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FUNCTION Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (PubMed:10873595, PubMed:11159893, PubMed:11932330, PubMed:12724351, PubMed:14610227, PubMed:16908597, PubMed:18501590, PubMed:20507927, PubMed:22201122, PubMed:23531488, PubMed:25132355, PubMed:26383540, PubMed:27576593, PubMed:28408210, PubMed:29871943, PubMed:34628357). 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) (PubMed:11932330, PubMed:12409283). 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 (PubMed:11159893). Mediates the intestinal uptake of sulfated steroids (PubMed:12724351, PubMed:28408210). 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 (PubMed:16908597, PubMed:25132355). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC (PubMed:35714613). Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (PubMed:26383540). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, PubMed:29871943, 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 (PubMed:14610227, PubMed:19129463, PubMed:22201122). 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 (PubMed:19129463, PubMed:20507927, PubMed:26277985). Hydrogencarbonate/HCO3(-) acts as a probable counteranion that exchanges for organic anions (PubMed:19129463). Cytoplasmic glutamate may also act as counteranion in the placenta (PubMed:26277985). An inwardly directed proton gradient has also been proposed as the driving force of E1S uptake with a (H(+):E1S) stoichiometry of (1:1) (PubMed:20507927).FUNCTION Has estrone 3-sulfate (E1S) transport activity comparable with the full-length isoform 1.CATALYTIC ACTIVITY dehydroepiandrosterone 3-sulfate(out) = dehydroepiandrosterone 3-sulfate(in)CATALYTIC ACTIVITY estrone 3-sulfate(out) = estrone 3-sulfate(in)CATALYTIC ACTIVITY estrone 3-sulfate(out) + hydrogencarbonate(in) = estrone 3-sulfate(in) + hydrogencarbonate(out)CATALYTIC ACTIVITY taurocholate(out) = taurocholate(in)CATALYTIC ACTIVITY coproporphyrin III(out) = coproporphyrin III(in)CATALYTIC ACTIVITY substance P(out) = substance P(in)CATALYTIC ACTIVITY pregnenolone sulfate(out) = pregnenolone sulfate(in)CATALYTIC ACTIVITY prostaglandin E2(out) = prostaglandin E2(in)CATALYTIC ACTIVITY prostaglandin D2(out) = prostaglandin D2(in)CATALYTIC ACTIVITY L-thyroxine(out) = L-thyroxine(in)ACTIVITY REGULATION E1S, DHEA-S and PregS transports are regulated by steroid hormones. In the case of testosterone, transport of E1S and DHEA-S was inhibited, whereas progesterone stimulated E1S, DHEA-S and PregS uptake (PubMed:16908597). Progesterone stimulates high-affinity uptake of E1S whereas it inhibits low-affinity uptake of E1S (Ref.25). Progesterone doesn't affect the uptake of PGE2 (Ref.25).BIOPHYSICOCHEMICAL PROPERTIES Estrone 3-sulfate transport exhibits a biphasic saturation kinetics, with Km and Vmax values of high- and low-affinity sites due to the presence of multiple binding sites.SUBCELLULAR LOCATION Expressed at the basal membrane of hepatocytes, syncytiotrophoblast and Sertoli cells (PubMed:11159893, PubMed:11932330, PubMed:12409283, PubMed:35307651). Localized to the basolateral membrane of enterocytes (PubMed:28408210). Also found at the apical membrane of enterocytes (PubMed:12724351, PubMed:28408210).ALTERNATIVE PRODUCTS Strongly expressed in the liver, at the sinusoidal membrane of the hepatocytes (PubMed:10873595, PubMed:11159893, PubMed:23531488). Expressed in the kidney (PubMed:11159893). Expressed in placental trophoblasts and syncytiotrophoblast (PubMed:11159893, PubMed:11932330, PubMed:12409283, PubMed:26277985). Expressed in the small intestine (PubMed:10873595, PubMed:11159893, PubMed:12724351, PubMed:23531488, PubMed:28408210). Expressed in the blood-brain barrier, in endothelial cells of brain capillaries (PubMed:11159893, PubMed:25132355). Expressed in the retina, in the inner nuclear layer and the inner plexiform layer (PubMed:25132355). Expressed in skelettal muscles (PubMed:23531488). In testis, primarily localized to the basal membrane of Sertoli cells and weakly expressed within the tubules (PubMed:10873595, PubMed:11159893, PubMed:35307651). Also expressed in pancreas, lung, heart, colon, ovary and spleen (PubMed:10873595, PubMed:11159893). Expressed in fetal brain, heart, kidney, liver, lung, skeletal muscle, spleen and pancreas (PubMed:10873595).TISSUE SPECIFICITY Highest expression in brain. Predominant isoform compared to isoform 3 in small intestine duodenum, kidney, placenta, and skeletal muscle.TISSUE SPECIFICITY Predominant isoform compared to isoform 1 in liver. Also expressed in small intestine duodenum, kidney, brain, placenta, and skeletal muscle.INDUCTION Its expression is regulated by HNF4A.DOMAIN A conserved histidine residue in the third transmembrane domain (His-136) might play an essential role in the pH sensitivity of SLCO2B1/OATP2B1-mediated substrate transport (PubMed:19129463). Transmembrane domain 1 (TM1) may be localized within the substrate binding pocket (PubMed:29871943).MISCELLANEOUS Most likely contributes to the oral absorption and the disposition of a wide range of drugs in the intestine and the liver (PubMed:10873595, PubMed:11159893, PubMed:12724351, PubMed:14610227, PubMed:23531488, PubMed:26277985, PubMed:27576593, Ref.25).SIMILARITY Belongs to the organo anion transporter (TC 2.A.60) family.CAUTION While some reports have shown that E1S transport exhibited single-saturation kinetics (PubMed:11932330, PubMed:14610227), other studies demonstrated a biphasic saturation kinetics (PubMed:11932330, PubMed:14610227, PubMed:22201122, Ref.25). Despite a previous report that demonstrated a pH-dependent substrate uptake and a transport stimulation at low pH (PubMed:14610227), another study did not observe any pH-dependent E1S and taurocholate transport (PubMed:14610227, PubMed:23531488). Was shown to mediate bile acid taurocholate transport at low pH in some studies (PubMed:14610227, PubMed:29871943), but not others (PubMed:11159893, PubMed:23531488, PubMed:29871943). The enterocyte localization of SLCO2B1/OATP2B1 remains uncertain. While some authors found it in the apical membrane (PubMed:12724351), consistent with a function as uptake carrier contributing to the intestinal absorption of drugs, other studies demonstrated a basolateral membrane expression, supporting a physiological role in substrate uptake from the blood flow and intestinal clearance (PubMed:12724351, PubMed:28408210).SEQUENCE CAUTION Extended N-terminus.
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