MRP1

MRP1, or multidrug resistance protein 1, is a transmembrane efflux transporter encoded by the ABCC1 gene in humans. It belongs to the ATP-binding cassette (ABC) transporter superfamily and is expressed in a wide range of tissues, including the lung, liver, kidney, intestine, placenta, and the blood–brain barrier. Its primary function is to export a broad spectrum of substrates out of cells, using energy from ATP hydrolysis. These substrates include organic anions, glutathione (GSH) conjugates, glucuronides, and sulfate conjugates, as well as several endogenous compounds such as leukotriene C4 and prostaglandins. By moving these molecules across membranes, MRP1 contributes to cellular detoxification and influences drug disposition.

MRP1 is a member of the MRP/ABCC subfamily of ABC transporters. It is organized as a half-transporter containing one transmembrane domain and one nucleotide-binding domain, with two such halves assembling to form a functional dimer. The protein features the characteristic Walker motifs and the ABC signature sequence LSGGQ in its nucleotide-binding domains. ATP binding and hydrolysis provide the energy required to drive substrate transport across the cell membrane.

Tissue distribution and clinical relevance are central to MRP1’s role. It is widely expressed and can affect the pharmacokinetics of drugs by reducing intestinal absorption, promoting hepatic and renal excretion, and limiting penetration into protected tissues such as the brain. In cancer, overexpression of MRP1 can contribute to multidrug resistance by lowering intracellular drug concentrations. This has made MRP1 a target of research for chemosensitizers and inhibitors, though clinical success has been limited due to toxicity and redundancy with other transporters.

The ABCC1 gene, located on chromosome 16p13.11, encodes the human MRP1 protein, which localizes to the plasma membrane in many cell types and participates in both normal physiology and pharmacology.