{"gene":"PBANKA_0524300","run_date":"2026-09-07T10:55:50","timeline":{"discoveries":[{"year":2022,"finding":"PBANKA_0524300 (IPIS2) was identified as a protein that co-immunoprecipitates with IBIS1, a signature member of intraerythrocytic Plasmodium berghei-induced membrane structures (IBIS), placing IPIS2 in the IBIS complex in infected erythrocytes.","method":"Co-immunoprecipitation with IBIS1 followed by mass spectrometry identification","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP/MS identification, single lab, validated by localization","pmids":["36126089"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"PBANKA_0524300 (IPIS2) localizes to IBIS in infected red blood cells and co-localizes with IBIS1 in the liver-stage parasitophorous vacuole membrane, as determined by immunofluorescence assays.","method":"Immunofluorescence assay / live imaging","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization by immunofluorescence, single lab, two compartments tested","pmids":["36126089"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"finding":"Gene deletion of PBANKA_0524300 (IPIS2) revealed it is required for efficient blood-stage growth; erythrocytes infected with IPIS2-deficient schizonts failed to bind CD36 as efficiently as wild-type P. berghei-infected cells and consequently failed to effectively sequester out of circulating blood.","method":"Gene deletion (loss-of-function) with CD36-binding assay and sequestration phenotype readout","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Strong — clean gene KO with specific molecular phenotype (CD36 binding) and cellular consequence (sequestration defect), single lab with multiple orthogonal readouts","pmids":["36126089"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"current_model":"PBANKA_0524300 (IPIS2) is a tryptophan-rich domain-containing protein that localizes to intraerythrocytic Plasmodium berghei-induced membrane structures (IBIS) in infected erythrocytes and to the parasitophorous vacuole membrane in liver-stage parasites; it is required for efficient blood-stage growth because its loss impairs CD36 binding of infected schizonts, thereby preventing effective sequestration of infected erythrocytes from circulating blood."},"narrative":{"mechanistic_narrative":"PBANKA_0524300 (IPIS2) is a tryptophan-rich domain-containing protein of Plasmodium berghei that contributes to remodeling of the host erythrocyte and to establishing sequestration of infected cells during blood-stage infection [PMID:36126089]. It is a component of the intraerythrocytic P. berghei-induced membrane structures (IBIS), where it physically associates with the signature IBIS protein IBIS1 and localizes to these structures in infected red blood cells, while also co-localizing with IBIS1 at the parasitophorous vacuole membrane in liver-stage parasites [PMID:36126089]. Functionally, IPIS2 is required for efficient blood-stage growth: its deletion impairs the ability of schizont-infected erythrocytes to bind the host receptor CD36, so that infected cells fail to sequester out of the circulation [PMID:36126089]. Beyond its membership in the IBIS complex and its role in CD36-mediated sequestration, no further mechanistic detail — including the molecular basis by which IPIS2 promotes CD36 binding — has been characterized in the available corpus.","teleology":[{"year":2022,"claim":"To place an uncharacterized tryptophan-rich protein into a functional context, IPIS2 was shown to be a physical component of the IBIS complex, establishing it as part of the host-cell-remodeling machinery rather than an isolated protein.","evidence":"Co-immunoprecipitation with IBIS1 followed by mass spectrometry in infected erythrocytes","pmids":["36126089"],"confidence":"Medium","gaps":["Direct versus indirect interaction with IBIS1 within the complex is not resolved","Full composition and stoichiometry of the IBIS complex containing IPIS2 not defined","No structural information on how IPIS2 associates with IBIS"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"To determine where IPIS2 acts, its subcellular distribution was mapped, showing it occupies IBIS in blood-stage infected erythrocytes and the parasitophorous vacuole membrane in liver stage, indicating stage-specific deployment at host-parasite interfaces.","evidence":"Immunofluorescence and live imaging across blood and liver stages","pmids":["36126089"],"confidence":"Medium","gaps":["Mechanism of trafficking/export of IPIS2 to these compartments unknown","Topology and membrane orientation of IPIS2 not established"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"To test whether IPIS2 has a required function, gene deletion demonstrated it is needed for efficient blood-stage growth and specifically for CD36 binding, linking the IBIS-localized protein to the sequestration of infected erythrocytes.","evidence":"Gene deletion with CD36-binding assay and in vivo sequestration readout in P. berghei","pmids":["36126089"],"confidence":"High","gaps":["Molecular mechanism connecting IPIS2 to CD36 ligand presentation on the erythrocyte surface unknown","Whether IPIS2 acts directly or via trafficking/organizing another surface ligand not determined","Contribution of the liver-stage PVM localization to phenotype not addressed"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"How IPIS2 mechanistically enables CD36 binding — whether by exporting or organizing a surface adhesin, or by structuring the IBIS/host-membrane interface — remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No identified surface adhesin downstream of IPIS2","No structure or domain-function dissection of the tryptophan-rich region","No biochemical demonstration of direct CD36 contact"],"attribution":[{"species":"Plasmodium berghei","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["IBIS complex (with IBIS1)"],"partners":["IBIS1"],"other_free_text":["Tryptophan-rich domain-containing protein of Plasmodium berghei [#0].","Deletion impairs CD36 binding of schizont-infected erythrocytes and blocks sequestration from circulating blood [#2].","All findings derive from a single study in Plasmodium berghei; no substrate, structure, or direct CD36-contact mechanism is established in the corpus."]}},"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":"16329993","id":"PMC_16329993","title":"Plasmodium falciparum TryThrA antigen synthetic peptides block in vitro merozoite invasion to erythrocytes.","date":"2005","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/16329993","citation_count":16,"is_preprint":false,"source_species":["Pb"],"role":"primary","match_terms":["TryThrA"],"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":"20638483","id":"PMC_20638483","title":"Plasmodium vivax: immunological properties of tryptophan-rich antigens PvTRAg 35.2 and PvTRAg 80.6.","date":"2010","source":"Microbes and infection","url":"https://pubmed.ncbi.nlm.nih.gov/20638483","citation_count":14,"is_preprint":false,"source_species":["Pb"],"role":"primary","match_terms":["PfTryThrA"],"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":["IPIS2","tryptophan-rich protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25467946","id":"PMC_25467946","title":"Humoral immune responses to a recombinant Plasmodium vivax tryptophan-rich antigen among Plasmodium vivax-infected patients and its localization in the parasite.","date":"2014","source":"Applied biochemistry and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/25467946","citation_count":1,"is_preprint":false,"source_species":["Pb"],"role":"primary","match_terms":["PfTryThrA"],"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":8577,"output_tokens":825,"usd":0.019053,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5524,"output_tokens":1906,"usd":0.037635,"stage2_stop_reason":"end_turn"},"total_usd":0.056688,"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\": \"PBANKA_0524300 (IPIS2) was identified as a protein that co-immunoprecipitates with IBIS1, a signature member of intraerythrocytic Plasmodium berghei-induced membrane structures (IBIS), placing IPIS2 in the IBIS complex in infected erythrocytes.\",\n      \"method\": \"Co-immunoprecipitation with IBIS1 followed by mass spectrometry identification\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP/MS identification, single lab, validated by localization\",\n      \"pmids\": [\"36126089\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"PBANKA_0524300 (IPIS2) localizes to IBIS in infected red blood cells and co-localizes with IBIS1 in the liver-stage parasitophorous vacuole membrane, as determined by immunofluorescence assays.\",\n      \"method\": \"Immunofluorescence assay / live imaging\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization by immunofluorescence, single lab, two compartments tested\",\n      \"pmids\": [\"36126089\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Gene deletion of PBANKA_0524300 (IPIS2) revealed it is required for efficient blood-stage growth; erythrocytes infected with IPIS2-deficient schizonts failed to bind CD36 as efficiently as wild-type P. berghei-infected cells and consequently failed to effectively sequester out of circulating blood.\",\n      \"method\": \"Gene deletion (loss-of-function) with CD36-binding assay and sequestration phenotype readout\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — clean gene KO with specific molecular phenotype (CD36 binding) and cellular consequence (sequestration defect), single lab with multiple orthogonal readouts\",\n      \"pmids\": [\"36126089\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PBANKA_0524300 (IPIS2) is a tryptophan-rich domain-containing protein that localizes to intraerythrocytic Plasmodium berghei-induced membrane structures (IBIS) in infected erythrocytes and to the parasitophorous vacuole membrane in liver-stage parasites; it is required for efficient blood-stage growth because its loss impairs CD36 binding of infected schizonts, thereby preventing effective sequestration of infected erythrocytes from circulating blood.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PBANKA_0524300 (IPIS2) is a tryptophan-rich domain-containing protein of Plasmodium berghei that contributes to remodeling of the host erythrocyte and to establishing sequestration of infected cells during blood-stage infection [#2]. It is a component of the intraerythrocytic P. berghei-induced membrane structures (IBIS), where it physically associates with the signature IBIS protein IBIS1 and localizes to these structures in infected red blood cells, while also co-localizing with IBIS1 at the parasitophorous vacuole membrane in liver-stage parasites [#0, #1]. Functionally, IPIS2 is required for efficient blood-stage growth: its deletion impairs the ability of schizont-infected erythrocytes to bind the host receptor CD36, so that infected cells fail to sequester out of the circulation [#2]. Beyond its membership in the IBIS complex and its role in CD36-mediated sequestration, no further mechanistic detail — including the molecular basis by which IPIS2 promotes CD36 binding — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2022,\n      \"claim\": \"To place an uncharacterized tryptophan-rich protein into a functional context, IPIS2 was shown to be a physical component of the IBIS complex, establishing it as part of the host-cell-remodeling machinery rather than an isolated protein.\",\n      \"evidence\": \"Co-immunoprecipitation with IBIS1 followed by mass spectrometry in infected erythrocytes\",\n      \"pmids\": [\"36126089\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct versus indirect interaction with IBIS1 within the complex is not resolved\",\n        \"Full composition and stoichiometry of the IBIS complex containing IPIS2 not defined\",\n        \"No structural information on how IPIS2 associates with IBIS\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To determine where IPIS2 acts, its subcellular distribution was mapped, showing it occupies IBIS in blood-stage infected erythrocytes and the parasitophorous vacuole membrane in liver stage, indicating stage-specific deployment at host-parasite interfaces.\",\n      \"evidence\": \"Immunofluorescence and live imaging across blood and liver stages\",\n      \"pmids\": [\"36126089\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mechanism of trafficking/export of IPIS2 to these compartments unknown\",\n        \"Topology and membrane orientation of IPIS2 not established\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To test whether IPIS2 has a required function, gene deletion demonstrated it is needed for efficient blood-stage growth and specifically for CD36 binding, linking the IBIS-localized protein to the sequestration of infected erythrocytes.\",\n      \"evidence\": \"Gene deletion with CD36-binding assay and in vivo sequestration readout in P. berghei\",\n      \"pmids\": [\"36126089\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Molecular mechanism connecting IPIS2 to CD36 ligand presentation on the erythrocyte surface unknown\",\n        \"Whether IPIS2 acts directly or via trafficking/organizing another surface ligand not determined\",\n        \"Contribution of the liver-stage PVM localization to phenotype not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How IPIS2 mechanistically enables CD36 binding — whether by exporting or organizing a surface adhesin, or by structuring the IBIS/host-membrane interface — remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No identified surface adhesin downstream of IPIS2\",\n        \"No structure or domain-function dissection of the tryptophan-rich region\",\n        \"No biochemical demonstration of direct CD36 contact\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"IBIS (intraerythrocytic P. berghei-induced membrane structures)\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"parasitophorous vacuole membrane\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"host erythrocyte remodeling / cytoadherence and sequestration\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\"IBIS complex (with IBIS1)\"],\n    \"partners\": [\"IBIS1\"],\n    \"other_free_text\": [\n      \"Tryptophan-rich domain-containing protein of Plasmodium berghei [#0].\",\n      \"Deletion impairs CD36 binding of schizont-infected erythrocytes and blocks sequestration from circulating blood [#2].\",\n      \"All findings derive from a single study in Plasmodium berghei; no substrate, structure, or direct CD36-contact mechanism is established in the corpus.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"PbANKA","gene_id":"PBANKA_0524300","name":null,"product":"tryptophan-rich protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0516000","name":null,"product":"sporozoite and liver stage tryptophan-rich protein, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"IPIS2","evaluation":null}