal of pharmaceutics.Int J Pharm.2015 Nov 10;495(1):588-98. doi: 10.1016/j.ijpharm.2015.09.042. Epub 2015 Sep 21.
- The purpose of present study was to assess the enhancing effect of resveratrol (Res) on the absorption of bestatin and clarify the related molecular mechanism. Res facilitated bestatin absorption by down-regulating both protein and gene levels of multidrug resistance 1 (Mdr1) and Multidrug resistanc
- PMID 26394120
- Fasiglifam (TAK-875) Inhibits Hepatobiliary Transporters: A Possible Factor Contributing to Fasiglifam-Induced Liver Injury.
- Li X1, Zhong K1, Guo Z1, Zhong D1, Chen X2.
- Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.2015 Nov;43(11):1751-9. doi: 10.1124/dmd.115.064121. Epub 2015 Aug 14.
- Fasiglifam (TAK-875), a selective G-protein-coupled receptor 40 agonist, was developed for the treatment of type 2 diabetes mellitus; however, its development was terminated in phase III clinical trials because of liver safety concerns. Our preliminary study indicated that intravenous administration
- PMID 26276582
Japanese Journal
- ポルフィリン生合成とヘム代謝におけるヒトABCトランスポーターの役割
- 田村 藍,安 然,大西 裕子 [他],石川 智久
- 日本薬理学雑誌 : FOLIA PHARMACOLOGICA JAPONICA 130(4), 270-274, 2007-10-01
- … の特徴に基づいて7つのサブファミリー（AからG）に分類される．これまでの臨床的研究結果から，ヒトABCトランスポーター遺伝子の異常によって様々な疾患が引き起こされることが判明した．例えば，ABCC2（cMOAT/MRP2）の遺伝子変異はビリルビン抱合体の輸送障害を起こしDubin-Johnson症候群を引き起こす．さらに最近の研究によって，ヒトABCトランスポーターのうちABCB6，ABCG2，ABCC1，ABCC2がポルフィリン生合成やヘム代謝 …
- NAID 10020167460
- ABCC2(MRP2/cMOAT)遺伝子の突然変異と機能的SNPs (特集 ゲノム創薬の新展開:薬物トランスポーターのファーマコゲノミクス)
- Homozygous mutation Arg_<768> Trp in the ABC-transporter encoding gene MRP2/cMOAT/ABCC2 causes Dubin-Johnson syndrome in a Caucasian patient
- Materna Verena,Lage Hermann
- Journal of human genetics 48(9), 484-486, 2003-09-01
- NAID 10011710383
Related Links
- ABCC2 ABCC2 A gene on chromosome 10q24 that encodes a protein of the MRP subfamily of the superfamily of ATP-binding cassette (ABC) transporters, which transport various molecules across extra- and intracellular ...
- What is the meaning of CMOAT acronym/abbreviation and what does CMOAT stand for? Get the Definition of CMOAT and CMOAT definition by All Acronyms Dictionary - 1 CMOAT acronym and abbreviation record for your search.
- Acronym Definition cMOAT Canalicular Multispecific Organic Anion Transporter Want to thank TFD for its existence? Tell a friend about us, add a link to this page, add the site to iGoogle, or visit the webmaster's page for free fun ...
Related Pictures
★リンクテーブル★
[★]
- 英
- canalicular multispecific organic anion transporter、cMOAT
- 関
- 胆管側多選択性有機アニオントランス・ーター
[★]
胆管側多選択性有機アニオントランス・ーター、胆管側多選択性有機アニオン輸送体
- 関
- cMOAT
[★]
- 英
- canalicular multispecific organic anion transporter、cMOAT
- 関
- 胆管側多選択性有機アニオン輸送体