TAS2R14

Last updated
TAS2R14
Identifiers
Aliases TAS2R14 , T2R14, TRB1, taste 2 receptor member 14
External IDs OMIM: 604790 MGI: 2681298 HomoloGene: 87013 GeneCards: TAS2R14
Orthologs
SpeciesHumanMouse
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]

Contents

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
MutationdbSNP
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]

LocationBW number [12] Residue
TM22.61W66
ECL13.28L85
ECL13.29T86
ECL13.3N87
TM33.32W89
TM33.33T90
TM33.36N93
TM33.37H94
ECL25.42T182
ECL25.43S183
TM55.46F186
TM55.47I187
TM66.48Y240
TM66.49A241
TM66.51F243
TM66.55F247
TM77.36I263
TM77.39Q266
TM77.42G269

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

Related Research Articles

Aftertaste is the taste intensity of a food or beverage that is perceived immediately after that food or beverage is removed from the mouth. The aftertastes of different foods and beverages can vary by intensity and over time, but the unifying feature of aftertaste is that it is perceived after a food or beverage is either swallowed or spat out. The neurobiological mechanisms of taste signal transduction from the taste receptors in the mouth to the brain have not yet been fully understood. However, the primary taste processing area located in the insula has been observed to be involved in aftertaste perception.

<span class="mw-page-title-main">TAS2R16</span> Protein-coding gene in the species Homo sapiens

TAS2R16 is a bitter taste receptor and one of the 25 TAS2Rs. TAS2Rs are receptors that belong to the G-protein-coupled receptors (GPCRs) family. These receptors detect various bitter substances found in nature as agonists, and get stimulated. TAS2R16 receptor is mainly expressed within taste buds present on the surface of the tongue and palate epithelium. TAS2R16 is activated by bitter β-glucopyranosides

<span class="mw-page-title-main">Taste receptor</span> Type of cellular receptor that facilitates taste

A taste receptor or tastant is a type of cellular receptor which facilitates the sensation of taste. When food or other substances enter the mouth, molecules interact with saliva and are bound to taste receptors in the oral cavity and other locations. Molecules which give a sensation of taste are considered "sapid".

<span class="mw-page-title-main">TAS2R38</span> Protein-coding gene in the species Homo sapiens

Taste receptor 2 member 38 is a protein that in humans is encoded by the TAS2R38 gene. TAS2R38 is a bitter taste receptor; varying genotypes of TAS2R38 influence the ability to taste both 6-n-propylthiouracil (PROP) and phenylthiocarbamide (PTC). Though it has often been proposed that varying taste receptor genotypes could influence tasting ability, TAS2R38 is one of the few taste receptors shown to have this function.

<span class="mw-page-title-main">TAS2R1</span> Member of the 25 known human bitter taste receptors

Taste receptor type 2 member 1 (TAS2R1/T2R1) is a protein that in humans is encoded by the TAS2R1 gene. 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. 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.

<span class="mw-page-title-main">TAS2R4</span> Protein-coding gene in the species Homo sapiens

Taste receptor type 2 member 4 is a protein that in humans is encoded by the TAS2R4 gene.

<span class="mw-page-title-main">TAS2R9</span> Protein-coding gene in the species Homo sapiens

Taste receptor type 2 member 9 is a protein that in humans is encoded by the TAS2R9 gene.

<span class="mw-page-title-main">TAS2R10</span> Protein-coding gene in the species Homo sapiens

Taste receptor type 2 member 10 is a protein that in humans is encoded by the TAS2R10 gene. The protein is responsible for bitter taste recognition in mammals. It serves as a defense mechanism to prevent consumption of toxic substances which often have a characteristic bitter taste.

<span class="mw-page-title-main">TAS2R5</span> Protein-coding gene in the species Homo sapiens

Taste receptor type 2 member 5 is a protein that in humans is encoded by the TAS2R5 gene.

<span class="mw-page-title-main">TAS1R1</span> Protein

Taste receptor type 1 member 1 is a protein that in humans is encoded by the TAS1R1 gene.

<span class="mw-page-title-main">TAS1R2</span> Protein

T1R2 - Taste receptor type 1 member 2 is a protein that in humans is encoded by the TAS1R2 gene.

<span class="mw-page-title-main">TAS1R3</span> Mammalian protein found in Homo sapiens

Taste receptor type 1 member 3 is a protein that in humans is encoded by the TAS1R3 gene. The TAS1R3 gene encodes the human homolog of mouse Sac taste receptor, a major determinant of differences between sweet-sensitive and -insensitive mouse strains in their responsiveness to sucrose, saccharin, and other sweeteners.

<span class="mw-page-title-main">TAS2R41</span> Protein-coding gene in the species Homo sapiens

Taste receptor type 2 member 41 is a protein that in humans is encoded by the TAS2R41 gene.

<span class="mw-page-title-main">TAS2R43</span> Protein-coding gene in the species Homo sapiens

Taste receptor type 2 member 43 is a protein that in humans is encoded by the TAS2R43 gene.

<span class="mw-page-title-main">TAS2R31</span> Protein-coding gene in the species Homo sapiens

Taste receptor, type 2, member 31, also known as TAS2R31, is a protein which in humans is encoded by the TAS2R31 gene. This bitter taste receptor has been shown to respond to saccharin in vitro.

<span class="mw-page-title-main">TAS2R46</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">TAS2R19</span> Protein-coding gene in the species Homo sapiens

Taste receptor type 2 member 19 is a protein that in humans is encoded by the TAS2R19 gene. It seems to be involved in the perception of salt and bitter tastes.

<span class="mw-page-title-main">TAS2R20</span> Protein-coding gene in the species Homo sapiens

Taste receptor type 2 member 20 is a protein that in humans is encoded by the TAS2R20 gene.

<span class="mw-page-title-main">TAS2R50</span> Protein-coding gene in the species Homo sapiens

Taste receptor type 2 member 50 is a protein that in humans is encoded by the TAS2R50 gene.

<span class="mw-page-title-main">TAS2R60</span> Protein-coding gene in the species Homo sapiens

Taste receptor type 2 member 60 is a protein that in humans is encoded by the TAS2R60 gene.

References

  1. 1 2 3 ENSG00000261984, ENSG00000276541 GRCh38: Ensembl release 89: ENSG00000212127, ENSG00000261984, ENSG00000276541 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. 1 2 3 "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. General Subjects. 1862 (10): 2162–2173. doi:10.1016/j.bbagen.2018.07.009. PMID   30009876. S2CID   51628536.
  12. ↑ Ballesteros JA, Weinstein H (1995-01-01). "[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, Niv MY (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. 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, Reed DR (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. 1 2 Gentiluomo M, Crifasi L, Luddi A, Locci D, Barale R, Piomboni P, Campa D (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, Dupré DJ (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.

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