{"gene":"TG_225790","gene_symbol":"TRXL2","run_date":"2026-09-08T11:06:44","timeline":{"discoveries":[{"year":2013,"finding":"TrxL2 is a component of a multi-protein complex that coats the cortical microtubules of Toxoplasma gondii, identified by coimmunoprecipitation of TrxL1-associated proteins. TrxL2 is a close homolog of TrxL1 and was found as a novel member of this cortical microtubule-associated complex.","method":"Coimmunoprecipitation (Co-IP) followed by mass spectrometry to identify TrxL1-associated complex members","journal":"Eukaryotic cell","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single Co-IP/MS identification of TrxL2 as complex member; no direct functional or structural characterization of TrxL2 itself in this paper","pmids":["23873863"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"finding":"Cryo-EM single-particle analysis of cortical microtubules determined ex vivo structure and identified TrxL2 (together with TrxL1 and SPM1) as a bona fide microtubule inner protein (MIP). TrxL2, TrxL1, and SPM1 form a mesh on the luminal surface of cortical microtubules and simultaneously stabilize the tubulin lattice in both longitudinal and lateral directions. Deletion of these MIPs (including TrxL2) compromises microtubule stability and integrity under chemical challenge.","method":"Single-particle cryo-EM structure determination of ex vivo cortical microtubules; genetic deletion of MIPs with chemical stability assays (detergent/cold treatment)","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 1 / Strong — near-atomic cryo-EM structure with functional validation by MIP deletion and stability phenotype, multiple orthogonal methods in a single rigorous study","pmids":["34031406"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TrxL2 is a microtubule inner protein (MIP) that, together with TrxL1 and SPM1, forms a luminal mesh on the cortical microtubules of Toxoplasma gondii, simultaneously stabilizing the tubulin lattice in longitudinal and lateral directions; it is recruited to the cortical microtubules as part of a multi-protein complex, and its deletion compromises microtubule stability under detergent and cold challenge."},"narrative":{"mechanistic_narrative":"TrxL2 is a microtubule inner protein (MIP) that lines the luminal surface of the cortical microtubules of Toxoplasma gondii, where it stabilizes the tubulin lattice [PMID:34031406]. It was first identified as a novel member of a multi-protein complex coating the cortical microtubules, recovered through coimmunoprecipitation of TrxL1-associated proteins, to which it is a close homolog [PMID:23873863]. Cryo-EM of ex vivo cortical microtubules established TrxL2, together with TrxL1 and SPM1, as bona fide MIPs that form a mesh on the luminal microtubule surface and simultaneously reinforce the lattice in both longitudinal and lateral directions [PMID:34031406]. Genetic deletion of these MIPs, including TrxL2, compromises microtubule stability and integrity under detergent and cold challenge, defining its role in cortical microtubule robustness [PMID:34031406]. Beyond its structural role as a lattice-stabilizing MIP, no additional biochemical activity of TrxL2 has been characterized in the available corpus.","teleology":[{"year":2013,"claim":"Establishing whether TrxL2 associates with the cortical cytoskeleton, its identification as a member of the TrxL1-associated cortical microtubule complex placed it physically within a microtubule-coating assembly.","evidence":"Coimmunoprecipitation of TrxL1-associated proteins followed by mass spectrometry in Toxoplasma gondii","pmids":["23873863"],"confidence":"Medium","gaps":["Single Co-IP/MS identification without reciprocal validation or direct functional characterization of TrxL2","Does not resolve whether TrxL2 binds microtubules directly or indirectly via the complex","No localization defined at the luminal versus outer microtubule surface"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2021,"claim":"To determine where TrxL2 sits on the microtubule and what it contributes structurally, cryo-EM resolved it as a luminal microtubule inner protein and deletion assays showed it is required for lattice stability.","evidence":"Single-particle cryo-EM of ex vivo cortical microtubules plus genetic MIP deletion with detergent/cold stability assays in Toxoplasma gondii","pmids":["34031406"],"confidence":"High","gaps":["Individual contribution of TrxL2 versus TrxL1 and SPM1 to the stabilizing mesh is not separated","Mechanism of TrxL2 recruitment into the microtubule lumen is unknown","Whether TrxL2 retains any thioredoxin-like enzymatic activity is not addressed"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How TrxL2 is targeted into the microtubule lumen and whether it has any biochemical activity beyond its structural MIP role remain open.","evidence":"","pmids":[],"confidence":"High","gaps":["No recruitment or assembly mechanism defined","No enzymatic or redox activity tested","Contribution to parasite morphology or motility not established in the corpus"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TrxL1/TrxL2/SPM1 cortical microtubule inner protein (MIP) mesh"],"partners":["TRXL1","SPM1"],"other_free_text":["TrxL2 is a close homolog of TrxL1 [#0].","TrxL2 is a microtubule inner protein (MIP) lining the luminal surface of cortical microtubules and stabilizes the tubulin lattice in longitudinal and lateral directions [#1].","Deletion of TrxL2 (with the other MIPs) reduces cortical microtubule stability under detergent and cold challenge [#1]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"34031406","id":"PMC_34031406","title":"Cryo-EM structure of cortical microtubules from human parasite Toxoplasma gondii identifies their microtubule inner proteins.","date":"2021","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/34031406","citation_count":64,"is_preprint":false},{"pmid":"23873863","id":"PMC_23873863","title":"Novel thioredoxin-like proteins are components of a protein complex coating the cortical microtubules of Toxoplasma gondii.","date":"2013","source":"Eukaryotic cell","url":"https://pubmed.ncbi.nlm.nih.gov/23873863","citation_count":48,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3387,"output_tokens":731,"usd":0.010563,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5449,"output_tokens":1793,"usd":0.036035,"stage2_stop_reason":"end_turn"},"total_usd":0.046598,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"TrxL2 is a component of a multi-protein complex that coats the cortical microtubules of Toxoplasma gondii, identified by coimmunoprecipitation of TrxL1-associated proteins. TrxL2 is a close homolog of TrxL1 and was found as a novel member of this cortical microtubule-associated complex.\",\n      \"method\": \"Coimmunoprecipitation (Co-IP) followed by mass spectrometry to identify TrxL1-associated complex members\",\n      \"journal\": \"Eukaryotic cell\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single Co-IP/MS identification of TrxL2 as complex member; no direct functional or structural characterization of TrxL2 itself in this paper\",\n      \"pmids\": [\"23873863\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Cryo-EM single-particle analysis of cortical microtubules determined ex vivo structure and identified TrxL2 (together with TrxL1 and SPM1) as a bona fide microtubule inner protein (MIP). TrxL2, TrxL1, and SPM1 form a mesh on the luminal surface of cortical microtubules and simultaneously stabilize the tubulin lattice in both longitudinal and lateral directions. Deletion of these MIPs (including TrxL2) compromises microtubule stability and integrity under chemical challenge.\",\n      \"method\": \"Single-particle cryo-EM structure determination of ex vivo cortical microtubules; genetic deletion of MIPs with chemical stability assays (detergent/cold treatment)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — near-atomic cryo-EM structure with functional validation by MIP deletion and stability phenotype, multiple orthogonal methods in a single rigorous study\",\n      \"pmids\": [\"34031406\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TrxL2 is a microtubule inner protein (MIP) that, together with TrxL1 and SPM1, forms a luminal mesh on the cortical microtubules of Toxoplasma gondii, simultaneously stabilizing the tubulin lattice in longitudinal and lateral directions; it is recruited to the cortical microtubules as part of a multi-protein complex, and its deletion compromises microtubule stability under detergent and cold challenge.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TrxL2 is a microtubule inner protein (MIP) that lines the luminal surface of the cortical microtubules of Toxoplasma gondii, where it stabilizes the tubulin lattice [#1]. It was first identified as a novel member of a multi-protein complex coating the cortical microtubules, recovered through coimmunoprecipitation of TrxL1-associated proteins, to which it is a close homolog [#0]. Cryo-EM of ex vivo cortical microtubules established TrxL2, together with TrxL1 and SPM1, as bona fide MIPs that form a mesh on the luminal microtubule surface and simultaneously reinforce the lattice in both longitudinal and lateral directions [#1]. Genetic deletion of these MIPs, including TrxL2, compromises microtubule stability and integrity under detergent and cold challenge, defining its role in cortical microtubule robustness [#1]. Beyond its structural role as a lattice-stabilizing MIP, no additional biochemical activity of TrxL2 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2013,\n      \"claim\": \"Establishing whether TrxL2 associates with the cortical cytoskeleton, its identification as a member of the TrxL1-associated cortical microtubule complex placed it physically within a microtubule-coating assembly.\",\n      \"evidence\": \"Coimmunoprecipitation of TrxL1-associated proteins followed by mass spectrometry in Toxoplasma gondii\",\n      \"pmids\": [\"23873863\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Single Co-IP/MS identification without reciprocal validation or direct functional characterization of TrxL2\",\n        \"Does not resolve whether TrxL2 binds microtubules directly or indirectly via the complex\",\n        \"No localization defined at the luminal versus outer microtubule surface\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2021,\n      \"claim\": \"To determine where TrxL2 sits on the microtubule and what it contributes structurally, cryo-EM resolved it as a luminal microtubule inner protein and deletion assays showed it is required for lattice stability.\",\n      \"evidence\": \"Single-particle cryo-EM of ex vivo cortical microtubules plus genetic MIP deletion with detergent/cold stability assays in Toxoplasma gondii\",\n      \"pmids\": [\"34031406\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Individual contribution of TrxL2 versus TrxL1 and SPM1 to the stabilizing mesh is not separated\",\n        \"Mechanism of TrxL2 recruitment into the microtubule lumen is unknown\",\n        \"Whether TrxL2 retains any thioredoxin-like enzymatic activity is not addressed\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How TrxL2 is targeted into the microtubule lumen and whether it has any biochemical activity beyond its structural MIP role remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No recruitment or assembly mechanism defined\",\n        \"No enzymatic or redox activity tested\",\n        \"Contribution to parasite morphology or motility not established in the corpus\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008017\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0005200\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005874\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0046785\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"TrxL1/TrxL2/SPM1 cortical microtubule inner protein (MIP) mesh\"],\n    \"partners\": [\"TrxL1\", \"SPM1\"],\n    \"other_free_text\": [\n      \"TrxL2 is a close homolog of TrxL1 [#0].\",\n      \"TrxL2 is a microtubule inner protein (MIP) lining the luminal surface of cortical microtubules and stabilizes the tubulin lattice in longitudinal and lateral directions [#1].\",\n      \"Deletion of TrxL2 (with the other MIPs) reduces cortical microtubule stability under detergent and cold challenge [#1].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_225790","name":"TRXL2","product":"thioredoxin-like protein 2","uniprot_acc":"A0A125YFI4","chromosome":"TGME49_chrX","start_pos":2038359},{"strain":"GT1","gene_id":"TGGT1_225790","name":null,"product":"PDI family protein","uniprot_acc":null,"chromosome":"TGGT1_chrX","start_pos":1946861},{"strain":"RH88","gene_id":"TGRH88_045420","name":null,"product":"PDI family protein","uniprot_acc":null,"chromosome":"CM023091","start_pos":5529307},{"strain":"VEG","gene_id":"TGVEG_225790","name":null,"product":"PDI family protein","uniprot_acc":"B9PMI4","chromosome":"TGVEG_chrX","start_pos":1938606}]}