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ATP-binding cassette sub-family C member 5 (ABCC5)
- Target
- ABCC5
- Molecular classification
- Transporter, ATP-binding cassette transporter (ABC transporter), Multidrug resistance protein (MRP subfamily)
01
Overview
ATP-binding cassette sub-family C member 5 (ABCC5, also known as multidrug resistance-associated protein 5 or MRP5) is a membrane-bound ATP-dependent transporter of the ABC protein superfamily. It facilitates the efflux of a broad spectrum of physiological compounds and xenobiotics, including cyclic nucleotides (cAMP, cGMP), nucleotide analog drugs, folic acid, and glutamate conjugates, thus contributing to cellular detoxification and pharmacoresistance. ABCC5 is highly expressed in various tissues including the blood-brain barrier and has a significant role in multidrug resistance by lowering intracellular concentrations of chemotherapeutic and antiretroviral agents, with elevated expression associated with poor prognosis and resistance in cancer and HIV therapy. Structurally, ABCC5 contains multiple transmembrane domains and nucleotide binding domains that hydrolyze ATP to drive transport.
- Other names
- Multidrug resistance-associated protein 5MRP5MOAT-CMulti-specific organic anion transporter CpABC11SMRP
02
Mechanism of action
ATP-dependent efflux pump that transports substrates (including drugs and toxins) out of cells, lowering intracellular drug concentrations and promoting drug resistance
03
Biological functions
Export of endogenous metabolites (e.g., cAMP, cGMP, folic acid, N-lactoyl-amino acids)Efflux of glutamate conjugates and analogsATP-dependent export of xenobiotics and drugsDrug resistance (multidrug resistance mechanism)Cellular export of cyclic nucleotidesHeme translocation from cytosol to secretory pathwayPotential regulation of secretion (e.g., glucagon-like peptide 1)
04
Disease associations
Cancer (including drug resistance, poor prognosis, and bone metastasis in breast cancer)Acute lymphoblastic leukemia (drug resistance)HIV infection (antiretroviral therapy resistance)Currarino syndromeGlaucoma (primary angle-closure)
05
Safety considerations
Therapeutic challenge due to enhancement of multidrug resistance in cancersLimits brain levels of drugs and endogenous compounds, complicating CNS drug administrationMay mediate resistance to antiviral and anticancer nucleotide analog drugs; implications for efficacy of therapies in HIV and leukemia
06
Interacting drugs
6-mercaptopurine
4 more in the full profile.
07
Biomarkers
High ABCC5 expression as a marker for poor cancer prognosis and for multidrug resistance potentialPossible biomarker for predicting resistance to thiopurine drugs in leukemia and efficacy of certain antiviral therapies
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