TAS2R46
TAS2R46 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | TAS2R46,T2R46, T2R54, taste 2 receptor member 46 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM:612774;MGI:2681256;HomoloGene:135705;GeneCards:TAS2R46;OMA:TAS2R46 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Taste receptors for bitter substances (T2Rs/TAS2Rs) belong to the family ofG-protein coupled receptorsand are related toclass A-like GPCRs. There are 25 known T2Rs in humans responsible for bitter taste perception.[5]
Taste receptor type 2 member 46is aproteinthat in humans is encoded by theTAS2R46gene.[6][7]
Gene
[edit]TAS2R46 gene (Taste receptor type 2 member 46) is a Protein Coding gene. This gene maps to the taste receptor gene cluster on chromosome 12.[8]hTAS2R46 is a bitter receptor broadly tuned to sesquiterpene lactones, related clerodane diterpenoids,labdane diterpenes and more.
Structure
[edit]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 with cryo-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 46this 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 are Atropine and Strychnine.
Strychnine is known as a strong poison that suppresses the nerve system. Strychnine even makes an appearance in the famousAgathaChristienovelThe Mysterious Affair at Styles.
Atropine injection is used to treat heart rate disorders of various types, and is used in drops to treatlazy eyecondition.
Clinical significance
[edit]TAS2R46 was associated withInflammatory Bowel Disease[12]
SNPs
[edit]Obtained from[9]
Receptor | Location | BW number | Residue | MAF | dbSNP |
TAS2R46 | IC3 | L228M | 0.3359 | rs2708380 |
Known mutations
[edit]Known mutations of TAS2R46 include the following:[9]
Receptor | Location | BW number | Residue | References |
TAS2R46 | TM2 | 2.6 | N65 | [13][14] |
TAS2R46 | TM2 | 2.61 | W66 | [13][14][15] |
TAS2R46 | TM2 | 2.64 | T69 | [13][14] |
TAS2R46 | TM2 | 2.65 | E70 | [13][15][14][16] |
TAS2R46 | EC1 | 2.66 | L71 | [16][17] |
TAS2R46 | TM3 | 3.26 | I82 | [13][14][16] |
TAS2R46 | TM3 | 3.29 | Y85 | [13][14] |
TAS2R46 | TM3 | 3.3 | N86 | [13][14] |
TAS2R46 | TM3 | 3.32 | W88 | [13][14] |
TAS2R46 | TM3 | 3.33 | A89 | [13][15][14] |
TAS2R46 | TM3 | 3.36 | N92 | [13][15][14][18][16][17] |
TAS2R46 | TM3 | 3.37 | H93 | [13][15][14] |
TAS2R46 | TM3 | 3.4 | N96 | [13][15][14] |
TAS2R46 | TM4 | 4.6 | I147 | [13][14] |
TAS2R46 | EC2 | 4.65 | N150 | [16] |
TAS2R46 | EC2 | 4.76 | N161 | [16] |
TAS2R46 | TM5 | 5.38 | S175 | [13] |
TAS2R46 | TM5 | 5.39 | N176 | [13][15][14][16][17] |
TAS2R46 | TM5 | 5.43 | T180 | [13][14] |
TAS2R46 | TM5 | 5.47 | N184 | [13][14] |
TAS2R46 | TM6 | 6.51 | Y241 | [13][14][16][17] |
TAS2R46 | TM6 | 6.52 | F242 | [13][14][18] |
TAS2R46 | TM6 | 6.54 | S244 | [13][14] |
TAS2R46 | TM6 | 6.55 | I245 | [13][14] |
TAS2R46 | TM6 | 6.58 | S248 | [13][14] |
TAS2R46 | TM6 | 6.59 | V249 | [13][14] |
TAS2R46 | EC3 | 6.62 | E253 | [16] |
TAS2R46 | TM7 | 7.35 | E261 | [13][14][16] |
TAS2R46 | TM7 | 7.39 | E265 | [13][15][14][16] |
TAS2R46 | TM7 | 7.42 | A268 | [13][15][14][16] |
TAS2R46 | TM7 | 7.43 | F269 | [13][15][16] |
References
[edit]- ^abcENSG00000262525, ENSG00000226761 GRCh38: Ensembl release 89: ENSG00000278111, ENSG00000262525, ENSG00000226761–Ensembl,May 2017
- ^abcGRCm38: Ensembl release 89: ENSMUSG00000059382–Ensembl,May 2017
- ^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^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.PMID20022913.
- ^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.PMID12379855.S2CID20426192.
- ^"Entrez Gene: TAS2R46 taste receptor, type 2, member 46".
- ^ab"TAS2R46".GeneCards.
- ^abcd"hTAS2R46 - Taste receptor type 2 member 46".BitterDB.The Hebrew University of Jerusalem.
- ^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.PMID36108005.S2CID252310278.(This paper currently has anexpression of concern,seedoi:10.1126/science.adf8367,PMID36413140,Retraction Watch )
- ^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.PMC3592821.PMID23520545.
- ^"Inflammatory Bowel Disease 11 (IBD11)".MalaCards-Human disease database.Weizmann Institute of Science.
- ^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.PMID26575934.
- ^abcdefghijklmnopqrstuvwxyDi Pizio A, Levit A, Slutzki M, Behrens M, Karaman R, Niv MY (2016).Comparing Class A GPCRs to bitter taste receptors: Structural motifs, ligand interactions and agonist-to-antagonist ratios.Methods in Cell Biology. Vol. 132. pp. 401–427.doi:10.1016/bs.mcb.2015.10.005.PMID26928553.
- ^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.PMC2890741.PMID20534469.
- ^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.PMC5592726.PMID28932739.
- ^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.S2CID56035188.
- ^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.PMC3669430.PMID23741366.
Further reading
[edit]- 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.PMID11696554.
- 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.PMID12139982.S2CID37807140.
- 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.PMID12581520.S2CID718601.
- Conte C, Ebeling M, Marcuz A, Nef P, Andres-Barquin PJ (2003). "Identification and characterization of human taste receptor genes belonging to the TAS2R family".Cytogenetic and Genome Research.98(1): 45–53.doi:10.1159/000068546.PMID12584440.S2CID1542970.
- 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.PMID15496549.
- 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.PMC1449719.PMID15744053.
This article incorporates text from theUnited States National Library of Medicine,which is in thepublic domain.