{"gene":"TG_267680","gene_symbol":"MIC12","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2005,"finding":"TgROM2, a rhomboid intramembrane-cleaving serine protease, cleaves chimeric proteins containing the transmembrane domains of TgMIC12, identifying TgMIC12 as a substrate for rhomboid-mediated intramembrane proteolysis during host cell invasion.","method":"In vitro/cell-based cleavage assay using chimeric proteins containing TgMIC12 TM domains as substrates for TgROM2","journal":"International journal for parasitology","confidence":"Medium","confidence_rationale":"Tier 1 / Weak — direct enzymatic cleavage assay demonstrated substrate relationship, but single lab, single method, using chimeric (not native) substrate","pmids":["15913633"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgMIC12 is a microneme transmembrane protein whose transmembrane domain serves as a substrate for the rhomboid intramembrane serine protease TgROM2, implicating it in the proteolytic shedding cascade that facilitates host cell invasion by Toxoplasma gondii."},"narrative":{"mechanistic_narrative":"TgMIC12 is a Toxoplasma gondii microneme transmembrane protein implicated in the intramembrane proteolytic shedding cascade that accompanies host cell invasion [PMID:15913633]. Its transmembrane domain serves as a substrate for the rhomboid intramembrane-cleaving serine protease TgROM2, as demonstrated by cleavage of chimeric reporters bearing the TgMIC12 TM segment [PMID:15913633]. Beyond this single substrate relationship, no further mechanistic detail — including the native protein's function, adhesive partners, or invasion phenotype — has been characterized in the available corpus.","teleology":[{"year":2005,"claim":"To establish which micronemal proteins are processed by parasite rhomboid proteases during invasion, this work tested whether the TgMIC12 transmembrane domain is a cleavage substrate, defining TgMIC12 as part of the rhomboid-mediated shedding cascade.","evidence":"In vitro/cell-based cleavage assay using chimeric proteins carrying TgMIC12 TM domains as substrates for TgROM2, in Toxoplasma gondii","pmids":["15913633"],"confidence":"Medium","gaps":["Cleavage was shown with chimeric constructs, not the native full-length TgMIC12 protein","Demonstrated by a single lab with a single method; no reciprocal or in vivo confirmation","The biological function of TgMIC12 and the consequence of its cleavage for invasion were not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The native function of TgMIC12, its adhesive or receptor-binding partners, its subcellular trafficking, and the functional consequence of TgROM2-mediated cleavage for host cell invasion remain uncharacterized in the available corpus.","evidence":"No further discoveries in the timeline","pmids":[],"confidence":"Medium","gaps":["No functional or knockout phenotype for TgMIC12 reported","No identification of binding partners or ligands","No structural characterization"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGROM2 (RHOMBOID INTRAMEMBRANE SERINE PROTEASE; CLEAVES THE TGMIC12 TRANSMEMBRANE DOMAIN)"],"other_free_text":["TgMIC12 is a microneme transmembrane protein of Toxoplasma gondii whose TM domain is a substrate for rhomboid-mediated intramembrane proteolysis during host cell invasion [#0].","GO:0008233 is cited as the activity of the interacting protease TgROM2, not of TgMIC12 itself; TgMIC12 is the substrate."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"15913633","id":"PMC_15913633","title":"Apicomplexan rhomboids have a potential role in microneme protein cleavage during host cell invasion.","date":"2005","source":"International journal for parasitology","url":"https://pubmed.ncbi.nlm.nih.gov/15913633","citation_count":98,"is_preprint":false},{"pmid":"29973272","id":"PMC_29973272","title":"Discovery of new Toxoplasma gondii antigenic proteins using a high throughput protein microarray approach screening sera of murine model infected orally with oocysts and tissue cysts.","date":"2018","source":"Parasites & vectors","url":"https://pubmed.ncbi.nlm.nih.gov/29973272","citation_count":24,"is_preprint":false},{"pmid":"41321568","id":"PMC_41321568","title":"Evaluation of immune protection of a multi-antigenic DNA vaccine encoding TgROP6 and TgMIC12 against Toxoplasma gondii infection.","date":"2025","source":"Frontiers in veterinary science","url":"https://pubmed.ncbi.nlm.nih.gov/41321568","citation_count":0,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3814,"output_tokens":347,"usd":0.008323,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":4930,"output_tokens":1234,"usd":0.02775,"stage2_stop_reason":"end_turn"},"total_usd":0.036073,"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\": 2005,\n      \"finding\": \"TgROM2, a rhomboid intramembrane-cleaving serine protease, cleaves chimeric proteins containing the transmembrane domains of TgMIC12, identifying TgMIC12 as a substrate for rhomboid-mediated intramembrane proteolysis during host cell invasion.\",\n      \"method\": \"In vitro/cell-based cleavage assay using chimeric proteins containing TgMIC12 TM domains as substrates for TgROM2\",\n      \"journal\": \"International journal for parasitology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Weak — direct enzymatic cleavage assay demonstrated substrate relationship, but single lab, single method, using chimeric (not native) substrate\",\n      \"pmids\": [\"15913633\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"TgMIC12 is a microneme transmembrane protein whose transmembrane domain serves as a substrate for the rhomboid intramembrane serine protease TgROM2, implicating it in the proteolytic shedding cascade that facilitates host cell invasion by Toxoplasma gondii.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgMIC12 is a Toxoplasma gondii microneme transmembrane protein implicated in the intramembrane proteolytic shedding cascade that accompanies host cell invasion [#0]. Its transmembrane domain serves as a substrate for the rhomboid intramembrane-cleaving serine protease TgROM2, as demonstrated by cleavage of chimeric reporters bearing the TgMIC12 TM segment [#0]. Beyond this single substrate relationship, no further mechanistic detail — including the native protein's function, adhesive partners, or invasion phenotype — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2005,\n      \"claim\": \"To establish which micronemal proteins are processed by parasite rhomboid proteases during invasion, this work tested whether the TgMIC12 transmembrane domain is a cleavage substrate, defining TgMIC12 as part of the rhomboid-mediated shedding cascade.\",\n      \"evidence\": \"In vitro/cell-based cleavage assay using chimeric proteins carrying TgMIC12 TM domains as substrates for TgROM2, in Toxoplasma gondii\",\n      \"pmids\": [\"15913633\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Cleavage was shown with chimeric constructs, not the native full-length TgMIC12 protein\",\n        \"Demonstrated by a single lab with a single method; no reciprocal or in vivo confirmation\",\n        \"The biological function of TgMIC12 and the consequence of its cleavage for invasion were not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The native function of TgMIC12, its adhesive or receptor-binding partners, its subcellular trafficking, and the functional consequence of TgROM2-mediated cleavage for host cell invasion remain uncharacterized in the available corpus.\",\n      \"evidence\": \"No further discoveries in the timeline\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No functional or knockout phenotype for TgMIC12 reported\",\n        \"No identification of binding partners or ligands\",\n        \"No structural characterization\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008233\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0044409\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TgROM2 (rhomboid intramembrane serine protease; cleaves the TgMIC12 transmembrane domain)\"],\n    \"other_free_text\": [\n      \"TgMIC12 is a microneme transmembrane protein of Toxoplasma gondii whose TM domain is a substrate for rhomboid-mediated intramembrane proteolysis during host cell invasion [#0].\",\n      \"GO:0008233 is cited as the activity of the interacting protease TgROM2, not of TgMIC12 itself; TgMIC12 is the substrate.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_267680","name":"MIC12","product":"microneme protein MIC12","uniprot_acc":"S8GGF0","chromosome":"TGME49_chrIX","start_pos":459845},{"strain":"GT1","gene_id":"TGGT1_267680","name":null,"product":"microneme protein MIC12","uniprot_acc":null,"chromosome":"TGGT1_chrIX","start_pos":294592},{"strain":"RH88","gene_id":"TGRH88_010430","name":null,"product":"microneme protein MIC12","uniprot_acc":null,"chromosome":"CM023090","start_pos":509732},{"strain":"VEG","gene_id":"TGVEG_267680","name":null,"product":"microneme protein MIC12","uniprot_acc":"B9QP44","chromosome":"TGVEG_chrIX","start_pos":486509}]}