{"gene":"PF3D7_1312900","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2009,"finding":"PF3D7_1312900 (EIF4G) was isolated from P. falciparum and shown by direct biochemical interaction assays to interact with PfeIF4E, PfeIF4A (PfH45), and PfPABP, establishing its role as a scaffold protein within the eIF4F translation initiation complex in the malaria parasite.","method":"Biochemical isolation, co-immunoprecipitation/pull-down interaction assays","journal":"Parasitology international","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct binding interactions demonstrated between EIF4G and multiple partners (eIF4E, eIF4A, PABP) in a single study with biochemical methods, but single lab and no structural or mutagenesis validation","pmids":["19751846"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"finding":"EIF4G (PF3D7_1312900) was found to be excluded from the DOZI/CITH messenger ribonucleoprotein (mRNP) complex in P. berghei female gametocytes, while eIF4E and PABP were included; this exclusion indicates that translation-initiation-promoting activity of EIF4G is absent from the translationally repressed mRNP granules in gametocytes.","method":"Affinity purification coupled with mass spectrometric analysis of the DOZI/CITH mRNP complex","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mass-spectrometry-based affinity purification with functional context; single study but rigorous proteomic identification; finding is a negative result (exclusion) that is mechanistically informative","pmids":["20169188"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2021,"finding":"EIF4G (PF3D7_1312900) was detected as a 5' cap-enriched protein in P. falciparum asexual stage parasites using a 5' cap affinity matrix, consistent with its membership in the eIF4F complex, though with low reproducibility across replicates.","method":"5' cap affinity matrix enrichment coupled with proteomic (mass spectrometric) analysis","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (affinity enrichment), and the paper itself notes low reproducibility of EIF4G detection","pmids":["34890716"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1312900 (EIF4G) functions as a scaffold protein within the P. falciparum eIF4F translation initiation complex, directly interacting with eIF4E, eIF4A, and PABP; it is detectably associated with 5' capped mRNAs in asexual stages, and is specifically excluded from the translationally repressed DOZI/CITH mRNP granules of P. berghei female gametocytes, consistent with its role in promoting active translation initiation."},"narrative":{"mechanistic_narrative":"PF3D7_1312900 (EIF4G) functions as a scaffold protein of the eIF4F cap-binding translation initiation complex in the malaria parasite [PMID:19751846]. In P. falciparum, it engages the core initiation machinery through direct biochemical interactions with the cap-binding protein PfeIF4E, the RNA helicase PfeIF4A (PfH45), and poly(A)-binding protein PfPABP, positioning it to bridge cap recognition and poly(A) recognition during initiation [PMID:19751846]. Consistent with this role, EIF4G is detectably enriched on 5' capped mRNA in asexual-stage parasites [PMID:34890716]. In P. berghei female gametocytes, EIF4G is specifically excluded from the translationally repressed DOZI/CITH mRNP granules that retain eIF4E and PABP, indicating that removal of its initiation-promoting scaffold activity accompanies the storage of untranslated messages [PMID:20169188]. Beyond these interaction and localization findings, the structural basis of partner binding, the domains mediating each contact, and any regulatory control of EIF4G activity have not been characterized in the available corpus.","teleology":[{"year":2009,"claim":"Before this work it was unknown whether the parasite assembles a canonical eIF4F complex; demonstrating direct binding of EIF4G to eIF4E, eIF4A, and PABP established it as the organizing scaffold of P. falciparum translation initiation.","evidence":"Biochemical isolation and co-immunoprecipitation/pull-down interaction assays in P. falciparum","pmids":["19751846"],"confidence":"Medium","gaps":["No structural or mutagenesis mapping of the binding surfaces for eIF4E, eIF4A, or PABP","Single-lab result without independent replication","Functional consequence of complex assembly for translation not directly tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2010,"claim":"It was unclear how translationally repressed maternal mRNAs are held silent in gametocytes; finding that EIF4G is excluded from DOZI/CITH mRNP granules while eIF4E and PABP are retained showed that loss of the initiation scaffold marks the repressed state.","evidence":"Affinity purification and mass spectrometry of the DOZI/CITH mRNP complex in P. berghei female gametocytes","pmids":["20169188"],"confidence":"Medium","gaps":["Mechanism of EIF4G exclusion from the granules is not defined","Finding is in P. berghei and not confirmed for the P. falciparum ortholog","Does not establish whether re-recruitment of EIF4G reactivates translation"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2021,"claim":"To test whether EIF4G physically associates with capped transcripts in growing parasites, a 5' cap affinity approach detected it among cap-enriched proteins, corroborating its eIF4F membership in asexual stages.","evidence":"5' cap affinity matrix enrichment coupled with mass spectrometry in P. falciparum asexual parasites","pmids":["34890716"],"confidence":"Low","gaps":["The authors note low reproducibility of EIF4G detection across replicates","Single method and single lab, no orthogonal validation","Does not quantify the fraction of EIF4G engaged with capped mRNA"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The structural architecture of EIF4G, the domains mediating each partner contact, and the regulatory signals that recruit or exclude it from mRNP complexes remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No structural model or domain-level interaction mapping","No genetic loss-of-function analysis of EIF4G in either species","Mechanism coupling EIF4G status to translational repression versus activation unresolved"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["eIF4F cap-binding translation initiation complex"],"partners":["PFEIF4E","PFEIF4A (PFH45)","PFPABP"],"other_free_text":["In P. falciparum, EIF4G binds eIF4E, eIF4A, and PABP as the eIF4F scaffold and is cap-enriched in asexual stages [#0, #2]","In P. berghei female gametocytes, EIF4G is excluded from translationally repressed DOZI/CITH mRNP granules that retain eIF4E and PABP [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"20169188","id":"PMC_20169188","title":"Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development.","date":"2010","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/20169188","citation_count":216,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EIF4G"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19641745","id":"PMC_19641745","title":"Identification and bioinformatics characterization of translation initiation complex eIF4F components and poly(A)-binding protein from Plasmodium falciparum.","date":"2009","source":"Communicative & integrative biology","url":"https://pubmed.ncbi.nlm.nih.gov/19641745","citation_count":19,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EIF4G","PfEIF4G"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"19751846","id":"PMC_19751846","title":"Isolation and functional characterization of eIF4F components and poly(A)-binding protein from Plasmodium falciparum.","date":"2009","source":"Parasitology international","url":"https://pubmed.ncbi.nlm.nih.gov/19751846","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EIF4G","PfEIF4G"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21331256","id":"PMC_21331256","title":"PfeIF4E and PfeIF4A colocalize and their double-stranded RNA inhibits Plasmodium falciparum proliferation.","date":"2010","source":"Communicative & integrative biology","url":"https://pubmed.ncbi.nlm.nih.gov/21331256","citation_count":13,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EIF4G"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"34890716","id":"PMC_34890716","title":"Identification of mRNA 5' cap-associated proteins in the human malaria parasite Plasmodium falciparum.","date":"2021","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/34890716","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EIF4G"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38018538","id":"PMC_38018538","title":"Architecture, domain organization, and functional signatures of trypanosomatid keIF4A1s and Plasmodium peIF4A1s suggest conserved functions.","date":"2023","source":"Journal of biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/38018538","citation_count":1,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EIF4G"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"42615421","id":"PMC_42615421","title":"Poly(A)-binding proteins in trypanosomatids and Plasmodium.","date":"2026","source":"Journal of biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/42615421","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EIF4G"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5824,"output_tokens":940,"usd":0.015786,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5639,"output_tokens":1931,"usd":0.038235,"stage2_stop_reason":"end_turn"},"total_usd":0.054021,"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\": 2009,\n      \"finding\": \"PF3D7_1312900 (EIF4G) was isolated from P. falciparum and shown by direct biochemical interaction assays to interact with PfeIF4E, PfeIF4A (PfH45), and PfPABP, establishing its role as a scaffold protein within the eIF4F translation initiation complex in the malaria parasite.\",\n      \"method\": \"Biochemical isolation, co-immunoprecipitation/pull-down interaction assays\",\n      \"journal\": \"Parasitology international\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct binding interactions demonstrated between EIF4G and multiple partners (eIF4E, eIF4A, PABP) in a single study with biochemical methods, but single lab and no structural or mutagenesis validation\",\n      \"pmids\": [\"19751846\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"EIF4G (PF3D7_1312900) was found to be excluded from the DOZI/CITH messenger ribonucleoprotein (mRNP) complex in P. berghei female gametocytes, while eIF4E and PABP were included; this exclusion indicates that translation-initiation-promoting activity of EIF4G is absent from the translationally repressed mRNP granules in gametocytes.\",\n      \"method\": \"Affinity purification coupled with mass spectrometric analysis of the DOZI/CITH mRNP complex\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mass-spectrometry-based affinity purification with functional context; single study but rigorous proteomic identification; finding is a negative result (exclusion) that is mechanistically informative\",\n      \"pmids\": [\"20169188\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"EIF4G (PF3D7_1312900) was detected as a 5' cap-enriched protein in P. falciparum asexual stage parasites using a 5' cap affinity matrix, consistent with its membership in the eIF4F complex, though with low reproducibility across replicates.\",\n      \"method\": \"5' cap affinity matrix enrichment coupled with proteomic (mass spectrometric) analysis\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (affinity enrichment), and the paper itself notes low reproducibility of EIF4G detection\",\n      \"pmids\": [\"34890716\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1312900 (EIF4G) functions as a scaffold protein within the P. falciparum eIF4F translation initiation complex, directly interacting with eIF4E, eIF4A, and PABP; it is detectably associated with 5' capped mRNAs in asexual stages, and is specifically excluded from the translationally repressed DOZI/CITH mRNP granules of P. berghei female gametocytes, consistent with its role in promoting active translation initiation.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1312900 (EIF4G) functions as a scaffold protein of the eIF4F cap-binding translation initiation complex in the malaria parasite [#0]. In P. falciparum, it engages the core initiation machinery through direct biochemical interactions with the cap-binding protein PfeIF4E, the RNA helicase PfeIF4A (PfH45), and poly(A)-binding protein PfPABP, positioning it to bridge cap recognition and poly(A) recognition during initiation [#0]. Consistent with this role, EIF4G is detectably enriched on 5' capped mRNA in asexual-stage parasites [#2]. In P. berghei female gametocytes, EIF4G is specifically excluded from the translationally repressed DOZI/CITH mRNP granules that retain eIF4E and PABP, indicating that removal of its initiation-promoting scaffold activity accompanies the storage of untranslated messages [#1]. Beyond these interaction and localization findings, the structural basis of partner binding, the domains mediating each contact, and any regulatory control of EIF4G activity have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Before this work it was unknown whether the parasite assembles a canonical eIF4F complex; demonstrating direct binding of EIF4G to eIF4E, eIF4A, and PABP established it as the organizing scaffold of P. falciparum translation initiation.\",\n      \"evidence\": \"Biochemical isolation and co-immunoprecipitation/pull-down interaction assays in P. falciparum\",\n      \"pmids\": [\"19751846\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural or mutagenesis mapping of the binding surfaces for eIF4E, eIF4A, or PABP\",\n        \"Single-lab result without independent replication\",\n        \"Functional consequence of complex assembly for translation not directly tested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"It was unclear how translationally repressed maternal mRNAs are held silent in gametocytes; finding that EIF4G is excluded from DOZI/CITH mRNP granules while eIF4E and PABP are retained showed that loss of the initiation scaffold marks the repressed state.\",\n      \"evidence\": \"Affinity purification and mass spectrometry of the DOZI/CITH mRNP complex in P. berghei female gametocytes\",\n      \"pmids\": [\"20169188\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism of EIF4G exclusion from the granules is not defined\",\n        \"Finding is in P. berghei and not confirmed for the P. falciparum ortholog\",\n        \"Does not establish whether re-recruitment of EIF4G reactivates translation\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"To test whether EIF4G physically associates with capped transcripts in growing parasites, a 5' cap affinity approach detected it among cap-enriched proteins, corroborating its eIF4F membership in asexual stages.\",\n      \"evidence\": \"5' cap affinity matrix enrichment coupled with mass spectrometry in P. falciparum asexual parasites\",\n      \"pmids\": [\"34890716\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"The authors note low reproducibility of EIF4G detection across replicates\",\n        \"Single method and single lab, no orthogonal validation\",\n        \"Does not quantify the fraction of EIF4G engaged with capped mRNA\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The structural architecture of EIF4G, the domains mediating each partner contact, and the regulatory signals that recruit or exclude it from mRNP complexes remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No structural model or domain-level interaction mapping\",\n        \"No genetic loss-of-function analysis of EIF4G in either species\",\n        \"Mechanism coupling EIF4G status to translational repression versus activation unresolved\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008135\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0003743\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0016281\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006413\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"complexes\": [\"eIF4F cap-binding translation initiation complex\"],\n    \"partners\": [\"PfeIF4E\", \"PfeIF4A (PfH45)\", \"PfPABP\"],\n    \"other_free_text\": [\n      \"In P. falciparum, EIF4G binds eIF4E, eIF4A, and PABP as the eIF4F scaffold and is cap-enriched in asexual stages [#0, #2]\",\n      \"In P. berghei female gametocytes, EIF4G is excluded from translationally repressed DOZI/CITH mRNP granules that retain eIF4E and PABP [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1312900","name":null,"product":"eukaryotic translation initation factor 4 gamma","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1411300","name":null,"product":"eukaryotic translation initation factor 4 gamma, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1413500","name":null,"product":"eukaryotic translation initation factor 4 gamma, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"EIF4G","evaluation":null}