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Gene Review

SLC22A6  -  solute carrier family 22 (organic anion...

Homo sapiens

Synonyms: HOAT1, OAT1, Organic anion transporter 1, PAH transporter, PAHT, ...
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Disease relevance of SLC22A6

  • More important, the findings from the present study implicate the activity of OAT1 in the uptake and toxicity of Hg (when in the form of Hcy-S-Hg-S-Hcy in the extracellular compartment) in proximal tubular epithelial cells in vivo [1].
  • Accumulation of Indoxyl Sulfate in OAT1/3-Positive Tubular Cells in Kidneys of Patients With Chronic Renal Failure [2].
  • The present study demonstrates the key role of OAT1 expression in the impaired elimination of PAH after 3 days of obstructive cholestasis [3].
  • In this investigation, a theoretical three-dimensional model was generated for human OAT1 (hOAT1) based on fold recognition to the crystal structure of the glycerol 3-phosphate transporter (GlpT) from Escherichia coli [4].
  • We show that the recombinant retrovirus transfers the human OAT (hOAT) gene into C9 [5].

High impact information on SLC22A6

  • A cDNA probe (HOAT1) for ornithine aminotransferase (OAT) has recently been used to map (1) the structural gene for this enzyme to chromosome 10 and (2) several related DNA sequences to the X chromosome [6].
  • The RFLPs, which are detected by noncoding single-copy probes from the OAT gene and by subclones of the HOAT1 cDNA, all map on human chromosome 10, producing an overall level of heterozygosity for the OAT locus of 83% [6].
  • Little uptake was determined for cidofovir, whereas PAH uptake was similar to wild-type hOAT1 [4].
  • The structural hOAT1 model shows that helices 5, 7, 8, 10, and 11 surround an electronegative putative active site ( approximately 830A(3)) [4].
  • In contrast, a simultaneous replacement of all asparagines in both mOAT1 and hOAT1 impaired the trafficking of the transporters to the plasma membrane [7].

Chemical compound and disease context of SLC22A6


Biological context of SLC22A6


Anatomical context of SLC22A6

  • This question was addressed in Xenopus laevis oocytes expressing human organic anion transporter 1 (hOAT1), 3 (hOAT3), and winter flounder OAT (fOat1) [13].
  • In the present study, we investigated the effect of disrupting putative glycosylation sites in mOAT1 as well as its human counterpart, hOAT1, by mutating asparagine to glutamine and assessing mutant transporters in HeLa cells [7].
  • It was independent of the conserved canonical PKC consensus sites in hOAT1, however, and was unaffected by agents that destabilize actin filaments or microtubules, which altered baseline hOAT1-mediated p-aminohippurate uptake activity in oocytes [14].
  • To test this hypothesis directly, the transport and toxicity of mercuric-thiol conjugates were characterized in a Madin-Darby canine kidney cell line stably transfected with the human organic anion transporter 1 (hOAT1) [8].
  • However, reverse transcription-polymerase chain reaction revealed hOAT1 expression in human brain and skeletal muscle, as well [15].

Associations of SLC22A6 with chemical compounds


Physical interactions of SLC22A6

  • The IC(50) of steviol for hOAT1-mediated PAH transport was 11.1 microM compared with 62.6 microM for hOAT3-mediated ES uptake [13].

Other interactions of SLC22A6

  • Despite large interbatch differences, hOAT1 and hOAT3 mRNA levels correlated well, and there was a good correlation between the uptake of PAH and PCG by kidney slices [17].
  • Immunohistochemical analyses showed that both hOAT1 and hOAT3 were localized to the basolateral membrane of the proximal tubules in the cortex, and hOCT2 was localized to the basolateral membrane of the proximal tubules in both the cortex and medullary ray [21].
  • EGF- and PGE2-mediated stimulation of organic anion uptake was abolished by inhibition of PKA in rabbit S2 tubules and IHKE-hOAT1, respectively [22].
  • In addition, hOAT3 mediated famotidine uptake, but hOAT1 and hOCT2 did not show famotidine transport [23].
  • Recently three proteins, playing central roles in the bidirectional transport of urate in renal proximal tubules, were identified: two members of the organic anion transporter (OAT) family, OAT1 and OAT3, and a protein that designated renal urate-anion exchanger (URAT1) [24].

Analytical, diagnostic and therapeutic context of SLC22A6


  1. Homocysteine and the renal epithelial transport and toxicity of inorganic mercury: role of basolateral transporter organic anion transporter 1. Zalups, R.K., Ahmad, S. J. Am. Soc. Nephrol. (2004) [Pubmed]
  2. Accumulation of Indoxyl Sulfate in OAT1/3-Positive Tubular Cells in Kidneys of Patients With Chronic Renal Failure. Taki, K., Nakamura, S., Miglinas, M., Enomoto, A., Niwa, T. Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation. (2006) [Pubmed]
  3. Renal elimination of p-aminohippurate (PAH) in response to three days of biliary obstruction in the rat. The role of OAT1 and OAT3. Brandoni, A., Anzai, N., Kanai, Y., Endou, H., Torres, A.M. Biochim. Biophys. Acta (2006) [Pubmed]
  4. A Three-dimensional Model of Human Organic Anion Transporter 1: AROMATIC AMINO ACIDS REQUIRED FOR SUBSTRATE TRANSPORT. Perry, J.L., Dembla-Rajpal, N., Hall, L.A., Pritchard, J.B. J. Biol. Chem. (2006) [Pubmed]
  5. Correction of ornithine-delta-aminotransferase deficiency in a Chinese hamster ovary cell line mediated by retrovirus gene transfer. Lacorazza, H.D., Jendoubi, M. Gene Ther. (1995) [Pubmed]
  6. The ornithine aminotransferase (OAT) locus: analysis of RFLPs in gyrate atrophy. Ramesh, V., Benoit, L.A., Crawford, P., Harvey, P.T., Shows, T.B., Shih, V.E., Gusella, J.F. Am. J. Hum. Genet. (1988) [Pubmed]
  7. Role of glycosylation in the organic anion transporter OAT1. Tanaka, K., Xu, W., Zhou, F., You, G. J. Biol. Chem. (2004) [Pubmed]
  8. Human renal organic anion transporter 1-dependent uptake and toxicity of mercuric-thiol conjugates in Madin-Darby canine kidney cells. Aslamkhan, A.G., Han, Y.H., Yang, X.P., Zalups, R.K., Pritchard, J.B. Mol. Pharmacol. (2003) [Pubmed]
  9. Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxicity of antiviral nucleotide analogs. Cihlar, T., Ho, E.S., Lin, D.C., Mulato, A.S. Nucleosides Nucleotides Nucleic Acids (2001) [Pubmed]
  10. Functional consequences of single nucleotide polymorphisms in the human organic anion transporter hOAT1 (SLC22A6). Bleasby, K., Hall, L.A., Perry, J.L., Mohrenweiser, H.W., Pritchard, J.B. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  11. Torsemide renal clearance and genetic variation in luminal and basolateral organic anion transporters. Vormfelde, S.V., Schirmer, M., Hagos, Y., Toliat, M.R., Engelhardt, S., Meineke, I., Burckhardt, G., Nürnberg, P., Brockmöller, J. British journal of clinical pharmacology. (2006) [Pubmed]
  12. Analyses of 5' regulatory region polymorphisms in human SLC22A6 (OAT1) and SLC22A8 (OAT3). Bhatnagar, V., Xu, G., Hamilton, B.A., Truong, D.M., Eraly, S.A., Wu, W., Nigam, S.K. J. Hum. Genet. (2006) [Pubmed]
  13. Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8). Srimaroeng, C., Chatsudthipong, V., Aslamkhan, A.G., Pritchard, J.B. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  14. Protein kinase C activation downregulates human organic anion transporter 1-mediated transport through carrier internalization. Wolff, N.A., Thies, K., Kuhnke, N., Reid, G., Friedrich, B., Lang, F., Burckhardt, G. J. Am. Soc. Nephrol. (2003) [Pubmed]
  15. The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1. Cihlar, T., Lin, D.C., Pritchard, J.B., Fuller, M.D., Mendel, D.B., Sweet, D.H. Mol. Pharmacol. (1999) [Pubmed]
  16. Methotrexate-loxoprofen interaction: involvement of human organic anion transporters hOAT1 and hOAT3. Uwai, Y., Taniguchi, R., Motohashi, H., Saito, H., Okuda, M., Inui, K. Drug Metab. Pharmacokinet. (2004) [Pubmed]
  17. Characterization of the Uptake of Organic Anion Transporter (OAT) 1 and OAT3 Substrates by Human Kidney Slices. Nozaki, Y., Kusuhara, H., Kondo, T., Hasegawa, M., Shiroyanagi, Y., Nakazawa, H., Okano, T., Sugiyama, Y. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  18. Renal Transport of Adefovir, Cidofovir, and Tenofovir by SLC22A Family Members (hOAT1, hOAT3, and hOCT2). Uwai, Y., Ida, H., Tsuji, Y., Katsura, T., Inui, K. Pharm. Res. (2007) [Pubmed]
  19. Human organic anion transporters mediate the transport of tetracycline. Babu, E., Takeda, M., Narikawa, S., Kobayashi, Y., Yamamoto, T., Cha, S.H., Sekine, T., Sakthisekaran, D., Endou, H. Jpn. J. Pharmacol. (2002) [Pubmed]
  20. The chloride dependence of the human organic anion transporter 1 (hOAT1) is blunted by mutation of a single amino acid. Rizwan, A.N., Krick, W., Burckhardt, G. J. Biol. Chem. (2007) [Pubmed]
  21. Gene expression levels and immunolocalization of organic ion transporters in the human kidney. Motohashi, H., Sakurai, Y., Saito, H., Masuda, S., Urakami, Y., Goto, M., Fukatsu, A., Ogawa, O., Inui, K. J. Am. Soc. Nephrol. (2002) [Pubmed]
  22. Action of EGF and PGE2 on basolateral organic anion uptake in rabbit proximal renal tubules and hOAT1 expressed in human kidney epithelial cells. Sauvant, C., Hesse, D., Holzinger, H., Evans, K.K., Dantzler, W.H., Gekle, M. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  23. Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A). Motohashi, H., Uwai, Y., Hiramoto, K., Okuda, M., Inui, K. Eur. J. Pharmacol. (2004) [Pubmed]
  24. Development of High-specificity Antibodies against Renal Urate Transporters Using Genetic Immunization. Xu, G., Chen, X., Wu, D., Shi, S., Wang, J., Ding, R., Hong, Q., Feng, Z., Lin, S., Lu, Y. J. Biochem. Mol. Biol. (2006) [Pubmed]
  25. Molecular cloning and functional analyses of OAT1 and OAT3 from cynomolgus monkey kidney. Tahara, H., Shono, M., Kusuhara, H., Kinoshita, H., Fuse, E., Takadate, A., Otagiri, M., Sugiyama, Y. Pharm. Res. (2005) [Pubmed]
  26. Organic anion and cation transporter expression and function during embryonic kidney development and in organ culture models. Sweet, D.H., Eraly, S.A., Vaughn, D.A., Bush, K.T., Nigam, S.K. Kidney Int. (2006) [Pubmed]
  27. Expression studies and functional characterization of renal human organic anion transporter 1 isoforms. Bahn, A., Ebbinghaus, C., Ebbinghaus, D., Ponimaskin, E.G., Fuzesï, L., Burckhardt, G., Hagos, Y. Drug Metab. Dispos. (2004) [Pubmed]
  28. Genomic structure and in vivo expression of the human organic anion transporter 1 (hOAT1) gene. Bahn, A., Prawitt, D., Buttler, D., Reid, G., Enklaar, T., Wolff, N.A., Ebbinghaus, C., Hillemann, A., Schulten, H.J., Gunawan, B., Füzesi, L., Zabel, B., Burckhardt, G. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  29. Molecular cloning and functional expression of a multispecific organic anion transporter from human kidney. Hosoyamada, M., Sekine, T., Kanai, Y., Endou, H. Am. J. Physiol. (1999) [Pubmed]
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