{"id":"63371d09-b568-55af-8c3f-6693c753a797","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-h2-coupling-selectivity","predicate":"supports","statement":"Human H2 receptor W222A/V mutations abolished measured Gs activation while retaining Gq responses; the structural Gq complex used a G-alpha-s/q chimera.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"7b351e15-9265-5110-8c27-d1f58ba4ff75","mechanism_event_label":"A receptor can use more than one signaling partner, with separable structural requirements.","subject":{"id":"2944d4f5-f948-5826-a518-e6b7b2631750","slug":"hrh2","display_name":"Human histamine H2 receptor / HRH2","entity_type_key":"protein"},"object":{"id":"d41a4ffd-9c4d-5780-be6a-3928fa79b23f","slug":"human-hrh2-gq-coupling","display_name":"Human H2 receptor Gq coupling","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"7b351e15-9265-5110-8c27-d1f58ba4ff75","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-h2-coupling-selectivity-event","event_type":"observed_relationship","label":"A receptor can use more than one signaling partner, with separable structural requirements.","description":"Human H2 receptor W222A/V mutations abolished measured Gs activation while retaining Gq responses; the structural Gq complex used a G-alpha-s/q chimera.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2944d4f5-f948-5826-a518-e6b7b2631750","slug":"hrh2","display_name":"Human histamine H2 receptor / HRH2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d41a4ffd-9c4d-5780-be6a-3928fa79b23f","slug":"human-hrh2-gq-coupling","display_name":"Human H2 receptor Gq coupling","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"44374451-3436-5136-a8ae-5dcc6d8c353b","slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"847daefd-ce13-541a-b426-919975168a3d","slug":"histamine","display_name":"Histamine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human receptor mutagenesis and G-protein dissociation assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Do not label H2 as exclusively Gs-coupled; chimera-supported structure and native Gq signaling are distinct evidence types.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Histidine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"histidine","display_name":"L-Histidine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A receptor can use more than one signaling partner, with separable structural requirements.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Structural basis of ligand recognition and activation of the histamine receptor family. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39333117/ · DOI 10.1038/s41467-024-52585-y","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b0ae9000-983e-5384-9126-fc73364f67f1","evidence_kind":"source_excerpt","locator":"Lines 258-264","start_line":258,"end_line":264,"excerpt":"## histidine-h2-coupling-selectivity\nA receptor can use more than one signaling partner, with separable structural requirements.\nHuman H2 receptor W222A/V mutations abolished measured Gs activation while retaining Gq responses; the structural Gq complex used a G-alpha-s/q chimera.\nModel: Recombinant human receptor mutagenesis and G-protein dissociation assays.\nLimitations: Do not label H2 as exclusively Gs-coupled; chimera-supported structure and native Gq signaling are distinct evidence types.\nEvidence access: Primary full text\nStructural basis of ligand recognition and activation of the histamine receptor family. · 2024 · https://pubmed.ncbi.nlm.nih.gov/39333117/ · DOI 10.1038/s41467-024-52585-y","model_system":"Recombinant human receptor mutagenesis and G-protein dissociation assays.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"ce59e6c9-1213-523b-9d0b-400b7a81cd1c","stable_key":"import-911fb3c7-8cc3-5667-b677-5682fab67648","title":"L-Histidine: supply, catabolism, histamine, receptors and cross-nutrient mechanisms (2026-09-19)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"cb672530ec8b4a4542d0f3957e80ca76bb0449e9f988845b0f7681f623c4ec9b","revision_id":"19a7f26c-d9a1-5411-a81d-025f3d98a452","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}