Biology:TAS2R14

From HandWiki
A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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.[1]

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.[2]

Gene

TAS2R14 gene[3][4][5] (Taste receptor type 2 member 14) is a Protein Coding gene. This gene maps to the taste receptor gene cluster on chromosome 12p13.[6]

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.

Mutagenesis data (obtained from BitterDB[7][8])

Location BW number[9] Residue References
TM2 2.61 W66 doi: 10.1016/j.bbagen.2018.07.009
ECL1 3.28 L85 doi: 10.1016/j.bbagen.2018.07.009
ECL1 3.29 T86 doi: 10.1016/j.bbagen.2018.07.009
ECL1 3.3 N87 doi: 10.1016/j.bbagen.2018.07.009
TM3 3.32 W89 doi: 10.1016/j.bbagen.2018.07.009
TM3 3.33 T90 doi: 10.1016/j.bbagen.2018.07.009
TM3 3.36 N93 doi: 10.1016/j.bbagen.2018.07.009
TM3 3.37 H94 doi: 10.1016/j.bbagen.2018.07.009
ECL2 5.42 T182 doi: 10.1016/j.bbagen.2018.07.009
ECL2 5.43 S183 doi: 10.1016/j.bbagen.2018.07.009
TM5 5.46 F186 doi: 10.1016/j.bbagen.2018.07.009
TM5 5.47 I187 doi: 10.1016/j.bbagen.2018.07.009
TM6 6.48 Y240 doi: 10.1016/j.bbagen.2018.07.009
TM6 6.49 A241 doi: 10.1016/j.bbagen.2018.07.009
TM6 6.51 F243 doi: 10.1016/j.bbagen.2018.07.009
TM6 6.55 F247 doi: 10.1016/j.bbagen.2018.07.009
TM7 7.36 I263 doi: 10.1016/j.bbagen.2018.07.009
TM7 7.39 Q266 doi: 10.1016/j.bbagen.2018.07.009
TM7 7.42 G269 doi: 10.1016/j.bbagen.2018.07.009

3D model (from BitterDB[7][8])

A homology model can be found and downloaded here.[2]

Signal transduction pathways of T2Rs

TAS2Rs activation produces modulation of a broad range of signal transduction pathways. 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.[10]

Ligands (from BitterDB[7][8])

Up to now, 151 ligands were identified for T2R14 and are summarized in BitterDB,[7][8] in addition to 12 synthetic flufenamic acid derivatives.[11]  

Function

This gene product belongs to the family of candidate 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.[12] This gene maps to the taste receptor gene cluster on chromosome 12p13.[5]

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.[13]

Extra-oral roles of TAS2R14

TAS2R14 was shown to be expressed in many tissues in the human body including the heart,[14] thyroid,[15] stomach,[16] skin,[17] urogenital,[18][19][20][21] immune system,[22] and more.

TAS2R14 extra-oral function

  • 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).[23]
  • T2R14 causes inhibition of IgE-dependent mast cells.[24]
  • Associations between single nucleotide polymorphisms in TAS214 gene and male infertility were observed.[20]

See also

References

  1. ↑ "The molecular receptive ranges of human TAS2R bitter taste receptors". Chemical Senses 35 (2): 157–70. February 2010. doi:10.1093/chemse/bjp092. PMID 20022913. 
  2. ↑ 2.0 2.1 "Promiscuity and selectivity of bitter molecules and their receptors". Bioorganic & Medicinal Chemistry 23 (14): 4082–91. July 2015. doi:10.1016/j.bmc.2015.04.025. PMID 25934224. https://www.sciencedirect.com/science/article/abs/pii/S0968089615003235. 
  3. ↑ "A novel family of mammalian taste receptors". Cell 100 (6): 693–702. March 2000. doi:10.1016/S0092-8674(00)80705-9. PMID 10761934. 
  4. ↑ "A family of candidate taste receptors in human and mouse". Nature 404 (6778): 601–4. April 2000. doi:10.1038/35007072. PMID 10766242. Bibcode: 2000Natur.404..601M. 
  5. ↑ 5.0 5.1 "Entrez Gene: TAS2R14 taste receptor, type 2, member 14". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=50840. 
  6. ↑ "TAS2R14 Gene - GeneCards | T2R14 Protein | T2R14 Antibody". https://www.genecards.org/cgi-bin/carddisp.pl?gene=TAS2R14&keywords=t2r14.. 
  7. ↑ 7.0 7.1 7.2 7.3 "BitterDB: a database of bitter compounds". Nucleic Acids Research 40 (Database issue): D413-9. January 2012. doi:10.1093/nar/gkr755. PMID 21940398. 
  8. ↑ 8.0 8.1 8.2 8.3 "BitterDB: taste ligands and receptors database in 2019". Nucleic Acids Research 47 (D1): D1179–D1185. January 2019. doi:10.1093/nar/gky974. PMID 30357384. 
  9. ↑ Ballesteros, Juan A.; Weinstein, Harel (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"] (in en). Methods in Neurosciences 25: 366–428. doi:10.1016/S1043-9471(05)80049-7. ISBN 9780121852955. ISSN 1043-9471. https://www.sciencedirect.com/science/article/pii/S1043947105800497. 
  10. ↑ "Rapid kinetics of second messenger formation in olfactory transduction". Nature 345 (6270): 65–8. May 1990. doi:10.1038/345065a0. PMID 2158631. Bibcode: 1990Natur.345...65B. https://pubmed.ncbi.nlm.nih.gov/2158631/. 
  11. ↑ "Rational design of agonists for bitter taste receptor TAS2R14: from modeling to bench and back". Cellular and Molecular Life Sciences 77 (3): 531–542. February 2020. doi:10.1007/s00018-019-03194-2. PMID 31236627. https://pubmed.ncbi.nlm.nih.gov/31236627/. 
  12. ↑ "The human taste receptor hTAS2R14 responds to a variety of different bitter compounds". Biochemical and Biophysical Research Communications 319 (2): 479–85. June 2004. doi:10.1016/j.bbrc.2004.05.019. PMID 15178431. 
  13. ↑ "Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction". Nature Medicine 16 (11): 1299–304. November 2010. doi:10.1038/nm.2237. PMID 20972434. 
  14. ↑ "Expression, regulation and putative nutrient-sensing function of taste GPCRs in the heart". PLOS ONE 8 (5): e64579. 2013. doi:10.1371/journal.pone.0064579. PMID 23696900. Bibcode: 2013PLoSO...864579F. 
  15. ↑ "TAS2R bitter taste receptors regulate thyroid function". FASEB Journal 29 (1): 164–72. January 2015. doi:10.1096/fj.14-262246. PMID 25342133. 
  16. ↑ Liszt, Kathrin Ingrid; Ley, Jakob Peter; Lieder, Barbara; Behrens, Maik; Stöger, Verena; Reiner, Angelika; Hochkogler, Christina Maria; Köck, Elke et al. (2017-07-25). "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. PMID 28696284. Bibcode: 2017PNAS..114E6260L. 
  17. ↑ "Personalized expression of bitter 'taste' receptors in human skin". PLOS ONE 13 (10): e0205322. 2018. doi:10.1371/journal.pone.0205322. PMID 30332676. Bibcode: 2018PLoSO..1305322S. 
  18. ↑ "Members of RTP and REEP gene families influence functional bitter taste receptor expression". The Journal of Biological Chemistry 281 (29): 20650–9. July 2006. doi:10.1074/jbc.M513637200. PMID 16720576. 
  19. ↑ "Bitter taste receptors as targets for tocolytics in preterm labor therapy". FASEB Journal 31 (9): 4037–4052. September 2017. doi:10.1096/fj.201601323RR. PMID 28559440. 
  20. ↑ 20.0 20.1 "Taste receptor polymorphisms and male infertility". Human Reproduction 32 (11): 2324–2331. November 2017. doi:10.1093/humrep/dex305. PMID 29040583. 
  21. ↑ "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. April 2019. doi:10.1007/s11010-018-3464-z. PMID 30350307. https://pubmed.ncbi.nlm.nih.gov/30350307/. 
  22. ↑ "Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics". The European Respiratory Journal 42 (1): 65–78. July 2013. doi:10.1183/09031936.00077712. PMID 23222870. 
  23. ↑ "Nitric oxide production is stimulated by bitter taste receptors ubiquitously expressed in the sinonasal cavity". American Journal of Rhinology & Allergy 31 (2): 85–92. March 2017. doi:10.2500/ajra.2017.31.4424. PMID 28452704. 
  24. ↑ "Bitter taste receptor (TAS2R) agonists inhibit IgE-dependent mast cell activation". The Journal of Allergy and Clinical Immunology 134 (2): 475–8. August 2014. doi:10.1016/j.jaci.2014.02.029. PMID 24755408. https://pubmed.ncbi.nlm.nih.gov/24755408/. 

Further reading

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




Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:TAS2R14&oldid=3536892"