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Gene Review

SLC22A11  -  solute carrier family 22 (organic...

Homo sapiens

Synonyms: OAT4, Organic anion transporter 4, Solute carrier family 22 member 11, hOAT4
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Disease relevance of SLC22A11

  • Thus, hOAT4 is the long-postulated, low-affinity apical urate anion exchanger that facilitates HCTZ-associated hyperuricemia [1].

High impact information on SLC22A11


Biological context of SLC22A11

  • The two most frequent haplotypes at SLC22A11 showed an association with torsemide renal clearance [4].
  • In addition, Ka/Ks analysis of human, chimp and rodent genes suggests that OAT4 is under accelerated selection pressure, perhaps reflecting specific human environmental exposures during evolution [5].
  • However, the substrate specificity of OAT4 remains to be investigated in detail [6].
  • CONCLUSIONS: Genetic variation in the gene encoding the luminally expressed OAT4 rather than in the basolaterally expressed OATs may affect the renal clearance of torsemide [4].
  • The amino acid sequence of OAT4 showed 38 to 44% identity to those of other members of the OAT family [3].

Anatomical context of SLC22A11

  • The uptake of oxypurinol by another organic anion transporter (OAT), OAT4 (SLC22A11), which is also expressed at the apical membrane of proximal tubular epithelial cells, was negligible, whereas the uptake of [3H]estrone-3-sulfate by OAT4 was significantly inhibited by oxypurinol [7].
  • When human OAT3 (hOAT3) and hOAT4 were expressed in Xenopus laevis oocytes, only hOAT3 showed [3H]cortisol uptake in excess of that of water-injected control oocytes [8].
  • However, hOAT4 expressed in CHO-Lec1 cells had significantly lower binding affinity for its substrates compared with that expressed in parental CHO cells [9].
  • Finally, Caco-2 cells were shown to express organic anion transporter 4 (OAT4) mRNA, as was the human large intestine [10].

Associations of SLC22A11 with chemical compounds

  • HEK-OAT4 cells exhibited concentration-dependent uptake of estrone-3-sulfate, with a K(m) value of 20.9+/-3.53 muM [6].
  • Inhibitory effects of angiotensin II receptor antagonists and leukotriene receptor antagonists on the transport of human organic anion transporter 4 [6].
  • Although pranlukast is devoid of anionic motifs other than the tetrazole group, it potently inhibited the OAT4-mediated uptake of estrone-3-sulfate, indicating that a tetrazole group may be one important structural feature in substrate recognition by OAT4 [6].
  • In contrast, oxytetracycline, minocycline and doxycycline exhibited no significant inhibitory effects on the organic anion uptake by hOAT3 and hOAT4 [11].
  • We also searched for the potential inhibitors of OAT4 and identified candesartan, candesartan cilexetil, losartan, losartan carboxyl (EXP3174) and valsartan as inhibitors of OAT4, with K(i) values of 88.9, 135.2, 24.8, 13.8 and 19.6 muM, respectively [6].

Other interactions of SLC22A11

  • METHODS: We analysed 22 polymorphisms in the OAT coding genes SLC22A6, SLC22A8 and SLC22A11 and their haplotypes and measured torsemide renal clearance in 95 healthy men [4].
  • In conclusion, these results suggest that methotrexate is taken up via hOAT3 and hOAT1 at the basolateral side of the proximal tubule and effluxed or taken up at the apical side via hOAT4 [12].

Analytical, diagnostic and therapeutic context of SLC22A11


  1. Human renal organic anion transporter 4 operates as an asymmetric urate transporter. Hagos, Y., Stein, D., Ugele, B., Burckhardt, G., Bahn, A. J. Am. Soc. Nephrol. (2007) [Pubmed]
  2. Syncytial fusion of human trophoblast depends on caspase 8. Black, S., Kadyrov, M., Kaufmann, P., Ugele, B., Emans, N., Huppertz, B. Cell Death Differ. (2004) [Pubmed]
  3. Molecular cloning and characterization of multispecific organic anion transporter 4 expressed in the placenta. Cha, S.H., Sekine, T., Kusuhara, H., Yu, E., Kim, J.Y., Kim, D.K., Sugiyama, Y., Kanai, Y., Endou, H. J. Biol. Chem. (2000) [Pubmed]
  4. 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]
  5. Analyses of coding region polymorphisms in apical and basolateral human organic anion transporter (OAT) genes [OAT1 (NKT), OAT2, OAT3, OAT4, URAT (RST)]. Xu, G., Bhatnagar, V., Wen, G., Hamilton, B.A., Eraly, S.A., Nigam, S.K. Kidney Int. (2005) [Pubmed]
  6. Inhibitory effects of angiotensin II receptor antagonists and leukotriene receptor antagonists on the transport of human organic anion transporter 4. Yamashita, F., Ohtani, H., Koyabu, N., Ushigome, F., Satoh, H., Murakami, H., Uchiumi, T., Nakamura, T., Kuwano, M., Tsujimoto, M., Sawada, Y. J. Pharm. Pharmacol. (2006) [Pubmed]
  7. Involvement of uric acid transporter in increased renal clearance of the xanthine oxidase inhibitor oxypurinol induced by a uricosuric agent, benzbromarone. Iwanaga, T., Kobayashi, D., Hirayama, M., Maeda, T., Tamai, I. Drug Metab. Dispos. (2005) [Pubmed]
  8. Presence of organic anion transporters 3 (OAT3) and 4 (OAT4) in human adrenocortical cells. Asif, A.R., Steffgen, J., Metten, M., Grunewald, R.W., Müller, G.A., Bahn, A., Burckhardt, G., Hagos, Y. Pflugers Arch. (2005) [Pubmed]
  9. The role of N-linked glycosylation in protein folding, membrane targeting, and substrate binding of human organic anion transporter hOAT4. Zhou, F., Xu, W., Hong, M., Pan, Z., Sinko, P.J., Ma, J., You, G. Mol. Pharmacol. (2005) [Pubmed]
  10. Site-specific accumulation of the cancer preventive dietary polyphenol ellagic acid in epithelial cells of the aerodigestive tract. Whitley, A.C., Sweet, D.H., Walle, T. J. Pharm. Pharmacol. (2006) [Pubmed]
  11. 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]
  12. Characterization of methotrexate transport and its drug interactions with human organic anion transporters. Takeda, M., Khamdang, S., Narikawa, S., Kimura, H., Hosoyamada, M., Cha, S.H., Sekine, T., Endou, H. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  13. Modulation of renal apical organic anion transporter 4 function by two PDZ domain-containing proteins. Miyazaki, H., Anzai, N., Ekaratanawong, S., Sakata, T., Shin, H.J., Jutabha, P., Hirata, T., He, X., Nonoguchi, H., Tomita, K., Kanai, Y., Endou, H. J. Am. Soc. Nephrol. (2005) [Pubmed]
  14. Mutational analysis of histidine residues in human organic anion transporter 4 (hOAT4). Zhou, F., Pan, Z., Ma, J., You, G. Biochem. J. (2004) [Pubmed]
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