{"gene":"PKNH_1300700","run_date":"2026-09-08T15:24:05","timeline":{"discoveries":[{"year":2022,"finding":"In P. berghei, a tryptophan-rich domain-containing protein (IPIS2, an orthologue of PKNH_1300700 family members) was identified by immunoprecipitation with IBIS1 (a signature component of intraerythrocytic Plasmodium berghei-induced membrane structures, IBIS) and found to localize to IBIS in infected red blood cells and to the liver-stage parasitophorous vacuole membrane. Deletion of IPIS2 caused a defect in blood-stage growth and, specifically, erythrocytes infected with IPIS2-deficient schizonts failed to bind CD36 as efficiently as wild-type, resulting in impaired sequestration out of circulating blood.","method":"Immunoprecipitation with IBIS1 (Co-IP/MS), immunofluorescence localization, gene deletion (loss-of-function), CD36-binding adhesion assay","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP/MS, clean gene deletion with defined cellular phenotype (sequestration defect), direct localization; single lab, single study","pmids":["36126089"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2015,"finding":"SLTRiP (sporozoite- and liver stage-expressed tryptophan-rich protein, a family member expressed in P. berghei/rodent malaria) forms large multimers. The protein is exported to the cytosol of infected hepatocytes during early infection. Parasites deficient in SLTRiP showed moderate defects in liver-stage development, establishing an auxiliary but non-essential role in liver-stage parasite development.","method":"Protein multimerization assay (biochemical), immunofluorescence assay (localization/export), gene knockout with quantitative liver-stage development readout (18S rRNA copies), transcriptome profiling of knockout-infected hepatocytes","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — gene deletion with defined developmental phenotype and direct localization by IFA, multiple orthogonal methods; single lab","pmids":["25960542"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2011,"finding":"In P. falciparum, the tryptophan-rich protein PArt (Pf10_0026), a member of the same Plasmodium-specific tryptophan-rich domain gene family, showed dose-dependent protein-level increase upon artesunate treatment. Transgenic parasites overexpressing PArt displayed tolerance to high-dose artesunate exposure (increased survival, reduced growth retardation vs. wild-type controls). Gene disruption of PArt could not be achieved, suggesting an essential function. Bioinformatic analysis placed PArt within a Plasmodium-specific family defined by a novel HMM tryptophan-rich domain profile.","method":"Immunodetection with PArt-specific sera (dose-response), transgenic overexpression with artesunate survival assay, attempted gene disruption (negative result for essentiality inference), bioinformatic HMM family classification","journal":"Antimicrobial agents and chemotherapy","confidence":"Low","confidence_rationale":"Tier 3 / Weak — overexpression phenotype in a single lab, no direct molecular mechanism established; gene disruption result is negative/inconclusive","pmids":["21464256"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PKNH_1300700 encodes a tryptophan-rich protein whose closest experimentally characterized orthologs (in P. berghei) localize to intraerythrocytic membrane structures (IBIS) and the liver-stage parasitophorous vacuole membrane, form multimers, are exported into the host cell cytosol during liver-stage infection, and are required for efficient CD36-mediated sequestration of infected erythrocytes and for normal liver-stage development; no direct mechanistic experiments have been performed on the P. knowlesi PKNH_1300700 protein itself."},"narrative":{"mechanistic_narrative":"PKNH_1300700 encodes a Plasmodium tryptophan-rich domain protein; no direct experiments have been performed on the P. knowlesi protein itself, and its function is inferred entirely from characterized orthologs and family members in other Plasmodium species. In P. berghei, the orthologous protein IPIS2 localizes to intraerythrocytic Plasmodium-induced membrane structures (IBIS) and to the liver-stage parasitophorous vacuole membrane, associates with the IBIS component IBIS1, and is required for efficient CD36-mediated binding and sequestration of infected erythrocytes out of circulation [PMID:36126089]. Another family member, SLTRiP, forms large multimers and is exported into the cytosol of infected hepatocytes, where it supports normal liver-stage development [PMID:25960542]. Beyond these ortholog and family-member studies, no mechanistic detail specific to PKNH_1300700 has been characterized in the available corpus.","teleology":[{"year":2011,"claim":"The first question was whether members of this Plasmodium-specific tryptophan-rich family have any functional consequence for the parasite; a P. falciparum family member (PArt) was linked to drug tolerance and possible essentiality, establishing that these proteins are not inert.","evidence":"Immunodetection dose-response, transgenic overexpression with artesunate survival assay and failed gene disruption in P. falciparum, plus HMM family classification","pmids":["21464256"],"confidence":"Low","gaps":["Overexpression phenotype from a single lab with no direct molecular mechanism established; gene-disruption failure is inconclusive for essentiality","Concerns a P. falciparum family member (PArt), not PKNH_1300700 or its direct ortholog","No localization or interaction data for PKNH_1300700 itself"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"claim":"To ask what these tryptophan-rich proteins do at the cell-biological level, the family member SLTRiP was shown to multimerize and to be exported into the hepatocyte cytosol, defining an auxiliary role in liver-stage development.","evidence":"Biochemical multimerization assay, IFA localization/export, gene knockout with 18S rRNA liver-stage readout and transcriptome profiling in P. berghei","pmids":["25960542"],"confidence":"Medium","gaps":["The molecular partners and export machinery for SLTRiP are not defined","Findings are for a P. berghei family member, not experimentally shown for PKNH_1300700","Only a moderate, non-essential developmental phenotype was observed"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":2022,"claim":"The mechanistic peak so far assigned a concrete host-interaction role: the PKNH_1300700 ortholog IPIS2 associates with IBIS1, localizes to induced membrane structures and the liver-stage PVM, and is required for CD36-mediated sequestration of infected erythrocytes.","evidence":"Reciprocal Co-IP/MS with IBIS1, immunofluorescence localization, gene deletion, and CD36-binding adhesion assay in P. berghei","pmids":["36126089"],"confidence":"Medium","gaps":["Single lab, single study; direct binding of the protein to CD36 versus an indirect requirement is not resolved","How the protein reaches the erythrocyte surface and organizes IBIS is unknown","Demonstrated in P. berghei ortholog, not in PKNH_1300700 itself"],"attribution":[{"species":"Plasmodium berghei","strain":""}]},{"year":null,"claim":"Whether PKNH_1300700 of P. knowlesi shares the localization, IBIS/PVM association, multimerization, export, and CD36-sequestration functions of its P. berghei orthologs remains entirely untested.","evidence":"No direct experiments on the P. knowlesi protein exist in the corpus","pmids":[],"confidence":"Low","gaps":["No localization, interaction, knockout, or adhesion data exist for PKNH_1300700 itself","It is unknown whether P. knowlesi sequestration depends on this protein","The relationship between the erythrocytic (IBIS/CD36) and liver-stage roles is unresolved even in orthologs"],"attribution":[{"species":"Plasmodium knowlesi","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["IBIS1-associated complex at intraerythrocytic Plasmodium-induced membrane structures (shown for P. berghei ortholog IPIS2) [#0]"],"partners":["IBIS1 (P. BERGHEI ORTHOLOG IPIS2, CO-IP/MS) [#0]","HOST CD36 (REQUIRED FOR CD36-MEDIATED ERYTHROCYTE SEQUESTRATION; DIRECT VS INDIRECT BINDING UNRESOLVED) [#0]"],"other_free_text":["PKNH_1300700 is a member of a Plasmodium-specific tryptophan-rich domain gene family defined by a novel HMM profile [#2]; all functional data derive from orthologs (P. berghei IPIS2, SLTRiP) and a family member (P. falciparum PArt), not from PKNH_1300700 itself.","In P. falciparum, the family member PArt shows artesunate-induced protein increase and confers artesunate tolerance on overexpression, with failed gene disruption suggesting essentiality [#2]."]}},"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":["Pk"],"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":18,"is_preprint":false,"source_species":["Pk"],"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":["Pk"],"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":14,"is_preprint":false,"source_species":["Pk"],"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":["Pk"],"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":["Pk"],"role":"primary","match_terms":["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":["Pk"],"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":["Pk"],"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":["Pk"],"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":7414,"output_tokens":1165,"usd":0.019859,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5953,"output_tokens":2443,"usd":0.04542,"stage2_stop_reason":"end_turn"},"total_usd":0.065279,"stage1_batch_id":"msgbatch_01S4WrhSkksYHeZXxqf3za3o","stage2_batch_id":"msgbatch_019VBBeuW6G52X8gZfsFDfb5","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2022,\n      \"finding\": \"In P. berghei, a tryptophan-rich domain-containing protein (IPIS2, an orthologue of PKNH_1300700 family members) was identified by immunoprecipitation with IBIS1 (a signature component of intraerythrocytic Plasmodium berghei-induced membrane structures, IBIS) and found to localize to IBIS in infected red blood cells and to the liver-stage parasitophorous vacuole membrane. Deletion of IPIS2 caused a defect in blood-stage growth and, specifically, erythrocytes infected with IPIS2-deficient schizonts failed to bind CD36 as efficiently as wild-type, resulting in impaired sequestration out of circulating blood.\",\n      \"method\": \"Immunoprecipitation with IBIS1 (Co-IP/MS), immunofluorescence localization, gene deletion (loss-of-function), CD36-binding adhesion assay\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP/MS, clean gene deletion with defined cellular phenotype (sequestration defect), direct localization; single lab, single study\",\n      \"pmids\": [\"36126089\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"SLTRiP (sporozoite- and liver stage-expressed tryptophan-rich protein, a family member expressed in P. berghei/rodent malaria) forms large multimers. The protein is exported to the cytosol of infected hepatocytes during early infection. Parasites deficient in SLTRiP showed moderate defects in liver-stage development, establishing an auxiliary but non-essential role in liver-stage parasite development.\",\n      \"method\": \"Protein multimerization assay (biochemical), immunofluorescence assay (localization/export), gene knockout with quantitative liver-stage development readout (18S rRNA copies), transcriptome profiling of knockout-infected hepatocytes\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — gene deletion with defined developmental phenotype and direct localization by IFA, multiple orthogonal methods; single lab\",\n      \"pmids\": [\"25960542\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"In P. falciparum, the tryptophan-rich protein PArt (Pf10_0026), a member of the same Plasmodium-specific tryptophan-rich domain gene family, showed dose-dependent protein-level increase upon artesunate treatment. Transgenic parasites overexpressing PArt displayed tolerance to high-dose artesunate exposure (increased survival, reduced growth retardation vs. wild-type controls). Gene disruption of PArt could not be achieved, suggesting an essential function. Bioinformatic analysis placed PArt within a Plasmodium-specific family defined by a novel HMM tryptophan-rich domain profile.\",\n      \"method\": \"Immunodetection with PArt-specific sera (dose-response), transgenic overexpression with artesunate survival assay, attempted gene disruption (negative result for essentiality inference), bioinformatic HMM family classification\",\n      \"journal\": \"Antimicrobial agents and chemotherapy\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — overexpression phenotype in a single lab, no direct molecular mechanism established; gene disruption result is negative/inconclusive\",\n      \"pmids\": [\"21464256\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PKNH_1300700 encodes a tryptophan-rich protein whose closest experimentally characterized orthologs (in P. berghei) localize to intraerythrocytic membrane structures (IBIS) and the liver-stage parasitophorous vacuole membrane, form multimers, are exported into the host cell cytosol during liver-stage infection, and are required for efficient CD36-mediated sequestration of infected erythrocytes and for normal liver-stage development; no direct mechanistic experiments have been performed on the P. knowlesi PKNH_1300700 protein itself.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PKNH_1300700 encodes a Plasmodium tryptophan-rich domain protein; no direct experiments have been performed on the P. knowlesi protein itself, and its function is inferred entirely from characterized orthologs and family members in other Plasmodium species. In P. berghei, the orthologous protein IPIS2 localizes to intraerythrocytic Plasmodium-induced membrane structures (IBIS) and to the liver-stage parasitophorous vacuole membrane, associates with the IBIS component IBIS1, and is required for efficient CD36-mediated binding and sequestration of infected erythrocytes out of circulation [#0]. Another family member, SLTRiP, forms large multimers and is exported into the cytosol of infected hepatocytes, where it supports normal liver-stage development [#1]. Beyond these ortholog and family-member studies, no mechanistic detail specific to PKNH_1300700 has been characterized in the available corpus.\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2011,\n      \"claim\": \"The first question was whether members of this Plasmodium-specific tryptophan-rich family have any functional consequence for the parasite; a P. falciparum family member (PArt) was linked to drug tolerance and possible essentiality, establishing that these proteins are not inert.\",\n      \"evidence\": \"Immunodetection dose-response, transgenic overexpression with artesunate survival assay and failed gene disruption in P. falciparum, plus HMM family classification\",\n      \"pmids\": [\"21464256\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Overexpression phenotype from a single lab with no direct molecular mechanism established; gene-disruption failure is inconclusive for essentiality\",\n        \"Concerns a P. falciparum family member (PArt), not PKNH_1300700 or its direct ortholog\",\n        \"No localization or interaction data for PKNH_1300700 itself\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"To ask what these tryptophan-rich proteins do at the cell-biological level, the family member SLTRiP was shown to multimerize and to be exported into the hepatocyte cytosol, defining an auxiliary role in liver-stage development.\",\n      \"evidence\": \"Biochemical multimerization assay, IFA localization/export, gene knockout with 18S rRNA liver-stage readout and transcriptome profiling in P. berghei\",\n      \"pmids\": [\"25960542\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular partners and export machinery for SLTRiP are not defined\",\n        \"Findings are for a P. berghei family member, not experimentally shown for PKNH_1300700\",\n        \"Only a moderate, non-essential developmental phenotype was observed\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"The mechanistic peak so far assigned a concrete host-interaction role: the PKNH_1300700 ortholog IPIS2 associates with IBIS1, localizes to induced membrane structures and the liver-stage PVM, and is required for CD36-mediated sequestration of infected erythrocytes.\",\n      \"evidence\": \"Reciprocal Co-IP/MS with IBIS1, immunofluorescence localization, gene deletion, and CD36-binding adhesion assay in P. berghei\",\n      \"pmids\": [\"36126089\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab, single study; direct binding of the protein to CD36 versus an indirect requirement is not resolved\",\n        \"How the protein reaches the erythrocyte surface and organizes IBIS is unknown\",\n        \"Demonstrated in P. berghei ortholog, not in PKNH_1300700 itself\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium berghei\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PKNH_1300700 of P. knowlesi shares the localization, IBIS/PVM association, multimerization, export, and CD36-sequestration functions of its P. berghei orthologs remains entirely untested.\",\n      \"evidence\": \"No direct experiments on the P. knowlesi protein exist in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No localization, interaction, knockout, or adhesion data exist for PKNH_1300700 itself\",\n        \"It is unknown whether P. knowlesi sequestration depends on this protein\",\n        \"The relationship between the erythrocytic (IBIS/CD36) and liver-stage roles is unresolved even in orthologs\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium knowlesi\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0042803 protein homodimerization activity\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020002 host cell plasma membrane\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0020005 symbiont-containing vacuole membrane\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0020030 intracellular membrane-bounded organelle (IBIS induced membrane structures)\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0030430 host cell cytoplasm\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409 entry into host / cytoadherence-mediated sequestration\", \"supporting_discovery_ids\": [0]},\n      {\"term_id\": \"GO:0044117 growth of symbiont in host (liver-stage development)\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\n      \"IBIS1-associated complex at intraerythrocytic Plasmodium-induced membrane structures (shown for P. berghei ortholog IPIS2) [#0]\"\n    ],\n    \"partners\": [\n      \"IBIS1 (P. berghei ortholog IPIS2, Co-IP/MS) [#0]\",\n      \"host CD36 (required for CD36-mediated erythrocyte sequestration; direct vs indirect binding unresolved) [#0]\"\n    ],\n    \"other_free_text\": [\n      \"PKNH_1300700 is a member of a Plasmodium-specific tryptophan-rich domain gene family defined by a novel HMM profile [#2]; all functional data derive from orthologs (P. berghei IPIS2, SLTRiP) and a family member (P. falciparum PArt), not from PKNH_1300700 itself.\",\n      \"In P. falciparum, the family member PArt shows artesunate-induced protein increase and confers artesunate tolerance on overexpression, with failed gene disruption suggesting essentiality [#2].\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"PkH","gene_id":"PKNH_1300700","name":null,"product":"tryptophan-rich protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}