{"id":"5adb5d09-0e2a-5586-a9b8-5a31b04c254a","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-hzip4-degradation","predicate":"stimulates","statement":"Elevated zinc stimulated human ZIP4 ubiquitination and degradation; a cytoplasmic histidine-rich region was required for this degradation response but dispensable for zinc-induced endocytosis.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"49359de3-55cf-5842-8c4f-a700e5f0bcf7","mechanism_event_label":"Human ZIP4 has a zinc-triggered disposal response that is separate from removal from the surface.","subject":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"object":{"id":"32891bbc-5f05-5eec-bcf5-d4a85d64665a","slug":"zip4-degradation","display_name":"ZIP4 protein degradation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"49359de3-55cf-5842-8c4f-a700e5f0bcf7","stable_key":"6d38d43e-01e4-5641-93be-65654271e242:zinc-trans-hzip4-degradation-event","event_type":"biochemical_relationship","label":"Human ZIP4 has a zinc-triggered disposal response that is separate from removal from the surface.","description":"Elevated zinc stimulated human ZIP4 ubiquitination and degradation; a cytoplasmic histidine-rich region was required for this degradation response but dispensable for zinc-induced endocytosis.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"3d7744ad-4103-5c95-90a3-23bdeee45db4","slug":"slc39a4","display_name":"Human ZIP4 (SLC39A4)","entity_type_key":"protein"},"role":"regulated_transporter","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"49c806c2-7041-5020-8b3b-fa04ffa122ac","slug":"zinc-ion","display_name":"Zinc(II) ion","entity_type_key":"ion"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"32891bbc-5f05-5eec-bcf5-d4a85d64665a","slug":"zip4-degradation","display_name":"ZIP4 protein degradation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cultured cells expressing human ZIP4 with mutational analysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Elevated zinc exposure; detailed concentration and cell lineage not specified in the abstract.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Abstract extraction; the region requirement does not mean every histidine acts as an independent sensor. This is zinc exposure, not demonstrated dietary deficiency.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Zinc research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"zinc","display_name":"Zinc","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human protein in cultured cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Human ZIP4 has a zinc-triggered disposal response that is separate from removal from the surface.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[zinc-trans-17202136] A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. (2007). https://pubmed.ncbi.nlm.nih.gov/17202136/ DOI: 10.1074/jbc.m610552200","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Cellular zinc-uptake machinery","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"d55a2647-f684-54b5-b401-30db2831572f","evidence_kind":"source_excerpt","locator":"Lines 258-269","start_line":258,"end_line":269,"excerpt":"### zinc-trans-hzip4-degradation\nElevated zinc stimulated human ZIP4 ubiquitination and degradation; a cytoplasmic histidine-rich region was required for this degradation response but dispensable for zinc-induced endocytosis.\nCondition category: normal\nnutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Human ZIP4 has a zinc-triggered disposal response that is separate from removal from the surface.\norganism: Human protein in cultured cells\ntissue_or_cell_type: Cellular zinc-uptake machinery\nexperimental_model: Cultured cells expressing human ZIP4 with mutational analysis\nlimitations: Abstract extraction; the region requirement does not mean every histidine acts as an independent sensor. This is zinc exposure, not demonstrated dietary deficiency.\nexposure: Elevated zinc exposure; detailed concentration and cell lineage not specified in the abstract.\ncross_nutrient: false\n[zinc-trans-17202136] A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. (2007). https://pubmed.ncbi.nlm.nih.gov/17202136/ DOI: 10.1074/jbc.m610552200","model_system":"Cultured cells expressing human ZIP4 with mutational analysis","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [zinc-trans-17202136] A histidine-rich cluster mediates the ubiquitination and degradation of the human zinc transporter, hZIP4, and protects against zinc cytotoxicity. (2007). https://pubmed.ncbi.nlm.nih.gov/17202136/ DOI: 10.1074/jbc.m610552200","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"c5ee0fee-ce5c-58de-905a-10fb0ea0723c","stable_key":"import-6d38d43e-01e4-5641-93be-65654271e242","title":"Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"2e731dd54477ec1254e97df3323e1208d38f1375effed19252e71ab4f600d13a","revision_id":"c72258b9-ac09-5408-9d44-a921ad1f96a3","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}