TAS2R14

TAS2R14 gene (Taste receptor type 2 member 14) is a Protein Coding gene. This gene maps to the taste receptor gene cluster on chromosome 12p13.{{Cite web|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=TAS2R14&keywords=t2r14.|access-date=2021-08-03|website=www.genecards.org|title=TAS2R14 Gene - GeneCards | T2R14 Protein | T2R14 Antibody }}

An important paralog of this gene is TAS2R13.

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

Data obtained from [https://www.ncbi.nlm.nih.gov/snp/ 1000 genomes project].

The following residues have been subjected to site-directed mutagenesis.{{cite journal | vauthors = Nowak S, Di Pizio A, Levit A, Niv MY, Meyerhof W, Behrens M | title = Reengineering the ligand sensitivity of the broadly tuned human bitter taste receptor TAS2R14 | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1862 | issue = 10 | pages = 2162–2173 | date = October 2018 | pmid = 30009876 | doi = 10.1016/j.bbagen.2018.07.009| s2cid = 51628536 }}

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.{{cite journal | vauthors = Breer H, Boekhoff I, Tareilus E | title = Rapid kinetics of second messenger formation in olfactory transduction | journal = Nature | volume = 345 | issue = 6270 | pages = 65–68 | date = May 1990 | pmid = 2158631 | doi = 10.1038/345065a0 | s2cid = 511452 | bibcode = 1990Natur.345...65B }}

To date, 151 ligands have been identified for T2R14,{{cite journal | vauthors = Wiener A, Shudler M, Levit A, Niv MY | title = BitterDB: a database of bitter compounds | journal = Nucleic Acids Research | volume = 40 | issue = Database issue | pages = D413–D419 | date = January 2012 | pmid = 21940398 | pmc = 3245057 | doi = 10.1093/nar/gkr755 }}{{cite journal | vauthors = Dagan-Wiener A, Di Pizio A, Nissim I, Bahia MS, Dubovski N, Margulis E, Niv MY | title = BitterDB: taste ligands and receptors database in 2019 | journal = Nucleic Acids Research | volume = 47 | issue = D1 | pages = D1179–D1185 | date = January 2019 | pmid = 30357384 | pmc = 6323989 | doi = 10.1093/nar/gky974 }} in addition to 12 synthetic flufenamic acid derivatives.{{cite journal | vauthors = Di Pizio A, Waterloo LA, Brox R, Löber S, Weikert D, Behrens M, Gmeiner P, Niv MY | title = Rational design of agonists for bitter taste receptor TAS2R14: from modeling to bench and back | journal = Cellular and Molecular Life Sciences | volume = 77 | issue = 3 | pages = 531–542 | date = February 2020 | pmid = 31236627 | doi = 10.1007/s00018-019-03194-2 | s2cid = 195329795 | pmc = 11104859 }} TAS2R14 agonist 28.1 is one of the most potent agonists yet developed for this target.Waterloo L, Hübner H, Fierro F, Pfeiffer T, Brox R, Löber S, Weikert D, Niv MY, Gmeiner P. Discovery of 2-Aminopyrimidines as Potent Agonists for the Bitter Taste Receptor TAS2R14. J Med Chem. 2023 Mar 9;66(5):3499-3521. {{doi|10.1021/acs.jmedchem.2c01997}} {{pmid|36847646}} 

In addition to the tongue, TAS2R14 is expressed in many other tissues including the heart,{{cite journal | vauthors = Foster SR, Porrello ER, Purdue B, Chan HW, Voigt A, Frenzel S, Hannan RD, Moritz KM, Simmons DG, Molenaar P, Roura E, Boehm U, Meyerhof W, Thomas WG | title = Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart | journal = PLOS ONE | volume = 8 | issue = 5 | pages = e64579 | date = 2013 | pmid = 23696900 | pmc = 3655793 | doi = 10.1371/journal.pone.0064579 | doi-access = free | bibcode = 2013PLoSO...864579F }} thyroid,{{cite journal | vauthors = Clark AA, Dotson CD, Elson AE, Voigt A, Boehm U, Meyerhof W, Steinle NI, Munger SD | title = TAS2R bitter taste receptors regulate thyroid function | journal = FASEB Journal | volume = 29 | issue = 1 | pages = 164–172 | date = January 2015 | pmid = 25342133 | pmc = 4285546 | doi = 10.1096/fj.14-262246 | doi-access = free }} stomach,{{cite journal | vauthors = Liszt KI, Ley JP, Lieder B, Behrens M, Stöger V, Reiner A, Hochkogler CM, Köck E, Marchiori A, Hans J, Widder S, Krammer G, Sanger GJ, Somoza MM, Meyerhof W, Somoza V | title = Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 30 | pages = E6260–E6269 | date = July 2017 | pmid = 28696284 | pmc = 5544304 | doi = 10.1073/pnas.1703728114 | doi-access = free | bibcode = 2017PNAS..114E6260L }} skin,{{cite journal | vauthors = Shaw L, Mansfield C, Colquitt L, Lin C, Ferreira J, Emmetsberger J, Reed DR | title = Personalized expression of bitter 'taste' receptors in human skin | journal = PLOS ONE | volume = 13 | issue = 10 | pages = e0205322 | date = 2018 | pmid = 30332676 | pmc = 6192714 | doi = 10.1371/journal.pone.0205322 | doi-access = free | bibcode = 2018PLoSO..1305322S }} urogenital,{{cite journal | vauthors = Behrens M, Bartelt J, Reichling C, Winnig M, Kuhn C, Meyerhof W | title = Members of RTP and REEP gene families influence functional bitter taste receptor expression | journal = The Journal of Biological Chemistry | volume = 281 | issue = 29 | pages = 20650–20659 | date = July 2006 | pmid = 16720576 | doi = 10.1074/jbc.M513637200 | doi-access = free }}{{cite journal | vauthors = Zheng K, Lu P, Delpapa E, Bellve K, Deng R, Condon JC, Fogarty K, Lifshitz LM, Simas TA, Shi F, ZhuGe R | title = Bitter taste receptors as targets for tocolytics in preterm labor therapy | journal = FASEB Journal | volume = 31 | issue = 9 | pages = 4037–4052 | date = September 2017 | pmid = 28559440 | pmc = 5572693 | doi = 10.1096/fj.201601323RR | doi-access = free }}{{cite journal | vauthors = Gentiluomo M, Crifasi L, Luddi A, Locci D, Barale R, Piomboni P, Campa D | title = Taste receptor polymorphisms and male infertility | journal = Human Reproduction | volume = 32 | issue = 11 | pages = 2324–2331 | date = November 2017 | pmid = 29040583 | doi = 10.1093/humrep/dex305 | doi-access = free }}{{cite journal | vauthors = Martin LT, Nachtigal MW, Selman T, Nguyen E, Salsman J, Dellaire G, Dupré DJ | title = Bitter taste receptors are expressed in human epithelial ovarian and prostate cancers cells and noscapine stimulation impacts cell survival | journal = Molecular and Cellular Biochemistry | volume = 454 | issue = 1–2 | pages = 203–214 | date = April 2019 | pmid = 30350307 | doi = 10.1007/s11010-018-3464-z | s2cid = 53035462 }} immune system,{{cite journal | vauthors = Orsmark-Pietras C, James A, Konradsen JR, Nordlund B, Söderhäll C, Pulkkinen V, Pedroletti C, Daham K, Kupczyk M, Dahlén B, Kere J, Dahlén SE, Hedlin G, Melén E | title = Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics | journal = The European Respiratory Journal | volume = 42 | issue = 1 | pages = 65–78 | date = July 2013 | pmid = 23222870 | doi = 10.1183/09031936.00077712 | doi-access = free }} and more.

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.{{cite journal | vauthors = Behrens M, Brockhoff A, Kuhn C, Bufe B, Winnig M, Meyerhof W | title = The human taste receptor hTAS2R14 responds to a variety of different bitter compounds | journal = Biochemical and Biophysical Research Communications | volume = 319 | issue = 2 | pages = 479–485 | date = June 2004 | pmid = 15178431 | doi = 10.1016/j.bbrc.2004.05.019 }} This gene maps to the taste receptor gene cluster on chromosome 12p13.

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.{{cite journal | vauthors = Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS, Liggett SB | title = Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction | journal = Nature Medicine | volume = 16 | issue = 11 | pages = 1299–1304 | date = November 2010 | pmid = 20972434 | pmc = 3066567 | doi = 10.1038/nm.2237 }}

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).{{cite journal | vauthors = Yan CH, Hahn S, McMahon D, Bonislawski D, Kennedy DW, Adappa ND, Palmer JN, Jiang P, Lee RJ, Cohen NA | title = Nitric oxide production is stimulated by bitter taste receptors ubiquitously expressed in the sinonasal cavity | journal = American Journal of Rhinology & Allergy | volume = 31 | issue = 2 | pages = 85–92 | date = March 2017 | pmid = 28452704 | pmc = 5356199 | doi = 10.2500/ajra.2017.31.4424 }}

T2R14 causes inhibition of IgE-dependent mast cells.{{cite journal | vauthors = Ekoff M, Choi JH, James A, Dahlén B, Nilsson G, Dahlén SE | title = Bitter taste receptor (TAS2R) agonists inhibit IgE-dependent mast cell activation | journal = The Journal of Allergy and Clinical Immunology | volume = 134 | issue = 2 | pages = 475–478 | date = August 2014 | pmid = 24755408 | doi = 10.1016/j.jaci.2014.02.029 }}

Associations between single nucleotide polymorphisms in TAS214 gene and male infertility were observed.

• Taste receptor

{{Reflist}}

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• {{cite journal | vauthors = Behrens M, Bartelt J, Reichling C, Winnig M, Kuhn C, Meyerhof W | title = Members of RTP and REEP gene families influence functional bitter taste receptor expression | journal = The Journal of Biological Chemistry | volume = 281 | issue = 29 | pages = 20650–20659 | date = July 2006 | pmid = 16720576 | doi = 10.1074/jbc.M513637200 | doi-access = free }}

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{{G protein-coupled receptors|g3}}

Category:Human taste receptors