{"gene":"PF3D7_0825200","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2015,"finding":"PF3D7_0825200 (IF3a, referred to as PfIF3a in the paper) localises exclusively to the mitochondrion of P. falciparum, as demonstrated by immunofluorescence and subcellular fractionation experiments using specific antisera.","method":"Immunofluorescence microscopy and subcellular fractionation with Western blotting using anti-PfIF3a antiserum","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by two orthogonal methods (immunofluorescence + fractionation) in a single lab, with functional consequence (mitochondrial translation initiation)","pmids":["25689481"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"PF3D7_0825200 (IF3a) exhibits ribosome anti-association activity, and monosome splitting by PF3D7_0825200 is enhanced by the ribosome recycling factor PfRRF2 and PfEF-G(Mit), placing it in the mitochondrial translation initiation pathway.","method":"In vitro ribosome anti-association and monosome splitting assays with purified components","journal":"Molecular microbiology","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro biochemical reconstitution assay demonstrating enzymatic/functional activity with defined partners, single lab but multiple orthogonal functional tests","pmids":["25689481"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Anti-PfIF3a (PF3D7_0825200) antiserum used as a mitochondrial marker in subcellular fractionation showed enrichment of only the lower-molecular-weight (processed/mature) form of IF3a in the mitochondrial pellet fraction, consistent with mitochondrial targeting sequence cleavage upon import.","method":"Subcellular fractionation and Western blotting with anti-PfIF3a antiserum","journal":"PloS one","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — subcellular fractionation with Western blot used as a mitochondrial marker; single method, single paper, reported as a secondary finding in a study focused on PfHsp60","pmids":["26317863"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0825200 (IF3a) is a nuclear-encoded mitochondrial translation initiation factor in P. falciparum that localises exclusively to the mitochondrion, exhibits ribosome anti-association activity, and promotes monosome splitting—an activity that is enhanced by cooperation with the ribosome recycling factor PfRRF2 and the mitochondrial elongation factor PfEF-G(Mit)."},"narrative":{"mechanistic_narrative":"PF3D7_0825200 (IF3a) is a nuclear-encoded mitochondrial translation initiation factor of Plasmodium falciparum that localises exclusively to the mitochondrion, as shown by immunofluorescence and subcellular fractionation [PMID:25689481]. Only the lower-molecular-weight, processed form of the protein is recovered in the mitochondrial fraction, consistent with cleavage of a mitochondrial targeting sequence upon import [PMID:26317863]. Functionally, IF3a acts in mitochondrial translation initiation by exhibiting ribosome anti-association activity: it splits monosomes, and this activity is enhanced in cooperation with the ribosome recycling factor PfRRF2 and the mitochondrial elongation factor PfEF-G(Mit) [PMID:25689481]. Beyond this mitochondrial ribosome-splitting role and its cooperation with PfRRF2 and PfEF-G(Mit) [PMID:25689481], no further mechanistic detail for PF3D7_0825200 has been characterized in the available corpus.","teleology":[{"year":2015,"claim":"Establishing where IF3a acts answered whether this initiation factor functions in cytoplasmic or organellar translation, placing it in the mitochondrion.","evidence":"Immunofluorescence microscopy and subcellular fractionation with anti-PfIF3a antiserum in P. falciparum","pmids":["25689481"],"confidence":"Medium","gaps":["Localization shown in a single lab; sub-mitochondrial positioning (matrix vs membrane association) not resolved","Does not address whether the protein is essential for parasite viability"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Reconstitution defined the biochemical activity of IF3a, showing it splits monosomes through ribosome anti-association and cooperates with PfRRF2 and PfEF-G(Mit) in mitochondrial translation initiation.","evidence":"In vitro ribosome anti-association and monosome-splitting assays with purified components","pmids":["25689481"],"confidence":"High","gaps":["The structural basis of ribosome binding and the interface with PfRRF2/PfEF-G(Mit) is not resolved","In vitro activity has not been linked to a defined phenotype in living parasites","The order and kinetics of factor recruitment during initiation are not established"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"Detection of a processed lower-molecular-weight form addressed how the nuclear-encoded protein reaches the mitochondrion, indicating import-coupled cleavage of a targeting sequence.","evidence":"Subcellular fractionation and Western blotting with anti-PfIF3a antiserum, reported as a secondary marker finding","pmids":["26317863"],"confidence":"Medium","gaps":["Single method used as a mitochondrial marker in a study focused on another protein; the cleavage site and processing protease were not identified","Import pathway components were not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether IF3a is essential for P. falciparum mitochondrial function and blood-stage growth, and its structural mechanism of ribosome engagement, remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic knockout, knockdown, or conditional depletion of PF3D7_0825200 in the corpus","No structure of IF3a or of its complexes with the mitochondrial ribosome or partner factors","No demonstration of essentiality or drug-target potential"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PFRRF2","PFEF-G(MIT)"],"other_free_text":["Only the processed (mature, lower-molecular-weight) form of IF3a is recovered in the mitochondrial fraction, consistent with cleavage of a mitochondrial targeting sequence upon import [#2].","Monosome-splitting/ribosome anti-association activity of IF3a is enhanced by cooperation with PfRRF2 and PfEF-G(Mit) [#1]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"21741312","id":"PMC_21741312","title":"Protein translation in Plasmodium parasites.","date":"2011","source":"Trends in parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/21741312","citation_count":75,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25689481","id":"PMC_25689481","title":"Targeting and function of proteins mediating translation initiation in organelles of Plasmodium falciparum.","date":"2015","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/25689481","citation_count":14,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfIF3a"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36750737","id":"","title":"Population genetic analysis of Plasmodium knowlesi reveals differential selection and exchange events between Borneo and Peninsular sub-populations.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/36750737","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IF3a"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26317863","id":"","title":"Characterization of Precursor PfHsp60 in Plasmodium falciparum Cytosol during Its Asexual Development in Human Erythrocytes.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26317863","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["IF3a"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5831,"output_tokens":867,"usd":0.015249,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5577,"output_tokens":1827,"usd":0.03678,"stage2_stop_reason":"end_turn"},"total_usd":0.052029,"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\": 2015,\n      \"finding\": \"PF3D7_0825200 (IF3a, referred to as PfIF3a in the paper) localises exclusively to the mitochondrion of P. falciparum, as demonstrated by immunofluorescence and subcellular fractionation experiments using specific antisera.\",\n      \"method\": \"Immunofluorescence microscopy and subcellular fractionation with Western blotting using anti-PfIF3a antiserum\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by two orthogonal methods (immunofluorescence + fractionation) in a single lab, with functional consequence (mitochondrial translation initiation)\",\n      \"pmids\": [\"25689481\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"PF3D7_0825200 (IF3a) exhibits ribosome anti-association activity, and monosome splitting by PF3D7_0825200 is enhanced by the ribosome recycling factor PfRRF2 and PfEF-G(Mit), placing it in the mitochondrial translation initiation pathway.\",\n      \"method\": \"In vitro ribosome anti-association and monosome splitting assays with purified components\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro biochemical reconstitution assay demonstrating enzymatic/functional activity with defined partners, single lab but multiple orthogonal functional tests\",\n      \"pmids\": [\"25689481\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Anti-PfIF3a (PF3D7_0825200) antiserum used as a mitochondrial marker in subcellular fractionation showed enrichment of only the lower-molecular-weight (processed/mature) form of IF3a in the mitochondrial pellet fraction, consistent with mitochondrial targeting sequence cleavage upon import.\",\n      \"method\": \"Subcellular fractionation and Western blotting with anti-PfIF3a antiserum\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — subcellular fractionation with Western blot used as a mitochondrial marker; single method, single paper, reported as a secondary finding in a study focused on PfHsp60\",\n      \"pmids\": [\"26317863\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0825200 (IF3a) is a nuclear-encoded mitochondrial translation initiation factor in P. falciparum that localises exclusively to the mitochondrion, exhibits ribosome anti-association activity, and promotes monosome splitting—an activity that is enhanced by cooperation with the ribosome recycling factor PfRRF2 and the mitochondrial elongation factor PfEF-G(Mit).\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0825200 (IF3a) is a nuclear-encoded mitochondrial translation initiation factor of Plasmodium falciparum that localises exclusively to the mitochondrion, as shown by immunofluorescence and subcellular fractionation [#0]. Only the lower-molecular-weight, processed form of the protein is recovered in the mitochondrial fraction, consistent with cleavage of a mitochondrial targeting sequence upon import [#2]. Functionally, IF3a acts in mitochondrial translation initiation by exhibiting ribosome anti-association activity: it splits monosomes, and this activity is enhanced in cooperation with the ribosome recycling factor PfRRF2 and the mitochondrial elongation factor PfEF-G(Mit) [#1]. Beyond this mitochondrial ribosome-splitting role and its cooperation with PfRRF2 and PfEF-G(Mit) [#0, #1], no further mechanistic detail for PF3D7_0825200 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Establishing where IF3a acts answered whether this initiation factor functions in cytoplasmic or organellar translation, placing it in the mitochondrion.\",\n      \"evidence\": \"Immunofluorescence microscopy and subcellular fractionation with anti-PfIF3a antiserum in P. falciparum\",\n      \"pmids\": [\"25689481\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Localization shown in a single lab; sub-mitochondrial positioning (matrix vs membrane association) not resolved\",\n        \"Does not address whether the protein is essential for parasite viability\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Reconstitution defined the biochemical activity of IF3a, showing it splits monosomes through ribosome anti-association and cooperates with PfRRF2 and PfEF-G(Mit) in mitochondrial translation initiation.\",\n      \"evidence\": \"In vitro ribosome anti-association and monosome-splitting assays with purified components\",\n      \"pmids\": [\"25689481\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The structural basis of ribosome binding and the interface with PfRRF2/PfEF-G(Mit) is not resolved\",\n        \"In vitro activity has not been linked to a defined phenotype in living parasites\",\n        \"The order and kinetics of factor recruitment during initiation are not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Detection of a processed lower-molecular-weight form addressed how the nuclear-encoded protein reaches the mitochondrion, indicating import-coupled cleavage of a targeting sequence.\",\n      \"evidence\": \"Subcellular fractionation and Western blotting with anti-PfIF3a antiserum, reported as a secondary marker finding\",\n      \"pmids\": [\"26317863\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single method used as a mitochondrial marker in a study focused on another protein; the cleavage site and processing protease were not identified\",\n        \"Import pathway components were not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether IF3a is essential for P. falciparum mitochondrial function and blood-stage growth, and its structural mechanism of ribosome engagement, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic knockout, knockdown, or conditional depletion of PF3D7_0825200 in the corpus\",\n        \"No structure of IF3a or of its complexes with the mitochondrial ribosome or partner factors\",\n        \"No demonstration of essentiality or drug-target potential\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0043022\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0003743\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0032543\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PfRRF2\", \"PfEF-G(Mit)\"],\n    \"other_free_text\": [\n      \"Only the processed (mature, lower-molecular-weight) form of IF3a is recovered in the mitochondrial fraction, consistent with cleavage of a mitochondrial targeting sequence upon import [#2].\",\n      \"Monosome-splitting/ribosome anti-association activity of IF3a is enhanced by cooperation with PfRRF2 and PfEF-G(Mit) [#1].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0825200","name":null,"product":"translation initiation factor IF-3","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0705400","name":null,"product":"translation initiation factor IF-3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1319200","name":null,"product":"translation initiation factor IF-3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"IF3a","evaluation":null}