Protein: Organic anion transporter 3 (Oat3) (Organic anion/dicarboxylate exchanger) (Solute carrier family 22 member 8) (Q9R1U7)
Organism: Rattus norvegicus (Rat)
Function: Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient. Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain. Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule. May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside (By similarity). May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate (By similarity). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor). May contribute to the release of cortisol in the adrenals (By similarity). Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile. Regulates the CSF concentration of histamine H(2)-receptor antagonists cimetidine and ranitidine at the CP. Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the uptake from brain of organic anions, such as E1S, PAH, and OTA. Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body.
Subcellular location: Basolateral cell membrane {ECO:0000269|PubMed:15389674}; Multi-pass membrane protein {ECO:0000305}. Note=Localizes on the brush border membrane of the choroid epithelial cells. Localizes to the basolateral membrane of the proximal tubular cells. Localizes on the abluminal and possibly, luminal membrane of the brain capillary endothelial cells (BCEC). {ECO:0000269|PubMed:11861777, ECO:0000269|PubMed:11961115, ECO:0000269|PubMed:12684544}.
Interaction partners:
- Solute carrier family 22 member 7
- Solute carrier family 2 member 9
- Multidrug and toxin extrusion protein 1
- ATP-binding cassette sub-family C member 2
- Solute carrier organic anion transporter family member 2B1
- Solute carrier organic anion transporter family member 4C1
- ATP-binding cassette subfamily C member 4
- Broad substrate specificity ATP-binding cassette transporter ABCG2
- Solute carrier organic anion transporter family member 1A1
- Solute carrier organic anion transporter family member 1A4
Sequence:
MTFSEILDRVGSMGPFQYLHVTLLALPVLGIANHNLLQIFTATTPVHHCRPPPNASIGPWVLPLDPNGKPEKCLRFVHLPNASLPNDTQRATEPCLDGWIYNSTRDTIVIEWDLVCSSNKLKEMAQSIFMAGILVGGPVIGELSDRFGRKPILTWSYLMLAASGSGAAFSPSLPVYMIFRFLCGCSISGISLSTVILNVEWVPTSMRAISSTSIGYCYTIGQFILSGLAYAIPQWRWLQLTSSAPFFIFSLLSWWVPESIRWLVLSGKYSKALKTLQRVATFNGKKEEGKKLTIEELKFNLQKDITSAKVKYGLSDLFRVSILRRVTFCLSLAWFSTGFAYYSLAMGVEEFGVNIYILQIIFGGVDIPAKFITILSLSYLGRRITQSFLLLLAGGAILALIFVPSEMQLLRTALAVFGKGCLSGSFSCLFLYTSELYPTVLRQTGMGISNVWARVGSMIAPLVKITGELQPFIPNVIFGTTALLGGSAAFFLLETLNRPLPETIEDIQNWHKQVQKTKQESEAEKASQIIPLKTGG