{"gene":"PF3D7_1467400","run_date":"2026-09-08T14:19:07","timeline":{"discoveries":[{"year":2001,"finding":"RPL22 (PF3D7_1467400) is predicted to be a nuclear-encoded apicoplast-targeted protein based on bipartite N-terminal targeting signals (signal peptide + transit peptide); computational feature analysis of transit peptides identified net positive charge and enrichment in asparagine, lysine, and isoleucine residues as characteristic features of apicoplast-targeting sequences.","method":"Computational prediction (PATS neural network, principal component analysis, self-organizing maps) applied to P. falciparum nuclear-encoded protein precursors","journal":"Gene","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no direct experimental validation of RPL22 targeting","pmids":["11738814"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"finding":"RPL22 (PF3D7_1467400) is predicted to associate with the apicoplast-encoded ribosomal protein L4 (PfRpl4) and the large subunit rRNA to form the 50S ribosome polypeptide exit tunnel in the apicoplast. In azithromycin-resistant parasite lines, the PfRpl4 protein acquired a G76V mutation whereas the PfRpl22 sequence remained unchanged, consistent with PfRpl4 being the primary determinant of azithromycin binding at the exit tunnel.","method":"Resistance selection in culture (P. falciparum 7G8 and Dd2 lines), Sanger sequencing of resistance loci, molecular modeling of PfRpl4–AZ interaction","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 4 / Weak — RPL22 involvement is structural modeling/prediction only; no direct biochemical or genetic experiment performed on RPL22 itself; its sequence was reported unchanged in resistant lines","pmids":["17110371"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":"7G8"},{"species":"Plasmodium falciparum","strain":"Dd2"}]}],"current_model":"RPL22 (PF3D7_1467400) is a nuclear-encoded, apicoplast-targeted 50S ribosomal protein predicted to form part of the large subunit polypeptide exit tunnel together with PfRpl4 and the apicoplast large subunit rRNA, but no direct biochemical or structural experiments have been performed on this protein itself."},"narrative":{"mechanistic_narrative":"RPL22 (PF3D7_1467400) is a nuclear-encoded protein predicted to be targeted to the apicoplast via a bipartite N-terminal signal-plus-transit-peptide sequence [PMID:11738814], where it is modeled as a component of the apicoplast 50S ribosomal large subunit [PMID:17110371]. Structural modeling places it at the polypeptide exit tunnel alongside the apicoplast-encoded PfRpl4 and the large subunit rRNA; in azithromycin-resistant P. falciparum lines (7G8 and Dd2) the PfRpl22 sequence remained unchanged while PfRpl4 acquired a G76V mutation, so RPL22 itself was not implicated as a determinant of azithromycin binding [PMID:17110371]. Beyond these computational and modeling-based assignments, no direct biochemical, genetic, or structural experiment has been performed on RPL22 itself in the available corpus, and its role is established only as a predicted member of the apicoplast large ribosomal subunit.","teleology":[{"year":2001,"claim":"To ask whether RPL22 is imported into the apicoplast, feature analysis of nuclear-encoded precursors classified it as an apicoplast-targeted protein carrying a bipartite N-terminal targeting signal.","evidence":"Computational prediction (PATS neural network, PCA, self-organizing maps) on P. falciparum protein precursors","pmids":["11738814"],"confidence":"Low","gaps":["Targeting is a computational prediction never validated experimentally by trafficking or localization assays","No confirmation that the encoded protein is expressed or imported","Cleavage site and processing of the bipartite signal not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2006,"claim":"To place RPL22 within the apicoplast ribosome and evaluate its role in azithromycin action, resistance selection and modeling assigned it to the 50S large-subunit exit tunnel but showed its sequence unchanged in resistant lines, pointing to PfRpl4 rather than RPL22 as the drug-binding determinant.","evidence":"Azithromycin resistance selection in P. falciparum 7G8 and Dd2, Sanger sequencing of loci, molecular modeling of the exit tunnel","pmids":["17110371"],"confidence":"Low","gaps":["RPL22 placement in the exit tunnel is modeling/prediction, not biochemical or structural evidence","No direct genetic or biochemical experiment was performed on RPL22 itself","Physical association of RPL22 with PfRpl4 and the large-subunit rRNA is inferred, not demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":"7G8"},{"species":"Plasmodium falciparum","strain":"Dd2"}]},{"year":null,"claim":"Whether RPL22 is genuinely imported into the apicoplast, physically incorporated into the 50S subunit, and required for apicoplast ribosome function or parasite viability remains experimentally unaddressed.","evidence":"No direct localization, interaction, structural, or gene-disruption data on RPL22 in the corpus","pmids":[],"confidence":"Low","gaps":["No experimental localization confirming apicoplast import","No biochemical or structural demonstration of ribosome incorporation","No knockout/knockdown establishing an essential or dispensable role"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Apicoplast 50S large ribosomal subunit (predicted)"],"partners":["PFRPL4 (APICOPLAST-ENCODED L4, PREDICTED EXIT-TUNNEL NEIGHBOR)","APICOPLAST LARGE SUBUNIT RRNA (PREDICTED)"],"other_free_text":["RPL22 (PF3D7_1467400) is characterized only as a nuclear-encoded, predicted apicoplast-targeted large ribosomal subunit protein; no direct biochemical, genetic, or structural experiment has been performed on the protein itself.","In azithromycin-resistant P. falciparum 7G8 and Dd2 lines, the PfRpl22 sequence was unchanged, and PfRpl4 (not RPL22) carried the G76V resistance mutation."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"11738814","id":"PMC_11738814","title":"Deciphering apicoplast targeting signals--feature extraction from nuclear-encoded precursors of Plasmodium falciparum apicoplast proteins.","date":"2001","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/11738814","citation_count":175,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"17110371","id":"PMC_17110371","title":"In vitro efficacy, resistance selection, and structural modeling studies implicate the malarial parasite apicoplast as the target of azithromycin.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17110371","citation_count":126,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["L22","PfRPL22"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3960,"output_tokens":723,"usd":0.011362,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5395,"output_tokens":1862,"usd":0.036762,"stage2_stop_reason":"end_turn"},"total_usd":0.048124,"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\": 2001,\n      \"finding\": \"RPL22 (PF3D7_1467400) is predicted to be a nuclear-encoded apicoplast-targeted protein based on bipartite N-terminal targeting signals (signal peptide + transit peptide); computational feature analysis of transit peptides identified net positive charge and enrichment in asparagine, lysine, and isoleucine residues as characteristic features of apicoplast-targeting sequences.\",\n      \"method\": \"Computational prediction (PATS neural network, principal component analysis, self-organizing maps) applied to P. falciparum nuclear-encoded protein precursors\",\n      \"journal\": \"Gene\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no direct experimental validation of RPL22 targeting\",\n      \"pmids\": [\"11738814\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"RPL22 (PF3D7_1467400) is predicted to associate with the apicoplast-encoded ribosomal protein L4 (PfRpl4) and the large subunit rRNA to form the 50S ribosome polypeptide exit tunnel in the apicoplast. In azithromycin-resistant parasite lines, the PfRpl4 protein acquired a G76V mutation whereas the PfRpl22 sequence remained unchanged, consistent with PfRpl4 being the primary determinant of azithromycin binding at the exit tunnel.\",\n      \"method\": \"Resistance selection in culture (P. falciparum 7G8 and Dd2 lines), Sanger sequencing of resistance loci, molecular modeling of PfRpl4–AZ interaction\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — RPL22 involvement is structural modeling/prediction only; no direct biochemical or genetic experiment performed on RPL22 itself; its sequence was reported unchanged in resistant lines\",\n      \"pmids\": [\"17110371\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"7G8\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"Dd2\"}\n      ]\n    }\n  ],\n  \"current_model\": \"RPL22 (PF3D7_1467400) is a nuclear-encoded, apicoplast-targeted 50S ribosomal protein predicted to form part of the large subunit polypeptide exit tunnel together with PfRpl4 and the apicoplast large subunit rRNA, but no direct biochemical or structural experiments have been performed on this protein itself.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"RPL22 (PF3D7_1467400) is a nuclear-encoded protein predicted to be targeted to the apicoplast via a bipartite N-terminal signal-plus-transit-peptide sequence [#0], where it is modeled as a component of the apicoplast 50S ribosomal large subunit [#1]. Structural modeling places it at the polypeptide exit tunnel alongside the apicoplast-encoded PfRpl4 and the large subunit rRNA; in azithromycin-resistant P. falciparum lines (7G8 and Dd2) the PfRpl22 sequence remained unchanged while PfRpl4 acquired a G76V mutation, so RPL22 itself was not implicated as a determinant of azithromycin binding [#1]. Beyond these computational and modeling-based assignments, no direct biochemical, genetic, or structural experiment has been performed on RPL22 itself in the available corpus, and its role is established only as a predicted member of the apicoplast large ribosomal subunit.\",\n  \"teleology\": [\n    {\n      \"year\": 2001,\n      \"claim\": \"To ask whether RPL22 is imported into the apicoplast, feature analysis of nuclear-encoded precursors classified it as an apicoplast-targeted protein carrying a bipartite N-terminal targeting signal.\",\n      \"evidence\": \"Computational prediction (PATS neural network, PCA, self-organizing maps) on P. falciparum protein precursors\",\n      \"pmids\": [\n        \"11738814\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Targeting is a computational prediction never validated experimentally by trafficking or localization assays\",\n        \"No confirmation that the encoded protein is expressed or imported\",\n        \"Cleavage site and processing of the bipartite signal not defined\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"To place RPL22 within the apicoplast ribosome and evaluate its role in azithromycin action, resistance selection and modeling assigned it to the 50S large-subunit exit tunnel but showed its sequence unchanged in resistant lines, pointing to PfRpl4 rather than RPL22 as the drug-binding determinant.\",\n      \"evidence\": \"Azithromycin resistance selection in P. falciparum 7G8 and Dd2, Sanger sequencing of loci, molecular modeling of the exit tunnel\",\n      \"pmids\": [\n        \"17110371\"\n      ],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"RPL22 placement in the exit tunnel is modeling/prediction, not biochemical or structural evidence\",\n        \"No direct genetic or biochemical experiment was performed on RPL22 itself\",\n        \"Physical association of RPL22 with PfRpl4 and the large-subunit rRNA is inferred, not demonstrated\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"7G8\"\n        },\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"Dd2\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether RPL22 is genuinely imported into the apicoplast, physically incorporated into the 50S subunit, and required for apicoplast ribosome function or parasite viability remains experimentally unaddressed.\",\n      \"evidence\": \"No direct localization, interaction, structural, or gene-disruption data on RPL22 in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No experimental localization confirming apicoplast import\",\n        \"No biochemical or structural demonstration of ribosome incorporation\",\n        \"No knockout/knockdown establishing an essential or dispensable role\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Plasmodium falciparum\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\n        \"term_id\": \"GO:0003735\",\n        \"supporting_discovery_ids\": [\n          1\n        ]\n      }\n    ],\n    \"localization\": [\n      {\n        \"term_id\": \"GO:0009507\",\n        \"supporting_discovery_ids\": [\n          0,\n          1\n        ]\n      }\n    ],\n    \"pathway\": [\n      {\n        \"term_id\": \"GO:0006412\",\n        \"supporting_discovery_ids\": [\n          1\n        ]\n      }\n    ],\n    \"complexes\": [\n      \"Apicoplast 50S large ribosomal subunit (predicted)\"\n    ],\n    \"partners\": [\n      \"PfRpl4 (apicoplast-encoded L4, predicted exit-tunnel neighbor)\",\n      \"Apicoplast large subunit rRNA (predicted)\"\n    ],\n    \"other_free_text\": [\n      \"RPL22 (PF3D7_1467400) is characterized only as a nuclear-encoded, predicted apicoplast-targeted large ribosomal subunit protein; no direct biochemical, genetic, or structural experiment has been performed on the protein itself.\",\n      \"In azithromycin-resistant P. falciparum 7G8 and Dd2 lines, the PfRpl22 sequence was unchanged, and PfRpl4 (not RPL22) carried the G76V resistance mutation.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1467400","name":null,"product":"50S ribosomal protein L22, apicoplast, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1330700","name":null,"product":"50S ribosomal protein L22, apicoplast, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1213900","name":null,"product":"50S ribosomal protein L22, apicoplast, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"RPL22","evaluation":null}