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TAS2R46

From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens

TAS2R46
Identifiers
AliasesTAS2R46, T2R46, T2R54, taste 2 receptor member 46
External IDsOMIM:612774;MGI:2681256;HomoloGene:135705;GeneCards:TAS2R46;OMA:TAS2R46 - orthologs
Gene location (Human)
Chromosome 12 (human)
Chr.Chromosome 12 (human)[1]
Chromosome 12 (human)
Genomic location for TAS2R46
Genomic location for TAS2R46
Band12p13.2Start11,061,365bp[1]
End11,062,294bp[1]
Gene location (Mouse)
Chromosome 6 (mouse)
Chr.Chromosome 6 (mouse)[2]
Chromosome 6 (mouse)
Genomic location for TAS2R46
Genomic location for TAS2R46
Band6 G1|6 64.03 cMStart132,633,916bp[2]
End132,634,807bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • testicle

  • corpus callosum

  • Achilles tendon

  • tonsil

  • epithelium of colon

  • muscle of thigh

  • skeletal muscle tissue

  • cell

  • stromal cell of endometrium

  • ventricular zone
    n/a
More reference expression data
BioGPS
n/a
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo /QuickGO
Orthologs
SpeciesHumanMouse
Entrez

259292

387348

Ensembl

ENSG00000278111
ENSG00000262525
ENSG00000226761

ENSMUSG00000059382

UniProt

P59540

Q7M721

RefSeq (mRNA)

NM_176887

NM_207023

RefSeq (protein)

NP_795368

NP_996906

Location (UCSC)Chr 12: 11.06 – 11.06 MbChr 6: 132.63 – 132.63 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Taste receptor type 2 member 46 is aprotein that in humans is encoded by theTAS2R46gene.[5][6]

Taste receptors for bitter substances (T2Rs/TAS2Rs) belong to the family ofG-protein coupled receptors and are related toclass A-like GPCRs. There are 25 known T2Rs in humans responsible for bitter taste perception.[7]

Gene

[edit]

TAS2R46 gene (Taste receptor type 2 member 46) is aprotein-coding gene. This gene maps to thetaste receptorgene cluster on chromosome 12.[8] hTAS2R46 is a bitter receptor broadly tuned tosesquiterpene lactones, relatedclerodane diterpenoids,labdane diterpenes and more.

Structure

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In 2022, the solved structure of Tas2r46[9] was published in the scientific journal Science[10] making it the first Tas2r with a solved structure. The structure of Tas2r46 was solved withcryo-EM and can be downloaded in theProtein Data Bank, under the following names:

7xp6- Cryo-EM structure of a class T GPCR in active state,7xp5- Cryo-EM structure of a class T GPCR in ligand-free state,7xp4- Cryo-EM structure of a class T GPCR in apo state.

There is also a prediction structure available inAlphafold, namedTaste receptor type 2 member 46 this is a computational prediction and not an experimental structure.

Tissue distribution

[edit]

TAS2R46 was shown to be expressed in other tissues in the human body apart from the oral cavity including human bone marrow stromal-derived cells (MSC) and their relatives,vascular smooth muscle cells (VSMC).[11]

Ligands

[edit]

Up to now, 68 ligands were identified for T2R46 and are summarized in[9]

Some of TAS2R46 ligands are approved as drugs;[8] two of the more known ligands of TAS2R46 areatropine andstrychnine.

Strychnine is known as a strong poison that suppresses the nerve system. Strychnine even makes an appearance in the famousAgatha Christie novelThe Mysterious Affair at Styles.

Atropine injection is used to treat heart rate disorders of various types, and is used in drops to treatlazy eye condition.

Oligoporin D is one of the most potent agonists known for TAS2R46, and thus one of the most bitter substances known.[12]

Clinical significance

[edit]

TAS2R46 was associated withInflammatory Bowel Disease[13]

SNPs

[edit]

Obtained from[9]

ReceptorLocationBW numberResidueMAFdbSNP
TAS2R46IC3L228M0.3359rs2708380

Known mutations

[edit]

Known mutations of TAS2R46 include the following:[9]

ReceptorLocationBW numberResidueReferences
TAS2R46TM22.6N65[14][15]
TAS2R46TM22.61W66[14][15][16]
TAS2R46TM22.64T69[14][15]
TAS2R46TM22.65E70[14][16][15][17]
TAS2R46EC12.66L71[17][18]
TAS2R46TM33.26I82[14][15][17]
TAS2R46TM33.29Y85[14][15]
TAS2R46TM33.3N86[14][15]
TAS2R46TM33.32W88[14][15]
TAS2R46TM33.33A89[14][16][15]
TAS2R46TM33.36N92[14][16][15][19][17][18]
TAS2R46TM33.37H93[14][16][15]
TAS2R46TM33.4N96[14][16][15]
TAS2R46TM44.6I147[14][15]
TAS2R46EC24.65N150[17]
TAS2R46EC24.76N161[17]
TAS2R46TM55.38S175[14]
TAS2R46TM55.39N176[14][16][15][17][18]
TAS2R46TM55.43T180[14][15]
TAS2R46TM55.47N184[14][15]
TAS2R46TM66.51Y241[14][15][17][18]
TAS2R46TM66.52F242[14][15][19]
TAS2R46TM66.54S244[14][15]
TAS2R46TM66.55I245[14][15]
TAS2R46TM66.58S248[14][15]
TAS2R46TM66.59V249[14][15]
TAS2R46EC36.62E253[17]
TAS2R46TM77.35E261[14][15][17]
TAS2R46TM77.39E265[14][16][15][17]
TAS2R46TM77.42A268[14][16][15][17]
TAS2R46TM77.43F269[14][16][17]

References

[edit]
  1. ^abcENSG00000262525, ENSG00000226761 GRCh38: Ensembl release 89: ENSG00000278111, ENSG00000262525, ENSG00000226761 –Ensembl, May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000059382 –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. ^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.
  6. ^"Entrez Gene: TAS2R46 taste receptor, type 2, member 46".
  7. ^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.
  8. ^ab"TAS2R46".GeneCards.
  9. ^abcd"hTAS2R46 - Taste receptor type 2 member 46".BitterDB. The Hebrew University of Jerusalem.
  10. ^Xu W, Wu L, Liu S, Liu X, Cao X, Zhou C, et al. (September 2022). "Structural basis for strychnine activation of human bitter taste receptor TAS2R46".Science.377 (6612):1298–1304.Bibcode:2022Sci...377.1298X.doi:10.1126/science.abo1633.PMID 36108005.S2CID 252310278. (This paper currently has anexpression of concern, seedoi:10.1126/science.adf8367, PMID 36413140,  Retraction Watch. If this is an intentional citation to a such a paper, please replace{{expression of concern|...}} with{{expression of concern|...|intentional=yes}}.)
  11. ^Lund TC, Kobs AJ, Kramer A, Nyquist M, Kuroki MT, Osborn J, et al. (2013)."Bone marrow stromal and vascular smooth muscle cells have chemosensory capacity via bitter taste receptor expression".PLOS ONE.8 (3) e58945.Bibcode:2013PLoSO...858945L.doi:10.1371/journal.pone.0058945.PMC 3592821.PMID 23520545.
  12. ^Schmitz LM, Lang T, Steuer A, Koppelmann L, Di Pizio A, Arnold N, Behrens M (Feb 2025)."Taste-Guided Isolation of Bitter Compounds from the Mushroom Amaropostia stiptica Activates a Subset of Human Bitter Taste Receptors".J Agric Food Chem.73 (8):4850–4858.doi:10.1021/acs.jafc.4c12651.PMC 11869282.PMID 39945763.
  13. ^"Inflammatory Bowel Disease 11 (IBD11)".MalaCards-Human disease database. Weizmann Institute of Science.
  14. ^abcdefghijklmnopqrstuvwxyzaaSandal M, Behrens M, Brockhoff A, Musiani F, Giorgetti A, Carloni P, Meyerhof W (September 2015). "Evidence for a Transient Additional Ligand Binding Site in the TAS2R46 Bitter Taste Receptor".Journal of Chemical Theory and Computation.11 (9):4439–4449.doi:10.1021/acs.jctc.5b00472.PMID 26575934.
  15. ^abcdefghijklmnopqrstuvwxyDi Pizio A, Levit A, Slutzki M, Behrens M, Karaman R, Niv MY (2016). "Comparing Class a GPCRS to bitter taste receptors".G Protein-Coupled Receptors - Signaling, Trafficking and Regulation. Methods in Cell Biology. Vol. 132. pp. 401–427.doi:10.1016/bs.mcb.2015.10.005.ISBN 978-0-12-803595-5.PMID 26928553.
  16. ^abcdefghijBrockhoff A, Behrens M, Niv MY, Meyerhof W (June 2010)."Structural requirements of bitter taste receptor activation".Proceedings of the National Academy of Sciences of the United States of America.107 (24):11110–11115.Bibcode:2010PNAS..10711110B.doi:10.1073/pnas.0913862107.PMC 2890741.PMID 20534469.
  17. ^abcdefghijklmFierro F, Suku E, Alfonso-Prieto M, Giorgetti A, Cichon S, Carloni P (2017)."Agonist Binding to Chemosensory Receptors: A Systematic Bioinformatics Analysis".Frontiers in Molecular Biosciences.4: 63.doi:10.3389/fmolb.2017.00063.PMC 5592726.PMID 28932739.
  18. ^abcdSuku E, Fierro F, Giorgetti A, Alfonso-Prieto M, Carloni P (March 2017)."Multi-scale simulations of membrane proteins: the case of bitter taste receptors".Journal of Science: Advanced Materials and Devices.2 (1):15–21.doi:10.1016/j.jsamd.2017.03.001.S2CID 56035188.
  19. ^abMarchiori A, Capece L, Giorgetti A, Gasparini P, Behrens M, Carloni P, Meyerhof W (2013)."Coarse-grained/molecular mechanics of the TAS2R38 bitter taste receptor: experimentally-validated detailed structural prediction of agonist binding".PLOS ONE.8 (5) e64675.Bibcode:2013PLoSO...864675M.doi:10.1371/journal.pone.0064675.PMC 3669430.PMID 23741366.

Further reading

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This article incorporates text from theUnited States National Library of Medicine, which is in thepublic domain.

Neurotransmitter
Adrenergic
Purinergic
Serotonin
Other
Metabolites and
signaling molecules
Eicosanoid
Other
Peptide
Neuropeptide
Other
Miscellaneous
Taste, bitter
Orphan
Other
Adhesion
Orphan
Other
Taste, sweet
Other
Frizzled
Smoothened
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