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Gene Review

SLC22A3  -  solute carrier family 22 (organic cation...

Homo sapiens

Synonyms: EMT, EMTH, Extraneuronal monoamine transporter, OCT3, Organic cation transporter 3, ...
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Disease relevance of SLC22A3


Psychiatry related information on SLC22A3

  • Moreover, SLC22A3 (which encodes OCT3) is a candidate gene for MAP dependence because it is located within a chromosomal region associated with substance dependence [6].

High impact information on SLC22A3


Chemical compound and disease context of SLC22A3

  • (6) The consistent factor associated with EMT was only high-GOP solution (60 patients, n = 178, beta coefficient 0.312, p = 0.000; 46 patients, n = 137, beta coef: 0.228, p = 0.000) and not numbers of peritonitis episodes, duration of angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker medication, or diabetes [9].

Biological context of SLC22A3


Anatomical context of SLC22A3


Associations of SLC22A3 with chemical compounds

  • Famotidine seems to be one of the most potent inhibitors of hOCT3 yet identified [11].
  • Corticosterone was about 100 fold more potent as inhibitor of hOCT3 than of hOCT1 or hOCT2, and O-methylisoprenaline (OMI) inhibited almost exclusively hOCT3 [12].
  • Decynium-22 inhibited hOCT3 with 10 fold higher potency than hOCT1 and hOCT2 [12].
  • Progesterone and beta-Oestradiol preferentially inhibited hOCT3 and hOCT1, whereas prazosin was a potent inhibitor of hOCT1 and hOCT3 [12].
  • Phenoxybenzamine (PbA) inhibited with about equal apparent potency all three hOCTs, whereas the PbA derivative SKF550 ((9-fluorenyl)-N-methyl-beta-chloroethylamine) preferentially inhibited hOCT3 and hOCT2 [12].

Other interactions of SLC22A3

  • SLC22A2 and SLC22A3, two genes downstream of IGF2R that are imprinted in the mouse, showed no T1D association [15].
  • Modeling analyses predicted multiplicity of the uptake mechanisms with the high-affinity systems characterized by K(m) of 5.1 microM for carnitine and 1.6 mM for TEA, apparently similar to the reported hOCTN2 parameter for carnitine, and that of EMT/hOCT3 for TEA [16].
  • The EMT gene is 77 kb, and the OCT2 gene is 45 kb in size [14].
  • Cultures were pretreated with either corticosterone, a specific inhibitor of EMT, or reserpine, a specific inhibitor of VMAT-2 [17].
  • The EMT promoter, located within a CpG island, lacks a consensus TATA box but contains a prototypical initiator element and a number of potential binding sites for ubiquitous transcription factors Sp1 and NF-1 [14].

Analytical, diagnostic and therapeutic context of SLC22A3

  • For the EMT gene, two transcription start points were identified by inverse polymerase chain reaction based on mRNA from Caki-1 cells [14].
  • Moreover, quantitative analysis showed a significant lower expression of NET and EMT mRNAs in pre-eclamptic placentae as compared to the control group [18].
  • The expression of OCT3 in human kidney was confirmed by RT-PCR [19].
  • TGF-beta1-induced apoptosis and EMT were associated with the activation of protein kinase A (PKA) and signal transducers and activators of transcription 3 (STAT3) [3].
  • The present study demonstrates the usefulness of OCT3/4 immunohistochemistry in a diagnostic setting of a consecutively collected series of more than 200 testicular tumours and over 80 testicular biopsies [20].


  1. The localisation of the extraneuronal monoamine transporter (EMT) in rat brain. Haag, C., Berkels, R., Gründemann, D., Lazar, A., Taubert, D., Schömig, E. J. Neurochem. (2004) [Pubmed]
  2. SarCNU, a nitrosourea analog on a day 1, 5, and 9 oral schedule: a phase I and pharmacokinetic study in patients with advanced solid tumors. Panasci, L., Stinson, S.F., Melnychuk, D., Sandor, V., Miller, W.H., Batist, G., Patenaude, F., Bangash, N., Panarello, L., Alaoui-Jamali, M., Sausville, E. J. Clin. Oncol. (2003) [Pubmed]
  3. Regulation of Transforming Growth Factor-{beta}1-Induced Apoptosis and Epithelial-to-Mesenchymal Transition by Protein Kinase A and Signal Transducers and Activators of Transcription 3. Yang, Y., Pan, X., Lei, W., Wang, J., Shi, J., Li, F., Song, J. Cancer Res. (2006) [Pubmed]
  4. Host microvasculature influence on tumor vascular morphology and endothelial gene expression. Roberts, W.G., Delaat, J., Nagane, M., Huang, S., Cavenee, W.K., Palade, G.E. Am. J. Pathol. (1998) [Pubmed]
  5. OCT4: A sensitive and specific biomarker for intratubular germ cell neoplasia of the testis. Jones, T.D., Ulbright, T.M., Eble, J.N., Cheng, L. Clin. Cancer Res. (2004) [Pubmed]
  6. Association Between Gene Polymorphisms of SLC22A3 and Methamphetamine Use Disorder. Aoyama, N., Takahashi, N., Kitaichi, K., Ishihara, R., Saito, S., Maeno, N., Ji, X., Takagi, K., Sekine, Y., Iyo, M., Harano, M., Komiyama, T., Yamada, M., Sora, I., Ujike, H., Iwata, N., Inada, T., Ozaki, N. Alcohol. Clin. Exp. Res. (2006) [Pubmed]
  7. CD28 is associated with and induces the immediate tyrosine phosphorylation and activation of the Tec family kinase ITK/EMT in the human Jurkat leukemic T-cell line. August, A., Gibson, S., Kawakami, Y., Kawakami, T., Mills, G.B., Dupont, B. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  8. Ventricular choline transport: a role for organic cation transporter 2 expressed in choroid plexus. Sweet, D.H., Miller, D.S., Pritchard, J.B. J. Biol. Chem. (2001) [Pubmed]
  9. The effect of low glucose degradation product dialysis solution on epithelial-to-mesenchymal transition in continuous ambulatory peritoneal dialysis patients. Do, J.Y., Kim, Y.L., Park, J.W., Cho, K.H., Kim, T.W., Yoon, K.W., Kim, C.D., Park, S.H., Han, J.H., Song, I.H. Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. (2005) [Pubmed]
  10. Cloning of the mouse and human solute carrier 22a3 (Slc22a3/SLC22A3) identifies a conserved cluster of three organic cation transporters on mouse chromosome 17 and human 6q26-q27. Verhaagh, S., Schweifer, N., Barlow, D.P., Zwart, R. Genomics (1999) [Pubmed]
  11. Differential substrate and inhibitory activities of ranitidine and famotidine toward human organic cation transporter 1 (hOCT1; SLC22A1), hOCT2 (SLC22A2), and hOCT3 (SLC22A3). Bourdet, D.L., Pritchard, J.B., Thakker, D.R. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  12. Expression and pharmacological profile of the human organic cation transporters hOCT1, hOCT2 and hOCT3. Hayer-Zillgen, M., Brüss, M., Bönisch, H. Br. J. Pharmacol. (2002) [Pubmed]
  13. Identity of the organic cation transporter OCT3 as the extraneuronal monoamine transporter (uptake2) and evidence for the expression of the transporter in the brain. Wu, X., Kekuda, R., Huang, W., Fei, Y.J., Leibach, F.H., Chen, J., Conway, S.J., Ganapathy, V. J. Biol. Chem. (1998) [Pubmed]
  14. Gene structures of the human non-neuronal monoamine transporters EMT and OCT2. Gründemann, D., Schömig, E. Hum. Genet. (2000) [Pubmed]
  15. The insulin-like growth factor-II receptor gene is associated with type 1 diabetes: evidence of a maternal effect. McCann, J.A., Xu, Y.Q., Frechette, R., Guazzarotti, L., Polychronakos, C. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  16. Carnitine/xenobiotics transporters in the human mammary gland epithelia, MCF12A. Kwok, B., Yamauchi, A., Rajesan, R., Chan, L., Dhillon, U., Gao, W., Xu, H., Wang, B., Takahashi, S., Semple, J., Tamai, I., Nezu, J., Tsuji, A., Harper, P., Ito, S. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  17. Histamine uptake by human endometrial cells expressing the organic cation transporter EMT and the vesicular monoamine transporter-2. Noskova, V., Bottalico, B., Olsson, H., Ehinger, A., Pilka, R., Casslén, B., Hansson, S.R. Mol. Hum. Reprod. (2006) [Pubmed]
  18. Norepinephrine transporter (NET), serotonin transporter (SERT), vesicular monoamine transporter (VMAT2) and organic cation transporters (OCT1, 2 and EMT) in human placenta from pre-eclamptic and normotensive pregnancies. Bottalico, B., Larsson, I., Brodszki, J., Hernandez-Andrade, E., Casslén, B., Marsál, K., Hansson, S.R. Placenta (2004) [Pubmed]
  19. Structure, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Wu, X., Huang, W., Ganapathy, M.E., Wang, H., Kekuda, R., Conway, S.J., Leibach, F.H., Ganapathy, V. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  20. Diagnostic value of OCT3/4 for pre-invasive and invasive testicular germ cell tumours. de Jong, J., Stoop, H., Dohle, G.R., Bangma, C.H., Kliffen, M., van Esser, J.W., van den Bent, M., Kros, J.M., Oosterhuis, J.W., Looijenga, L.H. J. Pathol. (2005) [Pubmed]
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