{"gene":"PF3D7_0717900","run_date":"2026-09-08T12:51:27","timeline":{"discoveries":[{"year":2013,"finding":"TRX2 (PF3D7_0717900) is a bona fide component of the PTEX (Plasmodium translocon of exported proteins) complex, validated by genetic tagging and co-localization experiments. Knockout of TRX2 in P. berghei results in reduced growth rates in vivo and in vitro, and reduced capacity to cause severe disease in a cerebral malaria model, demonstrating that TRX2 is important for optimizing PTEX activity but is not essential for parasite survival.","method":"Genetic tagging (epitope tag knock-in), genetic deletion (knockout parasites), in vivo and in vitro growth assays, cerebral malaria mouse model","journal":"Molecular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal validation of complex membership by genetic tagging, loss-of-function knockout with defined phenotypic readouts across multiple assays and models","pmids":["23869529"],"is_preprint":false,"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"finding":"TRX2 (PF3D7_0717900) is expressed not only in asexual blood stages but also in early gametocytes, mosquito stages, and liver stages, consistent with protein export occurring across multiple life-cycle stages.","method":"Expression profiling of PTEX components across life-cycle stages (stage-specific protein detection)","journal":"Molecular microbiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct detection across multiple life stages in a single study, but method details (e.g., Western blot vs. IFA) not fully specified in abstract","pmids":["23869529"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2017,"finding":"TRX2 (PF3D7_0717900), described as a poor substrate for thioredoxin reductase, can be reduced by the glutathione system (glutathione/glutaredoxin pathway) in P. falciparum, demonstrating functional cross-talk between the glutathione and thioredoxin antioxidant systems that may compensate for restricted access to thioredoxin reductase in certain subcellular compartments.","method":"In vitro biochemical assay measuring reduction of thioredoxins by glutathione system components","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — in vitro enzymatic assay establishing a biochemical activity, but single lab and single method","pmids":["28479253"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0717900 (TRX2) is a thioredoxin-like protein that functions as a non-essential but functionally important component of the PTEX export translocon in Plasmodium, where it optimizes parasite growth and virulence; biochemically, it is a poor substrate for thioredoxin reductase but can be reduced by the glutathione system, suggesting cross-talk between antioxidant pathways compensates for its restricted access to canonical reduction machinery."},"narrative":{"mechanistic_narrative":"PF3D7_0717900 (TRX2) is a thioredoxin-like protein that functions as a non-essential but functionally important component of the PTEX (Plasmodium translocon of exported proteins) complex, where it optimizes protein export and parasite virulence [PMID:23869529]. Genetic tagging and co-localization confirm TRX2 as a bona fide PTEX subunit, and its deletion in P. berghei reduces growth rates in vivo and in vitro and attenuates severe disease in a cerebral malaria model, establishing that it tunes PTEX activity without being required for survival [PMID:23869529]. TRX2 is expressed across asexual blood stages, early gametocytes, mosquito stages, and liver stages, consistent with protein export operating throughout the life cycle [PMID:23869529]. Biochemically, TRX2 is a poor substrate for thioredoxin reductase but can be reduced by the glutathione/glutaredoxin system in P. falciparum, indicating cross-talk between the glutathione and thioredoxin antioxidant pathways that may supply reducing equivalents where thioredoxin reductase access is limited [PMID:28479253]. Beyond its role in PTEX and this redox cross-talk, no further mechanistic detail for PF3D7_0717900 has been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Whether TRX2 is genuinely part of the export machinery and whether it is required for parasite viability was unknown; tagging and knockout defined it as a real PTEX subunit that optimizes but is not essential for growth and virulence.","evidence":"Epitope-tag knock-in and co-localization plus genetic knockout with in vivo/in vitro growth assays and a cerebral malaria mouse model","pmids":["23869529"],"confidence":"High","gaps":["The specific biochemical contribution of TRX2 to translocation (e.g. substrate unfolding or disulfide handling) within PTEX is not resolved","No structural placement of TRX2 relative to other PTEX components is defined","Whether the P. berghei knockout phenotype quantitatively matches P. falciparum is not established"],"attribution":[{"species":"Plasmodium berghei","strain":""},{"species":"Plasmodium falciparum","strain":""}]},{"year":2013,"claim":"It was unclear whether TRX2-dependent export is restricted to blood stages; expression profiling showed TRX2 is present across asexual, gametocyte, mosquito, and liver stages, consistent with export throughout the life cycle.","evidence":"Stage-specific protein detection of PTEX components across life-cycle stages","pmids":["23869529"],"confidence":"Medium","gaps":["The detection method (Western vs. IFA) and quantitation are not fully specified","Whether TRX2 is functionally required at each of these stages was not tested"],"attribution":[{"species":"Plasmodium falciparum","strain":""},{"species":"Plasmodium berghei","strain":""}]},{"year":2017,"claim":"How TRX2 is kept reduced was unclear given it is a poor thioredoxin reductase substrate; in vitro assays showed it can instead be reduced by the glutathione system, revealing antioxidant pathway cross-talk.","evidence":"In vitro biochemical assay measuring reduction of thioredoxins by glutathione system components in P. falciparum","pmids":["28479253"],"confidence":"Medium","gaps":["Single lab and single in vitro method; not confirmed in the cellular/PTEX context","The physiological electron donor for TRX2 within the PTEX compartment is not established","The functional consequence of glutathione-mediated reduction for export activity is untested"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The precise catalytic/redox function of TRX2 during protein translocation and how its redox state is regulated in vivo remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No defined in vivo substrate or redox partner of TRX2 within PTEX","No structural or mechanistic model linking its thioredoxin-like activity to translocation","Reduction by the glutathione system not yet demonstrated in the native compartment"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PTEX (Plasmodium translocon of exported proteins)"],"partners":[],"other_free_text":["Non-essential PTEX component whose deletion reduces parasite growth and cerebral malaria severity in P. berghei [#0]","Expressed across asexual blood, early gametocyte, mosquito, and liver stages [#1]","Poor substrate for thioredoxin reductase but reducible by the glutathione/glutaredoxin system in P. falciparum, indicating antioxidant pathway cross-talk [#2]"]}},"prefetch_data":{},"corpus_meta":[{"pmid":"23869529","id":"PMC_23869529","title":"The Plasmodium translocon of exported proteins (PTEX) component thioredoxin-2 is important for maintaining normal blood-stage growth.","date":"2013","source":"Molecular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/23869529","citation_count":72,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["thioredoxin-like protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30514877","id":"PMC_30514877","title":"The origins of malaria artemisinin resistance defined by a genetic and transcriptomic background.","date":"2018","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/30514877","citation_count":42,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["thioredoxin-like protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"28479253","id":"PMC_28479253","title":"Glutathione and thioredoxin systems of the malaria parasite Plasmodium falciparum: Partners in crime?","date":"2017","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/28479253","citation_count":16,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["thioredoxin-like protein"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4002,"output_tokens":975,"usd":0.013315,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5652,"output_tokens":1950,"usd":0.038505,"stage2_stop_reason":"end_turn"},"total_usd":0.05182,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"TRX2 (PF3D7_0717900) is a bona fide component of the PTEX (Plasmodium translocon of exported proteins) complex, validated by genetic tagging and co-localization experiments. Knockout of TRX2 in P. berghei results in reduced growth rates in vivo and in vitro, and reduced capacity to cause severe disease in a cerebral malaria model, demonstrating that TRX2 is important for optimizing PTEX activity but is not essential for parasite survival.\",\n      \"method\": \"Genetic tagging (epitope tag knock-in), genetic deletion (knockout parasites), in vivo and in vitro growth assays, cerebral malaria mouse model\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal validation of complex membership by genetic tagging, loss-of-function knockout with defined phenotypic readouts across multiple assays and models\",\n      \"pmids\": [\"23869529\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"TRX2 (PF3D7_0717900) is expressed not only in asexual blood stages but also in early gametocytes, mosquito stages, and liver stages, consistent with protein export occurring across multiple life-cycle stages.\",\n      \"method\": \"Expression profiling of PTEX components across life-cycle stages (stage-specific protein detection)\",\n      \"journal\": \"Molecular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct detection across multiple life stages in a single study, but method details (e.g., Western blot vs. IFA) not fully specified in abstract\",\n      \"pmids\": [\"23869529\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"TRX2 (PF3D7_0717900), described as a poor substrate for thioredoxin reductase, can be reduced by the glutathione system (glutathione/glutaredoxin pathway) in P. falciparum, demonstrating functional cross-talk between the glutathione and thioredoxin antioxidant systems that may compensate for restricted access to thioredoxin reductase in certain subcellular compartments.\",\n      \"method\": \"In vitro biochemical assay measuring reduction of thioredoxins by glutathione system components\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — in vitro enzymatic assay establishing a biochemical activity, but single lab and single method\",\n      \"pmids\": [\"28479253\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_0717900 (TRX2) is a thioredoxin-like protein that functions as a non-essential but functionally important component of the PTEX export translocon in Plasmodium, where it optimizes parasite growth and virulence; biochemically, it is a poor substrate for thioredoxin reductase but can be reduced by the glutathione system, suggesting cross-talk between antioxidant pathways compensates for its restricted access to canonical reduction machinery.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0717900 (TRX2) is a thioredoxin-like protein that functions as a non-essential but functionally important component of the PTEX (Plasmodium translocon of exported proteins) complex, where it optimizes protein export and parasite virulence [#0]. Genetic tagging and co-localization confirm TRX2 as a bona fide PTEX subunit, and its deletion in P. berghei reduces growth rates in vivo and in vitro and attenuates severe disease in a cerebral malaria model, establishing that it tunes PTEX activity without being required for survival [#0]. TRX2 is expressed across asexual blood stages, early gametocytes, mosquito stages, and liver stages, consistent with protein export operating throughout the life cycle [#1]. Biochemically, TRX2 is a poor substrate for thioredoxin reductase but can be reduced by the glutathione/glutaredoxin system in P. falciparum, indicating cross-talk between the glutathione and thioredoxin antioxidant pathways that may supply reducing equivalents where thioredoxin reductase access is limited [#2]. Beyond its role in PTEX and this redox cross-talk, no further mechanistic detail for PF3D7_0717900 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Whether TRX2 is genuinely part of the export machinery and whether it is required for parasite viability was unknown; tagging and knockout defined it as a real PTEX subunit that optimizes but is not essential for growth and virulence.\",\n      \"evidence\": \"Epitope-tag knock-in and co-localization plus genetic knockout with in vivo/in vitro growth assays and a cerebral malaria mouse model\",\n      \"pmids\": [\"23869529\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The specific biochemical contribution of TRX2 to translocation (e.g. substrate unfolding or disulfide handling) within PTEX is not resolved\",\n        \"No structural placement of TRX2 relative to other PTEX components is defined\",\n        \"Whether the P. berghei knockout phenotype quantitatively matches P. falciparum is not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"It was unclear whether TRX2-dependent export is restricted to blood stages; expression profiling showed TRX2 is present across asexual, gametocyte, mosquito, and liver stages, consistent with export throughout the life cycle.\",\n      \"evidence\": \"Stage-specific protein detection of PTEX components across life-cycle stages\",\n      \"pmids\": [\"23869529\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The detection method (Western vs. IFA) and quantitation are not fully specified\",\n        \"Whether TRX2 is functionally required at each of these stages was not tested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"},\n        {\"species\": \"Plasmodium berghei\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"How TRX2 is kept reduced was unclear given it is a poor thioredoxin reductase substrate; in vitro assays showed it can instead be reduced by the glutathione system, revealing antioxidant pathway cross-talk.\",\n      \"evidence\": \"In vitro biochemical assay measuring reduction of thioredoxins by glutathione system components in P. falciparum\",\n      \"pmids\": [\"28479253\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single lab and single in vitro method; not confirmed in the cellular/PTEX context\",\n        \"The physiological electron donor for TRX2 within the PTEX compartment is not established\",\n        \"The functional consequence of glutathione-mediated reduction for export activity is untested\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise catalytic/redox function of TRX2 during protein translocation and how its redox state is regulated in vivo remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No defined in vivo substrate or redox partner of TRX2 within PTEX\",\n        \"No structural or mechanistic model linking its thioredoxin-like activity to translocation\",\n        \"Reduction by the glutathione system not yet demonstrated in the native compartment\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0015035\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0046903\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"complexes\": [\"PTEX (Plasmodium translocon of exported proteins)\"],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Non-essential PTEX component whose deletion reduces parasite growth and cerebral malaria severity in P. berghei [#0]\",\n      \"Expressed across asexual blood, early gametocyte, mosquito, and liver stages [#1]\",\n      \"Poor substrate for thioredoxin reductase but reducible by the glutathione/glutaredoxin system in P. falciparum, indicating antioxidant pathway cross-talk [#2]\"\n    ]\n  }\n}","audit_flag":{"gene":"PF3D7_0717900","tier":"IDENTITY_CHECK","verdict":"identity unverified","subtype":"names_other_cards","uniprot_band":"","rules_fired":"R12","issue":"No cited paper names this card; 1 of 2 cited papers name other catalogue genes (PF3D7_1105600, PF3D7_1116800, PF3D7_1345100). The summary may describe one of those genes."},"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0717900","name":null,"product":"thioredoxin-like protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0615600","name":null,"product":"thioredoxin-like protein","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0312900","name":null,"product":"thioredoxin-like protein","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"","evaluation":null}