Solute carrier family 46 member 3 (SLC46A3)

Solute carrier family 46 member 3 (SLC46A3) is a lysosomal membrane transporter belonging to the major facilitator superfamily and SLC46 family. It preferentially recognizes and transports lipophilic steroid conjugates and bile acids using a proton-coupled mechanism, and is critical for the lysosomal export of catabolites generated from noncleavable linker antibody-drug conjugates, such as T-DM1 and other maytansine-based ADCs, into the cytoplasm. Expression of SLC46A3 is associated with cellular sensitivity to these ADCs, as its absence results in lysosomal entrapment of drug catabolites and therapeutic resistance. Besides its role in drug transport, SLC46A3 is also implicated in hepatic copper homeostasis, lipid metabolism, and innate immune responses by transporting pathogen-associated and immunostimulatory molecules in myeloid cells. Its inhibition or downregulation can attenuate the cytotoxic effects of key anti-cancer drugs, and it may also serve as a biomarker for ADC responsiveness.

Other names

Lysosomal proton-coupled steroid conjugate and bile acid symporter SLC46A3FKSG16DKFZp686A1775FLJ42613solute carrier family 46 member 3lysosomal proton-coupled steroid conjugate and bile acid transporterS46A3_HUMAN

Lysosomal export (efflux) of noncleavable ADC catabolites, enabling cytotoxic activity in the cytoplasm. Proton-coupled, transporter-mediated movement of substrates such as steroid conjugates, bile acids, and Lys-SMCC-DM1 from lysosomes to cytoplasm.