179 © The Authors Journal compilation © 2011 Biochemical Society Essays Biochem. (2011) 50, 179–207; doi:10.1042/BSE0500179 10 Mammalian multidrug‑resistance proteins (MRPs) Andrew J. Slot, Steven V. Molinski and Susan P.C. Cole 1 Division of Cancer Biology and Genetics, Queen’s University Cancer Research Institute, Kingston, ON, Canada, K7L 3N6 Abstract Subfamily C of the human ABC (ATP‑binding cassette) superfamily contains nine proteins that are often referred to as the MRPs (multidrug‑resistance proteins). The ‘short’ MRP/ABCC transporters (MRP4, MRP5, MRP8 and ABCC12) have a typical ABC structure with four domains comprising two membrane‑spanning domains (MSD1 and MSD2) each followed by a nucleotide‑binding domain (NBD1 and NBD2). The ‘long’ MRP/ABCCs (MRP1, MRP2, MRP3, ABCC6 and MRP7) have five domains with the extra domain, MSD0, at the N‑terminus. The proteins encoded by the ABCC6 and ABCC12 genes are not known to transport drugs and are therefore referred to as ABCC6 and ABCC12 (rather than MRP6 and MRP9) respectively. A large number of molecules are transported across the plasma membrane by the MRPs. Many are organic anions derived from exogenous sources such as conjugated drug metabolites. Others are endogenous metabolites such as the cysteinyl leukotrienes and prostaglandins which have important signalling functions in the cell. Some MRPs share a degree of overlap in substrate specifcity (at least in vitro), but differences in transport kinetics are often substantial. In some cases, the in vivo substrates 1 To whom correspondence should be addressed (email spc.cole@queensu.ca).