{"gene":"TG_305930","gene_symbol":"ISC4","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2016,"finding":"ISC4 was used as bait for proximity-dependent biotin identification (BioID) at the IMC sutures, demonstrating biotin-dependent labeling of the sutures and identifying two new ISC proteins and five transverse suture-specific proteins (TSCs), establishing ISC4 as a component of the IMC sutures that localizes to both transverse and longitudinal sutures.","method":"Proximity-dependent biotin identification (BioID) using ISC4 as bait, followed by fluorescence microscopy validation","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — BioID proximity labeling with ISC4 as bait, single lab, validated by microscopy localization","pmids":["27696623"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"ISC4 is a component of the Toxoplasma gondii inner membrane complex (IMC) sutures, localizing to both transverse and longitudinal sutures, and has been used as a BioID bait to define the suture proteome including identification of transverse suture-specific proteins (TSCs); however, its precise molecular function beyond structural suture occupancy has not been experimentally established."},"narrative":{"mechanistic_narrative":"ISC4 is a component of the inner membrane complex (IMC) sutures of Toxoplasma gondii, localizing to both the transverse and longitudinal sutures [PMID:27696623]. Deployed as a BioID bait, ISC4 defined the suture proteome, driving identification of two additional ISC proteins and five transverse suture-specific proteins (TSCs) [PMID:27696623]. Beyond this structural suture occupancy, no molecular function for ISC4 has been characterized in the available corpus.","teleology":[{"year":2016,"claim":"Establishing where an uncharacterized IMC-associated protein resides and what it neighbors was needed to place it in the parasite cytoskeletal architecture; using ISC4 as a BioID bait localized it to both transverse and longitudinal sutures and mapped its proximal proteome.","evidence":"Proximity-dependent biotin identification (BioID) with ISC4 as bait plus fluorescence microscopy validation in Toxoplasma gondii","pmids":["27696623"],"confidence":"Medium","gaps":["The molecular function of ISC4 beyond structural suture occupancy is not established","Whether ISC4 is required for suture integrity, parasite viability, or division is not tested","Direct binding partners versus mere proximity-labeled neighbors are not distinguished"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical activity of ISC4 and its functional contribution to suture assembly or parasite fitness remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No enzymatic or structural activity assigned","No loss-of-function phenotype characterized","No direct interaction partners validated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TWO ISC PROTEINS (BIOID-PROXIMAL)","FIVE TRANSVERSE SUTURE-SPECIFIC PROTEINS (TSCS, BIOID-PROXIMAL)"],"other_free_text":["Used as a BioID bait to define the IMC suture proteome [#0]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"27696623","id":"PMC_27696623","title":"Novel insights into the composition and function of the Toxoplasma IMC sutures.","date":"2016","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/27696623","citation_count":59,"is_preprint":false},{"pmid":"27548677","id":"PMC_27548677","title":"Virus-Like Nanoparticle Vaccine Confers Protection against Toxoplasma gondii.","date":"2016","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/27548677","citation_count":33,"is_preprint":false},{"pmid":"21829561","id":"PMC_21829561","title":"Subcellular antigen location influences T-cell activation during acute infection with Toxoplasma gondii.","date":"2011","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/21829561","citation_count":33,"is_preprint":false},{"pmid":"25088010","id":"PMC_25088010","title":"Identification and characterization of Toxoplasma SIP, a conserved apicomplexan cytoskeleton protein involved in maintaining the shape, motility and virulence of the parasite.","date":"2014","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/25088010","citation_count":28,"is_preprint":false},{"pmid":"27586039","id":"PMC_27586039","title":"Cross-protection induced by Toxoplasma gondii virus-like particle vaccine upon intraperitoneal route challenge.","date":"2016","source":"Acta tropica","url":"https://pubmed.ncbi.nlm.nih.gov/27586039","citation_count":15,"is_preprint":false},{"pmid":"34634933","id":"PMC_34634933","title":"A Novel Toxoplasma Inner Membrane Complex Suture-Associated Protein Regulates Suture Protein Targeting and Colocalizes with Membrane Trafficking Machinery.","date":"2021","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/34634933","citation_count":12,"is_preprint":false},{"pmid":"40801525","id":"PMC_40801525","title":"Co-dependent formation of the Toxoplasma gondii subpellicular microtubules and inner membrane skeleton.","date":"2025","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/40801525","citation_count":11,"is_preprint":false},{"pmid":"19820829","id":"PMC_19820829","title":"Toxoplasma gondii: further studies on the subpellicular network.","date":"2009","source":"Memorias do Instituto Oswaldo Cruz","url":"https://pubmed.ncbi.nlm.nih.gov/19820829","citation_count":11,"is_preprint":false},{"pmid":"38270431","id":"PMC_38270431","title":"Apical annuli are specialised sites of post-invasion secretion of dense granules in Toxoplasma.","date":"2024","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/38270431","citation_count":10,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":23418,"output_tokens":368,"usd":0.037887,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4967,"output_tokens":1014,"usd":0.025093,"stage2_stop_reason":"end_turn"},"total_usd":0.0,"stage1_batch_id":"msgbatch_01WgHz6kceqm573AGLyz57at","stage2_batch_id":"msgbatch_01LK4wDYj5zYquahv7gi9893","note":"batch pricing = 50% of standard","skipped":true,"corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"paper list: removed papers about other genes"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"ISC4 was used as bait for proximity-dependent biotin identification (BioID) at the IMC sutures, demonstrating biotin-dependent labeling of the sutures and identifying two new ISC proteins and five transverse suture-specific proteins (TSCs), establishing ISC4 as a component of the IMC sutures that localizes to both transverse and longitudinal sutures.\",\n      \"method\": \"Proximity-dependent biotin identification (BioID) using ISC4 as bait, followed by fluorescence microscopy validation\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — BioID proximity labeling with ISC4 as bait, single lab, validated by microscopy localization\",\n      \"pmids\": [\"27696623\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"ISC4 is a component of the Toxoplasma gondii inner membrane complex (IMC) sutures, localizing to both transverse and longitudinal sutures, and has been used as a BioID bait to define the suture proteome including identification of transverse suture-specific proteins (TSCs); however, its precise molecular function beyond structural suture occupancy has not been experimentally established.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"ISC4 is a component of the inner membrane complex (IMC) sutures of Toxoplasma gondii, localizing to both the transverse and longitudinal sutures [#0]. Deployed as a BioID bait, ISC4 defined the suture proteome, driving identification of two additional ISC proteins and five transverse suture-specific proteins (TSCs) [#0]. Beyond this structural suture occupancy, no molecular function for ISC4 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2016,\n      \"claim\": \"Establishing where an uncharacterized IMC-associated protein resides and what it neighbors was needed to place it in the parasite cytoskeletal architecture; using ISC4 as a BioID bait localized it to both transverse and longitudinal sutures and mapped its proximal proteome.\",\n      \"evidence\": \"Proximity-dependent biotin identification (BioID) with ISC4 as bait plus fluorescence microscopy validation in Toxoplasma gondii\",\n      \"pmids\": [\n        \"27696623\"\n      ],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular function of ISC4 beyond structural suture occupancy is not established\",\n        \"Whether ISC4 is required for suture integrity, parasite viability, or division is not tested\",\n        \"Direct binding partners versus mere proximity-labeled neighbors are not distinguished\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of ISC4 and its functional contribution to suture assembly or parasite fitness remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No enzymatic or structural activity assigned\",\n        \"No loss-of-function phenotype characterized\",\n        \"No direct interaction partners validated\"\n      ],\n      \"attribution\": [\n        {\n          \"species\": \"Toxoplasma gondii\",\n          \"strain\": \"\"\n        }\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\n        \"term_id\": \"IMC sutures (transverse and longitudinal)\",\n        \"supporting_discovery_ids\": [0],\n        \"attribution\": [\n          {\n            \"species\": \"Toxoplasma gondii\",\n            \"strain\": \"\"\n          }\n        ]\n      }\n    ],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [\n      \"Two ISC proteins (BioID-proximal)\",\n      \"Five transverse suture-specific proteins (TSCs, BioID-proximal)\"\n    ],\n    \"other_free_text\": [\n      \"Used as a BioID bait to define the IMC suture proteome [#0]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_305930","name":"ISC4","product":"IMC sutures component ISC4","uniprot_acc":"A0A125YFD7","chromosome":"TGME49_chrIX","start_pos":5675687},{"strain":"GT1","gene_id":"TGGT1_305930","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrIX","start_pos":5457389},{"strain":"RH88","gene_id":"TGRH88_017490","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023090","start_pos":5799006},{"strain":"VEG","gene_id":"TGVEG_305930","name":null,"product":"hypothetical protein","uniprot_acc":"B6KR92","chromosome":"TGVEG_chrIX","start_pos":5714449}]}