{"gene":"PF3D7_1420300","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2016,"finding":"HEP1 (PF3D7_1420300) was identified as a putative Hep1 orthologue in P. falciparum that interacts with PfHsp70-3: co-expression of HEP1 with PfHsp70-3 enhanced the solubility of PfHsp70-3, and HEP1 specifically suppressed thermally induced aggregation of PfHsp70-3 but not of malate dehydrogenase or citrate synthase, demonstrating chaperone-escort specificity for PfHsp70-3.","method":"Co-expression in heterologous system, in vitro aggregation suppression assay with thermal stress","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro biochemical reconstitution (aggregation assay) with specificity controls, but single lab, single study","pmids":["27253881"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"finding":"Zinc ions are essential for HEP1 (PF3D7_1420300) function: chelation of zinc by EDTA abrogated the ability of HEP1 to suppress the aggregation of PfHsp70-3, establishing that the DNL-type zinc finger is required for its chaperone-escort activity.","method":"In vitro aggregation suppression assay with EDTA zinc chelation","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro functional assay with chemical perturbation, single lab, single study","pmids":["27253881"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"HEP1 (PF3D7_1420300) is a zinc-dependent chaperone-escort protein in P. falciparum that specifically prevents the self-aggregation of the mitochondrial chaperone PfHsp70-3 through a mechanism requiring intact zinc coordination at its DNL-type zinc finger domain."},"narrative":{"mechanistic_narrative":"HEP1 (PF3D7_1420300) is a DNL-type zinc finger protein in Plasmodium falciparum that functions as a chaperone-escort factor for the mitochondrial-type chaperone PfHsp70-3 [PMID:27253881]. Co-expression of HEP1 with PfHsp70-3 enhances the solubility of the chaperone, and HEP1 specifically suppresses the thermally induced aggregation of PfHsp70-3 but not of unrelated substrates such as malate dehydrogenase or citrate synthase, establishing substrate specificity for PfHsp70-3 [PMID:27253881]. This escort activity depends on zinc coordination: chelation of zinc with EDTA abolishes HEP1's ability to prevent PfHsp70-3 aggregation, indicating that an intact DNL-type zinc finger is required for function [PMID:27253881]. Beyond this in vitro anti-aggregation activity toward PfHsp70-3, no further mechanistic detail — including cellular localization, in vivo function, or essentiality — has been characterized for PF3D7_1420300 in the available corpus.","teleology":[{"year":2016,"claim":"Whether P. falciparum encodes a functional Hep1-type escort protein and which chaperone it acts on was unknown; identifying HEP1 as a specific anti-aggregation partner of PfHsp70-3 established its role as a chaperone-escort protein.","evidence":"Co-expression in a heterologous system and in vitro thermal aggregation suppression assays with specificity controls (MDH, citrate synthase)","pmids":["27253881"],"confidence":"Medium","gaps":["Not tested in vivo in the parasite; cellular localization and essentiality not addressed","Direct physical binding stoichiometry/affinity to PfHsp70-3 not resolved","Single lab, single study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2016,"claim":"Whether the DNL-type zinc finger is functionally required was unknown; demonstrating that zinc chelation abolishes anti-aggregation activity established zinc coordination as essential for HEP1 escort function.","evidence":"In vitro aggregation suppression assay with EDTA-mediated zinc chelation","pmids":["27253881"],"confidence":"Medium","gaps":["EDTA chelation is a bulk perturbation; specific zinc-coordinating residues not mutationally defined","Structural basis of zinc-dependent PfHsp70-3 engagement not determined","Single lab, single study"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The in vivo role of PF3D7_1420300 in the parasite — its subcellular localization, requirement for PfHsp70-3 function during the life cycle, and essentiality — remains uncharacterized.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No in-parasite genetic or localization data in the corpus","No structural model of the HEP1–PfHsp70-3 interaction","Zinc-coordinating residues not individually mapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFHSP70-3"],"other_free_text":["Chaperone-escort protein that specifically suppresses thermally induced aggregation of PfHsp70-3 but not of malate dehydrogenase or citrate synthase [#0]","Anti-aggregation activity requires zinc; abolished by EDTA chelation, implicating the DNL-type zinc finger [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"27253881","id":"PMC_27253881","title":"Plasmodium falciparum Hep1 Is Required to Prevent the Self Aggregation of PfHsp70-3.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27253881","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HEP1","PfHEP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32529065","id":"","title":"Identification of Plasmodium falciparum HSP70-2 as a resident of the Plasmodium export compartment.","date":"2020","source":"Heliyon","url":"https://pubmed.ncbi.nlm.nih.gov/32529065","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HEP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"27901110","id":"","title":"The rodent malaria liver stage survives in the rapamycin-induced autophagosome of infected Hepa1-6 cells.","date":"2016","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/27901110","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HEP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21698150","id":"","title":"The IFN-γ-inducible GTPase, Irga6, protects mice against Toxoplasma gondii but not against Plasmodium berghei and some other intracellular pathogens.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21698150","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["HEP1"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6754,"output_tokens":630,"usd":0.014856,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5195,"output_tokens":1596,"usd":0.032938,"stage2_stop_reason":"end_turn"},"total_usd":0.047794,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"HEP1 (PF3D7_1420300) was identified as a putative Hep1 orthologue in P. falciparum that interacts with PfHsp70-3: co-expression of HEP1 with PfHsp70-3 enhanced the solubility of PfHsp70-3, and HEP1 specifically suppressed thermally induced aggregation of PfHsp70-3 but not of malate dehydrogenase or citrate synthase, demonstrating chaperone-escort specificity for PfHsp70-3.\",\n      \"method\": \"Co-expression in heterologous system, in vitro aggregation suppression assay with thermal stress\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro biochemical reconstitution (aggregation assay) with specificity controls, but single lab, single study\",\n      \"pmids\": [\"27253881\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Zinc ions are essential for HEP1 (PF3D7_1420300) function: chelation of zinc by EDTA abrogated the ability of HEP1 to suppress the aggregation of PfHsp70-3, establishing that the DNL-type zinc finger is required for its chaperone-escort activity.\",\n      \"method\": \"In vitro aggregation suppression assay with EDTA zinc chelation\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct in vitro functional assay with chemical perturbation, single lab, single study\",\n      \"pmids\": [\"27253881\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"HEP1 (PF3D7_1420300) is a zinc-dependent chaperone-escort protein in P. falciparum that specifically prevents the self-aggregation of the mitochondrial chaperone PfHsp70-3 through a mechanism requiring intact zinc coordination at its DNL-type zinc finger domain.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"HEP1 (PF3D7_1420300) is a DNL-type zinc finger protein in Plasmodium falciparum that functions as a chaperone-escort factor for the mitochondrial-type chaperone PfHsp70-3 [#0]. Co-expression of HEP1 with PfHsp70-3 enhances the solubility of the chaperone, and HEP1 specifically suppresses the thermally induced aggregation of PfHsp70-3 but not of unrelated substrates such as malate dehydrogenase or citrate synthase, establishing substrate specificity for PfHsp70-3 [#0]. This escort activity depends on zinc coordination: chelation of zinc with EDTA abolishes HEP1's ability to prevent PfHsp70-3 aggregation, indicating that an intact DNL-type zinc finger is required for function [#1]. Beyond this in vitro anti-aggregation activity toward PfHsp70-3, no further mechanistic detail — including cellular localization, in vivo function, or essentiality — has been characterized for PF3D7_1420300 in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether P. falciparum encodes a functional Hep1-type escort protein and which chaperone it acts on was unknown; identifying HEP1 as a specific anti-aggregation partner of PfHsp70-3 established its role as a chaperone-escort protein.\",\n      \"evidence\": \"Co-expression in a heterologous system and in vitro thermal aggregation suppression assays with specificity controls (MDH, citrate synthase)\",\n      \"pmids\": [\n        \"27253881\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Not tested in vivo in the parasite; cellular localization and essentiality not addressed\",\n        \"Direct physical binding stoichiometry/affinity to PfHsp70-3 not resolved\",\n        \"Single lab, single study\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Whether the DNL-type zinc finger is functionally required was unknown; demonstrating that zinc chelation abolishes anti-aggregation activity established zinc coordination as essential for HEP1 escort function.\",\n      \"evidence\": \"In vitro aggregation suppression assay with EDTA-mediated zinc chelation\",\n      \"pmids\": [\n        \"27253881\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"EDTA chelation is a bulk perturbation; specific zinc-coordinating residues not mutationally defined\",\n        \"Structural basis of zinc-dependent PfHsp70-3 engagement not determined\",\n        \"Single lab, single study\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The in vivo role of PF3D7_1420300 in the parasite — its subcellular localization, requirement for PfHsp70-3 function during the life cycle, and essentiality — remains uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No in-parasite genetic or localization data in the corpus\",\n        \"No structural model of the HEP1–PfHsp70-3 interaction\",\n        \"Zinc-coordinating residues not individually mapped\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0051082\",\n        \"supporting_discovery_ids\": [0, 1]\n      },\n      {\n        \"term_id\": \"GO:0008270\",\n        \"supporting_discovery_ids\": [1]\n      }\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0006457\",\n        \"supporting_discovery_ids\": [0]\n      }\n    ],\n    \"complexes\": [],\n    \"partners\": [\n      \"PfHsp70-3\"\n    ],\n    \"other_free_text\": [\n      \"Chaperone-escort protein that specifically suppresses thermally induced aggregation of PfHsp70-3 but not of malate dehydrogenase or citrate synthase [#0]\",\n      \"Anti-aggregation activity requires zinc; abolished by EDTA chelation, implicating the DNL-type zinc finger [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1420300","name":null,"product":"DNL-type zinc finger protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1022900","name":null,"product":"DNL-type zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1337700","name":null,"product":"DNL-type zinc finger protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"HEP1","evaluation":null}