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]
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]
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]
| 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] |  |
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]
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.
Click on genes, proteins and metabolites below to link to respective articles. [§ 1]
Dubin–Johnson syndrome is a rare, autosomal recessive, benign disorder that causes an isolated increase of conjugated bilirubin in the serum. Classically, the condition causes a black liver due to the deposition of a pigment similar to melanin. This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile, and is similar to Rotor syndrome. It is usually asymptomatic, but may be diagnosed in early infancy based on laboratory tests. No treatment is usually needed.
Multidrug resistance-associated protein 6 (MRP6) also known as ATP-binding cassette sub-family C member 6 (ABCC6) and multi-specific organic anion transporter E (MOAT-E) is a protein that in humans is encoded by the ABCC6 gene. The protein encoded by the ABCC6 gene is a member of the superfamily of ATP-binding cassette (ABC) transporters.
Rotor syndrome is a rare cause of mixed direct (conjugated) and indirect (unconjugated) hyperbilirubinemia, relatively benign, autosomal recessive bilirubin disorder characterized by non-hemolytic jaundice due to the chronic elevation of predominantly conjugated bilirubin.
In microbiology, efflux is the moving of a variety of different compounds out of cells, such as antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals, bacterial metabolites and neurotransmitters. All microorganisms, with a few exceptions, have highly conserved DNA sequences in their genome that encode efflux pumps. Efflux pumps actively move substances out of a microorganism, in a process known as active efflux, which is a vital part of xenobiotic metabolism. This active efflux mechanism is responsible for various types of resistance to bacterial pathogens within bacterial species - the most concerning being antibiotic resistance because microorganisms can have adapted efflux pumps to divert toxins out of the cytoplasm and into extracellular media.
ATP-binding cassette sub-family C member 4 (ABCC4), also known as the multidrug resistance-associated protein 4 (MRP4) or multi-specific organic anion transporter B (MOAT-B), is a protein that in humans is encoded by the ABCC4 gene.
Multidrug resistance-associated protein 1 (MRP1) is a protein that in humans is encoded by the ABCC1 gene.
In enzymology, a xenobiotic-transporting ATPase (EC 3.6.3.44) is an enzyme that catalyzes the chemical reaction
Canalicular multispecific organic anion transporter 2 is a protein that in humans is encoded by the ABCC3 gene.
Multidrug resistance-associated protein 5 is a protein that in humans is encoded by the ABCC5 gene.
Equilibrative nucleoside transporter 2 (ENT2) is a protein that in humans is encoded by the SLC29A2 gene.
Solute carrier family 22 member 11 is a protein that in humans is encoded by the SLC22A11 gene.
Solute carrier family 22 member 8, or organic anion transporter 3 (OAT3), is a protein that in humans is encoded by the SLC22A8 gene.
Solute carrier organic anion transporter family member 1A2 is a protein that in humans is encoded by the SLCO1A2 gene.
Multidrug and toxin extrusion protein 1 (MATE1), also known as solute carrier family 47 member 1, is a protein that in humans is encoded by the SLC47A1 gene. SLC47A1 belongs to the MATE family of transporters that are found in bacteria, archaea and eukaryotes.
Multidrug resistance-associated protein 7 is a protein that in humans is encoded by the ABCC10 gene.
Solute carrier family 22 member 7 is a protein that in humans is encoded by the gene SLC22A7.
Solute carrier family 22 member 9 is a protein that in humans is encoded by the SLC22A9 gene.
The organic anion transporter 1 (OAT1) also known as solute carrier family 22 member 6 (SLC22A6) is a protein that in humans is encoded by the SLC22A6 gene. It is a member of the organic anion transporter (OAT) family of proteins. OAT1 is a transmembrane protein that is expressed in the brain, the placenta, the eyes, smooth muscles, and the basolateral membrane of proximal tubular cells of the kidneys. It plays a central role in renal organic anion transport. Along with OAT3, OAT1 mediates the uptake of a wide range of relatively small and hydrophilic organic anions from plasma into the cytoplasm of the proximal tubular cells of the kidneys. From there, these substrates are transported into the lumen of the nephrons of the kidneys for excretion. OAT1 homologs have been identified in rats, mice, rabbits, pigs, flounders, and nematodes.
Eluxadoline, sold under the brand names Viberzi and Truberzi, is a medication taken by mouth for the treatment of diarrhea and abdominal pain in individuals with diarrhea-predominant irritable bowel syndrome (IBS-D). It was approved for use in the United States in 2015. The drug originated from Janssen Pharmaceutica and was developed by Actavis.
Bilirubin glucuronide is a water-soluble reaction intermediate over the process of conjugation of indirect bilirubin. Bilirubin glucuronide itself belongs to the category of conjugated bilirubin along with bilirubin di-glucuronide. However, only the latter one is primarily excreted into the bile in the normal setting.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
