Mediates the Na(+)-independent uptake of organic anions ( ). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (  , ). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions . Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment . Involved in the clearance of bile acids and organic anions from the liver . Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop . Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition . May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs . May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel . May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (, ).
Subcellular locations: Basolateral cell membrane, Basal cell membrane
Localized to the basolateral membrane of hepatocytes . Localized to the basal membrane of Sertoli cells .
Highly expressed in liver, in particular at the basolateral membrane of hepatocytes near the central vein (, ). Expressed in the placenta . In testis, primarily localized to the basal membrane of Sertoli cells and weakly expressed in Leydig cells and within the tubules .