TAS2R14

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

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
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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] TAS2R14 agonist 28.1 is one of the most potent agonists yet developed for this target.^[17] 

Tissue distribution

In addition to the tongue, TAS2R14 is expressed in many other tissues including the heart,^[18] thyroid,^[19] stomach,^[20] skin,^[21] urogenital,^{[22][23][24][25]} immune system,^[26] 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.^[27] 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.^[28]

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).^[29]

T2R14 causes inhibition of IgE-dependent mast cells.^[30]

Associations between single nucleotide polymorphisms in TAS214 gene and male infertility were observed.^[24]

See also

• Taste receptor