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

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 that in humans is encoded by the ABCC2 gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

.

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

Hepatocyte

A hepatocyte is a cell of the main tissue of the liver. Hepatocytes make up 70-80% of the liver's cytoplasmic mass.These cells are involved in:* Protein synthesis* Protein storage* Transformation of carbohydrates...

 and functions in biliary transport. Substrates include anticancer drug

Chemotherapy

Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

s such as vinblastine

Vinblastine

Vinblastine is an antimicrotubule drug used to treat certain kinds of cancer, including Hodgkin's lymphoma, non-small cell lung cancer, breast cancer, head and neck cancer, and testicular cancer. It is also used to treat Langerhan cell histiocytosis....

; 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

Ion

An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...

.

MRP2 inhibitors

Drug	Class	Indications	Source	Structure
probenecid Probenecid Probenecid is a uricosuric drug that increases uric acid excretion in the urine. It is primarily used in treating gout and hyperuricemia.Probenecid was developed as an alternative to caronamide...	uricosuric Uricosuric Uricosuric medications are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. In general, this effect is achieved by action on the proximal tubule...	gout Gout Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...   hyperuricemia Hyperuricemia Hyperuricemia is a level of uric acid in the blood that is abnormally high. In humans, the upper end of the normal range is 360 µmol/L for women and 400 µmol/L for men.-Causes:...
furosemide Furosemide Furosemide or frusemide is a loop diuretic used in the treatment of congestive heart failure and edema. It is most commonly marketed by Sanofi-Aventis under the brand name Lasix...	loop diuretic Loop diuretic Loop diuretics are diuretics that act on the ascending loop of Henle in the kidney. They are primarily used in medicine to treat hypertension and edema often due to congestive heart failure or renal insufficiency...	heart failure  edema Edema Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
ritonavir Ritonavir Ritonavir, with trade name Norvir , is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS....	protease inhibitor Protease inhibitor Protease inhibitor can refer to:* Protease inhibitor : a class of medication that inhibits viral protease* Protease inhibitor : molecules that inhibit proteases...	antiretroviral
saquinavir Saquinavir Saquinavir is an antiretroviral drug used in HIV therapy. It falls in the protease inhibitor class. Two formulations have been marketed:*a hard-gel capsule formulation of the mesylate, with trade name Invirase, which requires combination with ritonavir to increase the saquinavir bioavailability;*a...	protease inhibitor Protease inhibitor Protease inhibitor can refer to:* Protease inhibitor : a class of medication that inhibits viral protease* Protease inhibitor : molecules that inhibit proteases...	antiretroviral
lamivudine Lamivudine Lamivudine is a potent nucleoside analog reverse transcriptase inhibitor .It is marketed by GlaxoSmithKline with the brand names Zeffix, Heptovir, Epivir, and Epivir-HBV.Lamivudine has been used for treatment of chronic hepatitis B at a lower dose than for treatment of HIV...	Nucleoside analog	antiviral Antiviral drug Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
abacavir Abacavir Abacavir is a nucleoside analog reverse transcriptase inhibitor used to treat HIV and AIDS. It is available under the trade name Ziagen and in the combination formulations Trizivir and Kivexa/Epzicom...	Nucleoside analog	antiretroviral
emtricitabine Emtricitabine Emtricitabine , with trade name Emtriva , is a nucleoside reverse transcriptase inhibitor for the treatment of HIV infection in adults and children....	Nucleoside analog	antiviral Antiviral drug Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
efavirenz Efavirenz Efavirenz is a non-nucleoside reverse transcriptase inhibitor and is used as part of highly active antiretroviral therapy for the treatment of a human immunodeficiency virus type 1....	NNRTI	antiretroviral
delavirdine Delavirdine Delavirdine is a non-nucleoside reverse transcriptase inhibitor marketed by ViiV Healthcare. It is used as part of highly active antiretroviral therapy for the treatment of human immunodeficiency virus type 1. It is presented as the mesylate...	NNRTI	antiretroviral
nevirapine	NNRTI	antiretroviral
cidofovir Cidofovir Cidofovir is an injectable antiviral medication for the treatment of cytomegalovirus retinitis in patients with AIDS. It suppresses CMV replication by selective inhibition of viral DNA polymerase and therefore prevention of viral replication and transcription...	nucleoside phosphonate	antiviral Antiviral drug Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
adefovir Adefovir Adefovir dipivoxil, previously called bis-POM PMEA, with trade names Preveon and Hepsera, is an orally-administered nucleotide analog reverse transcriptase inhibitor .-Uses:...	nucleoside phosphonate	antiviral Antiviral drug Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
tenofovir	nucleoside phosphonate	antiviral Antiviral drug Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...

Dubin-Johnson syndrome

Several different mutations in this gene have been observed in patients with Dubin-Johnson syndrome

Dubin-Johnson syndrome

Dubin–Johnson syndrome is an autosomal recessive disorder that causes an increase of conjugated bilirubin in the serum without elevation of liver enzymes . This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile, and is similar to...

 (DJS), an autosomal recessive disorder characterized by conjugated hyperbilirubinemia.

Iatrogenic Fanconi syndrome

Many negatively charged metabolic waste products are eliminated from the body by the kidneys. These organic anion

Organic anion

Organic anions are chemically heterogeneous substances possessing a carbon backbone and a net negative charge. Organic anions are conjugate bases of organic acids. The following table lists some of the organic anions and their conjugate acids which are substrates of the organic acid transporter ...

s 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

Lumen (anatomy)

A lumen in biology is the inside space of a tubular structure, such as an artery or intestine...

 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

Cytoplasm

The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within 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

Adefovir

Adefovir dipivoxil, previously called bis-POM PMEA, with trade names Preveon and Hepsera, is an orally-administered nucleotide analog reverse transcriptase inhibitor .-Uses:...

 is a MRP2 inhibitor that has been linked to kidney disease. Tenofovir and cidofovir

Cidofovir

Cidofovir is an injectable antiviral medication for the treatment of cytomegalovirus retinitis in patients with AIDS. It suppresses CMV replication by selective inhibition of viral DNA polymerase and therefore prevention of viral replication and transcription...

are also nucleoside phosphonates that inhibit MRP2 and have been associated with Fanconi syndrome.

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