TAS2R1 explained

Taste receptor type 2 member 1 (TAS2R1/T2R1) is a protein that in humans is encoded by the TAS2R1 gene.^{[1] [2] [3]} It belongs to the G protein-coupled receptor (GPCR) family and is related to class A-like GPCRs, they contain 7 transmembrane helix bundles and short N-terminus loop. Furthermore, TAS2R1 is member of the 25 known human bitter taste receptors, which enable the perception of bitter taste in the mouth cavity. Increasing evidence indicates a functional role of TAS2Rs in extra-oral tissues.^[4]

Expression and function

Extra-oral roles of TAS2Rs

Bitter taste receptors are expressed in taste receptor cells, which organized into taste buds on the papillae of the tongue and palate epithelium.

In addition, TAS2Rs were found to be expressed in extra-oral tissues, e.g. brain, lungs, gastrointestinal tract, etc. So far, less is known about their function however, for example it was shown that:

• TAS2Rs mediate relaxation of airway smooth muscles.^[5]
• TAS2R43 is involved in secretion of gastric acid in the stomach.^[6]

Extra-oral roles of TAS2R1

• TAS2R1, TAS2R4, TAS2R10, TAS2R38 and TAS2R49 were found to be down-regulated in breast cancer cells^[7] .
• TAS2R1, causes vasoconstrictor responses in the pulmonary circuit and relaxation in the airways^[8] .

Structure of TAS2R1 receptor

Based on a recent homology model from BitterDB^{[9] [10]} several conserved motifs, which are counterparts to Class A GPCRs were found:

• Transmembrane helix 1: N^1.50xxI^1.53
• Transmembrane helix 2: L^2.46xxxR^2.50
• Transmembrane helix 3: F^3.49Y^3.50xxK^3.53
• Transmembrane helix 5: P^5.50
• Transmembrane helix 6: F^6.44xxxY^6.46
• Transmembrane helix 7: H^7.49S^7.50xxL^7.53

Numbering is according to the Balleros-Weinstein system.

Unlike in Class A GPCRs, in transmembrane helix 4 no DRY^[11] motif was found as well as position 6.50 is not conserved.

TAS2R1 gene

This gene encodes a member of a family of candidate taste receptors that are members of the G protein-coupled receptor superfamily and that are specifically expressed by taste receptor cells of the tongue and palate epithelia. This intronless taste receptor gene encodes a 7-transmembrane receptor protein, functioning as a bitter taste receptor.

SNPs

In T2R1 two SNPs are known in R111H and R206W (dbSNP).

Transcription factors

So far, AML1a, AP-1, AREB6, FOXL1, IRF-7A, Lmo2, NF-E2, NF-E2 p45 were found as the top transcription factor binding sites by QIAGEN in the TAS2R1 gene promoter.

Mutagenesis data

Several mutations have been shown to influence binding of a ligand to TAS2R1 (based on BitterDB):

Receptor region	BW number	Residue	Reference
TM1	1.5	N24	doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983
TM1	1.53	I27	doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983
TM2	2.5	R55	doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983
TM2	2.56	F61	doi: 10.1074/jbc.M111.246983
TM2	2.61	N66	doi: 10.3389/fmolb.2017.00063 doi: 10.1021/acs.jctc.5b00472 doi: 10.1016/bs.mcb.2015.10.005 doi: 10.1074/jbc.M111.246983
ECL1		E74	doi: 10.3389/fmolb.2017.00063
TM3	3.32	L85	doi: 10.1016/bs.mcb.2015.10.005 doi: 10.3109/10799893.2011.578141
TM3	3.33	L86	doi: 10.1016/bs.mcb.2015.10.005 doi: 10.3109/10799893.2011.578141
TM3	3.36	N89	doi: 10.1016/bs.mcb.2015.10.005 doi: 10.1074/jbc.M111.246983 doi: doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983
TM3	3.37	E90	doi: 10.1016/bs.mcb.2015.10.005 doi: 10.3109/10799893.2011.578141
TM3	3.41	W94	doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983
TM3	3.46	L99	doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983
TM5	5.46	E182	doi: 10.1016/bs.mcb.2015.10.005 doi: 10.3109/10799893.2011.578141
TM5	5.61	L197	doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983
TM5	5.64	S200	doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983
TM5	5.65	L201	doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983
TM7	7.39	I263	doi: 10.1016/bs.mcb.2015.10.005 doi: 10.3109/10799893.2011.578141
TM7	7.49	H273	doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983
TM7	7.53	L277	doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983
TM7	7.54	I278	doi: 10.1021/acs.jctc.5b00472 doi: 10.1074/jbc.M111.246983

Ligands

Up to now, 39 ligands for T2R1 were identified in BitterDB, among them L-amino acids, peptides, humulones, small molecules etc.

See also

• Taste receptor

Further reading

• Kinnamon SC . A plethora of taste receptors . Neuron . 25 . 3 . 507–10 . 2000 . 10774719 . 10.1016/S0896-6273(00)81054-5 . free .
• Margolskee RF . Molecular mechanisms of bitter and sweet taste transduction . J. Biol. Chem. . 277 . 1 . 1–4 . 2002 . 11696554 . 10.1074/jbc.R100054200 . free .
• Montmayeur JP, Matsunami H . Receptors for bitter and sweet taste . Curr. Opin. Neurobiol. . 12 . 4 . 366–71 . 2002 . 12139982 . 10.1016/S0959-4388(02)00345-8 . 37807140 .
• Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, Zuker CS, Ryba NJ . T2Rs function as bitter taste receptors . Cell . 100 . 6 . 703–11 . 2000 . 10761935 . 10.1016/S0092-8674(00)80706-0 . 7293493 . free .
• Firestein S . The good taste of genomics . Nature . 404 . 6778 . 552–3 . 2000 . 10766221 . 10.1038/35007167 . 35741332 . free .
• Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ . Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways . Cell . 112 . 3 . 293–301 . 2003 . 12581520 . 10.1016/S0092-8674(03)00071-0 . 718601 . free .
• Fischer A, Gilad Y, Man O, Pääbo S . Evolution of bitter taste receptors in humans and apes . Mol. Biol. Evol. . 22 . 3 . 432–6 . 2005 . 15496549 . 10.1093/molbev/msi027 . free .
• Go Y, Satta Y, Takenaka O, Takahata N . Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates . Genetics . 170 . 1 . 313–26 . 2006 . 15744053 . 1449719 . 10.1534/genetics.104.037523 .

Notes and References

1. Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS . A novel family of mammalian taste receptors . Cell . 100 . 6 . 693–702 . Apr 2000 . 10761934 . 10.1016/S0092-8674(00)80705-9 . 14604586 . free .
2. Matsunami H, Montmayeur JP, Buck LB . A family of candidate taste receptors in human and mouse . Nature . 404 . 6778 . 601–4 . Apr 2000 . 10766242 . 10.1038/35007072 . 2000Natur.404..601M . 4336913 .
3. Web site: Entrez Gene: TAS2R1 taste receptor, type 2, member 1.
4. Lu. Ping. Zhang. Cheng-Hai. Lifshitz. Lawrence M.. ZhuGe. Ronghua. 2017-01-04. Extraoral bitter taste receptors in health and disease. The Journal of General Physiology. 149. 2. 181–197. 10.1085/jgp.201611637. 28053191. 0022-1295. 5299619.
5. Deshpande. Deepak A. Wang. Wayne C H. McIlmoyle. Elizabeth L. Robinett. Kathryn S. Schillinger. Rachel M. An. Steven S. Sham. James S K. Liggett. Stephen B. 2010-10-24. Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction. Nature Medicine. 16. 11. 1299–1304. 10.1038/nm.2237. 20972434. 1078-8956. 3066567.
6. Liszt. Kathrin Ingrid. Ley. Jakob Peter. Lieder. Barbara. Behrens. Maik. Stöger. Verena. Reiner. Angelika. Hochkogler. Christina Maria. Köck. Elke. Marchiori. Alessandro. 2017-07-10. Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells. Proceedings of the National Academy of Sciences. 114. 30. E6260–E6269. 10.1073/pnas.1703728114. 28696284. 0027-8424. 5544304. free. 2017PNAS..114E6260L .
7. Singh. Nisha. Chakraborty. Raja. Bhullar. Rajinder Pal. Chelikani. Prashen. April 2014. Differential expression of bitter taste receptors in non-cancerous breast epithelial and breast cancer cells. Biochemical and Biophysical Research Communications. 446. 2. 499–503. 10.1016/j.bbrc.2014.02.140. 24613843. 0006-291X.
8. Upadhyaya. Jasbir D.. Singh. Nisha. Sikarwar. Anurag S.. Chakraborty. Raja. Pydi. Sai P.. Bhullar. Rajinder P.. Dakshinamurti. Shyamala. Chelikani. Prashen. 2014-10-23. Dextromethorphan Mediated Bitter Taste Receptor Activation in the Pulmonary Circuit Causes Vasoconstriction. PLOS ONE. 9. 10. e110373. 10.1371/journal.pone.0110373. 25340739. 4207743. 1932-6203. 2014PLoSO...9k0373U. free.
9. Wiener. Ayana. Shudler. Marina. Levit. Anat. Niv. Masha Y.. 2011-09-22. BitterDB: a database of bitter compounds. Nucleic Acids Research. 40. D1. D413–D419. 10.1093/nar/gkr755. 21940398. 3245057. 1362-4962.
10. Dagan-Wiener. Ayana. Di Pizio. Antonella. Nissim. Ido. Bahia. Malkeet S. Dubovski. Nitzan. Margulis. Eitan. Niv. Masha Y. 2018-10-24. BitterDB: taste ligands and receptors database in 2019. Nucleic Acids Research. 47. D1. D1179–D1185. 10.1093/nar/gky974. 30357384. 6323989. 0305-1048.
11. Rovati. G. E.. Capra. V.. Neubig. R. R.. 2007-01-12. The Highly Conserved DRY Motif of Class A G Protein-Coupled Receptors: Beyond the Ground State. Molecular Pharmacology. 71. 4. 959–964. 10.1124/mol.106.029470. 17192495. 15536186. 0026-895X.