Solute carrier family 22 member 6
Also known as: OAT1, PAHT, SLC22A6
Function
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. 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. 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. Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion. Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP. Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain. May transport glutamate. 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. 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. Xenobiotics include the mycotoxin ochratoxin (OTA). May also contribute to the transport of organic compounds in testes across the blood-testis-barrier.
Classification
- Family (Pfam)
- PF00083 Sugar_tr
- InterPro
- MFS_dom, MFS_sugar_transport-like, MFS_trans_sf, Orgcat_transp/SVOP
- Functional cluster
- G Protein-Coupled Receptors
Experimental structures · PDB · 12
- 9J02 EM 3.36A
- 9J04 EM 3.15A
- 9J06 EM 3.68A
- 9KKK EM 3.85A
- 9KL5 EM 3.33A
- 9KLZ EM 3.88A
- 9M8Y EM 3.27A
- 9M9V EM 3.31A
- 9MAU EM 2.87A
- 9MC8 EM 3.31A
- 9U55 EM 3.17A
- 9UNX EM 3.45A
A predicted model is available from AlphaFold.
Gene Ontology · 20
- GO:0009925 basal plasma membrane
- GO:0016323 basolateral plasma membrane
- GO:0005901 caveola
- GO:0070062 extracellular exosome
- GO:0005886 plasma membrane
- GO:0032991 protein-containing complex
- GO:0015139 alpha-ketoglutarate transmembrane transporter activity
- GO:0015297 antiporter activity
- GO:0015132 prostaglandin transmembrane transporter activity
- GO:0015291 secondary active transmembrane transporter activity
- GO:0005452 solute:inorganic anion antiporter activity
- GO:0022857 transmembrane transporter activity
- GO:0042910 xenobiotic transmembrane transporter activity
- GO:0015742 alpha-ketoglutarate transport
- GO:0072237 metanephric proximal tubule development
- GO:0015711 organic anion transport
- GO:0015732 prostaglandin transport
- GO:0051260 protein homooligomerization
- GO:0097254 renal tubular secretion
- GO:0043252 sodium-independent organic anion transport
Drugs targeting this protein · 2
- PRATOSARTAN inhibitor
- PROBENECID inhibitor
Related proteins · sequence + function similarity
- Solute carrier family 22 member 6 1.00
- Solute carrier family 22 member 6 1.00
- Solute carrier family 22 member 6 0.99
- Solute carrier family 22 member 6 0.98
- Solute carrier family 22 member 6 0.97
- Solute carrier family 22 member 12 0.96
- Solute carrier family 22 member 6 0.95
- Solute carrier family 22 member 12 0.95
- Solute carrier family 22 member 6 0.95
- Solute carrier family 22 member 11 0.94
- Organic anion transporter 3 0.94
- Organic anion transporter 3 0.94
Co-cited proteins · studied together in the literature
- Organic anion transporter 3 9 shared papers
- Solute carrier family 22 member 6 1 shared papers
- Solute carrier family 22 member 6 3 shared papers
- Solute carrier family 22 member 6 1 shared papers
- Organic anion transporter 3 2 shared papers
- Solute carrier family 22 member 7 2 shared papers
- Solute carrier family 22 member 11 1 shared papers
- Solute carrier family 22 member 1 2 shared papers
- Solute carrier family 22 member 2 2 shared papers
- ATP-binding cassette sub-family C member 10 1 shared papers
- Solute carrier organic anion transporter family member 1C1 1 shared papers
- Sodium/nucleoside cotransporter 2 1 shared papers
Literature · 24 cited papers
- Localization of Xenobiotic Transporters Expressed at the Human Blood-Testis Barrier. Drug Metab. Dispos. · 2022
- 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
- Human organic anion transporter 2 is distinct from organic anion transporters 1 and 3 with respect to transport function. Am. J. Physiol. · 2015
- Transport of xanthurenic acid by rat/human organic anion transporters OAT1 and OAT3. Biosci. Biotechnol. Biochem. · 2013
- Interaction and transport of kynurenic acid via human organic anion transporters hOAT1 and hOAT3. Pharmacol. Res. · 2012
- Human organic anion transporters 1 (hOAT1/SLC22A6) and 3 (hOAT3/SLC22A8) transport edaravone (MCI-186; 3-methyl-1-phenyl-2-pyrazolin-5-one) and its sulfate conjugate. Drug Metab. Dispos. · 2007
- A three-dimensional model of human organic anion transporter 1: aromatic amino acids required for substrate transport. J. Biol. Chem. · 2006
- Human chromosome 11 DNA sequence and analysis including novel gene identification. Nature · 2006
- Analyses of coding region polymorphisms in apical and basolateral human organic anion transporter (OAT) genes [OAT1 (NKT), OAT2, OAT3, OAT4, URAT (RST)]. Kidney Int. · 2005
- Functional consequences of single nucleotide polymorphisms in the human organic anion transporter hOAT1 (SLC22A6). J. Pharmacol. Exp. Ther. · 2005
- Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8). J. Pharmacol. Exp. Ther. · 2005
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- … and 12 more in the literature graph