{"gene":"PF3D7_1442200","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2020,"finding":"PF3D7_1442200 (YihA2) localizes to the mitochondrion of P. falciparum, as determined by targeting experiments with the recombinant protein.","method":"Subcellular localization experiment (organelle targeting assay with recombinant protein)","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment with specific antibodies and recombinant protein, single lab, two complementary methods (targeting assay + co-immunoprecipitation)","pmids":["32057832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"PF3D7_1442200 (YihA2), expressed as a recombinant protein, exhibits GTPase activity in vitro.","method":"In vitro GTPase activity assay with recombinant protein","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro enzymatic assay, single lab, single method","pmids":["32057832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"PF3D7_1442200 (YihA2) interacts with surrogate E. coli ribosomes (large subunit) in a nucleotide-independent manner in vitro, and in vivo co-immunoprecipitation with specific antibodies confirmed its complexation with the mitochondrial ribosomal large subunit (LSU) of P. falciparum.","method":"In vitro ribosome-binding assay with surrogate E. coli ribosomes; in vivo co-immunoprecipitation with specific antibodies","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-immunoprecipitation plus in vitro binding assay, single lab, two orthogonal methods","pmids":["32057832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"PF3D7_1442200 (YihA2) carries a large C-terminal extension with a strongly positively charged stretch, which is hypothesized (but not experimentally confirmed in this study) to compensate for absent helices of the central protuberance in the fragmented rRNA of Plasmodium mitoribosomes.","method":"Sequence/structural analysis (bioinformatic prediction; no experimental validation reported)","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/sequence inference only, no experimental confirmation of this specific structural role","pmids":["32057832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1442200 (YihA2) is a mitochondrion-targeted GTPase in P. falciparum that binds the large subunit of organellar ribosomes in a nucleotide-independent manner, implicating it in mitochondrial ribosome assembly, and it possesses a distinctive positively charged C-terminal extension whose functional role has not yet been experimentally resolved."},"narrative":{"mechanistic_narrative":"PF3D7_1442200 (YihA2) is a mitochondrion-targeted GTPase of Plasmodium falciparum implicated in the assembly of the organellar ribosome [PMID:32057832]. Recombinant PF3D7_1442200 localizes to the P. falciparum mitochondrion [PMID:32057832] and hydrolyzes GTP in vitro [PMID:32057832]. It binds the large ribosomal subunit in a nucleotide-independent manner—engaging surrogate E. coli large subunits in vitro and co-immunoprecipitating with the P. falciparum mitochondrial large subunit (LSU) in vivo—placing it in complex with the mitoribosomal LSU [PMID:32057832]. Beyond these findings, no functional consequence of GTP hydrolysis, no assembly intermediate, and no direct role for its positively charged C-terminal extension has been experimentally established in the available corpus.","teleology":[{"year":2020,"claim":"Establishing where PF3D7_1442200 acts: whether this GTP-binding protein operates in the parasite mitochondrion was unknown, and targeting experiments placed it in that organelle, framing it as a candidate factor for mitochondrial gene expression.","evidence":"Organelle targeting assay with recombinant protein in P. falciparum","pmids":["32057832"],"confidence":"Medium","gaps":["Localization inferred from a recombinant targeting assay rather than endogenous tagging","Does not establish the specific submitochondrial context of function"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Confirming enzymatic identity: it was unknown whether the annotated GTP-binding protein is catalytically active, and an in vitro assay demonstrated GTPase activity, supporting a nucleotide-dependent functional cycle.","evidence":"In vitro GTPase activity assay with recombinant protein","pmids":["32057832"],"confidence":"Medium","gaps":["Kinetic parameters and physiological triggers of hydrolysis not defined","Single method, single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Assigning a molecular target: whether PF3D7_1442200 engages ribosomes was unknown, and binding to the large subunit in vitro together with in vivo co-IP of the mitochondrial LSU established it as a mitoribosome-associated factor acting independently of nucleotide state.","evidence":"In vitro binding to surrogate E. coli large subunits plus reciprocal in vivo co-immunoprecipitation with specific antibodies in P. falciparum","pmids":["32057832"],"confidence":"Medium","gaps":["Direct assembly role vs. mere association not demonstrated by loss-of-function","In vitro binding used a heterologous E. coli ribosome surrogate"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Probing structural specialization: the parasite mitoribosome has fragmented rRNA, and sequence analysis identified a positively charged C-terminal extension hypothesized to substitute for missing central-protuberance helices, but this role was not tested.","evidence":"Bioinformatic sequence/structural analysis without experimental validation","pmids":["32057832"],"confidence":"Low","gaps":["Structural role of the C-terminal extension is computational inference only, not experimentally confirmed","No mutagenesis of the charged stretch reported"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The physiological consequence of PF3D7_1442200's GTPase cycle for mitoribosome LSU maturation, and the functional role of its C-terminal extension, remain unresolved.","evidence":"No loss-of-function or structural study in the corpus","pmids":[],"confidence":"Low","gaps":["No genetic knockout/knockdown phenotype","No structure of the protein bound to the mitoribosome","C-terminal extension function untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Mitochondrial ribosome large subunit (LSU) complex"],"partners":["MITOCHONDRIAL RIBOSOMAL LARGE SUBUNIT (P. FALCIPARUM)"],"other_free_text":["Interacts with the large ribosomal subunit in a nucleotide-independent manner [#2].","Possesses a positively charged C-terminal extension of unresolved function, hypothesized computationally to compensate for fragmented central-protuberance rRNA [#3]."]}},"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":"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":["PfYihA2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4346,"output_tokens":1002,"usd":0.014034,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5767,"output_tokens":1975,"usd":0.039105,"stage2_stop_reason":"end_turn"},"total_usd":0.053139,"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\": 2020,\n      \"finding\": \"PF3D7_1442200 (YihA2) localizes to the mitochondrion of P. falciparum, as determined by targeting experiments with the recombinant protein.\",\n      \"method\": \"Subcellular localization experiment (organelle targeting assay with recombinant protein)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment with specific antibodies and recombinant protein, single lab, two complementary methods (targeting assay + co-immunoprecipitation)\",\n      \"pmids\": [\"32057832\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PF3D7_1442200 (YihA2), expressed as a recombinant protein, exhibits GTPase activity in vitro.\",\n      \"method\": \"In vitro GTPase activity assay with recombinant protein\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro enzymatic assay, single lab, single method\",\n      \"pmids\": [\"32057832\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PF3D7_1442200 (YihA2) interacts with surrogate E. coli ribosomes (large subunit) in a nucleotide-independent manner in vitro, and in vivo co-immunoprecipitation with specific antibodies confirmed its complexation with the mitochondrial ribosomal large subunit (LSU) of P. falciparum.\",\n      \"method\": \"In vitro ribosome-binding assay with surrogate E. coli ribosomes; in vivo co-immunoprecipitation with specific antibodies\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-immunoprecipitation plus in vitro binding assay, single lab, two orthogonal methods\",\n      \"pmids\": [\"32057832\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"PF3D7_1442200 (YihA2) carries a large C-terminal extension with a strongly positively charged stretch, which is hypothesized (but not experimentally confirmed in this study) to compensate for absent helices of the central protuberance in the fragmented rRNA of Plasmodium mitoribosomes.\",\n      \"method\": \"Sequence/structural analysis (bioinformatic prediction; no experimental validation reported)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/sequence inference only, no experimental confirmation of this specific structural role\",\n      \"pmids\": [\"32057832\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_1442200 (YihA2) is a mitochondrion-targeted GTPase in P. falciparum that binds the large subunit of organellar ribosomes in a nucleotide-independent manner, implicating it in mitochondrial ribosome assembly, and it possesses a distinctive positively charged C-terminal extension whose functional role has not yet been experimentally resolved.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1442200 (YihA2) is a mitochondrion-targeted GTPase of Plasmodium falciparum implicated in the assembly of the organellar ribosome [#0, #1, #2]. Recombinant PF3D7_1442200 localizes to the P. falciparum mitochondrion [#0] and hydrolyzes GTP in vitro [#1]. It binds the large ribosomal subunit in a nucleotide-independent manner—engaging surrogate E. coli large subunits in vitro and co-immunoprecipitating with the P. falciparum mitochondrial large subunit (LSU) in vivo—placing it in complex with the mitoribosomal LSU [#2]. Beyond these findings, no functional consequence of GTP hydrolysis, no assembly intermediate, and no direct role for its positively charged C-terminal extension has been experimentally established in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Establishing where PF3D7_1442200 acts: whether this GTP-binding protein operates in the parasite mitochondrion was unknown, and targeting experiments placed it in that organelle, framing it as a candidate factor for mitochondrial gene expression.\",\n      \"evidence\": \"Organelle targeting assay with recombinant protein in P. falciparum\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Medium\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Localization inferred from a recombinant targeting assay rather than endogenous tagging\", \"Does not establish the specific submitochondrial context of function\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Confirming enzymatic identity: it was unknown whether the annotated GTP-binding protein is catalytically active, and an in vitro assay demonstrated GTPase activity, supporting a nucleotide-dependent functional cycle.\",\n      \"evidence\": \"In vitro GTPase activity assay with recombinant protein\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Medium\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Kinetic parameters and physiological triggers of hydrolysis not defined\", \"Single method, single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Assigning a molecular target: whether PF3D7_1442200 engages ribosomes was unknown, and binding to the large subunit in vitro together with in vivo co-IP of the mitochondrial LSU established it as a mitoribosome-associated factor acting independently of nucleotide state.\",\n      \"evidence\": \"In vitro binding to surrogate E. coli large subunits plus reciprocal in vivo co-immunoprecipitation with specific antibodies in P. falciparum\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Medium\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Direct assembly role vs. mere association not demonstrated by loss-of-function\", \"In vitro binding used a heterologous E. coli ribosome surrogate\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Probing structural specialization: the parasite mitoribosome has fragmented rRNA, and sequence analysis identified a positively charged C-terminal extension hypothesized to substitute for missing central-protuberance helices, but this role was not tested.\",\n      \"evidence\": \"Bioinformatic sequence/structural analysis without experimental validation\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Low\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"Structural role of the C-terminal extension is computational inference only, not experimentally confirmed\", \"No mutagenesis of the charged stretch reported\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The physiological consequence of PF3D7_1442200's GTPase cycle for mitoribosome LSU maturation, and the functional role of its C-terminal extension, remain unresolved.\",\n      \"evidence\": \"No loss-of-function or structural study in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}],\n      \"gaps\": [\"No genetic knockout/knockdown phenotype\", \"No structure of the protein bound to the mitoribosome\", \"C-terminal extension function untested\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0003924\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0005525\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0043022\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005739\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000027\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [\"Mitochondrial ribosome large subunit (LSU) complex\"],\n    \"partners\": [\"Mitochondrial ribosomal large subunit (P. falciparum)\"],\n    \"other_free_text\": [\n      \"Interacts with the large ribosomal subunit in a nucleotide-independent manner [#2].\",\n      \"Possesses a positively charged C-terminal extension of unresolved function, hypothesized computationally to compensate for fragmented central-protuberance rRNA [#3].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1442200","name":null,"product":"GTP-binding protein YihA2","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1306100","name":null,"product":"GTP-binding protein YihA2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1240100","name":null,"product":"GTP-binding protein YihA2, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"YihA2","evaluation":null}