Affinage

TAS1R1

Taste receptor type 1 member 1 · UniProt Q7RTX1

Length
841 aa
Mass
93.1 kDa
Annotated
2026-06-10
93 papers in source corpus 28 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TAS1R1 (T1R1) is the ligand-binding subunit of the heterodimeric class C GPCR T1R1/T1R3, a cell-surface sensor of extracellular L-amino acid availability whose canonical role is umami taste transduction but which broadly couples amino acid sensing to anabolic signaling across many tissues (PMID:22959271, PMID:23222068, PMID:25253867). Specificity for L-glutamate and synergy with 5'-ribonucleotides (IMP) reside in the T1R1 Venus flytrap (VFT) domain: an orthosteric site sets acidic amino acid selectivity while distinct non-orthosteric VFT residues modulate broad amino acid responsiveness, and IMP both potentiates L-amino acid binding and binds independently to the extracellular domain (PMID:24214976, PMID:24633359, PMID:29084235, PMID:36098631). A separate allosteric pocket in the T1R1 transmembrane domain binds modulators such as methional, with specific pocket residues determining a species-dependent switch between positive and negative allosteric modulation (PMID:30087430). In taste tissue, T1R1/T1R3 is specifically required for umami IMP-glutamate synergism and behavioral L-glutamate detection, while residual T1R-independent and mGluR-dependent mechanisms also contribute (PMID:23339178, PMID:25253867). As a metabolic amino acid sensor the receptor directly activates mTORC1 and suppresses autophagy: knockdown reduces amino-acid-stimulated mTORC1 signaling, blocks translation initiation, and induces autophagy, and T1R-knockout mice show elevated autophagy in heart, muscle, and liver upon fasting (PMID:22959271, PMID:23222068). Downstream it engages distinct G-protein routes—Gq driving a PLCβ–Ca²⁺–ERK1/2 cascade versus an mTORC1 arm independent of Gq and Ca²⁺—to govern protein synthesis, including β-casein production and milk yield in mammary epithelium (PMID:26168033, PMID:27727170, PMID:28497545, PMID:30268610, PMID:37918588). Beyond taste and mammary tissue, T1R1/T1R3 mediates amino acid-stimulated CCK secretion from enteroendocrine cells via a PLC/TRPM5 pathway, initiates colonic peristaltic reflexes, relaxes gastric smooth muscle through Gαi coupling, maintains spermatozoa quiescence by restraining Ca²⁺ and cAMP, and modulates neutrophil and NK cell function (PMID:23203156, PMID:25324508, PMID:31721379, PMID:22427794, PMID:25301019, PMID:30259960). Human polymorphisms (A110V, R507Q) in the T1R1 ligand-binding domain impair MSG responses, establishing a direct genotype-to-function link (PMID:21422378).

Mechanistic history

Synthesis pass · year-by-year structured walk · 27 steps
  1. 2011 Medium

    Established that natural T1R1 ligand-binding-domain variants causally alter receptor function, linking human sequence variation to glutamate sensing.

    Evidence Functional expression of polymorphic T1R1 variants in HEK293 with Ca²⁺ reporter assay and homology modeling

    PMID:21422378

    Open questions at the time
    • No in vivo or human perceptual-threshold confirmation
    • Single lab; small set of variants
  2. 2012 High

    Reframed T1R1/T1R3 from a taste receptor into a general cell-surface amino acid sensor that drives mTORC1 and represses autophagy, defining its core anabolic role.

    Evidence siRNA knockdown across cell lines, T1R3-knockout fasting mice, mTORC1 localization and autophagy-flux readouts

    PMID:22959271 PMID:23222068

    Open questions at the time
    • Mechanism by which the membrane receptor relays to intracellular mTORC1 not defined
    • G-protein dependence of the mTORC1 arm not resolved here
  3. 2012 High

    Showed T1R1/T1R3 operates in non-taste epithelia, mediating amino-acid-stimulated CCK secretion in enteroendocrine cells.

    Evidence siRNA knockdown in STC-1 cells with CCK secretion assay, gurmarin/IMP pharmacology, tissue explants

    PMID:23203156

    Open questions at the time
    • Intracellular transduction (PLC/TRPM5) not yet dissected at this stage
    • Whether enteroendocrine signaling is physiologically relevant in vivo not tested
  4. 2012 High

    Identified a role in spermatozoa, where T1R1 restrains basal Ca²⁺ and cAMP to maintain quiescence and prevent premature acrosomal reaction.

    Evidence Tas1r1-deficient reporter mouse with immunolocalization, Ca²⁺ imaging, cAMP and acrosomal reaction assays

    PMID:22427794

    Open questions at the time
    • Ligand and G-protein coupling in sperm not defined
    • Fertility consequences not quantified
  5. 2013 High

    Demonstrated genetically that T1R1/T1R3 is specifically required for umami IMP-glutamate synergism while a T1R-independent and mGluR-based glutamate mechanism persists.

    Evidence T1R1-knockout mice with gustatory nerve recordings, single-cell RT-PCR, mGluR antagonism, conditioned taste aversion

    PMID:23339178

    Open questions at the time
    • Identity of the residual T1R-independent receptor unresolved
    • Molecular basis of synergism not structurally defined here
  6. 2013 High

    Dissected the structural determinants of ligand specificity, separating an orthosteric acidic-amino-acid site from non-orthosteric VFT modulatory sites in T1R1.

    Evidence Human-mouse chimeric receptors, site-directed mutagenesis of 12 residues, heterologous functional assay, molecular modeling

    PMID:24214976

    Open questions at the time
    • No atomic structure to confirm modeled sites at this stage
    • Functional impact in native taste cells not tested
  7. 2014 Medium

    Extended ligand repertoire by mapping L-theanine to the canonical orthosteric site, with IMP synergy.

    Evidence Heterologous T1R1/T1R3 calcium assay with VFT site-directed mutagenesis

    PMID:24633359

    Open questions at the time
    • Single study, single lab
    • Physiological relevance of theanine sensing untested
  8. 2014 High

    Confirmed at the behavioral level that L-glutamate/IMP detection depends on T1R1/T1R3, with a low-affinity T1R-independent residual pathway.

    Evidence Operant psychophysical detection across multiple T1R-knockout genotypes with amiloride and IMP tools

    PMID:25253867

    Open questions at the time
    • Identity of the low-affinity backup mechanism unknown
    • Central processing not addressed
  9. 2014 Medium

    Identified an immune role: T1R1/T1R3 in neutrophils transduces amino acid signals into MAPK-driven chemotaxis and dampens LPS-induced inflammatory cytokine output.

    Evidence Receptor expression profiling plus Ca²⁺/MAPK, chemotaxis, and NF-κB/STAT3 assays in primary neutrophils

    PMID:25301019

    Open questions at the time
    • No genetic knockout to confirm receptor dependence
    • Downstream G-protein not identified
  10. 2014 High

    Showed gut motility control: luminal MSG via colonic T1R1/T1R3 triggers the peristaltic reflex and CGRP release.

    Evidence Immunostaining, three-chamber peristalsis preparations, T1R1-knockout mice, pellet propulsion assay

    PMID:25324508

    Open questions at the time
    • Cellular relay from enteroendocrine sensing to enteric reflex not fully mapped
    • G-protein coupling not defined here
  11. 2015 Medium

    Separated the downstream branches, establishing that Gq and Ca²⁺ drive ERK1/2 whereas the mTORC1 arm is Gq- and Ca²⁺-independent, and Gi/G12/13 are not involved in β-cells.

    Evidence Pharmacological/genetic G-protein inhibition (PTX, UBO-QIC, p115-RGS), Ca²⁺ chelation, phosphorylation assays in MIN6 cells

    PMID:26168033

    Open questions at the time
    • The G-protein-independent route to mTORC1 remains undefined
    • Single cell-type context
  12. 2016 Medium

    Defined a methionine-sensing PLCβ–Ca²⁺–ERK1/2 cascade in muscle linking T1R1/T1R3 to protein synthesis.

    Evidence siRNA knockdown, Ca²⁺ measurement, PLCβ inhibition, and protein-synthesis readouts in C2C12 myotubes

    PMID:27727170

    Open questions at the time
    • Single lab
    • In vivo muscle relevance not tested
  13. 2017 Medium

    Demonstrated in vivo that T1R1 controls mammary milk protein synthesis through mTOR, regulating milk yield and β-casein and feedback on amino acid transporters.

    Evidence T1R1-knockout mice, milk yield quantification, mTOR pathway Western blots, transporter and β-casein qPCR, mammary explants

    PMID:28497545

    Open questions at the time
    • Direct ligand sensing in mammary tissue not biophysically shown
    • Single lab
  14. 2017 Medium

    Provided direct biophysical evidence that the isolated T1R1 VFT binds L-amino acids with micromolar affinity and that IMP both potentiates and independently binds the extracellular domain.

    Evidence Bacterial expression/refolding of cat T1R1-NTD, CD, SEC-MALS, intrinsic tryptophan fluorescence binding

    PMID:29084235

    Open questions at the time
    • Non-human ortholog domain in isolation
    • No structure of the bound state
  15. 2018 High

    Localized a transmembrane-domain allosteric site distinct from the VFT and showed pocket residues determine species-dependent PAM-versus-NAM behavior of methional.

    Evidence Human/mouse chimeric receptors, site-directed mutagenesis, calcium reporter assay, molecular modeling

    PMID:30087430

    Open questions at the time
    • No crystal structure of the TM allosteric pocket
    • Endogenous physiological modulators unknown
  16. 2018 Medium

    Confirmed conservation of the amino-acid-sensing-to-mTOR axis in bovine mammary epithelium via Ca²⁺ elevation and β-casein output.

    Evidence siRNA knockdown in primary bovine mammary cells with Ca²⁺, mTOR pathway, and CSN2 readouts

    PMID:30268610

    Open questions at the time
    • Single lab
    • Direct receptor-ligand binding not measured
  17. 2018 Medium

    Extended the receptor to NK cell anti-tumor function, where T1R1/T1R3 overexpression boosts amino-acid-driven cytotoxicity via Akt/mTORC1.

    Evidence Lentiviral T1R1/T1R3 overexpression in hepatic NK cells with cytotoxicity, effector molecule, and phosphorylation assays

    PMID:30259960

    Open questions at the time
    • Gain-of-function only; no loss-of-function confirmation
    • Endogenous expression level relevance unclear
  18. 2019 Medium

    Identified KLF5 as a transcriptional regulator of Tas1r1 via a proximal-promoter GT box during myogenic differentiation.

    Evidence Luciferase reporter, GT-box mutagenesis, KLF5 overexpression/CRISPR KO, ChIP-seq

    PMID:30982802

    Open questions at the time
    • Regulation in taste or other tissues untested
    • Upstream signals controlling KLF5 here not defined
  19. 2019 Medium

    Established an inhibitory smooth-muscle role: gastric T1R1/T1R3 couples through Gαi2 to suppress acetylcholine-induced contraction and Ca²⁺ release.

    Evidence Receptor detection in isolated SMCs, isometric contraction recording, Ca²⁺ assays, PTX, G-protein activation assay

    PMID:31721379

    Open questions at the time
    • No genetic knockout in this tissue
    • Single lab
  20. 2019 Medium

    Showed branched-chain amino acids drive CCK secretion through T1R1/T1R3 in porcine jejunum.

    Evidence Porcine jejunum stimulation with lactisole inhibition and receptor expression analysis

    PMID:31098606

    Open questions at the time
    • Pharmacological inhibition only; no genetic confirmation
    • Signaling pathway not dissected
  21. 2020 Medium

    Defined the enteroendocrine transduction pathway: L-glutamate sensing by T1R1/T1R3 drives CCK release through PLC/TRPM5.

    Evidence Porcine duodenal model with PLC/TRPM5 inhibitors, T1R3 antagonist, T1R1 allosteric activator, and in vivo rat MSG

    PMID:32478409

    Open questions at the time
    • G-protein linking receptor to PLC not identified
    • Single lab
  22. 2022 Medium

    Linked T1R1 amino acid sensing to systemic lipid metabolism through altered BCAA handling and lipogenic/catabolic gene programs.

    Evidence Tas1r1-knockout mice with body composition, liver lipid quantification, proteomics and amino acid metabolomics

    PMID:35968935

    Open questions at the time
    • Correlative multi-omics; direct molecular link to lipid pathways not established
    • Tissue origin of the metabolic phenotype not resolved
  23. 2022 Medium

    Quantified weak 1:1 umami-ligand binding to the human T1R1-VFT and captured ligand-induced conformational stabilization of the active pocket.

    Evidence Purified human T1R1-VFT with fluorescence quenching, CD, ITC-derived thermodynamics, molecular dynamics

    PMID:36098631

    Open questions at the time
    • Isolated domain, not full heterodimer
    • No experimental structure of bound complex
  24. 2023 Medium

    Showed L-Glu/T1R1/T1R3 signaling promotes Leydig-cell steroidogenesis via cAMP and represses autophagy, tying the receptor to testosterone synthesis.

    Evidence RNAi silencing of T1R3 with agonist stimulation, testosterone/cAMP measurement, steroidogenic enzyme qPCR, autophagy Western blots in porcine Leydig cells

    PMID:38035949

    Open questions at the time
    • G-protein coupling driving cAMP not identified
    • Single lab; ortholog system
  25. 2023 Medium

    Traced a TAS1R1-mTOR-DDX39B-PKM2-HDAC3 axis controlling histone H3 acetylation to explain valine-driven milk synthesis.

    Evidence Knockdown/overexpression in primary BMEC with nuclear fractionation, co-IP, histone acetylation assay, and in vivo valine supplementation

    PMID:37918588

    Open questions at the time
    • Long mechanistic chain established largely in one cell system
    • Direct receptor-to-mTOR step not biochemically defined
  26. 2025 Medium

    Provided the first crystal structure of a Tas1r1/Tas1r3 LBD heterodimer and explained stereochemical promiscuity through inter-subdomain interactions stabilizing the active conformation.

    Evidence Crystal structure of pufferfish Tas1r1/Tas1r3 LBD with mutagenesis and functional assays (preprint)

    PMID:bio_10.1101_2025.11.24.689453

    Open questions at the time
    • Preprint, not peer-reviewed
    • Ortholog structure; human full-length receptor architecture still unresolved
  27. 2025 Medium

    Identified a vascular/neuronal role in penile tissue where T1R1/T1R3 promotes smooth-muscle relaxation by enhancing NO and H2S signaling.

    Evidence Immunohistochemistry, isometric force recording with NOS/H2S/Ca²⁺-channel inhibitors and H2S measurement in rat corpus cavernosum

    PMID:41183583

    Open questions at the time
    • No genetic confirmation
    • Receptor coupling to gasotransmitter production not biochemically defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the plasma-membrane receptor mechanistically relays amino acid occupancy to intracellular mTORC1 in a G-protein-independent manner, and the structure of the full-length human T1R1/T1R3 in its active signaling state, remain unresolved.
  • No defined molecular bridge from receptor to mTORC1
  • No active-state full-length human structure
  • Endogenous physiological allosteric modulators unidentified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0008289 lipid binding 2 GO:0140299 molecular sensor activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-9612973 Autophagy 2 R-HSA-9709957 Sensory Perception 2
Partners
TAS1R3
Complex memberships
T1R1/T1R3 umami receptor heterodimer

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2012 The heterodimeric GPCR T1R1/T1R3 acts as a cell-surface sensor of extracellular amino acid availability that directly activates mTORC1 and inhibits autophagy. Knockdown of T1R1/T1R3 reduced amino-acid-stimulated mTORC1 signaling, altered mTORC1 localization, downregulated pathway inhibitors, upregulated amino acid transporters, blocked translation initiation, and induced autophagy. Fasted TAS1R3-knockout mice showed increased autophagy in heart, skeletal muscle, and liver. siRNA knockdown in cell lines, T1R3 knockout mice (fasting model), mTORC1 localization assay, autophagy readouts (LC3, flux), amino acid transporter expression Molecular cell / Autophagy High 22959271 23222068
2012 T1R1/T1R3 expressed in intestinal enteroendocrine (STC-1) cells mediates L-amino acid (Phe, Leu, Glu)-stimulated CCK secretion. siRNA knockdown of T1R1 in STC-1 cells significantly reduced Phe-, Leu-, and Glu-induced (but not Trp-induced) CCK release. IMP potentiated Phe-, Leu-, and Glu-induced but not Trp-induced CCK secretion, consistent with T1R1/T1R3 pharmacology. Gurmarin (T1R3 inhibitor) blocked the same subset of responses. siRNA knockdown of T1R1 in STC-1 cells, CCK secretion assay, pharmacological inhibition (gurmarin, NPS2143), mouse intestinal tissue explants American journal of physiology. Gastrointestinal and liver physiology High 23203156
2013 Two distinct determinants govern ligand specificity of T1R1/T1R3: (1) the orthosteric binding site in the Venus flytrap (VFT) domain of T1R1 determines acidic amino acid selectivity (human-type L-Glu preference), and (2) non-orthosteric, non-IMP-allosteric sites in the T1R1 VFT domain modulate broad amino acid responsiveness (mouse-type). Chimeric human-mouse receptors and site-directed mutagenesis identified 12 key residues; non-orthosteric residues modulated receptor activity independently of IMP. Chimeric human-mouse receptor analysis, site-directed mutagenesis, heterologous expression functional assay, molecular modeling, non-human primate T1R1 comparative analysis The Journal of biological chemistry High 24214976
2012 Tas1r1 and Tas1r3 are expressed in murine and human spermatozoa, localized to distinct flagellum segments and the acrosomal cap. Tas1r1 deletion (knockout) resulted in spermatogenic abnormalities, increased spontaneous acrosomal reaction, significantly elevated cytosolic Ca²⁺ levels, and higher basal cAMP concentrations in freshly isolated sperm, suggesting T1R1 maintains sperm quiescence. Tas1r1-deficient mCherry reporter mouse, immunolocalization, Ca²⁺ imaging, cAMP measurement, acrosomal reaction assay PloS one High 22427794
2013 T1R1-knockout mice showed a serious deficit in IMP-glutamate synergy (measured by gustatory nerve recording) but retained substantial residual glutamate responses, demonstrating that T1R1/T1R3 is specifically required for umami synergism. Single-cell RT-PCR showed some T1R1-expressing taste cells co-express all three T1R subunits. mGluR antagonists inhibited glutamate responses in both WT and KO mice, indicating mGluRs contribute independently to umami detection. T1R1 knockout mice, chorda tympani and glossopharyngeal nerve recordings, taste cell recordings, single-cell RT-PCR, mGluR pharmacological antagonism, conditioned taste aversion The Journal of physiology High 23339178
2014 L-Theanine activates T1R1/T1R3 and shows synergistic response with IMP. Site-directed mutagenesis of the T1R1 Venus flytrap domain demonstrated that L-theanine binds at the canonical L-amino acid orthosteric binding site of T1R1. Heterologous expression of T1R1/T1R3 in reporter cells, functional calcium assay, site-directed mutagenesis of T1R1 VFT domain Amino acids Medium 24633359
2014 T1R1/T1R3 activation by luminal monosodium glutamate (MSG) in colonic enteroendocrine cells initiates the peristaltic reflex (ascending contraction, descending relaxation) and CGRP release. IMP augmented MSG-induced effects. In T1R1-knockout mice, MSG failed to elicit a peristaltic reflex (whereas mucosal stroking did), and L-cysteine (but not L-tryptophan) mimicked MSG, consistent with T1R1/T1R3 pharmacology. Immunostaining for T1R1/T1R3 in colonic tissue, flat-sheet three-chamber preparations measuring ascending/descending peristalsis and CGRP release, T1R1-knockout mice, video pellet propulsion assay American journal of physiology. Gastrointestinal and liver physiology High 25324508
2015 Amino-acid activation of ERK1/2 and mTORC1 through T1R1/T1R3 in MIN6 pancreatic β-cells uses distinct downstream pathways: Gq is required for ERK1/2 but not mTORC1 activation; Ca²⁺ entry is required for ERK1/2 but dispensable for mTORC1; G(i) and G(12/13) are not involved in either pathway. GLP-1 (Gs-coupled) activated ERK1/2 but not cAMP, distinguishing the mechanism. Pertussis toxin (Gi inhibitor), UBO-QIC (Gq inhibitor), p115-RGS (G12/13 inhibitor) overexpression, Ca²⁺ chelation, cAMP measurement, ERK1/2 and mTORC1 phosphorylation assays in MIN6 cells Molecular endocrinology Medium 26168033
2016 In C2C12 myotubes, methionine regulates mTORC1 through T1R1/T1R3 via a PLCβ-Ca²⁺-ERK1/2 signal transduction cascade. siRNA knockdown of T1R1/T1R3 reduced Met-stimulated mTORC1 activation and protein synthesis. siRNA knockdown of T1R1/T1R3, intracellular Ca²⁺ measurement, PLCβ inhibition, ERK1/2 and mTORC1 phosphorylation assays, protein synthesis measurement in C2C12 myotubes International journal of molecular sciences Medium 27727170
2017 T1R1 knockout mice showed reduced milk yield and repressed β-casein synthesis in the mammary gland, with decreased phosphorylation of 4EBP1 and S6K (mTOR pathway). T1R1 knockout also increased amino acid transporter expression (SLC3A2, SLC7A5, SLC1A5), indicating T1R1/T1R3 modulates mTOR to regulate milk protein synthesis in vivo. T1R1 knockout mice, weigh-suckle-weigh milk yield quantification, Western blot for mTOR pathway, qPCR for AA transporters and β-casein, mammary explant pharmacological inhibition Molecular nutrition & food research Medium 28497545
2018 Methional, a food flavor compound, acts as a positive allosteric modulator (PAM) of human T1R1/T1R3 and as a negative allosteric modulator (NAM) of mouse T1R1/T1R3. Interspecies chimeric receptor analysis and site-directed mutagenesis showed methional binds to two distinct sites in the transmembrane domain of T1R1 (not the extracellular VFT domain), and specific residues at the bottom of the allosteric pocket determine PAM vs. NAM switching. Heterologous expression of human and mouse T1R1/T1R3, interspecies chimeric receptors, site-directed mutagenesis, functional calcium reporter assay, molecular modeling Scientific reports High 30087430
2018 In bovine mammary epithelial cells, TAS1R1/TAS1R3 senses extracellular amino acids (particularly Met and Val) and activates mTOR signaling via intracellular Ca²⁺ elevation. TAS1R1 knockdown by siRNA decreased intracellular Ca²⁺, reduced mTOR/S6K1/4EBP1 phosphorylation, and lowered β-casein (CSN2) mRNA abundance in response to Met and Val. siRNA knockdown of TAS1R1 in primary bovine mammary epithelial cells, intracellular Ca²⁺ measurement, Western blot for mTOR pathway, qPCR for CSN2 Journal of dairy science Medium 30268610
2011 Human genetic polymorphisms in T1R1 (A110V and R507Q in the N-terminal ligand-binding domain) severely impaired in vitro T1R1/T1R3 receptor response to MSG when functionally expressed. A molecular model of the T1R1 LBD provided mechanistic explanation for how these substitutions disrupt glutamate sensing. Functional expression of polymorphic T1R1 variants in HEK293 cells, Ca²⁺ reporter assay, molecular homology modeling Chemical senses Medium 21422378
2014 Behavioral detection of L-glutamate requires the T1R1/T1R3 receptor: T1R1 and T1R3 KO mice could not detect IMP alone, and their sensitivity to MSG+IMP was significantly impaired. However, partial residual detection at high concentrations by single-subunit KOs suggests a low-affinity T1R-independent mechanism exists. T1R2 KO mice behaved like WT controls. Operant psychophysical taste-detection paradigm in T1R1 KO, T1R2 KO, T1R3 KO, and T1R2+T1R3 KO mice; amiloride blockade of Na⁺ channel; IMP as T1R1/T1R3-selective potentiator The Journal of neuroscience High 25253867
2014 T1R1/T1R3 expressed in mouse neutrophils mediates L-alanine- and L-serine-stimulated ERK and p38 MAPK phosphorylation and chemotactic migration, and attenuates LPS-induced TNF-α and cytokine production via inhibition of NF-κB and STAT3 phosphorylation. RNA sequencing and qRT-PCR for receptor expression in neutrophils, functional Ca²⁺/MAPK phosphorylation assays, chemotaxis assay, LPS stimulation + cytokine measurement, NF-κB and STAT3 activity BMB reports Medium 25301019
2019 Gastric smooth muscle cells (SMCs) express T1R1 and T1R3, and MSG activation of T1R1/T1R3 inhibits acetylcholine-induced contractions and Ca²⁺ release in both antrum and fundus. The inhibitory effect was blocked by pertussis toxin, indicating Gαi protein coupling. MSG+IMP selectively activated Gαi2. RT-PCR and Western blot for T1R1/T1R3 in isolated SMCs, isometric contraction recording in muscle strips, Ca²⁺ measurement in SMCs, pertussis toxin, G-protein activation assay Neurogastroenterology and motility Medium 31721379
2019 Branched-chain amino acids (L-leucine, L-isoleucine) stimulate CCK secretion from porcine jejunum via T1R1/T1R3: lactisole (T1R1/T1R3 inhibitor) significantly decreased L-leucine-, L-isoleucine-, and BCAA-mix-induced CCK secretion and attenuated T1R1/T1R3 mRNA/protein upregulation. Porcine jejunum tissue stimulation, CCK secretion assay, lactisole pharmacological inhibition, qPCR and Western blot for T1R1/T1R3 Food & function Medium 31098606
2020 L-glutamate stimulates CCK secretion via T1R1/T1R3 through a PLC/TRPM5-dependent intracellular signaling pathway in porcine duodenum. Inhibition of PLC or TRPM5 abolished L-Glu-induced CCK release. T1R3 antagonist attenuated and T1R1 allosteric ligand augmented the response. Oral MSG in rats increased plasma CCK and duodenal T1R1, PLCβ2, and TRPM5 expression. Porcine duodenal model, CCK secretion assay, PLC and TRPM5 inhibitors, T1R3 antagonist, T1R1 allosteric activator, in vivo rat oral MSG, qPCR/Western blot Journal of the science of food and agriculture Medium 32478409
2017 The T1R1-VFT (Venus flytrap) domain expressed in bacteria binds L-amino acids with micromolar affinity (measured by intrinsic tryptophan fluorescence). IMP potentiates L-amino acid binding and also binds independently to the extracellular domain in the absence of L-amino acids. The renatured cat T1R1-NTD behaves as a monomer by SEC-MALS. Bacterial expression and refolding of cat T1R1-NTD, circular dichroism, SEC-MALS, intrinsic tryptophan fluorescence binding assay PloS one Medium 29084235
2022 Purified human T1R1-VFT domain binds umami ligands (MSG, disodium succinate, beefy meaty peptide, IMP) in a 1:1 stoichiometry with weak affinity (Ka ~252–1169 M⁻¹), driven by hydrogen bonds, van der Waals forces, and electrostatic interactions (static fluorescence quenching). Ligand binding induces conformational changes in T1R1-VFT including slight α-helix unfolding and stabilization of the active pocket conformation. Purified T1R1-VFT protein, multi-spectroscopic techniques (fluorescence quenching, CD), ITC-derived thermodynamics, molecular dynamics simulation Journal of agricultural and food chemistry Medium 36098631
2019 KLF5 (Krüppel-like factor 5) regulates Tas1r1 transcription in C2C12 myoblasts by binding a GT box in the 148-bp proximal promoter. Luciferase reporter assays showed promoter activity; GT box mutagenesis reduced it significantly. KLF5 overexpression increased and KLF5 KO decreased Tas1r1 expression. KLF5 ChIP-seq showed binding to the GT box during myogenic differentiation. Luciferase reporter assay, site-directed mutagenesis of GT box, siRNA knockdown of Sp4 and Klf5, Klf5 overexpression, Klf5 CRISPR KO cell lines, ENCODE ChIP-seq data Biomedical research (Tokyo) Medium 30982802
2018 T1R1/T1R3 expressed in hepatic CD49a⁺CD49b⁻ NK cells in a mouse HCC model mediates amino-acid-stimulated enhancement of NK cell tumoricidal activity. Lentiviral overexpression of T1R1 and T1R3 in normal hepatic NK cells increased tumor cell lysis, perforin/granzyme B production, IFN-γ, T-bet expression, and activated Akt/mTORC1 signaling in response to amino acids. Lentiviral T1R1/T1R3 overexpression in hepatic NK cells, in vitro cytotoxicity assay, perforin/granzyme B/IFN-γ measurement, Akt/mTORC1 phosphorylation assay European journal of immunology Medium 30259960
2022 Tas1r1 ablation in mice reduced fat mass, adipocyte size, liver triglyceride and total cholesterol levels, reduced lipogenesis gene expression, and promoted lipid catabolism. Proteomics identified upregulation of oxysterol 7α-hydroxylase and IGFBP2; amino acid metabolomics showed decreased branched-chain amino acids consistent with altered BCKDH levels, linking TAS1R1 to lipid metabolism via amino acid sensing. Tas1r1 KO mice, body composition analysis, liver lipid quantification, targeted hepatic amino acid metabolomics, proteomics, parallel reaction monitoring, gene expression Journal of agricultural and food chemistry Medium 35968935
2023 L-Glu activation of T1R1/T1R3 in testicular Leydig cells enhances testosterone synthesis by increasing intracellular cAMP and upregulating StAR, 3β-HSD1, CYP17A1, and 17β-HSD3 expression. T1R3 silencing decreased testosterone and cAMP. T1R1/T1R3 activation suppressed autophagy markers (LC3, Beclin-1) while silencing T1R3 increased them, linking the receptor to mTOR-dependent autophagy control in Leydig cells. RNAi silencing of T1R3 in porcine Leydig cells, L-Glu agonist stimulation, testosterone and cAMP measurement, qPCR for steroidogenic enzymes, Western blot for autophagy markers The Journal of steroid biochemistry and molecular biology Medium 38035949
2023 Valine promotes milk synthesis through a TAS1R1-mTOR-DDX39B signaling pathway in bovine mammary epithelial cells. DDX39B governs PKM2 nuclear accumulation, weakening HDAC3-histone H3 interaction and increasing histone H3 acetylation, promoting milk protein and fat synthesis. TAS1R1 knockdown reversed valine-stimulated milk synthesis. Primary BMEC isolation, TAS1R1 knockdown, DDX39B knockdown/overexpression, nuclear fractionation for PKM2, co-IP for HDAC3-H3, histone acetylation assay, in vivo mouse valine supplementation International journal of biological macromolecules Medium 37918588
2025 Crystal structure of the ligand-binding domain (LBD) of pufferfish Tas1r1/Tas1r3 heterodimer revealed a conserved core architecture with the TAS1R family. Pufferfish Tas1r1/Tas1r3 binds and responds to both L- and D-amino acids (stereochemical promiscuity). Structural and mutational analyses showed that inter-subdomain interactions that prevent full cleft opening stabilize the active conformation even with opposite-chirality ligands, explaining stereochemical non-selectivity. Crystal structure determination of Tas1r1/Tas1r3 LBD heterodimer, site-directed mutagenesis, functional receptor assay bioRxivpreprint Medium bio_10.1101_2025.11.24.689453
2025 T1R1/T1R3 is expressed in nerve fibers of the rat corpus cavernosum and in the endothelium of the dorsal penile artery. MSG (T1R1/T1R3 agonist) enhanced relaxations induced by EFS, NO donor SNAP, and H2S donor GYY4137, and increased H2S production in the corpus cavernosum. MSG-induced relaxation was reduced by neuronal voltage-gated Ca²⁺ channel inhibition, indicating neuronal T1R1/T1R3 coupling to H2S production promotes smooth muscle relaxation. Immunohistochemistry, isometric force recording in corpus cavernosum strips, EFS, pharmacological inhibitors (NOS, H2S synthase, Ca²⁺ channels), endothelium removal, H2S measurement European journal of pharmacology Medium 41183583

Source papers

Stage 0 corpus · 93 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 The G protein-coupled taste receptor T1R1/T1R3 regulates mTORC1 and autophagy. Molecular cell 154 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 141 23203156
2018 Molecular docking and simulation of the synergistic effect between umami peptides, monosodium glutamate and taste receptor T1R1/T1R3. Food chemistry 134 30236733
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
2022 Characteristics of umami peptides identified from porcine bone soup and molecular docking to the taste receptor T1R1/T1R3. Food chemistry 113 35398684
2013 Two distinct determinants of ligand specificity in T1R1/T1R3 (the umami taste receptor). The Journal of biological chemistry 102 24214976
2021 In-silico investigation of umami peptides with receptor T1R1/T1R3 for the discovering potential targets: A combined modeling approach. Biomaterials 86 34998173
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 85 36325587
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
2013 Taste responses in mice lacking taste receptor subunit T1R1. The Journal of physiology 77 23339178
2024 Taste properties and mechanism of umami peptides from fermented goose bones based on molecular docking and molecular dynamics simulation using umami receptor T1R1/T1R3. Food chemistry 75 38301563
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 75 37189274
2021 Novel umami peptides from tilapia lower jaw and molecular docking to the taste receptor T1R1/T1R3. Food chemistry 69 34111693
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
2016 The structure features of umami hexapeptides for the T1R1/T1R3 receptor. Food chemistry 62 27979247
2014 Interaction between umami peptide and taste receptor T1R1/T1R3. Cell biochemistry and biophysics 62 25331670
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
2012 Genetic labeling of Tas1r1 and Tas2r131 taste receptor cells in mice. Chemical senses 61 23010799
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
2022 Novel umami peptide from Hypsizygus marmoreus hydrolysate and molecular docking to the taste receptor T1R1/T1R3. Food chemistry 55 36099828
2019 Understanding the molecular mechanism of umami recognition by T1R1-T1R3 using molecular dynamics simulations. Biochemical and biophysical research communications 54 31092329
2018 High-performance bioelectronic tongue using ligand binding domain T1R1 VFT for umami taste detection. Biosensors & bioelectronics 47 30005383
2022 Typical Umami Ligand-Induced Binding Interaction and Conformational Change of T1R1-VFT. Journal of agricultural and food chemistry 45 36098631
2016 Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells. International journal of molecular sciences 45 27727170
2014 Activation of the umami taste receptor (T1R1/T1R3) initiates the peristaltic reflex and pellet propulsion in the distal colon. American journal of physiology. Gastrointestinal and liver physiology 45 25324508
2018 Methionine and valine activate the mammalian target of rapamycin complex 1 pathway through heterodimeric amino acid taste receptor (TAS1R1/TAS1R3) and intracellular Ca2+ in bovine mammary epithelial cells. Journal of dairy science 44 30268610
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 42 37005743
2011 Human genetic polymorphisms in T1R1 and T1R3 taste receptor subunits affect their function. Chemical senses 41 21422378
2014 L-Theanine elicits umami taste via the T1R1 + T1R3 umami taste receptor. Amino acids 39 24633359
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 36 31098606
2018 Positive/Negative Allosteric Modulation Switching in an Umami Taste Receptor (T1R1/T1R3) by a Natural Flavor Compound, Methional. Scientific reports 34 30087430
2022 A novel umami electrochemical biosensor based on AuNPs@ZIF-8/Ti3C2 MXene immobilized T1R1-VFT. Food chemistry 33 35944333
2012 Amino acid regulation of autophagy through the GPCR TAS1R1-TAS1R3. Autophagy 33 23222068
2021 Human-like performance umami electrochemical biosensor by utilizing co-electrodeposition of ligand binding domain T1R1-VFT and Prussian blue. Biosensors & bioelectronics 32 34534889
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
2024 Screening and identification of novel umami peptides from yeast proteins: Insights into their mechanism of action on receptors T1R1/T1R3. Food chemistry 26 39265305
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
2022 Umami polypeptide detection system targeting the human T1R1 receptor and its taste-presenting mechanism. Biomaterials 25 35792387
2014 Mouse neutrophils express functional umami taste receptor T1R1/T1R3. BMB reports 24 25301019
2017 Milk protein synthesis is regulated by T1R1/T1R3, a G protein-coupled taste receptor, through the mTOR pathway in the mouse mammary gland. Molecular nutrition & food research 22 28497545
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 21 38775286
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
2014 The importance of the presence of a 5'-ribonucleotide and the contribution of the T1R1 + T1R3 heterodimer and an additional low-affinity receptor in the taste detection of L-glutamate as assessed psychophysically. The Journal of neuroscience : the official journal of the Society for Neuroscience 19 25253867
2009 Tas1R1-Tas1R3 taste receptor variants in human fungiform papillae. Neuroscience letters 19 19146926
2013 Do polymorphisms in the TAS1R1 gene contribute to broader differences in human taste intensity? Chemical senses 18 24000232
2023 Novel Umami Peptides from Hypsizygus marmoreus and Interaction with Umami Receptor T1R1/T1R3. Foods (Basel, Switzerland) 17 36832778
2023 Identification and Characterization of Novel Umami Peptides from Protein Hydrolysates of and Their Interaction with T1R1/T1R3 Receptor. Journal of agricultural and food chemistry 16 37709731
2022 Taste peptides derived from Stropharia rugosoannulata fermentation mycelium and molecular docking to the taste receptor T1R1/T1R3. Frontiers in nutrition 16 35967776
2016 Amino acids regulate mTOR pathway and milk protein synthesis in a mouse mammary epithelial cell line is partly mediated by T1R1/T1R3. European journal of nutrition 16 27539583
2015 Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells. Molecular endocrinology (Baltimore, Md.) 15 26168033
2018 TAS1R1 and TAS1R3 Polymorphisms Relate to Energy and Protein-Rich Food Choices from a Buffet Meal Respectively. Nutrients 14 30518043
2017 An Examination of the Role of L-Glutamate and Inosine 5'-Monophosphate in Hedonic Taste-Guided Behavior by Mice Lacking the T1R1 + T1R3 Receptor. Chemical senses 14 28334294
2023 Identifying Umami Peptides Specific to the T1R1/T1R3 Receptor via Phage Display. Journal of agricultural and food chemistry 13 37523494
2022 Synergistic Effect of Kokumi-Active γ-Glutamyl Peptides and l-Glutamate on Enhancing Umami Sensation and Stimulating Cholecystokinin Secretion via T1R1/T1R3 Activation in STC-1 Cells. Journal of agricultural and food chemistry 13 36318610
2019 Bitter taste receptor T2R7 and umami taste receptor subunit T1R1 are expressed highly in Vimentin-negative taste bud cells in chickens. Biochemical and biophysical research communications 13 30782484
2015 Dried bonito dashi: taste qualities evaluated using conditioned taste aversion methods in wild-type and T1R1 knockout mice. Chemical senses 13 25604941
2024 Novel umami-enhancing peptides of beef M. Semimembranosus hydrolysates and interactions with the T1R1/T1R3 taste receptor. Food chemistry 12 39332374
2018 DNA Methylation of T1R1 Gene in the Vegetarian Adaptation of Grass Carp Ctenopharyngodon idella. Scientific reports 12 29720695
2023 Development of sensitive and stable electrochemical impedimetric biosensor based on T1R1 receptor and its application to detection of umami substances. Food chemistry 10 37156142
2021 The umami receptor T1R1-T1R3 heterodimer is rarely formed in chickens. Scientific reports 10 34112880
2020 Expression analysis of taste receptor genes (T1R1, T1R3, and T2R4) in response to bacterial, viral and parasitic infection in rainbow trout, Oncorhynchus mykiss. Fish & shellfish immunology 10 32244029
2024 Taste-Active Peptides from Triple-Enzymatically Hydrolyzed Straw Mushroom Proteins Enhance Salty Taste: An Elucidation of Their Effect on the T1R1/T1R3 Taste Receptor via Molecular Docking. Foods (Basel, Switzerland) 9 38611301
2019 Expression and function of umami receptors T1R1/T1R3 in gastric smooth muscle. Neurogastroenterology and motility 9 31721379
2025 Umami-enhancing peptides from Acetes chinensis: Insights into taste mechanism through multiligand docking with T1R1/T1R3. Food chemistry 8 41033031
2024 Identification and screening of umami peptides from skipjack tuna (Katsuwonus pelamis) hydrolysates using EAD/CID based micro-UPLC-QTOF-MS and the molecular interaction with T1R1/T1R3 taste receptor. Journal of chromatography. A 7 39181096
2020 l-Glutamate stimulates cholecystokinin secretion via the T1R1/T1R3 mediated PLC/TRPM5 transduction pathway. Journal of the science of food and agriculture 7 32478409
2018 Taste sensitivity to a mixture of monosodium glutamate and inosine 5'-monophosphate by mice lacking both subunits of the T1R1+T1R3 amino acid receptor. American journal of physiology. Regulatory, integrative and comparative physiology 7 29443544
2018 Taste receptor T1R1/T1R3 promotes the tumoricidal activity of hepatic CD49a+ CD49b- natural killer cells. European journal of immunology 7 30259960
2019 Krüppel-like factor 5 (Klf5) regulates expression of mouse T1R1 amino acid receptor gene (Tas1r1) in C2C12 myoblast cells. Biomedical research (Tokyo, Japan) 6 30982802
2023 Valine promotes milk synthesis by regulating PKM2 nuclear accumulation and histone H3 acetylation through the TAS1R1-mTOR-DDX39B signaling pathway. International journal of biological macromolecules 5 37918588
2025 Virtual screening of umami peptides during sufu ripening based on machine learning and molecular docking to umami receptor T1R1/T1R3. Food chemistry 4 40367822
2025 Molecular Recognition and Modification Strategies of Umami Dipeptides with T1R1/T1R3 Receptors. Molecules (Basel, Switzerland) 4 40649291
2024 Identification of umami peptides and mechanism of the interaction with umami receptors T1R1/T1R3 in pigeon meat. Animal bioscience 4 39483023
2023 Expression of the umami taste receptor T1R1/T1R3 in porcine testis of: Function in regulating testosterone synthesis and autophagy in Leydig cells. The Journal of steroid biochemistry and molecular biology 4 38035949
2022 Ablation of Tas1r1 Reduces Lipid Accumulation Through Reducing the de Novo Lipid Synthesis and Improving Lipid Catabolism in Mice. Journal of agricultural and food chemistry 4 35968935
2022 Conditioned Taste Aversion to L-Amino Acid Taste Stimuli and Oral Transcriptional Changes to Type 1 Taste Receptors T1R1 and T1R3 on Chronic Exposure to L-Alanine Solution in Chickens. The journal of poultry science 4 36382058
2025 Identification and Taste Characteristics of Six Novel Umami Peptides from Mytilus coruscus and Their Interaction with the T1R1/T1R3 Receptor. Journal of agricultural and food chemistry 3 40384580
2015 A regulatory gene network related to the porcine umami taste receptor (TAS1R1/TAS1R3). Animal genetics 3 26554867
2025 Identification of Novel Umami Peptides from Low-Salt Dry-Cured Ham Skin and Revelation of the Umami Mechanism through Molecular Docking with T1R1/T1R3. Journal of agricultural and food chemistry 2 40136010
2025 Transglutaminase-catalyzed glycosylation of egg white peptides: Structural modulation and molecular mechanism of umami enhancement via T1R1/T1R3 interactions. Food research international (Ottawa, Ont.) 2 40922226
2020 Comparative Analysis of the Umami Taste Receptor Gene Tas1r1 in Mustelidae. Zoological science 2 32282143
2017 T1R1/T1R3 Taste Receptor Suppresses Granulocyte-Mediated Neuroinflammation after Spinal Cord Injury. Journal of neurotrauma 2 28474538
2025 In silico analysis of soybean-derived umami peptides: Discovery and interaction mechanisms with T1R1/T1R3 receptor. Food chemistry: X 1 40486061
2026 Major aromatic components of Chinese cigar and their mechanisms of action with T1R1 receptors. Scientific reports 0 41680428
2026 An integrated in silico and multi-omics workflow identifies novel microbiota-derived umami peptides and elucidates T1R1/T1R3 binding mechanisms. Food chemistry 0 42070357
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 L-Theanine activates the mTOR signaling pathway through TAS1R1-FRMD6 to promote milk synthesis in bovine mammary epithelial cells. The Journal of nutritional biochemistry 0 42097464
2026 The role of taste receptor T1R1/T1R3 in autophagy regulation of spermatogenic cells and its association with spermatogenesis in Xiang pigs. Animal reproduction science 0 42161209
2026 Discovery, molecular docking, and umami-enhancing synergy of five novel umami peptides from Dictyophora rubrovolvata: Insights into T1R1/T1R3 interaction. Food chemistry 0 42172749
2026 Screening of umami peptides from shrimp juice based on molecular docking and kinetic modeling, and investigation of their interaction mechanisms with T1R1/T1R3 receptors. Food chemistry 0 42258942
2025 Meaty Aroma Compounds Enhance MSG Umami Perception Through Allosteric Modulation of T1R1/T1R3 Receptor: Evidence from Nasal Clip Sensory Evaluation and Molecular Dynamics Simulation. Foods (Basel, Switzerland) 0 40941155
2025 Unexpected loss of TAS1R1-TAS1R3 umami taste receptor function in carnivorous Lyncodontini mustelids. Chemical senses 0 41128640
2025 Expression and activity of the umami taste receptor (TAS1R1/TAS1R3) in rat corpus cavernosum. European journal of pharmacology 0 41183583

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