Affinage

TAS1R3

Taste receptor type 1 member 3 · UniProt Q7RTX0

Length
852 aa
Mass
93.4 kDa
Annotated
2026-04-28
100 papers in source corpus 33 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAS1R3 (T1R3) is a class C G protein-coupled receptor that functions as a broadly tuned chemosensor by heterodimerizing with T1R2 to form the sweet taste receptor or with T1R1 to form the umami taste receptor, and by homodimerizing to serve as a glucose and calcium sensor in extraoral tissues (PMID:11326277, PMID:12869700, PMID:24200979, PMID:22773945). Its multidomain architecture provides distinct ligand-interaction sites: the Venus flytrap domain and cysteine-rich domain engage sweet proteins such as thaumatin and brazzein, while the transmembrane domain harbors overlapping binding pockets for the agonist cyclamate and the antagonist lactisole, which also inhibits T1R3 homodimer signaling in pancreatic β-cells (PMID:15299024, PMID:15668251, PMID:16076846, PMID:25994004). Beyond taste cells, T1R3 couples to downstream effectors including gustducin, PLCβ–Ca²⁺–ERK1/2, and mTORC1 pathways in intestinal enteroendocrine cells, pancreatic β-cells, and skeletal muscle, where it regulates SGLT1 expression, gut hormone secretion, insulin secretion, autophagy, and amino acid–dependent mTORC1 activation (PMID:17724332, PMID:22959271, PMID:26168033). T1R3 also maintains intestinal tuft cell homeostasis and type 2 immunity, and regulates osteoclast-mediated bone resorption (PMID:31980480, PMID:29019082).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2001 High

    Identifying TAS1R3 as the Sac locus gene product established it as the molecular determinant of strain-dependent sweet taste sensitivity and placed it within the class C GPCR family.

    Evidence Positional cloning and expression analysis in mouse taste tissue

    PMID:11326277

    Open questions at the time
    • Receptor function had not been demonstrated in heterologous systems
    • Dimerization partners were not yet defined experimentally
    • Mechanism of Ile60Thr polymorphism effect was inferred from modeling, not tested functionally
  2. 2003 High

    Knockout of T1R3 abolished responses to artificial sweeteners but only diminished responses to sugars and umami compounds, revealing T1R3-independent taste pathways and establishing T1R3 as necessary for artificial sweetener but not solely for sugar detection.

    Evidence Tas1r3 knockout mice with behavioral preference tests and chorda tympani/glossopharyngeal nerve recordings

    PMID:12869700

    Open questions at the time
    • Identity of T1R3-independent sugar/umami sensors was unknown
    • Whether residual responses involved other T1R family members or entirely different pathways was unresolved
  3. 2005 High

    Mapping ligand-binding determinants across T1R3 domains resolved how a single subunit accommodates diverse sweeteners: the cysteine-rich domain engages sweet proteins, the Venus flytrap domain binds small-molecule sweeteners, and the transmembrane domain harbors overlapping agonist (cyclamate) and antagonist (lactisole) sites that control receptor activation.

    Evidence Interspecies chimeric receptors, systematic alanine-scanning mutagenesis, and heterologous expression assays

    PMID:15299024 PMID:15668251 PMID:16076846 PMID:16271873

    Open questions at the time
    • No experimental 3D structure of T1R3 was available
    • Binding site information for many natural sweeteners was still absent
    • How conformational changes propagate from extracellular to transmembrane domain was unresolved
  4. 2007 High

    Discovery of functional T1R3/gustducin expression in intestinal enteroendocrine cells extended T1R3 biology beyond taste, showing it regulates SGLT1 expression and gut hormone secretion in response to luminal sugars.

    Evidence T1R3 and gustducin knockout mice with dietary sugar exposure, SGLT1 mRNA/protein measurement, and GLUTag cell stimulation

    PMID:17724332

    Open questions at the time
    • Downstream signaling pathway from T1R3 to SGLT1 transcription was not defined
    • Relative contributions of T1R2/T1R3 heterodimer versus T1R3 homodimer in gut were unclear
  5. 2008 High

    Demonstrating that Tas1r3 knockout mice show altered calcium and magnesium taste preference and reduced chorda tympani responses established T1R3 as a gustatory divalent cation receptor, expanding its known ligand repertoire beyond sweet and umami compounds.

    Evidence Knockout mice, congenic strains, two-bottle preference tests, and chorda tympani electrophysiology

    PMID:18593862

    Open questions at the time
    • Whether calcium binds T1R3 directly or modulates through the CaSR or another mechanism was not resolved
    • The divalent cation binding site on T1R3 was not mapped
  6. 2012 High

    T1R1/T1R3 was shown to function as a direct amino acid sensor regulating mTORC1 activity and autophagy, establishing taste receptors as intracellular nutrient-sensing GPCRs beyond the canonical Rag GTPase pathway.

    Evidence siRNA knockdown and Tas1r3 knockout mice with mTORC1 localization imaging, translation, and autophagy assays in multiple cell types and in vivo tissues

    PMID:22959271 PMID:23222068

    Open questions at the time
    • Direct physical interaction between T1R1/T1R3 and mTORC1 machinery was not demonstrated
    • Whether T1R1/T1R3 senses amino acids at the plasma membrane or intracellularly was unclear
    • Relationship to Rag-dependent amino acid sensing was not resolved
  7. 2013 High

    Identification of five specific cysteine-rich domain residues required for thaumatin recognition refined the molecular basis of sweet protein binding and confirmed species-specific determinants reside in the T1R3 CRD.

    Evidence Systematic mutagenesis of all 16 candidate CRD residues with cell-based functional assays

    PMID:23370115

    Open questions at the time
    • No co-crystal structure of CRD with sweet protein
    • Whether these residues make direct contacts or affect CRD conformation was not distinguished
  8. 2013 High

    T1R3 was shown to function as a homodimeric glucose sensor in pancreatic β-cells, promoting mitochondrial ATP production and insulin secretion independently of T1R2, establishing a metabolic amplification role for taste receptors in β-cells.

    Evidence shRNA knockdown in MIN6 cells, non-metabolizable T1R3 agonists (3-O-methylglucose), ATP reporter assays, and pharmacological antagonism

    PMID:24200979

    Open questions at the time
    • Whether T1R3 homodimer couples to gustducin or other Gα subunits in β-cells was not resolved
    • The precise mechanism linking T1R3 activation to mitochondrial metabolism was not mapped
  9. 2014 High

    Luminal amino acid sensing by T1R1/T1R3 in colonic enteroendocrine cells was shown to initiate peristaltic reflexes and CGRP release, demonstrating a physiological role for umami receptors in gut motility.

    Evidence T1R1 knockout mice with electrophysiology of peristaltic reflex, CGRP release assay, and video imaging of fecal pellet propulsion

    PMID:25324508

    Open questions at the time
    • Whether T1R3 is required independently of T1R1 for colonic peristalsis was not tested
    • Downstream neural circuit from CGRP release to peristalsis was not delineated
  10. 2015 Medium

    Dissection of G protein coupling in β-cells established that T1R1/T1R3 activates ERK1/2 via Gq and Ca²⁺ entry, while mTORC1 activation proceeds through a distinct, Gq-independent pathway, revealing bifurcated signaling downstream of the receptor.

    Evidence Pharmacological inhibitors (UBO-QIC for Gq, pertussis toxin for Gi, p115-RGS for G12/13) and Ca²⁺ chelation in MIN6 cells

    PMID:26168033

    Open questions at the time
    • The Gα subunit mediating mTORC1 activation was not identified
    • Whether the same bifurcated signaling operates in non-β-cell tissues was not tested
    • Pharmacological tools used may have off-target effects
  11. 2015 High

    Lactisole was shown to inhibit T1R3 homodimer-mediated glucose sensing in β-cells, attenuating sweetener-induced Ca²⁺ elevation and glucose-stimulated insulin secretion, validating the transmembrane domain antagonist site in an extraoral physiological context.

    Evidence Pharmacological inhibition with Ca²⁺/cAMP imaging, insulin secretion, and ATP/NADH measurements in MIN6 cells and primary mouse islets

    PMID:25994004

    Open questions at the time
    • Whether lactisole sensitivity differs between T1R3 homodimer and T1R2/T1R3 heterodimer in β-cells was not quantitatively compared
    • In vivo metabolic consequences of T1R3 inhibition in β-cells were not examined
  12. 2020 Medium

    TAS1R3 was found to be required for intestinal tuft cell homeostasis and type 2 immune responses to protozoan parasites, establishing a role for taste receptor signaling in innate immune surveillance in the gut epithelium.

    Evidence Tas1r3 knockout mice challenged with Tritrichomonas muris and succinate, with tuft cell enumeration in the distal small intestine

    PMID:31980480

    Open questions at the time
    • The ligand sensed by T1R3 in tuft cells was not identified
    • Whether T1R3 acts as heterodimer or homodimer in tuft cells was unknown
    • Downstream signaling from T1R3 to tuft cell expansion was not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • Despite extensive pharmacological and mutagenesis mapping, no experimental 3D structure of T1R3 (alone or in complex) has been determined, and the mechanism by which T1R3 homodimer signals couple to mitochondrial metabolism and mTORC1 remain incompletely defined.
  • No experimental cryo-EM or crystal structure of T1R3 or its complexes exists
  • The identity of the Gα subunit coupling T1R3 homodimer to mTORC1 is unknown
  • How T1R3 distinguishes between homodimeric and heterodimeric signaling outcomes is unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 7 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-9709957 Sensory Perception 5 R-HSA-162582 Signal Transduction 3 R-HSA-8963743 Digestion and absorption 2 R-HSA-168256 Immune System 1 R-HSA-9612973 Autophagy 1
Complex memberships
T1R1/T1R3 umami taste receptorT1R2/T1R3 sweet taste receptorT1R3/T1R3 homodimer

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 TAS1R3 (T1R3) was identified as a G protein-coupled receptor expressed selectively in taste receptor cells, encoded by the Sac locus on chromosome 4, which determines sweet taste sensitivity differences between mouse strains. A polymorphism (Ile60Thr) in T1R3 from non-taster strains is predicted to interfere with dimerization. Positional cloning, sequence analysis, expression analysis in taste tissue, comparative genomics Nature genetics High 11326277
2003 Mice lacking T1R3 showed no preference for artificial sweeteners and had diminished but not abolished behavioral and nerve responses to sugars and umami compounds, indicating T1R3-independent pathways also exist in taste cells. T1R3 knockout mice, behavioral preference tests, nerve electrophysiology Science High 12869700
2005 Lactisole inhibits sweet taste by interacting with the transmembrane domain of human T1R3. Four key residues within the transmembrane region of hT1R3 are required for sensitivity to lactisole, identified by alanine substitution mutagenesis and interspecies chimeric receptors. Interspecies chimeric receptors, alanine-scanning mutagenesis, heterologous expression, molecular modeling/docking The Journal of biological chemistry High 15668251
2004 The cysteine-rich region of T1R3 determines responses to intensely sweet proteins (brazzein, monellin, thaumatin). Mutations in this region of human T1R3 affected receptor activity toward these proteins, implicating the cysteine-rich domain as an important ligand-interaction site. Interspecies chimeric receptors, site-directed mutagenesis, heterologous expression The Journal of biological chemistry High 15299024
2005 Cyclamate activates the sweet receptor through the transmembrane domain of hT1R3. Six residues in the transmembrane domain specifically determine responsiveness to cyclamate, identified by chimera analysis and alanine-scanning mutagenesis. The transmembrane domain of T1R3 likely plays a critical role in converting the receptor from ground to active state, with overlapping binding pockets for agonist cyclamate and inverse agonist lactisole. Mixed-species receptor pairings, chimeric receptor analysis, directed mutagenesis, molecular modeling/docking The Journal of biological chemistry High 16076846
2005 The T1R2 and T1R3 subunits each independently bind sweet stimuli with distinct affinities and conformational changes. A single amino acid change in T1R3 associated with decreased sweet sensitivity in mice drastically reduces ligand affinities for T1R3, demonstrating that individual subunits extend the receptive range of the heteromeric sweet receptor. Heterologous expression, ligand binding assays, mutagenesis Current biology High 16271873
2007 T1R3 and gustducin expressed in intestinal enteroendocrine cells underlie sugar sensing in the gut and regulate SGLT1 mRNA and protein expression. T1R3 knockout mice failed to upregulate SGLT1 in response to dietary sugar or artificial sweeteners, and artificial sweeteners acting on sweet taste receptors on GLUTag enteroendocrine cells stimulated gut hormone secretion implicated in SGLT1 upregulation. T1R3 and gustducin knockout mice, dietary sugar exposure, RT-PCR, protein expression, enteroendocrine cell stimulation assays Proceedings of the National Academy of Sciences High 17724332
2007 The taste-modifying sweet protein neoculin requires the extracellular amino terminal domain (ATD) of hT1R3 for its reception. Calcium imaging in HEK cells expressing chimeric human/mouse T1R3 identified the ATD of hT1R3 as a new sweetener-binding region. Calcium imaging, heterologous expression, human/mouse chimeric T1R3 constructs Biochemical and biophysical research communications Medium 17499612
2008 T1R3 functions as a gustatory calcium and magnesium receptor. Mice null for Tas1r3 preferred calcium and magnesium solutions avoided by wild-type mice, oral calcium elicited less chorda tympani nerve activity in Tas1r3 KO mice, and a V689A substitution unique to PWK strain may underlie its strong calcium/magnesium preference. Tas1r3 knockout mice, congenic mice, genome scan, two-bottle preference tests, chorda tympani electrophysiology, sequence analysis Physiological genomics High 18593862
2012 The heterodimeric GPCR T1R1/T1R3 functions as a direct sensor of amino acid availability and the fed state, regulating mTORC1 localization and activity. Knockdown of T1R1 or T1R3 impairs amino acid-induced mTORC1 signaling, alters mTORC1 localization, upregulates amino acid transporters, blocks translation initiation, and induces autophagy. Fasted TAS1R3-/- mice have increased autophagy in heart, skeletal muscle, and liver. siRNA knockdown, T1R3 knockout mice, mTORC1 localization by imaging, translation and autophagy assays Molecular cell High 22959271 23222068
2012 T1R3 is a human calcium taste receptor. Calcium activates hTAS1R3-transfected HEK293 cells, and this response is attenuated by lactisole (an hT1R3 inhibitor). Trained human volunteers reported that lactisole reduces the calcium intensity of calcium lactate, confirming T1R3 mediates calcium taste perception. Heterologous expression in HEK293 cells, pharmacological inhibition with lactisole, human psychophysics Scientific reports High 22773945
2012 Recombinant hT1R3 N-terminal domain (hT1R3-NTD) was expressed, refolded, and shown to form a dimer. The refolded hT1R3-NTD binds sucralose with millimolar affinity, demonstrating the NTD is functional for ligand binding. Recombinant protein expression, in vitro refolding, size-exclusion chromatography, tryptophan fluorescence quenching, microcalorimetry Protein expression and purification High 22450161
2013 T1R1/T1R3 umami receptor exhibits species-dependent ligand specificity determined by two distinct determinants: amino acid selectivity at the orthosteric site (12 key residues in the Venus flytrap domain of T1R1) and receptor activity modulation at non-orthosteric sites distinct from the IMP allosteric site. Chimeric human-mouse receptors, point mutagenesis, functional expression assays, molecular modeling The Journal of biological chemistry High 24214976
2013 T1R3 functions as a glucose-sensing receptor (homodimer) in pancreatic β-cells, promoting glucose metabolism. Activation by sucralose or 3-O-methylglucose (non-metabolizable T1R3 agonist) increases intracellular ATP and augments mitochondrial metabolism. Knockdown of T1R3 with shRNA attenuates ATP response to high glucose and reduces glucose-induced insulin secretion. Luciferase ATP reporter assay in MIN6 cells, shRNA knockdown, pharmacological agonists/antagonists Endocrine journal High 24200979
2014 L-Theanine activates the T1R1+T1R3 umami taste receptor and shows synergy with IMP. Site-directed mutagenesis revealed that L-theanine binds to the L-amino acid binding site in the Venus flytrap domain of T1R1. Heterologous expression, functional assay, site-directed mutagenesis Amino acids Medium 24633359
2014 Activation of the umami taste receptor T1R1/T1R3 by luminal MSG or L-cysteine in enteroendocrine cells of the colon initiates the peristaltic reflex, calcitonin gene-related peptide (CGRP) release, and increases velocity of fecal pellet propulsion. In T1R1-/- mice, MSG failed to elicit peristaltic reflex. IMP potentiated MSG effects, consistent with T1R1/T1R3 activation. T1R1 knockout mice, electrophysiology of peristaltic reflex, CGRP release assay, video recording of pellet propulsion, immunostaining American journal of physiology. Gastrointestinal and liver physiology High 25324508
2014 Mouse neutrophils express functional umami taste receptor T1R1/T1R3. Stimulation with T1R1/T1R3 ligands (L-alanine, L-serine) elicited ERK and p38 MAPK phosphorylation and chemotactic migration, and reduced LPS-induced cytokine production by inhibiting NF-κB and STAT3 signaling. RNA sequencing, qRT-PCR, signaling assays (ERK, p38 phosphorylation), chemotaxis assay, NF-κB/STAT3 activity BMB reports Medium 25301019
2015 Lactisole inhibits the glucose-sensing receptor T1R3 (homodimer) in mouse pancreatic β-cells. In MIN6 cells and HEK293 cells stably expressing mouse T1R3, lactisole attenuated sweetener-induced Ca2+ elevation but not cAMP elevation, inhibited sweetener-induced insulin secretion, and reduced glucose-induced ATP, NADH, and insulin secretion. Pharmacological inhibition, Ca2+ and cAMP imaging, insulin secretion assay, NADH/ATP measurements, mouse islets The Journal of endocrinology High 25994004
2016 Methionine regulates mTORC1 via T1R1/T1R3-PLCβ-Ca2+-ERK1/2 signal transduction in C2C12 myotubes. Among several L-amino acids, methionine was specifically identified as a potent activator of mTORC1 via this receptor-dependent pathway. siRNA knockdown, Ca2+ measurements, mTORC1 pathway phosphorylation assays, C2C12 myotube model International journal of molecular sciences Medium 27727170
2017 Activation of T1R3 by sucralose in pulmonary microvascular endothelial cells protects against LPS- and thrombin-induced barrier dysfunction, reducing Src, PAK, MLC2, HSP27, and p110αPI3K phosphorylation/expression. T1R3 siRNA knockdown abolished this protective effect. In vivo, sucralose attenuated bacteria-induced lung edema. siRNA knockdown, endothelial permeability assay, signaling protein phosphorylation, in vivo edema model American journal of physiology. Lung cellular and molecular physiology Medium 28971978
2017 T1R3 homomeric sweet taste receptor negatively regulates adipogenesis in 3T3-L1 cells via Gαs-mediated microtubule disassembly and consequent RhoA/ROCK activation. GEF-H1 (microtubule-localized Rho GEF) knockdown blocked sweetener-induced RhoA activation, and dominant-negative RhoA blocked sweetener-induced repression of PPARγ and C/EBPα. Dominant-negative and constitutively active Gαs mutants, siRNA knockdown of GEF-H1, RhoA activity assays, microtubule imaging, adipogenesis markers PloS one Medium 28472098
2018 Methional acts as an allosteric modulator of T1R1/T1R3 by binding to the transmembrane domain of T1R1, functioning as a positive allosteric modulator (PAM) for human T1R1/T1R3 and a negative allosteric modulator (NAM) for mouse T1R1/T1R3. Interspecies chimeric receptor analysis and site-directed mutagenesis identified two distinct binding sites in the T1R1 transmembrane domain whose occupancy underlies the PAM/NAM switch. Heterologous expression, chimeric receptor analysis, site-directed mutagenesis, molecular modeling Scientific reports High 30087430
2013 Five amino acid residues in the cysteine-rich domain (CRD) of human T1R3 (Q504K, A537T, R556P, S559P, R560K) are specifically required for response to the sweet-tasting protein thaumatin, as identified by conversion of each of 16 CRD residues to their mouse counterparts and functional testing. Site-directed mutagenesis, cell-based functional assay Biochimie High 23370115
2014 Human T1R3 surface expression requires co-expression with human T1R2, unlike mouse T1r3 which is expressed alone. The Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain regions that inhibit membrane trafficking unless T1R2 is co-expressed, establishing distinct human/mouse membrane trafficking systems for the sweet receptor. Tagged receptor expression in HEK293 cells, domain-swapped chimeras, truncation mutants, surface expression assay PloS one Medium 25029362
2020 TAS1R3 regulates small intestinal tuft cell homeostasis and type 2 immune responses to protozoa (Tritrichomonas muris) and succinate in the distal small intestine. Tas1r3-deficient mice had severely impaired tuft cell responses in the ileum and reduced tuft cell numbers at homeostasis, particularly in the distal small intestine. Tas1r3 knockout mice, tuft cell counting, immune challenge with protozoa and succinate, comparison with helminth challenge ImmunoHorizons Medium 31980480
2020 Artificial sweeteners (sucralose, aspartame, saccharin) disrupt intestinal epithelial tight junctions and increase barrier permeability through activation of the sweet taste receptor T1R3. T1R3 siRNA knockdown attenuated these effects. Aspartame-induced permeability was mediated through reactive oxygen species production and claudin 3 internalization. Caco-2 cell model, siRNA knockdown, permeability assay, claudin 3 surface expression, ROS measurement Nutrients Medium 32580504
2018 TAS1R3 and putative signaling partner TAS1R2 are expressed in primary osteoclasts and their expression positively correlates with differentiation status. Loss of TAS1R3 leads to reduced bone resorption (>60% reduction in C-telopeptide) without affecting bone formation, indicating TAS1R3 regulates osteoclast function. Tas1r3 knockout mice, serum bone turnover markers, primary osteoclast culture, expression analysis Journal of physiology and biochemistry Medium 29019082
2018 Gli3 is a negative regulator of Tas1r3-expressing taste receptor cells. Conditional knockout of Gli3 in posterior tongue resulted in larger taste buds with more Tas1r3+ cells and Lgr5+ stem cells, increased sweet and umami lick responses, and altered glossopharyngeal nerve responses, establishing Gli3 as a suppressor of stem cell proliferation affecting Tas1r3+ cell numbers. Conditional knockout mice, single-cell RNA-Seq, PCR, immunohistochemistry, taste organoids, electrophysiology, behavioral lick tests PLoS genetics High 29415007
2021 Predicted 3D structure of the active Tas1R3/1R3' homodimer complexed with gustducin G protein and sucrose was generated by computational modeling. The model reveals that Venus flytrap domains undergo ~100° rotation to adopt closed-closed conformation upon activation, while the intracellular region relaxes to open conformation. GGust makes ionic anchors to intracellular loops 1 and 2 of Tas1R3. Computational structure prediction, molecular modeling/docking Journal of the American Chemical Society Low 34585929
2024 Steviol rebaudiosides bind to four distinct sites of the T1R2/T1R3 sweet taste receptor complex: VFD2, VFD3, TMD2, and TMD3. The C20 carboxy terminus of the Gα protein can bind to the intracellular region of either TMD2 or TMD3, altering GPCR affinity to a high-affinity state for steviol glycosides. Radiolabeled ligand binding experiments, computational docking Communications chemistry Medium 39424933
2015 MyoD and Myogenin (muscle regulatory factors) regulate T1R3 promoter activity, and T1R3 expression increases with skeletal muscle differentiation of C2C12 myoblasts. A repressive element upstream of the human T1R3 promoter was identified by functional analysis. Comparative genomics, luciferase reporter assays, murine myoblast differentiation model Biochemical and biophysical research communications Medium 26545778
2015 Amino acid-induced ERK1/2 and mTORC1 activation by T1R1/T1R3 in MIN6 β-cells proceed through distinct signaling pathways: Gq is required for ERK1/2 but not mTORC1 activation; Ca2+ entry is required for ERK1/2 but dispensable for mTORC1 activation; Gi and G12/13 are not central to either pathway. Pertussis toxin, UBO-QIC (Gq inhibitor), p115-RGS overexpression (G12/13 inhibitor), Ca2+ chelation, signaling assays in MIN6 cells Molecular endocrinology Medium 26168033

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 T1R3 and gustducin in gut sense sugars to regulate expression of Na+-glucose cotransporter 1. Proceedings of the National Academy of Sciences of the United States of America 672 17724332
2003 Detection of sweet and umami taste in the absence of taste receptor T1r3. Science (New York, N.Y.) 463 12869700
2001 Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac. Nature genetics 384 11326277
2005 Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste. The Journal of biological chemistry 237 15668251
2004 The cysteine-rich region of T1R3 determines responses to intensely sweet proteins. The Journal of biological chemistry 217 15299024
2005 Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detection of sweet stimuli. Current biology : CB 199 16271873
2011 Glucose transporters and ATP-gated K+ (KATP) metabolic sensors are present in type 1 taste receptor 3 (T1r3)-expressing taste cells. Proceedings of the National Academy of Sciences of the United States of America 166 21383163
2005 Identification of the cyclamate interaction site within the transmembrane domain of the human sweet taste receptor subunit T1R3. The Journal of biological chemistry 164 16076846
2012 The G protein-coupled taste receptor T1R1/T1R3 regulates mTORC1 and autophagy. Molecular cell 153 22959271
2009 Allelic polymorphism within the TAS1R3 promoter is associated with human taste sensitivity to sucrose. Current biology : CB 151 19559618
2004 Polymorphisms in the taste receptor gene (Tas1r3) region are associated with saccharin preference in 30 mouse strains. The Journal of neuroscience : the official journal of the Society for Neuroscience 144 14749438
2012 Sensing of amino acids by the gut-expressed taste receptor T1R1-T1R3 stimulates CCK secretion. American journal of physiology. Gastrointestinal and liver physiology 139 23203156
2005 From small sweeteners to sweet proteins: anatomy of the binding sites of the human T1R2_T1R3 receptor. Journal of medicinal chemistry 116 16107151
2010 T1R3 is expressed in brush cells and ghrelin-producing cells of murine stomach. Cell and tissue research 111 20063013
2022 Characteristics of umami peptides identified from porcine bone soup and molecular docking to the taste receptor T1R1/T1R3. Food chemistry 107 35398684
2002 Why are sweet proteins sweet? Interaction of brazzein, monellin and thaumatin with the T1R2-T1R3 receptor. FEBS letters 107 12208493
2013 Two distinct determinants of ligand specificity in T1R1/T1R3 (the umami taste receptor). The Journal of biological chemistry 101 24214976
2021 In-silico investigation of umami peptides with receptor T1R1/T1R3 for the discovering potential targets: A combined modeling approach. Biomaterials 85 34998173
2009 T1R2 and T1R3 subunits are individually unnecessary for normal affective licking responses to Polycose: implications for saccharide taste receptors in mice. American journal of physiology. Regulatory, integrative and comparative physiology 85 19158407
2022 Decoding of the Saltiness Enhancement Taste Peptides from the Yeast Extract and Molecular Docking to the Taste Receptor T1R1/T1R3. Journal of agricultural and food chemistry 81 36325587
2015 Sugar-induced cephalic-phase insulin release is mediated by a T1r2+T1r3-independent taste transduction pathway in mice. American journal of physiology. Regulatory, integrative and comparative physiology 79 26157055
2010 Gut T1R3 sweet taste receptors do not mediate sucrose-conditioned flavor preferences in mice. American journal of physiology. Regulatory, integrative and comparative physiology 79 20926763
2023 Identification of Novel Umami Peptides in Chicken Breast Soup through a Sensory-Guided Approach and Molecular Docking to the T1R1/T1R3 Taste Receptor. Journal of agricultural and food chemistry 72 37189274
2022 Taste mechanism of umami peptides from Chinese traditional fermented fish (Chouguiyu) based on molecular docking using umami receptor T1R1/T1R3. Food chemistry 68 35504076
2020 The Taste Receptor TAS1R3 Regulates Small Intestinal Tuft Cell Homeostasis. ImmunoHorizons 68 31980480
2020 Artificial Sweeteners Disrupt Tight Junctions and Barrier Function in the Intestinal Epithelium through Activation of the Sweet Taste Receptor, T1R3. Nutrients 68 32580504
2004 Allelic variation of the Tas1r3 taste receptor gene selectively affects behavioral and neural taste responses to sweeteners in the F2 hybrids between C57BL/6ByJ and 129P3/J mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 66 14999080
2021 Novel umami peptides from tilapia lower jaw and molecular docking to the taste receptor T1R1/T1R3. Food chemistry 64 34111693
2016 The structure features of umami hexapeptides for the T1R1/T1R3 receptor. Food chemistry 62 27979247
2014 Interaction between umami peptide and taste receptor T1R1/T1R3. Cell biochemistry and biophysics 61 25331670
2007 Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice. Physiological genomics 61 17911381
2009 Nonsynonymous single nucleotide polymorphisms in human tas1r1, tas1r3, and mGluR1 and individual taste sensitivity to glutamate. The American journal of clinical nutrition 60 19571223
2017 Salivary leptin and TAS1R2/TAS1R3 polymorphisms are related to sweet taste sensitivity and carbohydrate intake from a buffet meal in healthy young adults. The British journal of nutrition 59 29110749
2007 Taste-modifying sweet protein, neoculin, is received at human T1R3 amino terminal domain. Biochemical and biophysical research communications 57 17499612
2011 Expression and distribution of the sweet taste receptor isoforms T1R2 and T1R3 in human and rat bladders. The Journal of urology 56 22019168
2012 T1R3: a human calcium taste receptor. Scientific reports 55 22773945
2022 Novel umami peptide from Hypsizygus marmoreus hydrolysate and molecular docking to the taste receptor T1R1/T1R3. Food chemistry 54 36099828
2012 Orosensory detection of sucrose, maltose, and glucose is severely impaired in mice lacking T1R2 or T1R3, but Polycose sensitivity remains relatively normal. American journal of physiology. Regulatory, integrative and comparative physiology 54 22621968
2013 The taste of D- and L-amino acids: In vitro binding assays with cloned human bitter (TAS2Rs) and sweet (TAS1R2/TAS1R3) receptors. Food chemistry 53 24360415
2019 Understanding the molecular mechanism of umami recognition by T1R1-T1R3 using molecular dynamics simulations. Biochemical and biophysical research communications 52 31092329
2004 Expression of the sweet receptor protein, T1R3, in the human liver and pancreas. The Journal of veterinary medical science 52 15585941
2008 Involvement of T1R3 in calcium-magnesium taste. Physiological genomics 51 18593862
2005 Initial licking responses of mice to sweeteners: effects of tas1r3 polymorphisms. Chemical senses 51 16135742
2012 The role of T1r3 and Trpm5 in carbohydrate-induced obesity in mice. Physiology & behavior 50 22683548
2016 Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells. International journal of molecular sciences 45 27727170
2014 Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon. American journal of physiology. Gastrointestinal and liver physiology 45 25324508
2018 Methionine and valine activate the mammalian target of rapamycin complex 1 pathway through heterodimeric amino acid taste receptor (TAS1R1/TAS1R3) and intracellular Ca2+ in bovine mammary epithelial cells. Journal of dairy science 44 30268610
2009 Interactions between the human sweet-sensing T1R2-T1R3 receptor and sweeteners detected by saturation transfer difference NMR spectroscopy. Biochimica et biophysica acta 44 19664591
2013 Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor T1R3. Endocrine journal 41 24200979
2011 Human genetic polymorphisms in T1R1 and T1R3 taste receptor subunits affect their function. Chemical senses 41 21422378
2009 Contribution of the T1r3 taste receptor to the response properties of central gustatory neurons. Journal of neurophysiology 41 19279151
2015 Impaired Glucose Metabolism in Mice Lacking the Tas1r3 Taste Receptor Gene. PloS one 40 26107521
2013 Impact of T1r3 and Trpm5 on carbohydrate preference and acceptance in C57BL/6 mice. Chemical senses 40 23547138
2014 L-Theanine elicits umami taste via the T1R1 + T1R3 umami taste receptor. Amino acids 39 24633359
2006 Genomic structure of swine taste receptor family 1 member 3, TAS1R3, and its expression in tissues. Cytogenetic and genome research 39 16974084
2003 The mechanism of interaction of sweet proteins with the T1R2-T1R3 receptor: evidence from the solution structure of G16A-MNEI. Journal of molecular biology 39 12706725
2019 Branched chain amino acids stimulate gut satiety hormone cholecystokinin secretion through activation of the umami taste receptor T1R1/T1R3 using an in vitro porcine jejunum model. Food & function 34 31098606
2013 Sucrose-conditioned flavor preferences in sweet ageusic T1r3 and Calhm1 knockout mice. Physiology & behavior 33 24384370
2012 Amino acid regulation of autophagy through the GPCR TAS1R1-TAS1R3. Autophagy 33 23222068
2018 Positive/Negative Allosteric Modulation Switching in an Umami Taste Receptor (T1R1/T1R3) by a Natural Flavor Compound, Methional. Scientific reports 32 30087430
2010 T1r3 taste receptor involvement in gustatory neural responses to ethanol and oral ethanol preference. Physiological genomics 32 20145204
2014 Return of the glucoreceptor: Glucose activates the glucose-sensing receptor T1R3 and facilitates metabolism in pancreatic β-cells. Journal of diabetes investigation 31 25969708
2012 Recombinant expression, in vitro refolding, and biophysical characterization of the N-terminal domain of T1R3 taste receptor. Protein expression and purification 31 22450161
2009 Phenoxy herbicides and fibrates potently inhibit the human chemosensory receptor subunit T1R3. Journal of medicinal chemistry 31 19817384
2024 From Molecular Dynamics to Taste Sensory Perception: A Comprehensive Study on the Interaction of Umami Peptides with the T1R1/T1R3-VFT Receptor. Journal of agricultural and food chemistry 30 38488059
2015 Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells. The Journal of endocrinology 30 25994004
2017 Activation of the sweet taste receptor, T1R3, by the artificial sweetener sucralose regulates the pulmonary endothelium. American journal of physiology. Lung cellular and molecular physiology 29 28971978
2015 Glucose-Sensing Receptor T1R3: A New Signaling Receptor Activated by Glucose in Pancreatic β-Cells. Biological & pharmaceutical bulletin 28 25947913
2006 Expression and purification of functional ligand-binding domains of T1R3 taste receptors. Chemical senses 28 16621970
2008 Gurmarin sensitivity of sweet taste responses is associated with co-expression patterns of T1r2, T1r3, and gustducin. Biochemical and biophysical research communications 27 18174025
2017 Evaluation of the association between the TAS1R2 and TAS1R3 variants and food intake and nutritional status in children. Genetics and molecular biology 26 28497839
2012 Functional characterization of the heterodimeric sweet taste receptor T1R2 and T1R3 from a New World monkey species (squirrel monkey) and its response to sweet-tasting proteins. Biochemical and biophysical research communications 26 23000410
2023 Peptidomics Screening and Molecular Docking with Umami Receptors T1R1/T1R3 of Novel Umami Peptides from Oyster (Crassostrea gigas) Hydrolysates. Journal of agricultural and food chemistry 25 38131198
2014 Mouse neutrophils express functional umami taste receptor T1R1/T1R3. BMB reports 24 25301019
2010 The T1R2/T1R3 sweet receptor and TRPM5 ion channel taste targets with therapeutic potential. Progress in molecular biology and translational science 24 20691962
2024 Screening and identification of novel umami peptides from yeast proteins: Insights into their mechanism of action on receptors T1R1/T1R3. Food chemistry 23 39265305
2018 Gli3 is a negative regulator of Tas1r3-expressing taste cells. PLoS genetics 23 29415007
2013 Five amino acid residues in cysteine-rich domain of human T1R3 were involved in the response for sweet-tasting protein, thaumatin. Biochimie 23 23370115
2017 Milk protein synthesis is regulated by T1R1/T1R3, a G protein-coupled taste receptor, through the mTOR pathway in the mouse mammary gland. Molecular nutrition & food research 22 28497545
2015 Muscle regulatory factors regulate T1R3 taste receptor expression. Biochemical and biophysical research communications 22 26545778
2014 Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3. PloS one 20 25029362
2012 Anticonvulsant activity of artificial sweeteners: a structural link between sweet-taste receptor T1R3 and brain glutamate receptors. Bioorganic & medicinal chemistry letters 20 22579423
2018 Activation of the sweet taste receptor T1R3 by sucralose attenuates VEGF-induced vasculogenesis in a cell model of the retinal microvascular endothelium. Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie 19 30353220
2005 No relationship between sequence variation in protein coding regions of the Tas1r3 gene and saccharin preference in rats. Chemical senses 19 15741599
2003 Taste receptor T1R3 is an essential molecule for the cellular recognition of the disaccharide trehalose. In vitro cellular & developmental biology. Animal 19 12892531
2024 Exploring the Relationship between Small Peptides and the T1R1/T1R3 Umami Taste Receptor for Umami Peptide Prediction: A Combined Approach. Journal of agricultural and food chemistry 18 38775286
2017 Loss of the nutrient sensor TAS1R3 leads to reduced bone resorption. Journal of physiology and biochemistry 18 29019082
2020 Residual Glucose Taste in T1R3 Knockout but not TRPM5 Knockout Mice. Physiology & behavior 17 32417232
2012 Glucose transporter/T1R3-expressing cells in rat tracheal epithelium. Journal of anatomy 17 22640462
2009 Tas1R1-Tas1R3 taste receptor variants in human fungiform papillae. Neuroscience letters 17 19146926
2022 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. Nutrients 16 36432589
2024 Steviol rebaudiosides bind to four different sites of the human sweet taste receptor (T1R2/T1R3) complex explaining confusing experiments. Communications chemistry 15 39424933
2023 Novel Umami Peptides from Hypsizygus marmoreus and Interaction with Umami Receptor T1R1/T1R3. Foods (Basel, Switzerland) 15 36832778
2015 Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells. Molecular endocrinology (Baltimore, Md.) 15 26168033
2022 TAS1R3 and TAS2R38 Polymorphisms Affect Sweet Taste Perception: An Observational Study on Healthy and Obese Subjects. Nutrients 14 35565677
2021 Predicted Structure of Fully Activated Tas1R3/1R3' Homodimer Bound to G Protein and Natural Sugars: Structural Insights into G Protein Activation by a Class C Sweet Taste Homodimer with Natural Sugars. Journal of the American Chemical Society 14 34585929
2018 TAS1R1 and TAS1R3 Polymorphisms Relate to Energy and Protein-Rich Food Choices from a Buffet Meal Respectively. Nutrients 14 30518043
2017 An Examination of the Role of L-Glutamate and Inosine 5'-Monophosphate in Hedonic Taste-Guided Behavior by Mice Lacking the T1R1 + T1R3 Receptor. Chemical senses 14 28334294
2017 T1R3 homomeric sweet taste receptor regulates adipogenesis through Gαs-mediated microtubules disassembly and Rho activation in 3T3-L1 cells. PloS one 14 28472098
2023 Identifying Umami Peptides Specific to the T1R1/T1R3 Receptor via Phage Display. Journal of agricultural and food chemistry 13 37523494