TAS2R46

Taste receptor type 2 member 46 is a protein that in humans is encoded by the TAS2R46 gene.
Taste receptors for bitter substances 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.

Gene

TAS2R46 gene is a protein-coding gene. This gene maps to the taste receptor gene cluster on chromosome 12. 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 was published in the scientific journal Science 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:
- Cryo-EM structure of a class T GPCR in active state,- Cryo-EM structure of a class T GPCR in ligand-free state,- Cryo-EM structure of a class T GPCR in apo state.
There is also a prediction structure available in Alphafold, named 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 and their relatives, vascular smooth muscle cells.

Ligands

Up to now, 68 ligands were identified for T2R46 and are summarized in
Some of TAS2R46 ligands are approved as drugs; 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.

Clinical significance

TAS2R46 was associated with Inflammatory Bowel Disease

SNPs

Obtained from

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

Known mutations

Known mutations of TAS2R46 include the following:

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