Affinage

TAS1R1

Taste receptor type 1 member 1 · UniProt Q7RTX1

Length
841 aa
Mass
93.1 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAS1R1 encodes the ligand-binding subunit of the T1R1/T1R3 heterodimeric class C GPCR that functions as the primary sensor of L-amino acids across taste, gut, immune, reproductive, and metabolic contexts. The T1R1 Venus flytrap domain contains an orthosteric site for L-amino acids (especially L-glutamate in humans) and distinct allosteric sites for nucleotide enhancers such as IMP, with species-specific tuning determined by key residues in both the VFT and transmembrane domains (PMID:24214976, PMID:30087430, PMID:24633359). Receptor activation couples through PLCβ → Ca²⁺ → ERK1/2 to stimulate mTORC1 and suppress autophagy in multiple tissues, while in enteroendocrine cells it drives CCK secretion and in colonic mucosa it initiates the peristaltic reflex (PMID:22959271, PMID:23203156, PMID:25324508). In spermatozoa, constitutive T1R1 activity maintains quiescence by suppressing basal Ca²⁺ and cAMP, and in neutrophils, amino acid sensing through T1R1/T1R3 triggers chemotaxis and modulates inflammatory cytokine production (PMID:22427794, PMID:25301019).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2009 Medium

    Establishing that human genetic variation in TAS1R1 explains individual differences in umami perception linked specific SNPs in the ligand-binding domain to MSG sensitivity, grounding human taste phenotypes in receptor sequence.

    Evidence Human genotype–phenotype association with psychophysical taste testing

    PMID:19571223

    Open questions at the time
    • No functional reconstitution of variant receptors in this study
    • Population sample limited in ethnic diversity
    • Effect sizes on taste thresholds not fully delineated
  2. 2010 Medium

    Demonstrating that Tas1r1 pseudogenization in the giant panda correlates with dietary shift to herbivory established an evolutionary framework linking T1R1 function to amino acid dietary dependence.

    Evidence Comparative genomic sequencing of Tas1r1 across carnivores, dN/dS and molecular clock analysis

    PMID:20573776

    Open questions at the time
    • Correlational evolutionary evidence without direct functional rescue
    • Does not address whether other amino acid sensors compensate
  3. 2011 Medium

    Functional reconstitution of TAS1R1 SNP variants (A110V, R507Q) confirmed that specific residues in the N-terminal domain are required for MSG responsiveness, moving from association to mechanism.

    Evidence Heterologous expression of variant receptors with Ca²⁺ functional assay and molecular modeling

    PMID:21422378

    Open questions at the time
    • Single-lab study
    • No crystal structure to validate modeled binding changes
  4. 2012 High

    Identification of T1R1/T1R3 as a cell-surface amino acid sensor that activates mTORC1 and suppresses autophagy revealed a metabolic signaling role far beyond taste, confirmed in vivo by increased autophagy in TAS1R3-knockout mice.

    Evidence siRNA knockdown with mTORC1 localization/phosphorylation assays in cell lines; TAS1R3-KO mouse autophagy phenotyping in heart, muscle, and liver

    PMID:22959271 PMID:23222068

    Open questions at the time
    • Downstream signaling intermediates between receptor and mTORC1 not fully mapped
    • Relative contribution of T1R1/T1R3 versus other amino acid sensors (SLC38A9, Sestrin2) not resolved
  5. 2012 High

    Demonstrating that T1R1 knockdown in enteroendocrine cells selectively reduces amino acid-stimulated CCK secretion established the receptor as a gut nutrient sensor coupling luminal amino acids to hormone release.

    Evidence siRNA knockdown in STC-1 cells, CCK ELISA, pharmacological inhibition, intestinal tissue explants

    PMID:23203156

    Open questions at the time
    • In vivo KO confirmation in gut CCK release not yet shown in this study
    • Downstream signaling pathway to CCK vesicle exocytosis not defined
  6. 2012 High

    Characterization of Tas1r1-null spermatozoa revealed a non-gustatory role in maintaining sperm quiescence via tonic suppression of Ca²⁺ and cAMP, expanding receptor function to reproductive physiology.

    Evidence Tas1r1-deficient reporter mouse, acrosomal reaction assay, intracellular Ca²⁺ and cAMP measurements, immunofluorescence

    PMID:22427794

    Open questions at the time
    • Ligand that activates T1R1/T1R3 in reproductive tract not identified
    • Whether constitutive receptor activity versus tonic agonism underlies quiescence is unresolved
  7. 2012 Medium

    Genetic reporter mapping showed T1R1-expressing taste cells are predominantly in fungiform papillae, segregated from bitter cells, and can co-express T1R2/T1R3 sweet receptor subunits, clarifying the cellular organization of taste receptor expression.

    Evidence Tas1r1-mCherry knock-in reporter mouse, fluorescence microscopy, single-cell RT-PCR

    PMID:23010799

    Open questions at the time
    • Functional consequence of T1R1/T1R2/T1R3 co-expression not tested
    • Reporter fidelity versus endogenous protein not independently validated
  8. 2013 High

    Chimeric and mutant receptor analyses resolved that T1R1 ligand specificity depends on two separable determinants in its VFT domain—an orthosteric amino acid site and non-orthosteric modulatory sites—establishing the structural basis for species-specific tuning.

    Evidence Human–mouse chimeric receptors, site-directed mutagenesis (12 residues), functional heterologous expression assays, molecular modeling

    PMID:24214976

    Open questions at the time
    • No high-resolution crystal or cryo-EM structure available
    • Precise IMP-binding residues not fully resolved
  9. 2013 High

    T1R1-KO mice showed abolished IMP synergy in nerve recordings but retained residual glutamate responses via mGluR1/mGluR4, defining T1R1 as essential for umami synergy but not the sole glutamate detector in taste.

    Evidence T1R1 knockout mouse, chorda tympani and glossopharyngeal nerve recordings, mGluR antagonist pharmacology

    PMID:23339178

    Open questions at the time
    • Quantitative contribution of each mGluR to residual response not fully delineated
    • Central processing of parallel glutamate signals not addressed
  10. 2014 High

    Discovery that T1R1/T1R3 activation by luminal amino acids initiates the colonic peristaltic reflex and CGRP release, confirmed by loss-of-function in T1R1-KO mice, extended the gut chemosensory role to motility control.

    Evidence T1R1-KO mice, flat-sheet colonic preparation, electrophysiology, CGRP ELISA

    PMID:25324508

    Open questions at the time
    • Cell type (enterochromaffin, enteroendocrine, or neuronal) initiating the reflex not resolved
    • Downstream neural circuit not mapped
  11. 2014 Medium

    Identification of functional T1R1/T1R3 in neutrophils that drives amino acid-induced chemotaxis and attenuates NF-κB/TNF-α signaling expanded the receptor's role to innate immune modulation.

    Evidence RNA-seq, signaling assays, chemotaxis assay, cytokine ELISA in mouse neutrophils

    PMID:25301019

    Open questions at the time
    • Single-lab finding not yet replicated independently
    • In vivo immune phenotype of T1R1-KO not assessed
    • Receptor coupling (Gα subunit) in neutrophils not identified
  12. 2016 Medium

    Delineation of the T1R1/T1R3 → PLCβ → Ca²⁺ → ERK1/2 → mTORC1 signaling cascade for methionine in myotubes provided the first ordered intracellular signaling pathway downstream of the receptor.

    Evidence siRNA knockdown in C2C12 myotubes, Ca²⁺ measurement, ERK1/2 and mTORC1 phosphorylation assays

    PMID:27727170

    Open questions at the time
    • Single-lab study
    • Whether PLCβ is directly activated by Gα or βγ subunits not determined
  13. 2017 Medium

    Biophysical reconstitution of the isolated T1R1 VFT domain demonstrated direct, IMP-potentiated L-amino acid binding with micromolar affinity, confirming that the extracellular domain is sufficient for ligand recognition.

    Evidence Recombinant cat T1R1-NTD expressed in E. coli, intrinsic fluorescence binding assay, CD spectroscopy, SEC-MALS

    PMID:29084235

    Open questions at the time
    • Refolded protein may not fully recapitulate native conformation
    • Binding affinities not validated for human T1R1
  14. 2018 High

    Identification of methional as a transmembrane-domain allosteric modulator whose PAM/NAM activity switches between human and mouse T1R1 revealed a second modulatory site in the TMD, distinct from the VFT allosteric pocket.

    Evidence Interspecies chimeric receptors, site-directed mutagenesis, functional assays, molecular modeling

    PMID:30087430

    Open questions at the time
    • No direct structural visualization of the TMD allosteric pocket
    • Endogenous TMD modulators not identified
  15. 2022 Medium

    Thermodynamic and conformational characterization of purified T1R1-VFT binding to multiple umami ligands established 1:1 stoichiometry and α-helix unfolding upon ligand engagement, providing a mechanistic model for VFT activation.

    Evidence Recombinant T1R1-VFT, fluorescence quenching, ITC, molecular dynamics simulation

    PMID:36098631

    Open questions at the time
    • Full-length receptor structure in active/inactive states still lacking
    • Single-lab biophysical study

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the full-length T1R1/T1R3 heterodimer, the identity of endogenous ligands in non-taste tissues, the precise Gα subunit coupling in each cell type, and the relative contribution of T1R1/T1R3 versus other amino acid sensors to mTORC1 regulation remain unresolved.
  • No cryo-EM or crystal structure of full-length heterodimer
  • Endogenous ligands in reproductive tract and immune cells unknown
  • Gα coupling specificity in non-taste tissues not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 6 GO:0098772 molecular function regulator activity 1
Localization
GO:0005576 extracellular region 4 GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-8963743 Digestion and absorption 3 R-HSA-9612973 Autophagy 2 R-HSA-9709957 Sensory Perception 2 R-HSA-168256 Immune System 1
Partners
TAS1R2TAS1R3
Complex memberships
T1R1/T1R3 heterodimer

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 The heterodimeric GPCR T1R1/T1R3 functions as a direct sensor of extracellular amino acid availability and regulates mTORC1 signaling; knockdown of T1R1/T1R3 reduces amino acid-stimulated mTORC1 activation, alters mTORC1 localization, downregulates pathway inhibitors, upregulates amino acid transporters, blocks translation initiation, and induces autophagy. siRNA knockdown in cell lines, mTORC1 localization imaging, phosphorylation assays, autophagy assays Molecular cell High 22959271
2012 TAS1R1-TAS1R3 senses extracellular amino acids at the cell surface, activates mTORC1, and inhibits autophagy; fasted TAS1R3−/− mice show increased autophagy in heart, skeletal muscle and liver, confirming the in vivo role. Knockout mouse model, autophagy assays in multiple tissues Autophagy High 23222068
2012 T1R1-T1R3 expressed in gut enteroendocrine (STC-1) cells senses L-amino acids (Phe, Leu, Glu but not Trp) and drives CCK secretion; siRNA knockdown of T1R1 in STC-1 cells significantly reduces Phe-, Leu-, and Glu-stimulated (but not Trp-stimulated) CCK release; IMP potentiates this response, consistent with canonical T1R1/T1R3 pharmacology. siRNA knockdown, CCK ELISA, pharmacological inhibition (gurmarin), intestinal tissue explants American journal of physiology. Gastrointestinal and liver physiology High 23203156
2013 T1R1/T1R3 ligand specificity is determined by two distinct determinants in the Venus flytrap (VFT) domain of T1R1: an orthosteric ligand-binding site controlling acidic amino acid selectivity, and non-orthosteric sites that modulate receptor activity independently of IMP allosteric modulation; 12 key residues were identified by chimeric receptor and point-mutant analysis. Chimeric human-mouse receptor analysis, site-directed mutagenesis, heterologous receptor expression assays, molecular modeling The Journal of biological chemistry High 24214976
2013 T1R1-knockout mice show a severe deficit in IMP-elicited umami synergy in gustatory nerve recordings but retain substantial residual glutamate responses mediated by metabotropic glutamate receptors (mGluR1/mGluR4); T1R1-expressing taste cells also contribute partly to sweet sensitivity. T1R1 knockout mouse, chorda tympani and glossopharyngeal nerve recordings, mGluR antagonist pharmacology, single-cell RT-PCR, conditioned taste aversion The Journal of physiology High 23339178
2012 Tas1r1 and Tas1r3 are expressed in murine and human spermatozoa, localized to the flagellum and acrosomal cap; Tas1r1-null spermatozoa display spermatogenic abnormalities, increased spontaneous acrosomal reaction, and significantly elevated basal cytosolic Ca²⁺ and cAMP concentrations, indicating that Tas1r1 maintains sperm quiescence through constitutive or tonic receptor activity. Tas1r1-deficient mCherry reporter mouse, acrosomal reaction assays, intracellular Ca²⁺ and cAMP measurements, immunofluorescence localization PloS one High 22427794
2014 Activation of luminal T1R1/T1R3 by monosodium glutamate or L-cysteine in the distal colon initiates the peristaltic reflex (ascending contraction, descending relaxation) and CGRP release; T1R1-knockout mice fail to show MSG-evoked peristaltic reflex, confirming receptor necessity. T1R1 knockout mice, flat-sheet colonic preparation, electrophysiology, CGRP ELISA, video pellet propulsion recording American journal of physiology. Gastrointestinal and liver physiology High 25324508
2016 Methionine activates mTORC1 via the T1R1/T1R3 → PLCβ → Ca²⁺ → ERK1/2 signal transduction cascade in C2C12 myotubes; siRNA knockdown of T1R1 abolishes Met-induced mTORC1 activation. siRNA knockdown, Ca²⁺ measurement, ERK1/2 phosphorylation assay, mTORC1 activity assay International journal of molecular sciences Medium 27727170
2018 Methionine and valine activate mTOR signaling in bovine mammary epithelial cells through TAS1R1/TAS1R3 by elevating intracellular Ca²⁺; TAS1R1 siRNA knockdown decreases intracellular Ca²⁺ and reduces mTOR, S6K1, and 4EBP1 phosphorylation, as well as β-casein (CSN2) mRNA abundance. siRNA knockdown, intracellular Ca²⁺ measurement, Western blot for mTOR pathway components, RT-qPCR Journal of dairy science Medium 30268610
2018 Methional acts as an allosteric modulator of T1R1/T1R3 by binding the transmembrane domain of T1R1; it serves as a positive allosteric modulator (PAM) for human T1R1/T1R3 and a negative allosteric modulator (NAM) for mouse T1R1/T1R3; the PAM/NAM switch depends on specific amino acid residues at the bottom of the allosteric pocket in the T1R1 transmembrane domain. Interspecies chimeric receptor expression, site-directed mutagenesis, functional receptor assays, molecular modeling Scientific reports High 30087430
2014 L-Theanine activates T1R1+T1R3 and elicits umami taste; site-directed mutagenesis shows L-theanine binds the L-amino acid orthosteric binding site in the Venus flytrap domain of T1R1 and shows synergy with IMP. Functional receptor expression assay, site-directed mutagenesis, IMP synergy assay Amino acids High 24633359
2011 Nonsynonymous SNPs in TAS1R1 (A110V and R507Q in the N-terminal ligand-binding domain) severely impair in vitro T1R1/T1R3 response to MSG; molecular modeling provides structural explanation for the functional loss. Functional expression of SNP variants in heterologous cells, Ca²⁺ assay, molecular modeling Chemical senses Medium 21422378
2009 Nonsynonymous SNPs C329T (A110V) and G1114A in TAS1R1 are significantly associated with glutamate nontasting/tasting phenotypes in humans, implicating specific residues of the TAS1R1 ligand-binding domain in individual differences in MSG sensitivity. Human population genotyping, psychophysical taste testing, RT-PCR and immunohistochemistry of fungiform papillae The American journal of clinical nutrition Medium 19571223
2012 Genetic labeling experiments in Tas1r1-mCherry reporter mice show Tas1r1-expressing taste cells are predominantly located in fungiform papillae, are completely segregated from bitter (Tas2r131) cells, and are also present in the testis; approximately 50% of mCherry cells co-express T1R2 and T1R3, indicating T1R1 cells can participate in both umami and sweet receptor complexes. Knock-in reporter mouse, fluorescence microscopy, single-cell RT-PCR Chemical senses Medium 23010799
2014 Mouse neutrophils express functional T1R1/T1R3; stimulation with L-alanine or L-serine (T1R1/T1R3 ligands) elicits ERK and p38 MAPK phosphorylation, chemotactic migration, and attenuation of LPS-induced TNF-α production via inhibition of NF-κB activity and STAT3 phosphorylation. RNA sequencing, qRT-PCR, signaling assays (Western blot), chemotaxis assay, cytokine ELISA BMB reports Medium 25301019
2019 Branched chain amino acids (L-leucine, L-isoleucine) stimulate CCK secretion from porcine jejunum via T1R1/T1R3; pre-treatment with lactisole (a T1R1/T1R3 inhibitor) significantly reduces BCAA-induced CCK secretion and attenuates upregulation of T1R1/T1R3 expression. Porcine jejunum tissue explants, pharmacological inhibition with lactisole, CCK ELISA, RT-PCR and Western blot Food & function Medium 31098606
2017 The Venus flytrap (VFT) domain of the cat T1R1 (cT1R1-NTD) expressed in E. coli and refolded can bind L-amino acids with Kd in the micromolar range; IMP potentiates L-amino acid binding and IMP itself binds the extracellular domain in the absence of L-amino acids. Recombinant protein expression and refolding, intrinsic tryptophan fluorescence binding assay, circular dichroism, size-exclusion chromatography/light scattering PloS one Medium 29084235
2018 The T1R1 VFT (Venus flytrap) domain immobilized on a graphene FET biosensor binds monosodium glutamate with ~1 nM sensitivity; IMP enhances the signal analogously to the human taste system, confirming that the isolated VFT domain retains functional umami ligand binding. Recombinant VFT domain production, graphene FET biosensor, real-time binding measurement Biosensors & bioelectronics Medium 30005383
2022 Purified T1R1-VFT binds umami ligands (MSG, disodium succinate, beefy meaty peptide, IMP) at a 1:1 stoichiometry via hydrogen bond, van der Waals, and electrostatic interactions; binding is spontaneous, exothermic, and induces conformational changes (α-helix unfolding) that stabilize the active pocket conformation. Recombinant protein production, multispectroscopic techniques (fluorescence quenching), isothermal titration calorimetry, molecular dynamics simulation Journal of agricultural and food chemistry Medium 36098631
2010 The giant panda Tas1r1 gene is a pseudogene; the functional constraint on Tas1r1 was relaxed ~4.2 Ma, coinciding with the dietary switch to bamboo, establishing a causal link between loss of T1R1 umami receptor function and herbivory. Sequencing of all six Tas1r1 exons across carnivore species, dN/dS ratio analysis, molecular clock estimation Molecular biology and evolution Medium 20573776

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway. Blood 459 20448110
2009 Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells. Journal of immunology (Baltimore, Md. : 1950) 392 19570826
2004 Differentiation of Tr1 cells by immature dendritic cells requires IL-10 but not CD25+CD4+ Tr cells. Blood 369 15479730
2012 Probiotic Bifidobacterium breve induces IL-10-producing Tr1 cells in the colon. PLoS pathogens 254 22693446
2006 Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. The Journal of clinical investigation 231 17099776
2014 Tr1 cells and the counter-regulation of immunity: natural mechanisms and therapeutic applications. Current topics in microbiology and immunology 192 25004813
2012 The G protein-coupled taste receptor T1R1/T1R3 regulates mTORC1 and autophagy. Molecular cell 153 22959271
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
2011 Type 1 regulatory T cells (Tr1) in autoimmunity. Seminars in immunology 132 21840222
2011 Induction of regulatory Tr1 cells and inhibition of T(H)17 cells by IL-27. Seminars in immunology 129 21893418
2010 Pseudogenization of the umami taste receptor gene Tas1r1 in the giant panda coincided with its dietary switch to bamboo. Molecular biology and evolution 125 20573776
2013 Nonpathogenic bacteria alleviating atopic dermatitis inflammation induce IL-10-producing dendritic cells and regulatory Tr1 cells. The Journal of investigative dermatology 118 23812300
2011 Killing of myeloid APCs via HLA class I, CD2 and CD226 defines a novel mechanism of suppression by human Tr1 cells. European journal of immunology 117 21469116
2011 ECM components guide IL-10 producing regulatory T-cell (TR1) induction from effector memory T-cell precursors. Proceedings of the National Academy of Sciences of the United States of America 117 21518860
1983 RNA polymerase pausing and transcript release at the lambda tR1 terminator in vitro. The Journal of biological chemistry 109 6308007
2022 Characteristics of umami peptides identified from porcine bone soup and molecular docking to the taste receptor T1R1/T1R3. Food chemistry 107 35398684
2013 Two distinct determinants of ligand specificity in T1R1/T1R3 (the umami taste receptor). The Journal of biological chemistry 101 24214976
2008 IL-10 suppressor activity and ex vivo Tr1 cell function are impaired in multiple sclerosis. European journal of immunology 100 18200504
2008 Tr1 and naturally occurring regulatory T cells induce IgG4 in B cells through GITR/GITR-L interaction, IL-10 and TGF-beta. European journal of immunology 100 18924213
2016 IL-10 Receptor Signaling Is Essential for TR1 Cell Function In Vivo. Journal of immunology (Baltimore, Md. : 1950) 95 28003377
2012 Birch pollen immunotherapy results in long-term loss of Bet v 1-specific TH2 responses, transient TR1 activation, and synthesis of IgE-blocking antibodies. The Journal of allergy and clinical immunology 95 23021882
2015 Tumor-infiltrating plasmacytoid dendritic cells promote immunosuppression by Tr1 cells in human liver tumors. Oncoimmunology 93 26155417
1987 Sequence elements essential for rho-dependent transcription termination at lambda tR1. The Journal of biological chemistry 89 3038914
2016 Blimp-1-Dependent IL-10 Production by Tr1 Cells Regulates TNF-Mediated Tissue Pathology. PLoS pathogens 88 26765224
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
2021 In-silico investigation of umami peptides with receptor T1R1/T1R3 for the discovering potential targets: A combined modeling approach. Biomaterials 85 34998173
2001 High-resolution genetic mapping of the saccharin preference locus (Sac) and the putative sweet taste receptor (T1R1) gene (Gpr70) to mouse distal Chromosome 4. Mammalian genome : official journal of the International Mammalian Genome Society 84 11178737
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
2011 In vivo induction of Tr1 cells via mucosal dendritic cells and AHR signaling. PloS one 79 21886804
2013 Taste responses in mice lacking taste receptor subunit T1R1. The Journal of physiology 77 23339178
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
2003 Induction of autoantigen-specific Th2 and Tr1 regulatory T cells and modulation of autoimmune diabetes. Journal of immunology (Baltimore, Md. : 1950) 66 12847240
1986 Transcription termination at lambda tR1 is mediated by interaction of rho with specific single-stranded domains near the 3' end of cro mRNA. Cell 66 2428503
2017 ITK signalling via the Ras/IRF4 pathway regulates the development and function of Tr1 cells. Nature communications 65 28635957
2021 Novel umami peptides from tilapia lower jaw and molecular docking to the taste receptor T1R1/T1R3. Food chemistry 64 34111693
2009 Antigen-specific dependence of Tr1-cell therapy in preclinical models of islet transplant. Diabetes 63 19934002
2016 The structure features of umami hexapeptides for the T1R1/T1R3 receptor. Food chemistry 62 27979247
2012 Expression of Tas1 taste receptors in mammalian spermatozoa: functional role of Tas1r1 in regulating basal Ca²⁺ and cAMP concentrations in spermatozoa. PloS one 62 22427794
2004 Specialization in tolerance: innate CD(4+)CD(25+) versus acquired TR1 and TH3 regulatory T cells. Transplantation 62 14726762
2014 Interaction between umami peptide and taste receptor T1R1/T1R3. Cell biochemistry and biophysics 61 25331670
2012 Genetic labeling of Tas1r1 and Tas2r131 taste receptor cells in mice. Chemical senses 61 23010799
2016 Tr1-Like T Cells - An Enigmatic Regulatory T Cell Lineage. Frontiers in immunology 60 27683580
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
2021 Clonally expanded EOMES+ Tr1-like cells in primary and metastatic tumors are associated with disease progression. Nature immunology 55 34017124
2019 FoxO3 reverses 5-fluorouracil resistance in human colorectal cancer cells by inhibiting the Nrf2/TR1 signaling pathway. Cancer letters 55 31811910
2022 Novel umami peptide from Hypsizygus marmoreus hydrolysate and molecular docking to the taste receptor T1R1/T1R3. Food chemistry 54 36099828
2019 Understanding the molecular mechanism of umami recognition by T1R1-T1R3 using molecular dynamics simulations. Biochemical and biophysical research communications 52 31092329
2021 Tr1 Cells as a Key Regulator for Maintaining Immune Homeostasis in Transplantation. Frontiers in immunology 49 33981317
2018 High-performance bioelectronic tongue using ligand binding domain T1R1 VFT for umami taste detection. Biosensors & bioelectronics 47 30005383
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
2022 Typical Umami Ligand-Induced Binding Interaction and Conformational Change of T1R1-VFT. Journal of agricultural and food chemistry 44 36098631
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
2017 IL-10-Engineered Human CD4+ Tr1 Cells Eliminate Myeloid Leukemia in an HLA Class I-Dependent Mechanism. Molecular therapy : the journal of the American Society of Gene Therapy 44 28807569
2009 Clinical grade production of IL-10 producing regulatory Tr1 lymphocytes for cell therapy of chronic inflammatory diseases. International immunopharmacology 43 19539556
1996 RS cyclophilins: identification of an NK-TR1-related cyclophilin. Gene 42 8973360
2011 Human genetic polymorphisms in T1R1 and T1R3 taste receptor subunits affect their function. Chemical senses 41 21422378
2023 Conserved Sites and Recognition Mechanisms of T1R1 and T2R14 Receptors Revealed by Ensemble Docking and Molecular Descriptors and Fingerprints Combined with Machine Learning. Journal of agricultural and food chemistry 39 37005743
2014 L-Theanine elicits umami taste via the T1R1 + T1R3 umami taste receptor. Amino acids 39 24633359
2012 Enhanced GITR/GITRL interactions augment IL-27 expression and induce IL-10-producing Tr-1 like cells. European journal of immunology 38 22678896
2005 Exposure to myeloma cell lysates affects the immune competence of dendritic cells and favors the induction of Tr1-like regulatory T cells. European journal of immunology 38 15761844
2017 Generation of donor-specific Tr1 cells to be used after kidney transplantation and definition of the timing of their in vivo infusion in the presence of immunosuppression. Journal of translational medicine 36 28222739
2015 Oral administration of a select mixture of Bacillus probiotics generates Tr1 cells in weaned F4ab/acR- pigs challenged with an F4+ ETEC/VTEC/EPEC strain. Veterinary research 36 26384321
2011 Glycoantigens induce human peripheral Tr1 cell differentiation with gut-homing specialization. The Journal of biological chemistry 36 21228275
2009 Increased expression of regulatory Tr1 cells in recurrent hepatitis C after liver transplantation. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons 35 19624566
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
2018 Intramuscular vaccination of guinea pigs with the live-attenuated human herpes simplex vaccine VC2 stimulates a transcriptional profile of vaginal Th17 and regulatory Tr1 responses. Vaccine 34 29655629
2017 AhR activation increases IL-2 production by alloreactive CD4+ T cells initiating the differentiation of mucosal-homing Tim3+ Lag3+ Tr1 cells. European journal of immunology 33 28833046
2016 Differentiation and Characterization of Tr1 Cells. Current protocols in immunology 33 27038462
2012 Amino acid regulation of autophagy through the GPCR TAS1R1-TAS1R3. Autophagy 33 23222068
2022 A novel umami electrochemical biosensor based on AuNPs@ZIF-8/Ti3C2 MXene immobilized T1R1-VFT. Food chemistry 32 35944333
2021 Human-like performance umami electrochemical biosensor by utilizing co-electrodeposition of ligand binding domain T1R1-VFT and Prussian blue. Biosensors & bioelectronics 32 34534889
2018 Positive/Negative Allosteric Modulation Switching in an Umami Taste Receptor (T1R1/T1R3) by a Natural Flavor Compound, Methional. Scientific reports 32 30087430
2015 Helitrons shaping the genomic architecture of Drosophila: enrichment of DINE-TR1 in α- and β-heterochromatin, satellite DNA emergence, and piRNA expression. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 32 26408292
2019 Deleterious somatic variants in 473 consecutive individuals with ovarian cancer: results of the observational AGO-TR1 study (NCT02222883). Journal of medical genetics 31 30979843
2014 Phenotype alterations in regulatory T-cell subsets in primary HIV infection and identification of Tr1-like cells as the main interleukin 10-producing CD4+ T cells. The Journal of infectious diseases 31 25281758
2013 IL-27 paves different roads to Tr1. European journal of immunology 31 23504674
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
2018 Human placenta-derived mesenchymal stem cells ameliorate GVHD by modulating Th17/Tr1 balance via expression of PD-L2. Life sciences 26 30393022
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
2015 Adult-onset type 1 diabetes patients display decreased IGRP-specific Tr1 cells in blood. Clinical immunology (Orlando, Fla.) 25 26341315
1997 Cloning and sequencing of the gene encoding the cell surface glycoprotein of Haloarcula japonica strain TR-1. Extremophiles : life under extreme conditions 25 9680334
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
2022 Umami polypeptide detection system targeting the human T1R1 receptor and its taste-presenting mechanism. Biomaterials 24 35792387
2017 Genome Sequence of Desulfurella amilsii Strain TR1 and Comparative Genomics of Desulfurellaceae Family. Frontiers in microbiology 24 28265263
2014 Mouse neutrophils express functional umami taste receptor T1R1/T1R3. BMB reports 24 25301019
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
2016 Cisplatin induces tolerogenic dendritic cells in response to TLR agonists via the abundant production of IL-10, thereby promoting Th2- and Tr1-biased T-cell immunity. Oncotarget 23 27172902
2011 Targeting human inducible regulatory T cells (Tr1) in patients with cancer: blocking of adenosine-prostaglandin E₂ cooperation. Expert opinion on biological therapy 22 21702720
2019 Lactobacillus pentosus Modulates Immune Response by Inducing IL-10 Producing Tr1 Cells. Immune network 21 31921469
2018 Diagnosis of Li-Fraumeni Syndrome: Differentiating TP53 germline mutations from clonal hematopoiesis: Results of the observational AGO-TR1 trial. Human mutation 21 30216591
2005 Dendritic cells engineered to express CD40L continuously produce IL12 and resist negative signals from Tr1/Th3 dominated tumors. Cancer immunology, immunotherapy : CII 21 16175400
2022 Roles of type 1 regulatory T (Tr1) cells in allergen-specific immunotherapy. Frontiers in allergy 20 35991310
2017 Biophysical and functional characterization of the N-terminal domain of the cat T1R1 umami taste receptor expressed in Escherichia coli. PloS one 20 29084235
2011 Isolation, expansion and functional assessment of CD4+CD25+FoxP3+ regulatory T cells and Tr1 cells from uremic patients awaiting kidney transplantation. Transplant immunology 20 21958749
2017 Prostaglandin E2 inhibits Tr1 cell differentiation through suppression of c-Maf. PloS one 19 28604806
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
2022 Mesenchymal Stem Cells Alleviate Inflammatory Bowel Disease Via Tr1 Cells. Stem cell reviews and reports 18 35274217
2013 Do polymorphisms in the TAS1R1 gene contribute to broader differences in human taste intensity? Chemical senses 18 24000232