SLCO1B1
Domain
A conserved histidine residue in the third TMD (His-115) may play an essential role in the pH sensitivity of SLCO1B1/OATP1B1-mediated substrate transport.
Function
Mediates the Na(+)-independent uptake of organic anions (PubMed:10358072, PubMed:15159445, PubMed:17412826). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:11159893, PubMed:12196548, PubMed:12568656, PubMed:15159445, PubMed:15970799, PubMed:16627748, PubMed:17412826, PubMed:19129463, PubMed:26979622). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Involved in the clearance of endogenous and exogenous substrates from the liver (PubMed:10358072, PubMed:10601278). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). 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 pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:10601278, PubMed:15159445, PubMed:15970799). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate (PubMed:23243220). 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 (PubMed:16624871, PubMed:16627748). Shows a pH-sensitive substrate specificity towards prostaglandin E2 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 (PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463).
Involvement in disease
Hyperbilirubinemia, Rotor type
HBLRR
An autosomal recessive form of primary conjugated hyperbilirubinemia. Affected individuals develop mild jaundice not associated with hemolysis shortly after birth or in childhood. They have delayed plasma clearance of the unconjugated anionic dye bromsulphthalein and prominent urinary excretion of coproporphyrin I. Hepatic pigmentation is normal.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the organo anion transporter (TC 2.A.60) family.
Tissue Specificity
Highly expressed in liver, at the basolateral membranes of centrilobular hepatocytes (PubMed:10358072, PubMed:10601278, PubMed:10873595, PubMed:12196548, PubMed:22232210). Expressed in liver (at protein level) (PubMed:15159445). Expressed in fetal liver (PubMed:10873595). Not detected in heart, brain, placenta, lung, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and leukocyte (PubMed:10358072, PubMed:10873595). In testis, primarily localized to the basal membrane of Sertoli cells and weakly expressed in Leydig cells and within the tubules (PubMed:35307651).
Cellular localization
- Basolateral cell membrane
- Multi-pass membrane protein
- Basal cell membrane
- Multi-pass membrane protein
- Detected in basolateral membranes of hepatocytes (PubMed:12196548). Localized to the basal membrane of Sertoli cells (PubMed:35307651).
Alternative names
LST1, OATP1B1, OATP2, OATPC, SLC21A6, SLCO1B1, Solute carrier organic anion transporter family member 1B1, Liver-specific organic anion transporter 1, OATP-C, Organic anion transporter SLC21A6, Sodium-independent organic anion-transporting polypeptide 2, Solute carrier family 21 member 6, LST-1, OATP-2