title: Structure and function of multidrug and toxin extrusion proteins (MATEs) and their relevance to drug therapy and personalized medicine.
abstract: Multidrug and toxin extrusion (MATE; SLC47A) proteins are membrane transporters mediating the excretion of organic cations and zwitterions into bile and urine and thereby contributing to the hepatic and renal elimination of many xenobiotics. Transported substrates include creatinine as endogenous substrate, the vitamin thiamine and a number of drug agents with in part chemically different structures such as the antidiabetic metformin, the antiviral agents acyclovir and ganciclovir as well as the antibiotics cephalexin and cephradine. This review summarizes current knowledge on the structural and molecular features of human MATE transporters including data on expression and localization in different tissues, important aspects on regulation and their functional role in drug transport. The role of genetic variation of MATE proteins for drug pharmacokinetics and drug response will be discussed with consequences for personalized medicine.
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany. anne.nies@ikp-stuttgart.de.|University of Tübingen, Tübingen, Germany. anne.nies@ikp-stuttgart.de.
authors.forename: Anne T
authors.initials: AT
authors.lastname: Nies
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.|University of Tübingen, Tübingen, Germany.|Tissue and Cell Research Center Munich, Daiichi Sankyo Europe GmbH, Martinsried, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Damme
authors.affiliation: Department of Urology, University Hospital Tübingen, Tübingen, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kruck
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.|University of Tübingen, Tübingen, Germany.
authors.forename: Elke
authors.initials: E
authors.lastname: Schaeffeler
authors.affiliation: Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.|Department of Clinical Pharmacology, University Hospital Tübingen, Tübingen, Germany.|Department of Pharmacy and Biochemistry, University Tübingen, Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Schwab
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019295:Computational Biology; D004358:Drug Therapy; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D009928:Organ Specificity; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000737:chemistry; D010766:Phosphorylation; D057285:Precision Medicine; D011499:Protein Processing, Post-Translational; D016415:Sequence Alignment; D013045:Species Specificity; D013379:Substrate Specificity
chemical_list: D027701:Organic Cation Transport Proteins; D004364:Pharmaceutical Preparations; C521869:SLC47A1 protein, human; C521870:SLC47A2 protein, human
keywords: Function; MATE; Metformin; Multidrug and toxin extrusion; Polymorphisms; SLC47