{"gene":"PF3D7_1217300","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2018,"finding":"PfEngA (PF3D7_1217300) localizes to the mitochondrion of P. falciparum, representing the first confirmed localization of an EngA homologue in eukaryotic mitochondria.","method":"Subcellular fractionation and/or fluorescence localization experiments (direct localization experiment)","journal":"Parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with functional context (mitoribosome association), single lab, multiple orthogonal methods (localization + co-immunoprecipitation + GTPase assay)","pmids":["29642957"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"PfEngA (PF3D7_1217300) interacts with parasite mitoribosomes in vivo, and GTP stimulates its interaction with the 50S subunit of E. coli surrogate ribosomes, indicating GTP-dependent ribosome binding.","method":"Co-immunoprecipitation (in vivo) and in vitro ribosome-binding assay with nucleotide supplementation","journal":"Parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP plus in vitro biochemical assay, single lab, two orthogonal methods","pmids":["29642957"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"PfEngA (PF3D7_1217300) is over-expressed upon methyl methanesulfonate-induced DNA damage, indicating a role in the mitochondrial genotoxic stress response.","method":"Drug treatment (MMS) followed by expression analysis","journal":"Parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single method (expression change upon stress), no direct functional epistasis established","pmids":["29642957"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"PfEngA (PF3D7_1217300) has lower sensitivity to an E. coli EngA inhibitor compared to bacterial EngA, suggesting structural/functional differences from bacterial counterparts.","method":"In vitro inhibitor sensitivity assay","journal":"Parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single biochemical assay, no mechanistic detail on the binding site","pmids":["29642957"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"PfEngA (PF3D7_1217300) is implicated in mitochondrial ribosome assembly in P. falciparum, acting alongside PfObg1 and PfYihA2 GTPases as an assembly factor for the mitoribosome large subunit.","method":"Inference from combined co-immunoprecipitation data across GTPases reported in prior and current study","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — cited as part of a combined model based on prior published data, not a new direct experiment on PF3D7_1217300 in this paper","pmids":["32057832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1217300 (EngA) is a GTP-binding protein that localizes to the P. falciparum mitochondrion, interacts with mitoribosomes in vivo in a GTP-stimulated manner (binding to the 50S/LSU subunit), participates in mitochondrial ribosome assembly alongside other GTPases, and is upregulated in response to mitochondrial genotoxic stress, with demonstrated differences in inhibitor sensitivity relative to bacterial EngA homologs."},"narrative":{"mechanistic_narrative":"PF3D7_1217300 (EngA) is a GTP-binding protein that localizes to the mitochondrion of Plasmodium falciparum and functions in mitochondrial ribosome biogenesis [PMID:29642957]. It associates with parasite mitoribosomes in vivo, and this interaction is GTP-dependent: nucleotide supplementation stimulates its binding to the large (50S) subunit of surrogate ribosomes, consistent with a role as a GTP-regulated assembly factor for the mitoribosomal large subunit [PMID:29642957]. Beyond mitoribosome association, GTP-dependent ribosome binding, and mitochondrial localization, no further mechanistic detail about PF3D7_1217300 has been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing where PF3D7_1217300 acts answered whether an EngA homologue operates in a eukaryotic mitochondrion, placing the protein in the parasite's organellar translation machinery.","evidence":"Subcellular fractionation and fluorescence localization in P. falciparum","pmids":["29642957"],"confidence":"Medium","gaps":["Localization does not establish which mitochondrial process the protein directly executes","No import signal or targeting mechanism defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Whether PF3D7_1217300 physically engages the translation apparatus and whether its GTP-binding activity is functionally coupled to that engagement was resolved by showing GTP-stimulated binding to the ribosomal large subunit.","evidence":"In vivo co-immunoprecipitation with parasite mitoribosomes plus in vitro 50S-binding assay with nucleotide supplementation using E. coli surrogate ribosomes","pmids":["29642957"],"confidence":"Medium","gaps":["Binding to the native parasite large subunit shown in vivo but the GTP-stimulation assay used a bacterial surrogate ribosome","The functional consequence of binding (assembly step, maturation, quality control) not directly demonstrated","GTP hydrolysis cycle and its coupling to release from the ribosome not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"To probe physiological regulation, expression under stress was tested, linking PF3D7_1217300 abundance to mitochondrial genotoxic insult.","evidence":"Methyl methanesulfonate treatment followed by expression analysis in P. falciparum","pmids":["29642957"],"confidence":"Low","gaps":["Single method (expression change on stress) with no functional epistasis established","Whether upregulation reflects a direct role in the genotoxic stress response or a downstream consequence is unresolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Comparing inhibitor sensitivity addressed whether the parasite protein is pharmacologically distinct from its bacterial counterparts, a prerequisite for considering it as a selective drug target.","evidence":"In vitro inhibitor sensitivity assay against an E. coli EngA inhibitor","pmids":["29642957"],"confidence":"Low","gaps":["Single biochemical assay with no mechanistic detail on the inhibitor binding site","Structural basis of the reduced sensitivity not determined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Integrating co-immunoprecipitation data across parasite GTPases positioned PF3D7_1217300 within a proposed multi-factor assembly pathway for the mitoribosomal large subunit.","evidence":"Inference from combined co-immunoprecipitation data across GTPases (PfObg1, PfYihA2) rather than a new direct experiment on PF3D7_1217300","pmids":["32057832"],"confidence":"Low","gaps":["No new direct experiment on PF3D7_1217300 in this study; the role is inferred from a combined model","The ordering and interdependence of the individual GTPases in assembly is not established","Direct evidence that loss of PF3D7_1217300 impairs assembly is absent"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The direct catalytic and functional role of PF3D7_1217300 in mitoribosome maturation remains unresolved.","evidence":"No loss-of-function, structural, or GTPase-cycle study on the native parasite protein reported in the corpus","pmids":[],"confidence":"Low","gaps":["No genetic knockdown/knockout phenotype for PF3D7_1217300","No structure or defined GTP hydrolysis mechanism","No demonstration of the specific assembly step it catalyzes on the parasite large subunit"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["mitoribosome (large/50S subunit association)"],"partners":["PARASITE MITORIBOSOME","PFOBG1 (PROPOSED CO-ASSEMBLY GTPASE, MODEL-LEVEL)","PFYIHA2 (PROPOSED CO-ASSEMBLY GTPASE, MODEL-LEVEL)"],"other_free_text":["GTP stimulates PF3D7_1217300 binding to the ribosomal large subunit, demonstrated with an E. coli surrogate ribosome [#1].","PF3D7_1217300 shows lower sensitivity to an E. coli EngA inhibitor than the bacterial protein, indicating structural/functional divergence [#3].","PF3D7_1217300 is upregulated upon MMS-induced DNA damage [#2]."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"18174226","id":"PMC_18174226","title":"Characterization and evolutionary history of an archaeal kinase involved in selenocysteinyl-tRNA formation.","date":"2008","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/18174226","citation_count":31,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GTP"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38977907","id":"PMC_38977907","title":"CRISPR-based functional profiling of the Toxoplasma gondii genome during acute murine infection.","date":"2024","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/38977907","citation_count":27,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GTP"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"29642957","id":"PMC_29642957","title":"Characterization of mitochondrion-targeted GTPases in Plasmodium falciparum.","date":"2018","source":"Parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/29642957","citation_count":7,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["EngA","GTP","PfEngA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36945434","id":"PMC_36945434","title":"Functional profiling of the Toxoplasma genome during acute mouse infection.","date":"2023","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/36945434","citation_count":4,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GTP"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true},{"pmid":"32057832","id":"PMC_32057832","title":"YihA GTPases localize to the apicoplast and mitochondrion of the malaria parasite and interact with LSU of organellar ribosomes.","date":"2020","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/32057832","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfEngA"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5210,"output_tokens":1207,"usd":0.016868,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6061,"output_tokens":2520,"usd":0.046652,"stage2_stop_reason":"end_turn"},"total_usd":0.06352,"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\": \"PfEngA (PF3D7_1217300) localizes to the mitochondrion of P. falciparum, representing the first confirmed localization of an EngA homologue in eukaryotic mitochondria.\",\n      \"method\": \"Subcellular fractionation and/or fluorescence localization experiments (direct localization experiment)\",\n      \"journal\": \"Parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with functional context (mitoribosome association), single lab, multiple orthogonal methods (localization + co-immunoprecipitation + GTPase assay)\",\n      \"pmids\": [\"29642957\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PfEngA (PF3D7_1217300) interacts with parasite mitoribosomes in vivo, and GTP stimulates its interaction with the 50S subunit of E. coli surrogate ribosomes, indicating GTP-dependent ribosome binding.\",\n      \"method\": \"Co-immunoprecipitation (in vivo) and in vitro ribosome-binding assay with nucleotide supplementation\",\n      \"journal\": \"Parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP plus in vitro biochemical assay, single lab, two orthogonal methods\",\n      \"pmids\": [\"29642957\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PfEngA (PF3D7_1217300) is over-expressed upon methyl methanesulfonate-induced DNA damage, indicating a role in the mitochondrial genotoxic stress response.\",\n      \"method\": \"Drug treatment (MMS) followed by expression analysis\",\n      \"journal\": \"Parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single method (expression change upon stress), no direct functional epistasis established\",\n      \"pmids\": [\"29642957\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PfEngA (PF3D7_1217300) has lower sensitivity to an E. coli EngA inhibitor compared to bacterial EngA, suggesting structural/functional differences from bacterial counterparts.\",\n      \"method\": \"In vitro inhibitor sensitivity assay\",\n      \"journal\": \"Parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single biochemical assay, no mechanistic detail on the binding site\",\n      \"pmids\": [\"29642957\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PfEngA (PF3D7_1217300) is implicated in mitochondrial ribosome assembly in P. falciparum, acting alongside PfObg1 and PfYihA2 GTPases as an assembly factor for the mitoribosome large subunit.\",\n      \"method\": \"Inference from combined co-immunoprecipitation data across GTPases reported in prior and current study\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — cited as part of a combined model based on prior published data, not a new direct experiment on PF3D7_1217300 in this paper\",\n      \"pmids\": [\"32057832\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1217300 (EngA) is a GTP-binding protein that localizes to the P. falciparum mitochondrion, interacts with mitoribosomes in vivo in a GTP-stimulated manner (binding to the 50S/LSU subunit), participates in mitochondrial ribosome assembly alongside other GTPases, and is upregulated in response to mitochondrial genotoxic stress, with demonstrated differences in inhibitor sensitivity relative to bacterial EngA homologs.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1217300 (EngA) is a GTP-binding protein that localizes to the mitochondrion of Plasmodium falciparum and functions in mitochondrial ribosome biogenesis [#0, #1]. It associates with parasite mitoribosomes in vivo, and this interaction is GTP-dependent: nucleotide supplementation stimulates its binding to the large (50S) subunit of surrogate ribosomes, consistent with a role as a GTP-regulated assembly factor for the mitoribosomal large subunit [#1]. Beyond mitoribosome association, GTP-dependent ribosome binding, and mitochondrial localization, no further mechanistic detail about PF3D7_1217300 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing where PF3D7_1217300 acts answered whether an EngA homologue operates in a eukaryotic mitochondrion, placing the protein in the parasite's organellar translation machinery.\",\n      \"evidence\": \"Subcellular fractionation and fluorescence localization in P. falciparum\",\n      \"pmids\": [\"29642957\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Localization does not establish which mitochondrial process the protein directly executes\",\n        \"No import signal or targeting mechanism defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Whether PF3D7_1217300 physically engages the translation apparatus and whether its GTP-binding activity is functionally coupled to that engagement was resolved by showing GTP-stimulated binding to the ribosomal large subunit.\",\n      \"evidence\": \"In vivo co-immunoprecipitation with parasite mitoribosomes plus in vitro 50S-binding assay with nucleotide supplementation using E. coli surrogate ribosomes\",\n      \"pmids\": [\"29642957\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Binding to the native parasite large subunit shown in vivo but the GTP-stimulation assay used a bacterial surrogate ribosome\",\n        \"The functional consequence of binding (assembly step, maturation, quality control) not directly demonstrated\",\n        \"GTP hydrolysis cycle and its coupling to release from the ribosome not defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To probe physiological regulation, expression under stress was tested, linking PF3D7_1217300 abundance to mitochondrial genotoxic insult.\",\n      \"evidence\": \"Methyl methanesulfonate treatment followed by expression analysis in P. falciparum\",\n      \"pmids\": [\"29642957\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single method (expression change on stress) with no functional epistasis established\",\n        \"Whether upregulation reflects a direct role in the genotoxic stress response or a downstream consequence is unresolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Comparing inhibitor sensitivity addressed whether the parasite protein is pharmacologically distinct from its bacterial counterparts, a prerequisite for considering it as a selective drug target.\",\n      \"evidence\": \"In vitro inhibitor sensitivity assay against an E. coli EngA inhibitor\",\n      \"pmids\": [\"29642957\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single biochemical assay with no mechanistic detail on the inhibitor binding site\",\n        \"Structural basis of the reduced sensitivity not determined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Integrating co-immunoprecipitation data across parasite GTPases positioned PF3D7_1217300 within a proposed multi-factor assembly pathway for the mitoribosomal large subunit.\",\n      \"evidence\": \"Inference from combined co-immunoprecipitation data across GTPases (PfObg1, PfYihA2) rather than a new direct experiment on PF3D7_1217300\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No new direct experiment on PF3D7_1217300 in this study; the role is inferred from a combined model\",\n        \"The ordering and interdependence of the individual GTPases in assembly is not established\",\n        \"Direct evidence that loss of PF3D7_1217300 impairs assembly is absent\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct catalytic and functional role of PF3D7_1217300 in mitoribosome maturation remains unresolved.\",\n      \"evidence\": \"No loss-of-function, structural, or GTPase-cycle study on the native parasite protein reported in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic knockdown/knockout phenotype for PF3D7_1217300\",\n        \"No structure or defined GTP hydrolysis mechanism\",\n        \"No demonstration of the specific assembly step it catalyzes on the parasite large subunit\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GTP binding\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"ribosome binding\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"ribosome large subunit binding\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"mitochondrion\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"mitochondrial ribosome large subunit assembly\", \"supporting_discovery_ids\": [1, 4]},\n      {\"term_id\": \"response to genotoxic stress\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"mitoribosome (large/50S subunit association)\"\n    ],\n    \"partners\": [\n      \"parasite mitoribosome\",\n      \"PfObg1 (proposed co-assembly GTPase, model-level)\",\n      \"PfYihA2 (proposed co-assembly GTPase, model-level)\"\n    ],\n    \"other_free_text\": [\n      \"GTP stimulates PF3D7_1217300 binding to the ribosomal large subunit, demonstrated with an E. coli surrogate ribosome [#1].\",\n      \"PF3D7_1217300 shows lower sensitivity to an E. coli EngA inhibitor than the bacterial protein, indicating structural/functional divergence [#3].\",\n      \"PF3D7_1217300 is upregulated upon MMS-induced DNA damage [#2].\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_1217300","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 2 of 2 cited papers name other catalogue genes (PF3D7_1411600, PF3D7_0513400, PF3D7_0812220). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1217300","name":null,"product":"GTP-binding protein EngA","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1432900","name":null,"product":"GTP-binding protein EngA, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1436900","name":null,"product":"GTP-binding protein EngA, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"EngA","evaluation":null}