MATE Family Transporter Proteins for Organic Cation Excretion

Instead of searching for mammalian homologues of known kidney transporters (conventional approach), the inventors inverted the approach by searching for mammalian orthologues of bacterial multidrug efflux pumps (MATE family). This reverse strategy led to the discovery of MATE1 and MATE2-K as the molecular entities responsible for organic cation excretion, resolving the identification failure of the conventional approach

The inventors performed preliminary action by first identifying the molecular entities (MATE1 and MATE2-K) through database searching and sequence analysis before developing the functional assay system. This preliminary identification of target molecules enabled the subsequent development of effective assays for drug and waste excretion, avoiding the time loss that would have occurred if assays were developed without known targets

The inventors applied the universality principle by recognizing that the MATE family proteins in mammals share functional characteristics with bacterial multidrug efflux pumps despite sequence divergence. This universal functional approach allowed identification of MATE1 and MATE2-K as multifunctional transporters handling various organic cations, drugs, and waste products, overcoming the difficulty of detection through functional rather than sequence-based identification