{"gene":"TG_262010","gene_symbol":"CAM2","run_date":"2026-09-08T16:59:51+00:00","timeline":{"discoveries":[{"year":2017,"finding":"CaM1 and CaM2 are individually dispensable but their combined loss produces a synthetic lethal phenotype, indicating functional redundancy between these two calmodulin-like proteins in Toxoplasma gondii.","method":"CRISPR/Cas9-mediated gene editing (double knockout epistasis)","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Moderate — clean genetic KO with defined lethal phenotype, two orthogonal genetic tools (CRISPR + AID), single lab","pmids":["28475612"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"finding":"CAM2 (along with CaM1 and CaM3) localizes to the conoid at the apical tip of the parasite, overlapping with myosin H (MyoH).","method":"Super-resolution microscopy","journal":"PLoS pathogens","confidence":"High","confidence_rationale":"Tier 2 / Moderate — direct super-resolution localization experiment, single lab, spatially precise result","pmids":["28475612"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"finding":"CAM2 (along with CaM1 and CaM3) contributes to parasite motility, invasion, and egress from host cells, acting downstream of microneme and rhoptry secretion.","method":"Auxin-induced degron (AID)-mediated conditional degradation combined with phenotypic assays (motility, invasion, egress)","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean loss-of-function with defined cellular phenotypes but CaM2's individual contribution is inferred partly from redundancy and combined-knockdown data, single lab","pmids":["28475612"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"finding":"Proximity biotinylation (BirA fusions) with CaM2 (and CaM1/CaM3) labeled apical proteins including myosin H (MyoH) and its light chain MLC7, suggesting physical interaction; disruption of MyoH caused redistribution of CaM2 (and CaM1), consistent with a functional association.","method":"BioID proximity biotinylation and MyoH disruption with imaging readout","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — proximity labeling (not direct Co-IP) plus genetic epistasis showing MyoH disruption affects CaM2 localization; interaction is inferred, not directly confirmed by pull-down; single lab","pmids":["28475612"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"CAM2 is a calmodulin-like protein that localizes to the conoid of Toxoplasma gondii, functions redundantly with CaM1 to support parasite motility, invasion, and egress downstream of microneme/rhoptry secretion, and is associated with the conoid motor protein MyoH (and its light chain MLC7) based on proximity biotinylation and genetic epistasis."},"narrative":{"mechanistic_narrative":"CAM2 is a calmodulin-like protein of Toxoplasma gondii that supports the apical motility machinery driving parasite gliding, host-cell invasion, and egress [PMID:28475612]. It localizes to the conoid at the parasite's apical tip, where it overlaps with the conoid myosin MyoH [PMID:28475612]. CAM2 functions redundantly with CaM1: either protein is individually dispensable, but their combined loss is synthetically lethal, establishing overlapping roles among the conoid calmodulin-like proteins [PMID:28475612]. Functionally, CAM2 acts downstream of microneme and rhoptry secretion in the invasion/egress program [PMID:28475612]. Proximity biotinylation places CAM2 near MyoH and its light chain MLC7, and disruption of MyoH causes CAM2 to redistribute, consistent with a functional association with the conoid myosin motor [PMID:28475612]. Beyond these findings, no further biochemical or structural detail of CAM2 has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Whether the conoid calmodulin-like proteins had non-overlapping essential roles was unknown; genetic epistasis established that CaM1 and CAM2 are functionally redundant, each dispensable alone but jointly essential.","evidence":"CRISPR/Cas9 double-knockout epistasis in T. gondii","pmids":["28475612"],"confidence":"High","gaps":["Does not resolve which molecular functions are shared versus unique between CaM1 and CAM2","Molecular basis of the redundancy (shared partners, shared calcium targets) not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"claim":"The subcellular site of action was unknown; super-resolution imaging placed CAM2 at the apical conoid overlapping MyoH, defining where it operates within the invasion machinery.","evidence":"Super-resolution microscopy of tagged CAM2 in T. gondii","pmids":["28475612"],"confidence":"High","gaps":["Does not establish direct binding to any conoid protein","Spatial overlap with MyoH does not prove physical interaction"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"claim":"The cellular process CAM2 supports was unclear; conditional degradation showed it contributes to motility, invasion, and egress acting downstream of microneme and rhoptry secretion.","evidence":"Auxin-induced degron depletion with motility/invasion/egress assays in T. gondii","pmids":["28475612"],"confidence":"Medium","gaps":["CAM2's individual contribution is inferred partly from redundancy and combined-knockdown data","The specific step in the motility cascade CAM2 controls is not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"claim":"Whether CAM2 physically partners with the conoid motor was unknown; proximity biotinylation labeled MyoH and MLC7, and MyoH disruption redistributed CAM2, indicating a functional association with the myosin motor.","evidence":"BioID proximity biotinylation plus MyoH disruption with imaging readout in T. gondii","pmids":["28475612"],"confidence":"Medium","gaps":["Interaction inferred from proximity labeling and epistasis, not confirmed by reciprocal Co-IP or pull-down","Whether CAM2 binds MyoH directly or via MLC7/other bridging proteins is undefined","No structural or stoichiometric characterization of a CAM2-MyoH complex"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How CAM2's calmodulin-like activity is regulated (e.g. calcium binding) and its direct molecular targets at the conoid remain unresolved.","evidence":"","pmids":[],"confidence":"Low","gaps":["No demonstration of calcium binding or calcium-dependent target engagement for CAM2","No direct binding partner confirmed biochemically","No structural model of CAM2 or its complexes"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["MYOH (MYOSIN H)","MLC7 (MYOH LIGHT CHAIN)","CAM1"],"other_free_text":["CAM2 is a calmodulin-like protein localizing to the apical conoid of Toxoplasma gondii.","Functionally redundant with CaM1: individually dispensable, jointly synthetically lethal.","Contributes to motility, host-cell invasion, and egress downstream of microneme/rhoptry secretion.","Associates functionally with the conoid myosin MyoH; MyoH disruption redistributes CAM2."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"28475612","id":"PMC_28475612","title":"Calmodulin-like proteins localized to the conoid regulate motility and cell invasion by Toxoplasma gondii.","date":"2017","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/28475612","citation_count":84,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2883,"output_tokens":999,"usd":0.011817,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5865,"output_tokens":2123,"usd":0.0412,"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\": 2017,\n      \"finding\": \"CaM1 and CaM2 are individually dispensable but their combined loss produces a synthetic lethal phenotype, indicating functional redundancy between these two calmodulin-like proteins in Toxoplasma gondii.\",\n      \"method\": \"CRISPR/Cas9-mediated gene editing (double knockout epistasis)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean genetic KO with defined lethal phenotype, two orthogonal genetic tools (CRISPR + AID), single lab\",\n      \"pmids\": [\"28475612\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"CAM2 (along with CaM1 and CaM3) localizes to the conoid at the apical tip of the parasite, overlapping with myosin H (MyoH).\",\n      \"method\": \"Super-resolution microscopy\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct super-resolution localization experiment, single lab, spatially precise result\",\n      \"pmids\": [\"28475612\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"CAM2 (along with CaM1 and CaM3) contributes to parasite motility, invasion, and egress from host cells, acting downstream of microneme and rhoptry secretion.\",\n      \"method\": \"Auxin-induced degron (AID)-mediated conditional degradation combined with phenotypic assays (motility, invasion, egress)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean loss-of-function with defined cellular phenotypes but CaM2's individual contribution is inferred partly from redundancy and combined-knockdown data, single lab\",\n      \"pmids\": [\"28475612\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Proximity biotinylation (BirA fusions) with CaM2 (and CaM1/CaM3) labeled apical proteins including myosin H (MyoH) and its light chain MLC7, suggesting physical interaction; disruption of MyoH caused redistribution of CaM2 (and CaM1), consistent with a functional association.\",\n      \"method\": \"BioID proximity biotinylation and MyoH disruption with imaging readout\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — proximity labeling (not direct Co-IP) plus genetic epistasis showing MyoH disruption affects CaM2 localization; interaction is inferred, not directly confirmed by pull-down; single lab\",\n      \"pmids\": [\"28475612\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"CAM2 is a calmodulin-like protein that localizes to the conoid of Toxoplasma gondii, functions redundantly with CaM1 to support parasite motility, invasion, and egress downstream of microneme/rhoptry secretion, and is associated with the conoid motor protein MyoH (and its light chain MLC7) based on proximity biotinylation and genetic epistasis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CAM2 is a calmodulin-like protein of Toxoplasma gondii that supports the apical motility machinery driving parasite gliding, host-cell invasion, and egress [#2]. It localizes to the conoid at the parasite's apical tip, where it overlaps with the conoid myosin MyoH [#1]. CAM2 functions redundantly with CaM1: either protein is individually dispensable, but their combined loss is synthetically lethal, establishing overlapping roles among the conoid calmodulin-like proteins [#0]. Functionally, CAM2 acts downstream of microneme and rhoptry secretion in the invasion/egress program [#2]. Proximity biotinylation places CAM2 near MyoH and its light chain MLC7, and disruption of MyoH causes CAM2 to redistribute, consistent with a functional association with the conoid myosin motor [#3]. Beyond these findings, no further biochemical or structural detail of CAM2 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Whether the conoid calmodulin-like proteins had non-overlapping essential roles was unknown; genetic epistasis established that CaM1 and CAM2 are functionally redundant, each dispensable alone but jointly essential.\",\n      \"evidence\": \"CRISPR/Cas9 double-knockout epistasis in T. gondii\",\n      \"pmids\": [\"28475612\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Does not resolve which molecular functions are shared versus unique between CaM1 and CAM2\",\n        \"Molecular basis of the redundancy (shared partners, shared calcium targets) not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The subcellular site of action was unknown; super-resolution imaging placed CAM2 at the apical conoid overlapping MyoH, defining where it operates within the invasion machinery.\",\n      \"evidence\": \"Super-resolution microscopy of tagged CAM2 in T. gondii\",\n      \"pmids\": [\"28475612\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Does not establish direct binding to any conoid protein\",\n        \"Spatial overlap with MyoH does not prove physical interaction\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The cellular process CAM2 supports was unclear; conditional degradation showed it contributes to motility, invasion, and egress acting downstream of microneme and rhoptry secretion.\",\n      \"evidence\": \"Auxin-induced degron depletion with motility/invasion/egress assays in T. gondii\",\n      \"pmids\": [\"28475612\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"CAM2's individual contribution is inferred partly from redundancy and combined-knockdown data\",\n        \"The specific step in the motility cascade CAM2 controls is not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Whether CAM2 physically partners with the conoid motor was unknown; proximity biotinylation labeled MyoH and MLC7, and MyoH disruption redistributed CAM2, indicating a functional association with the myosin motor.\",\n      \"evidence\": \"BioID proximity biotinylation plus MyoH disruption with imaging readout in T. gondii\",\n      \"pmids\": [\"28475612\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Interaction inferred from proximity labeling and epistasis, not confirmed by reciprocal Co-IP or pull-down\",\n        \"Whether CAM2 binds MyoH directly or via MLC7/other bridging proteins is undefined\",\n        \"No structural or stoichiometric characterization of a CAM2-MyoH complex\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How CAM2's calmodulin-like activity is regulated (e.g. calcium binding) and its direct molecular targets at the conoid remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No demonstration of calcium binding or calcium-dependent target engagement for CAM2\",\n        \"No direct binding partner confirmed biochemically\",\n        \"No structural model of CAM2 or its complexes\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0005516\", \"supporting_discovery_ids\": [3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020009\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0052126\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"MyoH (myosin H)\", \"MLC7 (MyoH light chain)\", \"CaM1\"],\n    \"other_free_text\": [\n      \"CAM2 is a calmodulin-like protein localizing to the apical conoid of Toxoplasma gondii.\",\n      \"Functionally redundant with CaM1: individually dispensable, jointly synthetically lethal.\",\n      \"Contributes to motility, host-cell invasion, and egress downstream of microneme/rhoptry secretion.\",\n      \"Associates functionally with the conoid myosin MyoH; MyoH disruption redistributes CAM2.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_262010","name":"CAM2","product":"calmodulin CAM2","uniprot_acc":"S8F4K2","chromosome":"TGME49_chrVIIb","start_pos":1425971},{"strain":"GT1","gene_id":"TGGT1_262010","name":null,"product":"calmodulin CAM2","uniprot_acc":null,"chromosome":"TGGT1_chrVIIb","start_pos":1401611},{"strain":"RH88","gene_id":"TGRH88_068820","name":null,"product":"calmodulin CAM2","uniprot_acc":null,"chromosome":"CM023089","start_pos":1444667},{"strain":"VEG","gene_id":"TGVEG_262010","name":null,"product":"calmodulin CAM2","uniprot_acc":"B9PLU7","chromosome":"TGVEG_chrVIIb","start_pos":1440300}]}