TAS2R46
| TAS2R46 | |||
|---|---|---|---|
| Identifiers | |||
Gene ontology | |||
| Molecular function | |||
| Cellular component | |||
| Biological process | |||
| Sources:Amigo / QuickGO | |||
Ensembl | |||||||||
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| UniProt | |||||||||
| RefSeq (mRNA) | |||||||||
| RefSeq (protein) | |||||||||
| Location (UCSC) | Chr 12: 11.06 – 11.06 Mb | Chr 6: 132.63 – 132.63 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Taste receptors for bitter substances (T2Rs/TAS2Rs) belong to the family of
Taste receptor type 2 member 46 is a protein that in humans is encoded by the TAS2R46 gene.[6][7]
Gene
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
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 the Protein 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 in Alphafold, named Taste receptor type 2 member 46 this is a computational prediction and not an experimental structure.
Tissue distribution
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
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 famous Agatha Christie novel The Mysterious Affair at Styles.
Atropine injection is used to treat heart rate disorders of various types, and is used in drops to treat lazy eye condition.
Clinical significance
TAS2R46 was associated with Inflammatory Bowel Disease[12]
SNPs
Obtained from[9]
| Receptor | Location | BW number | Residue | MAF | dbSNP |
| TAS2R46 | IC3 | L228M | 0.3359 | rs2708380 |
Known mutations
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
- ^ a b c ENSG00000262525, ENSG00000226761 GRCh38: Ensembl release 89: ENSG00000278111, ENSG00000262525, ENSG00000226761 – Ensembl, May 2017
- ^ a b c GRCm38: 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.
- PMID 20022913.
- S2CID 20426192.
- ^ "Entrez Gene: TAS2R46 taste receptor, type 2, member 46".
- ^ a b "TAS2R46". GeneCards.
- ^ a b c d "hTAS2R46 - Taste receptor type 2 member 46". BitterDB. The Hebrew University of Jerusalem.
- S2CID 252310278.
- PMID 23520545.
- ^ "Inflammatory Bowel Disease 11 (IBD11)". MalaCards-Human disease database. Weizmann Institute of Science.
- ^ PMID 26575934.
- ^ PMID 26928553.
- ^ PMID 20534469.
- ^ PMID 28932739.
- ^ S2CID 56035188.
- ^ PMID 23741366.
Further reading
- Margolskee RF (January 2002). "Molecular mechanisms of bitter and sweet taste transduction". The Journal of Biological Chemistry. 277 (1): 1–4. PMID 11696554.
- Montmayeur JP, Matsunami H (August 2002). "Receptors for bitter and sweet taste". Current Opinion in Neurobiology. 12 (4): 366–371. S2CID 37807140.
- 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. S2CID 718601.
- 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. S2CID 1542970.
- 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. 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. PMID 15744053.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.