Protein: Organic anion transporter 3 (O88909)
Organism: Mus musculus (Mouse)
Function: Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient (By similarity). 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. E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange. Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule. Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate. Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins (By similarity). 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). 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. 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). 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) (By similarity). Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) 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) (By similarity). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
Subcellular location: Basolateral cell membrane; Multi-pass membrane protein. Note=Localized to the basolateral side of all renal epithelia except the glomerulus. 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) (By similarity)
Sequence: MTFSEILDRVGSMGPFQYLHVTLLALPILGIANHNLLQIFTATTPDHHCRPPPNASLEPWVLPLGPNGKPEKCLRFVHLPNASLPNDTQGATEPCLDGWIYNSTRDTIVTEWDLVCGSNKLKEMAQSVFMAGILVGGPVFGELSDRFGRKPILTWSYLLLAASGSSAAFSPSLTVYMIFRFLCGCSISGISLSTIILNVEWVPTSTRAISSTTIGYCYTIGQFILPGLAYAVPQWRWLQLSVSAAFFIFSLLSWWVPESIRWLVLSGKFSKALKTLQRVATFNGKKEEGEKLTVEELKFNLQKDITSAKVKYGLSDLFRVSILRRVTFCLSLAWFATGFAYYSLAMGVEEFGVNIYILQIIFGGVDIPAKFITILSISYLGRRITQGFLLILAGVAILALIFVSSEMQLLRTALAVFGKGCLSGSFSCLFLYTSELYPTVLRQTGMGISNIWARVGSMIAPLVKITGELQPFIPNVIFGTMTLLGGSAAFFLLETLNRPLPETIEDIQDWYQQTKKTKQEPEAEKASQTIPLKTGGP
InterPro domains: - IPR004749: Organic cation transport protein/SVOP (family) [11-503]
- IPR005828: Major facilitator, sugar transporter-like (family) [118-502]
- IPR036259: MFS transporter superfamily (homologous_superfamily) [95-507]
- IPR020846: Major facilitator superfamily domain (domain) [83-497]
Interaction partners: - Solute carrier family 22 member 7
- Solute carrier family 2, facilitated glucose transporter 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 sub-family C member 4
- Solute carrier organic anion transporter family member 1A6
- Sodium-dependent phosphate transport protein 1
- Solute carrier organic anion transporter family member 1A4
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005215 (transporter activity), GO:0022857 (transmembrane transporter activity), GO:0015101 (organic cation transmembrane transporter activity), GO:0008514 (organic anion transmembrane transporter activity)
Biological Process (BP): GO:0008150 (biological process), GO:0051179 (localization), GO:0032501 (multicellular organismal process), GO:0051234 (establishment of localization), GO:0003008 (system process), GO:0003014 (renal system process), GO:0007588 (excretion), GO:0006810 (transport), GO:0097254 (renal tubular secretion), GO:0006811 (monoatomic ion transport), GO:0071702 (organic substance transport), GO:0006820 (monoatomic anion transport), GO:0015711 (organic anion transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0045178 (basal part of cell), GO:0045177 (apical part of cell), GO:0071944 (cell periphery), GO:0016020 (membrane), GO:0009925 (basal plasma membrane), GO:0098590 (plasma membrane region), GO:0005886 (plasma membrane), GO:0016324 (apical plasma membrane), GO:0016323 (basolateral plasma membrane)