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Gene Review

SLC5A5  -  solute carrier family 5 (sodium/iodide...

Homo sapiens

Synonyms: NIS, Na(+)/I(-) cotransporter, Na(+)/I(-) symporter, Sodium-iodide symporter, Sodium/iodide cotransporter, ...
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Disease relevance of SLC5A5


Psychiatry related information on SLC5A5

  • Official statistics showed that alcohol consumption in the CCEE/NIS rose from the 1960s to the mid-1980s, and then remained stable or fell in most countries [4].

High impact information on SLC5A5


Chemical compound and disease context of SLC5A5


Biological context of SLC5A5

  • Our data indicate that hNIS is not a major antigen in autoimmune thyroid disease, as it is the target of humoral autoimmunity in only a few patients with GD and HT [3].
  • The expression of the NIS gene is up-regulated by TSH through the cAMP pathway and the characterization of the promoter region of the rat NIS gene revealed the existence of a degenerate cAMP response element (CRE) sequence [12].
  • Increased intracellular iodide concentration is mediated by IgG, which activates the upstream enhancer of the sodium/iodide symporter (NIS) [13].
  • The molecular processes explaining the principles of radioiodine treatment remained unresolved until the genetics and the functionality of the human sodium-iodide symporter (hNIS) were recently identified [13].
  • No significant difference between the two genotypes was found for Pax8, sodium iodide symporter, and iodothyronine deiodinase 1 [14].

Anatomical context of SLC5A5

  • The Na+/I- symporter (NIS) is important in hormone synthesis in the thyroid gland [2].
  • OBJECTIVE: Reduced expression or defective targeting of the sodium/iodide symporter (NIS) to the cell membrane in thyroid tumours has been reported [12].
  • No correlation was found in hNIS mRNA expression between primary and lymph node metastatic tissues [15].
  • In the thyroid tumor cell lines TPC-1 and B-CPAP, APE/Ref-1 was not effective by itself, and it also failed to increase PAX8 stimulation on NIS promoter activity [16].
  • We have studied the role of flavonoids on the iodide transport and the growth of the human follicular thyroid cancer cell line (FTC133) which was stably transfected with the human Na(+)/I(-) symporter (hNIS) [17].

Associations of SLC5A5 with chemical compounds


Physical interactions of SLC5A5


Regulatory relationships of SLC5A5


Other interactions of SLC5A5

  • Higher tumor stages (stages >I vs stage I) were associated with lower expression of NIS (P = 0.03) and TPO (P < 0.01) [1].
  • The correlation of mRNA levels between hNIS and thyroid-specific genes, thyrotropin (TSH) receptor, and thyroglobulin (Tg), were also investigated [15].
  • CONCLUSIONS: Our results have indicated for the first time that reduced levels of CREB expression are a feature of thyroid carcinomas, and confirm that different factors are likely to modulate NIS expression [12].
  • The level of hNIS mRNA was correlated with the levels of TSH receptor (r = 0.449, p < 0.05), but not with Tg mRNA [15].
  • This is the first demonstration of both extensive and local homologies between one thyroid autoantigen (NIS) and microbiological proteins [27].

Analytical, diagnostic and therapeutic context of SLC5A5

  • Northern blot analysis revealed that incubation of these cells with TSH or forskolin for 24 h increased the abundance of NIS messenger ribonucleic acid (mRNA) 2.3- and 2.5-fold, respectively [2].
  • The levels of hNIS mRNA in lymph node metastatic tissues were evaluated by RT-PCR [15].
  • Our results significantly indicate that co-expression of TPO in NIS transfected cells mediates iodination on the one hand but on the other hand does not contribute to augmentation of a putative NIS-based radioiodide concentrator gene therapy [28].
  • Consequently, the hNIS protein could be readily detected by Western blot analysis 48-h post-infection at 10 infectious virus particles per cell [7].
  • Antipeptide antibodies raised against the carboxyl-terminal region of the human sodium/iodide (Na+/I-) symporter (hNIS) were used to investigate by immunohistochemistry the presence and distribution of the hNIS protein in normal thyroid tissues, in some pathological nonneoplastic thyroid tissues, and in different histotypes of thyroid neoplasms [29].


  1. Expression of the Na+/I- symporter gene in human thyroid tumors: a comparison study with other thyroid-specific genes. Lazar, V., Bidart, J.M., Caillou, B., Mahé, C., Lacroix, L., Filetti, S., Schlumberger, M. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  2. Increased expression of the Na+/I- symporter in cultured human thyroid cells exposed to thyrotropin and in Graves' thyroid tissue. Saito, T., Endo, T., Kawaguchi, A., Ikeda, M., Nakazato, M., Kogai, T., Onaya, T. J. Clin. Endocrinol. Metab. (1997) [Pubmed]
  3. Low frequency of autoantibodies to the human Na(+)/I(-) symporter in patients with autoimmune thyroid disease. Seissler, J., Wagner, S., Schott, M., Lettmann, M., Feldkamp, J., Scherbaum, W.A., Morgenthaler, N.G. J. Clin. Endocrinol. Metab. (2000) [Pubmed]
  4. Alcohol consumption and related problems. Lehto, J. World health statistics quarterly. Rapport trimestriel de statistiques sanitaires mondiales. (1993) [Pubmed]
  5. Molecular analysis of the sodium/iodide symporter: impact on thyroid and extrathyroid pathophysiology. De La Vieja, A., Dohan, O., Levy, O., Carrasco, N. Physiol. Rev. (2000) [Pubmed]
  6. The sodium/iodide Symporter (NIS): characterization, regulation, and medical significance. Dohán, O., De la Vieja, A., Paroder, V., Riedel, C., Artani, M., Reed, M., Ginter, C.S., Carrasco, N. Endocr. Rev. (2003) [Pubmed]
  7. Kinetics of iodide uptake and efflux in various human thyroid cancer cells by expressing sodium iodide symporter gene via a recombinant adenovirus. Lee, W.W., Lee, B., Kim, S.J., Jin, J., Moon, D.H., Lee, H. Oncol. Rep. (2003) [Pubmed]
  8. Nonradioactive iodide effectively induces apoptosis in genetically modified lung cancer cells. Zhang, L., Sharma, S., Zhu, L.X., Kogai, T., Hershman, J.M., Brent, G.A., Dubinett, S.M., Huang, M. Cancer Res. (2003) [Pubmed]
  9. The promoter of the human sodium/iodide-symporter gene responds to retinoic acid. Schmutzler, C., Schmitt, T.L., Glaser, F., Loos, U., Köhrle, J. Mol. Cell. Endocrinol. (2002) [Pubmed]
  10. Altered gene expression profiles by sodium/iodide symporter gene transfection in a human anaplastic thyroid carcinoma cell line using a radioactive complementary DNA microarray. Gol Choe, J., Kim, Y.R., Kim, K.N., Choo, H.J., Shin, J.H., Lee, Y.J., Chung, J.K., Kim, M.K. Nuclear medicine communications. (2005) [Pubmed]
  11. Probasin promoter (ARR(2)PB)-driven, prostate-specific expression of the human sodium iodide symporter (h-NIS) for targeted radioiodine therapy of prostate cancer. Kakinuma, H., Bergert, E.R., Spitzweg, C., Cheville, J.C., Lieber, M.M., Morris, J.C. Cancer Res. (2003) [Pubmed]
  12. Expression of cAMP response element-binding protein and sodium iodide symporter in benign non-functioning and malignant thyroid tumours. Luciani, P., Buci, L., Conforti, B., Tonacchera, M., Agretti, P., Elisei, R., Vivaldi, A., Cioppi, F., Biliotti, G., Manca, G., Vitti, P., Serio, M., Peri, A. Eur. J. Endocrinol. (2003) [Pubmed]
  13. The current status of radioiodine therapy for benign thyroid disorders. van Isselt, J.W., van Dongen, A.J. Hellenic journal of nuclear medicine. (2004) [Pubmed]
  14. Hypothyroidism in thyroid transcription factor 1 haploinsufficiency is caused by reduced expression of the thyroid-stimulating hormone receptor. Moeller, L.C., Kimura, S., Kusakabe, T., Liao, X.H., Van Sande, J., Refetoff, S. Mol. Endocrinol. (2003) [Pubmed]
  15. Expressions of human sodium iodide symporter mRNA in primary and metastatic papillary thyroid carcinomas. Park, H.J., Kim, J.Y., Park, K.Y., Gong, G., Hong, S.J., Ahn, I.M. Thyroid (2000) [Pubmed]
  16. Transcriptional regulation of human sodium/iodide symporter gene: a role for redox factor-1. Puppin, C., Arturi, F., Ferretti, E., Russo, D., Sacco, R., Tell, G., Damante, G., Filetti, S. Endocrinology (2004) [Pubmed]
  17. Differential effects of natural flavonoids on growth and iodide content in a human Na*/I- symporter-transfected follicular thyroid carcinoma cell line. Schröder-van der Elst, J.P., van der Heide, D., Romijn, J.A., Smit, J.W. Eur. J. Endocrinol. (2004) [Pubmed]
  18. Lithium as adjuvant to radioiodine therapy in differentiated thyroid carcinoma: clinical and in vitro studies. Liu, Y.Y., van der Pluijm, G., Karperien, M., Stokkel, M.P., Pereira, A.M., Morreau, J., Kievit, J., Romijn, J.A., Smit, J.W. Clin. Endocrinol. (Oxf) (2006) [Pubmed]
  19. Thyroid-stimulating hormone and cyclic AMP activate p38 mitogen-activated protein kinase cascade. Involvement of protein kinase A, rac1, and reactive oxygen species. Pomerance, M., Abdullah, H.B., Kamerji, S., Correze, C., Blondeau, J.P. J. Biol. Chem. (2000) [Pubmed]
  20. Effect of Iodide on Human Choriogonadotropin, Sodium-Iodide Symporter Expression, and Iodide Uptake in BeWo Choriocarcinoma Cells. Li, H., Richard, K., McKinnon, B., Mortimer, R.H. J. Clin. Endocrinol. Metab. (2007) [Pubmed]
  21. Increased expression of AP2 and Sp1 transcription factors in human thyroid tumors: a role in NIS expression regulation? Chiefari, E., Brunetti, A., Arturi, F., Bidart, J.M., Russo, D., Schlumberger, M., Filetti, S. BMC Cancer (2002) [Pubmed]
  22. Expression of hypothalamic-pituitary-thyroid axis related genes in the human skin. Slominski, A., Wortsman, J., Kohn, L., Ain, K.B., Venkataraman, G.M., Pisarchik, A., Chung, J.H., Giuliani, C., Thornton, M., Slugocki, G., Tobin, D.J. J. Invest. Dermatol. (2002) [Pubmed]
  23. Effects of histone acetylation on sodium iodide symporter promoter and expression of thyroid-specific transcription factors. Puppin, C., D'Aurizio, F., D'Elia, A.V., Cesaratto, L., Tell, G., Russo, D., Filetti, S., Ferretti, E., Tosi, E., Mattei, T., Pianta, A., Pellizzari, L., Damante, G. Endocrinology (2005) [Pubmed]
  24. Ectopic expression of the thyroperoxidase gene augments radioiodide uptake and retention mediated by the sodium iodide symporter in non-small cell lung cancer. Huang, M., Batra, R.K., Kogai, T., Lin, Y.Q., Hershman, J.M., Lichtenstein, A., Sharma, S., Zhu, L.X., Brent, G.A., Dubinett, S.M. Cancer Gene Ther. (2001) [Pubmed]
  25. Differential regulation of apical and basal iodide transporters in the thyroid by thyroglobulin. Suzuki, K., Kohn, L.D. J. Endocrinol. (2006) [Pubmed]
  26. Establishment of a human hepatocellular carcinoma cell line highly expressing sodium iodide symporter for radionuclide gene therapy. Kang, J.H., Chung, J.K., Lee, Y.J., Shin, J.H., Jeong, J.M., Lee, D.S., Lee, M.C. J. Nucl. Med. (2004) [Pubmed]
  27. Homologies of the thyroid sodium-iodide symporter with bacterial and viral proteins. Benvenga, S., Alesci, S., Trimarchi, F., Facchiano, A. J. Endocrinol. Invest. (1999) [Pubmed]
  28. Iodination of proteins in TPO transfected thyroid cancer cells is independent of NIS. Wenzel, A., Upadhyay, G., Schmitt, T.L., Loos, U. Mol. Cell. Endocrinol. (2003) [Pubmed]
  29. Na+/I- symporter distribution in human thyroid tissues: an immunohistochemical study. Caillou, B., Troalen, F., Baudin, E., Talbot, M., Filetti, S., Schlumberger, M., Bidart, J.M. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
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