Affinage

Showing TAS1R2 — T1R2 is a alias.

TAS1R2

Taste receptor type 1 member 2 · UniProt Q8TE23

Length
839 aa
Mass
95.2 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAS1R2 is the ligand-binding subunit of the heterodimeric sweet taste receptor T1R2/T1R3, a class C G protein-coupled receptor that constitutes the principal detector of simple sugars and high-potency sweeteners; genetic ablation of T1R2 abolishes behavioral responses to sucrose, glucose, and maltose while sparing responses to glucose polymers (PMID:21940444, PMID:22621968, PMID:19158407). The extracellular Venus flytrap domain (VFT) of T1R2 forms the primary small-molecule binding site: the isolated hTAS1R2-VFT folds and binds sweet stimuli at physiological affinities, and the substitutions D278A and E382A that abolish full-length receptor responses also cripple ligand binding by the isolated domain (PMID:36012481), with additional contact residues (I67, R317) governing potency and species-specific sensitivity to sulfamate sweeteners (PMID:40706454, PMID:36806908). Beyond the VFT, sweet-tasting proteins such as brazzein and thaumatin engage a secondary interaction surface involving the subunit interface and the T1R3 cysteine-rich domain (PMID:20302879, PMID:21329673), while the T1R2 transmembrane domain provides an allosteric site for modulators including the inhibitor amiloride (PMID:30120716). Receptor surface expression requires co-assembly of human T1R2 and T1R3 VFT modules (PMID:25029362), and alternative splicing of T1R2 — including PTBP1-driven skipping of exon 4 — produces non-functional heterodimers that suppress sweet perception (PMID:36484118). Beyond the tongue, T1R2 is expressed in the gut, brain, and other peripheral tissues (PMID:20965149, PMID:34776881), where it acts as a glucose sensor: in the upper intestine it enhances glucose absorption by promoting apical GLUT2 trafficking through GLP-2 secretion and intestinal neuronal activation (PMID:30201274), and in skeletal muscle it drives an ERK1/2–PARP1 axis that consumes NAD, such that muscle-specific T1R2 loss elevates NAD, improves mitochondrial capacity, and enhances endurance (PMID:38851747). A common partial-loss-of-function variant (Ile191Val) reducing receptor surface availability lowers postprandial glucose excursions in human carriers (PMID:34509698).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2005 High

    Established that each T1R subunit binds sweet ligands independently with distinct affinities, explaining how the heterodimer achieves a broad receptive range rather than acting as a single binding entity.

    Evidence Ligand-binding assays on individual subunits with site-directed mutagenesis and mouse behavioral phenotyping

    PMID:16271873

    Open questions at the time
    • Did not assign which natural sugars and sweeteners map to which subunit
    • Conformational changes inferred rather than structurally resolved
  2. 2010 High

    Resolved how sweet proteins activate the receptor, showing they act through multi-point interactions at the subunit interface rather than the small-molecule pocket, distinguishing two modes of receptor activation.

    Evidence Brazzein and receptor mutagenesis, chimeric receptors in HEK293 cells, and human taste panels; complemented by NMR of a sweet-protein mutant

    PMID:12706725 PMID:20302879

    Open questions at the time
    • Exact spatial arrangement of the sweet-protein contact surface not crystallographically defined
    • Stoichiometry of multi-point engagement unresolved
  3. 2011 Medium

    Mapped the molecular requirements for sweet-protein recognition to the T1R3 cysteine-rich domain and a specific thaumatin residue, defining a determinant of species-specific sweet-protein responsiveness.

    Evidence Chimeric human/mouse receptor assays and thaumatin site-directed mutagenesis in HEK293 cells

    PMID:21329673 PMID:21867681

    Open questions at the time
    • Role of T1R2 in sweet-protein binding versus T1R3 not fully separated
    • Structural basis of the charge requirement at thaumatin Arg82 not visualized
  4. 2012 High

    Defined the in vivo ligand scope of the receptor genetically, demonstrating the T1R2/T1R3 heterodimer is the principal receptor for simple sugars but not glucose polymers, which use a separate mechanism.

    Evidence T1R2, T1R3, and double knockout mice with brief-access and operant taste tests

    PMID:19158407 PMID:21940444 PMID:22621968

    Open questions at the time
    • Identity of the glucose-polymer receptor not determined
    • Residual non-T1R sugar sensing not characterized
  5. 2014 Medium

    Explained the obligate heterodimeric assembly of the human receptor by showing T1R3 surface expression depends on T1R2 and that both VFT modules are required for trafficking.

    Evidence Tagged constructs, domain-swap chimeras, and truncation mutants with surface expression assays in HEK293 cells

    PMID:25029362

    Open questions at the time
    • Chaperone or trafficking machinery mediating assembly not identified
    • Species difference in independent mouse T1r3 trafficking not mechanistically explained
  6. 2018 Medium

    Identified the T1R2 transmembrane domain as an allosteric modulator site, locating amiloride binding to the TMD distinct from the T1R3 lactisole site and explaining species-dependent amiloride sensitivity.

    Evidence Chimeric human/squirrel monkey/mouse receptors and perillartine activation of the isolated T1R2 TMD in cell-based assays

    PMID:30120716

    Open questions at the time
    • TMD allosteric pocket not structurally defined
    • Physiological relevance of amiloride modulation unaddressed
  7. 2018 High

    Extended T1R2 function beyond taste to intestinal nutrient handling, defining a T1R2 to GLP-2 to neuronal activation to GLUT2 trafficking pathway that enhances glucose absorption.

    Evidence T1R2 knockout mice with in vivo and ex vivo glucose absorption, GLUT2 trafficking assays, and pharmacological blockade

    PMID:30201274

    Open questions at the time
    • G protein and intracellular signaling steps coupling T1R2 to GLP-2 release not dissected
    • Whether intestinal effect requires T1R3 co-expression not isolated here
  8. 2021 Medium

    Established a direct human genotype-physiology link, showing a common partial-loss-of-function TAS1R2 variant reduces receptor surface availability and lowers postprandial glucose excursions.

    Evidence In vitro receptor membrane-availability assays plus oral glucose tolerance tests in genotyped human participants

    PMID:34509698

    Open questions at the time
    • Tissue site (gut vs peripheral) driving the glucose phenotype not localized
    • Mechanism connecting reduced surface receptor to lower glucose excursion not traced
  9. 2022 High

    Confirmed the T1R2 VFT as the primary small-molecule binding determinant by reconstituting the isolated domain and validating key binding residues biochemically.

    Evidence Bacterially expressed hTAS1R2-VFT with CD, SEC-MALS, mutagenesis (D278A, E382A), and tryptophan fluorescence binding; complemented by full-subunit dimer biophysics

    PMID:34782704 PMID:36012481

    Open questions at the time
    • High-resolution structure of the ligand-bound VFT not solved
    • How VFT closure couples to TMD activation not addressed
  10. 2022 High

    Revealed splicing as a regulatory layer over sweet receptor function, showing PTBP1-driven exon skipping generates dominant-negative T1R2 isoforms that suppress sweet perception, including in response to infection.

    Evidence Splice variant cloning, heterologous functional assays, in vivo behavioral tests, PTBP1 knockdown/overexpression, and LPS challenge in mice

    PMID:34409805 PMID:36484118

    Open questions at the time
    • Physiological triggers regulating PTBP1 in taste tissue beyond LPS not defined
    • Magnitude of splicing control on human sweet perception not quantified
  11. 2024 High

    Defined a peripheral metabolic role for T1R2 in skeletal muscle, establishing an ERK1/2-PARP1-NAD axis through which the receptor acts as a glucose surveyor controlling mitochondrial capacity and endurance.

    Evidence Muscle-specific TAS1R2 knockout mice with PARP1 activity, NAD measurement, mitochondrial and endurance assays, and ERK1/2 phosphorylation readouts; consistent preprint precursor

    PMID:36798161 PMID:38851747

    Open questions at the time
    • G protein coupling linking muscle T1R2 to ERK1/2 not identified
    • Whether muscle T1R2 functions as a heterodimer with T1R3 not established
  12. 2024 Medium

    Refined the multi-site model of receptor pharmacology, mapping sweetener binding to four distinct VFT and TMD sites and linking Galpha C-terminus engagement to a high-affinity receptor state.

    Evidence Radioligand binding with computational docking at four sites and G protein coupling analysis

    PMID:39424933

    Open questions at the time
    • Docking-based site assignments lack experimental structural confirmation
    • Functional hierarchy among the four sites not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How VFT ligand binding is allosterically transduced through the TMD to specific G protein outputs across taste, gut, and muscle contexts remains unresolved.
  • No experimental full-length receptor structure linking domains
  • Tissue-specific G protein partners and effector branches not mapped
  • Whether peripheral T1R2 always requires T1R3 unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0140299 molecular sensor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 2 R-HSA-9709957 Sensory Perception 2 R-HSA-382551 Transport of small molecules 1
Partners
PTBP1TAS1R3
Complex memberships
T1R2/T1R3 sweet taste receptor heterodimer

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 Each of the two subunits of the heteromeric T1R2:T1R3 sweet taste receptor binds sweet stimuli independently but with distinct affinities and conformational changes; a single amino acid change in T1R3 associated with decreased sweet sensitivity in mice drastically reduced ligand affinity for T1R3, demonstrating that individual T1R subunits increase the receptive range of the sweet taste receptor. Ligand-binding assays with individual subunits, site-directed mutagenesis, behavioral phenotyping in mice Current biology : CB High 16271873
2002 Sweet-tasting proteins (brazzein, monellin, thaumatin) interact with the T1R2-T1R3 receptor at a secondary allosteric binding site distinct from the 'glutamate-like' (Venus flytrap) pocket used by small-molecule sweeteners, and stabilize the active (free form II) conformation of the receptor. Computational docking with a homology model of T1R2-T1R3; structural reasoning from protein mutant analysis FEBS letters Low 12208493
2005 Homology modeling of the T1R2-T1R3 extracellular ligand-binding domain on mGluR1 identified four binding sites for low-molecular-weight sweeteners and a secondary site for sweet proteins; docking experiments showed sweet proteins bind the secondary site, accounting for sweetness synergy. Homology modeling based on mGluR1 crystal structure; in silico docking Journal of medicinal chemistry Low 16107151
2003 NMR solution structure of the G16A mutant of single-chain monellin (MNEI) showed that the sweetness-reducing mutation does not affect glucophore positions but displaces secondary structural elements on the protein surface, establishing that sweet proteins do not act via a 'sweet finger' mechanism but rather through a conformational interaction with a secondary site on T1R2-T1R3. NMR solution structure determination of sweet protein mutant; comparison with wild-type structure Journal of molecular biology Medium 12706725
2010 Mutagenesis of brazzein surface residues and T1R2/T1R3 chimeras established that brazzein activates the sweet receptor through multi-point interactions; the Venus flytrap module of T1R2 is important for brazzein agonism; a T1R2 R217A mutation in lobe 2 at the subunit interface selectively reduced brazzein activity by altering subunit-subunit interaction rather than direct ligand binding. Site-directed mutagenesis of brazzein and receptor subunits; chimeric receptor assays in HEK293 cells; human taste panel; in vitro receptor activity assay Journal of molecular biology High 20302879
2009 Saturation transfer difference (STD) NMR spectroscopy directly detected binding of sweet agonists and antagonists to the full heterodimeric T1R2/T1R3 receptor in membranes from HEK293 cells, allowing distinction between mutations that alter ligand-binding sites versus those affecting downstream signal transduction. STD NMR spectroscopy on membrane-expressed receptor Biochimica et biophysica acta Medium 19664591
2011 The cysteine-rich domain (CRD) of human T1R3 (not T1R2) is necessary for the interaction of the T1R2-T1R3 heterodimer with the sweet-tasting protein thaumatin, as demonstrated by chimeric human-mouse receptor assays showing that hT1R2/mT1R3 responds to sucralose but not thaumatin. Chimeric human/mouse receptor expression in HEK293 cells; functional assay Biochemical and biophysical research communications Medium 21329673
2011 Arg82 of thaumatin is a critical residue for interaction with human T1R2-T1R3; charge inversion at Arg82 (R82E) abolished receptor activation even at 1 mM, while Lys67 mutations were less disruptive, indicating a strict spatial charge requirement at position 82 for receptor binding. Site-directed mutagenesis of thaumatin; cell-based receptor assay in HEK293 cells expressing human sweet receptors Biochemical and biophysical research communications Medium 21867681
2012 T1R2 knockout and T1R3 knockout mice displayed severely impaired licking responses to sucrose, glucose, and maltose, but retained relatively normal concentration-dependent responding to Polycose (glucose polymer), establishing that the T1R2+T1R3 heterodimer is the principal receptor for simple sugars but not for glucose polymers, which activate a separate receptor mechanism. T1R2 and T1R3 knockout mice; T1R2/T1R3 double knockout mice; brief-access taste tests and two-response operant discrimination The Journal of neuroscience; American journal of physiology. Regulatory, integrative and comparative physiology High 19158407 21940444 22621968
2014 Human T1R3 surface expression requires co-expression with human T1R2, whereas mouse T1r3 reaches the membrane independently; domain-swap chimeras showed the Venus flytrap module and cysteine-rich domain (CRD) of human T1R3 contain regions that inhibit T1R3 membrane trafficking when expressed alone, and the Venus flytrap modules of both human T1R2 and T1R3 are needed for proper membrane trafficking of the heterodimer. Tagged T1R2/T1R3 constructs expressed in HEK293 cells; domain-swap chimeras; truncation mutants; surface expression assay PloS one Medium 25029362
2010 T1R2-LacZ reporter knock-in mice revealed that T1R2 is expressed in taste tissue, the gastrointestinal tract (where T1R3 is also expressed), and unexpectedly in the testis; homozygous T1R2 deletion mice lacked T1R2 protein, confirming the knock-in allele. T1R2-LacZ reporter knock-in mouse; LacZ staining; immunohistochemistry with validated antibody Biochemical and biophysical research communications Medium 20965149
2018 T1R2 receptor signaling in the upper intestine enhances glucose absorption specifically in response to glucose-rich meals by regulating GLUT2 transporter trafficking to the apical membrane of enterocytes; these effects were dependent on GLP-2 secretion and subsequent intestinal neuronal activation; high-sucrose feeding in wild-type mice rapidly downregulated intestinal STRs, reducing glucose absorption. T1R2 knockout mice; in vivo glucose absorption measurements; ex vivo intact intestinal preparations; GLUT2 trafficking assays; pharmacological blockade Molecular metabolism High 30201274
2016 Global disruption of T1R2 in mice fed a high-fat/low-carbohydrate diet resulted in reduced fat mass, increased lean mass, hyperactivity, protection from diet-induced hyperinsulinemia, increased glucose oxidation rates, and decreased liver triglyceride accumulation; sweet taste receptors (T1r2/T1r3) were upregulated in adipose tissue in response to HF/LC diet and positively correlated with fat mass and glucose intolerance. T1R2 knockout mice; high-fat diet feeding; body composition, energy balance, glucose homeostasis, and tissue substrate metabolism measurements American journal of physiology. Endocrinology and metabolism Medium 26884387
2021 The Ile191Val common variant of TAS1R2 causes a partial loss of function through reduced receptor availability at the plasma membrane; human Val minor allele carriers show reduced plasma glucose excursions during an OGTT compared to Ile/Ile carriers, effects not explained by differences in beta-cell function or insulin sensitivity. In vitro biochemical assays of receptor membrane availability; oral glucose tolerance tests in human participants; genotyping Molecular metabolism Medium 34509698
2018 The heptahelical domain (TMD) of T1R2 is the allosteric binding site for the sweet inhibitor amiloride; this was distinct from the T1R3-binding site of lactisole; using chimeric human/squirrel monkey/mouse T1R2 and T1R3 receptors and the agonist perillartine (which activates the single TMD of T1R2), the T1R2 TMD was identified as the molecular determinant mediating species-dependent amiloride sensitivity. Chimeric human/squirrel monkey/mouse T1R2/T1R3 receptors in cell-based functional assays; perillartine activation of isolated T1R2 TMD Journal of molecular neuroscience : MN Medium 30120716
2012 Squirrel monkey T1R2/T1R3 responds to natural sugars and some sweet proteins (thaumatin at high concentrations) but not to aspartame, neotame, cyclamate, saccharin, or monellin; the residues in T1R2 determine species-dependent sensitivity to saccharin, while residues in either T1R2 or T1R3 underlie sweet taste differences toward monellin between humans and squirrel monkeys. Cloning and heterologous expression of squirrel monkey T1R2/T1R3; cell-based functional assays; chimeric receptor analyses; molecular modeling Biochemical and biophysical research communications Medium 23000410
2021 The purified human TAS1R2 subunit forms a dimer in detergent solution and binds high-potency sweeteners with Kd values consistent with physiological detection thresholds, as measured by intrinsic tryptophan fluorescence; circular dichroism confirmed proper folding with secondary structure. Overexpression in stable HEK293S inducible cell line; detergent solubilization and purification; size exclusion chromatography coupled with light scattering; circular dichroism; tryptophan fluorescence binding assay Scientific reports Medium 34782704
2022 The isolated Venus flytrap domain of human TAS1R2 (hTAS1R2-VFT) expressed in E. coli is a functional monomer that binds sweet stimuli with Kd values consistent with physiological detection; single amino acid substitutions D278A and E382A (known to abolish full-length receptor response) drastically reduced ligand affinity of the isolated VFT domain, confirming these residues as key binding-site determinants. Heterologous expression of hTAS1R2-VFT in E. coli; circular dichroism; SEC-MALS; site-directed mutagenesis; intrinsic tryptophan fluorescence binding assay International journal of molecular sciences High 36012481
2021 The T1R2 splicing isoform T1R2_Δe3p (lacking part of exon 3) forms a non-functional heterodimer with T1R3 that cannot be activated by sweet stimuli and significantly downregulates canonical T1R2/T1R3 function; local LPS injection significantly increased the expression ratio of T1R2_Δe3p in mouse taste buds, providing a mechanism by which bacterial infection suppresses sweet taste perception. RT-PCR identification of splicing isoform; heterologous expression in vitro functional assays; local LPS injection in mice; quantitative RT-PCR Hua xi kou qiang yi xue za zhi Medium 34409805
2022 Skipping of Tas1r2 exon 4 produces a truncated isoform (Tas1r2_Δe4) lacking amino acids in the Venus flytrap domain; this truncated isoform generates non-functional T1R2/T1R3 heterodimers that reduce sweet taste responses to all tested sweet compounds in vitro and in vivo. The splicing factor PTBP1 promotes exon 4 skipping by binding a polypyrimidine-rich silencer in exon 4, thereby decreasing sweet taste receptor function and sweet taste perception in mice. Identification and cloning of splicing variant; heterologous expression cell-based assays; in vivo behavioral sweet taste tests; PTBP1 knockdown/overexpression; RNA-binding analysis Chemical senses High 36484118
2024 TAS1R2 in skeletal muscle acts as a glucose sensor that stimulates ERK1/2-dependent phosphorylation and activation of PARP1 (a major NAD consumer); muscle-specific deletion of TAS1R2 suppresses PARP1 activity, elevates NAD levels, and enhances mitochondrial capacity and running endurance in mice. Plasma glucose negatively correlates with muscle NAD, implicating TAS1R2 as a peripheral energy surveyor. Muscle-specific TAS1R2 knockout mice; PARP1 activity assays; NAD measurement; mitochondrial function assays; running endurance tests; glucose/agonist stimulation with ERK1/2 phosphorylation readout Nature communications High 38851747
2023 The TAS1R2 sweet taste receptor regulates skeletal muscle mass and fitness through an ERK2-PARP1-NAD signaling axis; muscle-specific deletion of TAS1R2 elevated NAD levels, improved mitochondrial function, increased muscle mass and strength, and prolonged running endurance; deletion also ameliorated muscle decline in obese and aged mice. Muscle-specific TAS1R2 knockout mice; metabolic phenotyping; NAD, PARP1, and ERK2 measurements; voluntary wheel running; grip strength; aged and obese mouse models Research square (preprint)preprint Medium 36798161
2020 Inhibition of TAS1R2/TAS1R3 by the inverse agonist lactisole blocked perception of sweet thermal taste (warming of tongue from 20–35°C), establishing that TAS1R2/TAS1R3 receptor activation is necessary for thermal sweet taste perception in humans. Human psychophysics; pharmacological inhibition with lactisole; temperature-controlled flow gustometer Chemical senses Medium 32072157
2021 l-glucose activates the sweet taste receptor TAS1R2/TAS1R3 in cell-based functional assays at thresholds similar to d-glucose; computational docking to the VFT domain of TAS1R2 identified two sub-pockets (A and B), each compatible with one enantiomer, with both sharing overlapping polar contact residues. Cell-based functional assay (HEK293T transfection); computational docking to TAS1R2 VFT domain Food chemistry Medium 34715629
2023 Serine 147 in the binding site of T1R3 VFT domain is required for T1R3 activation by both l- and d-glucose; mutation S147A completely abolishes T1R3 monomer activation. The R317G variant in the VFT domain of T1R2 (present in ~20% of the world population based on the NM_152232.4 reference) markedly reduces TAS1R2 sensitivity in vitro. Mutagenesis; transient transfection of individual T1R2 and T1R3 monomers and heterodimers in HEK293T cells; cell-based functional assay; comparison of TAS1R2 reference sequences Chemical senses Medium 36806908
2024 Steviol glycosides and other sweeteners bind to four distinct sites on the T1R2/T1R3 heterodimer: VFD2 (TAS1R2 Venus flytrap), VFD3 (TAS1R3 Venus flytrap), TMD2 (TAS1R2 transmembrane domain), and TMD3 (TAS1R3 transmembrane domain); the C20 carboxy terminus of the Gα protein binds to the intracellular region of either TMD2 or TMD3, altering GPCR affinity to a high-affinity state for steviol glycosides. Radioligand binding experiments; computational docking at four receptor sites; G protein coupling analysis Communications chemistry Medium 39424933
2025 A single amino acid substitution in TAS1R2 (Ile-67 in humans vs. Leu-70 in mice) in the Venus flytrap domain explains species-specific differences in sulfamate sweetener (saccharin, acesulfame K) sensitivity; mouse-type I67L mutation in human TAS1R2 decreased receptor activity and sulfamate binding, while the reverse L70I mutation in mouse Tas1r2 increased activity and binding. Chimeric TAS1R2/TAS1R3 analyses; single amino acid substitution mutagenesis; HEK293 cell-based functional assays; molecular dynamics simulations Food chemistry High 40706454
2016 The rhesus monkey Tas1r2 paired with human TAS1R3 responds to natural sugars, amino acids, artificial sweeteners, and sweet proteins, but amiloride does not inhibit rhesus monkey Tas1r2-mediated responses; the monomeric Tas1r2 transmembrane domain (without counterpart T1R3) can be activated by perillartine in humans, rhesus monkey, and squirrel monkey but not mouse. Cloning, expression, and functional characterization of rhesus monkey Tas1r2 in cell-based assays; chimeric and monomeric receptor assays; molecular modeling PloS one Medium 27479072
2008 Co-expression ratios of T1r2, T1r3, and gustducin in fungiform papillae are significantly lower in gurmarin-weakly-sensitive BALB mice than in gurmarin-sensitive B6 and dpa congenic mice, linking co-expression levels of these sweet receptor components with sensitivity to gurmarin-mediated sweet taste suppression. Quantitative in situ hybridization for T1r2, T1r3, and gustducin co-expression in taste tissues of different mouse strains; comparison with gurmarin-sensitivity phenotype Biochemical and biophysical research communications Low 18174025
2013 D- and L-amino acids show specific enantiomeric activities on the TAS1R2-TAS1R3 sweet receptor as demonstrated by in vitro binding assays using cells overexpressing the receptor, providing direct evidence that the stereochemistry of amino acids determines their interaction with the sweet receptor. Cell-based binding/functional assay using cells overexpressing TAS1R2-TAS1R3 Food chemistry Low 24360415
2022 Whole-brain mapping using T1r2-Cre knock-in mice showed that T1R2 is expressed not only in taste cells but also in various neuronal and glial populations in the brain, in circumventricular organs, and in vascular structures; immunohistochemistry confirmed co-expression with NPY and POMC neurons in the hypothalamic arcuate nucleus and with canonical taste signaling molecules in perivascular cells of the median eminence. T1r2-Cre knock-in mice with reporter; whole-brain Cre-labeled cell mapping; immunohistochemistry for neuropeptide co-expression Frontiers in neuroanatomy Medium 34776881
2021 Non-nutritive sweetener exposure (sodium saccharin and rebaudioside A) dose-dependently regulated T1R2 expression in the ovary and uterus of guinea pigs; low-dose saccharin increased ovarian T1R2 expression and ovary weight, while high-dose saccharin suppressed ovarian T1R2 and caused adverse ovarian/uterine morphological effects. In vivo sweetener administration; immunohistochemistry; protein expression analysis in ovary and uterus Animal science journal Low 32219957
2024 Hyperactivation of TAS1R2-TAS1R3 with sucralose elevated plasma insulin responses during an OGTT; inhibition with lactisole correlated with decreased plasma glucose; sucralose sweetness ratings correlated with early increases in glucose and insulin, showing bidirectional regulation of glucose metabolism by TAS1R2-TAS1R3 in humans. Oral glucose tolerance tests in healthy humans with sucralose or lactisole co-administration; plasma glucose, insulin, glucagon measurement; sweet taste psychophysics PloS one Medium 38691547
2022 Exendin-4 (GLP-1 receptor agonist) reduced glucose absorption in streptozotocin-diabetic mice by suppressing T1R2/T1R3 sweet taste receptor signaling and downstream molecules (PLCβ2, α-gustducin, IP3, cAMP), as well as SGLT1 and GLUT2 levels in the duodenum. STZ-diabetic mouse model; exendin-4 treatment; Western blotting and RT-qPCR for receptor and signaling molecules; glucose and transporter level measurement Translational research Low 35385790

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detection of sweet stimuli. Current biology : CB 200 16271873
2005 From small sweeteners to sweet proteins: anatomy of the binding sites of the human T1R2_T1R3 receptor. Journal of medicinal chemistry 117 16107151
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 113 20943793
2002 Why are sweet proteins sweet? Interaction of brazzein, monellin and thaumatin with the T1R2-T1R3 receptor. FEBS letters 108 12208493
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 86 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
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 66 26279452
2016 Sweet Taste Receptor TAS1R2 Polymorphism (Val191Val) Is Associated with a Higher Carbohydrate Intake and Hypertriglyceridemia among the Population of West Mexico. Nutrients 65 26907331
2010 Evolution of the sweet taste receptor gene Tas1r2 in bats. Molecular biology and evolution 65 20558596
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
2011 Expression and distribution of the sweet taste receptor isoforms T1R2 and T1R3 in human and rat bladders. The Journal of urology 58 22019168
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 55 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 54 24360415
2012 Association of GLUT2 and TAS1R2 genotypes with risk for dental caries. Caries research 49 23257979
2018 T1R2 receptor-mediated glucose sensing in the upper intestine potentiates glucose absorption through activation of local regulatory pathways. Molecular metabolism 46 30201274
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
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
2016 Disruption of the sugar-sensing receptor T1R2 attenuates metabolic derangements associated with diet-induced obesity. American journal of physiology. Endocrinology and metabolism 34 26884387
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
2019 T1R2+T1R3-independent chemosensory inputs contributing to behavioral discrimination of sugars in mice. American journal of physiology. Regulatory, integrative and comparative physiology 30 30624973
2017 Evaluation of the association between the TAS1R2 and TAS1R3 variants and food intake and nutritional status in children. Genetics and molecular biology 28 28497839
2015 GLUT2 and TAS1R2 Polymorphisms and Susceptibility to Dental Caries. Caries research 28 26112465
2008 Gurmarin sensitivity of sweet taste responses is associated with co-expression patterns of T1r2, T1r3, and gustducin. Biochemical and biophysical research communications 28 18174025
2009 Analyses of sweet receptor gene (Tas1r2) and preference for sweet stimuli in species of Carnivora. The Journal of heredity 27 19366814
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
2021 Biophysical and functional characterization of the human TAS1R2 sweet taste receptor overexpressed in a HEK293S inducible cell line. Scientific reports 24 34782704
2015 Polymorphisms in sweet taste genes (TAS1R2 and GLUT2), sweet liking, and dental caries prevalence in an adult Italian population. Genes & nutrition 24 26268603
2010 The T1R2/T1R3 sweet receptor and TRPM5 ion channel taste targets with therapeutic potential. Progress in molecular biology and translational science 24 20691962
2014 Distinct human and mouse membrane trafficking systems for sweet taste receptors T1r2 and T1r3. PloS one 21 25029362
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
2021 Taste and chirality: l-glucose sweetness is mediated by TAS1R2/TAS2R3 receptor. Food chemistry 19 34715629
2021 Investigating mechanism of sweetness intensity differences through dynamic analysis of sweetener-T1R2-membrane systems. Food chemistry 19 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 19 30120716
2024 Steviol rebaudiosides bind to four different sites of the human sweet taste receptor (T1R2/T1R3) complex explaining confusing experiments. Communications chemistry 18 39424933
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 18 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 17 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 17 34509698
2016 Oxaliplatin Alters Expression of T1R2 Receptor and Sensitivity to Sweet Taste in Rats. Biological & pharmaceutical bulletin 15 27040630
2024 Activation and inhibition of the sweet taste receptor TAS1R2-TAS1R3 differentially affect glucose tolerance in humans. PloS one 14 38691547
2022 Functional Characterization of the Venus Flytrap Domain of the Human TAS1R2 Sweet Taste Receptor. International journal of molecular sciences 14 36012481
2021 Whole-Brain Mapping of the Expression Pattern of T1R2, a Subunit Specific to the Sweet Taste Receptor. Frontiers in neuroanatomy 14 34776881
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
2019 Unnatural Tripeptides as Potent Positive Allosteric Modulators of T1R2/T1R3. ACS medicinal chemistry letters 12 31098002
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
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
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 10 38931195
2023 Revisiting the Sweet Taste Receptor T1R2-T1R3 through Molecular Dynamics Simulations Coupled with a Noncovalent Interactions Analysis. The journal of physical chemistry. B 10 36705604
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
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 10 28768658
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
2022 Pharmacology of TAS1R2/TAS1R3 Receptors and Sweet Taste. Handbook of experimental pharmacology 8 33582884
2022 Exendin-4 inhibits small intestinal glucose sensing and absorption through repression of T1R2/T1R3 sweet taste receptor signalling in streptozotocin diabetic mice. Translational research : the journal of laboratory and clinical medicine 8 35385790
2023 Systematic analysis reveals novel insight into the molecular determinants of function, diversity and evolution of sweet taste receptors T1R2/T1R3 in primates. Frontiers in molecular biosciences 7 36762208
2025 TAS1R2/TAS1R3 Single-Nucleotide Polymorphisms Affect Sweet Taste Receptor Activation by Sweeteners: The SWEET Project. Nutrients 6 40289963
2024 T1R2/T1R3 polymorphism affects sweet and fat perception: Correlation between SNP and BMI in the context of obesity development. Human genetics 6 39107667
2023 Sensitivity of human sweet taste receptor subunits T1R2 and T1R3 to activation by glucose enantiomers. Chemical senses 6 36806908
2023 Sucralose regulates postprandial blood glucose in mice through intestinal sweet taste receptors Tas1r2/Tas1r3. Journal of the science of food and agriculture 6 37938171
2020 Sweet Thermal Taste: Perceptual Characteristics in Water and Dependence on TAS1R2/TAS1R3. Chemical senses 6 32072157
2022 The Ile191Val Variant of the TAS1R2 Subunit of Sweet Taste Receptors Is Associated With Reduced HbA1c in a Human Cohort With Variable Levels of Glucose Homeostasis. Frontiers in nutrition 5 35662939
2022 Behavioral responses to sweet compounds via T1R2-independent pathways in chickens. Poultry science 5 35679679
2021 TAS1R2 sweet taste receptor genetic variation and dietary intake in Korean females. Appetite 4 33930495
2021 TAS1R2 rs35874116 and TRPM5 rs886277 polymorphisms are not related with risk of obesity. International journal of clinical practice 4 34157195
2024 A partial loss-of-function variant (Ile191Val) of the TAS1R2 glucose receptor is associated with enhanced responses to exercise training in older adults with obesity: A translational study. Metabolism: clinical and experimental 3 39393515
2022 Relationship between the TAS2R38 and TAS1R2 polymorphisms and the dental status in obese children. Dental and medical problems 3 35510485
2022 T1R2-mediated sweet sensing in a lizard. Current biology : CB 3 36473437
2021 Regulation effect of lipopolysaccharide on the alternative splicing and function of sweet taste receptor T1R2. Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology 3 34409805
2020 Design, synthesis and evaluation of unnatural peptides as T1R2/T1R3 PAMs. Bioorganic & medicinal chemistry letters 3 32063432
2014 Diverse contributions of Tas1r2/Tas2rs within the rat and mouse soft palate to sweet and bitter neural responses. Neuroscience letters 3 24699177
2013 Expression of synaptogyrin-1 in T1R2-expressing type II taste cells and type III taste cells of rat circumvallate taste buds. Cell and tissue research 3 23636420
2024 Exendin-4 blockade of T1R2/T1R3 activation improves Pseudomonas aeruginosa-related pneumonia in an animal model of chemically induced diabetes. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 2 38748233
2024 Millettia dubia De Wild. (Fabaceae): Structural analysis of the oleanane-type glycosides and stimulation of the sweet taste receptors TAS1R2/TAS1R3. Phytochemistry 2 38971498
2024 Ligand-Dependent and G Protein-Dependent Properties for the Sweet Taste Heterodimer, TAS1R2/1R3. The journal of physical chemistry. B 2 39231438
2023 The TAS1R2 sweet taste receptor regulates skeletal muscle mass and fitness. Research square 2 36798161
2022 Sweet taste perception in mice is blunted by PTBP1-regulated skipping of Tas1r2 exon 4. Chemical senses 2 36484118
2026 Sweet Protein Allosteric Binding and Activation of the Human T1R2/R3 Sweet Receptor: A Simulation Model Validated by in Vitro Receptor Activation Assay. Biochemistry 1 41591896
2026 Molecular mechanism of aspartame recognition by the human sweet taste receptor T1R2-T1R3 revealed by homology modeling and molecular dynamics simulations. Journal of computer-aided molecular design 1 41803465
2025 Low TAS1R2 Sweet Taste Receptor Expression in Skeletal Muscle of Genetically Diverse BXD Mice Mirrors Transcriptomic Signatures of Loss-of-Function Mice. Nutrients 1 40507187
2025 Quantifying human sweetness perception via a TAS1R2/TAS1R3-based model-predicted sweetness score. Food chemistry: X 1 41036456
2024 Novel gurmarin-like peptides from Gymnema sylvestre and their interactions with the sweet taste receptor T1R2/T1R3. Chemical senses 1 38695158
2024 Association between LTF/MMP20/CA6/TAS1R2 polymorphisms and susceptibility to dental caries. Clinical oral investigations 1 39212776
2026 On the Origin and Evolution of Sweet Taste Mediated by Tas1r2-Tas1r3 in Vertebrates. Integrative zoology 0 41618601
2026 Characterization of the Sweet Taste Receptor T1R2/T1R3 From Chimpanzee and Comparison With the Human T1R2/T1R3. American journal of primatology 0 41859945
2026 Targeting sweet taste receptor T1R2/T1R3: a new strategy for metabolic disease regulation and intervention of multiple organ diseases. Food chemistry. Molecular sciences 0 41953277
2026 Identification of novel sweet peptides from Meretrix lyrata and their molecular interaction with TAS1R2/TAS1R3. Food chemistry 0 41956049
2026 SUMO-assisted expression of a soluble and functional Venus flytrap domain of the human sweet taste receptor TAS1R2 in Escherichiacoli. Protein expression and purification 0 42070759
2026 Sweet Taste Receptor Genetic Variation TAS1R2 rs35874116 Is Associated with Dietary Quality in a Korean Population. Nutrients 0 42075037
2026 Dietary soybean or seaweed (Kappaphycus sp.) modulates taste-related gene (tas1r1 and tas1r2.2) expression in Nile tilapia (Oreochromis niloticus). Comparative biochemistry and physiology. Part D, Genomics & proteomics 0 42092395
2026 Structural and Energetic Determinants of Sweet Protein Recognition: Mechanistic Insights into Thaumatin Binding to the Human T1R2/T1R3 Receptor. International journal of molecular sciences 0 42123697
2025 A single amino acid substitution in TAS1R2 defines species-specific sweet sensitivity to sulfamates in humans and mice. Food chemistry 0 40706454
2025 [Identification of critical quality attributes related to property and flavor of Jianwei Xiaoshi Tablets based on T1R2/T1R3/TRPV1-HEMT biosensor]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 0 40904079
2025 Associations of TAS1R2 and TAS2R38 Genetic Variants with Sugar-Sweetened Beverage Intake and Obesity Risk in Kuwaiti Adolescents: A Cross-Sectional Study. Children (Basel, Switzerland) 0 41007057
2025 Relaxation of selective constraint on the sweet-taste receptor gene TAS1R2 in lorisiform primates. Scientific reports 0 41198840
2025 Molecular Dynamics Insights into TAS1R2 Transmembrane Domain Activation. International journal of molecular sciences 0 41373621
2024 Determination of sweetener specificity of horse gut-expressed sweet taste receptor T1R2-T1R3 and its significance for energy provision and hydration. Frontiers in veterinary science 0 38410741
2022 End-to-end dataflow engineering framework of honey manufacturing from intermediates to process by TAS1R2@AuNPs/SPCE biosensor coupled with quality transfer principle. Fundamental research 0 40166091

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