{"gene":"PF3D7_1401200","run_date":"2026-09-08T14:19:06","timeline":{"discoveries":[{"year":2021,"finding":"PF3D7_1401200 physically associates with all members of the RhopH complex (CLAG3, RhopH2, RhopH3) in the infected red blood cell compartment, showing the strongest association among 13 tested exported proteins in reciprocal immunoprecipitation assays.","method":"Reciprocal immunoprecipitation / co-immunoprecipitation and mass spectrometry-based proteomics","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — reciprocal Co-IP supported by MS proteomics, single lab, two orthogonal methods confirming the interaction","pmids":["33774908"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"finding":"Conditional knockdown of PF3D7_1401200 had no effect on sorbitol uptake, indicating it is not individually required for new permeability pathway (NPP) activity in the red blood cell membrane.","method":"Conditional knockdown with NPP activity assay (sorbitol uptake)","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean conditional KO with defined functional readout (NPP/sorbitol assay), single lab; result is a negative finding for NPP function","pmids":["33774908"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1401200 is a P. falciparum exported protein that physically interacts—most strongly among tested exported proteins—with all three members of the RhopH complex (CLAG3, RhopH2, RhopH3) in the infected red blood cell compartment, but is not individually required for new permeability pathway activity as assessed by sorbitol uptake upon conditional knockdown."},"narrative":{"mechanistic_narrative":"PF3D7_1401200 is a Plasmodium falciparum exported protein that operates in the infected red blood cell compartment as a physical partner of the RhopH complex [PMID:33774908]. In reciprocal immunoprecipitation and mass spectrometry assays, it associated with all three RhopH members—CLAG3, RhopH2, and RhopH3—and showed the strongest association among 13 tested exported proteins, marking it as a prominent RhopH-interacting factor rather than an incidental one [PMID:33774908]. Despite this association, conditional knockdown of PF3D7_1401200 did not alter sorbitol uptake, indicating it is not individually required for new permeability pathway (NPP) activity at the red blood cell membrane [PMID:33774908]. Beyond this RhopH-complex association and the NPP-dispensability result, the corpus establishes no independent molecular function, catalytic activity, or structure for PF3D7_1401200; its role remains defined only through its interaction with the RhopH complex.","teleology":[{"year":2021,"claim":"It was unknown which exported proteins engage the RhopH complex in the host cell; testing a panel of exported proteins established PF3D7_1401200 as the strongest RhopH-associating candidate, placing it in the machinery surrounding CLAG3/RhopH2/RhopH3.","evidence":"Reciprocal co-immunoprecipitation and mass spectrometry across 13 tested exported proteins in P. falciparum-infected red blood cells","pmids":["33774908"],"confidence":"Medium","gaps":["Direct versus indirect binding within the complex not resolved","Interaction interface and stoichiometry unknown","Whether the association is constitutive or stage/condition-dependent not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2021,"claim":"Given the RhopH complex's link to solute transport, the key question was whether PF3D7_1401200 contributes to NPP function; conditional knockdown with no effect on sorbitol uptake showed it is dispensable for NPP activity individually.","evidence":"Conditional knockdown coupled to sorbitol-uptake NPP assay in P. falciparum","pmids":["33774908"],"confidence":"Medium","gaps":["Possible redundancy with other exported partners not excluded","Non-NPP functions of the protein not assessed","Effect of knockdown on RhopH complex assembly, trafficking, or stability not measured"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The intrinsic molecular function of PF3D7_1401200 and the purpose of its strong RhopH association remain undefined.","evidence":"No further experimental characterization present in the corpus","pmids":[],"confidence":"Medium","gaps":["No molecular activity or substrate identified","No structural model or domain assignment","Functional consequence of the RhopH interaction for the parasite unknown"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["RhopH complex (CLAG3, RhopH2, RhopH3) — physical association only [#0]"],"partners":["CLAG3 [#0]","RHOPH2 [#0]","RHOPH3 [#0]"],"other_free_text":["Exported protein localizing to the infected red blood cell compartment [#0]","Not individually required for new permeability pathway (NPP) activity by sorbitol uptake upon conditional knockdown [#1]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"33774908","id":"PMC_33774908","title":"Characterisation of complexes formed by parasite proteins exported into the host cell compartment of Plasmodium falciparum infected red blood cells.","date":"2021","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/33774908","citation_count":23,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3295,"output_tokens":577,"usd":0.00927,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5101,"output_tokens":1417,"usd":0.030465,"stage2_stop_reason":"end_turn"},"total_usd":0.039735,"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\": 2021,\n      \"finding\": \"PF3D7_1401200 physically associates with all members of the RhopH complex (CLAG3, RhopH2, RhopH3) in the infected red blood cell compartment, showing the strongest association among 13 tested exported proteins in reciprocal immunoprecipitation assays.\",\n      \"method\": \"Reciprocal immunoprecipitation / co-immunoprecipitation and mass spectrometry-based proteomics\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — reciprocal Co-IP supported by MS proteomics, single lab, two orthogonal methods confirming the interaction\",\n      \"pmids\": [\"33774908\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"finding\": \"Conditional knockdown of PF3D7_1401200 had no effect on sorbitol uptake, indicating it is not individually required for new permeability pathway (NPP) activity in the red blood cell membrane.\",\n      \"year\": 2021,\n      \"method\": \"Conditional knockdown with NPP activity assay (sorbitol uptake)\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean conditional KO with defined functional readout (NPP/sorbitol assay), single lab; result is a negative finding for NPP function\",\n      \"pmids\": [\"33774908\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1401200 is a P. falciparum exported protein that physically interacts—most strongly among tested exported proteins—with all three members of the RhopH complex (CLAG3, RhopH2, RhopH3) in the infected red blood cell compartment, but is not individually required for new permeability pathway activity as assessed by sorbitol uptake upon conditional knockdown.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1401200 is a Plasmodium falciparum exported protein that operates in the infected red blood cell compartment as a physical partner of the RhopH complex [#0]. In reciprocal immunoprecipitation and mass spectrometry assays, it associated with all three RhopH members\\u2014CLAG3, RhopH2, and RhopH3\\u2014and showed the strongest association among 13 tested exported proteins, marking it as a prominent RhopH-interacting factor rather than an incidental one [#0]. Despite this association, conditional knockdown of PF3D7_1401200 did not alter sorbitol uptake, indicating it is not individually required for new permeability pathway (NPP) activity at the red blood cell membrane [#1]. Beyond this RhopH-complex association and the NPP-dispensability result, the corpus establishes no independent molecular function, catalytic activity, or structure for PF3D7_1401200; its role remains defined only through its interaction with the RhopH complex.\"\n  ,\n  \"teleology\": [\n    {\n      \"year\": 2021,\n      \"claim\": \"It was unknown which exported proteins engage the RhopH complex in the host cell; testing a panel of exported proteins established PF3D7_1401200 as the strongest RhopH-associating candidate, placing it in the machinery surrounding CLAG3/RhopH2/RhopH3.\",\n      \"evidence\": \"Reciprocal co-immunoprecipitation and mass spectrometry across 13 tested exported proteins in P. falciparum-infected red blood cells\",\n      \"pmids\": [\"33774908\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct versus indirect binding within the complex not resolved\",\n        \"Interaction interface and stoichiometry unknown\",\n        \"Whether the association is constitutive or stage/condition-dependent not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"Given the RhopH complex's link to solute transport, the key question was whether PF3D7_1401200 contributes to NPP function; conditional knockdown with no effect on sorbitol uptake showed it is dispensable for NPP activity individually.\",\n      \"evidence\": \"Conditional knockdown coupled to sorbitol-uptake NPP assay in P. falciparum\",\n      \"pmids\": [\"33774908\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Possible redundancy with other exported partners not excluded\",\n        \"Non-NPP functions of the protein not assessed\",\n        \"Effect of knockdown on RhopH complex assembly, trafficking, or stability not measured\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic molecular function of PF3D7_1401200 and the purpose of its strong RhopH association remain undefined.\",\n      \"evidence\": \"No further experimental characterization present in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No molecular activity or substrate identified\",\n        \"No structural model or domain assignment\",\n        \"Functional consequence of the RhopH interaction for the parasite unknown\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [\"RhopH complex (CLAG3, RhopH2, RhopH3) \\u2014 physical association only [#0]\"],\n    \"partners\": [\"CLAG3 [#0]\", \"RhopH2 [#0]\", \"RhopH3 [#0]\"],\n    \"other_free_text\": [\n      \"Exported protein localizing to the infected red blood cell compartment [#0]\",\n      \"Not individually required for new permeability pathway (NPP) activity by sorbitol uptake upon conditional knockdown [#1]\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1401200","name":null,"product":"Plasmodium exported protein, unknown function","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}