{"id":"c7813848-3706-5234-8fcd-1d3a215c5e21","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-tasl-loss-selectivity","predicate":"supports","statement":"Deleting TASL or SLC15A4 impaired the IRF response without abolishing the measured NF-kappaB or MAPK responses.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"2f564cda-93a2-51a3-9894-9a33a57534b1","mechanism_event_label":"Loss of the system selectively disrupted one signaling branch.","subject":{"id":"82eae972-7da8-5908-bfd7-1d3c73e869ec","slug":"tasl","display_name":"Human TLR adaptor interacting with SLC15A4 / TASL","entity_type_key":"protein"},"object":{"id":"c3fd75a1-e1a0-5c88-bc2d-c14522bf91c7","slug":"human-endolysosomal-tlr-irf-output","display_name":"Human endolysosomal TLR IRF signaling","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"2f564cda-93a2-51a3-9894-9a33a57534b1","stable_key":"911fb3c7-8cc3-5667-b677-5682fab67648:histidine-tasl-loss-selectivity-event","event_type":"observed_relationship","label":"Loss of the system selectively disrupted one signaling branch.","description":"Deleting TASL or SLC15A4 impaired the IRF response without abolishing the measured NF-kappaB or MAPK responses.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"82eae972-7da8-5908-bfd7-1d3c73e869ec","slug":"tasl","display_name":"Human TLR adaptor interacting with SLC15A4 / TASL","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c3fd75a1-e1a0-5c88-bc2d-c14522bf91c7","slug":"human-endolysosomal-tlr-irf-output","display_name":"Human endolysosomal TLR IRF signaling","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":"eca38509-73b3-5fc5-be33-2fa6d60ed1bb","slug":"slc15a4","display_name":"Human peptide/histidine transporter PHT1 / SLC15A4","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"0f2e1ba6-30ca-5b3f-9876-41572817fdd3","slug":"irf5","display_name":"Human interferon regulatory factor 5 / IRF5","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human immune-cell deletion experiments.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Does not imply all immune function is lost or a global histidine shortage.","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":"Loss of the system selectively disrupted one signaling branch.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32433612/ · DOI 10.1038/s41586-020-2282-0","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"bde9b47d-a2dc-53ee-b82c-67a712797528","evidence_kind":"source_excerpt","locator":"Lines 394-400","start_line":394,"end_line":400,"excerpt":"## histidine-tasl-loss-selectivity\nLoss of the system selectively disrupted one signaling branch.\nDeleting TASL or SLC15A4 impaired the IRF response without abolishing the measured NF-kappaB or MAPK responses.\nModel: Human immune-cell deletion experiments.\nLimitations: Does not imply all immune function is lost or a global histidine shortage.\nEvidence access: Primary full text\nTASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32433612/ · DOI 10.1038/s41586-020-2282-0","model_system":"Human immune-cell deletion experiments.","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; 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