Multidrug resistance-associated protein 2

ABCC2
Identifiers
Aliases	ABCC2, ABC30, CMOAT, DJS, MRP2, cMRP, Multidrug resistance-associated protein 2, ATP binding cassette subfamily C member 2
External IDs	OMIM: 601107; MGI: 1352447; HomoloGene: 68052; GeneCards: ABCC2; OMA:ABCC2 - orthologs
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q24.2 Start 99,782,640 bp[1] End 99,852,594 bp[1]
Gene location (Mouse) Chr. Chromosome 19 (mouse)[2] Band 19 C3|19 36.67 cM Start 43,770,631 bp[2] End 43,829,179 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right lobe of liver jejunal mucosa gallbladder duodenum human kidney mucosa of ileum testicle tibial nerve gonad sural nerve Top expressed in left lobe of liver duodenum right kidney proximal tubule jejunum human kidney yolk sac epithelium of small intestine ileum migratory enteric neural crest cell More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ATPase activity nucleotide binding protein binding ATP binding transporter activity protein domain specific binding ATPase-coupled transmembrane transporter activity organic anion transmembrane transporter activity ATPase-coupled inorganic anion transmembrane transporter activity bilirubin transmembrane transporter activity transmembrane transporter activity Cellular component integral component of membrane membrane cell surface plasma membrane apical plasma membrane brush border membrane intercellular canaliculus integral component of plasma membrane Biological process response to steroid hormone response to arsenic-containing substance prostaglandin transport response to methotrexate thyroid hormone transport xenobiotic transmembrane transport transmembrane transport cellular chloride ion homeostasis response to oxidative stress response to estrogen response to heat bilirubin transport female pregnancy mercury ion transport canalicular bile acid transport antibiotic metabolic process cellular response to lipopolysaccharide cellular response to interleukin-1 cellular response to interleukin-6 cellular response to tumor necrosis factor cellular response to dexamethasone stimulus response to antineoplastic agent benzylpenicillin metabolic process cellular response to hormone stimulus transport organic anion transport response to lipopolysaccharide response to glucagon Sources:Amigo / QuickGO
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: 99.78 – 99.85 Mb Chr 19: 43.77 – 43.83 Mb PubMed search [3] [4]
Wikidata
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 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 the apical membrane of proximal renal tubule endothelial cells where they are involved in the excretion of small organic anions.^[8]

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 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 buildup of organic anions in the cytoplasm of the cells.

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 iatrogenic Fanconi syndrome. The nucleoside phosphonate adefovir is a MRP2 inhibitor that has been linked to kidney disease.^[15] Tenofovir^[16] and cidofovir^[17] 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]}

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|alt=Irinotecan Pathway edit]]

Irinotecan Pathway edit

1. ^ The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP229".

See also

• ATP-binding cassette transporter

References

Further reading

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.