{"gene":"PF3D7_0812220","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2020,"finding":"YihA3 (PF3D7_0812220) was found to localize to both the apicoplast and cytosol of P. falciparum, as determined by subcellular fractionation/immunofluorescence with specific antibodies.","method":"Subcellular localization using specific antibodies; co-immunoprecipitation","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — localization established by direct experiment with antibodies in a single lab, dual-organelle localization supported by multiple approaches","pmids":["32057832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"YihA3 (PF3D7_0812220), expressed as a recombinant protein, functions as an active GTPase in vitro.","method":"In vitro GTPase activity assay with recombinant protein","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct in vitro biochemical assay demonstrating GTPase activity, but single lab, single method","pmids":["32057832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"YihA3 (PF3D7_0812220) interacts with surrogate E. coli ribosomal large subunit (LSU) in a nucleotide-independent manner in vitro, and co-immunoprecipitation with specific antibodies confirmed in vivo complexation of YihA3 with parasite organellar and/or cytosolic LSU, suggesting a role in late-stage LSU ribosome assembly in the apicoplast.","method":"Pulldown with surrogate E. coli ribosomes; co-immunoprecipitation with specific antibodies from P. falciparum lysate","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with specific antibodies combined with in vitro ribosome-binding assay, single lab","pmids":["32057832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"YihA3 (PF3D7_0812220) is a nuclear-encoded, active GTPase that localizes to both the apicoplast and cytosol of P. falciparum, where it interacts with the large subunit of organellar and/or cytosolic ribosomes in a nucleotide-independent manner, implicating it in late-stage ribosomal large subunit assembly in the apicoplast."},"narrative":{"mechanistic_narrative":"YihA3 (PF3D7_0812220) is a nuclear-encoded GTPase of Plasmodium falciparum implicated in ribosomal large subunit (LSU) biogenesis in the apicoplast [PMID:32057832]. It localizes to both the apicoplast and the cytosol [PMID:32057832] and functions as an active GTPase in vitro as a recombinant protein [PMID:32057832]. YihA3 binds the ribosomal large subunit — associating with surrogate E. coli LSU in a nucleotide-independent manner in vitro and co-immunoprecipitating with parasite organellar and/or cytosolic LSU in vivo — consistent with a role in late-stage LSU assembly [PMID:32057832]. Beyond this dual-organelle localization, GTPase activity, and LSU association, no further mechanistic detail for PF3D7_0812220 has been characterized in the available corpus.","teleology":[{"year":2020,"claim":"Establishing where YihA3 acts was the first step in assigning it a cellular role; the finding that it resides in both the apicoplast and cytosol placed it at the interface of organellar and cytosolic machinery.","evidence":"Subcellular fractionation and immunofluorescence with specific antibodies in P. falciparum","pmids":["32057832"],"confidence":"Medium","gaps":["Relative abundance and functional contribution in each compartment not quantified","Trafficking mechanism to the apicoplast not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Demonstrating intrinsic GTP hydrolysis confirmed YihA3 is a bona fide active GTPase rather than a degenerate nucleotide-binding protein, providing the enzymatic basis for its proposed regulatory role.","evidence":"In vitro GTPase activity assay with recombinant protein","pmids":["32057832"],"confidence":"Medium","gaps":["GTPase activation partners or GAP/GEF regulators not identified","Kinetic parameters and effect of ribosome binding on hydrolysis not resolved","Single lab, single method"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Linking YihA3 to the ribosome addressed what it acts upon; nucleotide-independent binding to the large subunit in vitro plus in vivo co-IP with parasite LSU implicated it in late-stage LSU assembly.","evidence":"Pulldown with surrogate E. coli ribosomes and reciprocal co-immunoprecipitation with specific antibodies from P. falciparum lysate","pmids":["32057832"],"confidence":"Medium","gaps":["Whether the in vivo interaction is with apicoplast, cytosolic, or both LSU populations not distinguished","Direct role in assembly not demonstrated by depletion or functional readout","Surrogate E. coli ribosome used in place of native apicoplast ribosome"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether YihA3 is essential and what specific step of LSU maturation its GTP hydrolysis regulates remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No genetic knockout/knockdown phenotype reported","No structural model of the YihA3–ribosome complex","Coupling between GTP hydrolysis cycle and LSU assembly steps undefined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Association with ribosomal large subunit (organellar and/or cytosolic LSU)"],"partners":["RIBOSOMAL LARGE SUBUNIT (PARASITE LSU; SURROGATE E. COLI LSU IN VITRO)"],"other_free_text":["Nuclear-encoded protein with dual apicoplast/cytosol localization","LSU binding is nucleotide-independent in vitro","Implicated in late-stage large subunit ribosome assembly in the apicoplast"]}},"prefetch_data":{},"corpus_meta":[{"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":["PfYihA3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"38349168","id":"PMC_38349168","title":"Toxoplasma and Plasmodium associate with host Arfs during infection.","date":"2024","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/38349168","citation_count":2,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["GTP"],"competing_organism_flag":true,"competing_organism_match":"Toxoplasma","competing_organism_only":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4527,"output_tokens":818,"usd":0.012925,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5473,"output_tokens":1842,"usd":0.036707,"stage2_stop_reason":"end_turn"},"total_usd":0.049632,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"YihA3 (PF3D7_0812220) was found to localize to both the apicoplast and cytosol of P. falciparum, as determined by subcellular fractionation/immunofluorescence with specific antibodies.\",\n      \"method\": \"Subcellular localization using specific antibodies; co-immunoprecipitation\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — localization established by direct experiment with antibodies in a single lab, dual-organelle localization supported by multiple approaches\",\n      \"pmids\": [\"32057832\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"YihA3 (PF3D7_0812220), expressed as a recombinant protein, functions as an active GTPase 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 — direct in vitro biochemical assay demonstrating GTPase activity, but single lab, single method\",\n      \"pmids\": [\"32057832\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"YihA3 (PF3D7_0812220) interacts with surrogate E. coli ribosomal large subunit (LSU) in a nucleotide-independent manner in vitro, and co-immunoprecipitation with specific antibodies confirmed in vivo complexation of YihA3 with parasite organellar and/or cytosolic LSU, suggesting a role in late-stage LSU ribosome assembly in the apicoplast.\",\n      \"method\": \"Pulldown with surrogate E. coli ribosomes; co-immunoprecipitation with specific antibodies from P. falciparum lysate\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with specific antibodies combined with in vitro ribosome-binding assay, single lab\",\n      \"pmids\": [\"32057832\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"YihA3 (PF3D7_0812220) is a nuclear-encoded, active GTPase that localizes to both the apicoplast and cytosol of P. falciparum, where it interacts with the large subunit of organellar and/or cytosolic ribosomes in a nucleotide-independent manner, implicating it in late-stage ribosomal large subunit assembly in the apicoplast.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"YihA3 (PF3D7_0812220) is a nuclear-encoded GTPase of Plasmodium falciparum implicated in ribosomal large subunit (LSU) biogenesis in the apicoplast [#0, #2]. It localizes to both the apicoplast and the cytosol [#0] and functions as an active GTPase in vitro as a recombinant protein [#1]. YihA3 binds the ribosomal large subunit — associating with surrogate E. coli LSU in a nucleotide-independent manner in vitro and co-immunoprecipitating with parasite organellar and/or cytosolic LSU in vivo — consistent with a role in late-stage LSU assembly [#2]. Beyond this dual-organelle localization, GTPase activity, and LSU association, no further mechanistic detail for PF3D7_0812220 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Establishing where YihA3 acts was the first step in assigning it a cellular role; the finding that it resides in both the apicoplast and cytosol placed it at the interface of organellar and cytosolic machinery.\",\n      \"evidence\": \"Subcellular fractionation and immunofluorescence with specific antibodies in P. falciparum\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Relative abundance and functional contribution in each compartment not quantified\",\n        \"Trafficking mechanism to the apicoplast not defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrating intrinsic GTP hydrolysis confirmed YihA3 is a bona fide active GTPase rather than a degenerate nucleotide-binding protein, providing the enzymatic basis for its proposed regulatory role.\",\n      \"evidence\": \"In vitro GTPase activity assay with recombinant protein\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"GTPase activation partners or GAP/GEF regulators not identified\",\n        \"Kinetic parameters and effect of ribosome binding on hydrolysis not resolved\",\n        \"Single lab, single method\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Linking YihA3 to the ribosome addressed what it acts upon; nucleotide-independent binding to the large subunit in vitro plus in vivo co-IP with parasite LSU implicated it in late-stage LSU assembly.\",\n      \"evidence\": \"Pulldown with surrogate E. coli ribosomes and reciprocal co-immunoprecipitation with specific antibodies from P. falciparum lysate\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether the in vivo interaction is with apicoplast, cytosolic, or both LSU populations not distinguished\",\n        \"Direct role in assembly not demonstrated by depletion or functional readout\",\n        \"Surrogate E. coli ribosome used in place of native apicoplast ribosome\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether YihA3 is essential and what specific step of LSU maturation its GTP hydrolysis regulates remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No genetic knockout/knockdown phenotype reported\",\n        \"No structural model of the YihA3–ribosome complex\",\n        \"Coupling between GTP hydrolysis cycle and LSU assembly steps undefined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\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:0020011\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0042273\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"Association with ribosomal large subunit (organellar and/or cytosolic LSU)\"\n    ],\n    \"partners\": [\n      \"Ribosomal large subunit (parasite LSU; surrogate E. coli LSU in vitro)\"\n    ],\n    \"other_free_text\": [\n      \"Nuclear-encoded protein with dual apicoplast/cytosol localization\",\n      \"LSU binding is nucleotide-independent in vitro\",\n      \"Implicated in late-stage large subunit ribosome assembly in the apicoplast\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0812220","name":null,"product":"GTP-binding protein YihA3","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1425350","name":null,"product":"GTP-binding protein YihA3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1428500","name":null,"product":"GTP-binding protein YihA3, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"YihA3","evaluation":null}