{{Short description|Protein-coding gene in humans}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox gene}} '''T1R2 - Taste receptor type 1 member 2''' is a protein that in humans is encoded by the ''TAS1R2'' gene.<ref name="entrez">{{cite web | title = Entrez Gene: TAS1R2 taste receptor, type 1, member 2 | url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=80834 }}</ref>
The sweet taste receptor is predominantly formed as a heterodimer of T1R2 and T1R3 by which different organisms sense this taste. The mammalian sweet taste receptor was first characterized by Charles Zuker lab in 2001.<ref>{{Cite journal | vauthors = Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS | title = Mammalian Sweet Taste Receptors | journal = Cell | volume = 106 | issue = 3 | pages = 381–390 | date = 2001-08-10 | pmid = 11509186 | doi = 10.1016/S0092-8674(01)00451-2 | doi-access = free }}</ref>
Some animals do not have the T1R2 monomer, such is the case for songbirds; in their case, sweetness is perceived through the umami taste receptor (T1R1 and T1R3).<ref>{{cite journal | vauthors = Toda Y, Ko MC, Liang Q, Miller ET, Rico-Guevara A, Nakagita T, Sakakibara A, Uemura K, Sackton T, Hayakawa T, Sin SY, Ishimaru Y, Misaka T, Oteiza P, Crall J, Edwards SV, Buttemer W, Matsumura S, Baldwin MW | title = Early origin of sweet perception in the songbird radiation | journal = Science | location = New York, N.Y. | volume = 373 | issue = 6551 | pages = 226–231 | date = July 2021 | pmid = 34244416 | doi = 10.1126/science.abf6505 | s2cid = 235769720 | bibcode = 2021Sci...373..226T }}</ref>
== Gene ==
In humans, the TAS1R2 gene is located on chromosome 1 at band p36.13 (coordinates 18,839,599–18,859,660 on the reverse strand, GRCh38), and encodes a class C G protein-coupled receptor involved in sweet taste perception.<ref name="entrez" /> The gene spans six exons and produces a protein of 839 amino acids that forms a functional heterodimer with TAS1R3 to detect sweet compounds.<ref name = "GeneCards">{{cite web | url = https://www.genecards.org/cgi-bin/carddisp.pl?gene=TAS1R2&search=tas1r2 | title = TAS1R2 Gene | work = GeneCards }}</ref> Its regulatory region contains multiple promoters and transcription factor binding sites, supporting tissue-specific gene expression.<ref name="Mainland_2009">{{cite journal | vauthors = Mainland JD, Matsunami H | title = Taste perception: how sweet it is (to be transcribed by you) | journal = Current Biology | volume = 19 | issue = 15 | pages = R655–6 | date = August 2009 | pmid = 19674550 | pmc = 2877383 | doi = 10.1016/j.cub.2009.06.050 | bibcode = 2009CBio...19.R655M }}</ref> Genetic variation in TAS1R2 has been linked to differences in sweet taste sensitivity, sugar intake, and metabolic traits.<ref name="Dias_2015">{{cite journal | vauthors = Dias AG, Eny KM, Cockburn M, Chiu W, Nielsen DE, Duizer L, El-Sohemy A | title = Variation in the TAS1R2 Gene, Sweet Taste Perception and Intake of Sugars | journal = Journal of Nutrigenetics and Nutrigenomics | volume = 8 | issue = 2 | pages = 81–90 | date = 2015 | pmid = 26279452 | doi = 10.1159/000430886 | doi-access = free }}</ref>
== Tissue distribution ==
T1R2+3 expressing cells are found in circumvallate papillae and foliate papillae near the back of the tongue and palate taste receptor cells in the roof of the mouth.<ref name="Nelson_2001" /> These cells are shown to synapse upon the chorda tympani and glossopharyngeal nerves to send their signals to the brain.<ref name="Beamis_1989">{{cite journal | vauthors = Beamis JF, Shapshay SM, Setzer S, Dumon JF | title = Teaching models for Nd:YAG laser bronchoscopy | journal = Chest | volume = 95 | issue = 6 | pages = 1316–1318 | date = June 1989 | pmid = 2721271 | doi = 10.1378/chest.95.6.1316 | doi-access = free }}</ref><ref name="Danilova_2003">{{cite journal | vauthors = Danilova V, Hellekant G | title = Comparison of the responses of the chorda tympani and glossopharyngeal nerves to taste stimuli in C57BL/6J mice | journal = BMC Neuroscience | volume = 4 | article-number = 5 | date = March 2003 | pmid = 12617752 | pmc = 153500 | doi = 10.1186/1471-2202-4-5 | doi-access = free }}</ref> T1R and T2R (bitter) channels are not expressed together in taste buds.<ref name="Nelson_2001" />
== Structure ==
The TAS1R2 protein is a member of the class C G protein-coupled receptor (GPCR) family and plays a critical role in sweet taste perception as part of the TAS1R2/TAS1R3 heterodimer. Structurally, TAS1R2 features a large extracellular N-terminal domain known as the venus flytrap domain (VFD), which is responsible for binding a wide range of sweet-tasting compounds, including natural sugars and high-potency sweeteners. This VFD is connected to a seven-transmembrane domain (TMD) by a cysteine-rich domain (CRD), forming the canonical architecture of class C GPCRs. The TMD itself consists of seven alpha-helical segments that span the cell membrane and are involved in signal transduction. The integrity of the structure is further stabilized by multiple disulfide bridges within the VFD, CRD, and between domains.<ref name="Kim_2024">{{cite journal | vauthors = Kim SK, Guthrie B, Goddard WA | title = Ligand-Dependent and G Protein-Dependent Properties for the Sweet Taste Heterodimer, TAS1R2/1R3 | journal = The Journal of Physical Chemistry B | volume = 128 | issue = 37 | pages = 8927–8932 | date = September 2024 | pmid = 39231438 | pmc = 11421092 | doi = 10.1021/acs.jpcb.4c04610 }}</ref> The overall architecture allows for ligand-induced conformational changes that are transmitted from the VFD through the CRD to the TMD, ultimately leading to G protein activation and downstream signaling.<ref name="Kim_2017">{{cite journal | vauthors = Kim SK, Chen Y, Abrol R, Goddard WA, Guthrie B | title = Activation mechanism of the G protein-coupled sweet receptor heterodimer with sweeteners and allosteric agonists | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 114 | issue = 10 | pages = 2568–2573 | date = March 2017 | pmid = 28228527 | pmc = 5347580 | doi = 10.1073/pnas.1700001114 | bibcode = 2017PNAS..114.2568K | doi-access = free }}</ref>
The atomic structure of human sweet taste receptor (T1R2+T1R3) was resolved at 2024 by the same group that discovered the receptor.<ref name="Juen_2025">{{Cite journal | vauthors = Juen Z, Lu Z, Yu R, Chang AN, Wang B, Fitzpatrick AW, Zuker CS | title = The structure of human sweetness | journal = Cell | date = May 2025 | volume = 188 | issue = 15 | pages = 4141–4153.e18 | pmid = 40339580 | doi = 10.1016/j.cell.2025.04.021 | language = en | doi-access = free }}</ref>
== Function ==
The TAS1R2 protein is a crucial component of the sweet taste receptor, functioning primarily as part of a heterodimer with TAS1R3. This receptor complex is responsible for detecting a wide variety of sweet compounds, including natural sugars, artificial sweeteners, and some amino acids, in taste bud cells of the tongue.<ref name="Belloir_2021">{{cite journal | vauthors = Belloir C, Brulé M, Tornier L, Neiers F, Briand L | title = Biophysical and functional characterization of the human TAS1R2 sweet taste receptor overexpressed in a HEK293S inducible cell line | journal = Scientific Reports | volume = 11 | issue = 1 | article-number = 22238 | date = November 2021 | pmid = 34782704 | pmc = 8593021 | doi = 10.1038/s41598-021-01731-3 | bibcode = 2021NatSR..1122238B }}</ref><ref name="Kochem_2024">{{cite journal | vauthors = Kochem MC, Hanselman EC, Breslin PA | title = Activation and inhibition of the sweet taste receptor TAS1R2-TAS1R3 differentially affect glucose tolerance in humans | journal = PLOS ONE | volume = 19 | issue = 5 | article-number = e0298239 | date = 2024 | pmid = 38691547 | pmc = 11062524 | doi = 10.1371/journal.pone.0298239 | bibcode = 2024PLoSO..1998239K | doi-access = free }}</ref> Upon binding of sweet molecules to the extracellular Venus flytrap domain of TAS1R2, the receptor undergoes conformational changes that trigger intracellular signaling cascades via G protein activation, ultimately leading to the perception of sweetness.<ref name="Kochem_2024" /> Beyond its role in taste, TAS1R2 is also expressed in other tissues, such as skeletal muscle and the intestine, where it acts as a nutrient sensor. In skeletal muscle, TAS1R2 detects ambient glucose levels and regulates metabolic pathways by modulating NAD homeostasis and mitochondrial function through an ERK1/2-PARP1 signaling axis, thereby influencing muscle fitness and energy metabolism.<ref name="Serrano_2023">{{cite journal | vauthors = Serrano J, Boyd J, Mason C, Smith KR, Karolyi K, Kondo S, Brown IS, Maurya SK, Meshram NN, Serna V, Gilger J, Branch DA, Gardell SJ, Baskin KK, Ayala JE, Pratley RE, Goodpaster BH, Coen PM, Kyriazis GA | title = The TAS1R2 sweet taste receptor regulates skeletal muscle mass and fitness | journal = Research Square | volume = | issue = | pages = | date = February 2023 | pmid = 36798161 | pmc = 9934781 | doi = 10.21203/rs.3.rs-2475555/v1 }}</ref><ref name="Serrano">{{cite journal | vauthors = Serrano J, Boyd J, Brown IS, Mason C, Smith KR, Karolyi K, Maurya SK, Meshram NN, Serna V, Link GM, Gardell SJ, Kyriazis GA | title = The TAS1R2 G-protein-coupled receptor is an ambient glucose sensor in skeletal muscle that regulates NAD homeostasis and mitochondrial capacity | journal = Nature Communications | volume = 15 | issue = 1 | article-number = 4915 | date = June 2024 | pmid = 38851747 | pmc = 11162498 | doi = 10.1038/s41467-024-49100-8 | bibcode = 2024NatCo..15.4915S }}</ref> Additionally, TAS1R2 activity in the gut can affect glucose absorption and insulin release, linking sweet taste perception to broader metabolic regulation.<ref name="Kochem_2024" /> Genetic variations in TAS1R2 have been shown to influence individual differences in sweet taste sensitivity, sugar intake, and metabolic responses to glucose.<ref name="Melis_2022">{{cite journal | vauthors = Melis M, Mastinu M, Naciri LC, Muroni P, Tomassini Barbarossa I | title = Associations between Sweet Taste Sensitivity and Polymorphisms (SNPs) in the TAS1R2 and TAS1R3 Genes, Gender, PROP Taster Status, and Density of Fungiform Papillae in a Genetically Homogeneous Sardinian Cohort | journal = Nutrients | volume = 14 | issue = 22 | date = November 2022 | page = 4903 | pmid = 36432589 | pmc = 9696868 | doi = 10.3390/nu14224903 | doi-access = free }}</ref><ref name="Chisini_2021">{{cite journal | vauthors = Chisini LA, Cademartori MG, Conde MC, Costa FD, Salvi LC, Tovo-Rodrigues L, Correa MB | title = Single nucleotide polymorphisms of taste genes and caries: a systematic review and meta-analysis | journal = Acta Odontologica Scandinavica | volume = 79 | issue = 2 | pages = 147–155 | date = March 2021 | pmid = 33103533 | doi = 10.1080/00016357.2020.1832253 | doi-access = free }}</ref>
The T1R2+3 receptor has been shown to respond to natural sugars sucrose, sorbitol and fructose, and to the artificial sweeteners saccharin, acesulfame potassium, dulcin, guanidinoacetic acid, cyclamate, sucralose, alitame, neotame and neohesperidin dihydrochalcone (NHDC).<ref name="Behrens_2021" /> Research initially suggested that rat receptors did not respond to many other natural and artificial sugars, such as glucose and aspartame, leading to the conclusion that there must be more than one type of sweet taste receptor.<ref name="Nelson_2001" /> Contradictory evidence, however, suggested that cells expressing the human T1R2+3 receptor showed sensitivity to both aspartame and glucose but cells expressing the rat T1R2+3 receptor were only slightly activated by glucose and showed no aspartame activation.<ref name="Li_2002">{{cite journal | vauthors = Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E | title = Human receptors for sweet and umami taste | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 7 | pages = 4692–4696 | date = April 2002 | pmid = 11917125 | pmc = 123709 | doi = 10.1073/pnas.072090199 | doi-access = free | bibcode = 2002PNAS...99.4692L }}</ref> These results are inconclusive about the existence of another sweet taste receptor, but show that the T1R2+3 receptors are responsible for a wide variety of different sweet tastes. Finally, T1R2+3 responses to non-sugar natural sweeteners such as steviol glycosides from the leaves of the Stevia plant and sweet proteins like thaumatin, monellin, and brazzein.<ref name="Behrens_2021" /> Another surprising ligand of the T1R2+3 is D<sub>2</sub>O, also known as heavy water which was shown to activate the human T1R2+3 receptor.<ref name="Masha Niv">{{cite journal | vauthors = Ben Abu N, Mason PE, Klein H, Dubovski N, Ben Shoshan-Galeczki Y, Malach E, Pražienková V, Maletínská L, Tempra C, Chamorro VC, Cvačka J, Behrens M, Niv MY, Jungwirth P | title = Sweet taste of heavy water | journal = Communications Biology | volume = 4 | issue = 1 | article-number = 440 | date = April 2021 | pmid = 33824405 | pmc = 8024362 | doi = 10.1038/s42003-021-01964-y | s2cid = 257085874 }}</ref>
== Receptor activation ==
In contrast to other class C GPCRs, sweet taste receptor exhibits great asymmetry during activation. Both ligand and G protein alpha subunit bind the TAS1R2, but not TAS1R3 subunit. TAS1R3 provides structural auxiliary support. Ligand binding to the VFT{{Clarify|reason=Please provide full name.|date=May 2026}} of T1R2 induced the closure of T1R2-VFT, but further opening the T1R3-VFT.<ref name="Juen_2025" />
The canonical activation mechanism of class C GPCRs follows a multiple-step process that requires communication between the venus flytrap domains (VFDs) that houses the orthosteric-binding site and the transmembrane domains (TMDs) via the cysteine-rich domains (CRDs).<ref name="Cheron_2019">{{cite journal | vauthors = Chéron JB, Soohoo A, Wang Y, Golebiowski J, Antonczak S, Jiang P, Fiorucci S | title = Conserved Residues Control the T1R3-Specific Allosteric Signaling Pathway of the Mammalian Sweet-Taste Receptor | journal = Chemical Senses | volume = 44 | issue = 5 | pages = 303–310 | date = May 2019 | pmid = 30893427 | pmc = 6538948 | doi = 10.1093/chemse/bjz015 }}</ref> Although the main binding site for most sweet compounds was found to reside in the VFT domain of T1R2, the T1R2 protein is not functional without formation of the 2+3 heterodimer.<ref>{{cite journal | vauthors = Yousif RH, Wahab HA, Shameli K, Khairudin NB | title = Exploring the molecular interactions between Neoculin and the human sweet taste receptors through computational approaches. | journal = Sains Malaysiana | date = March 2020 | volume = 49 | issue = 3 | pages = 517–525 | doi = 10.17576/jsm-2020-4903-06 | doi-access = free }}</ref><ref name="Nelson_2001">{{cite journal | vauthors = Nelson G, Hoon MA, Chandrashekar J, Zhang Y, Ryba NJ, Zuker CS | title = Mammalian sweet taste receptors | journal = Cell | volume = 106 | issue = 3 | pages = 381–390 | date = August 2001 | pmid = 11509186 | doi = 10.1016/S0092-8674(01)00451-2 | s2cid = 11886074 | doi-access = free }}</ref><ref name="Juen_2025" />
Natural sweeteners interact with the orthosteric binding pocket of T1R2. The closure of the T1R2 extracellular domain involves the rotation of both T1R2 and T1R3 VFDs. The signal is then transmitted to the TMDs via the CRDs. It has also been shown that sweet proteins modulate the receptor by interacting with the CRD. Some artificial sweeteners as well as the inhibitor of the sweet taste receptor – lactisole, were shown to interact with the allosteric binding sites of one of the sub-units in the TMD.<ref name="Cheron_2019" /><ref name="Behrens_2021">{{cite book | vauthors = Behrens M | chapter = Pharmacology of TAS1R2/TAS1R3 Receptors and Sweet Taste | title = Handbook of Experimental Pharmacology | volume = 275 | pages = 155–175 | year = 2021 | pmid = 33582884 | doi = 10.1007/164_2021_438 | isbn = 978-3-031-06449-4 | s2cid = 231927528 }}</ref>
== Signal transduction ==
T1R2 and T1R1 receptors have been shown to bind to G proteins, most often the gustducin Gα subunit, although a gusducin knock-out has shown small residual activity. T1R2 and T1R1 have also been shown to activate Gαo and Gαi protein subunits.<ref name="Sainz_2007">{{cite journal | vauthors = Sainz E, Cavenagh MM, LopezJimenez ND, Gutierrez JC, Battey JF, Northup JK, Sullivan SL | title = The G-protein coupling properties of the human sweet and amino acid taste receptors | journal = Developmental Neurobiology | volume = 67 | issue = 7 | pages = 948–959 | date = June 2007 | pmid = 17506496 | doi = 10.1002/dneu.20403 | s2cid = 29736077 }}</ref> This suggests that T1R1 and T1R2 are G protein-coupled receptors that inhibit adenylyl cyclases to decrease cyclic guanosine monophosphate (cGMP) levels in taste receptors.<ref name="Abaffy_2003">{{cite journal | vauthors = Abaffy T, Trubey KR, Chaudhari N | title = Adenylyl cyclase expression and modulation of cAMP in rat taste cells | journal = American Journal of Physiology. Cell Physiology | volume = 284 | issue = 6 | pages = C1420–C1428 | date = June 2003 | pmid = 12606315 | doi = 10.1152/ajpcell.00556.2002 | s2cid = 2704640 }}</ref> Research done by creating knock-outs of common channels activated by sensory G-protein second messenger systems has also shown a connection between sweet taste perception and the phosphatidylinositol (PIP2) pathway. The nonselective cation Transient Receptor Potential channel TRPM5 has been shown to correlate with both umami and sweet taste. Also, the phospholipase PLCβ2 was shown to similarly correlate with umami and sweet taste. This suggests that activation of the G-protein pathway and subsequent activation of PLC β2 and the TRPM5 channel in these taste cells functions to activate the cell.<ref name="Zhang_2003">{{cite journal | vauthors = Zhang Y, Hoon MA, Chandrashekar J, Mueller KL, Cook B, Wu D, Zuker CS, Ryba NJ | title = Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways | journal = Cell | volume = 112 | issue = 3 | pages = 293–301 | date = February 2003 | pmid = 12581520 | doi = 10.1016/S0092-8674(03)00071-0 | s2cid = 718601 | doi-access = free }}</ref>
== See also == * Taste receptor * TAS1R1 * TAS1R3
== References == {{reflist}}
== Further reading == {{refbegin|30em}} * {{cite journal | vauthors = Chandrashekar J, Hoon MA, Ryba NJ, Zuker CS | title = The receptors and cells for mammalian taste | journal = Nature | volume = 444 | issue = 7117 | pages = 288–294 | date = November 2006 | pmid = 17108952 | doi = 10.1038/nature05401 | s2cid = 4431221 | bibcode = 2006Natur.444..288C }} * {{cite journal | vauthors = Hoon MA, Adler E, Lindemeier J, Battey JF, Ryba NJ, Zuker CS | title = Putative mammalian taste receptors: a class of taste-specific GPCRs with distinct topographic selectivity | journal = Cell | volume = 96 | issue = 4 | pages = 541–551 | date = February 1999 | pmid = 10052456 | doi = 10.1016/S0092-8674(00)80658-3 | s2cid = 14773710 | doi-access = free }} * {{cite journal | vauthors = Li X, Staszewski L, Xu H, Durick K, Zoller M, Adler E | title = Human receptors for sweet and umami taste | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 7 | pages = 4692–4696 | date = April 2002 | pmid = 11917125 | pmc = 123709 | doi = 10.1073/pnas.072090199 | doi-access = free | bibcode = 2002PNAS...99.4692L }} * {{cite journal | vauthors = Spadaccini R, Trabucco F, Saviano G, Picone D, Crescenzi O, Tancredi T, Temussi PA | title = The mechanism of interaction of sweet proteins with the T1R2-T1R3 receptor: evidence from the solution structure of G16A-MNEI | journal = Journal of Molecular Biology | volume = 328 | issue = 3 | pages = 683–692 | date = May 2003 | pmid = 12706725 | doi = 10.1016/S0022-2836(03)00346-2 }} * {{cite journal | vauthors = Liao J, Schultz PG | title = Three sweet receptor genes are clustered in human chromosome 1 | journal = Mammalian Genome| volume = 14 | issue = 5 | pages = 291–301 | date = May 2003 | pmid = 12856281 | doi = 10.1007/s00335-002-2233-0 | s2cid = 30665284 }} * {{cite journal | vauthors = Zhao GQ, Zhang Y, Hoon MA, Chandrashekar J, Erlenbach I, Ryba NJ, Zuker CS | title = The receptors for mammalian sweet and umami taste | journal = Cell | volume = 115 | issue = 3 | pages = 255–266 | date = October 2003 | pmid = 14636554 | doi = 10.1016/S0092-8674(03)00844-4 | s2cid = 11773362 | doi-access = free }} * {{cite journal | vauthors = Galindo-Cuspinera V, Winnig M, Bufe B, Meyerhof W, Breslin PA | title = A TAS1R receptor-based explanation of sweet 'water-taste' | journal = Nature | volume = 441 | issue = 7091 | pages = 354–357 | date = May 2006 | pmid = 16633339 | doi = 10.1038/nature04765 | s2cid = 291228 | bibcode = 2006Natur.441..354G }} * {{cite journal | vauthors = Behrens M, Bartelt J, Reichling C, Winnig M, Kuhn C, Meyerhof W | title = Members of RTP and REEP gene families influence functional bitter taste receptor expression | journal = The Journal of Biological Chemistry | volume = 281 | issue = 29 | pages = 20650–20659 | date = July 2006 | pmid = 16720576 | doi = 10.1074/jbc.M513637200 | doi-access = free }} {{refend}}
== External links == * [http://omim.org/entry/606226 TASTE RECEPTOR TYPE 1, MEMBER 2; TAS1R2]
{{G protein-coupled receptors|g3}} {{NLM content}}
Category:Human taste receptors