{"gene":"TG_261780","gene_symbol":"MIC7","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2002,"finding":"TgMIC7 is a transmembrane microneme protein containing multiple EGF-like domains, a transmembrane-spanning domain, and a short cytoplasmic tail; sorting signals to the micronemes are encoded in this short cytoplasmic tail.","method":"Characterization of protein topology and mutational analysis of cytoplasmic tail sorting signals; localization by immunofluorescence/subcellular fractionation","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization experiments and domain characterization in a single focused study with multiple orthogonal approaches","pmids":["11861763"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2002,"finding":"TgMIC7 gene expression is predominantly in bradyzoites (not tachyzoites), suggesting it functions as an escorter in the bradyzoite stage analogously to how TgMIC6 and TgMIC8 function in tachyzoites.","method":"Stage-specific gene expression analysis (transcriptional profiling of tachyzoite vs. bradyzoite stages)","journal":"Journal of cell science","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, expression-based inference with no direct functional experiment on MIC7 escorter activity in bradyzoites","pmids":["11861763"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"MIC7 is N-myristoylated at its N-terminus, and this myristoylated N-terminus faces the lumen of the micronemes, indicating that MIC7 enters the secretory pathway in an unconventional fashion with a luminally-oriented lipid modification.","method":"Chemoproteomic N-myristoylation profiling (metabolic labeling with alkyne-myristic acid analogue followed by click chemistry and mass spectrometry) combined with topology analysis","journal":"eLife","confidence":"High","confidence_rationale":"Tier 1 / Moderate — chemoproteomic identification of myristoylation with topology determination in a single rigorous study using multiple orthogonal methods","pmids":["32618271"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"finding":"MIC7 and its N-myristoylation play a crucial role in the initial steps of host cell invasion, likely during interaction with and penetration of the host cell membrane.","method":"Genetic loss-of-function (knockout or conditional depletion of MIC7) combined with mutagenesis of the myristoylation site, with invasion/penetration phenotypic readout","journal":"eLife","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined invasion phenotype and myristoylation-site mutagenesis in a single lab study","pmids":["32618271"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgMIC7 is a bradyzoite-expressed transmembrane microneme protein with EGF-like domains whose cytoplasmic tail encodes microneme-targeting sorting signals; it is uniquely N-myristoylated at its luminally-oriented N-terminus via an unconventional secretory pathway entry, and both MIC7 and its myristoylation are required for the initial steps of host cell invasion/penetration, likely functioning as an escorter in the bradyzoite stage."},"narrative":{"mechanistic_narrative":"TgMIC7 is a transmembrane microneme protein of Toxoplasma gondii that participates in the initial steps of host cell invasion [PMID:11861763, PMID:32618271]. Its ectodomain contains multiple EGF-like domains and is anchored by a transmembrane-spanning segment, while its short cytoplasmic tail encodes the sorting signals that direct the protein to the micronemes [PMID:11861763]. MIC7 is N-myristoylated at its N-terminus, and this lipidated N-terminus is oriented toward the microneme lumen, indicating an unconventional entry into the secretory pathway that places a lipid modification on the luminal face [PMID:32618271]. Both MIC7 and its N-myristoylation are required for efficient host cell invasion, acting during the interaction with and penetration of the host cell membrane [PMID:32618271]. Beyond these findings, the molecular partners and precise biochemical mechanism of MIC7 have not been characterized in the available corpus.","teleology":[{"year":2002,"claim":"Established MIC7 as a bona fide microneme protein and defined how it is trafficked, answering where the protein resides and what directs it there.","evidence":"Protein topology characterization and mutational analysis of the cytoplasmic tail with immunofluorescence/subcellular fractionation in T. gondii","pmids":["11861763"],"confidence":"Medium","gaps":["The specific sorting-machinery components that recognize the cytoplasmic tail were not identified","No functional role for the EGF-like domains was tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2002,"claim":"Placed MIC7 in the bradyzoite stage, framing it as a potential stage-specific escorter analogous to tachyzoite MIC6/MIC8.","evidence":"Stage-specific transcriptional profiling of tachyzoite versus bradyzoite stages in T. gondii","pmids":["11861763"],"confidence":"Low","gaps":["Escorter activity was inferred from expression and analogy, not demonstrated by any direct functional experiment","No bradyzoite-stage invasion phenotype was measured","Cargo escorted by MIC7, if any, was not identified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"Revealed that MIC7 carries a luminally-oriented N-myristoyl modification, answering how a lipid-modified microneme protein enters the secretory pathway and pointing to an unconventional trafficking route.","evidence":"Chemoproteomic N-myristoylation profiling (metabolic labeling with alkyne-myristate, click chemistry, mass spectrometry) combined with topology analysis in T. gondii","pmids":["32618271"],"confidence":"High","gaps":["The enzyme(s) and mechanism producing luminal orientation of the myristoyl group are not defined","How the lipid modification affects trafficking or folding was not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2020,"claim":"Demonstrated that MIC7 and its myristoylation are functionally required for invasion, connecting the protein and its lipid modification to the entry step of the parasite lifecycle.","evidence":"Genetic loss-of-function (knockout/conditional depletion) plus myristoylation-site mutagenesis with invasion/penetration readout in T. gondii","pmids":["32618271"],"confidence":"Medium","gaps":["The molecular event during membrane penetration that MIC7 mediates was not identified","Host-cell binding partners or interacting parasite proteins were not defined","Whether the invasion role operates in bradyzoites specifically was not tested"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The direct binding partners, escorted cargo, and biochemical function of MIC7 during membrane penetration remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No molecular partner or receptor for MIC7 has been identified","The proposed escorter activity has not been directly tested","No structural model of the EGF-domain ectodomain exists in the corpus"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["Contains multiple EGF-like domains, a transmembrane-spanning domain, and a short cytoplasmic tail carrying microneme-sorting signals [#0]","Predominantly expressed in the bradyzoite stage; proposed to act as a stage-specific escorter analogous to tachyzoite MIC6/MIC8 [#1]","N-terminal myristoyl group faces the microneme lumen, implying unconventional secretory-pathway entry [#2]","MIC7 and its N-myristoylation are required for the initial steps of host cell invasion/membrane penetration [#3]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"11861763","id":"PMC_11861763","title":"A family of transmembrane microneme proteins of Toxoplasma gondii contain EGF-like domains and function as escorters.","date":"2002","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/11861763","citation_count":135,"is_preprint":false},{"pmid":"32618271","id":"PMC_32618271","title":"Profiling of myristoylation in Toxoplasma gondii reveals an N-myristoylated protein important for host cell penetration.","date":"2020","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/32618271","citation_count":25,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3381,"output_tokens":1056,"usd":0.012991,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5967,"output_tokens":2293,"usd":0.04358,"stage2_stop_reason":"end_turn"},"total_usd":0.056571,"stage1_batch_id":"msgbatch_015xmQKDRqnTh9anE4m7LiD6","stage2_batch_id":"msgbatch_01JLpkFTVhoQBNgqHCKFrVVU","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2002,\n      \"finding\": \"TgMIC7 is a transmembrane microneme protein containing multiple EGF-like domains, a transmembrane-spanning domain, and a short cytoplasmic tail; sorting signals to the micronemes are encoded in this short cytoplasmic tail.\",\n      \"method\": \"Characterization of protein topology and mutational analysis of cytoplasmic tail sorting signals; localization by immunofluorescence/subcellular fractionation\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization experiments and domain characterization in a single focused study with multiple orthogonal approaches\",\n      \"pmids\": [\"11861763\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"TgMIC7 gene expression is predominantly in bradyzoites (not tachyzoites), suggesting it functions as an escorter in the bradyzoite stage analogously to how TgMIC6 and TgMIC8 function in tachyzoites.\",\n      \"method\": \"Stage-specific gene expression analysis (transcriptional profiling of tachyzoite vs. bradyzoite stages)\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, expression-based inference with no direct functional experiment on MIC7 escorter activity in bradyzoites\",\n      \"pmids\": [\"11861763\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"MIC7 is N-myristoylated at its N-terminus, and this myristoylated N-terminus faces the lumen of the micronemes, indicating that MIC7 enters the secretory pathway in an unconventional fashion with a luminally-oriented lipid modification.\",\n      \"method\": \"Chemoproteomic N-myristoylation profiling (metabolic labeling with alkyne-myristic acid analogue followed by click chemistry and mass spectrometry) combined with topology analysis\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — chemoproteomic identification of myristoylation with topology determination in a single rigorous study using multiple orthogonal methods\",\n      \"pmids\": [\"32618271\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"MIC7 and its N-myristoylation play a crucial role in the initial steps of host cell invasion, likely during interaction with and penetration of the host cell membrane.\",\n      \"method\": \"Genetic loss-of-function (knockout or conditional depletion of MIC7) combined with mutagenesis of the myristoylation site, with invasion/penetration phenotypic readout\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined invasion phenotype and myristoylation-site mutagenesis in a single lab study\",\n      \"pmids\": [\"32618271\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgMIC7 is a bradyzoite-expressed transmembrane microneme protein with EGF-like domains whose cytoplasmic tail encodes microneme-targeting sorting signals; it is uniquely N-myristoylated at its luminally-oriented N-terminus via an unconventional secretory pathway entry, and both MIC7 and its myristoylation are required for the initial steps of host cell invasion/penetration, likely functioning as an escorter in the bradyzoite stage.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgMIC7 is a transmembrane microneme protein of Toxoplasma gondii that participates in the initial steps of host cell invasion [#0, #3]. Its ectodomain contains multiple EGF-like domains and is anchored by a transmembrane-spanning segment, while its short cytoplasmic tail encodes the sorting signals that direct the protein to the micronemes [#0]. MIC7 is N-myristoylated at its N-terminus, and this lipidated N-terminus is oriented toward the microneme lumen, indicating an unconventional entry into the secretory pathway that places a lipid modification on the luminal face [#2]. Both MIC7 and its N-myristoylation are required for efficient host cell invasion, acting during the interaction with and penetration of the host cell membrane [#3]. Beyond these findings, the molecular partners and precise biochemical mechanism of MIC7 have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2002,\n      \"claim\": \"Established MIC7 as a bona fide microneme protein and defined how it is trafficked, answering where the protein resides and what directs it there.\",\n      \"evidence\": \"Protein topology characterization and mutational analysis of the cytoplasmic tail with immunofluorescence/subcellular fractionation in T. gondii\",\n      \"pmids\": [\"11861763\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The specific sorting-machinery components that recognize the cytoplasmic tail were not identified\",\n        \"No functional role for the EGF-like domains was tested\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Placed MIC7 in the bradyzoite stage, framing it as a potential stage-specific escorter analogous to tachyzoite MIC6/MIC8.\",\n      \"evidence\": \"Stage-specific transcriptional profiling of tachyzoite versus bradyzoite stages in T. gondii\",\n      \"pmids\": [\"11861763\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Escorter activity was inferred from expression and analogy, not demonstrated by any direct functional experiment\",\n        \"No bradyzoite-stage invasion phenotype was measured\",\n        \"Cargo escorted by MIC7, if any, was not identified\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Revealed that MIC7 carries a luminally-oriented N-myristoyl modification, answering how a lipid-modified microneme protein enters the secretory pathway and pointing to an unconventional trafficking route.\",\n      \"evidence\": \"Chemoproteomic N-myristoylation profiling (metabolic labeling with alkyne-myristate, click chemistry, mass spectrometry) combined with topology analysis in T. gondii\",\n      \"pmids\": [\"32618271\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The enzyme(s) and mechanism producing luminal orientation of the myristoyl group are not defined\",\n        \"How the lipid modification affects trafficking or folding was not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrated that MIC7 and its myristoylation are functionally required for invasion, connecting the protein and its lipid modification to the entry step of the parasite lifecycle.\",\n      \"evidence\": \"Genetic loss-of-function (knockout/conditional depletion) plus myristoylation-site mutagenesis with invasion/penetration readout in T. gondii\",\n      \"pmids\": [\"32618271\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular event during membrane penetration that MIC7 mediates was not identified\",\n        \"Host-cell binding partners or interacting parasite proteins were not defined\",\n        \"Whether the invasion role operates in bradyzoites specifically was not tested\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct binding partners, escorted cargo, and biochemical function of MIC7 during membrane penetration remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No molecular partner or receptor for MIC7 has been identified\",\n        \"The proposed escorter activity has not been directly tested\",\n        \"No structural model of the EGF-domain ectodomain exists in the corpus\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0018377\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0016020\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0006886\", \"supporting_discovery_ids\": [0, 2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"Contains multiple EGF-like domains, a transmembrane-spanning domain, and a short cytoplasmic tail carrying microneme-sorting signals [#0]\",\n      \"Predominantly expressed in the bradyzoite stage; proposed to act as a stage-specific escorter analogous to tachyzoite MIC6/MIC8 [#1]\",\n      \"N-terminal myristoyl group faces the microneme lumen, implying unconventional secretory-pathway entry [#2]\",\n      \"MIC7 and its N-myristoylation are required for the initial steps of host cell invasion/membrane penetration [#3]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_261780","name":"MIC7","product":"microneme protein MIC7","uniprot_acc":"A0A125YX17","chromosome":"TGME49_chrVIIb","start_pos":1530296},{"strain":"GT1","gene_id":"TGGT1_261780","name":null,"product":"microneme protein MIC7","uniprot_acc":null,"chromosome":"TGGT1_chrVIIb","start_pos":1506043},{"strain":"RH88","gene_id":"TGRH88_068940","name":null,"product":"microneme protein MIC7","uniprot_acc":null,"chromosome":"CM023089","start_pos":1550855},{"strain":"VEG","gene_id":"TGVEG_261780","name":null,"product":"microneme protein MIC7","uniprot_acc":"A0A125YX19","chromosome":"TGVEG_chrVIIb","start_pos":1546723}]}