{"gene":"TG_297120","gene_symbol":"IMC44","run_date":"2026-09-08T18:09:50+00:00","timeline":{"discoveries":[{"year":2023,"finding":"IMC44 is a novel daughter IMC protein whose localization at specific stages of endodyogeny is regulated by IMC43; depletion of IMC43 causes mislocalization of IMC44.","method":"Auxin-inducible degron (AID) depletion of IMC43 combined with localization assays of IMC44","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — AID knockdown with defined localization phenotype and two orthogonal methods (TurboID proximity labelling + yeast two-hybrid) in a single lab","pmids":["37782662"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"IMC44 physically interacts with the C-terminal domain of IMC43, as determined by pairwise yeast two-hybrid assays; the C-terminal domain of IMC43 is sufficient for this binding.","method":"Yeast two-hybrid (pairwise assay) and TurboID proximity labelling","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal interaction methods (TurboID + yeast two-hybrid), single lab","pmids":["37782662"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"finding":"IMC44 is recruited to daughter buds as part of an IMC43-IMC32-IMC44 bud assembly complex that forms the foundation of the daughter IMC during endodyogeny.","method":"TurboID proximity labelling, yeast two-hybrid, AID-mediated depletion with localization and morphology readouts","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal methods (TurboID, Y2H, AID) in a single lab establishing complex membership and pathway placement","pmids":["37782662"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"IMC44 is a novel daughter inner membrane complex (IMC) protein in Toxoplasma gondii that is recruited to nascent daughter buds during endodyogeny as part of a bud assembly complex; its proper localization depends on the essential C-terminal domain of IMC43, which directly binds IMC44 and coordinates its recruitment alongside IMC32 to form the foundational scaffold of the daughter IMC."},"narrative":{"mechanistic_narrative":"IMC44 is a daughter-specific inner membrane complex (IMC) protein in Toxoplasma gondii that is recruited to nascent daughter buds during endodyogeny as part of a foundational bud assembly complex [PMID:37782662]. It is incorporated into the daughter IMC together with IMC43 and IMC32, and its proper stage-specific localization depends on IMC43: depletion of IMC43 causes IMC44 to mislocalize [PMID:37782662]. IMC44 physically binds the C-terminal domain of IMC43, which is sufficient for this interaction, indicating that IMC43 directly coordinates IMC44 recruitment during bud formation [PMID:37782662]. Beyond its role as a component of this IMC43-IMC32-IMC44 assembly complex, no further biochemical activity or independent function of IMC44 has been characterized in the available corpus.","teleology":[{"year":2023,"claim":"Establishing that IMC44 is a bona fide daughter IMC protein whose recruitment is not autonomous answered whether it is an independent structural element or a downstream client of an organizing factor.","evidence":"Auxin-inducible degron depletion of IMC43 with localization assays of IMC44 in Toxoplasma gondii","pmids":["37782662"],"confidence":"Medium","gaps":["Whether IMC44 has any function or stability independent of IMC43 is not resolved","The consequence of IMC44 loss itself (its own depletion phenotype) is not established","The stage of endodyogeny at which IMC44 acts is only partially defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"Mapping a direct IMC44-IMC43 interaction to the IMC43 C-terminal domain answered how IMC44 is coordinated, showing the recruitment reflects a specific physical binding rather than mere co-localization.","evidence":"Pairwise yeast two-hybrid assays plus TurboID proximity labelling in Toxoplasma gondii","pmids":["37782662"],"confidence":"Medium","gaps":["The IMC44 residues/domain that contact IMC43 are not mapped","No structural model of the interaction","Whether the interaction is direct or bridged is not fully excluded (Y2H is heterologous)"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2023,"claim":"Placing IMC44 within an IMC43-IMC32-IMC44 bud assembly complex answered where in daughter IMC biogenesis it acts, defining it as part of the foundational scaffold laid down early in bud formation.","evidence":"TurboID proximity labelling, yeast two-hybrid, and AID depletion with localization and morphology readouts in Toxoplasma gondii","pmids":["37782662"],"confidence":"Medium","gaps":["The specific molecular contribution of IMC44 to scaffold assembly versus IMC32/IMC43 is not distinguished","The order of recruitment within the complex is not resolved","No cross-strain or in vivo confirmation of the complex"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The intrinsic molecular activity of IMC44 and its own loss-of-function phenotype remain unknown.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No IMC44-specific depletion phenotype reported","No biochemical or enzymatic activity assigned to IMC44","No structural or interface-level characterization of its binding to IMC43"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["IMC43-IMC32-IMC44 daughter bud assembly complex"],"partners":["IMC43 (BINDS VIA IMC43 C-TERMINAL DOMAIN)","IMC32"],"other_free_text":["IMC44 is a daughter IMC protein recruited during endodyogeny; its stage-specific localization depends on IMC43.","IMC44 binds the C-terminal domain of IMC43, which is sufficient for the interaction."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"37782662","id":"PMC_37782662","title":"Identification of IMC43, a novel IMC protein that collaborates with IMC32 to form an essential daughter bud assembly complex in Toxoplasma gondii.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/37782662","citation_count":11,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2947,"output_tokens":776,"usd":0.01024,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5548,"output_tokens":1880,"usd":0.03737,"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},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"IMC44 is a novel daughter IMC protein whose localization at specific stages of endodyogeny is regulated by IMC43; depletion of IMC43 causes mislocalization of IMC44.\",\n      \"method\": \"Auxin-inducible degron (AID) depletion of IMC43 combined with localization assays of IMC44\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — AID knockdown with defined localization phenotype and two orthogonal methods (TurboID proximity labelling + yeast two-hybrid) in a single lab\",\n      \"pmids\": [\"37782662\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"IMC44 physically interacts with the C-terminal domain of IMC43, as determined by pairwise yeast two-hybrid assays; the C-terminal domain of IMC43 is sufficient for this binding.\",\n      \"method\": \"Yeast two-hybrid (pairwise assay) and TurboID proximity labelling\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal interaction methods (TurboID + yeast two-hybrid), single lab\",\n      \"pmids\": [\"37782662\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"IMC44 is recruited to daughter buds as part of an IMC43-IMC32-IMC44 bud assembly complex that forms the foundation of the daughter IMC during endodyogeny.\",\n      \"method\": \"TurboID proximity labelling, yeast two-hybrid, AID-mediated depletion with localization and morphology readouts\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal methods (TurboID, Y2H, AID) in a single lab establishing complex membership and pathway placement\",\n      \"pmids\": [\"37782662\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"IMC44 is a novel daughter inner membrane complex (IMC) protein in Toxoplasma gondii that is recruited to nascent daughter buds during endodyogeny as part of a bud assembly complex; its proper localization depends on the essential C-terminal domain of IMC43, which directly binds IMC44 and coordinates its recruitment alongside IMC32 to form the foundational scaffold of the daughter IMC.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"IMC44 is a daughter-specific inner membrane complex (IMC) protein in Toxoplasma gondii that is recruited to nascent daughter buds during endodyogeny as part of a foundational bud assembly complex [#0, #2]. It is incorporated into the daughter IMC together with IMC43 and IMC32, and its proper stage-specific localization depends on IMC43: depletion of IMC43 causes IMC44 to mislocalize [#0, #2]. IMC44 physically binds the C-terminal domain of IMC43, which is sufficient for this interaction, indicating that IMC43 directly coordinates IMC44 recruitment during bud formation [#1]. Beyond its role as a component of this IMC43-IMC32-IMC44 assembly complex, no further biochemical activity or independent function of IMC44 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Establishing that IMC44 is a bona fide daughter IMC protein whose recruitment is not autonomous answered whether it is an independent structural element or a downstream client of an organizing factor.\",\n      \"evidence\": \"Auxin-inducible degron depletion of IMC43 with localization assays of IMC44 in Toxoplasma gondii\",\n      \"pmids\": [\"37782662\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Whether IMC44 has any function or stability independent of IMC43 is not resolved\",\n        \"The consequence of IMC44 loss itself (its own depletion phenotype) is not established\",\n        \"The stage of endodyogeny at which IMC44 acts is only partially defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Mapping a direct IMC44-IMC43 interaction to the IMC43 C-terminal domain answered how IMC44 is coordinated, showing the recruitment reflects a specific physical binding rather than mere co-localization.\",\n      \"evidence\": \"Pairwise yeast two-hybrid assays plus TurboID proximity labelling in Toxoplasma gondii\",\n      \"pmids\": [\"37782662\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The IMC44 residues/domain that contact IMC43 are not mapped\",\n        \"No structural model of the interaction\",\n        \"Whether the interaction is direct or bridged is not fully excluded (Y2H is heterologous)\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Placing IMC44 within an IMC43-IMC32-IMC44 bud assembly complex answered where in daughter IMC biogenesis it acts, defining it as part of the foundational scaffold laid down early in bud formation.\",\n      \"evidence\": \"TurboID proximity labelling, yeast two-hybrid, and AID depletion with localization and morphology readouts in Toxoplasma gondii\",\n      \"pmids\": [\"37782662\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The specific molecular contribution of IMC44 to scaffold assembly versus IMC32/IMC43 is not distinguished\",\n        \"The order of recruitment within the complex is not resolved\",\n        \"No cross-strain or in vivo confirmation of the complex\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The intrinsic molecular activity of IMC44 and its own loss-of-function phenotype remain unknown.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No IMC44-specific depletion phenotype reported\",\n        \"No biochemical or enzymatic activity assigned to IMC44\",\n        \"No structural or interface-level characterization of its binding to IMC43\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0070258\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0000281\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\n      \"IMC43-IMC32-IMC44 daughter bud assembly complex\"\n    ],\n    \"partners\": [\n      \"IMC43 (binds via IMC43 C-terminal domain)\",\n      \"IMC32\"\n    ],\n    \"other_free_text\": [\n      \"IMC44 is a daughter IMC protein recruited during endodyogeny; its stage-specific localization depends on IMC43.\",\n      \"IMC44 binds the C-terminal domain of IMC43, which is sufficient for the interaction.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_297120","name":"IMC44","product":"inner membrane complex protein IMC44","uniprot_acc":"S8FBD0","chromosome":"TGME49_chrII","start_pos":1549864},{"strain":"GT1","gene_id":"TGGT1_297120","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrII","start_pos":1525947},{"strain":"RH88","gene_id":"TGRH88_001980","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023083","start_pos":1725906},{"strain":"VEG","gene_id":"TGVEG_297120","name":null,"product":"hypothetical protein","uniprot_acc":"V4YNY2","chromosome":"TGVEG_chrII","start_pos":1558874}]}