{"gene":"PF3D7_1206700","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2016,"finding":"PF3D7_1206700 (EIF5/PfeIF5) was shown to interact with PfeIF2β (eukaryotic initiation factor 2β) in P. falciparum, confirming its canonical participation in the translation initiation complex. This interaction was established by binding assays using wild-type and mutated versions of PfeIF2β.","method":"Direct binding assay (pull-down/interaction studies with wild-type and mutated PfeIF2β); functional validation in Xenopus oocyte system","journal":"Frontiers in microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP/binding assay confirmed in context of PfeIF2β mutant analysis, single lab, one primary method but with mutational corroboration","pmids":["27303372"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"EIF5 (PF3D7_1206700) was detected as phosphorylated in P. falciparum intraerythrocytic stages in a proteome-wide PTM analysis, indicating that phosphorylation is a post-translational modification occurring on this translation initiation factor during asexual blood-stage development.","method":"Proteome-wide mass spectrometry-based PTM profiling","journal":"Molecular & cellular proteomics : MCP","confidence":"Low","confidence_rationale":"Tier 4 / Weak — large-scale proteomics screen, no functional follow-up specific to EIF5, single method, pan-gene catalog context","pmids":["33517144"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1206700 (EIF5) functions as a component of the P. falciparum translation initiation complex, where it interacts with PfeIF2β as part of the canonical eIF2 complex, and undergoes phosphorylation during intraerythrocytic development; beyond complex membership and this PTM detection, no further mechanistic detail has been experimentally established for this protein."},"narrative":{"mechanistic_narrative":"PF3D7_1206700 (EIF5) is a putative eukaryotic translation initiation factor of P. falciparum whose characterized role is participation in the translation initiation machinery through a physical interaction with PfeIF2β, established by binding assays with wild-type and mutated PfeIF2β [PMID:27303372]. Beyond this interaction, no catalytic activity, substrate, or functional consequence has been experimentally defined for EIF5 in the available corpus. The protein is detected as phosphorylated during intraerythrocytic asexual blood-stage development [PMID:33517144], but the responsible kinase and the functional impact of this modification have not been characterized.","teleology":[{"year":2016,"claim":"To place EIF5 within the parasite's translation initiation apparatus, its physical association with a core eIF2 subunit was tested, establishing that EIF5 interacts with PfeIF2β and thereby participates in the translation initiation complex.","evidence":"Direct binding/pull-down assays using wild-type and mutated PfeIF2β, with functional validation in a Xenopus oocyte system","pmids":["27303372"],"confidence":"Medium","gaps":["Single binding assay from one lab without reciprocal or orthogonal validation","The functional consequence of the EIF5–PfeIF2β interaction for translation initiation is not defined","The binding interface and stoichiometry on EIF5 itself are not mapped"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"To ask whether EIF5 is post-translationally regulated during blood-stage growth, a proteome-wide PTM survey detected EIF5 as phosphorylated in intraerythrocytic stages, indicating it is a substrate for phosphorylation during asexual development.","evidence":"Proteome-wide mass spectrometry-based PTM profiling of P. falciparum intraerythrocytic stages","pmids":["33517144"],"confidence":"Low","gaps":["Large-scale catalog detection with no functional follow-up specific to EIF5","Responsible kinase and phosphosite occupancy are unknown","Effect of phosphorylation on EIF5 activity or complex assembly is undetermined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether EIF5 has an intrinsic biochemical activity in translation initiation, and how its PfeIF2β interaction and phosphorylation contribute to parasite protein synthesis, remains unresolved.","evidence":"No functional or structural study of EIF5 itself beyond interaction and PTM detection exists in the corpus","pmids":[],"confidence":"Low","gaps":["No loss-of-function or essentiality data for EIF5","No structural model of EIF5 or its complex","No link between phosphorylation state and interaction with PfeIF2β"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Translation initiation complex (via interaction with PfeIF2β) [#0]"],"partners":["PFEIF2Β (EUKARYOTIC INITIATION FACTOR 2Β) [#0]"],"other_free_text":["Detected as phosphorylated during P. falciparum intraerythrocytic asexual blood-stage development [#1]","No intrinsic enzymatic activity, substrate, or loss-of-function phenotype has been established for EIF5 in the available corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"27303372","id":"PMC_27303372","title":"Identification of Plasmodium falciparum Translation Initiation eIF2β Subunit: Direct Interaction with Protein Phosphatase Type 1.","date":"2016","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27303372","citation_count":12,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfEIF5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"32019802","id":"","title":"RNA-Seq Analysis Illuminates the Early Stages of Plasmodium Liver Infection.","date":"2020","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/32019802","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EIF5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"33517144","id":"","title":"Protein Modification Characteristics of the Malaria Parasite Plasmodium falciparum and the Infected Erythrocytes.","date":"2020","source":"Molecular & cellular proteomics : MCP","url":"https://pubmed.ncbi.nlm.nih.gov/33517144","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EIF5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25493618","id":"","title":"Genome-wide regulatory dynamics of translation in the Plasmodium falciparum asexual blood stages.","date":"2014","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/25493618","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EIF5"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":6520,"output_tokens":632,"usd":0.01452,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5246,"output_tokens":1465,"usd":0.031427,"stage2_stop_reason":"end_turn"},"total_usd":0.045947,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"PF3D7_1206700 (EIF5/PfeIF5) was shown to interact with PfeIF2β (eukaryotic initiation factor 2β) in P. falciparum, confirming its canonical participation in the translation initiation complex. This interaction was established by binding assays using wild-type and mutated versions of PfeIF2β.\",\n      \"method\": \"Direct binding assay (pull-down/interaction studies with wild-type and mutated PfeIF2β); functional validation in Xenopus oocyte system\",\n      \"journal\": \"Frontiers in microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP/binding assay confirmed in context of PfeIF2β mutant analysis, single lab, one primary method but with mutational corroboration\",\n      \"pmids\": [\"27303372\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"EIF5 (PF3D7_1206700) was detected as phosphorylated in P. falciparum intraerythrocytic stages in a proteome-wide PTM analysis, indicating that phosphorylation is a post-translational modification occurring on this translation initiation factor during asexual blood-stage development.\",\n      \"method\": \"Proteome-wide mass spectrometry-based PTM profiling\",\n      \"journal\": \"Molecular & cellular proteomics : MCP\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — large-scale proteomics screen, no functional follow-up specific to EIF5, single method, pan-gene catalog context\",\n      \"pmids\": [\"33517144\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1206700 (EIF5) functions as a component of the P. falciparum translation initiation complex, where it interacts with PfeIF2β as part of the canonical eIF2 complex, and undergoes phosphorylation during intraerythrocytic development; beyond complex membership and this PTM detection, no further mechanistic detail has been experimentally established for this protein.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PF3D7_1206700 (EIF5) is a putative eukaryotic translation initiation factor of P. falciparum whose characterized role is participation in the translation initiation machinery through a physical interaction with PfeIF2\\u03b2, established by binding assays with wild-type and mutated PfeIF2\\u03b2 [#0]. Beyond this interaction, no catalytic activity, substrate, or functional consequence has been experimentally defined for EIF5 in the available corpus. The protein is detected as phosphorylated during intraerythrocytic asexual blood-stage development [#1], but the responsible kinase and the functional impact of this modification have not been characterized.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"To place EIF5 within the parasite's translation initiation apparatus, its physical association with a core eIF2 subunit was tested, establishing that EIF5 interacts with PfeIF2\\u03b2 and thereby participates in the translation initiation complex.\",\n      \"evidence\": \"Direct binding/pull-down assays using wild-type and mutated PfeIF2\\u03b2, with functional validation in a Xenopus oocyte system\",\n      \"pmids\": [\"27303372\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single binding assay from one lab without reciprocal or orthogonal validation\",\n        \"The functional consequence of the EIF5\\u2013PfeIF2\\u03b2 interaction for translation initiation is not defined\",\n        \"The binding interface and stoichiometry on EIF5 itself are not mapped\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To ask whether EIF5 is post-translationally regulated during blood-stage growth, a proteome-wide PTM survey detected EIF5 as phosphorylated in intraerythrocytic stages, indicating it is a substrate for phosphorylation during asexual development.\",\n      \"evidence\": \"Proteome-wide mass spectrometry-based PTM profiling of P. falciparum intraerythrocytic stages\",\n      \"pmids\": [\"33517144\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Large-scale catalog detection with no functional follow-up specific to EIF5\",\n        \"Responsible kinase and phosphosite occupancy are unknown\",\n        \"Effect of phosphorylation on EIF5 activity or complex assembly is undetermined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether EIF5 has an intrinsic biochemical activity in translation initiation, and how its PfeIF2\\u03b2 interaction and phosphorylation contribute to parasite protein synthesis, remains unresolved.\",\n      \"evidence\": \"No functional or structural study of EIF5 itself beyond interaction and PTM detection exists in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function or essentiality data for EIF5\",\n        \"No structural model of EIF5 or its complex\",\n        \"No link between phosphorylation state and interaction with PfeIF2\\u03b2\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006413\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"Translation initiation complex (via interaction with PfeIF2\\u03b2) [#0]\"],\n    \"partners\": [\"PfeIF2\\u03b2 (eukaryotic initiation factor 2\\u03b2) [#0]\"],\n    \"other_free_text\": [\n      \"Detected as phosphorylated during P. falciparum intraerythrocytic asexual blood-stage development [#1]\",\n      \"No intrinsic enzymatic activity, substrate, or loss-of-function phenotype has been established for EIF5 in the available corpus\"\n    ]\n  }\n}\n```","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1206700","name":null,"product":"eukaryotic translation initiation factor 5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0605300","name":null,"product":"eukaryotic translation initiation factor 5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1306700","name":null,"product":"eukaryotic translation initiation factor 5, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"EIF5","evaluation":null}