TAS2R1

TAS2R1
Identifiers
Aliases	TAS2R1 , T2R1, TRB7, taste 2 receptor member 1
External IDs	OMIM: 604796; MGI: 2681253; HomoloGene: 10480; GeneCards: TAS2R1; OMA:TAS2R1 - orthologs
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 right testis left testis stromal cell of endometrium epithelium of colon placenta caudate nucleus putamen nucleus accumbens hippocampal formation prefrontal cortex Top expressed in proximal tubule right kidney genital tubercle 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 system ^[16]

Unlike in Class A GPCRs, in transmembrane helix 4 no DRY ^[17] motif was found as well as position 6.50 is not conserved.

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	[18] [19]
TM1	1.53	I27	[18] [19]
TM2	2.5	R55	[18] [19]
TM2	2.56	F61	[19]
TM2	2.61	N66	[20] [18] [8] [19]
ECL1		E74	[20]
TM3	3.32	L85	[8] [21]
TM3	3.33	L86	[8] [21]
TM3	3.36	N89	[8] [19] [18]
TM3	3.37	E90	[8] [21]
TM3	3.41	W94	[18] [19]
TM3	3.46	L99	[18] [19]
TM5	5.46	E182	[8] [21]
TM5	5.61	L197	[18] [19]
TM5	5.64	S200	[18] [19]
TM5	5.65	L201	[18] [19]
TM7	7.39	I263	[8] [21]
TM7	7.49	H273	[18] [19]
TM7	7.53	L277	[18] [19]
TM7	7.54	I278	[18] [19]

Ligands

Up to now, 39 ligands for T2R1 were identified in BitterDB, among them L-amino acids, peptides, humulones, small molecules etc. ^[22]

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 (March 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 (April 2000). "A family of candidate taste receptors in human and mouse". Nature. 404 (6778): 601–604. 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". Comparing Class A GPCRs to bitter taste receptors: Structural motifs, ligand interactions and agonist-to-antagonist ratios. 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 CH, Lifshitz LM, ZhuGe R (February 2017). "Extraoral bitter taste receptors in health and disease". The Journal of General Physiology. 149 (2): 181–197. doi:10.1085/jgp.201611637. PMC   5299619 . PMID   28053191.
10. Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, et al. (November 2010). "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. PMC   3066567 . PMID   20972434.
11. Liszt KI, Ley JP, Lieder B, Behrens M, Stöger V, Reiner A, et al. (July 2017). "Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells". Proceedings of the National Academy of Sciences of the United States of America. 114 (30): E6260 –E6269. Bibcode:2017PNAS..114E6260L. doi: 10.1073/pnas.1703728114 . 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. PMID   24613843.
13. Upadhyaya JD, Singh N, Sikarwar AS, Chakraborty R, Pydi SP, Bhullar RP, et al. (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 . PMC   4207743 . PMID   25340739.
14. Wiener A, Shudler M, Levit A, Niv MY (January 2012). "BitterDB: a database of bitter compounds". Nucleic Acids Research. 40 (Database issue): D413 –D419. doi:10.1093/nar/gkr755. PMC   3245057 . PMID   21940398.
15. Dagan-Wiener A, Di Pizio A, Nissim I, Bahia MS, Dubovski N, Margulis E, et al. (January 2019). "BitterDB: taste ligands and receptors database in 2019". Nucleic Acids Research. 47 (D1): D1179 –D1185. doi:10.1093/nar/gky974. PMC   6323989 . PMID   30357384.
16. Ballesteros JA, Weinstein H (1995). "Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors". Receptor Molecular Biology. Methods in Neurosciences. Vol. 25. 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 (April 2007). "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. PMID   17192495. S2CID   15536186.
18. Sandal M, Behrens M, Brockhoff A, Musiani F, Giorgetti A, Carloni P, et al. (September 2015). "Evidence for a Transient Additional Ligand Binding Site in the TAS2R46 Bitter Taste Receptor". Journal of Chemical Theory and Computation. 11 (9): 4439–4449. doi:10.1021/acs.jctc.5b00472. PMID   26575934.
19. Singh N, Pydi SP, Upadhyaya J, Chelikani P (October 2011). "Structural basis of activation of bitter taste receptor T2R1 and comparison with Class A G-protein-coupled receptors (GPCRs)". The Journal of Biological Chemistry. 286 (41): 36032–36041. doi: 10.1074/jbc.M111.246983 . PMC   3195589 . PMID   21852241.
20. Fierro F, Suku E, Alfonso-Prieto M, Giorgetti A, Cichon S, Carloni P (2017). "Agonist Binding to Chemosensory Receptors: A Systematic Bioinformatics Analysis". Frontiers in Molecular Biosciences. 4: 63. doi: 10.3389/fmolb.2017.00063 . PMC   5592726 . PMID   28932739.
21. Dai W, You Z, Zhou H, Zhang J, Hu Y (June 2011). "Structure-function relationships of the human bitter taste receptor hTAS2R1: insights from molecular modeling studies". Journal of Receptor and Signal Transduction Research. 31 (3): 229–40. doi:10.3109/10799893.2011.578141. PMID   21619450.
22. "hTAS2R1". BitterDB. The Hebrew University of Jerusalem.

Further reading

• Kinnamon SC (March 2000). "A plethora of taste receptors". Neuron. 25 (3): 507–510. doi: 10.1016/S0896-6273(00)81054-5 . PMID   10774719.
• Margolskee RF (January 2002). "Molecular mechanisms of bitter and sweet taste transduction". The Journal of Biological Chemistry. 277 (1): 1–4. doi: 10.1074/jbc.R100054200 . PMID   11696554.
• Montmayeur JP, Matsunami H (August 2002). "Receptors for bitter and sweet taste". Current Opinion in Neurobiology. 12 (4): 366–371. doi:10.1016/S0959-4388(02)00345-8. PMID   12139982. S2CID   37807140.
• Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, et al. (March 2000). "T2Rs function as bitter taste receptors". Cell. 100 (6): 703–711. doi: 10.1016/S0092-8674(00)80706-0 . PMID   10761935. S2CID   7293493.
• Firestein S (April 2000). "The good taste of genomics". Nature. 404 (6778): 552–553. doi: 10.1038/35007167 . PMID   10766221. S2CID   35741332.
• Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, et al. (February 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 (March 2005). "Evolution of bitter taste receptors in humans and apes". Molecular Biology and Evolution. 22 (3): 432–436. doi: 10.1093/molbev/msi027 . PMID   15496549.
• Go Y, Satta Y, Takenaka O, Takahata N (May 2005). "Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates". Genetics. 170 (1): 313–326. 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.