Affinage

TAS1R2

Taste receptor type 1 member 2 · UniProt Q8TE23

Length
839 aa
Mass
95.2 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAS1R2 encodes the ligand-binding subunit of the TAS1R2–TAS1R3 heterodimeric G protein-coupled receptor that serves as the principal mammalian sweet taste receptor and a metabolic nutrient sensor in extra-gustatory tissues. The Venus Flytrap domain of TAS1R2 constitutes the primary orthosteric binding site for sugars, amino acids, and high-potency sweeteners, with critical residues D278 and E382 required for ligand affinity, while the transmembrane domain harbors a distinct allosteric site for modulators such as amiloride (PMID:36012481, PMID:30120716). Knockout studies demonstrate that TAS1R2 is essential for behavioral responses to sucrose, glucose, and saccharin but dispensable for Polycose detection; in the intestine, TAS1R2 promotes GLUT2-mediated glucose absorption through GLP-2 secretion and neuronal signaling, and in skeletal muscle it senses ambient glucose to activate ERK1/2–PARP1-dependent NAD consumption, thereby limiting mitochondrial capacity (PMID:19158407, PMID:30201274, PMID:38851747). A common human TAS1R2 Ile191Val variant reduces receptor plasma-membrane availability without altering ligand binding and is associated with attenuated oral glucose excursions, linking receptor trafficking to metabolic regulation (PMID:34509698).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2005 High

    Demonstrating that each subunit of the sweet receptor independently binds ligands resolved how a single heterodimer recognizes a chemically diverse set of sweeteners.

    Evidence Ligand binding assays and mutagenesis on individual T1R2 and T1R3 subunits

    PMID:16271873

    Open questions at the time
    • Relative contribution of each subunit to signaling efficacy was not quantified
    • Binding stoichiometry for asymmetric ligands unresolved
  2. 2009 High

    Loss-of-function studies in T1R2 knockout mice established TAS1R2 as a required component of the principal sweet taste receptor while revealing a T1R2-independent pathway for glucose polymer taste.

    Evidence T1R2 KO mice with brief-access and operant taste discrimination tests across multiple stimuli

    PMID:19158407 PMID:21940444 PMID:22621968

    Open questions at the time
    • Identity of the T1R2-independent Polycose receptor remains unknown
    • Neural circuit differences between sweet and Polycose pathways not mapped
  3. 2010 Medium

    Reporter knock-in mice revealed TAS1R2 expression beyond taste buds—in the gastrointestinal tract and testis—raising the question of non-gustatory function.

    Evidence T1R2-LacZ knock-in mouse with immunohistochemistry

    PMID:20965149

    Open questions at the time
    • Functional significance of testicular expression unknown
    • Cell-type resolution in GI tract limited
  4. 2010 High

    Mutagenesis of both the sweet protein brazzein and the TAS1R2 Venus Flytrap domain identified a multi-point interaction mechanism, mapping the primary agonist-binding locus to the T1R2 subunit.

    Evidence Site-directed mutagenesis of brazzein and hT1R2 residues, cell-based assay in HEK293 cells, human taste panel, chimeric receptors

    PMID:20302879

    Open questions at the time
    • No crystal or cryo-EM structure of VFT–protein sweetener complex
    • Allosteric coupling between VFT closure and TMD activation unresolved
  5. 2012 High

    Cross-species chimeric receptor experiments attributed species-specific sweetener selectivity to defined residues in TAS1R2, distinguishing VFT-mediated and TMD-mediated ligand recognition.

    Evidence Squirrel monkey/human/mouse chimeric T1R2/T1R3 constructs in HEK293 cells

    PMID:23000410 PMID:30120716

    Open questions at the time
    • Structural basis for species selectivity at atomic resolution lacking
    • Role of CRD linker in signal transmission between VFT and TMD not tested
  6. 2014 High

    Domain-swap and truncation analysis revealed that human T1R3 surface expression depends on co-expression with T1R2, establishing obligate heterodimerization for membrane trafficking in human cells.

    Evidence Tagged receptor constructs, domain-swapped chimeras, surface expression assays in HEK293 cells

    PMID:25029362

    Open questions at the time
    • Chaperone or ER-quality-control factors mediating co-dependence not identified
    • Whether trafficking requirement is conserved beyond primates is unclear
  7. 2018 High

    Intestinal TAS1R2 was shown to regulate glucose absorption by controlling apical GLUT2 trafficking through a GLP-2 and neuronal signaling cascade, establishing a mechanistic link between sweet taste receptor signaling and nutrient uptake.

    Evidence T1R2 KO mice, in vivo glucose absorption, GLUT2 localization in intact intestinal preparations

    PMID:30201274

    Open questions at the time
    • Specific enteroendocrine cell type(s) mediating GLP-2 release not isolated
    • Downstream G protein (gustducin vs. others) in intestinal cells not confirmed
  8. 2021 High

    The human Ile191Val variant was shown to reduce TAS1R2 membrane availability without altering ligand binding, and Val carriers exhibited reduced glucose excursions, linking receptor trafficking efficiency to metabolic outcomes in humans.

    Evidence In vitro membrane availability assays, human OGTT stratified by genotype

    PMID:34509698

    Open questions at the time
    • Effect size in diverse populations not replicated
    • Whether variant affects intestinal vs. taste bud function differentially is unknown
  9. 2022 High

    Biophysical reconstitution of the isolated TAS1R2 Venus Flytrap domain confirmed it as the primary sweet-ligand binding site, with D278A and E382A mutations drastically reducing affinity, closing a long-standing question about which domain confers sweet specificity.

    Evidence Recombinant hTAS1R2-VFT expressed in E. coli, mutagenesis, intrinsic tryptophan fluorescence binding assays

    PMID:36012481

    Open questions at the time
    • No structure of VFT in ligand-bound versus unbound state
    • Cooperativity between monomeric VFT binding and heterodimer activation not measured
  10. 2024 High

    Muscle-specific TAS1R2 deletion revealed a glucose-sensing pathway in skeletal muscle that signals through ERK1/2 to activate PARP1, consuming NAD and limiting mitochondrial capacity—an entirely new extra-gustatory role for the receptor.

    Evidence Muscle-specific TAS1R2 KO mice, ERK1/2 and PARP1 activity assays, NAD measurements, exercise endurance testing

    PMID:38851747

    Open questions at the time
    • G protein coupling partner in skeletal muscle not identified
    • Whether TAS1R3 is the obligate partner in muscle is untested
    • Physiological glucose concentration range that activates the pathway in vivo not delineated
  11. 2024 Medium

    Pharmacological activation and inhibition of intestinal TAS1R2-TAS1R3 in humans during OGTT bidirectionally modulated plasma glucose and insulin, providing direct translational evidence for the receptor's metabolic role.

    Evidence Randomized human OGTT with sucralose or lactisole, plasma glucose/insulin measurement

    PMID:38691547

    Open questions at the time
    • Small sample size limits generalizability
    • Cannot fully exclude extra-intestinal contributions of sucralose/lactisole

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution experimental structure of TAS1R2 (alone or in the heterodimer) exists, and the G protein coupling specificity and downstream signaling cascades in extra-gustatory tissues remain incompletely characterized.
  • Cryo-EM or crystal structure of TAS1R2-TAS1R3 heterodimer needed
  • G protein identity in intestine and muscle unknown
  • Role of TAS1R2 in testis entirely unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0140299 molecular sensor activity 2
Localization
GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-9709957 Sensory Perception 3 R-HSA-382551 Transport of small molecules 2 R-HSA-8963743 Digestion and absorption 1
Partners
ERK1ERK2GLUT2PARP1TAS1R3
Complex memberships
TAS1R2-TAS1R3 heterodimer

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 T1R2 and T1R3 subunits each bind sweet stimuli independently but with distinct affinities and conformational changes; ligand affinities for T1R3 are drastically reduced by a single amino acid change associated with decreased sweet taste sensitivity in mice, indicating individual subunits increase the receptive range of the sweet taste receptor. Ligand binding assays, site-directed mutagenesis, conformational change measurements on individual subunits Current biology : CB High 16271873
2002 Sweet-tasting proteins (brazzein, monellin, thaumatin) interact with the T1R2-T1R3 receptor not via the 'glutamate-like' pocket but by stabilizing the active form of the receptor at a secondary binding site, a mechanism distinct from small molecular weight sweeteners. Computational docking with homology model of T1R2-T1R3 receptor based on mGluR1 template FEBS letters Low 12208493
2005 Homology modeling of the T1R2-T1R3 heterodimer identified four ligand binding sites for low-molecular-weight sweeteners in the extracellular domain, and sweet proteins interact with a secondary site; models account for sweetness synergy. Homology modeling based on mGluR1 crystal structure, computational docking Journal of medicinal chemistry Low 16107151
2010 Key amino acid residues in brazzein at three interaction sites (Loop43, N/C-termini/Loop33, Loop9-19) are essential for activation of the T1R2-T1R3 sweet receptor; the Venus flytrap module of T1R2 is important for brazzein agonism; hT1R2 R217A mutation in lobe 2 affects subunit-subunit interaction rather than direct brazzein binding, supporting multi-point interaction mechanism. Site-directed mutagenesis of brazzein and receptor subunits, human taste panel, cell-based receptor assay in HEK293 cells, receptor chimeras Journal of molecular biology High 20302879
2009 Direct binding of sweet agonists and antagonists to the full heterodimeric T1R2-T1R3 receptor in native membranes from HEK293 cells was detected; STD NMR can distinguish mutations that alter ligand-binding sites from those affecting downstream signal transduction. Saturation transfer difference (STD) NMR spectroscopy on membranes from HEK293 cells expressing T1R2-T1R3 Biochimica et biophysica acta Medium 19664591
2009 T1R2 knockout mice display severely blunted licking responses to sucrose and Na-saccharin but retain relatively normal concentration-dependent licking to Polycose (glucose polymer mixture), indicating T1R2+T1R3 heterodimer is the principal receptor for sweet-tasting ligands but is individually unnecessary for normal Polycose responsiveness. T1R2 knockout mice, brief-access taste tests American journal of physiology. Regulatory, integrative and comparative physiology High 19158407
2011 T1R2 knockout and T1R3 knockout mice show severely impaired responding to glucose, maltose, and maltotriose, but T1R2+T1R3 double KO mice still display concentration-dependent responding to Polycose, demonstrating that glucose polymers stimulate a taste receptor independent of the T1R2+T1R3 heterodimer. T1R2 KO, T1R3 KO, T1R2/T1R3 double KO mice, brief-access taste tests The Journal of neuroscience : the official journal of the Society for Neuroscience High 21940444
2012 T1R2 KO and T1R3 KO mice show markedly decreased sensitivity to discriminate water from sucrose, glucose, or maltose in an operant procedure, but have normal EC50 values for Polycose, confirming T1R2+T1R3 heterodimer is the principal receptor for natural sweeteners but not all carbohydrate stimuli. T1R2 KO and T1R3 KO mice, operant two-response taste discrimination task American journal of physiology. Regulatory, integrative and comparative physiology High 22621968
2011 The cysteine-rich domain (CRD) of human T1R3 (not T1R2) is necessary for interaction with sweet-tasting protein thaumatin, as demonstrated by chimeric human-mouse sweet receptor constructs in HEK293 cells. Chimeric human-mouse T1R2/T1R3 receptor constructs expressed in HEK293 cells, functional assay Biochemical and biophysical research communications High 21329673
2011 Arg82 in thaumatin plays a central role in interaction with human T1R2-T1R3 sweet receptors; charge inversion at Arg82 (R82E) abolished receptor response even at 1 mM, while mutations at Lys67 had less effect. Site-directed mutagenesis of thaumatin, cell-based assay using HEK293 cells expressing human sweet receptors Biochemical and biophysical research communications High 21867681
2014 Human T1R3 surface expression requires coexpression with human T1R2 (but not vice versa for mouse), and both the Venus flytrap module and cysteine-rich domain of human T1R3 contain regions regulating membrane trafficking; the Venus flytrap module of both human T1R2 and T1R3 are needed for proper membrane trafficking, revealing distinct human and mouse trafficking systems. Tagged receptor constructs in HEK293 cells, domain-swapped chimeras, truncation mutants, surface expression assays PloS one High 25029362
2013 In vitro binding assays demonstrated specific enantiomeric activities of D- and L-amino acids on the TAS1R2-TAS1R3 sweet receptor, showing direct ligand-receptor interaction for multiple amino acid stereoisomers. Cell-based in vitro assay with HEK293 cells overexpressing TAS1R2/TAS1R3, binding assay Food chemistry Medium 24360415
2015 Sugar-induced cephalic-phase insulin release (CPIR) occurs in T1R3 knockout mice (lacking functional T1R2+T1R3 heterodimer) following oral but not intragastric glucose administration, demonstrating that CPIR is mediated by a T1R2+T1R3-independent taste transduction pathway. T1R3 KO mice, oral vs. intragastric glucose administration, insulin measurement, chorda tympani nerve recordings American journal of physiology. Regulatory, integrative and comparative physiology High 26157055
2018 T1R2-mediated glucose sensing in the upper intestine enhances glucose absorption by regulating GLUT2 transporter trafficking to the apical membrane of enterocytes; this effect is dependent on GLP-2 secretion and subsequent intestinal neuronal activation, as demonstrated in T1R2 knockout mice. T1R2 knockout mice, in vivo glucose absorption assay, ex vivo intact intestinal preparations, GLUT2 localization Molecular metabolism High 30201274
2016 Disruption of T1R2 in mice fed a high-fat/low-carbohydrate diet protects against diet-induced hyperinsulinemia and alters substrate utilization (increased glucose oxidation, decreased liver triglyceride accumulation); sweet taste receptors (T1r2/T1r3) are upregulated in adipose tissue in response to HF/LC diet and correlate with fat mass and glucose intolerance. T1R2 global knockout mice, metabolic phenotyping, body composition, glucose homeostasis assays American journal of physiology. Endocrinology and metabolism High 26884387
2021 The TAS1R2 Ile191Val variant causes partial loss of function through reduced receptor availability in the plasma membrane (not altered ligand binding); Val allele carriers have reduced glucose excursions during OGTT, supporting a peripheral (intestinal) role for TAS1R2 in metabolic regulation. In vitro biochemical assays for receptor membrane availability, oral glucose tolerance tests in human participants stratified by genotype Molecular metabolism High 34509698
2024 TAS1R2 in skeletal muscle acts as an ambient glucose sensor; receptor stimulation induces ERK1/2-dependent phosphorylation and activation of PARP1, a major NAD consumer; muscle-specific TAS1R2 deletion suppresses PARP1 activity, elevates NAD levels, and enhances mitochondrial capacity and running endurance. Muscle-specific TAS1R2 knockout mice, ERK1/2 phosphorylation assays, PARP1 activity assays, NAD measurements, exercise endurance testing Nature communications High 38851747
2018 The heptahelical (transmembrane) domain of T1R2 is the allosteric binding site for amiloride, a sweet taste inhibitor, and mediates species-dependent sensitivity; this site is distinct from the lactisole binding site on T1R3, as shown using human/squirrel monkey/mouse chimeric receptors. Chimeric T1R2/T1R3 receptors from human, squirrel monkey, and mouse expressed in HEK293 cells; perillartine as T1R2 TMD-specific agonist; functional assays Journal of molecular neuroscience : MN High 30120716
2021 L-glucose activates the TAS1R2/TAS1R3 sweet taste receptor in a dose-dependent manner in cell-based functional assays; computational docking to the VFT domain of TAS1R2 suggests two sub-pockets, each compatible with one glucose enantiomer, with shared hydrogen-bond interactions explaining similar detection thresholds for D- and L-glucose. Cell-based functional assay with TAS1R2/TAS1R3, human sensory detection thresholds, computational docking Food chemistry Medium 34715629
2021 Human TAS1R2 expressed and purified as a dimer from HEK293S cells is properly folded and capable of binding high-potency sweeteners with Kd values consistent with physiological detection thresholds, as measured by intrinsic tryptophan fluorescence and size-exclusion chromatography coupled to light scattering. Recombinant protein expression in stable tetracycline-inducible HEK293S cells, protein purification, circular dichroism, size-exclusion chromatography with light scattering, intrinsic tryptophan fluorescence Scientific reports Medium 34782704
2022 The Venus Flytrap domain of TAS1R2 (hTAS1R2-VFT) expressed as a monomer binds sweet stimuli with Kd values consistent with physiological detection; point mutations D278A and E382A that abolish full-length receptor response also drastically reduce VFT ligand affinity, confirming VFT as the primary sweet compound binding site. Recombinant hTAS1R2-VFT expression in E. coli, site-directed mutagenesis, intrinsic tryptophan fluorescence, size-exclusion chromatography with light scattering, circular dichroism International journal of molecular sciences High 36012481
2024 Steviol glycosides bind to four distinct sites on the T1R2/T1R3 heterodimer (VFD2, VFD3, TMD2, TMD3); the C20 carboxy terminus of the Gα protein can bind to the intracellular region of either TMD2 or TMD3, shifting the receptor to high-affinity state for steviol glycosides. Competitive binding experiments with radiolabeled ligands, computational docking studies Communications chemistry Medium 39424933
2012 Species-dependent sweet taste responses are determined by specific subunits: residues in T1R2 determine species-dependent saccharin responses, while residues in either T1R2 or T1R3 mediate species-dependent responses to monellin; squirrel monkey sweet receptor does not respond to aspartame, neotame, cyclamate, saccharin, or monellin, but responds to thaumatin. Cloning and functional characterization of squirrel monkey T1R2/T1R3, chimeric receptor assays in HEK293 cells, molecular modeling Biochemical and biophysical research communications High 23000410
2010 T1R2-LacZ knock-in mouse revealed T1R2 expression in taste tissue, gastrointestinal tract (where T1R3 is co-expressed), and unexpectedly in testis; homozygous T1R2 deletion mice lack T1R2 protein, confirming T1R2 as a required component of the sweet taste receptor system. T1R2-LacZ reporter knock-in mouse generation, immunohistochemistry with anti-T1R2 antibody Biochemical and biophysical research communications Medium 20965149
2024 Activation of TAS1R2-TAS1R3 with sucralose during OGTT elevated plasma insulin responses, and individual sucralose sweetness ratings correlated with early glucose and insulin increases; inhibition with lactisole was correlated with decreased plasma glucose, demonstrating bidirectional regulation of glucose metabolism by intestinal TAS1R2-TAS1R3 signaling in humans. Randomized human OGTT with sucralose or lactisole, plasma glucose/insulin/glucagon measurement, individual sweetness response assessment PloS one Medium 38691547

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 LIGHT, a novel ligand for lymphotoxin beta receptor and TR2/HVEM induces apoptosis and suppresses in vivo tumor formation via gene transfer. The Journal of clinical investigation 211 9739048
2005 Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detection of sweet stimuli. Current biology : CB 199 16271873
1998 Herpesvirus entry mediator ligand (HVEM-L), a novel ligand for HVEM/TR2, stimulates proliferation of T cells and inhibits HT29 cell growth. The Journal of biological chemistry 192 9765287
2005 Preligand assembly domain-mediated ligand-independent association between TRAIL receptor 4 (TR4) and TR2 regulates TRAIL-induced apoptosis. Proceedings of the National Academy of Sciences of the United States of America 189 16319225
2005 From small sweeteners to sweet proteins: anatomy of the binding sites of the human T1R2_T1R3 receptor. Journal of medicinal chemistry 116 16107151
1998 Cloning and characterization of mouse RIP140, a corepressor for nuclear orphan receptor TR2. Molecular and cellular biology 113 9774688
2010 Genetic variation in TAS1R2 (Ile191Val) is associated with consumption of sugars in overweight and obese individuals in 2 distinct populations. The American journal of clinical nutrition 112 20943793
2002 Why are sweet proteins sweet? Interaction of brazzein, monellin and thaumatin with the T1R2-T1R3 receptor. FEBS letters 107 12208493
2011 Nuclear receptors TR2 and TR4 recruit multiple epigenetic transcriptional corepressors that associate specifically with the embryonic β-type globin promoters in differentiated adult erythroid cells. Molecular and cellular biology 106 21670149
2002 An embryonic/fetal beta-type globin gene repressor contains a nuclear receptor TR2/TR4 heterodimer. The EMBO journal 98 12093744
1998 Antibodies to TR2 (herpesvirus entry mediator), a new member of the TNF receptor superfamily, block T cell proliferation, expression of activation markers, and production of cytokines. Journal of immunology (Baltimore, Md. : 1950) 96 9712045
1989 Molecular cloning of new human TR2 receptors: a class of steroid receptor with multiple ligand-binding domains. Biochemical and biophysical research communications 94 2597158
2003 Induction of caspase 8 by interferon gamma renders some neuroblastoma (NB) cells sensitive to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but reveals that a lack of membrane TR1/TR2 also contributes to TRAIL resistance in NB. Cancer research 87 12615731
2007 Embryonic and fetal beta-globin gene repression by the orphan nuclear receptors, TR2 and TR4. The EMBO journal 86 17431400
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
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
2002 Recent advances in the TR2 and TR4 orphan receptors of the nuclear receptor superfamily. The Journal of steroid biochemistry and molecular biology 79 12361719
2010 Key amino acid residues involved in multi-point binding interactions between brazzein, a sweet protein, and the T1R2-T1R3 human sweet receptor. Journal of molecular biology 77 20302879
2005 Co-expression patterns of the neuropeptides vasoactive intestinal peptide and cholecystokinin with the transduction molecules alpha-gustducin and T1R2 in rat taste receptor cells. Neuroscience 70 15561439
2015 Variation in the TAS1R2 Gene, Sweet Taste Perception and Intake of Sugars. Journal of nutrigenetics and nutrigenomics 65 26279452
2010 Evolution of the sweet taste receptor gene Tas1r2 in bats. Molecular biology and evolution 65 20558596
2008 Retinoic acid-stimulated sequential phosphorylation, PML recruitment, and SUMOylation of nuclear receptor TR2 to suppress Oct4 expression. Proceedings of the National Academy of Sciences of the United States of America 65 18682553
2016 Sweet Taste Receptor TAS1R2 Polymorphism (Val191Val) Is Associated with a Higher Carbohydrate Intake and Hypertriglyceridemia among the Population of West Mexico. Nutrients 64 26907331
2011 Behavioral evidence for a glucose polymer taste receptor that is independent of the T1R2+3 heterodimer in a mouse model. The Journal of neuroscience : the official journal of the Society for Neuroscience 64 21940444
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
1995 Multiple functions of the TR2-11 orphan receptor in modulating activation of two key cis-acting elements involved in the retinoic acid signal transduction system. The Journal of biological chemistry 57 8530418
2011 Expression and distribution of the sweet taste receptor isoforms T1R2 and T1R3 in human and rat bladders. The Journal of urology 56 22019168
2021 Isolation and Characterization of a Novel Salmonella Phage vB_SalP_TR2. Frontiers in microbiology 55 34234757
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
1995 Identification of human TR2 orphan receptor response element in the transcriptional initiation site of the simian virus 40 major late promoter. The Journal of biological chemistry 54 7890658
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
2012 Association of GLUT2 and TAS1R2 genotypes with risk for dental caries. Caries research 49 23257979
2006 SUMOylation of Tr2 orphan receptor involves Pml and fine-tunes Oct4 expression in stem cells. Nature structural & molecular biology 46 17187077
2018 T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways. Molecular metabolism 45 30201274
2007 The TR2 and TR4 orphan nuclear receptors repress Gata1 transcription. Genes & development 45 17974920
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
1996 p53 is a mediator for radiation-repressed human TR2 orphan receptor expression in MCF-7 cells, a new pathway from tumor suppressor to member of the steroid receptor superfamily. The Journal of biological chemistry 43 8663350
2011 Forced TR2/TR4 expression in sickle cell disease mice confers enhanced fetal hemoglobin synthesis and alleviated disease phenotypes. Proceedings of the National Academy of Sciences of the United States of America 42 22042865
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
1998 A novel nuclear receptor heterodimerization pathway mediated by orphan receptors TR2 and TR4. The Journal of biological chemistry 39 9737983
2002 Suppression of estrogen receptor-mediated transcription and cell growth by interaction with TR2 orphan receptor. The Journal of biological chemistry 38 12093804
2017 TR2 and TR4 Orphan Nuclear Receptors: An Overview. Current topics in developmental biology 35 28527578
2010 Generation and characterization of T1R2-LacZ knock-in mouse. Biochemical and biophysical research communications 34 20965149
2002 The neural differentiation gene Mash-1 has a distinct pattern of expression from the taste reception-related genes gustducin and T1R2 in the taste buds. Chemical senses 34 12052781
2016 Disruption of the sugar-sensing receptor T1R2 attenuates metabolic derangements associated with diet-induced obesity. American journal of physiology. Endocrinology and metabolism 33 26884387
1998 A bidirectional regulation between the TR2/TR4 orphan receptors (TR2/TR4) and the ciliary neurotrophic factor (CNTF) signaling pathway. The Journal of biological chemistry 29 9694834
2019 T1R2+T1R3-independent chemosensory inputs contributing to behavioral discrimination of sugars in mice. American journal of physiology. Regulatory, integrative and comparative physiology 28 30624973
2015 GLUT2 and TAS1R2 Polymorphisms and Susceptibility to Dental Caries. Caries research 28 26112465
2009 Analyses of sweet receptor gene (Tas1r2) and preference for sweet stimuli in species of Carnivora. The Journal of heredity 27 19366814
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
2001 The orphan nuclear receptor TR2 interacts directly with both class I and class II histone deacetylases. Molecular endocrinology (Baltimore, Md.) 27 11463856
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
2007 Orphan nuclear receptor TR2, a mediator of preadipocyte proliferation, is differentially regulated by RA through exchange of coactivator PCAF with corepressor RIP140 on a platform molecule GRIP1. Nucleic acids research 25 17389641
1986 Initiation of swimming activity by trigger neurons in the leech subesophageal ganglion. III. Sensory inputs to Tr1 and Tr2. Journal of comparative physiology. A, Sensory, neural, and behavioral physiology 25 3023604
2021 Biophysical and functional characterization of the human TAS1R2 sweet taste receptor overexpressed in a HEK293S inducible cell line. Scientific reports 24 34782704
2010 The T1R2/T1R3 sweet receptor and TRPM5 ion channel taste targets with therapeutic potential. Progress in molecular biology and translational science 24 20691962
2003 TR2 orphan receptor functions as negative modulator for androgen receptor in prostate cancer cells PC-3. The Prostate 24 12949936
1997 Distinct expression patterns and biological activities of two isoforms of the mouse orphan receptor TR2. The Journal of endocrinology 24 9071982
2015 Polymorphisms in sweet taste genes (TAS1R2 and GLUT2), sweet liking, and dental caries prevalence in an adult Italian population. Genes & nutrition 23 26268603
1998 Mechanisms of the mouse orphan nuclear receptor TR2-11-mediated gene suppression. The Journal of biological chemistry 23 9660764
2015 Compound loss of function of nuclear receptors Tr2 and Tr4 leads to induction of murine embryonic β-type globin genes. Blood 22 25561507
1999 Characterization of an inverted repeat with a zero spacer (IR0)-type retinoic acid response element from the mouse nuclear orphan receptor TR2-11 gene. Biochemistry 22 10393558
1997 The orphan nuclear receptor TR2 suppresses a DR4 hormone response element of the mouse CRABP-I gene promoter. Biochemistry 22 9369481
2011 The cysteine-rich domain of human T1R3 is necessary for the interaction between human T1R2-T1R3 sweet receptors and a sweet-tasting protein, thaumatin. Biochemical and biophysical research communications 21 21329673
2011 Introduction of a negative charge at Arg82 in thaumatin abolished responses to human T1R2-T1R3 sweet receptors. Biochemical and biophysical research communications 21 21867681
2014 Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3. PloS one 20 25029362
1998 A constitutive nuclear localization signal from the second zinc-finger of orphan nuclear receptor TR2. The Journal of endocrinology 20 9795341
2000 Constitutive activation of retinoic acid receptor beta2 promoter by orphan nuclear receptor TR2. The Journal of biological chemistry 19 10766818
2021 Investigating mechanism of sweetness intensity differences through dynamic analysis of sweetener-T1R2-membrane systems. Food chemistry 18 34915374
2018 The Heptahelical Domain of the Sweet Taste Receptor T1R2 Is a New Allosteric Binding Site for the Sweet Taste Modulator Amiloride That Modulates Sweet Taste in a Species-Dependent Manner. Journal of molecular neuroscience : MN 18 30120716
1998 Thyroid hormone direct repeat 4 response element is a positive regulatory element for the human TR2 orphan receptor, a member of steroid receptor superfamily. Molecular and cellular biochemistry 18 9879671
2021 Taste and chirality: l-glucose sweetness is mediated by TAS1R2/TAS2R3 receptor. Food chemistry 17 34715629
2016 Characterization of the Sweet Taste Receptor Tas1r2 from an Old World Monkey Species Rhesus Monkey and Species-Dependent Activation of the Monomeric Receptor by an Intense Sweetener Perillartine. PloS one 17 27479072
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
2021 The Ile191Val is a partial loss-of-function variant of the TAS1R2 sweet-taste receptor and is associated with reduced glucose excursions in humans. Molecular metabolism 16 34509698
2024 Steviol rebaudiosides bind to four different sites of the human sweet taste receptor (T1R2/T1R3) complex explaining confusing experiments. Communications chemistry 15 39424933
2016 Oxaliplatin Alters Expression of T1R2 Receptor and Sensitivity to Sweet Taste in Rats. Biological & pharmaceutical bulletin 15 27040630
2009 HDAC3 as a molecular chaperone for shuttling phosphorylated TR2 to PML: a novel deacetylase activity-independent function of HDAC3. PloS one 15 19204783
2006 Ligand-independent orphan receptor TR2 activation by phosphorylation at the DNA-binding domain. Proteomics 15 16317770
2005 Protein kinase C-mediated phosphorylation of orphan nuclear receptor TR2: effects on receptor stability and activity. Proteomics 15 16130175
2020 Influences of non-nutritive sweeteners on ovarian and uterine expression of T1R2 and T1R3 in peripubertal female guinea pigs. Animal science journal = Nihon chikusan Gakkaiho 14 32219957
2006 SmTR2/4, a Schistosoma mansoni homologue of TR2/TR4 orphan nuclear receptor. International journal for parasitology 14 16839558
1999 Identification of the histamine H1 receptor gene as a differentially repressed target of the human TR2 orphan receptor. Molecular and cellular biochemistry 14 10391141
2024 Activation and inhibition of the sweet taste receptor TAS1R2-TAS1R3 differentially affect glucose tolerance in humans. PloS one 12 38691547
2022 Functional Characterization of the Venus Flytrap Domain of the Human TAS1R2 Sweet Taste Receptor. International journal of molecular sciences 12 36012481
2021 Whole-Brain Mapping of the Expression Pattern of T1R2, a Subunit Specific to the Sweet Taste Receptor. Frontiers in neuroanatomy 12 34776881
1998 The genomic structure and chromosomal location of the human TR2 orphan receptor, a member of the steroid receptor superfamily. Endocrine 12 9704569
2024 Rethinking Sweetener Discovering: Multiparameter Modeling of Molecular Docking Results between the T1R2-T1R3 Receptor and Compounds with Different Tastes. Journal of agricultural and food chemistry 11 38508871
2019 Unnatural Tripeptides as Potent Positive Allosteric Modulators of T1R2/T1R3. ACS medicinal chemistry letters 11 31098002
2006 Transcriptional regulation of the human TR2 orphan receptor gene by nuclear factor 1-A. Biochemical and biophysical research communications 11 17010934
2024 The TAS1R2 G-protein-coupled receptor is an ambient glucose sensor in skeletal muscle that regulates NAD homeostasis and mitochondrial capacity. Nature communications 10 38851747
2021 Non-nutritive sweetener activation of the pig sweet taste receptor T1R2-T1R3 in vitro mirrors sweetener stimulation of the gut-expressed receptor in vivo. Biochemical and biophysical research communications 10 33486192
1998 Striking evolutionary conservation of a cis-element related to nuclear receptor target sites and present in TR2 orphan receptor genes. Biochemical and biophysical research communications 10 9535784
1997 Identification of the human aldolase A gene as the first induced target for the TR2 orphan receptor, a member of the steroid hormone receptor superfamily. Biochemical and biophysical research communications 10 9196064
1994 Molecular cloning of a novel member of the nuclear receptor superfamily related to the orphan receptor, TR2. Gene expression 10 7841789
2024 Artificial and Natural Sweeteners Biased T1R2/T1R3 Taste Receptors Transactivate Glycosylated Receptors on Cancer Cells to Induce Epithelial-Mesenchymal Transition of Metastatic Phenotype. Nutrients 9 38931195
2020 An in-silico layer-by-layer adsorption study of the interaction between Rebaudioside A and the T1R2 human sweet taste receptor: modelling and biosensing perspectives. Scientific reports 9 33110140
2017 The nuclear hormone receptor gene Nr2c1 (Tr2) is a critical regulator of early retina cell patterning. Developmental biology 9 28551284
2017 Detection of maltodextrin and its discrimination from sucrose are independent of the T1R2 + T1R3 heterodimer. American journal of physiology. Regulatory, integrative and comparative physiology 9 28768658