TAS2R46

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Lua error in Module:Infobox_gene at line 53: attempt to index field 'wikibase' (a nil value). Taste receptor type 2 member 46 is a protein that in humans is encoded by the TAS2R46 gene.[1][2]

Taste receptors for bitter substances (T2Rs/TAS2Rs) belong to the family of G-protein coupled receptors and are related to class A-like GPCRs. There are 25 known T2Rs in humans responsible for bitter taste perception.[3]

Gene

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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.[4] hTAS2R46 is a bitter receptor broadly tuned to sesquiterpene lactones, related clerodane diterpenoids, labdane diterpenes and more.

Structure

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In 2022, the solved structure of Tas2r46[5] was published in the scientific journal Science[6] 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

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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).[7]

Ligands

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Up to now, 68 ligands were identified for T2R46 and are summarized in [5]

Some of TAS2R46 ligands are approved as drugs;[4] 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.

Oligoporin D is one of the most potent agonists known for TAS2R46, and thus one of the most bitter substances known.[8]

Clinical significance

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TAS2R46 was associated with Inflammatory Bowel Disease[9]

SNPs

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Obtained from[5]

Receptor Location BW number Residue MAF dbSNP
TAS2R46 IC3 L228M 0.3359 rs2708380

Known mutations

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Known mutations of TAS2R46 include the following:[5]

Receptor Location BW number Residue References
TAS2R46 TM2 2.6 N65 [10][11]
TAS2R46 TM2 2.61 W66 [10][11][12]
TAS2R46 TM2 2.64 T69 [10][11]
TAS2R46 TM2 2.65 E70 [10][12][11][13]
TAS2R46 EC1 2.66 L71 [13][14]
TAS2R46 TM3 3.26 I82 [10][11][13]
TAS2R46 TM3 3.29 Y85 [10][11]
TAS2R46 TM3 3.3 N86 [10][11]
TAS2R46 TM3 3.32 W88 [10][11]
TAS2R46 TM3 3.33 A89 [10][12][11]
TAS2R46 TM3 3.36 N92 [10][12][11][15][13][14]
TAS2R46 TM3 3.37 H93 [10][12][11]
TAS2R46 TM3 3.4 N96 [10][12][11]
TAS2R46 TM4 4.6 I147 [10][11]
TAS2R46 EC2 4.65 N150 [13]
TAS2R46 EC2 4.76 N161 [13]
TAS2R46 TM5 5.38 S175 [10]
TAS2R46 TM5 5.39 N176 [10][12][11][13][14]
TAS2R46 TM5 5.43 T180 [10][11]
TAS2R46 TM5 5.47 N184 [10][11]
TAS2R46 TM6 6.51 Y241 [10][11][13][14]
TAS2R46 TM6 6.52 F242 [10][11][15]
TAS2R46 TM6 6.54 S244 [10][11]
TAS2R46 TM6 6.55 I245 [10][11]
TAS2R46 TM6 6.58 S248 [10][11]
TAS2R46 TM6 6.59 V249 [10][11]
TAS2R46 EC3 6.62 E253 [13]
TAS2R46 TM7 7.35 E261 [10][11][13]
TAS2R46 TM7 7.39 E265 [10][12][11][13]
TAS2R46 TM7 7.42 A268 [10][12][11][13]
TAS2R46 TM7 7.43 F269 [10][12][13]

References

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Further reading

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  • Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  • Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  • Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
  • Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).
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  • Lua error in Module:Citation/CS1/Configuration at line 2172: attempt to index field '?' (a nil value).

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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