{"gene":"PF3D7_1430400","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2018,"finding":"PfATG5 (PF3D7_1430400) is expressed in all intraerythrocytic stages of P. falciparum, partially colocalizes with ER, mitochondria, apicoplast, and PfAtg8, and is present on double-membrane-bound vesicles, consistent with a role in the parasite's autophagy machinery during intraerythrocytic development.","method":"Immunofluorescence/colocalization microscopy, expression analysis across intraerythrocytic stages, vesicle fractionation","journal":"Cell death discovery","confidence":"Medium","confidence_rationale":"Tier 3 / Weak — single lab, single set of localization methods, no functional rescue or mutagenesis; provides subcellular localization with partial functional inference","pmids":["30302277"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"finding":"PbATG5 transcript is upregulated in P. berghei ex vivo cultures treated with chloroquine and 5-fluorouracil, suggesting that ATG5 participates in the transcriptional autophagy response to drug-induced stress in the parasite.","method":"Transcriptional analysis (gene expression measurement) of PbATG5 in drug-treated ex vivo P. berghei cultures","journal":"Parasitology research","confidence":"Low","confidence_rationale":"Tier 4 / Weak — expression-level measurement only, no protein or functional data, single lab, single method","pmids":["38976068"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PF3D7_1430400 (ATG5) is expressed across all intraerythrocytic stages of P. falciparum and localizes to double-membrane vesicles and partially to the ER, mitochondria, apicoplast, and PfAtg8-positive structures, placing it within the parasite's autophagy conjugation machinery; its transcript is upregulated in P. berghei under drug-induced stress, but beyond these localization and expression observations, no direct biochemical activity, binding partner, or functional rescue experiment has been reported for this specific Plasmodium protein."},"narrative":{"mechanistic_narrative":"PF3D7_1430400 (ATG5) is a putative component of the Plasmodium autophagy machinery expressed throughout intraerythrocytic development of P. falciparum [PMID:30302277]. It localizes to double-membrane-bound vesicles and partially colocalizes with the endoplasmic reticulum, mitochondria, apicoplast, and PfAtg8, placing it in association with the parasite's autophagy conjugation and membrane-remodeling compartments during blood-stage growth [PMID:30302277]. Beyond this localization and expression profile, no direct biochemical activity, binding partner, substrate, or functional rescue has been characterized for this protein in the available corpus. In P. berghei, the ATG5 transcript is upregulated in ex vivo cultures exposed to chloroquine and 5-fluorouracil, consistent with participation in a transcriptional autophagy response to drug-induced stress [PMID:38976068].","teleology":[{"year":2018,"claim":"To establish whether PF3D7_1430400 is part of the parasite autophagy apparatus, its expression and subcellular distribution across the blood stages were mapped, showing it is present throughout intraerythrocytic development and associates with autophagy-relevant membranes.","evidence":"Immunofluorescence/colocalization microscopy, stage-resolved expression analysis, and vesicle fractionation in P. falciparum","pmids":["30302277"],"confidence":"Medium","gaps":["No functional assay, mutagenesis, or rescue tests whether ATG5 is required for autophagy","No biochemical demonstration of a conjugation reaction or binding partner (e.g. direct interaction with PfAtg8)","Colocalization is only partial and does not establish causal recruitment to any organelle"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2024,"claim":"To probe whether ATG5 responds to antimalarial stress, its transcript levels were measured under drug exposure, revealing upregulation and implicating it in a stress-induced autophagy transcriptional program.","evidence":"Transcriptional (gene expression) analysis of PbATG5 in chloroquine- and 5-fluorouracil-treated ex vivo P. berghei cultures","pmids":["38976068"],"confidence":"Low","gaps":["Expression-level measurement only, with no protein or functional data to confirm an autophagy role","Does not distinguish a causal contribution to drug response from a nonspecific stress signature","Cross-species relevance to the P. falciparum ortholog not established"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"The core molecular function of ATG5 in Plasmodium — its enzymatic/conjugation activity, direct binding partners, and requirement for autophagy or parasite survival — remains undetermined.","evidence":"No direct biochemical, interaction, or loss-of-function evidence for this protein exists in the available corpus","pmids":[],"confidence":"Low","gaps":["No demonstrated binding partner or complex membership for PF3D7_1430400 itself","No knockout/knockdown or rescue defining its functional requirement","No structural or biochemical characterization of any conjugation activity"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Expressed across all intraerythrocytic stages of P. falciparum and present on double-membrane-bound vesicles [#0].","Partial colocalization with PfAtg8-positive structures links it to the autophagy machinery but no direct interaction has been demonstrated [#0].","In P. berghei, ATG5 transcript is upregulated under chloroquine and 5-fluorouracil treatment [#1].","No direct biochemical activity, binding partner, substrate, or functional rescue has been reported for PF3D7_1430400 in the available corpus."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"27185909","id":"PMC_27185909","title":"LAP-like process as an immune mechanism downstream of IFN-γ in control of the human malaria Plasmodium vivax liver stage.","date":"2016","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/27185909","citation_count":70,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATG5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26399761","id":"PMC_26399761","title":"Host cell autophagy contributes to Plasmodium liver development.","date":"2015","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/26399761","citation_count":68,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATG5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28573684","id":"PMC_28573684","title":"LC3-association with the parasitophorous vacuole membrane of Plasmodium berghei liver stages follows a noncanonical autophagy pathway.","date":"2017","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28573684","citation_count":49,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATG5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25426852","id":"PMC_25426852","title":"Characterization of the autophagy marker protein Atg8 reveals atypical features of autophagy in Plasmodium falciparum.","date":"2014","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/25426852","citation_count":42,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30302277","id":"PMC_30302277","title":"Basal and starvation-induced autophagy mediates parasite survival during intraerythrocytic stages of Plasmodium falciparum.","date":"2018","source":"Cell death discovery","url":"https://pubmed.ncbi.nlm.nih.gov/30302277","citation_count":25,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfATG5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34747313","id":"PMC_34747313","title":"A noncanonical autophagy is involved in the transfer of Plasmodium-microvesicles to astrocytes.","date":"2021","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/34747313","citation_count":9,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATG5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33771680","id":"PMC_33771680","title":"Plasmodium UIS3 avoids host cell-autonomous exclusion that requires GABARAPs but not LC3 and autophagy.","date":"2021","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/33771680","citation_count":6,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATG5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36869438","id":"PMC_36869438","title":"Biological functions and structural biology of Plasmodium falciparum autophagy-related proteins: The under-explored options for novel antimalarial drug design.","date":"2023","source":"Chemical biology & drug design","url":"https://pubmed.ncbi.nlm.nih.gov/36869438","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfATG5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38976068","id":"PMC_38976068","title":"Drug-induced ER stress leads to induction of programmed cell death pathways of the malaria parasite.","date":"2024","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/38976068","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PbATG5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42473197","id":"PMC_42473197","title":"Divergent Autophagy Pathways in Plasmodium: Mechanisms, Functions, and Therapeutic Potential.","date":"2026","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/42473197","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["ATG5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7826,"output_tokens":657,"usd":0.016667,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5245,"output_tokens":1717,"usd":0.034575,"stage2_stop_reason":"end_turn"},"total_usd":0.051242,"stage1_batch_id":"msgbatch_011BPjN2BL33F8cJXD1r7V7T","stage2_batch_id":"msgbatch_01Qwg6vP7qxkpL6Gsc7tajsb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"PfATG5 (PF3D7_1430400) is expressed in all intraerythrocytic stages of P. falciparum, partially colocalizes with ER, mitochondria, apicoplast, and PfAtg8, and is present on double-membrane-bound vesicles, consistent with a role in the parasite's autophagy machinery during intraerythrocytic development.\",\n      \"method\": \"Immunofluorescence/colocalization microscopy, expression analysis across intraerythrocytic stages, vesicle fractionation\",\n      \"journal\": \"Cell death discovery\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single set of localization methods, no functional rescue or mutagenesis; provides subcellular localization with partial functional inference\",\n      \"pmids\": [\"30302277\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"PbATG5 transcript is upregulated in P. berghei ex vivo cultures treated with chloroquine and 5-fluorouracil, suggesting that ATG5 participates in the transcriptional autophagy response to drug-induced stress in the parasite.\",\n      \"method\": \"Transcriptional analysis (gene expression measurement) of PbATG5 in drug-treated ex vivo P. berghei cultures\",\n      \"journal\": \"Parasitology research\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — expression-level measurement only, no protein or functional data, single lab, single method\",\n      \"pmids\": [\"38976068\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1430400 (ATG5) is expressed across all intraerythrocytic stages of P. falciparum and localizes to double-membrane vesicles and partially to the ER, mitochondria, apicoplast, and PfAtg8-positive structures, placing it within the parasite's autophagy conjugation machinery; its transcript is upregulated in P. berghei under drug-induced stress, but beyond these localization and expression observations, no direct biochemical activity, binding partner, or functional rescue experiment has been reported for this specific Plasmodium protein.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1430400 (ATG5) is a putative component of the Plasmodium autophagy machinery expressed throughout intraerythrocytic development of P. falciparum [#0]. It localizes to double-membrane-bound vesicles and partially colocalizes with the endoplasmic reticulum, mitochondria, apicoplast, and PfAtg8, placing it in association with the parasite's autophagy conjugation and membrane-remodeling compartments during blood-stage growth [#0]. Beyond this localization and expression profile, no direct biochemical activity, binding partner, substrate, or functional rescue has been characterized for this protein in the available corpus. In P. berghei, the ATG5 transcript is upregulated in ex vivo cultures exposed to chloroquine and 5-fluorouracil, consistent with participation in a transcriptional autophagy response to drug-induced stress [#1].\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"To establish whether PF3D7_1430400 is part of the parasite autophagy apparatus, its expression and subcellular distribution across the blood stages were mapped, showing it is present throughout intraerythrocytic development and associates with autophagy-relevant membranes.\",\n      \"evidence\": \"Immunofluorescence/colocalization microscopy, stage-resolved expression analysis, and vesicle fractionation in P. falciparum\",\n      \"pmids\": [\"30302277\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional assay, mutagenesis, or rescue tests whether ATG5 is required for autophagy\",\n        \"No biochemical demonstration of a conjugation reaction or binding partner (e.g. direct interaction with PfAtg8)\",\n        \"Colocalization is only partial and does not establish causal recruitment to any organelle\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"To probe whether ATG5 responds to antimalarial stress, its transcript levels were measured under drug exposure, revealing upregulation and implicating it in a stress-induced autophagy transcriptional program.\",\n      \"evidence\": \"Transcriptional (gene expression) analysis of PbATG5 in chloroquine- and 5-fluorouracil-treated ex vivo P. berghei cultures\",\n      \"pmids\": [\"38976068\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Expression-level measurement only, with no protein or functional data to confirm an autophagy role\",\n        \"Does not distinguish a causal contribution to drug response from a nonspecific stress signature\",\n        \"Cross-species relevance to the P. falciparum ortholog not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The core molecular function of ATG5 in Plasmodium — its enzymatic/conjugation activity, direct binding partners, and requirement for autophagy or parasite survival — remains undetermined.\",\n      \"evidence\": \"No direct biochemical, interaction, or loss-of-function evidence for this protein exists in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No demonstrated binding partner or complex membership for PF3D7_1430400 itself\",\n        \"No knockout/knockdown or rescue defining its functional requirement\",\n        \"No structural or biochemical characterization of any conjugation activity\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005783\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0020011\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0030659\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006914\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0033554\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Expressed across all intraerythrocytic stages of P. falciparum and present on double-membrane-bound vesicles [#0].\",\n      \"Partial colocalization with PfAtg8-positive structures links it to the autophagy machinery but no direct interaction has been demonstrated [#0].\",\n      \"In P. berghei, ATG5 transcript is upregulated under chloroquine and 5-fluorouracil treatment [#1].\",\n      \"No direct biochemical activity, binding partner, substrate, or functional rescue has been reported for PF3D7_1430400 in the available corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1430400","name":null,"product":"autophagy protein 5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1014300","name":null,"product":"autophagy protein 5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1328300","name":null,"product":"autophagy protein 5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"ATG5","evaluation":null}