{"gene":"PF3D7_1001900","run_date":"2026-09-08T16:26:55","timeline":{"discoveries":[{"year":2018,"finding":"PfJ23 (PF3D7_1001900) is a mostly α-helical protein that displays different oligomeric forms under reducing versus non-reducing conditions, as determined by in vitro and in silico analysis of recombinant protein.","method":"In vitro biochemical characterization and in silico secondary structure prediction of recombinant PfJ23","journal":"Pathogens and disease","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro assay with recombinant protein, single lab, single study","pmids":["30576479"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Purified PfSBP1 (Pf skeleton binding protein 1) directly interacts with both recombinant and native PfJ23 (PF3D7_1001900), and the two proteins partially co-localize during parasite development in infected erythrocytes.","method":"Direct interaction shown by pulldown/binding assay with purified recombinant proteins and confirmed with native parasite protein; co-localization by immunofluorescence","journal":"Pathogens and disease","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct binding assay with recombinant and native protein plus co-localization, single lab, two orthogonal methods","pmids":["30576479"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"Both recombinant and parasite-expressed PfJ23 (PF3D7_1001900) bind to the cytoplasmic tail of PfEMP1, and the two proteins partly co-localize during parasite development.","method":"In vitro binding assay with recombinant proteins and parasite-expressed PfJ23; co-localization by immunofluorescence","journal":"Pathogens and disease","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct binding assay with recombinant and native protein plus co-localization, single lab, two orthogonal methods","pmids":["30576479"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"finding":"PfSBP1 and the cytoplasmic tail of PfEMP1 can simultaneously bind PfJ23 (PF3D7_1001900) in vitro, forming a trimeric complex, suggesting PfJ23 harbors distinct binding sites for each partner.","method":"In vitro ternary complex formation assay with purified recombinant proteins","journal":"Pathogens and disease","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro reconstitution of ternary complex, single lab, single study","pmids":["30576479"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PfJ23 (PF3D7_1001900) is a mostly α-helical, PEXEL-positive exported protein that exists in different oligomeric states under reducing and non-reducing conditions; it harbors distinct binding sites for the Maurer's cleft marker PfSBP1 and the cytoplasmic tail of the virulence factor PfEMP1, and can simultaneously engage both partners in a trimeric complex in vitro, implicating PfJ23 in the export pathway of PEXEL-negative proteins to the infected erythrocyte surface."},"narrative":{"mechanistic_narrative":"PfJ23 (PF3D7_1001900) is a mostly α-helical exported protein of Plasmodium falciparum that functions as a molecular scaffold linking Maurer's cleft machinery to the virulence factor PfEMP1 [PMID:30576479]. Recombinant PfJ23 adopts different oligomeric forms under reducing versus non-reducing conditions, indicating redox-sensitive self-association [PMID:30576479]. It binds directly to the Maurer's cleft marker PfSBP1 (skeleton binding protein 1) and to the cytoplasmic tail of PfEMP1, and partially co-localizes with each during intraerythrocytic development [PMID:30576479]. Because PfSBP1 and the PfEMP1 cytoplasmic tail can engage PfJ23 simultaneously to form a trimeric complex in vitro, PfJ23 harbors distinct, non-overlapping binding sites for the two partners, positioning it as a bridging component in the trafficking of PEXEL-negative surface proteins to the infected erythrocyte membrane [PMID:30576479]. Beyond this in vitro interaction and localization evidence, the cellular consequences of PfJ23 function — including any loss-of-function phenotype — have not been characterized in the available corpus.","teleology":[{"year":2018,"claim":"Establishing the physical nature of PfJ23 answered whether the uncharacterized exported protein has a defined fold and quaternary behavior that could support a structural/scaffolding role.","evidence":"In vitro biochemical characterization and in silico secondary structure prediction of recombinant PfJ23","pmids":["30576479"],"confidence":"Medium","gaps":["No experimental high-resolution structure; secondary structure is predicted in silico","Physiological relevance of the redox-dependent oligomeric states in the parasite is untested","No mapping of which residues drive self-association"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Identifying PfSBP1 and the PfEMP1 cytoplasmic tail as direct binding partners placed PfJ23 within the PEXEL-negative protein export pathway rather than leaving it functionally orphan.","evidence":"Direct pulldown/binding assays with purified recombinant and native PfJ23 plus immunofluorescence co-localization in infected erythrocytes","pmids":["30576479"],"confidence":"Medium","gaps":["Co-localization is only partial, so the interaction may occur in a defined subcompartment or transiently","Binding sites on PfJ23 for each partner are not mapped at residue level","No demonstration that these interactions occur at endogenous stoichiometry in vivo"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2018,"claim":"Demonstrating simultaneous binding of both partners answered whether PfJ23 could act as a bridging scaffold, showing it can nucleate a trimeric complex with distinct sites for each partner.","evidence":"In vitro ternary complex reconstitution assay with purified recombinant proteins","pmids":["30576479"],"confidence":"Medium","gaps":["Ternary complex shown only in vitro with recombinant proteins; not reconstituted or validated in the parasite","Functional consequence of complex formation for PfEMP1 trafficking or surface presentation is untested","Whether complex assembly is regulated (e.g. by redox state or oligomerization) is unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"It remains unknown whether PfJ23 is functionally required for PfEMP1 export, cytoadherence, or parasite virulence in vivo.","evidence":"No gene-disruption, conditional knockdown, or phenotypic study of PF3D7_1001900 is present in the corpus","pmids":[],"confidence":"Low","gaps":["No loss-of-function genetics for PfJ23","No demonstration that PfJ23 is required for PfEMP1 surface display or cytoadherence","No structural map of the two binding interfaces"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PfJ23–PfSBP1–PfEMP1(cytoplasmic tail) trimeric complex (in vitro) [#3]"],"partners":["PFSBP1 (SKELETON BINDING PROTEIN 1) [#1]","PFEMP1 CYTOPLASMIC TAIL [#2]"],"other_free_text":["PfJ23 (PF3D7_1001900) is a PEXEL-positive exported protein; mostly α-helical with redox-dependent oligomeric states [#0]","Harbors distinct, non-overlapping binding sites for PfSBP1 and the PfEMP1 cytoplasmic tail, enabling simultaneous engagement [#3]","All current evidence derives from a single study using recombinant/native proteins and immunofluorescence; no loss-of-function or in vivo functional data for PF3D7_1001900 exist in the corpus"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"30576479","id":"PMC_30576479","title":"Plasmodium falciparum protein 'PfJ23' hosts distinct binding sites for major virulence factor 'PfEMP1' and Maurer's cleft marker 'PfSBP1'.","date":"2018","source":"Pathogens and disease","url":"https://pubmed.ncbi.nlm.nih.gov/30576479","citation_count":3,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfJ23"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37647112","id":"","title":"Timing of dense granule biogenesis in asexual malaria parasites.","date":"2023","source":"Microbiology (Reading, England)","url":"https://pubmed.ncbi.nlm.nih.gov/37647112","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["PfJ23"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3833,"output_tokens":1056,"usd":0.013669,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5832,"output_tokens":2161,"usd":0.041592,"stage2_stop_reason":"end_turn"},"total_usd":0.055261,"stage1_batch_id":"msgbatch_01NE1MTa8x1hW7Lo4tAaNzY1","stage2_batch_id":"msgbatch_0141vaQdeFvbo2q39AinvXM9","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2018,\n      \"finding\": \"PfJ23 (PF3D7_1001900) is a mostly α-helical protein that displays different oligomeric forms under reducing versus non-reducing conditions, as determined by in vitro and in silico analysis of recombinant protein.\",\n      \"method\": \"In vitro biochemical characterization and in silico secondary structure prediction of recombinant PfJ23\",\n      \"journal\": \"Pathogens and disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro assay with recombinant protein, single lab, single study\",\n      \"pmids\": [\"30576479\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Purified PfSBP1 (Pf skeleton binding protein 1) directly interacts with both recombinant and native PfJ23 (PF3D7_1001900), and the two proteins partially co-localize during parasite development in infected erythrocytes.\",\n      \"method\": \"Direct interaction shown by pulldown/binding assay with purified recombinant proteins and confirmed with native parasite protein; co-localization by immunofluorescence\",\n      \"journal\": \"Pathogens and disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct binding assay with recombinant and native protein plus co-localization, single lab, two orthogonal methods\",\n      \"pmids\": [\"30576479\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Both recombinant and parasite-expressed PfJ23 (PF3D7_1001900) bind to the cytoplasmic tail of PfEMP1, and the two proteins partly co-localize during parasite development.\",\n      \"method\": \"In vitro binding assay with recombinant proteins and parasite-expressed PfJ23; co-localization by immunofluorescence\",\n      \"journal\": \"Pathogens and disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct binding assay with recombinant and native protein plus co-localization, single lab, two orthogonal methods\",\n      \"pmids\": [\"30576479\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"PfSBP1 and the cytoplasmic tail of PfEMP1 can simultaneously bind PfJ23 (PF3D7_1001900) in vitro, forming a trimeric complex, suggesting PfJ23 harbors distinct binding sites for each partner.\",\n      \"method\": \"In vitro ternary complex formation assay with purified recombinant proteins\",\n      \"journal\": \"Pathogens and disease\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro reconstitution of ternary complex, single lab, single study\",\n      \"pmids\": [\"30576479\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PfJ23 (PF3D7_1001900) is a mostly α-helical, PEXEL-positive exported protein that exists in different oligomeric states under reducing and non-reducing conditions; it harbors distinct binding sites for the Maurer's cleft marker PfSBP1 and the cytoplasmic tail of the virulence factor PfEMP1, and can simultaneously engage both partners in a trimeric complex in vitro, implicating PfJ23 in the export pathway of PEXEL-negative proteins to the infected erythrocyte surface.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"PfJ23 (PF3D7_1001900) is a mostly α-helical exported protein of Plasmodium falciparum that functions as a molecular scaffold linking Maurer's cleft machinery to the virulence factor PfEMP1 [#0, #3]. Recombinant PfJ23 adopts different oligomeric forms under reducing versus non-reducing conditions, indicating redox-sensitive self-association [#0]. It binds directly to the Maurer's cleft marker PfSBP1 (skeleton binding protein 1) and to the cytoplasmic tail of PfEMP1, and partially co-localizes with each during intraerythrocytic development [#1, #2]. Because PfSBP1 and the PfEMP1 cytoplasmic tail can engage PfJ23 simultaneously to form a trimeric complex in vitro, PfJ23 harbors distinct, non-overlapping binding sites for the two partners, positioning it as a bridging component in the trafficking of PEXEL-negative surface proteins to the infected erythrocyte membrane [#3]. Beyond this in vitro interaction and localization evidence, the cellular consequences of PfJ23 function — including any loss-of-function phenotype — have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2018,\n      \"claim\": \"Establishing the physical nature of PfJ23 answered whether the uncharacterized exported protein has a defined fold and quaternary behavior that could support a structural/scaffolding role.\",\n      \"evidence\": \"In vitro biochemical characterization and in silico secondary structure prediction of recombinant PfJ23\",\n      \"pmids\": [\"30576479\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No experimental high-resolution structure; secondary structure is predicted in silico\",\n        \"Physiological relevance of the redox-dependent oligomeric states in the parasite is untested\",\n        \"No mapping of which residues drive self-association\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Identifying PfSBP1 and the PfEMP1 cytoplasmic tail as direct binding partners placed PfJ23 within the PEXEL-negative protein export pathway rather than leaving it functionally orphan.\",\n      \"evidence\": \"Direct pulldown/binding assays with purified recombinant and native PfJ23 plus immunofluorescence co-localization in infected erythrocytes\",\n      \"pmids\": [\"30576479\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Co-localization is only partial, so the interaction may occur in a defined subcompartment or transiently\",\n        \"Binding sites on PfJ23 for each partner are not mapped at residue level\",\n        \"No demonstration that these interactions occur at endogenous stoichiometry in vivo\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"Demonstrating simultaneous binding of both partners answered whether PfJ23 could act as a bridging scaffold, showing it can nucleate a trimeric complex with distinct sites for each partner.\",\n      \"evidence\": \"In vitro ternary complex reconstitution assay with purified recombinant proteins\",\n      \"pmids\": [\"30576479\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Ternary complex shown only in vitro with recombinant proteins; not reconstituted or validated in the parasite\",\n        \"Functional consequence of complex formation for PfEMP1 trafficking or surface presentation is untested\",\n        \"Whether complex assembly is regulated (e.g. by redox state or oligomerization) is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"It remains unknown whether PfJ23 is functionally required for PfEMP1 export, cytoadherence, or parasite virulence in vivo.\",\n      \"evidence\": \"No gene-disruption, conditional knockdown, or phenotypic study of PF3D7_1001900 is present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No loss-of-function genetics for PfJ23\",\n        \"No demonstration that PfJ23 is required for PfEMP1 surface display or cytoadherence\",\n        \"No structural map of the two binding interfaces\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [1, 2, 3]},\n      {\"term_id\": \"GO:0042803\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020030\", \"supporting_discovery_ids\": [1]},\n      {\"term_id\": \"GO:0033644\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0046903\", \"supporting_discovery_ids\": [3]}\n    ],\n    \"complexes\": [\n      \"PfJ23–PfSBP1–PfEMP1(cytoplasmic tail) trimeric complex (in vitro) [#3]\"\n    ],\n    \"partners\": [\n      \"PfSBP1 (skeleton binding protein 1) [#1]\",\n      \"PfEMP1 cytoplasmic tail [#2]\"\n    ],\n    \"other_free_text\": [\n      \"PfJ23 (PF3D7_1001900) is a PEXEL-positive exported protein; mostly α-helical with redox-dependent oligomeric states [#0]\",\n      \"Harbors distinct, non-overlapping binding sites for PfSBP1 and the PfEMP1 cytoplasmic tail, enabling simultaneous engagement [#3]\",\n      \"All current evidence derives from a single study using recombinant/native proteins and immunofluorescence; no loss-of-function or in vivo functional data for PF3D7_1001900 exist in the corpus\"\n    ]\n  }\n}\n```","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1001900","name":null,"product":"Plasmodium exported protein (hyp16), unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"PfJ23","evaluation":null}