TAS2R46

Taste receptor type 2 member 46 is a protein that in humans is encoded by the TAS2R46 gene.^[5][6]

TAS2R46
Identifiers
Aliases	TAS2R46, T2R46, T2R54, taste 2 receptor member 46
External IDs	OMIM: 612774; MGI: 2681256; HomoloGene: 135705; GeneCards: TAS2R46; OMA:TAS2R46 - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12p13.2 Start 11,061,365 bp[1] End 11,062,294 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 G1|6 64.03 cM Start 132,633,916 bp[2] End 132,634,807 bp[2]
RNA expression pattern Bgee Human Mouse (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 G protein-coupled receptor activity signal transducer activity bitter taste receptor activity Cellular component plasma membrane cell projection cilium membrane ciliary membrane integral component of membrane Biological process detection of chemical stimulus involved in sensory perception of bitter taste signal transduction response to stimulus sensory perception of taste G protein-coupled receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 6: 132.63 – 132.63 Mb PubMed search [3] [4]
Wikidata
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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.^[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.

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

Clinical significance

TAS2R46 was associated with Inflammatory Bowel Disease^[13]

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	[14][15]
TAS2R46	TM2	2.61	W66	[14][15][16]
TAS2R46	TM2	2.64	T69	[14][15]
TAS2R46	TM2	2.65	E70	[14][16][15][17]
TAS2R46	EC1	2.66	L71	[17][18]
TAS2R46	TM3	3.26	I82	[14][15][17]
TAS2R46	TM3	3.29	Y85	[14][15]
TAS2R46	TM3	3.3	N86	[14][15]
TAS2R46	TM3	3.32	W88	[14][15]
TAS2R46	TM3	3.33	A89	[14][16][15]
TAS2R46	TM3	3.36	N92	[14][16][15][19][17][18]
TAS2R46	TM3	3.37	H93	[14][16][15]
TAS2R46	TM3	3.4	N96	[14][16][15]
TAS2R46	TM4	4.6	I147	[14][15]
TAS2R46	EC2	4.65	N150	[17]
TAS2R46	EC2	4.76	N161	[17]
TAS2R46	TM5	5.38	S175	[14]
TAS2R46	TM5	5.39	N176	[14][16][15][17][18]
TAS2R46	TM5	5.43	T180	[14][15]
TAS2R46	TM5	5.47	N184	[14][15]
TAS2R46	TM6	6.51	Y241	[14][15][17][18]
TAS2R46	TM6	6.52	F242	[14][15][19]
TAS2R46	TM6	6.54	S244	[14][15]
TAS2R46	TM6	6.55	I245	[14][15]
TAS2R46	TM6	6.58	S248	[14][15]
TAS2R46	TM6	6.59	V249	[14][15]
TAS2R46	EC3	6.62	E253	[17]
TAS2R46	TM7	7.35	E261	[14][15][17]
TAS2R46	TM7	7.39	E265	[14][16][15][17]
TAS2R46	TM7	7.42	A268	[14][16][15][17]
TAS2R46	TM7	7.43	F269	[14][16][17]