{"gene":"TG_204530","gene_symbol":"MIC11","run_date":"2026-09-08T11:06:14","timeline":{"discoveries":[{"year":2004,"finding":"TgMIC11 is a novel 16 kDa microneme protein that undergoes proteolytic maturation by two successive cleavages to remove an internal propeptide, resulting in a mature protein consisting of an alpha-chain and beta-chain tethered by a single disulfide bond.","method":"Biochemical characterization, proteolytic processing analysis, dual staining immunofluorescence","journal":"International journal for parasitology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (biochemical processing assays, immunofluorescence, structural characterization) in a focused mechanistic study","pmids":["15313131"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2004,"finding":"TgMIC11 localizes to the apical micronemes and is secreted in a calcium-dependent manner, consistent with a role in the early stages of host cell invasion.","method":"Dual staining immunofluorescence, calcium-dependent secretion assay","journal":"International journal for parasitology","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct localization experiment with functional context, calcium-dependent secretion confirmed experimentally","pmids":["15313131"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2026,"finding":"MIC11 is essential for PLP1-dependent host cell membrane permeabilization and parasite egress; deletion of MIC11 causes severe defects in membrane rupture and egress, and mechanistic analyses support a physical association between MIC11 and PLP1.","method":"CRISPR-based in vivo fitness screen, gene deletion (loss-of-function), scanning mutagenesis, mechanistic interaction analyses (MIC11–PLP1 association)","journal":"Nature communications","confidence":"High","confidence_rationale":"Tier 2 / Strong — CRISPR deletion with defined egress phenotype plus scanning mutagenesis identifying functional motifs plus demonstrated MIC11–PLP1 association, all in one rigorous study","pmids":["41935076"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2026,"finding":"The merozoite-specific paralogue MIC22 functionally complements MIC11 deletion, suggesting a conserved egress mechanism in the feline-restricted stages of T. gondii.","method":"Genetic complementation assay (MIC22 rescuing MIC11 deletion phenotype)","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional complementation demonstrated in a single study with a defined readout, but limited to abstract-level detail","pmids":["41935076"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgMIC11 is a soluble microneme protein that undergoes calcium-dependent secretion and proteolytic maturation (removal of an internal propeptide to yield a disulfide-linked alpha/beta-chain heterodimer); it is essential for PLP1-dependent host cell membrane permeabilization during parasite egress, acting through a direct association with PLP1, with functional motifs identified by scanning mutagenesis."},"narrative":{"mechanistic_narrative":"TgMIC11 is a soluble apical microneme protein of Toxoplasma gondii that functions in the parasite lytic cycle, undergoing calcium-dependent secretion and proteolytic maturation [PMID:15313131]. The 16 kDa protein is matured by two successive cleavages that remove an internal propeptide, yielding an alpha-chain and beta-chain held together by a single disulfide bond [PMID:15313131]. Functionally, MIC11 is essential for PLP1-dependent permeabilization of the host cell membrane during parasite egress: its deletion causes severe defects in membrane rupture and egress, and it acts through a direct physical association with PLP1, with functional motifs mapped by scanning mutagenesis [PMID:41935076]. The merozoite-specific paralogue MIC22 complements MIC11 loss, indicating a conserved egress mechanism across the feline-restricted stages [PMID:41935076].","teleology":[{"year":2004,"claim":"Establishing whether MIC11 is a genuine microneme protein and how it is structurally organized defined it as a novel secretory protein processed into a disulfide-linked heterodimer.","evidence":"Biochemical processing assays, structural characterization, and dual-staining immunofluorescence in T. gondii","pmids":["15313131"],"confidence":"High","gaps":["The protease(s) responsible for the two maturation cleavages were not identified","The functional consequence of the alpha/beta heterodimer architecture was not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2004,"claim":"Determining the subcellular localization and secretion behavior placed MIC11 at the apical micronemes and showed calcium-dependent release, consistent with an early host-interaction role.","evidence":"Dual-staining immunofluorescence and calcium-dependent secretion assay in T. gondii","pmids":["15313131"],"confidence":"High","gaps":["No molecular binding partner or substrate was identified at this stage","The specific step of the lytic cycle requiring MIC11 was not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2026,"claim":"Assigning a loss-of-function phenotype and a binding partner revealed MIC11 as an essential effector of PLP1-mediated host membrane permeabilization during egress rather than solely an invasion factor.","evidence":"CRISPR fitness screen, gene deletion, scanning mutagenesis, and MIC11–PLP1 interaction analyses in T. gondii","pmids":["41935076"],"confidence":"High","gaps":["The structural basis of the MIC11–PLP1 association is not resolved","How MIC11 mechanistically potentiates PLP1 membrane rupture is not defined","Whether the disulfide-linked mature form is the species that engages PLP1 is not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2026,"claim":"Testing paralogue redundancy showed the merozoite-specific MIC22 can substitute for MIC11, indicating the egress function is conserved across feline-restricted stages.","evidence":"Genetic complementation assay in which MIC22 rescues the MIC11 deletion phenotype in T. gondii","pmids":["41935076"],"confidence":"Medium","gaps":["Detail limited to abstract-level reporting","Whether MIC22 engages PLP1 through the same motifs as MIC11 is not shown","The physiological role of MIC22 in the natural merozoite stage was not directly tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The precise molecular mechanism by which MIC11 promotes PLP1-driven membrane permeabilization, and the structural determinants of the interaction, remain unresolved.","evidence":"","pmids":[],"confidence":"High","gaps":["No structural model of the MIC11–PLP1 complex","Identity of the maturation proteases unknown","Whether MIC11 acts before, during, or after PLP1 membrane insertion is undefined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["PLP1","MIC22 (FUNCTIONAL PARALOGUE)"],"other_free_text":["16 kDa microneme protein matured by two successive proteolytic cleavages removing an internal propeptide [#0]","Mature form is a disulfide-linked alpha-chain/beta-chain heterodimer [#0]","Secreted in a calcium-dependent manner from apical micronemes [#1]","Essential for PLP1-dependent host membrane permeabilization and parasite egress; functional motifs mapped by scanning mutagenesis [#2]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"23749087","id":"PMC_23749087","title":"Protective immunity induced by a DNA vaccine-encoding Toxoplasma gondii microneme protein 11 against acute toxoplasmosis in BALB/c mice.","date":"2013","source":"Parasitology research","url":"https://pubmed.ncbi.nlm.nih.gov/23749087","citation_count":30,"is_preprint":false},{"pmid":"15313131","id":"PMC_15313131","title":"The novel coccidian micronemal protein MIC11 undergoes proteolytic maturation by sequential cleavage to remove an internal propeptide.","date":"2004","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15313131","citation_count":22,"is_preprint":false},{"pmid":"24646180","id":"PMC_24646180","title":"Identification of genes expressed during Toxoplasma gondii infection by in vivo-induced antigen technology (IVIAT) with positive porcine sera.","date":"2014","source":"The Journal of parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/24646180","citation_count":4,"is_preprint":false},{"pmid":"41935076","id":"PMC_41935076","title":"An in vivo fitness gene of Toxoplasma, MIC11, is essential for PLP1-mediated egress from host cells.","date":"2026","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/41935076","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4370,"output_tokens":977,"usd":0.013883,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5900,"output_tokens":2114,"usd":0.041175,"stage2_stop_reason":"end_turn"},"total_usd":0.055058,"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\": 2004,\n      \"finding\": \"TgMIC11 is a novel 16 kDa microneme protein that undergoes proteolytic maturation by two successive cleavages to remove an internal propeptide, resulting in a mature protein consisting of an alpha-chain and beta-chain tethered by a single disulfide bond.\",\n      \"method\": \"Biochemical characterization, proteolytic processing analysis, dual staining immunofluorescence\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (biochemical processing assays, immunofluorescence, structural characterization) in a focused mechanistic study\",\n      \"pmids\": [\"15313131\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"TgMIC11 localizes to the apical micronemes and is secreted in a calcium-dependent manner, consistent with a role in the early stages of host cell invasion.\",\n      \"method\": \"Dual staining immunofluorescence, calcium-dependent secretion assay\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct localization experiment with functional context, calcium-dependent secretion confirmed experimentally\",\n      \"pmids\": [\"15313131\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"MIC11 is essential for PLP1-dependent host cell membrane permeabilization and parasite egress; deletion of MIC11 causes severe defects in membrane rupture and egress, and mechanistic analyses support a physical association between MIC11 and PLP1.\",\n      \"method\": \"CRISPR-based in vivo fitness screen, gene deletion (loss-of-function), scanning mutagenesis, mechanistic interaction analyses (MIC11–PLP1 association)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — CRISPR deletion with defined egress phenotype plus scanning mutagenesis identifying functional motifs plus demonstrated MIC11–PLP1 association, all in one rigorous study\",\n      \"pmids\": [\"41935076\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"The merozoite-specific paralogue MIC22 functionally complements MIC11 deletion, suggesting a conserved egress mechanism in the feline-restricted stages of T. gondii.\",\n      \"method\": \"Genetic complementation assay (MIC22 rescuing MIC11 deletion phenotype)\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional complementation demonstrated in a single study with a defined readout, but limited to abstract-level detail\",\n      \"pmids\": [\"41935076\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgMIC11 is a soluble microneme protein that undergoes calcium-dependent secretion and proteolytic maturation (removal of an internal propeptide to yield a disulfide-linked alpha/beta-chain heterodimer); it is essential for PLP1-dependent host cell membrane permeabilization during parasite egress, acting through a direct association with PLP1, with functional motifs identified by scanning mutagenesis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgMIC11 is a soluble apical microneme protein of Toxoplasma gondii that functions in the parasite lytic cycle, undergoing calcium-dependent secretion and proteolytic maturation [#0, #1]. The 16 kDa protein is matured by two successive cleavages that remove an internal propeptide, yielding an alpha-chain and beta-chain held together by a single disulfide bond [#0]. Functionally, MIC11 is essential for PLP1-dependent permeabilization of the host cell membrane during parasite egress: its deletion causes severe defects in membrane rupture and egress, and it acts through a direct physical association with PLP1, with functional motifs mapped by scanning mutagenesis [#2]. The merozoite-specific paralogue MIC22 complements MIC11 loss, indicating a conserved egress mechanism across the feline-restricted stages [#3].\",\n  \"teleology\": [\n    {\n      \"year\": 2004,\n      \"claim\": \"Establishing whether MIC11 is a genuine microneme protein and how it is structurally organized defined it as a novel secretory protein processed into a disulfide-linked heterodimer.\",\n      \"evidence\": \"Biochemical processing assays, structural characterization, and dual-staining immunofluorescence in T. gondii\",\n      \"pmids\": [\"15313131\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The protease(s) responsible for the two maturation cleavages were not identified\",\n        \"The functional consequence of the alpha/beta heterodimer architecture was not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Determining the subcellular localization and secretion behavior placed MIC11 at the apical micronemes and showed calcium-dependent release, consistent with an early host-interaction role.\",\n      \"evidence\": \"Dual-staining immunofluorescence and calcium-dependent secretion assay in T. gondii\",\n      \"pmids\": [\"15313131\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No molecular binding partner or substrate was identified at this stage\",\n        \"The specific step of the lytic cycle requiring MIC11 was not established\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Assigning a loss-of-function phenotype and a binding partner revealed MIC11 as an essential effector of PLP1-mediated host membrane permeabilization during egress rather than solely an invasion factor.\",\n      \"evidence\": \"CRISPR fitness screen, gene deletion, scanning mutagenesis, and MIC11\\u2013PLP1 interaction analyses in T. gondii\",\n      \"pmids\": [\"41935076\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The structural basis of the MIC11\\u2013PLP1 association is not resolved\",\n        \"How MIC11 mechanistically potentiates PLP1 membrane rupture is not defined\",\n        \"Whether the disulfide-linked mature form is the species that engages PLP1 is not established\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Testing paralogue redundancy showed the merozoite-specific MIC22 can substitute for MIC11, indicating the egress function is conserved across feline-restricted stages.\",\n      \"evidence\": \"Genetic complementation assay in which MIC22 rescues the MIC11 deletion phenotype in T. gondii\",\n      \"pmids\": [\"41935076\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Detail limited to abstract-level reporting\",\n        \"Whether MIC22 engages PLP1 through the same motifs as MIC11 is not shown\",\n        \"The physiological role of MIC22 in the natural merozoite stage was not directly tested\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise molecular mechanism by which MIC11 promotes PLP1-driven membrane permeabilization, and the structural determinants of the interaction, remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No structural model of the MIC11\\u2013PLP1 complex\",\n        \"Identity of the maturation proteases unknown\",\n        \"Whether MIC11 acts before, during, or after PLP1 membrane insertion is undefined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005515\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0051715\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"PLP1\", \"MIC22 (functional paralogue)\"],\n    \"other_free_text\": [\n      \"16 kDa microneme protein matured by two successive proteolytic cleavages removing an internal propeptide [#0]\",\n      \"Mature form is a disulfide-linked alpha-chain/beta-chain heterodimer [#0]\",\n      \"Secreted in a calcium-dependent manner from apical micronemes [#1]\",\n      \"Essential for PLP1-dependent host membrane permeabilization and parasite egress; functional motifs mapped by scanning mutagenesis [#2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_204530","name":"MIC11","product":"microneme protein MIC11","uniprot_acc":"A0A125YJF8","chromosome":"TGME49_chrVIIa","start_pos":1730526},{"strain":"GT1","gene_id":"TGGT1_204530","name":null,"product":"microneme protein MIC11","uniprot_acc":null,"chromosome":"TGGT1_chrVIIa","start_pos":1632334},{"strain":"RH88","gene_id":"TGRH88_034580","name":null,"product":"microneme protein MIC11","uniprot_acc":null,"chromosome":"CM023088","start_pos":1821973},{"strain":"VEG","gene_id":"TGVEG_204530","name":null,"product":"microneme protein MIC11","uniprot_acc":"B9PUW8","chromosome":"TGVEG_chrVIIa","start_pos":1814036}]}