TAS2R46

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)
End	11,062,294 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	132,634,807 bp
RNA expression pattern
	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
	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
	259292
	387348
	ENSG00000278111; ENSG00000262525; ENSG00000226761
	ENSMUSG00000059382
	P59540
	Q7M721
	NM_176887
	NM_207023
	NP_795368
	NP_996906
	Wikidata
View/Edit Human	View/Edit Mouse

Taste receptor type 2 member 46 is a protein that in humans is encoded by the TAS2R46 gene.⁵⁶

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 Tas2r46⁹ was published in the scientific journal Science¹⁰ 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 Disease¹³

SNPs

Obtained from⁹


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	¹⁴¹⁵
TAS2R46	TM2	2.61	W66	¹⁴¹⁵¹⁶
TAS2R46	TM2	2.64	T69	¹⁴¹⁵
TAS2R46	TM2	2.65	E70	¹⁴¹⁶¹⁵¹⁷
TAS2R46	EC1	2.66	L71	¹⁷¹⁸
TAS2R46	TM3	3.26	I82	¹⁴¹⁵¹⁷
TAS2R46	TM3	3.29	Y85	¹⁴¹⁵
TAS2R46	TM3	3.3	N86	¹⁴¹⁵
TAS2R46	TM3	3.32	W88	¹⁴¹⁵
TAS2R46	TM3	3.33	A89	¹⁴¹⁶¹⁵
TAS2R46	TM3	3.36	N92	¹⁴¹⁶¹⁵¹⁹¹⁷¹⁸
TAS2R46	TM3	3.37	H93	¹⁴¹⁶¹⁵
TAS2R46	TM3	3.4	N96	¹⁴¹⁶¹⁵
TAS2R46	TM4	4.6	I147	¹⁴¹⁵
TAS2R46	EC2	4.65	N150	¹⁷
TAS2R46	EC2	4.76	N161	¹⁷
TAS2R46	TM5	5.38	S175	¹⁴
TAS2R46	TM5	5.39	N176	¹⁴¹⁶¹⁵¹⁷¹⁸
TAS2R46	TM5	5.43	T180	¹⁴¹⁵
TAS2R46	TM5	5.47	N184	¹⁴¹⁵
TAS2R46	TM6	6.51	Y241	¹⁴¹⁵¹⁷¹⁸
TAS2R46	TM6	6.52	F242	¹⁴¹⁵¹⁹
TAS2R46	TM6	6.54	S244	¹⁴¹⁵
TAS2R46	TM6	6.55	I245	¹⁴¹⁵
TAS2R46	TM6	6.58	S248	¹⁴¹⁵
TAS2R46	TM6	6.59	V249	¹⁴¹⁵
TAS2R46	EC3	6.62	E253	¹⁷
TAS2R46	TM7	7.35	E261	¹⁴¹⁵¹⁷
TAS2R46	TM7	7.39	E265	¹⁴¹⁶¹⁵¹⁷
TAS2R46	TM7	7.42	A268	¹⁴¹⁶¹⁵¹⁷
TAS2R46	TM7	7.43	F269	¹⁴¹⁶¹⁷

References

ENSG00000262525, ENSG00000226761 GRCh38: Ensembl release 89: ENSG00000278111, ENSG00000262525, ENSG00000226761 – Ensembl, May 2017
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.
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. PMID 12379855. S2CID 20426192.
"Entrez Gene: TAS2R46 taste receptor, type 2, member 46".
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. PMID 20022913.
"TAS2R46". GeneCards.
"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. PMID 36108005. S2CID 252310278. (This paper currently has an expression of concern, see doi:10.1126/science.adf8367, PMID 36413140, 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. PMC 3592821. PMID 23520545.
Schmitz LM, Lang T, Steuer A, Koppelmann L, Di Pizio A, Arnold N, Behrens M (Feb 2025). "Taste-Guided Isolation of Bitter Compounds from the Mushroom Amaropostia stiptica Activates a Subset of Human Bitter Taste Receptors". J Agric Food Chem. 73 (8): 4850–4858. doi:10.1021/acs.jafc.4c12651. PMC 11869282. PMID 39945763.
"Inflammatory Bowel Disease 11 (IBD11)". MalaCards-Human disease database. Weizmann Institute of Science.
Sandal 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. PMID 26575934.
Di Pizio A, Levit A, Slutzki M, Behrens M, Karaman R, Niv MY (2016). "Comparing Class a GPCRS to bitter taste receptors". G Protein-Coupled Receptors - Signaling, Trafficking and Regulation. Methods in Cell Biology. Vol. 132. pp. 401–427. doi:10.1016/bs.mcb.2015.10.005. ISBN 978-0-12-803595-5. PMID 26928553.
Brockhoff 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. PMC 2890741. PMID 20534469.
Fierro 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. PMC 5592726. PMID 28932739.
Suku 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. S2CID 56035188.
Marchiori 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. PMC 3669430. PMID 23741366.