Oatp1b4 - dog New
Oatp1b4 (organic anion transporting polypeptide 1b4), cynomolgus monkey
Gene name: Solute carrier organic anion transporter family member 1B4 (Slco1b4)
In humans and other primates, an evolutionarily closely related pair of OATP1B transporters, OATP1B1 and OATP1B3, jointly mediate the uptake of a broad range of xenobiotics into hepatocytes and are therefore key contributors to hepatic drug elimination. Since the gene duplication event resulting in the split of the ancestral SLCO1B transporter gene occurred uniquely on the primate evolutionary lineage, carnivores, including dogs, have no direct OATP1B1/1B3 ortholog. Based on phylogenetic relationship and functional similarity, the dog Oatp1b4 protein – whose gene is now officially referred to as SLCO1B2 (NCBI Gene ID: 403519) – has been identified as the closest canine relative of human liver-specific OATP1Bs. Just like its human counterparts, dog Oatp1b4 is a broad substrate range liver-specific transporter that transports not only common OATP1B substrates such as bromosulfophthalein, taurocholate, or estradiol 17-β-D-glucuronide, but also the OATP1B3-selective substrate CCK-8. Dog Oatp1b4 is a ca. 85-kDa glycosylated protein with 68% and 71% protein identity to human OATP1B1 and OATP1B3, respectively. Further studies have confirmed that Oatp1b4 is indeed the predominant Oatp in the dog liver, and it is in large part responsible for the hepatic clearance of typical OATP substrates.
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