{"id":"6a61029e-6e97-5346-8557-e10e98a58286","stable_key":"a8baf7e9-80e4-5d8c-adec-9a63e84d2f21:l-cysteine-ado-protein-stability","predicate":"regulates_oxygen_dependent_stability","statement":"ADO-dependent N-terminal cysteine oxidation regulated RGS4/5 stability through the N-degron pathway in human cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"35520448-c315-5cdf-a457-77c23c6680bc","mechanism_event_label":"Oxidation can mark a signaling regulator for degradation rather than merely damage it.","subject":{"id":"fdeeed42-76ed-5016-b0bc-c1bf9120af3d","slug":"ado","display_name":"Human 2-aminoethanethiol dioxygenase / ADO","entity_type_key":"protein"},"object":{"id":"0ab9d700-c4d9-589c-8575-6cfa5a68572c","slug":"rgs4","display_name":"Human regulator of G-protein signaling 4 / RGS4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"35520448-c315-5cdf-a457-77c23c6680bc","stable_key":"a8baf7e9-80e4-5d8c-adec-9a63e84d2f21:l-cysteine-ado-protein-stability-event","event_type":"observed_relationship","label":"Oxidation can mark a signaling regulator for degradation rather than merely damage it.","description":"ADO-dependent N-terminal cysteine oxidation regulated RGS4/5 stability through the N-degron pathway in human cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"fdeeed42-76ed-5016-b0bc-c1bf9120af3d","slug":"ado","display_name":"Human 2-aminoethanethiol dioxygenase / ADO","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"0ab9d700-c4d9-589c-8575-6cfa5a68572c","slug":"rgs4","display_name":"Human regulator of G-protein signaling 4 / RGS4","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ca899f13-50ad-55e5-ab99-329ae0038c74","slug":"l-cysteine","display_name":"L-Cysteine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f52e36ad-972a-52c2-b8e9-1cbacffeedbc","slug":"protein-n-terminal-cysteine","display_name":"Protein-incorporated N-terminal cysteine residue","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"ea79d404-ae5e-5f2a-8e87-4feadb7f2b81","slug":"rgs5","display_name":"Human regulator of G-protein signaling 5 / RGS5","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary full text","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human-cell ADO and oxygen perturbations with N-degron readouts.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The downstream pathway requires additional machinery; dietary cysteine effects were not tested.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit.","comparator":null,"unit":null,"notes":"","entity":{"slug":"l-cysteine","display_name":"L-Cysteine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"Oxidation can mark a signaling regulator for degradation rather than merely damage it.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d4068cef-6317-5ee3-8336-c4556c853e29","evidence_kind":"source_excerpt","locator":"Lines 428-434","start_line":428,"end_line":434,"excerpt":"## l-cysteine-ado-protein-stability\nOxidation can mark a signaling regulator for degradation rather than merely damage it.\nADO-dependent N-terminal cysteine oxidation regulated RGS4/5 stability through the N-degron pathway in human cells.\nModel: Human-cell ADO and oxygen perturbations with N-degron readouts.\nLimitations: The downstream pathway requires additional machinery; dietary cysteine effects were not tested.\nEvidence access: Primary full text\nConserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112","model_system":"Human-cell ADO and oxygen perturbations with N-degron readouts.","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":"654560f6-8d7f-596b-8722-48d94053cfe3","stable_key":"import-a8baf7e9-80e4-5d8c-adec-9a63e84d2f21","title":"L-Cysteine: sulfur allocation, redox supply 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":"f722669e54eab08ffe7289f9d79ddfc443014ed8c4bc5ba10ce2635470d22498","revision_id":"8ae25609-a031-5782-9c62-6cad8767ea46","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}