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)
End	9,712,378 bp
Gene location (Mouse)
Chr.	Chromosome 15 (mouse)
End	32,178,440 bp
RNA expression pattern
	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
	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
	50834
	57254
	ENSG00000169777
	ENSMUSG00000045267
	Q9NYW7
	Q9JKT2
	NM_019599; NM_001386348
	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 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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000169777 – Ensembl, May 2017
^ ^a ^b ^c 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 (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.
^ 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.
^ "Entrez Gene: TAS2R1 taste receptor, type 2, member 1".
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ 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.
^ ^a ^b 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m 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.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ 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.
^ ^a ^b 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.
^ ^a ^b ^c ^d ^e 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.
^ "hTAS2R1". BitterDB. The Hebrew University of Jerusalem.