TAS2R14

TAS2R14
Identifiers
Aliases	TAS2R14, T2R14, TRB1, taste 2 receptor member 14
External IDs	OMIM: 604790; MGI: 2681298; HomoloGene: 87013; GeneCards: TAS2R14; OMA:TAS2R14 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12p13.2 Start 10,937,408 bp[1] End 11,171,573 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 G1|6 64.03 cM Start 133,031,780 bp[2] End 133,032,779 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in testicle corpus callosum cerebellar hemisphere right hemisphere of cerebellum right ovary C1 segment left ovary endometrium gastric mucosa body of uterus Top expressed in spermatid More reference expression data BioGPS n/a
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 detection of chemical stimulus involved in sensory perception of bitter taste signal transduction response to stimulus sensory perception of taste G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 50840 387616 Ensembl ENSG00000212127 ENSG00000261984 ENSG00000276541 ENSMUSG00000071147 UniProt Q9NYV8 Q7TQA4 RefSeq (mRNA) NM_023922 NM_021562 RefSeq (protein) NP_076411 NP_067537 Location (UCSC) Chr 12: 10.94 – 11.17 Mb Chr 6: 133.03 – 133.03 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Taste receptor type 2 member 14 is a protein that in humans is encoded by the TAS2R14 gene.^[5][6][7]

Taste receptors for bitter substances (T2Rs/TAS2Rs) belong to the family of G-protein coupled receptors and are related to class A-like GPCRs. There are 25 known T2Rs in humans responsible for bitter taste perception.^[8]

Bitter taste receptor hTAS2R14 is one of the human bitter taste receptors, recognizing an enormous variety of structurally different molecules, including natural and synthetic bitter compounds.^[9]

Gene

TAS2R14 gene^[5][7] (Taste receptor type 2 member 14) is a Protein Coding gene. This gene maps to the taste receptor gene cluster on chromosome 12p13.^[10]

An important paralog of this gene is TAS2R13.

SNPs

Taste receptors harbor many polymorphisms, and several SNPs have a profound impact on the gene function and expression.

Common TAS2R14 SNPs location

Mutation	dbSNP
I5M	rs79297986
F63L	rs142263768
C67S	rs140545738
T86A	rs16925868
N87Y	rs146833217
I118V	rs4140968
F198L	rs202123922
L201F	rs35804287
K211R	rs111614880

Data obtained from 1000 genomes project.

Site-directed mutagenesis

The following residues have been subjected to site-directed mutagenesis.^[11]

Location	BW number[12]	Residue
TM2	2.61	W66
ECL1	3.28	L85
ECL1	3.29	T86
ECL1	3.3	N87
TM3	3.32	W89
TM3	3.33	T90
TM3	3.36	N93
TM3	3.37	H94
ECL2	5.42	T182
ECL2	5.43	S183
TM5	5.46	F186
TM5	5.47	I187
TM6	6.48	Y240
TM6	6.49	A241
TM6	6.51	F243
TM6	6.55	F247
TM7	7.36	I263
TM7	7.39	Q266
TM7	7.42	G269

Signal transduction pathways

TAS2Rs activation produces modulation of a broad range of signal transduction pathways. The Gαgusducin (Gαgus), which belongs to the Gαi subfamily, was first identified and cloned in 1992 in taste tissue, and has high similarity to the Gα-transducin (Gαtrans) in the retina. Gα16gus44, a chimeric Gα16 (type of Gαq), harboring 44 gustducin specific sequence at its C terminus, or Gαqi5, a Gαq protein containing the five carboxyl-terminal amino acids from Gαi, are often used in order to couple the taste receptor to Gαq pathway and measure calcium or IP3 release. Specifically, stimulation of a GPCR receptor, coupled to Gαq, results in the activation of phospholipase C β2 (PLC), which then stimulates the second messengers 1,4,5-inositol trisphosphate (IP3) and diacylglycerol (DAG). IP3 causes the release of Ca+2 from intracellular stores. Calcium opens Ca-activated TRP ion channels and leads to depolarization of the cell as well as to release of neurotransmitters.^[13]

Ligands

To date, 151 ligands have been identified for T2R14,^[14][15] in addition to 12 synthetic flufenamic acid derivatives.^[16]  

Tissue distribution

In addition to the tongue, TAS2R14 is expressed in many other tissues including the heart,^[17] thyroid,^[18] stomach,^[19] skin,^[20] urogenital,^{[21][22][23][24]} immune system,^[25] and more.

Function

This gene product belongs to the family of taste receptors that are members of the G-protein-coupled receptor superfamily. These proteins are specifically expressed in the taste receptor cells of the tongue and palate epithelia. They are organized in the genome in clusters and are genetically linked to loci that influence bitter perception in mice and humans. In functional expression studies, TAS2R14 responds to (−)-α-thujone, the primary neurotoxic agent in absinthe, and picrotoxin, a poison found in fishberries.^[26] This gene maps to the taste receptor gene cluster on chromosome 12p13.^[7]

TAS2R14 is also expressed in the smooth muscle of human airways, along with several other bitter taste receptors. Their activation in these cells causes an increase in intracellular calcium ion, which in turn triggers the opening of potassium channels which hyperpolarize the membrane and cause the smooth muscle to relax. Hence, activation of these receptors leads to bronchodilation.^[27]

In the respiratory system, several TAS2R subtypes: TAS2R4, TAS2R16, TAS2R14 and TAS2R38, were found to play important roles in innate immune nitric oxide production (NO).^[28]

T2R14 causes inhibition of IgE-dependent mast cells.^[29]

Associations between single nucleotide polymorphisms in TAS214 gene and male infertility were observed.^[23]

See also

• Taste receptor

References

1. ENSG00000261984, ENSG00000276541 GRCh38: Ensembl release 89: ENSG00000212127, ENSG00000261984, ENSG00000276541 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000071147 – 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: TAS2R14 taste receptor, type 2, member 14".
8. Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E, Bufe B, et al. (February 2010). "The molecular receptive ranges of human TAS2R bitter taste receptors". Chemical Senses. 35 (2): 157–170. doi:10.1093/chemse/bjp092. PMID 20022913.
9. Di Pizio A, Niv MY (July 2015). "Promiscuity and selectivity of bitter molecules and their receptors". Bioorganic & Medicinal Chemistry. 23 (14): 4082–4091. doi:10.1016/j.bmc.2015.04.025. PMID 25934224.
10. "TAS2R14 Gene - GeneCards | T2R14 Protein | T2R14 Antibody". www.genecards.org. Retrieved 2021-08-03.
11. Nowak S, Di Pizio A, Levit A, Niv MY, Meyerhof W, Behrens M (October 2018). "Reengineering the ligand sensitivity of the broadly tuned human bitter taste receptor TAS2R14". Biochimica et Biophysica Acta (BBA) - General Subjects. 1862 (10): 2162–2173. doi:10.1016/j.bbagen.2018.07.009. PMID 30009876. S2CID 51628536.
12. Ballesteros JA, Weinstein H (January 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. 25: 366–428. doi:10.1016/S1043-9471(05)80049-7. ISBN 9780121852955. ISSN 1043-9471.
13. Breer H, Boekhoff I, Tareilus E (May 1990). "Rapid kinetics of second messenger formation in olfactory transduction". Nature. 345 (6270): 65–68. Bibcode:1990Natur.345...65B. doi:10.1038/345065a0. PMID 2158631. S2CID 511452.
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. Di Pizio A, Waterloo LA, Brox R, Löber S, Weikert D, Behrens M, et al. (February 2020). "Rational design of agonists for bitter taste receptor TAS2R14: from modeling to bench and back". Cellular and Molecular Life Sciences. 77 (3): 531–542. doi:10.1007/s00018-019-03194-2. PMC 11104859. PMID 31236627. S2CID 195329795.
17. Foster SR, Porrello ER, Purdue B, Chan HW, Voigt A, Frenzel S, et al. (2013). "Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart". PLOS ONE. 8 (5): e64579. Bibcode:2013PLoSO...864579F. doi:10.1371/journal.pone.0064579. PMC 3655793. PMID 23696900.
18. Clark AA, Dotson CD, Elson AE, Voigt A, Boehm U, Meyerhof W, et al. (January 2015). "TAS2R bitter taste receptors regulate thyroid function". FASEB Journal. 29 (1): 164–172. doi:10.1096/fj.14-262246. PMC 4285546. PMID 25342133.
19. 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.
20. Shaw L, Mansfield C, Colquitt L, Lin C, Ferreira J, Emmetsberger J, et al. (2018). "Personalized expression of bitter 'taste' receptors in human skin". PLOS ONE. 13 (10): e0205322. Bibcode:2018PLoSO..1305322S. doi:10.1371/journal.pone.0205322. PMC 6192714. PMID 30332676.
21. Behrens M, Bartelt J, Reichling C, Winnig M, Kuhn C, Meyerhof W (July 2006). "Members of RTP and REEP gene families influence functional bitter taste receptor expression". The Journal of Biological Chemistry. 281 (29): 20650–20659. doi:10.1074/jbc.M513637200. PMID 16720576.
22. Zheng K, Lu P, Delpapa E, Bellve K, Deng R, Condon JC, et al. (September 2017). "Bitter taste receptors as targets for tocolytics in preterm labor therapy". FASEB Journal. 31 (9): 4037–4052. doi:10.1096/fj.201601323RR. PMC 5572693. PMID 28559440.
23. Gentiluomo M, Crifasi L, Luddi A, Locci D, Barale R, Piomboni P, et al. (November 2017). "Taste receptor polymorphisms and male infertility". Human Reproduction. 32 (11): 2324–2331. doi:10.1093/humrep/dex305. PMID 29040583.
24. Martin LT, Nachtigal MW, Selman T, Nguyen E, Salsman J, Dellaire G, et al. (April 2019). "Bitter taste receptors are expressed in human epithelial ovarian and prostate cancers cells and noscapine stimulation impacts cell survival". Molecular and Cellular Biochemistry. 454 (1–2): 203–214. doi:10.1007/s11010-018-3464-z. PMID 30350307. S2CID 53035462.
25. Orsmark-Pietras C, James A, Konradsen JR, Nordlund B, Söderhäll C, Pulkkinen V, et al. (July 2013). "Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics". The European Respiratory Journal. 42 (1): 65–78. doi:10.1183/09031936.00077712. PMID 23222870.
26. Behrens M, Brockhoff A, Kuhn C, Bufe B, Winnig M, Meyerhof W (June 2004). "The human taste receptor hTAS2R14 responds to a variety of different bitter compounds". Biochemical and Biophysical Research Communications. 319 (2): 479–485. doi:10.1016/j.bbrc.2004.05.019. PMID 15178431.
27. 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.
28. Yan CH, Hahn S, McMahon D, Bonislawski D, Kennedy DW, Adappa ND, et al. (March 2017). "Nitric oxide production is stimulated by bitter taste receptors ubiquitously expressed in the sinonasal cavity". American Journal of Rhinology & Allergy. 31 (2): 85–92. doi:10.2500/ajra.2017.31.4424. PMC 5356199. PMID 28452704.
29. Ekoff M, Choi JH, James A, Dahlén B, Nilsson G, Dahlén SE (August 2014). "Bitter taste receptor (TAS2R) agonists inhibit IgE-dependent mast cell activation". The Journal of Allergy and Clinical Immunology. 134 (2): 475–478. doi:10.1016/j.jaci.2014.02.029. PMID 24755408.

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.
• 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.
• Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, et al. (2006). "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry". Journal of Proteome Research. 4 (6): 2070–2080. doi:10.1021/pr0502065. PMC 1850943. PMID 16335952.
• Behrens M, Bartelt J, Reichling C, Winnig M, Kuhn C, Meyerhof W (July 2006). "Members of RTP and REEP gene families influence functional bitter taste receptor expression". The Journal of Biological Chemistry. 281 (29): 20650–20659. doi:10.1074/jbc.M513637200. PMID 16720576.

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