{"gene":"TG_309100","gene_symbol":"PEX3","run_date":"2026-09-08T15:15:13","timeline":{"discoveries":[{"year":2017,"finding":"Bioinformatic analysis identified a complete set of peroxins (including PEX3) in Toxoplasma gondii and other Coccidia, consistent with peroxisome biogenesis, division, and protein import machinery being present; life cycle stage-specific presence of peroxisomes in T. gondii was suggested.","method":"Bioinformatic/genomic screening for peroxins and peroxisomal targeting signals (PTS1/PTS2) across apicomplexan genomes","journal":"Genome biology and evolution","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational prediction only, no experimental validation of PEX3 protein function performed","pmids":["29126146"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2025,"finding":"Host cell peroxisomal biogenesis factor 3 (PEX3) physically interacts with T. gondii dense granule protein GRA23, as validated by pull-down/mass spectrometry, bimolecular fluorescence complementation (BiFC), and co-immunoprecipitation (Co-IP), suggesting parasite-mediated modulation of host peroxisomal functions.","method":"Pull-down assay coupled with mass spectrometry, bimolecular fluorescence complementation (BiFC), co-immunoprecipitation (Co-IP)","journal":"Frontiers in veterinary science","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — multiple orthogonal binding assays (pulldown-MS, BiFC, Co-IP) in a single study, but no functional consequence of the interaction experimentally demonstrated","pmids":["40417354"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"T. gondii PEX3 is predicted by genomic evidence to function as a peroxin involved in peroxisome biogenesis, and the host ortholog of PEX3 has been shown to physically interact with the parasite dense granule protein GRA23, suggesting the parasite may exploit or modulate host peroxisomal functions during infection; no direct in vivo or in vitro functional characterization of the T. gondii PEX3 protein itself has been reported."},"narrative":{"mechanistic_narrative":"PEX3 is predicted to be a peroxin of the peroxisome biogenesis machinery in Toxoplasma gondii, identified as part of a complete set of peroxins recovered by bioinformatic screening of apicomplexan genomes, consistent with the presence of peroxisome biogenesis, division, and protein import machinery in Coccidia [PMID:29126146]. No direct experimental characterization of the T. gondii PEX3 protein itself has been reported in the available corpus. In a distinct host-directed context, host cell PEX3 physically interacts with the T. gondii dense granule protein GRA23, as shown by pull-down/mass spectrometry, bimolecular fluorescence complementation, and co-immunoprecipitation, indicating the parasite may engage host peroxisomal factors during infection [PMID:40417354]. The functional consequences of this interaction and any activity of the parasite's own PEX3 remain uncharacterized in the available corpus.","teleology":[{"year":2017,"claim":"Whether T. gondii possesses the genetic capacity for peroxisome biogenesis was unknown; genomic screening established that a complete peroxin set, including PEX3, is present, placing PEX3 within a candidate peroxisome biogenesis pathway.","evidence":"Bioinformatic/genomic screening for peroxins and PTS1/PTS2 targeting signals across apicomplexan genomes","pmids":["29126146"],"confidence":"Low","gaps":["Computational prediction only; no experimental validation of T. gondii PEX3 protein function or localization","Whether peroxisomes are actually assembled at any life cycle stage is not demonstrated","No demonstrated role for PEX3 in parasite biology"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2025,"claim":"Whether the parasite engages host peroxisomal machinery was unaddressed; identification of a physical interaction between host PEX3 and the parasite dense granule protein GRA23 established a candidate parasite-host interface at the peroxisome.","evidence":"Pull-down/mass spectrometry, BiFC, and Co-IP in a single study","pmids":["40417354"],"confidence":"Medium","gaps":["No functional consequence of the PEX3-GRA23 interaction demonstrated","Interaction is with host PEX3, not the parasite's own PEX3 ortholog","Whether host peroxisomal function is modulated during infection is untested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical activity, localization, and in vivo role of the T. gondii PEX3 protein itself remain unknown, as does the functional outcome of the host PEX3-GRA23 interaction.","evidence":"No direct functional study of parasite PEX3 reported in the corpus","pmids":[],"confidence":"Low","gaps":["No knockout, knockdown, or rescue of T. gondii PEX3","No demonstration of peroxisome assembly or PEX3 localization in the parasite","No functional readout linking the host PEX3-GRA23 interaction to infection outcome"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["GRA23 (HOST PEX3 INTERACTS WITH PARASITE DENSE GRANULE PROTEIN GRA23)"],"other_free_text":["PEX3 identified computationally as part of a complete peroxin set in T. gondii and other Coccidia [#0].","Host cell PEX3, not the parasite ortholog, is the protein shown to bind parasite GRA23 [#1]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"29126146","id":"PMC_29126146","title":"Genomic and Proteomic Evidence for the Presence of a Peroxisome in the Apicomplexan Parasite Toxoplasma gondii and Other Coccidia.","date":"2017","source":"Genome biology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/29126146","citation_count":17,"is_preprint":false},{"pmid":"40417354","id":"PMC_40417354","title":"Molecular interactions of Toxoplasma gondii dense granule 23 (GRA23) with host proteins PEX3 and TRAP1.","date":"2025","source":"Frontiers in veterinary science","url":"https://pubmed.ncbi.nlm.nih.gov/40417354","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3287,"output_tokens":661,"usd":0.009888,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5381,"output_tokens":1500,"usd":0.032203,"stage2_stop_reason":"end_turn"},"total_usd":0.042091,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"Bioinformatic analysis identified a complete set of peroxins (including PEX3) in Toxoplasma gondii and other Coccidia, consistent with peroxisome biogenesis, division, and protein import machinery being present; life cycle stage-specific presence of peroxisomes in T. gondii was suggested.\",\n      \"method\": \"Bioinformatic/genomic screening for peroxins and peroxisomal targeting signals (PTS1/PTS2) across apicomplexan genomes\",\n      \"journal\": \"Genome biology and evolution\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational prediction only, no experimental validation of PEX3 protein function performed\",\n      \"pmids\": [\"29126146\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"Host cell peroxisomal biogenesis factor 3 (PEX3) physically interacts with T. gondii dense granule protein GRA23, as validated by pull-down/mass spectrometry, bimolecular fluorescence complementation (BiFC), and co-immunoprecipitation (Co-IP), suggesting parasite-mediated modulation of host peroxisomal functions.\",\n      \"method\": \"Pull-down assay coupled with mass spectrometry, bimolecular fluorescence complementation (BiFC), co-immunoprecipitation (Co-IP)\",\n      \"journal\": \"Frontiers in veterinary science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — multiple orthogonal binding assays (pulldown-MS, BiFC, Co-IP) in a single study, but no functional consequence of the interaction experimentally demonstrated\",\n      \"pmids\": [\"40417354\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"T. gondii PEX3 is predicted by genomic evidence to function as a peroxin involved in peroxisome biogenesis, and the host ortholog of PEX3 has been shown to physically interact with the parasite dense granule protein GRA23, suggesting the parasite may exploit or modulate host peroxisomal functions during infection; no direct in vivo or in vitro functional characterization of the T. gondii PEX3 protein itself has been reported.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PEX3 is predicted to be a peroxin of the peroxisome biogenesis machinery in Toxoplasma gondii, identified as part of a complete set of peroxins recovered by bioinformatic screening of apicomplexan genomes, consistent with the presence of peroxisome biogenesis, division, and protein import machinery in Coccidia [#0]. No direct experimental characterization of the T. gondii PEX3 protein itself has been reported in the available corpus. In a distinct host-directed context, host cell PEX3 physically interacts with the T. gondii dense granule protein GRA23, as shown by pull-down/mass spectrometry, bimolecular fluorescence complementation, and co-immunoprecipitation, indicating the parasite may engage host peroxisomal factors during infection [#1]. The functional consequences of this interaction and any activity of the parasite's own PEX3 remain uncharacterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Whether T. gondii possesses the genetic capacity for peroxisome biogenesis was unknown; genomic screening established that a complete peroxin set, including PEX3, is present, placing PEX3 within a candidate peroxisome biogenesis pathway.\",\n      \"evidence\": \"Bioinformatic/genomic screening for peroxins and PTS1/PTS2 targeting signals across apicomplexan genomes\",\n      \"pmids\": [\"29126146\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational prediction only; no experimental validation of T. gondii PEX3 protein function or localization\",\n        \"Whether peroxisomes are actually assembled at any life cycle stage is not demonstrated\",\n        \"No demonstrated role for PEX3 in parasite biology\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Whether the parasite engages host peroxisomal machinery was unaddressed; identification of a physical interaction between host PEX3 and the parasite dense granule protein GRA23 established a candidate parasite-host interface at the peroxisome.\",\n      \"evidence\": \"Pull-down/mass spectrometry, BiFC, and Co-IP in a single study\",\n      \"pmids\": [\"40417354\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional consequence of the PEX3-GRA23 interaction demonstrated\",\n        \"Interaction is with host PEX3, not the parasite's own PEX3 ortholog\",\n        \"Whether host peroxisomal function is modulated during infection is untested\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity, localization, and in vivo role of the T. gondii PEX3 protein itself remain unknown, as does the functional outcome of the host PEX3-GRA23 interaction.\",\n      \"evidence\": \"No direct functional study of parasite PEX3 reported in the corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No knockout, knockdown, or rescue of T. gondii PEX3\",\n        \"No demonstration of peroxisome assembly or PEX3 localization in the parasite\",\n        \"No functional readout linking the host PEX3-GRA23 interaction to infection outcome\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007031\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"GRA23 (host PEX3 interacts with parasite dense granule protein GRA23)\"],\n    \"other_free_text\": [\n      \"PEX3 identified computationally as part of a complete peroxin set in T. gondii and other Coccidia [#0].\",\n      \"Host cell PEX3, not the parasite ortholog, is the protein shown to bind parasite GRA23 [#1].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_309100","name":"PEX3","product":"peroxisomal biogenesis factor 3, putative","uniprot_acc":"A0A125YZQ1","chromosome":"TGME49_chrXI","start_pos":499403},{"strain":"GT1","gene_id":"TGGT1_309100","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrXI","start_pos":462313},{"strain":"RH88","gene_id":"TGRH88_048810","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023092","start_pos":538585},{"strain":"VEG","gene_id":"TGVEG_309100","name":null,"product":"peroxin-3","uniprot_acc":"B6KA01","chromosome":"TGVEG_chrXI","start_pos":507280}]}