{"gene":"PF3D7_0513400","run_date":"2026-09-07T10:55:52","timeline":{"discoveries":[{"year":2020,"finding":"YihA1 (PfYihA1/PF3D7_0513400) localizes to the apicoplast of P. falciparum, as determined by targeting experiments with the recombinant protein.","method":"Subcellular localization experiments (fluorescence microscopy/immunofluorescence with recombinant protein targeting assays)","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiment with specific antibodies and co-immunoprecipitation, single lab, two complementary methods","pmids":["32057832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Recombinant YihA1 (PfYihA1/PF3D7_0513400) possesses active 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":"YihA1 (PfYihA1/PF3D7_0513400) interacts with the large subunit (LSU) of the apicoplast ribosome in a nucleotide-independent manner, as shown by interaction with surrogate E. coli ribosomes in vitro and confirmed by co-immunoprecipitation with parasite organellar LSU using specific antibodies in vivo.","method":"In vitro ribosome-binding assay (surrogate E. coli ribosomes) and co-immunoprecipitation with specific antibodies from parasite lysates","journal":"Molecular and biochemical parasitology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP with specific antibodies plus in vitro binding assay, single lab, two orthogonal methods","pmids":["32057832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"Based on homology and localization, YihA1 (PfYihA1/PF3D7_0513400) is proposed to function in late-stage assembly of the apicoplast ribosomal large subunit, likely acting in combination with PfYihA3.","method":"Co-immunoprecipitation and localization (supporting role inferred from combined data; partly inferential)","journal":"Molecular and biochemical parasitology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — pathway placement is partly inferential from homology and localization data, single lab, no direct loss-of-function genetic epistasis experiment performed","pmids":["32057832"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"YihA1 (PF3D7_0513400) is an apicoplast-localized GTPase in P. falciparum that possesses intrinsic GTPase activity and physically interacts with the large subunit of the apicoplast ribosome in a nucleotide-independent manner, consistent with a role in late-stage apicoplast ribosomal large subunit assembly."},"narrative":{"mechanistic_narrative":"YihA1 (PF3D7_0513400) is an apicoplast-localized GTP-binding protein of Plasmodium falciparum implicated in biogenesis of the apicoplast ribosome [PMID:32057832]. Targeting experiments place the recombinant protein in the apicoplast [PMID:32057832], and it possesses intrinsic GTPase activity in vitro [PMID:32057832]. YihA1 binds the large subunit (LSU) of the apicoplast ribosome in a nucleotide-independent manner, as shown by association with surrogate E. coli ribosomes in vitro and reciprocal co-immunoprecipitation of parasite organellar LSU in vivo [PMID:32057832], consistent with a role in late-stage assembly of the apicoplast ribosomal large subunit [PMID:32057832]. Beyond this ribosome-association and GTPase activity, no loss-of-function phenotype, structural model, or substrate/effector mechanism for YihA1 has been characterized in the available corpus.","teleology":[{"year":2020,"claim":"Establishing where YihA1 acts was the first step; targeting experiments assigned the protein to the apicoplast, defining the organellar compartment in which any function must occur.","evidence":"Subcellular localization by targeting assays with recombinant protein in P. falciparum","pmids":["32057832"],"confidence":"Medium","gaps":["Localization shown with recombinant targeting rather than endogenous tagging","Sub-organellar distribution and timing across the life cycle not resolved"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"Whether the protein was an active enzyme was unknown; an in vitro assay demonstrated intrinsic GTPase activity, confirming it functions as a GTP-binding/hydrolyzing protein.","evidence":"In vitro GTPase activity assay with recombinant YihA1","pmids":["32057832"],"confidence":"Medium","gaps":["Kinetic parameters and regulatory cofactors not defined","Whether GTP hydrolysis is required for its cellular role untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"To link the GTPase to a process, its binding partner was identified; YihA1 was shown to associate with the apicoplast ribosomal large subunit nucleotide-independently, tying it to ribosome biology.","evidence":"In vitro binding to surrogate E. coli ribosomes plus reciprocal co-immunoprecipitation of parasite organellar LSU","pmids":["32057832"],"confidence":"Medium","gaps":["Direct LSU rRNA/protein contact sites not mapped","Nucleotide-independence measured indirectly; functional consequence unclear"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"The pathway role was inferred: combining homology, localization, and LSU binding, YihA1 was placed in late-stage assembly of the apicoplast large ribosomal subunit, possibly with PfYihA3.","evidence":"Inference from co-IP, localization, and homology (no loss-of-function genetics)","pmids":["32057832"],"confidence":"Low","gaps":["No direct loss-of-function or genetic epistasis experiment performed","Cooperation with PfYihA3 not experimentally demonstrated for YihA1 itself","Assembly-stage placement is inferential rather than shown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether YihA1 GTPase activity is essential for parasite viability and how it mechanistically drives large-subunit maturation remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No conditional knockdown/knockout phenotype for YihA1","No structure of YihA1 alone or on the ribosome","Functional relationship to PfYihA3 not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["apicoplast ribosome large subunit (LSU) association"],"partners":["APICOPLAST RIBOSOMAL LARGE SUBUNIT (LSU)","PFYIHA3 (PROPOSED FUNCTIONAL COOPERATION, NOT DIRECTLY DEMONSTRATED FOR YIHA1)"],"other_free_text":["Ribosome association is nucleotide-independent [#2].","Pathway placement in late-stage LSU assembly is inferential; no loss-of-function genetics for YihA1 exists in the corpus [#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":["PfYihA1"],"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":5093,"output_tokens":1031,"usd":0.015372,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5774,"output_tokens":2099,"usd":0.040673,"stage2_stop_reason":"end_turn"},"total_usd":0.056045,"stage1_batch_id":"msgbatch_01DbiymDmubkPpYvdbAu5a7V","stage2_batch_id":"msgbatch_012TbrWvMRH129T7PQ4SmvrJ","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"YihA1 (PfYihA1/PF3D7_0513400) localizes to the apicoplast of P. falciparum, as determined by targeting experiments with the recombinant protein.\",\n      \"method\": \"Subcellular localization experiments (fluorescence microscopy/immunofluorescence with recombinant protein targeting assays)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiment with specific antibodies and co-immunoprecipitation, single lab, two complementary methods\",\n      \"pmids\": [\"32057832\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"Recombinant YihA1 (PfYihA1/PF3D7_0513400) possesses active 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\": \"YihA1 (PfYihA1/PF3D7_0513400) interacts with the large subunit (LSU) of the apicoplast ribosome in a nucleotide-independent manner, as shown by interaction with surrogate E. coli ribosomes in vitro and confirmed by co-immunoprecipitation with parasite organellar LSU using specific antibodies in vivo.\",\n      \"method\": \"In vitro ribosome-binding assay (surrogate E. coli ribosomes) and co-immunoprecipitation with specific antibodies from parasite lysates\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP with specific antibodies 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\": \"Based on homology and localization, YihA1 (PfYihA1/PF3D7_0513400) is proposed to function in late-stage assembly of the apicoplast ribosomal large subunit, likely acting in combination with PfYihA3.\",\n      \"method\": \"Co-immunoprecipitation and localization (supporting role inferred from combined data; partly inferential)\",\n      \"journal\": \"Molecular and biochemical parasitology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — pathway placement is partly inferential from homology and localization data, single lab, no direct loss-of-function genetic epistasis experiment performed\",\n      \"pmids\": [\"32057832\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"YihA1 (PF3D7_0513400) is an apicoplast-localized GTPase in P. falciparum that possesses intrinsic GTPase activity and physically interacts with the large subunit of the apicoplast ribosome in a nucleotide-independent manner, consistent with a role in late-stage apicoplast ribosomal large subunit assembly.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"YihA1 (PF3D7_0513400) is an apicoplast-localized GTP-binding protein of Plasmodium falciparum implicated in biogenesis of the apicoplast ribosome [#0, #2]. Targeting experiments place the recombinant protein in the apicoplast [#0], and it possesses intrinsic GTPase activity in vitro [#1]. YihA1 binds the large subunit (LSU) of the apicoplast ribosome in a nucleotide-independent manner, as shown by association with surrogate E. coli ribosomes in vitro and reciprocal co-immunoprecipitation of parasite organellar LSU in vivo [#2], consistent with a role in late-stage assembly of the apicoplast ribosomal large subunit [#3]. Beyond this ribosome-association and GTPase activity, no loss-of-function phenotype, structural model, or substrate/effector mechanism for YihA1 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"Establishing where YihA1 acts was the first step; targeting experiments assigned the protein to the apicoplast, defining the organellar compartment in which any function must occur.\",\n      \"evidence\": \"Subcellular localization by targeting assays with recombinant protein in P. falciparum\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Localization shown with recombinant targeting rather than endogenous tagging\",\n        \"Sub-organellar distribution and timing across the life cycle not resolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Whether the protein was an active enzyme was unknown; an in vitro assay demonstrated intrinsic GTPase activity, confirming it functions as a GTP-binding/hydrolyzing protein.\",\n      \"evidence\": \"In vitro GTPase activity assay with recombinant YihA1\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Kinetic parameters and regulatory cofactors not defined\",\n        \"Whether GTP hydrolysis is required for its cellular role untested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To link the GTPase to a process, its binding partner was identified; YihA1 was shown to associate with the apicoplast ribosomal large subunit nucleotide-independently, tying it to ribosome biology.\",\n      \"evidence\": \"In vitro binding to surrogate E. coli ribosomes plus reciprocal co-immunoprecipitation of parasite organellar LSU\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Direct LSU rRNA/protein contact sites not mapped\",\n        \"Nucleotide-independence measured indirectly; functional consequence unclear\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"The pathway role was inferred: combining homology, localization, and LSU binding, YihA1 was placed in late-stage assembly of the apicoplast large ribosomal subunit, possibly with PfYihA3.\",\n      \"evidence\": \"Inference from co-IP, localization, and homology (no loss-of-function genetics)\",\n      \"pmids\": [\"32057832\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No direct loss-of-function or genetic epistasis experiment performed\",\n        \"Cooperation with PfYihA3 not experimentally demonstrated for YihA1 itself\",\n        \"Assembly-stage placement is inferential rather than shown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether YihA1 GTPase activity is essential for parasite viability and how it mechanistically drives large-subunit maturation remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No conditional knockdown/knockout phenotype for YihA1\",\n        \"No structure of YihA1 alone or on the ribosome\",\n        \"Functional relationship to PfYihA3 not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GTPase activity\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GTP binding\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"large ribosomal subunit binding\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"apicoplast\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"ribosomal large subunit assembly\", \"supporting_discovery_ids\": [2, 3]}\n    ],\n    \"complexes\": [\n      \"apicoplast ribosome large subunit (LSU) association\"\n    ],\n    \"partners\": [\n      \"apicoplast ribosomal large subunit (LSU)\",\n      \"PfYihA3 (proposed functional cooperation, not directly demonstrated for YihA1)\"\n    ],\n    \"other_free_text\": [\n      \"Ribosome association is nucleotide-independent [#2].\",\n      \"Pathway placement in late-stage LSU assembly is inferential; no loss-of-function genetics for YihA1 exists in the corpus [#3].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0513400","name":null,"product":"GTP-binding protein YihA1","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1113100","name":null,"product":"GTP-binding protein YihA1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1019700","name":null,"product":"GTP-binding protein YihA1, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"YihA1","evaluation":null}