GPCR, family 3, metabotropic glutamate receptor
Enable an agent to recognize metabotropic glutamate receptor family members, assess their molecular and functional state, and choose interpretable characterization or modulation actions.
Bundle → Layer → Finding → Questions Filled
6 bundles · 11 layers · 16 findings · 35 questions
Family and member identity Resolve what the registry label denotes and which receptor products belong to it.
Registry boundary
Establish the family-level referent and its relationship to neighboring receptor concepts.
Family label resolution
Treat the supplied name as a family-level working interpretation until its originating accession is verified.
- Which originating database accession and definition generated this exact registry label? provenance
- Does the accession represent a whole protein family, a domain signature or a narrower subfamily? boundary
- Does an existing Vercy world model already own this receptor-family concept? boundary
Member resolution
Identify the biological sequence underlying each receptor observation.
Subtype, species and isoform
Keep species, sequence version, subtype and splice form attached to every member-specific assertion.
- Which protein accession, organism and isoform identify the receptor studied? definition
- What curated annotation or sequence evidence supports its subtype and family membership? provenance
- Is its group assignment established for this lineage or extrapolated from mammalian nomenclature? boundary
Receptor architecture and assembly Represent the physical receptor that connects extracellular recognition to membrane signaling.
Domain integrity
Resolve ligand-recognition, connecting and membrane-spanning regions in the actual sequence.
Recognition-to-membrane continuity
Record evidence for the extracellular Venus flytrap region, cysteine-rich connecting region and seven-transmembrane region, including missing or modified segments.
- Which residue intervals support each expected domain and membrane helix? measurement
- Which truncations, substitutions or tags could interrupt ligand recognition or conformational transmission? boundary
Protomer assembly
Identify the interacting receptor units represented by an experiment or structure.
Assembly evidence
Require evidence for protomer composition and distinguish physical association from a functionally demonstrated receptor assembly.
- Which receptor protomers and stoichiometry are supported by the preparation? definition
- Does the evidence demonstrate proximity, stable association or functional cooperation? measurement
- Could overexpression, purification or stabilizing mutations have altered the observed assembly? boundary
Ligand recognition and modulation Separate ligand binding from the changes in receptor activity that binding produces.
Orthosteric recognition
Describe recognition and competition at the endogenous ligand site.
Binding and activation separation
Maintain independent records of ligand affinity, occupancy and functional response.
- What evidence places the ligand at the glutamate-recognition site? provenance
- Were affinity and response potency measured separately, and under which conditions? measurement
- What reference agonist and baseline define the ligand's efficacy? measurement
Allosteric effects
Describe modulation outside the orthosteric site without assuming identical behavior across subtypes.
Context-dependent modulation
Record positive, negative or neutral modulation and any intrinsic agonist activity as experimentally separate properties.
- Does the compound change agonist potency, maximum response, basal signaling or more than one of these? measurement
- Which agonist, receptor subtype and concentration range were used to establish the effect? provenance
- Which additional subtype controls are needed before using the compound as a selective probe? action
Coupling and functional state Connect receptor activation to measured intracellular signaling and its time dependence.
Signal transduction
Track receptor-to-G-protein and G-protein-to-effector relationships.
Coupling evidence
Use group classification to guide experiments while retaining direct coupling and downstream readouts as distinct evidence.
- Which G-protein partner was directly measured, and which was inferred from calcium, inositol phosphate or cyclic AMP responses? measurement
- Were native coupling partners or engineered promiscuous G proteins used? provenance
- Which perturbation would establish that the response depends on this receptor and the proposed pathway? action
Activation dynamics
Distinguish occupancy, conformation and signaling over time.
State assignment
State labels must identify their evidence modality; a structural example is the antagonist-bound inactive mGlu2 preparation described by [PDBe entry 7mtq](https://www.ebi.ac.uk/pdbe/entry/pdb/7mtq).
- Is the assigned state supported by structure, conformational sensing, G-protein engagement or downstream activity? provenance
- How do response onset, decay and recovery depend on exposure and washout time? measurement
- What evidence distinguishes desensitization from ligand loss, receptor internalization or assay exhaustion? boundary
Cellular context and assay interpretation Place receptor behavior in the membrane, cell type and experimental preparation where it was observed.
Localization and trafficking
Separate receptor production from delivery, retention and removal at the relevant membrane.
Available receptor pool
Record total abundance, surface availability and supported subcellular location separately.
- Which cell type and membrane compartment contain the receptor, and how was localization established? provenance
- What fraction of receptor is surface-accessible before and after stimulation? measurement
- Does reduced signaling persist after accounting for receptor abundance and trafficking? boundary
Experimental transferability
Determine which conclusions survive changes in construct, host system and readout.
Receptor-specific validation
Keep evidence from purified receptors, heterologous cells and native tissue distinguishable, with controls for endogenous glutamate-responsive targets.
- Which host cells, construct modifications, buffer conditions and readout define this result? provenance
- Which controls exclude endogenous receptors, off-target ligand effects and expression artifacts? boundary
- What orthogonal experiment is needed before transferring the conclusion to a native receptor context? action
Evidence and external alignment What the world already says about this thing, gathered so the model can be checked against it.
Reported evidence
Findings from the breadth pass, kept separate from the structural claims.
Check these first
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these check these first hold for the sense of GPCR, family 3, metabotropic glutamate receptor this model covers, and on what evidence? provenance
Kinds and varieties
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these kinds and varieties hold for the sense of GPCR, family 3, metabotropic glutamate receptor this model covers, and on what evidence? provenance
Identifiers and schemes
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these identifiers and schemes hold for the sense of GPCR, family 3, metabotropic glutamate receptor this model covers, and on what evidence? provenance
Real-world use
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these real-world use hold for the sense of GPCR, family 3, metabotropic glutamate receptor this model covers, and on what evidence? provenance
Failure modes and hazards
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these failure modes and hazards hold for the sense of GPCR, family 3, metabotropic glutamate receptor this model covers, and on what evidence? provenance
Neighbouring kinds and how to tell them apart
Recalled without web access and unsourced; every item is a lead to verify.
- Which of these neighbouring kinds and how to tell them apart hold for the sense of GPCR, family 3, metabotropic glutamate receptor this model covers, and on what evidence? provenance
Classifiers Filled
- Family
- Thing Registry
- Category
- Physical world and living systems
- Entry kind
- thing
- Plane
- PHY
- Domain
- PHY.MAT
- Other names and narrower kinds
- GPCR, family 3, metabotropic glutamate receptor 8, GPCR, family 3, metabotropic glutamate receptor 5, GPCR, family 3, metabotropic glutamate receptor 7, GPCR, family 3, metabotropic glutamate receptor 2, GPCR, family 3, metabotropic glutamate receptor 4, GPCR, family 3, metabotropic glutamate receptor 3, GPCR, family 3, metabotropic glutamate receptor 6, GPCR, family 3, metabotropic glutamate receptor 1
What it is Filled
Metabotropic glutamate receptors are a family of class C (family 3) G protein-coupled membrane receptors that detect extracellular glutamate and regulate intracellular signalling and neuronal excitability rather than directly forming an ion channel.
In scope
- Protein-family membership, species, receptor subtype and isoform identity
- Glutamate-recognition domains, membrane topology and receptor assembly
- Ligand occupancy, receptor conformation and functional competence
- G-protein coupling and measured downstream responses
- Cellular localization, trafficking and receptor-specific experimental evidence
Out of scope
- Glutamate synthesis, metabolism and bulk chemical specifications
- Ionotropic glutamate receptor channels
- Other class C GPCR families except as identification controls
- GRM gene regulation and inheritance beyond links needed to identify receptor products
- Whole neural circuits, diseases and therapeutic efficacy
- Commercial reagent formulation, manufacturing and chemical hazard classification
Why it exists Filled
Enable an agent to recognize metabotropic glutamate receptor family members, assess their molecular and functional state, and choose interpretable characterization or modulation actions.
Distinguishing features Filled
- Require evidence identifying the metabotropic glutamate receptor branch; a generic class C GPCR annotation alone is insufficient.
- Separate the label 'family 3' from the individual subtype mGlu3 and from pharmacological group III.
- Distinguish metabotropic signaling from an intrinsic glutamate-gated ion-channel mechanism using receptor annotation and functional evidence.
- Use sequence-supported extracellular ligand-recognition and seven-transmembrane architecture as a combined identification test, while flagging fragments and engineered constructs.
- Assign mammalian subtypes to group I, II or III only after establishing member identity; the conventional grouping is documented in the [NC-IUPHAR receptor guide](https://pmc.ncbi.nlm.nih.gov/articles/PMC2884589/).
What robots and AI may and may not do Filled
Must not
- Recommend unapproved compounds acting on these receptors for personal use.
- Present early research results as proven treatments.
- Interpret a person's genetic test result on a receptor gene as a diagnosis.
- Assist in making or using substances that act on these receptors to harm people.
Only with a human decision
- Using receptor research for decisions about a patient's treatment.
May
- Explain the structure, signalling and roles of metabotropic glutamate receptors from scientific sources.
- Summarise research and clinical trials involving these receptors with citations.
Moral aspects Filled
- Hope for new treatments for brain disorders can be exploited by unproven claims.
- Research involving animals and patients must weigh welfare and consent.
Who is affected
- Patients with neurological or psychiatric conditions
- Research participants
- Laboratory animals
Owners Filled
Steward
Nobody owns the receptors; researchers answer for their data and drug developers for their products.
Master systems
- Protein and gene databases
Links to other meta-models Filled
parent
- Q24725121 - registry parent class
What else AI and robots need to interact with it Filled
Identity and identifiers required Filled
- Vercy registry: vr.tr.gpcr-family-3-metabotropic-glutamate-receptor
- Wikidata: Q2033959 (https://www.wikidata.org/wiki/Q2033959)
Direct properties required Filled
- Member identity: Protein accession and version, organism, gene identifier, subtype, isoform
- Family assignment confidence: Curated membership; sequence-supported prediction; ambiguous; contradicted
- Pharmacological group: I; II; III; unresolved; assignment not applicable
- Construct completeness: Full-length native sequence; splice variant; fragment; tagged; mutated; chimeric
- Domain boundaries and topology: Residue intervals for extracellular domains, transmembrane helices and intracellular regions
- Assembly composition: Identified protomers, stoichiometry, homomeric or heteromeric assignment, evidence method
- Ligand affinity: Kd or Ki in mol/L, with ligand, binding model and assay conditions
- Functional potency and efficacy: EC50 or IC50 in mol/L; maximum response in assay units or relative to a named reference
- Observed signaling partner: G-protein family or subunit, downstream effector, assay system and evidence
- Surface availability: Surface fraction, receptors per cell or calibrated surface-label signal
- Functional state: Basal; ligand-bound; signaling-active; desensitized; internalized; unresolved
Recognition required Filled
- Molecular structure representations typically show a large extracellular ligand-binding domain connected to a seven-transmembrane domain.
- Structures commonly show paired receptor subunits, a feature shared with other class C G protein-coupled receptors.
- These receptors lack the ion-conducting pore arrangement of ionotropic glutamate receptors, but family identification still requires molecular evidence.
Capabilities and actions required Filled
- Classify a candidate protein against the family while preserving uncertain subtype assignments.
- Map variants and construct edits to receptor domains and prioritize functional checks.
- Choose binding and signaling measurements suited to the identified receptor and experimental system.
- Compare orthosteric and allosteric perturbations using explicit ligand, endpoint and concentration context.
- Diagnose whether an absent response reflects receptor identity, surface availability, coupling or assay limitations.
- Attach subtype-specific findings to this family model without creating duplicate registry concepts.
Hazards and failure modes required Filled
- Drugs acting on these receptors have failed in trials after promising early results.
- Altered receptor function is linked to several neurological disorders.
Standards and interfaces required Filled
- IUPHAR/BPS receptor nomenclature, International Union of Basic and Clinical Pharmacology.
Context of use required Filled
- Metabotropic glutamate receptors occur in cell membranes and are studied especially for their roles in nervous system signalling.
- They are encountered in molecular neuroscience and pharmacological research investigating how glutamate changes cellular signalling and neuronal activity.
Sources Filled
- Wikidata item Q2033959: GPCR, family 3, metabotropic glutamate receptor - identity and sense of the item
- Wikipedia: Metabotropic glutamate receptor - general description of the item
Open questions
- Which authoritative accession corresponds to the exact registry label, and does it identify a family or a sequence signature?
- Does the existing Vercy catalogue already cover this concept under a synonym requiring linkage instead of a separate publication?
- What taxonomic range does the originating family entry cover, and how should members outside mammalian mGlu1-mGlu8 nomenclature be represented?
- Which proposed heteromeric assemblies have sufficient native-context evidence to support family-level modeling?
- Which architecture, coupling and trafficking assertions are conserved across verified members, and which require subtype-, isoform- or assay-specific qualification?
Machine files
Provenance
thing registry research (pass 2) · unreviewed
Built from: models/things/publications/thing-q2033959/spec.json