title: Critical domains within the sequence of human organic anion transporting polypeptides.
abstract: Organic anion-transporting polypeptides (human OATPs; other species Oatps; gene family SLC21/SLCO) play important roles in drug absorption and distribution. In recent years, much information has been obtained on substrates that are transported by OATPs. Computer-based hydropathy analysis predicts that OATP family members share several structural features including twelve transmembrane domains (TMs), conserved cysteine residues at extracellular loop 5, glycosylation sites, PDZ binding domains as well as putative phosphorylation sites. Studies on transmembrane domains have identified several amino acids that are essential for substrate uptake; while mutation of the conserved cysteine residues and glycosylation sites resulted in mis-processing transporter proteins. The interaction with PDZ proteins and phosphorylation modification of OATPs, on the other hand, mainly regulate the trafficking of these transporters. Although progress has been made on revealing the critical domains of OATPs, information is still limited and more studies on these aspects are needed. A better understanding of the important structural domains of OATPs will shed light on future targeted drug design and a more in-depth analysis of inter-individual variability of drug disposition.
authors.affiliation: College of Life Science, South China Agricultural University, Guangzhou, China. mh2788@scau.edu.cn.
authors.forename: Mei
authors.initials: M
authors.lastname: Hong
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D006031:Glycosylation; D006801:Humans; D027361:Organic Anion Transporters / Q000737:chemistry*; D010766:Phosphorylation; D017434:Protein Structure, Tertiary
chemical_list: D000596:Amino Acids; D027361:Organic Anion Transporters