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- Taste 2 receptors
Taste 2 receptors C
Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).
Overview
Taste 2 receptors or Bitter taste receptors (TAS2Rs) are G protein-coupled receptors expressed in oral sensory cells and a variety of non-gustatory tissues. The ~25 human TAS2Rs share low amino acid sequence identities with other GPCR families and are classified as broadly tuned "generalist" receptors with numerous, chemically diverse bitter agonists, as narrowly tuned "specialist" receptors with very few activators, as intermediately tuned receptors with an average number of agonists, or receptors specialized to interact with chemically defined activators [38]. The number of functional bitter taste receptor genes varies among species and orthologues might not be functionally conserved. Due to their expression in various tissues, the signal transduction of TAS2Rs is complex. Some TAS2Rs interact with drugs such as analgesic, anti-inflammatory, and antibacterial compounds. The specialist database BitterDB contains additional information on bitter compounds and receptors [15]. Recently, several experimental cryo-electron structures of TAS2Rs have been published [42].
Receptors
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Further reading
* Key recommended reading is highlighted with an asterisk
Andres-Barquin PJ, Conte C. (2004) Molecular basis of bitter taste: the T2R family of G protein-coupled receptors. Cell Biochem Biophys, 41 (1): 99-112. [PMID:15371642]
Bachmanov AA, Beauchamp GK. (2007) Taste receptor genes. Annu Rev Nutr, 27: 389-414. [PMID:17444812]
* Behrens M. (2025) International Union of Basic and Clinical Pharmacology. CXVII: Taste 2 receptors-Structures, functions, activators, and blockers. Pharmacol Rev, 77 (1): 100001. [PMID:39952694]
* Egan JM. (2024) Physiological Integration of Taste and Metabolism. N Engl J Med, 390 (18): 1699-1710. [PMID:38718360]
Kinnamon SC. (2012) Taste receptor signalling - from tongues to lungs. Acta Physiol (Oxf), 204 (2): 158-68. [PMID:21481196]
Meyerhof W. (2005) Elucidation of mammalian bitter taste. Rev Physiol Biochem Pharmacol, 154: 37-72. [PMID:16032395]
* Palmer RK. (2019) A Pharmacological Perspective on the Study of Taste. Pharmacol Rev, 71 (1): 20-48. [PMID:30559245]
Temussi PA. (2009) Sweet, bitter and umami receptors: a complex relationship. Trends Biochem Sci, 34 (6): 296-302. [PMID:19443222]
Tepper BJ. (2008) Nutritional implications of genetic taste variation: the role of PROP sensitivity and other taste phenotypes. Annu Rev Nutr, 28: 367-88. [PMID:18407743]
* Wooding SP, Ramirez VA, Behrens M. (2021) Bitter taste receptors: Genes, evolution and health. Evol Med Public Health, 9 (1): 431-447. [PMID:35154779]
Yarmolinsky DA, Zuker CS, Ryba NJ. (2009) Common sense about taste: from mammals to insects. Cell, 139 (2): 234-44. [PMID:19837029]
References
1. Behrens M, Blank K, Meyerhof W. (2017) Blends of Non-caloric Sweeteners Saccharin and Cyclamate Show Reduced Off-Taste due to TAS2R Bitter Receptor Inhibition. Cell Chem Biol, 24 (10): 1199-1204.e2. [PMID:28919036]
2. Behrens M, Brockhoff A, Batram C, Kuhn C, Appendino G, Meyerhof W. (2009) The human bitter taste receptor hTAS2R50 is activated by the two natural bitter terpenoids andrographolide and amarogentin. J Agric Food Chem, 57 (21): 9860-6. [PMID:19817411]
3. Behrens M, Brockhoff A, Kuhn C, Bufe B, Winnig M, Meyerhof W. (2004) The human taste receptor hTAS2R14 responds to a variety of different bitter compounds. Biochem Biophys Res Commun, 319 (2): 479-85. [PMID:15178431]
4. Behrens M, Gu M, Fan S, Huang C, Meyerhof W. (2018) Bitter substances from plants used in traditional Chinese medicine exert biased activation of human bitter taste receptors. Chem Biol Drug Des, 91 (2): 422-433. [PMID:28834122]
5. Behrens M, Gunn HC, Ramos PC, Meyerhof W, Wooding SP. (2013) Genetic, functional, and phenotypic diversity in TAS2R38-mediated bitter taste perception. Chem Senses, 38 (6): 475-84. [PMID:23632915]
6. Behrens M, Redel U, Blank K, Meyerhof W. (2019) The human bitter taste receptor TAS2R7 facilitates the detection of bitter salts. Biochem Biophys Res Commun, 512 (4): 877-881. [PMID:30928101]
7. Born S, Levit A, Niv MY, Meyerhof W, Behrens M. (2013) The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands. J Neurosci, 33 (1): 201-13. [PMID:23283334]
8. Brockhoff A, Behrens M, Massarotti A, Appendino G, Meyerhof W. (2007) Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium. J Agric Food Chem, 55 (15): 6236-43. [PMID:17595105]
9. Brockhoff A, Behrens M, Roudnitzky N, Appendino G, Avonto C, Meyerhof W. (2011) Receptor agonism and antagonism of dietary bitter compounds. J Neurosci, 31 (41): 14775-82. [PMID:21994393]
10. Bufe B, Breslin PA, Kuhn C, Reed DR, Tharp CD, Slack JP, Kim UK, Drayna D, Meyerhof W. (2005) The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception. Curr Biol, 15 (4): 322-7. [PMID:15723792]
11. Bufe B, Hofmann T, Krautwurst D, Raguse JD, Meyerhof W. (2002) The human TAS2R16 receptor mediates bitter taste in response to beta-glucopyranosides. Nat Genet, 32 (3): 397-401. [PMID:12379855]
12. Caronia L, Xi R, Margolskee RF, Jiang P. (2023) Paxlovid mouth likely is mediated by activation of the TAS2R1 bitter receptor by nirmatrelvir. Biochem Biophys Res Commun, 682: 138-140. [PMID:37806252]
13. Chen S, Zhou X, Lu Y, Xu K, Wen J, Cui M. (2023) Anti-HIV drugs lopinavir/ritonavir activate bitter taste receptors. Chem Senses, 48. [PMID:37625013]
14. Cui M, Chen B, Xu K, Rigakou A, Diamantakos P, Melliou E, Logothetis DE, Magiatis P. (2021) Activation of specific bitter taste receptors by olive oil phenolics and secoiridoids. Sci Rep, 11 (1): 22340. [PMID:34785711]
15. Dagan-Wiener A, Di Pizio A, Nissim I, Bahia MS, Dubovski N, Margulis E, Niv MY. (2019) BitterDB: taste ligands and receptors database in 2019. Nucleic Acids Res, 47 (D1): D1179-D1185. [PMID:30357384]
16. Di Pizio A, Waterloo LAW, Brox R, Löber S, Weikert D, Behrens M, Gmeiner P, Niv MY. (2020) Rational design of agonists for bitter taste receptor TAS2R14: from modeling to bench and back. Cell Mol Life Sci, 77 (3): 531-542. [PMID:31236627]
17. Dotson CD, Zhang L, Xu H, Shin YK, Vigues S, Ott SH, Elson AE, Choi HJ, Shaw H, Egan JM et al.. (2008) Bitter taste receptors influence glucose homeostasis. PLoS One, 3 (12): e3974. [PMID:19092995]
18. Fierro F, Peri L, Hübner H, Tabor-Schkade A, Waterloo L, Löber S, Pfeiffer T, Weikert D, Dingjan T, Margulis E et al.. (2023) Inhibiting a promiscuous GPCR: iterative discovery of bitter taste receptor ligands. Cell Mol Life Sci, 80 (4): 114. [PMID:37012410]
19. Fletcher JN, Kinghorn AD, Slack JP, McCluskey TS, Odley A, Jia Z. (2011) In vitro evaluation of flavonoids from Eriodictyon californicum for antagonist activity against the bitterness receptor hTAS2R31. J Agric Food Chem, 59 (24): 13117-21. [PMID:22059530]
20. Fotsing JR, Darmohusodo V, Patron AP, Ching BW, Brady T, Arellano M, Chen Q, Davis TJ, Liu H, Servant G et al.. (2020) Discovery and Development of S6821 and S7958 as Potent TAS2R8 Antagonists. J Med Chem, 63 (9): 4957-4977. [PMID:32330040]
21. Greene TA, Alarcon S, Thomas A, Berdougo E, Doranz BJ, Breslin PA, Rucker JB. (2011) Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin. PLoS One, 6 (5): e20123. [PMID:21629661]
22. Hellfritsch C, Brockhoff A, Stähler F, Meyerhof W, Hofmann T. (2012) Human psychometric and taste receptor responses to steviol glycosides. J Agric Food Chem, 60 (27): 6782-93. [PMID:22616809]
23. Hu X, Ao W, Gao M, Wu L, Pei Y, Liu S, Wu Y, Zhao F, Sun Q, Liu J et al.. (2024) Bitter taste TAS2R14 activation by intracellular tastants and cholesterol. Nature, 631 (8020): 459-466. [PMID:38776963]
24. Intelmann D, Batram C, Kuhn C, Haseleu G, Meyerhof W, Hofmann T. (2009) Three TAS2R Bitter Taste Receptors Mediate the Psychophysical Responses to Bitter Compounds of Hops (Humulus lupulus L.) and Beer. Chemosensory Perception, 2: 118–132. DOI: 10.1007/s12078-009-9049-1
25. Jaggupilli A, Singh N, De Jesus VC, Gounni MS, Dhanaraj P, Chelikani P. (2019) Chemosensory bitter taste receptors (T2Rs) are activated by multiple antibiotics. FASEB J, 33 (1): 501-517. [PMID:30011231]
26. Jaggupilli A, Singh N, Jesus VC, Duan K, Chelikani P. (2018) Characterization of the Binding Sites for Bacterial Acyl Homoserine Lactones (AHLs) on Human Bitter Taste Receptors (T2Rs). ACS Infect Dis, 4 (7): 1146-1156. [PMID:29799189]
27. Kim UK, Jorgenson E, Coon H, Leppert M, Risch N, Drayna D. (2003) Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science, 299 (5610): 1221-5. [PMID:12595690]
28. Kim Y, Gumpper RH, Liu Y, Kocak DD, Xiong Y, Cao C, Deng Z, Krumm BE, Jain MK, Zhang S et al.. (2024) Author Correction: Bitter taste receptor activation by cholesterol and an intracellular tastant. Nature, 630 (8016): E5. [PMID:38789678]
29. Kim Y, Gumpper RH, Liu Y, Kocak DD, Xiong Y, Cao C, Deng Z, Krumm BE, Jain MK, Zhang S et al.. (2024) Bitter taste receptor activation by cholesterol and an intracellular tastant. Nature, 628 (8008): 664-671. [PMID:38600377]
30. Kohl S, Behrens M, Dunkel A, Hofmann T, Meyerhof W. (2013) Amino acids and peptides activate at least five members of the human bitter taste receptor family. J Agric Food Chem, 61 (1): 53-60. [PMID:23214402]
31. Kuhn C, Bufe B, Winnig M, Hofmann T, Frank O, Behrens M, Lewtschenko T, Slack JP, Ward CD, Meyerhof W. (2004) Bitter taste receptors for saccharin and acesulfame K. J Neurosci, 24 (45): 10260-5. [PMID:15537898]
32. Lang R, Lang T, Dunkel A, Ziegler F, Behrens M. (2022) Overlapping activation pattern of bitter taste receptors affect sensory adaptation and food perception. Front Nutr, 9: 1082698. [PMID:36601079]
33. Lang T, Di Pizio A, Risso D, Drayna D, Behrens M. (2023) Activation Profile of TAS2R2, the 26th Human Bitter Taste Receptor. Mol Nutr Food Res, 67 (11): e2200775. [PMID:36929150]
34. Lang T, Frank O, Lang R, Hofmann T, Behrens M. (2022) Activation Spectra of Human Bitter Taste Receptors Stimulated with Cyclolinopeptides Corresponding to Fresh and Aged Linseed Oil. J Agric Food Chem, 70 (14): 4382-4390. [PMID:35364812]
35. Lang T, Lang R, Di Pizio A, Mittermeier VK, Schlagbauer V, Hofmann T, Behrens M. (2020) Numerous Compounds Orchestrate Coffee's Bitterness. J Agric Food Chem, 68 (24): 6692-6700. [PMID:32437139]
36. Levit A, Nowak S, Peters M, Wiener A, Meyerhof W, Behrens M, Niv MY. (2014) The bitter pill: clinical drugs that activate the human bitter taste receptor TAS2R14. FASEB J, 28 (3): 1181-97. [PMID:24285091]
37. Mancuso G, Borgonovo G, Scaglioni L, Bassoli A. (2015) Phytochemicals from Ruta graveolens Activate TAS2R Bitter Taste Receptors and TRP Channels Involved in Gustation and Nociception. Molecules, 20 (10): 18907-22. [PMID:26501253]
38. Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E, Bufe B, Appendino G, Behrens M. (2010) The molecular receptive ranges of human TAS2R bitter taste receptors. Chem Senses, 35 (2): 157-70. [PMID:20022913]
39. Morini G, Winnig M, Vennegeerts T, Borgonovo G, Bassoli A. (2021) Vanillin Activates Human Bitter Taste Receptors TAS2R14, TAS2R20, and TAS2R39. Front Nutr, 8: 683627. [PMID:34307435]
40. Narukawa M, Noga C, Ueno Y, Sato T, Misaka T, Watanabe T. (2011) Evaluation of the bitterness of green tea catechins by a cell-based assay with the human bitter taste receptor hTAS2R39. Biochem Biophys Res Commun, 405 (4): 620-5. [PMID:21272567]
41. Nowak S, Di Pizio A, Levit A, Niv MY, Meyerhof W, Behrens M. (2018) Reengineering the ligand sensitivity of the broadly tuned human bitter taste receptor TAS2R14. Biochim Biophys Acta Gen Subj, 1862 (10): 2162-2173. [PMID:30009876]
42. Peri L, Matzov D, Huxley DR, Rainish A, Fierro F, Sapir L, Pfeiffer T, Waterloo L, Hübner H, Peleg Y et al.. (2024) A bitter anti-inflammatory drug binds at two distinct sites of a human bitter taste GPCR. Nat Commun, 15 (1): 9991. [PMID:39557861]
43. Pronin AN, Xu H, Tang H, Zhang L, Li Q, Li X. (2007) Specific alleles of bitter receptor genes influence human sensitivity to the bitterness of aloin and saccharin. Curr Biol, 17 (16): 1403-8. [PMID:17702579]
44. Pydi SP, Jaggupilli A, Nelson KM, Abrams SR, Bhullar RP, Loewen MC, Chelikani P. (2015) Abscisic Acid Acts as a Blocker of the Bitter Taste G Protein-Coupled Receptor T2R4. Biochemistry, 54 (16): 2622-31. [PMID:25844797]
45. Risso D, Behrens M, Sainz E, Meyerhof W, Drayna D. (2017) Probing the Evolutionary History of Human Bitter Taste Receptor Pseudogenes by Restoring Their Function. Mol Biol Evol, 34 (7): 1587-1595. [PMID:28333344]
46. Roland WS, Gouka RJ, Gruppen H, Driesse M, van Buren L, Smit G, Vincken JP. (2014) 6-methoxyflavanones as bitter taste receptor blockers for hTAS2R39. PLoS One, 9 (4): e94451. [PMID:24722342]
47. Roland WS, van Buren L, Gruppen H, Driesse M, Gouka RJ, Smit G, Vincken JP. (2013) Bitter taste receptor activation by flavonoids and isoflavonoids: modeled structural requirements for activation of hTAS2R14 and hTAS2R39. J Agric Food Chem, 61 (44): 10454-66. [PMID:24117141]
48. Roland WS, Vincken JP, Gouka RJ, van Buren L, Gruppen H, Smit G. (2011) Soy isoflavones and other isoflavonoids activate the human bitter taste receptors hTAS2R14 and hTAS2R39. J Agric Food Chem, 59 (21): 11764-71. [PMID:21942422]
49. Roudnitzky N, Behrens M, Engel A, Kohl S, Thalmann S, Hübner S, Lossow K, Wooding SP, Meyerhof W. (2015) Receptor Polymorphism and Genomic Structure Interact to Shape Bitter Taste Perception. PLoS Genet, 11 (9): e1005530. [PMID:26406243]
50. Sakurai T, Misaka T, Ueno Y, Ishiguro M, Matsuo S, Ishimaru Y, Asakura T, Abe K. (2010) The human bitter taste receptor, hTAS2R16, discriminates slight differences in the configuration of disaccharides. Biochem Biophys Res Commun, 402 (4): 595-601. [PMID:20965151]
51. Schmitz LM, Lang T, Steuer A, Koppelmann L, Di Pizio A, Arnold N, Behrens M. (2025) Taste-Guided Isolation of Bitter Compounds from the Mushroom Amaropostia stiptica Activates a Subset of Human Bitter Taste Receptors. J Agric Food Chem, 73 (8): 4850-4858. [PMID:39945763]
52. Schwiebert E, Wang Y, Xi R, Choma K, Streiff J, Flammer LJ, Rivers N, Ozdener MH, Margolskee RF, Christensen CM et al.. (2021) Inhibition of Bitter Taste from Oral Tenofovir Alafenamide. Mol Pharmacol, 99 (5): 319-327. [PMID:33824185]
53. Slack JP, Brockhoff A, Batram C, Menzel S, Sonnabend C, Born S, Galindo MM, Kohl S, Thalmann S, Ostopovici-Halip L et al.. (2010) Modulation of bitter taste perception by a small molecule hTAS2R antagonist. Curr Biol, 20 (12): 1104-9. [PMID:20537538]
54. Soares S, Kohl S, Thalmann S, Mateus N, Meyerhof W, De Freitas V. (2013) Different phenolic compounds activate distinct human bitter taste receptors. J Agric Food Chem, 61 (7): 1525-33. [PMID:23311874]
55. Soares S, Silva MS, García-Estevez I, Groβmann P, Brás N, Brandão E, Mateus N, de Freitas V, Behrens M, Meyerhof W. (2018) Human Bitter Taste Receptors Are Activated by Different Classes of Polyphenols. J Agric Food Chem, 66 (33): 8814-8823. [PMID:30056706]
56. Suess B, Brockhoff A, Meyerhof W, Hofmann T. (2018) The Odorant ( R)-Citronellal Attenuates Caffeine Bitterness by Inhibiting the Bitter Receptors TAS2R43 and TAS2R46. J Agric Food Chem, 66 (10): 2301-2311. [PMID:27569025]
57. Tao L, Wang D, Yuan Q, Zhao F, Zhang Y, Du T, Shen S, Xu HE, Li Y, Yang D et al.. (2024) Bitter taste receptor TAS2R14 activation and G protein assembly by an intracellular agonist. Cell Res, 34 (10): 735-738. [PMID:38969802]
58. Thalmann S, Behrens M, Meyerhof W. (2013) Major haplotypes of the human bitter taste receptor TAS2R41 encode functional receptors for chloramphenicol. Biochem Biophys Res Commun, 435 (2): 267-73. [PMID:23632330]
59. Thomas A, Sulli C, Davidson E, Berdougo E, Phillips M, Puffer BA, Paes C, Doranz BJ, Rucker JB. (2017) The Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket. Sci Rep, 7 (1): 7753. [PMID:28798468]
60. Upadhyaya J, Pydi SP, Singh N, Aluko RE, Chelikani P. (2010) Bitter taste receptor T2R1 is activated by dipeptides and tripeptides. Biochem Biophys Res Commun, 398 (2): 331-5. [PMID:20599705]
61. Wang X, Zhou C, Ao W, Wu L, Wu Y, Xu W, Liu S, Tan Q, Wang L, Zhao F et al.. (2025) Structural basis of β-glucopyranoside salicin recognition by a human bitter taste GPCR. Cell Rep, 44 (5): 115604. [PMID:40261795]
62. Wang Y, Zajac AL, Lei W, Christensen CM, Margolskee RF, Bouysset C, Golebiowski J, Zhao H, Fiorucci S, Jiang P. (2019) Metal Ions Activate the Human Taste Receptor TAS2R7. Chem Senses, 44 (5): 339-347. [PMID:31066447]
63. Waterloo L, Hübner H, Fierro F, Pfeiffer T, Brox R, Löber S, Weikert D, Niv MY, Gmeiner P. (2023) Discovery of 2-Aminopyrimidines as Potent Agonists for the Bitter Taste Receptor TAS2R14. J Med Chem, 66 (5): 3499-3521. [PMID:36847646]
64. Wooding S, Gunn H, Ramos P, Thalmann S, Xing C, Meyerhof W. (2010) Genetics and bitter taste responses to goitrin, a plant toxin found in vegetables. Chem Senses, 35 (8): 685-92. [PMID:20551074]
65. Xu W, Wu L, Liu S, Liu X, Cao X, Zhou C, Zhang J, Fu Y, Guo Y, Wu Y et al.. (2022) Structural basis for strychnine activation of human bitter taste receptor TAS2R46. Science, 377 (6612): 1298-1304. [PMID:36108005]
66. Yamazaki T, Sagisaka M, Ikeda R, Nakamura T, Matsuda N, Ishii T, Nakayama T, Watanabe T. (2014) The human bitter taste receptor hTAS2R39 is the primary receptor for the bitterness of theaflavins. Biosci Biotechnol Biochem, 78 (10): 1753-6. [PMID:25273142]
67. Ziegler F, Steuer A, Di Pizio A, Behrens M. (2023) Physiological activation of human and mouse bitter taste receptors by bile acids. Commun Biol, 6 (1): 612. [PMID:37286811]
68. (2025) Erratum for the Research Article "Structural basis for strychnine activation of human bitter taste receptor TAS2R46" by W. Xu et al. Science, 388 (6745): eadx9419. [PMID:40273273]
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Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors. Br J Pharmacol. 180 Suppl 2:S23-S144.
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