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TAS1R3  -  taste receptor, type 1, member 3

Homo sapiens

Synonyms: Sweet taste receptor T1R3, T1R3, TR3, Taste receptor type 1 member 3
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High impact information on TAS1R3

  • We now report the behavioral and physiological characterization of T1R1, T1R2, and T1R3 knockout mice [1].
  • In addition, TR3 could enhance p53-mediated apoptosis induced by UV irradiation [2].
  • TR3 downregulates p53 transcriptional activity by blocking its acetylation, leading to a decrease on the transcription level of MDM2 [2].
  • The expression level of MDM2 is negatively regulated by orphan receptor TR3 that mainly acts as a transcriptional factor to regulate gene expression [2].
  • Cyclamate does not activate the T1R1/T1R3 receptor by itself, but potentiates the receptor's response to l-glutamate [3].

Biological context of TAS1R3

  • Complete DNA sequences of TAS1R1-, TAS1R2-, and TAS1R3-coding regions, obtained from 88 individuals of African, Asian, European, and Native American origin, revealed substantial coding and noncoding diversity: polymorphisms are common in these genes, and polymorphic sites and SNP frequencies vary widely in human populations [4].
  • Taken together, these findings demonstrate the different functional roles of T1R3 and T1R2 and the presence of multiple ligand binding sites on the sweet taste receptor [3].
  • A search of the human genome database led us to identify three human candidate taste receptors, hT1R1, hT1R2, and hT1R3, which contain seven transmembrane domains [5].
  • The 6 exons/5 introns were structurally similar to those of humans and mice, but the 7 exons/6 introns structure of TAS1R3 was first observed in swine [6].
  • Using directed mutagenesis, we identified several amino acid residues within the transmembrane domain of T1R3 that determine differential responsiveness to cyclamate of the human versus mouse sweet receptors [7].

Anatomical context of TAS1R3

  • Responses of cultured cells expressing the human sweetener receptor directly parallel the psychophysical responses-water rinses remove the inhibitor from the heteromeric sweetener receptor TAS1R2-TAS1R3, which activates cells and results in the perception of strong sweetness from pure water [8].
  • Expression of the sweet receptor protein, T1R3, in the human liver and pancreas [9].
  • In the liver, both immunopositive and immunonegative reactions were detected; bile ducts and intercalated portions of the bile ductules were immunopositive to T1R3, while arterioles and venules were immunonegative in interlobular connective tissue [9].
  • The restricted localization of T1R3 in the duct cells of the liver and pancreas in the present study may indicate that T1R3 is involved in monitoring changes in the makeup of bile and pancreatic juices in the hepatic and pancreatic duct systems [9].
  • High expressions of TAS1R3 were revealed in tongue, kidney, and testis by real-time PCR [6].

Associations of TAS1R3 with chemical compounds

  • In contrast, human T1R1/T1R3 responds to the umami taste stimulus l-glutamate, and this response is enhanced by 5'-ribonucleotides, a hallmark of umami taste [10].
  • The cysteine-rich region of T1R3 determines responses to intensely sweet proteins [11].
  • Alanine substitution of residues in the transmembrane region of human T1R3 revealed 4 key residues required for sensitivity to lactisole [12].
  • Second, using a heterologous expression system, we demonstrate that T1R2 and T1R3 combine to function as a sweet receptor, recognizing sweet-tasting molecules as diverse as sucrose, saccharin, dulcin, and acesulfame-K [13].
  • I propose that sweet proteins, contrary to small ligands, do not bind to the 'glutamate-like' pocket but stabilize the free form II of the T1R2-T1R3 receptor by attachment to a secondary binding site [14].

Other interactions of TAS1R3

  • All possible dimers formed by combinations of the human T1R2 and T1R3 subunits, modeled on the A (closed) or B (open) chains of the extracellular ligand binding domain of the mGluR1 template, yield four ligand binding sites for low-molecular-weight sweeteners [15].
  • The two G-protein-coupled heteromer receptors that comprise an umami stimulus receptor (T1R1-T1R3) and a sweetener receptor (T1R2-T1R3) constitute a potential link between these two qualities of perception [16].

Analytical, diagnostic and therapeutic context of TAS1R3


  1. The receptors for mammalian sweet and umami taste. Zhao, G.Q., Zhang, Y., Hoon, M.A., Chandrashekar, J., Erlenbach, I., Ryba, N.J., Zuker, C.S. Cell (2003) [Pubmed]
  2. p53 mediates the negative regulation of MDM2 by orphan receptor TR3. Zhao, B.X., Chen, H.Z., Lei, N.Z., Li, G.D., Zhao, W.X., Zhan, Y.Y., Liu, B., Lin, S.C., Wu, Q. EMBO J. (2006) [Pubmed]
  3. Different functional roles of T1R subunits in the heteromeric taste receptors. Xu, H., Staszewski, L., Tang, H., Adler, E., Zoller, M., Li, X. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. Variation in the human TAS1R taste receptor genes. Kim, U.K., Wooding, S., Riaz, N., Jorde, L.B., Drayna, D. Chem. Senses (2006) [Pubmed]
  5. Three sweet receptor genes are clustered in human chromosome 1. Liao, J., Schultz, P.G. Mamm. Genome (2003) [Pubmed]
  6. Genomic structure of swine taste receptor family 1 member 3, TAS1R3, and its expression in tissues. Kiuchi, S., Yamada, T., Kiyokawa, N., Saito, T., Fujimoto, J., Yasue, H. Cytogenet. Genome Res. (2006) [Pubmed]
  7. Identification of the cyclamate interaction site within the transmembrane domain of the human sweet taste receptor subunit T1R3. Jiang, P., Cui, M., Zhao, B., Snyder, L.A., Benard, L.M., Osman, R., Max, M., Margolskee, R.F. J. Biol. Chem. (2005) [Pubmed]
  8. A TAS1R receptor-based explanation of sweet 'water-taste'. Galindo-Cuspinera, V., Winnig, M., Bufe, B., Meyerhof, W., Breslin, P.A. Nature (2006) [Pubmed]
  9. Expression of the sweet receptor protein, T1R3, in the human liver and pancreas. Taniguchi, K. J. Vet. Med. Sci. (2004) [Pubmed]
  10. Human receptors for sweet and umami taste. Li, X., Staszewski, L., Xu, H., Durick, K., Zoller, M., Adler, E. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  11. The cysteine-rich region of T1R3 determines responses to intensely sweet proteins. Jiang, P., Ji, Q., Liu, Z., Snyder, L.A., Benard, L.M., Margolskee, R.F., Max, M. J. Biol. Chem. (2004) [Pubmed]
  12. Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste. Jiang, P., Cui, M., Zhao, B., Liu, Z., Snyder, L.A., Benard, L.M., Osman, R., Margolskee, R.F., Max, M. J. Biol. Chem. (2005) [Pubmed]
  13. Mammalian sweet taste receptors. Nelson, G., Hoon, M.A., Chandrashekar, J., Zhang, Y., Ryba, N.J., Zuker, C.S. Cell (2001) [Pubmed]
  14. Why are sweet proteins sweet? Interaction of brazzein, monellin and thaumatin with the T1R2-T1R3 receptor. Temussi, P.A. FEBS Lett. (2002) [Pubmed]
  15. From small sweeteners to sweet proteins: anatomy of the binding sites of the human T1R2_T1R3 receptor. Morini, G., Bassoli, A., Temussi, P.A. J. Med. Chem. (2005) [Pubmed]
  16. The liaison of sweet and savory. Galindo-Cuspinera, V., Breslin, P.A. Chem. Senses (2006) [Pubmed]
  17. Characterization and long-term maintenance of rat taste cells in culture. Ozdener, H., Yee, K.K., Cao, J., Brand, J.G., Teeter, J.H., Rawson, N.E. Chem. Senses (2006) [Pubmed]
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