Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (       , ). Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) (, ). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver . Mediates the intestinal uptake of sulfated steroids (, ). Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain (, ). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons . May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC . Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition . Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 ( , Ref.25, ). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment ( ). The exact transport mechanism has not been yet deciphered but most likely involves an anion exchange, coupling the cellular uptake of organic substrate with the efflux of an anionic compound ( ). Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions . Cytoplasmic glutamate may also act as counteranion in the placenta . An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) .
Has estrone 3-sulfate (E1S) transport activity comparable with the full-length isoform 1.
Subcellular locations: Cell membrane, Basal cell membrane, Basolateral cell membrane, Apical cell membrane
Expressed at the basal membrane of hepatocytes, syncytiotrophoblast and Sertoli cells ( , ). Localized to the basolateral membrane of enterocytes . Also found at the apical membrane of enterocytes (, ).
Strongly expressed in the liver, at the sinusoidal membrane of the hepatocytes ( ). Expressed in the kidney . Expressed in placental trophoblasts and syncytiotrophoblast ( , ). Expressed in the small intestine (  ). Expressed in the blood-brain barrier, in endothelial cells of brain capillaries (, ). Expressed in the retina, in the inner nuclear layer and the inner plexiform layer . Expressed in skelettal muscles . In testis, primarily localized to the basal membrane of Sertoli cells and weakly expressed within the tubules ( ). Also expressed in pancreas, lung, heart, colon, ovary and spleen (, ). Expressed in fetal brain, heart, kidney, liver, lung, skeletal muscle, spleen and pancreas .
Highest expression in brain. Predominant isoform compared to isoform 3 in small intestine duodenum, kidney, placenta, and skeletal muscle.
Predominant isoform compared to isoform 1 in liver. Also expressed in small intestine duodenum, kidney, brain, placenta, and skeletal muscle.