TAS2R16

TAS2R16 (taste receptor, type 2, member 16) 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.^[5] TAS2R16 is activated by bitter β-glucopyranosides (such as salicin)^[6]

TAS2R16
Identifiers
Aliases	TAS2R16, T2R16, taste 2 receptor member 16, BGLPT
External IDs	OMIM: 604867; MGI: 2681247; HomoloGene: 9660; GeneCards: TAS2R16; OMA:TAS2R16 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7q31.32|7q31 Start 122,994,704 bp[1] End 122,995,700 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6|6 A3.1 Start 23,969,160 bp[2] End 23,970,059 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in tibialis anterior muscle gonad deltoid muscle hypothalamus n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity protein binding signal transducer activity bitter taste receptor activity Cellular component trans-Golgi network plasma membrane endoplasmic reticulum external side of 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 50833 387347 Ensembl ENSG00000128519 ENSMUSG00000043865 UniProt Q9NYV7 P59529 RefSeq (mRNA) NM_016945 NM_207022 RefSeq (protein) NP_058641 NP_996905 Location (UCSC) Chr 7: 122.99 – 123 Mb Chr 6: 23.97 – 23.97 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Other names

T2R16, Taste receptor 2 member 16, BGLPT.

Gene

The receptor is encoded by the TAS2R16 human gene which located on the long (q) arm of chromosome 7 at position 31.1-31.3, 997 bases.^[7][8] This gene is specifically expressed by taste receptor cells of the tongue and palate epithelia. Different individuals may have variations in the TAS2R16 gene, which can influence their sensitivity or preference for certain bitter compounds.

2D transmembrane protein diagram

Structure

TAS2R16 consists of 291 amino acids. Molecular weight: 33,986 (Da). The receptor has 7 transmembrane helices, 3 intracellular loops and 3 extracellular loops. there are some conserved residues (black) and residues for which mutagenesis data is available.^[9]

Function

The function of TAS2R16 is to bind to specific bitter-tasting molecules present in various foods, plants, and potentially harmful substances. When binding to these molecules, TAS2R16 initiates a signaling cascade that leads to the transmission of signals to the brain, which results in the perception of bitterness. TAS2R16 specifically is believed to play a central role in determining human preference to eat or avoid such vegetables with bitter β-glucosides, important dietary choices that ultimately influence human health.^[10]

The signaling pathway includes two essential components of the well-established taste signal transduction cascade: phospholipase C isoform β2 (PLCβ2) and the ion channel known as transient receptor potential cation channel subfamily M member 5 (TRPM5).^[11] Ca2+-flux signaling assays are commonly used to measure the function of TAS2R16 and other GPCRs, so this measurement represents the key function of the receptor.^[10]

Ligands (from BitterDB)

There are 13 known ligands for TAS2R16.^[12]

Diphenidol (synthetic)	D-salicin, Salicin
Sodium Benzoate (synthetic)	Phenyl beta -D-glucopyranoside
Amygdalin, D	Esculine Aesculin
Arbutin	2-Naphthyl beta-D-glucopyranoside
Helicin	Methyl beta-D-glucoside
sinigrin	2-nitro phenyl beta -D-glucopyranoside

The most well-studied natural ligand of TAS2R16 is salicin. In previous researches which analyzed how this receptor binds and signals, 38 residues that may be involved in signal transduction and 13 residues that contribute to ligand-specific interactions, were found to be involved.^[10]

β-glucoside analogues are specific agonists of TAS2R16 in humans. These analogues, such as natural toxins, are molecular scafold consists of a D-glucose monosaccharide linked by an oxygen atom to a phenyl group. Arbutin was the first known natural inverse agonist for TAS2Rs.^[5]

Many plants, including cruciferous vegetables such as broccoli and brussels sprouts, contain bitter β-glucosides such as salicin, sinigrin, arbutin, and amygdalin.^[10]

Single nucleotide polymorphisms

Taste receptors harbor many polymorphisms, and several SNPs have a profound impact on the gene function and expression.^[13]

Alleles	SNP ID
A > C, G	rs846664
C > T	rs860170
C > G, T	rs1204014
T > C, G	rs978739
A > C, T	rs846672
G > A, C, T	rs1308724

Recently studies have shown that mutation of the TAS2R16 gene could affect the intake of vegetables and anti-inflammatory food, which would influence age-related inflammatory diseases and increase the human lifespan. In addition, polymorphism of the TAS2R16 gene seems to affect body mass index, alcohol intake, smoking and drug compliance. Many bitter natural foods have the function of heat-clearing, detoxifying, anti-inflammatory, and antibacterial effects.^[14]

Alcohol dependence

Alcohol intake habits may be affected by the genetic diversity of taste preferences.^[13] Alcohol dependence is significantly associated with the coding single-nucleotide polymorphism (cSNP) K172N in the gene hTAS2R16, which codes for a taste receptor for bitter b-glucopyranosides.This gene is found on chromosome 7q in a region that has been linked to alcoholism in some studies.The risk of alcohol use is higher in people with the ancestral gene K172. Individuals with this allele are at increased risk of alcohol dependence, regardless of ethnicity. However, this risk allele is rare in European Americans, but 45% of African Americans carry the allele, makes it a much more significant risk factor in the African American population.^[15]

Longevity

In a population of 941 individuals ranging from 60 to 106 years of age from the South of Italy, five significant associations between the SNPs in the chromosome 7 cluster and longevity was found, Three of them – observed in TAS2R16. SNP rs978739 showed a statistically significant association with longevity. The frequency of homozygotes A/A increases gradually from 35% in the subjects aged 20 to 70 up to 55% in centenarians.^[16]

See also

• Taste receptor

References

1. GRCh38: Ensembl release 89: ENSG00000128519 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000043865 – 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. Itoigawa A, Hayakawa T, Suzuki-Hashido N, Imai H (June 2019). "A natural point mutation in the bitter taste receptor TAS2R16 causes inverse agonism of arbutin in lemur gustation". Proceedings. Biological Sciences. 286 (1904): 20190884. doi:10.1098/rspb.2019.0884. PMC 6571456. PMID 31161904.
6. Bufe B, Hofmann T, Krautwurst D, Raguse JD, Meyerhof W (November 2002). "The human TAS2R16 receptor mediates bitter taste in response to beta-glucopyranosides". Nature Genetics. 32 (3): 397–401. doi:10.1038/ng1014. PMID 12379855. S2CID 20426192.
7. GeneCards. "TAS2R16 Gene : Taste 2 Receptor Member 16".
8. BitterDB. "hTAS2R16 - Taste receptor type 2 member 16".
9. 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.
10. Thomas A, Sulli C, Davidson E, Berdougo E, Phillips M, Puffer BA, et al. (August 2017). "The Bitter Taste Receptor TAS2R16 Achieves High Specificity and Accommodates Diverse Glycoside Ligands by using a Two-faced Binding Pocket". Scientific Reports. 7 (1): 7753. Bibcode:2017NatSR...7.7753T. doi:10.1038/s41598-017-07256-y. PMC 5552880. PMID 28798468.
11. Jeruzal-Świątecka J, Fendler W, Pietruszewska W (July 2020). "Clinical Role of Extraoral Bitter Taste Receptors". International Journal of Molecular Sciences. 21 (14): 5156. doi:10.3390/ijms21145156. PMC 7404188. PMID 32708215.
12. "hTAS2R16 - Taste receptor type 2 member 16".
13. Kurshed AA, Ádány R, Diószegi J (December 2022). "The Impact of Taste Preference-Related Gene Polymorphisms on Alcohol Consumption Behavior: A Systematic Review". International Journal of Molecular Sciences. 23 (24): 15989. doi:10.3390/ijms232415989. PMC 9783388. PMID 36555636.
14. Yuan G, Yan H, Liu Y, Ding X, Qi X, Qu K, et al. (January 2022). "TAS2R16 introgression from banteng into indigenous Chinese cattle". Animal Biotechnology. 34 (4): 1681–1685. doi:10.1080/10495398.2021.2018334. PMID 34974802. S2CID 245645868.
15. Hinrichs AL, Wang JC, Bufe B, Kwon JM, Budde J, Allen R, et al. (January 2006). "Functional variant in a bitter-taste receptor (hTAS2R16) influences risk of alcohol dependence". American Journal of Human Genetics. 78 (1): 103–111. doi:10.1086/499253. PMC 1380207. PMID 16385453.
16. Campa D, De Rango F, Carrai M, Crocco P, Montesanto A, Canzian F, et al. (2012-11-02). Glendinning JI (ed.). "Bitter taste receptor polymorphisms and human aging". PLOS ONE. 7 (11): e45232. Bibcode:2012PLoSO...745232C. doi:10.1371/journal.pone.0045232. PMC 3487725. PMID 23133589.

Further reading

• Kinnamon SC (March 2000). "A plethora of taste receptors". Neuron. 25 (3): 507–510. doi:10.1016/S0896-6273(00)81054-5. PMID 10774719.
• Margolskee RF (January 2002). "Molecular mechanisms of bitter and sweet taste transduction". The Journal of Biological Chemistry. 277 (1): 1–4. doi:10.1074/jbc.R100054200. PMID 11696554.
• Montmayeur JP, Matsunami H (August 2002). "Receptors for bitter and sweet taste". Current Opinion in Neurobiology. 12 (4): 366–371. doi:10.1016/S0959-4388(02)00345-8. PMID 12139982. S2CID 37807140.
• 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.
• Chandrashekar J, Mueller KL, Hoon MA, Adler E, Feng L, Guo W, et al. (March 2000). "T2Rs function as bitter taste receptors". Cell. 100 (6): 703–711. doi:10.1016/S0092-8674(00)80706-0. PMID 10761935. S2CID 7293493.
• Firestein S (April 2000). "The good taste of genomics". Nature. 404 (6778): 552–553. doi:10.1038/35007167. PMID 10766221. S2CID 35741332.
• 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.
• Bufe B, Hofmann T, Krautwurst D, Raguse JD, Meyerhof W (November 2002). "The human TAS2R16 receptor mediates bitter taste in response to beta-glucopyranosides". Nature Genetics. 32 (3): 397–401. doi:10.1038/ng1014. PMID 12379855. S2CID 20426192.
• Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, et al. (February 2003). "Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways". Cell. 112 (3): 293–301. doi:10.1016/S0092-8674(03)00071-0. PMID 12581520. S2CID 718601.
• Fischer A, Gilad Y, Man O, Pääbo S (March 2005). "Evolution of bitter taste receptors in humans and apes". Molecular Biology and Evolution. 22 (3): 432–436. doi:10.1093/molbev/msi027. PMID 15496549.
• Go Y, Satta Y, Takenaka O, Takahata N (May 2005). "Lineage-specific loss of function of bitter taste receptor genes in humans and nonhuman primates". Genetics. 170 (1): 313–326. doi:10.1534/genetics.104.037523. PMC 1449719. PMID 15744053.
• Mueller KL, Hoon MA, Erlenbach I, Chandrashekar J, Zuker CS, Ryba NJ (March 2005). "The receptors and coding logic for bitter taste". Nature. 434 (7030): 225–229. Bibcode:2005Natur.434..225M. doi:10.1038/nature03352. PMID 15759003. S2CID 4383273.
• Hinrichs AL, Wang JC, Bufe B, Kwon JM, Budde J, Allen R, et al. (January 2006). "Functional variant in a bitter-taste receptor (hTAS2R16) influences risk of alcohol dependence". American Journal of Human Genetics. 78 (1): 103–111. doi:10.1086/499253. PMC 1380207. PMID 16385453.
• 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.

External links

• GeneCard for TAS2R16

• TAS2R16+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)