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TAS2R16

TAS2R16
Identifiers
AliasesTAS2R16, T2R16, taste 2 receptor member 16, BGLPT
External IDsOMIM: 604867; MGI: 2681247; HomoloGene: 9660; GeneCards: TAS2R16; OMA:TAS2R16 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_016945

NM_207022

RefSeq (protein)

NP_058641

NP_996905

Location (UCSC)Chr 7: 122.99 – 123 MbChr 6: 23.97 – 23.97 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

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.

A convenient representation of the receptor sequence and its TM regions, shown here for hTAS2R16. The seven TM helices are displayed as predicted by Topcons. The most conserved residue in each helix X (BW number X.50) has black background. Residues for which mutation data are available are marked with red.
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

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000128519Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000043865Ensembl, 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 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. ^ a b c d 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. ^ a b 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.

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