TAS2R1

TAS2R1
Identifiers
Aliases	TAS2R1 , T2R1, TRB7, taste 2 receptor member 1
External IDs	OMIM: 604796 MGI: 2681253 HomoloGene: 10480 GeneCards: TAS2R1
Gene location (Human) Chr. Chromosome 5 (human) [1] Band 5p15.31 Start 9,627,347 bp [1] End 9,712,378 bp [1]
Gene location (Mouse) Chr. Chromosome 15 (mouse) [2] Band 15|15 B3.1 Start 32,177,435 bp [2] End 32,178,440 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in stromal cell of endometrium placenta caudate nucleus putamen nucleus accumbens hippocampal formation prefrontal cortex right lobe of thyroid gland hippocampus proper mesencephalon Top expressed in proximal tubule More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity signal transducer activity taste receptor activity bitter taste receptor activity Cellular component plasma membrane membrane integral component of membrane Biological process G protein-coupled receptor signaling pathway detection of chemical stimulus involved in sensory perception of bitter taste signal transduction response to stimulus sensory perception of taste Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 50834 57254 Ensembl ENSG00000169777 ENSMUSG00000045267 UniProt Q9NYW7 Q9JKT2 RefSeq (mRNA) NM_019599 NM_001386348 NM_020503 RefSeq (protein) NP_062545 NP_065249 Location (UCSC) Chr 5: 9.63 – 9.71 Mb Chr 15: 32.18 – 32.18 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Taste receptor type 2 member 1 (TAS2R1/T2R1) is a protein that in humans is encoded by the TAS2R1 gene. ^{[5] [6] [7]} 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. ^[8] 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. ^[9]

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. ^[9] So far, less is known about their function however, for example it was shown that:

• TAS2Rs mediate relaxation of airway smooth muscles. ^[10]
• TAS2R43 is involved in secretion of gastric acid in the stomach. ^[11]

Extra-oral roles of TAS2R1

• TAS2R1, TAS2R4, TAS2R10, TAS2R38 and TAS2R49 were found to be down-regulated in breast cancer cells ^[12] .
• TAS2R1, causes vasoconstrictor responses in the pulmonary circuit and relaxation in the airways ^[13] .

Structure of TAS2R1 receptor

Based on a recent homology model from BitterDB ^{[14] [15]} several conserved motifs, which are counterparts to Class A GPCRs ^[8] 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 ^[16] system.

Unlike in Class A GPCRs, in transmembrane helix 4 no DRY ^[17] 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. ^[18]

See also

• Taste receptor

References

1. GRCh38: Ensembl release 89: ENSG00000169777 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000045267 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS (Apr 2000). "A novel family of mammalian taste receptors". Cell. 100 (6): 693–702. doi: 10.1016/S0092-8674(00)80705-9 . PMID   10761934. S2CID   14604586.
6. Matsunami H, Montmayeur JP, Buck LB (Apr 2000). "A family of candidate taste receptors in human and mouse". Nature. 404 (6778): 601–4. Bibcode:2000Natur.404..601M. doi:10.1038/35007072. PMID   10766242. S2CID   4336913.
7. "Entrez Gene: TAS2R1 taste receptor, type 2, member 1".
8. Di Pizio A, Levit A, Slutzki M, Behrens M, Karaman R, Niv MY (2016), "Comparing Class a GPCRS to bitter taste receptors", G Protein-Coupled Receptors - Signaling, Trafficking and Regulation, Methods in Cell Biology, vol. 132, Elsevier, pp. 401–427, doi:10.1016/bs.mcb.2015.10.005, ISBN   978-0-12-803595-5, PMID   26928553
9. Lu P, Zhang C, Lifshitz LM, ZhuGe R (2017-01-04). "Extraoral bitter taste receptors in health and disease". The Journal of General Physiology. 149 (2): 181–197. doi:10.1085/jgp.201611637. ISSN   0022-1295. PMC   5299619 . PMID   28053191.
10. Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS, Liggett SB (2010-10-24). "Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction". Nature Medicine. 16 (11): 1299–1304. doi:10.1038/nm.2237. ISSN   1078-8956. PMC   3066567 . PMID   20972434.
11. Liszt KI, Ley JP, Lieder B, Behrens M, Stöger V, Reiner A, Hochkogler CM, Köck E, Marchiori A (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. Bibcode:2017PNAS..114E6260L. doi: 10.1073/pnas.1703728114 . ISSN   0027-8424. PMC   5544304 . PMID   28696284.
12. Singh N, Chakraborty R, Bhullar RP, Chelikani P (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. doi:10.1016/j.bbrc.2014.02.140. ISSN   0006-291X. PMID   24613843.
13. Upadhyaya JD, Singh N, Sikarwar AS, Chakraborty R, Pydi SP, Bhullar RP, Dakshinamurti S, Chelikani P (2014-10-23). "Dextromethorphan Mediated Bitter Taste Receptor Activation in the Pulmonary Circuit Causes Vasoconstriction". PLOS ONE. 9 (10): e110373. Bibcode:2014PLoSO...9k0373U. doi: 10.1371/journal.pone.0110373 . ISSN   1932-6203. PMC   4207743 . PMID   25340739.
14. Wiener A, Shudler M, Levit A, Niv MY (2011-09-22). "BitterDB: a database of bitter compounds". Nucleic Acids Research. 40 (D1): D413–D419. doi:10.1093/nar/gkr755. ISSN   1362-4962. PMC   3245057 . PMID   21940398.
15. Dagan-Wiener A, Di Pizio A, Nissim I, Bahia MS, Dubovski N, Margulis E, Niv MY (2018-10-24). "BitterDB: taste ligands and receptors database in 2019". Nucleic Acids Research. 47 (D1): D1179–D1185. doi:10.1093/nar/gky974. ISSN   0305-1048. PMC   6323989 . PMID   30357384.
16. Ballesteros JA, Weinstein H (1995), "[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors", Methods in Neurosciences, Elsevier, pp. 366–428, doi:10.1016/s1043-9471(05)80049-7, ISBN   978-0-12-185295-5
17. Rovati GE, Capra V, Neubig RR (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. doi:10.1124/mol.106.029470. ISSN   0026-895X. PMID   17192495. S2CID   15536186.
18. "hTAS2R1". BitterDB. The Hebrew University of Jerusalem.

Further reading

• Kinnamon SC (2000). "A plethora of taste receptors". Neuron. 25 (3): 507–10. doi: 10.1016/S0896-6273(00)81054-5 . PMID   10774719.
• Margolskee RF (2002). "Molecular mechanisms of bitter and sweet taste transduction". J. Biol. Chem. 277 (1): 1–4. doi: 10.1074/jbc.R100054200 . PMID   11696554.
• Montmayeur JP, Matsunami H (2002). "Receptors for bitter and sweet taste". Curr. Opin. Neurobiol. 12 (4): 366–71. doi:10.1016/S0959-4388(02)00345-8. PMID   12139982. S2CID   37807140.
• Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, Zuker CS, Ryba NJ (2000). "T2Rs function as bitter taste receptors". Cell. 100 (6): 703–11. doi: 10.1016/S0092-8674(00)80706-0 . PMID   10761935. S2CID   7293493.
• Firestein S (2000). "The good taste of genomics". Nature. 404 (6778): 552–3. doi: 10.1038/35007167 . PMID   10766221. S2CID   35741332.
• Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ (2003). "Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways". Cell. 112 (3): 293–301. doi: 10.1016/S0092-8674(03)00071-0 . PMID   12581520. S2CID   718601.
• Fischer A, Gilad Y, Man O, Pääbo S (2005). "Evolution of bitter taste receptors in humans and apes". Mol. Biol. Evol. 22 (3): 432–6. doi: 10.1093/molbev/msi027 . PMID   15496549.
• Go Y, Satta Y, Takenaka O, Takahata N (2006). "Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates". Genetics. 170 (1): 313–26. doi:10.1534/genetics.104.037523. PMC   1449719 . PMID   15744053.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.