9j06

Structural highlights

Function

S22A6_HUMAN Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate (PubMed:11669456, PubMed:11907186, PubMed:14675047, PubMed:22108572, PubMed:23832370, PubMed:28534121, PubMed:9950961). Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine (PubMed:9887087). 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 (PubMed:28534121). Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion (PubMed:11907186). Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP (PubMed:26377792). Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain (PubMed:22108572, PubMed:23832370). May transport glutamate (PubMed:26377792). Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body (PubMed:11669456, PubMed:14675047). Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate (PubMed:14675047, PubMed:26377792). Xenobiotics include the mycotoxin ochratoxin (OTA) (PubMed:11669456). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier (PubMed:35307651).^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10]}

References

1. ↑ Jung KY, Takeda M, Kim DK, Tojo A, Narikawa S, Yoo BS, Hosoyamada M, Cha SH, Sekine T, Endou H. Characterization of ochratoxin A transport by human organic anion transporters. Life Sci. 2001 Sep 21;69(18):2123-35. PMID:11669456 doi:10.1016/s0024-3205(01)01296-6
2. ↑ Kimura H, Takeda M, Narikawa S, Enomoto A, Ichida K, Endou H. Human organic anion transporters and human organic cation transporters mediate renal transport of prostaglandins. J Pharmacol Exp Ther. 2002 Apr;301(1):293-8. PMID:11907186 doi:10.1124/jpet.301.1.293
3. ↑ Deguchi T, Kusuhara H, Takadate A, Endou H, Otagiri M, Sugiyama Y. Characterization of uremic toxin transport by organic anion transporters in the kidney. Kidney Int. 2004 Jan;65(1):162-74. PMID:14675047 doi:10.1111/j.1523-1755.2004.00354.x
4. ↑ Uwai Y, Honjo H, Iwamoto K. Interaction and transport of kynurenic acid via human organic anion transporters hOAT1 and hOAT3. Pharmacol Res. 2012 Feb;65(2):254-60. PMID:22108572 doi:10.1016/j.phrs.2011.11.003
5. ↑ Uwai Y, Honjo E. Transport of xanthurenic acid by rat/human organic anion transporters OAT1 and OAT3. Biosci Biotechnol Biochem. 2013;77(7):1517-21. PMID:23832370 doi:10.1271/bbb.130178
6. ↑ Henjakovic M, Hagos Y, Krick W, Burckhardt G, Burckhardt BC. Human organic anion transporter 2 is distinct from organic anion transporters 1 and 3 with respect to transport function. Am J Physiol Renal Physiol. 2015 Nov 15;309(10):F843-51. PMID:26377792 doi:10.1152/ajprenal.00140.2015
7. ↑ Ohashi A, Mamada K, Harada T, Naito M, Takahashi T, Aizawa S, Hasegawa H. Organic anion transporters, OAT1 and OAT3, are crucial biopterin transporters involved in bodily distribution of tetrahydrobiopterin and exclusion of its excess. Mol Cell Biochem. 2017 Nov;435(1-2):97-108. PMID:28534121 doi:10.1007/s11010-017-3060-7
8. ↑ Hau RK, Klein RR, Wright SH, Cherrington NJ. Localization of Xenobiotic Transporters Expressed at the Human Blood-Testis Barrier. Drug Metab Dispos. 2022 Jun;50(6):770-780. PMID:35307651 doi:10.1124/dmd.121.000748
9. ↑ Hosoyamada M, Sekine T, Kanai Y, Endou H. Molecular cloning and functional expression of a multispecific organic anion transporter from human kidney. Am J Physiol. 1999 Jan;276(1):F122-8. PMID:9887087 doi:10.1152/ajprenal.1999.276.1.F122
10. ↑ Lu R, Chan BS, Schuster VL. Cloning of the human kidney PAH transporter: narrow substrate specificity and regulation by protein kinase C. Am J Physiol. 1999 Feb;276(2):F295-303. PMID:9950961 doi:10.1152/ajprenal.1999.276.2.F295