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{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{cs1 config|name-list-style=vanc}}
{{Infobox_gene}}
{{Infobox_gene}}
'''Taste receptor type 2 member 14''' is a [[protein]] that in humans is encoded by the ''TAS2R14'' [[gene]].<ref name="pmid10761934">{{cite journal | vauthors = Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS | title = A novel family of mammalian taste receptors | journal = Cell | volume = 100 | issue = 6 | pages = 693–702 | date = March 2000 | pmid = 10761934 | pmc = | doi = 10.1016/S0092-8674(00)80705-9 | s2cid = 14604586 | doi-access = free }}</ref><ref name="pmid10766242">{{cite journal | vauthors = Matsunami H, Montmayeur JP, Buck LB | title = A family of candidate taste receptors in human and mouse | journal = Nature | volume = 404 | issue = 6778 | pages = 601–604 | date = April 2000 | pmid = 10766242 | pmc = | doi = 10.1038/35007072 | bibcode = 2000Natur.404..601M | s2cid = 4336913 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: TAS2R14 taste receptor, type 2, member 14| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=50840| access-date = }}</ref>
Taste receptors for bitter substances (T2Rs/TAS2Rs) belong to the family of [[G protein-coupled receptor|G-protein coupled receptors]] and are related to [[GPCR family A|class A]]-like GPCRs. There are 25 known T2Rs in humans responsible for bitter taste perception.<ref>{{cite journal | vauthors = Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E, Bufe B, Appendino G, Behrens M | display-authors = 6 | title = The molecular receptive ranges of human TAS2R bitter taste receptors | journal = Chemical Senses | volume = 35 | issue = 2 | pages = 157–70 | date = February 2010 | pmid = 20022913 | doi = 10.1093/chemse/bjp092 | doi-access = free }}</ref>


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.<ref name=":0">{{cite journal | vauthors = Di Pizio A, Niv MY | title = Promiscuity and selectivity of bitter molecules and their receptors | journal = Bioorganic & Medicinal Chemistry | volume = 23 | issue = 14 | pages = 4082–91 | date = July 2015 | pmid = 25934224 | doi = 10.1016/j.bmc.2015.04.025 | url = https://www.sciencedirect.com/science/article/abs/pii/S0968089615003235 }}</ref>
Taste receptors for bitter substances (T2Rs/TAS2Rs) belong to the family of [[G protein-coupled receptor|G-protein coupled receptors]] and are related to [[GPCR family A|class A]]-like GPCRs. There are 25 known T2Rs in humans responsible for bitter taste perception.<ref>{{cite journal | vauthors = Meyerhof W, Batram C, Kuhn C, Brockhoff A, Chudoba E, Bufe B, Appendino G, Behrens M | display-authors = 6 | title = The molecular receptive ranges of human TAS2R bitter taste receptors | journal = Chemical Senses | volume = 35 | issue = 2 | pages = 157–170 | date = February 2010 | pmid = 20022913 | doi = 10.1093/chemse/bjp092 | doi-access = free }}</ref>

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.<ref name=":0">{{cite journal | vauthors = Di Pizio A, Niv MY | title = Promiscuity and selectivity of bitter molecules and their receptors | journal = Bioorganic & Medicinal Chemistry | volume = 23 | issue = 14 | pages = 4082–4091 | date = July 2015 | pmid = 25934224 | doi = 10.1016/j.bmc.2015.04.025 }}</ref>


== Gene ==
== Gene ==
TAS2R14 [[gene]]<ref name="pmid10761934">{{cite journal | vauthors = Adler E, Hoon MA, Mueller KL, Chandrashekar J, Ryba NJ, Zuker CS | title = A novel family of mammalian taste receptors | journal = Cell | volume = 100 | issue = 6 | pages = 693–702 | date = March 2000 | pmid = 10761934 | doi = 10.1016/S0092-8674(00)80705-9 | s2cid = 14604586 | doi-access = free }}</ref><ref name="pmid10766242">{{cite journal | vauthors = Matsunami H, Montmayeur JP, Buck LB | title = A family of candidate taste receptors in human and mouse | journal = Nature | volume = 404 | issue = 6778 | pages = 601–4 | date = April 2000 | pmid = 10766242 | doi = 10.1038/35007072 | bibcode = 2000Natur.404..601M | s2cid = 4336913 }}</ref><ref name="entrez">{{cite web|title=Entrez Gene: TAS2R14 taste receptor, type 2, member 14|url=https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=50840}}</ref> ('''Taste receptor type 2 member 14''') is a Protein Coding gene. This gene maps to the taste receptor gene cluster on chromosome 12p13.<ref>{{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 &#124; T2R14 Protein &#124; T2R14 Antibody }}</ref>
TAS2R14 [[gene]]<ref name="pmid10761934" /><ref name="entrez" /> ('''Taste receptor type 2 member 14''') is a Protein Coding gene. This gene maps to the taste receptor gene cluster on chromosome 12p13.<ref>{{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 &#124; T2R14 Protein &#124; T2R14 Antibody }}</ref>


An important paralog of this gene is [[TAS2R13]].
An important paralog of this gene is [[TAS2R13]].
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Data obtained from [https://www.ncbi.nlm.nih.gov/snp/ 1000 genomes project].
Data obtained from [https://www.ncbi.nlm.nih.gov/snp/ 1000 genomes project].


== Site-directed mutagenesis ==
== [[Site-directed mutagenesis|Mutagenesis]] data (obtained from [http://bitterdb.agri.huji.ac.il/Receptor.php?id=14 BitterDB]<ref name=":1">{{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 = D413-9 | date = January 2012 | pmid = 21940398 | pmc = 3245057 | doi = 10.1093/nar/gkr755 }}</ref><ref name=":2">{{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 }}</ref>) ==

The following residues have been subjected to [[site-directed mutagenesis]].<ref name="pmid30009876">{{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 }}</ref>
{| class="wikitable"
{| class="wikitable"
|Location
|Location
|BW number<ref>{{Cite journal|date=1995-01-01|title=[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors|url=https://www.sciencedirect.com/science/article/pii/S1043947105800497|journal=Methods in Neurosciences|language=en|volume=25|pages=366–428|doi=10.1016/S1043-9471(05)80049-7|issn=1043-9471|last1=Ballesteros|first1=Juan A.|last2=Weinstein|first2=Harel|isbn=9780121852955}}</ref>
|BW number<ref>{{Cite journal|date=1995-01-01|title=[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors|url=https://www.sciencedirect.com/science/article/pii/S1043947105800497|journal=Methods in Neurosciences|language=en|volume=25|pages=366–428|doi=10.1016/S1043-9471(05)80049-7|issn=1043-9471|last1=Ballesteros|first1=Juan A.|last2=Weinstein|first2=Harel|isbn=9780121852955}}</ref>
|Residue
|Residue
|References
|-
|-
|TM2
|TM2
|2.61
|2.61
|W66
|W66

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|ECL1
|ECL1
|3.28
|3.28
|L85
|L85

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|ECL1
|ECL1
|3.29
|3.29
|T86
|T86

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|ECL1
|ECL1
|3.3
|3.3
|N87
|N87

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM3
|TM3
|3.32
|3.32
|W89
|W89

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM3
|TM3
|3.33
|3.33
|T90
|T90

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM3
|TM3
|3.36
|3.36
|N93
|N93

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM3
|TM3
|3.37
|3.37
|H94
|H94

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|ECL2
|ECL2
|5.42
|5.42
|T182
|T182

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|ECL2
|ECL2
|5.43
|5.43
|S183
|S183

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM5
|TM5
|5.46
|5.46
|F186
|F186

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM5
|TM5
|5.47
|5.47
|I187
|I187

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM6
|TM6
|6.48
|6.48
|Y240
|Y240

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM6
|TM6
|6.49
|6.49
|A241
|A241

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM6
|TM6
|6.51
|6.51
|F243
|F243

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM6
|TM6
|6.55
|6.55
|F247
|F247

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM7
|TM7
|7.36
|7.36
|I263
|I263

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM7
|TM7
|7.39
|7.39
|Q266
|Q266

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|-
|-
|TM7
|TM7
|7.42
|7.42
|G269
|G269

|doi: [[doi:10.1016/j.bbagen.2018.07.009|10.1016/j.bbagen.2018.07.009]]
|}
|}


⚫
== Signal transduction pathways ==
== 3D model (from [http://bitterdb.agri.huji.ac.il/Receptor.php?id=14 BitterDB]<ref name=":1" /><ref name=":2" />) ==
⚫
TAS2Rs activation produces modulation of a broad range of signal transduction pathways. The Gαgusducin (Gαgus), which belongs to the [[Gi alpha subunit|Gαi]] subfamily, was first identified and cloned in 1992 in
A [[Homology modeling|homology model]] can be found and downloaded [http://bitterdb.agri.huji.ac.il/Receptor.php?id=14 here].<ref name=":0" />

⚫
== Signal transduction pathways and cell-based functional assays for T2Rs ==
⚫
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.
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.
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 [[G protein-coupled receptor|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.<ref>{{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 = 65–8 | date = May 1990 | pmid = 2158631 | doi = 10.1038/345065a0 | bibcode = 1990Natur.345...65B | s2cid = 511452 | url = https://pubmed.ncbi.nlm.nih.gov/2158631/ }}</ref>
Specifically, stimulation of a [[G protein-coupled receptor|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.<ref>{{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 }}</ref>


== Ligands ==
== Ligands ==
Up to now, 151 ligands have been identified for T2R14 <ref>{{cite journal | vauthors = Di Pizio A, Waterloo LA, Brox R, Löber S, Weikert D, Behrens M, Gmeiner P, Niv MY | display-authors = 6 | 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 | url = https://pubmed.ncbi.nlm.nih.gov/31236627/ }}</ref>
To date, 151 ligands have been identified for T2R14,<ref name=":1">{{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 }}</ref><ref name=":2">{{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 }}</ref> in addition to 12 synthetic [[flufenamic acid]] derivatives.<ref>{{cite journal | vauthors = Di Pizio A, Waterloo LA, Brox R, Löber S, Weikert D, Behrens M, Gmeiner P, Niv MY | display-authors = 6 | 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 }}</ref>  

Synthesis of structural analogues of [[flufenamic acid]] led to 2-aminopyridines showing considerable efficacy <ref>{{Cite journal |last=Waterloo |first=Lukas |last2=Hübner |first2=Harald |last3=Fierro |first3=Fabrizio |last4=Pfeiffer |first4=Tara |last5=Brox |first5=Regine |last6=Löber |first6=Stefan |last7=Weikert |first7=Dorothee |last8=Niv |first8=Masha Y. |last9=Gmeiner |first9=Peter |date=2023-03-09 |title=Discovery of 2-Aminopyrimidines as Potent Agonists for the Bitter Taste Receptor TAS2R14 |url=https://pubs.acs.org/doi/10.1021/acs.jmedchem.2c01997 |journal=Journal of Medicinal Chemistry |language=en |volume=66 |issue=5 |pages=3499–3521 |doi=10.1021/acs.jmedchem.2c01997 |issn=0022-2623}}</ref>. In combination with an exchange of the carboxylic moiety with a tetrazole link, a set of promising new TAS2R14 agonists were developed. Among which, the most potent ligand showed a six-fold higher potency than [[flufenamic acid]] and remarkable selectivity over other TAS2Rs.


== Tissue distribution ==
In an aim to discover new antagonists for TAS2R14, in the lack of an experimental structure for the receptor, a mixed experimental-computational methodology was used to iteratively improve the performance of the predicted structure <ref>{{Cite journal |last=Fierro |first=Fabrizio |last2=Peri |first2=Lior |last3=Hübner |first3=Harald |last4=Tabor-Schkade |first4=Alina |last5=Waterloo |first5=Lukas |last6=Löber |first6=Stefan |last7=Pfeiffer |first7=Tara |last8=Weikert |first8=Dorothee |last9=Dingjan |first9=Tamir |last10=Margulis |first10=Eitan |last11=Gmeiner |first11=Peter |last12=Niv |first12=Masha Y. |date=2023-04-03 |title=Inhibiting a promiscuous GPCR: iterative discovery of bitter taste receptor ligands |url=https://doi.org/10.1007/s00018-023-04765-0 |journal=Cellular and Molecular Life Sciences |language=en |volume=80 |issue=4 |pages=114 |doi=10.1007/s00018-023-04765-0 |issn=1420-9071}}</ref>. This resulted in the identification of 10 novel antagonists and 200 novel agonists for TAS2R14.
⚫
In addition to the tongue, TAS2R14 is expressed in many other tissues including the [[heart]],<ref>{{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 | display-authors = 6 | 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 }}</ref> [[thyroid]],<ref>{{cite journal | vauthors = Clark AA, Dotson CD, Elson AE, Voigt A, Boehm U, Meyerhof W, Steinle NI, Munger SD | display-authors = 6 | 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 }}</ref> [[stomach]],<ref>{{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 | display-authors = 6 | 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 }}</ref> [[skin]],<ref>{{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 }}</ref> [[Genitourinary system|urogenital]],<ref>{{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 }}</ref><ref>{{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 | display-authors = 6 | 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 }}</ref><ref name=":3">{{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 }}</ref><ref>{{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 }}</ref> [[immune system]],<ref>{{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 | display-authors = 6 | 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 }}</ref> and more.


== Function ==
== Function ==


This gene product belongs to the family of candidate [[taste receptor]]s 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.<ref name="pmid15178431">{{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 = 479–85 | date = June 2004 | pmid = 15178431 | doi = 10.1016/j.bbrc.2004.05.019 }}</ref> This gene maps to the taste receptor gene cluster on chromosome 12p13.<ref name="entrez" />
This gene product belongs to the family of [[taste receptor]]s 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.<ref name="pmid15178431">{{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 }}</ref> This gene maps to the taste receptor gene cluster on chromosome 12p13.<ref name="entrez" />


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 channel]]s which [[hyperpolarization (biology)|hyperpolarize]] the membrane and cause the smooth muscle to relax. Hence, activation of these receptors leads to [[bronchodilation]].<ref name="pmid20972434">{{cite journal | vauthors = Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS, Liggett SB | display-authors = 6 | title = Bitter taste receptors on airway smooth muscle bronchodilate by localized calcium signaling and reverse obstruction | journal = Nature Medicine | volume = 16 | issue = 11 | pages = 1299–304 | date = November 2010 | pmid = 20972434 | pmc = 3066567 | doi = 10.1038/nm.2237 }}</ref>
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 channel]]s which [[hyperpolarization (biology)|hyperpolarize]] the membrane and cause the smooth muscle to relax. Hence, activation of these receptors leads to [[bronchodilation]].<ref name="pmid20972434">{{cite journal | vauthors = Deshpande DA, Wang WC, McIlmoyle EL, Robinett KS, Schillinger RM, An SS, Sham JS, Liggett SB | display-authors = 6 | 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 }}</ref>


⚫
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).<ref>{{cite journal | vauthors = Yan CH, Hahn S, McMahon D, Bonislawski D, Kennedy DW, Adappa ND, Palmer JN, Jiang P, Lee RJ, Cohen NA | display-authors = 6 | 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 }}</ref>
== Extra-oral roles of TAS2R14 ==
⚫
TAS2R14 was shown to be expressed in many tissues in the human body including the [[heart]],<ref>{{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 | display-authors = 6 | 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 | bibcode = 2013PLoSO...864579F | doi-access = free }}</ref> [[thyroid]],<ref>{{cite journal | vauthors = Clark AA, Dotson CD, Elson AE, Voigt A, Boehm U, Meyerhof W, Steinle NI, Munger SD | display-authors = 6 | title = TAS2R bitter taste receptors regulate thyroid function | journal = FASEB Journal | volume = 29 | issue = 1 | pages = 164–72 | date = January 2015 | pmid = 25342133 | pmc = 4285546 | doi = 10.1096/fj.14-262246 }}</ref> [[stomach]],<ref>{{Cite journal|last1=Liszt|first1=Kathrin Ingrid|last2=Ley|first2=Jakob Peter|last3=Lieder|first3=Barbara|last4=Behrens|first4=Maik|last5=Stöger|first5=Verena|last6=Reiner|first6=Angelika|last7=Hochkogler|first7=Christina Maria|last8=Köck|first8=Elke|last9=Marchiori|first9=Alessandro|last10=Hans|first10=Joachim|last11=Widder|first11=Sabine|date=2017-07-25|title=Caffeine induces gastric acid secretion via bitter taste signaling in gastric parietal cells|journal=Proceedings of the National Academy of Sciences|volume=114|issue=30|pages=E6260–E6269|doi=10.1073/pnas.1703728114|pmid=28696284|pmc=5544304|bibcode=2017PNAS..114E6260L |doi-access=free}}</ref> [[skin]],<ref>{{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 | bibcode = 2018PLoSO..1305322S | doi-access = free }}</ref> [[Genitourinary system|urogenital]],<ref>{{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 = 20650–9 | date = July 2006 | pmid = 16720576 | doi = 10.1074/jbc.M513637200 | doi-access = free }}</ref><ref>{{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 | display-authors = 6 | 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 }}</ref><ref name=":3">{{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 }}</ref><ref>{{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 | url = https://pubmed.ncbi.nlm.nih.gov/30350307/ }}</ref> [[immune system]],<ref>{{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 | display-authors = 6 | 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 }}</ref> and more.


⚫
T2R14 causes inhibition of IgE-dependent mast cells.<ref>{{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 }}</ref>
== TAS2R14 extra-oral function ==


⚫
Associations between [[Single-nucleotide polymorphism|single nucleotide polymorphisms]] in TAS214 gene and male infertility were observed.<ref name=":3" />
⚫
* 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).<ref>{{cite journal | vauthors = Yan CH, Hahn S, McMahon D, Bonislawski D, Kennedy DW, Adappa ND, Palmer JN, Jiang P, Lee RJ, Cohen NA | display-authors = 6 | 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 }}</ref>
⚫
* T2R14 causes inhibition of IgE-dependent mast cells.<ref>{{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 = 475–8 | date = August 2014 | pmid = 24755408 | doi = 10.1016/j.jaci.2014.02.029 | url = https://pubmed.ncbi.nlm.nih.gov/24755408/ }}</ref>
⚫
* Associations between [[Single-nucleotide polymorphism|single nucleotide polymorphisms]] in TAS214 gene and male infertility were observed.<ref name=":3" />


== See also ==
== See also ==
Line 188: Line 185:
== Further reading ==
== Further reading ==
{{refbegin|30em}}
{{refbegin|30em}}
* {{cite journal | vauthors = Kinnamon SC | title = A plethora of taste receptors | journal = Neuron | volume = 25 | issue = 3 | pages = 507–10 | date = March 2000 | pmid = 10774719 | doi = 10.1016/S0896-6273(00)81054-5 | doi-access = free }}
* {{cite journal | vauthors = Kinnamon SC | title = A plethora of taste receptors | journal = Neuron | volume = 25 | issue = 3 | pages = 507–510 | date = March 2000 | pmid = 10774719 | doi = 10.1016/S0896-6273(00)81054-5 | doi-access = free }}
* {{cite journal | vauthors = Margolskee RF | title = Molecular mechanisms of bitter and sweet taste transduction | journal = The Journal of Biological Chemistry | volume = 277 | issue = 1 | pages = 1–4 | date = January 2002 | pmid = 11696554 | doi = 10.1074/jbc.R100054200 | doi-access = free }}
* {{cite journal | vauthors = Margolskee RF | title = Molecular mechanisms of bitter and sweet taste transduction | journal = The Journal of Biological Chemistry | volume = 277 | issue = 1 | pages = 1–4 | date = January 2002 | pmid = 11696554 | doi = 10.1074/jbc.R100054200 | doi-access = free }}
* {{cite journal | vauthors = Montmayeur JP, Matsunami H | title = Receptors for bitter and sweet taste | journal = Current Opinion in Neurobiology | volume = 12 | issue = 4 | pages = 366–71 | date = August 2002 | pmid = 12139982 | doi = 10.1016/S0959-4388(02)00345-8 | s2cid = 37807140 }}
* {{cite journal | vauthors = Montmayeur JP, Matsunami H | title = Receptors for bitter and sweet taste | journal = Current Opinion in Neurobiology | volume = 12 | issue = 4 | pages = 366–371 | date = August 2002 | pmid = 12139982 | doi = 10.1016/S0959-4388(02)00345-8 | s2cid = 37807140 }}
* {{cite journal | vauthors = Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, Zuker CS, Ryba NJ | display-authors = 6 | title = T2Rs function as bitter taste receptors | journal = Cell | volume = 100 | issue = 6 | pages = 703–11 | date = March 2000 | pmid = 10761935 | doi = 10.1016/S0092-8674(00)80706-0 | s2cid = 7293493 | doi-access = free }}
* {{cite journal | vauthors = Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, Zuker CS, Ryba NJ | display-authors = 6 | title = T2Rs function as bitter taste receptors | journal = Cell | volume = 100 | issue = 6 | pages = 703–711 | date = March 2000 | pmid = 10761935 | doi = 10.1016/S0092-8674(00)80706-0 | s2cid = 7293493 | doi-access = free }}
* {{cite journal | vauthors = Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ | display-authors = 6 | title = Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways | journal = Cell | volume = 112 | issue = 3 | pages = 293–301 | date = February 2003 | pmid = 12581520 | doi = 10.1016/S0092-8674(03)00071-0 | s2cid = 718601 | doi-access = free }}
* {{cite journal | vauthors = Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ | display-authors = 6 | title = Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways | journal = Cell | volume = 112 | issue = 3 | pages = 293–301 | date = February 2003 | pmid = 12581520 | doi = 10.1016/S0092-8674(03)00071-0 | s2cid = 718601 | doi-access = free }}
* {{cite journal | vauthors = Fischer A, Gilad Y, Man O, Pääbo S | title = Evolution of bitter taste receptors in humans and apes | journal = Molecular Biology and Evolution | volume = 22 | issue = 3 | pages = 432–6 | date = March 2005 | pmid = 15496549 | doi = 10.1093/molbev/msi027 | doi-access = free }}
* {{cite journal | vauthors = Fischer A, Gilad Y, Man O, Pääbo S | title = Evolution of bitter taste receptors in humans and apes | journal = Molecular Biology and Evolution | volume = 22 | issue = 3 | pages = 432–436 | date = March 2005 | pmid = 15496549 | doi = 10.1093/molbev/msi027 | doi-access = free }}
* {{cite journal | vauthors = Go Y, Satta Y, Takenaka O, Takahata N | title = Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates | journal = Genetics | volume = 170 | issue = 1 | pages = 313–26 | date = May 2005 | pmid = 15744053 | pmc = 1449719 | doi = 10.1534/genetics.104.037523 }}
* {{cite journal | vauthors = Go Y, Satta Y, Takenaka O, Takahata N | title = Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates | journal = Genetics | volume = 170 | issue = 1 | pages = 313–326 | date = May 2005 | pmid = 15744053 | pmc = 1449719 | doi = 10.1534/genetics.104.037523 }}
* {{cite journal | vauthors = Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD | title = Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry | journal = Journal of Proteome Research | volume = 4 | issue = 6 | pages = 2070–80 | year = 2006 | pmid = 16335952 | pmc = 1850943 | doi = 10.1021/pr0502065 }}
* {{cite journal | vauthors = Liu T, Qian WJ, Gritsenko MA, Camp DG, Monroe ME, Moore RJ, Smith RD | title = Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry | journal = Journal of Proteome Research | volume = 4 | issue = 6 | pages = 2070–2080 | year = 2006 | pmid = 16335952 | pmc = 1850943 | doi = 10.1021/pr0502065 }}
* {{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 = 20650–9 | date = July 2006 | pmid = 16720576 | doi = 10.1074/jbc.M513637200 | doi-access = free }}
* {{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 }}
{{refend}}
{{refend}}


Revision as of 03:52, 27 May 2024

TAS2R14
Identifiers
AliasesTAS2R14, T2R14, TRB1, taste 2 receptor member 14
External IDsOMIM: 604790; MGI: 2681298; HomoloGene: 87013; GeneCards: TAS2R14; OMA:TAS2R14 - orthologs
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 MbChr 6: 133.03 – 133.03 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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

References

  1. ^ a b c ENSG00000261984, ENSG00000276541 GRCh38: Ensembl release 89: ENSG00000212127, ENSG00000261984, ENSG00000276541 – Ensembl, May 2017
  2. ^ a b c 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. ^ a b 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. ^ a b c "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 (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. 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.
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Further reading

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

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