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]
End	9,712,378 bp[1]
Gene location (Mouse)
Chr.	Chromosome 15 (mouse)[2]
End	32,178,294 bp[2]
RNA expression pattern
	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	• cell 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
	50834
	57254
	ENSG00000169777
	ENSMUSG00000045267
	Q9NYW7
	Q9JKT2
	NM_019599
	NM_020503
	NP_062545
	NP_065249
	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]

References

GRCh38: Ensembl release 89: ENSG00000169777 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000045267 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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.
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.
"Entrez Gene: TAS2R1 taste receptor, type 2, member 1".
Di Pizio, Antonella; Levit, Anat; Slutzki, Michal; Behrens, Maik; Karaman, Rafik; Niv, Masha Y. (2016), "Comparing Class A GPCRs to bitter taste receptors", Methods in Cell Biology, Elsevier, 132: 401–427, doi:10.1016/bs.mcb.2015.10.005, ISBN 9780128035955, PMID 26928553
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. doi:10.1085/jgp.201611637. ISSN 0022-1295. PMC 5299619. PMID 28053191.
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. doi:10.1038/nm.2237. ISSN 1078-8956. PMC 3066567. PMID 20972434.
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. doi:10.1073/pnas.1703728114. ISSN 0027-8424. PMC 5544304. PMID 28696284.
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. doi:10.1016/j.bbrc.2014.02.140. ISSN 0006-291X. PMID 24613843.
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. Bibcode:2014PLoSO...9k0373U. doi:10.1371/journal.pone.0110373. ISSN 1932-6203. PMC 4207743. PMID 25340739.
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. doi:10.1093/nar/gkr755. ISSN 1362-4962. PMC 3245057. PMID 21940398.
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. doi:10.1093/nar/gky974. ISSN 0305-1048. PMC 6323989. PMID 30357384.
Ballesteros, Juan A.; Weinstein, Harel (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 9780121852955
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. doi:10.1124/mol.106.029470. ISSN 0026-895X. PMID 17192495. S2CID 15536186.
"hTAS2R1". BitterDB. The Hebrew University of Jerusalem.