{"gene":"PBANKA_0623100","run_date":"2026-09-07T10:55:50","timeline":{"discoveries":[{"year":2022,"finding":"IPIS3 (PBANKA_0623100), a tryptophan-rich domain-containing protein, was identified as a co-precipitating partner of IBIS1 (a signature member of intraerythrocytic P. berghei-induced membrane structures) by immunoprecipitation. IPIS3 localizes to IBIS in infected red blood cells and to the parasitophorous vacuole membrane in liver-stage parasites. Gene deletion of IPIS3 revealed it is required for efficient blood-stage growth in P. berghei.","method":"Immunoprecipitation (co-IP with IBIS1), immunofluorescence localization, gene deletion (loss-of-function) with blood-stage growth phenotype readout","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal co-IP for complex membership, direct localization by immunofluorescence, and gene deletion with defined growth phenotype, all in a single lab study with multiple orthogonal methods","pmids":["36126089"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"IPIS3 (PBANKA_0623100) is a tryptophan-rich protein in P. berghei that associates with IBIS1-containing intraerythrocytic membrane structures in infected erythrocytes and with the parasitophorous vacuole membrane in liver stages, and is required for efficient blood-stage parasite growth as demonstrated by gene deletion."},"narrative":{"mechanistic_narrative":"IPIS3 (PBANKA_0623100) is a tryptophan-rich protein of Plasmodium berghei that contributes to the parasite-induced membrane compartments within infected host cells [PMID:36126089]. It was identified as a co-precipitating partner of IBIS1 and localizes to intraerythrocytic P. berghei-induced membrane structures (IBIS) in infected red blood cells and to the parasitophorous vacuole membrane in liver-stage parasites [PMID:36126089]. Gene deletion establishes that IPIS3 is required for efficient blood-stage parasite growth [PMID:36126089]. Beyond this single study, no further mechanistic detail — including the biochemical basis of its association with IBIS1, its membrane-targeting determinants, or its molecular activity — has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"The identity and functional role of proteins comprising P. berghei-induced membrane structures were incompletely defined; identifying IPIS3 as an IBIS1 partner established it as a component of these host-cell membrane compartments across both blood and liver stages, and gene deletion tied it to a fitness role.","evidence":"Co-immunoprecipitation with IBIS1, immunofluorescence localization, and gene deletion with blood-stage growth readout in P. berghei","pmids":["36126089"],"confidence":"Medium","gaps":["The biochemical nature and stoichiometry of the IPIS3–IBIS1 association are not resolved (single lab study without structural or reconstitution data)","The membrane-targeting determinants and how IPIS3 reaches both the IBIS and the liver-stage parasitophorous vacuole membrane are unknown","The molecular activity of the tryptophan-rich domain and the mechanistic basis of the blood-stage growth defect are undefined"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"It remains unknown what molecular function IPIS3 performs at these membrane structures and whether its role extends beyond structural complex membership to a defined biochemical activity.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No molecular activity assigned to the tryptophan-rich domain","No structural model of the IPIS3–IBIS1 complex","Mechanism linking IPIS3 loss to reduced blood-stage growth unresolved"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["IBIS1-associated intraerythrocytic membrane structure complex"],"partners":["IBIS1"],"other_free_text":["Tryptophan-rich domain-containing protein of Plasmodium berghei [#0]","Required for efficient blood-stage parasite growth as shown by gene deletion [#0]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"11704272","id":"PMC_11704272","title":"Properties of the Plasmodium falciparum homologue of a protective vaccine candidate of Plasmodium yoelii.","date":"2001","source":"Molecular and biochemical parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/11704272","citation_count":22,"is_preprint":false,"source_species":["Pb"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25960542","id":"PMC_25960542","title":"A Sporozoite- and Liver Stage-expressed Tryptophan-rich Protein Plays an Auxiliary Role in Plasmodium Liver Stage Development and Is a Potential Vaccine Candidate.","date":"2015","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/25960542","citation_count":19,"is_preprint":false,"source_species":["Pb"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"18603013","id":"PMC_18603013","title":"Immunological responses to a 39.8kDa Plasmodium vivax tryptophan-rich antigen (PvTRAg39.8) among humans.","date":"2008","source":"Microbes and infection","url":"https://pubmed.ncbi.nlm.nih.gov/18603013","citation_count":16,"is_preprint":false,"source_species":["Pb"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21464256","id":"PMC_21464256","title":"Artesunate tolerance in transgenic Plasmodium falciparum parasites overexpressing a tryptophan-rich protein.","date":"2011","source":"Antimicrobial agents and chemotherapy","url":"https://pubmed.ncbi.nlm.nih.gov/21464256","citation_count":15,"is_preprint":false,"source_species":["Pb"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"21283717","id":"PMC_21283717","title":"Plasmodium vivax tryptophan-rich antigen PvTRAg33.5 contains alpha helical structure and multidomain architecture.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21283717","citation_count":10,"is_preprint":false,"source_species":["Pb"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36126089","id":"PMC_36126089","title":"A member of the tryptophan-rich protein family is required for efficient sequestration of Plasmodium berghei schizonts.","date":"2022","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/36126089","citation_count":8,"is_preprint":false,"source_species":["Pb"],"role":"primary","match_terms":["IPIS3","tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"35744665","id":"PMC_35744665","title":"Genetic Diversity and Phylogenetic Relatedness of Plasmodium ovale curtisi and Plasmodium ovale wallikeri in sub-Saharan Africa.","date":"2022","source":"Microorganisms","url":"https://pubmed.ncbi.nlm.nih.gov/35744665","citation_count":1,"is_preprint":false,"source_species":["Pb"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41810678","id":"PMC_41810678","title":"Transcriptomics of Plasmodium vivax rosetting.","date":"2026","source":"Memorias do Instituto Oswaldo Cruz","url":"https://pubmed.ncbi.nlm.nih.gov/41810678","citation_count":0,"is_preprint":false,"source_species":["Pb"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"41983137","id":"PMC_41983137","title":"Poly(I:C) and R848 adjuvants elicit sizeable humoral immunity to liver stage malaria antigens.","date":"2026","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/41983137","citation_count":0,"is_preprint":false,"source_species":["Pb"],"role":"primary","match_terms":["tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7457,"output_tokens":441,"usd":0.014493,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4961,"output_tokens":1202,"usd":0.027428,"stage2_stop_reason":"end_turn"},"total_usd":0.041921,"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\": 2022,\n      \"finding\": \"IPIS3 (PBANKA_0623100), a tryptophan-rich domain-containing protein, was identified as a co-precipitating partner of IBIS1 (a signature member of intraerythrocytic P. berghei-induced membrane structures) by immunoprecipitation. IPIS3 localizes to IBIS in infected red blood cells and to the parasitophorous vacuole membrane in liver-stage parasites. Gene deletion of IPIS3 revealed it is required for efficient blood-stage growth in P. berghei.\",\n      \"method\": \"Immunoprecipitation (co-IP with IBIS1), immunofluorescence localization, gene deletion (loss-of-function) with blood-stage growth phenotype readout\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal co-IP for complex membership, direct localization by immunofluorescence, and gene deletion with defined growth phenotype, all in a single lab study with multiple orthogonal methods\",\n      \"pmids\": [\"36126089\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"IPIS3 (PBANKA_0623100) is a tryptophan-rich protein in P. berghei that associates with IBIS1-containing intraerythrocytic membrane structures in infected erythrocytes and with the parasitophorous vacuole membrane in liver stages, and is required for efficient blood-stage parasite growth as demonstrated by gene deletion.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"IPIS3 (PBANKA_0623100) is a tryptophan-rich protein of Plasmodium berghei that contributes to the parasite-induced membrane compartments within infected host cells [#0]. It was identified as a co-precipitating partner of IBIS1 and localizes to intraerythrocytic P. berghei-induced membrane structures (IBIS) in infected red blood cells and to the parasitophorous vacuole membrane in liver-stage parasites [#0]. Gene deletion establishes that IPIS3 is required for efficient blood-stage parasite growth [#0]. Beyond this single study, no further mechanistic detail — including the biochemical basis of its association with IBIS1, its membrane-targeting determinants, or its molecular activity — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"The identity and functional role of proteins comprising P. berghei-induced membrane structures were incompletely defined; identifying IPIS3 as an IBIS1 partner established it as a component of these host-cell membrane compartments across both blood and liver stages, and gene deletion tied it to a fitness role.\",\n      \"evidence\": \"Co-immunoprecipitation with IBIS1, immunofluorescence localization, and gene deletion with blood-stage growth readout in P. berghei\",\n      \"pmids\": [\"36126089\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The biochemical nature and stoichiometry of the IPIS3–IBIS1 association are not resolved (single lab study without structural or reconstitution data)\",\n        \"The membrane-targeting determinants and how IPIS3 reaches both the IBIS and the liver-stage parasitophorous vacuole membrane are unknown\",\n        \"The molecular activity of the tryptophan-rich domain and the mechanistic basis of the blood-stage growth defect are undefined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown what molecular function IPIS3 performs at these membrane structures and whether its role extends beyond structural complex membership to a defined biochemical activity.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No molecular activity assigned to the tryptophan-rich domain\",\n        \"No structural model of the IPIS3–IBIS1 complex\",\n        \"Mechanism linking IPIS3 loss to reduced blood-stage growth unresolved\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"parasitophorous vacuole membrane\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"host cell parasite-induced membrane structure (IBIS)\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [],\n    \"complexes\": [\"IBIS1-associated intraerythrocytic membrane structure complex\"],\n    \"partners\": [\"IBIS1\"],\n    \"other_free_text\": [\n      \"Tryptophan-rich domain-containing protein of Plasmodium berghei [#0]\",\n      \"Required for efficient blood-stage parasite growth as shown by gene deletion [#0]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"PbANKA","gene_id":"PBANKA_0623100","name":null,"product":"tryptophan-rich protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0200900","name":null,"product":"tryptophan-rich protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"IPIS3","evaluation":null}