{"gene":"TG_297060","gene_symbol":"PGM2","run_date":"2026-09-08T15:15:12","timeline":{"discoveries":[{"year":2017,"finding":"Genetic deletion of PGM2 (a phosphoglucomutase paralog) abrogated high Ca2+-flux-mediated microneme secretion triggered by the ionophore A23187, but did not affect basal constitutive microneme release or phosphatidic acid-triggered microneme secretion, placing PGM2 specifically in the ionophore/high-Ca2+ branch of microneme exocytosis.","method":"Reverse genetics (gene deletion), microneme secretion assays with A23187 ionophore and phosphatidic acid, in vivo acute infection mouse model","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype and multiple secretion pathway readouts, single lab","pmids":["29202046"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"finding":"Deletion of PGM2 alone or combined deletion of PGM2 and PRP1 did not impair tachyzoite lytic cycle completion (host cell invasion and egress) or acute virulence in mice, demonstrating that high-Ca2+-mediated, PGM2-dependent microneme secretion is dispensable for these processes.","method":"Genetic deletion (single and double knockout), plaque/lytic cycle assays, mouse acute infection model","journal":"mSphere","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with multiple functional readouts, single lab","pmids":["29202046"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"finding":"Crystal structure of Toxoplasma gondii PGMII (PGM2) was solved, revealing overall protein structure, oligomeric state, and active-site molecular details important for ligand recognition; antisense (vivoPMO)-mediated knockdown of PGM expression caused statistically significant reduction in parasite replication without host cell toxicity.","method":"X-ray crystallography, vivoPMO antisense knockdown, parasite replication assay","journal":"Frontiers in cellular and infection microbiology","confidence":"Medium","confidence_rationale":"Tier 1-2 / Moderate — crystal structure combined with functional knockdown, single lab","pmids":["30345257"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"Toxoplasma gondii PGM2 is a phosphoglucomutase paralog whose crystal structure has been solved; it functions specifically in high-Ca2+-flux-triggered microneme secretion (but not constitutive or phosphatidic acid-mediated release), and while its loss reduces ionophore-stimulated exocytosis, it is dispensable for lytic cycle completion and acute in vivo virulence."},"narrative":{"mechanistic_narrative":"Toxoplasma gondii PGM2 is a phosphoglucomutase paralog that functions specifically in the high-Ca2+-flux branch of microneme exocytosis [PMID:29202046]. Genetic deletion of PGM2 abrogates microneme secretion triggered by the calcium ionophore A23187 while leaving basal constitutive release and phosphatidic acid-triggered secretion intact, placing it selectively downstream of high-Ca2+ signaling [PMID:29202046]. This PGM2-dependent secretion is nevertheless dispensable for tachyzoite lytic cycle completion—invasion and egress—and for acute virulence in mice, both alone and in combination with PRP1 deletion [PMID:29202046]. The crystal structure of PGM2 has been solved, defining its oligomeric state and active-site features for ligand recognition, and antisense knockdown of PGM expression reduces parasite replication without host cell toxicity [PMID:30345257]. Beyond these findings, the enzymatic substrates and the molecular link between PGM2 catalysis and the calcium-triggered secretion machinery have not been characterized in the available corpus.","teleology":[{"year":2017,"claim":"To determine which branch of microneme exocytosis PGM2 acts in, deletion resolved that it is required specifically for high-Ca2+-triggered but not constitutive or phosphatidic acid-triggered secretion.","evidence":"Gene deletion with microneme secretion assays comparing A23187 ionophore and phosphatidic acid stimulation","pmids":["29202046"],"confidence":"Medium","gaps":["The catalytic substrate and how phosphoglucomutase activity connects to calcium-triggered exocytosis are undefined","Single-lab result"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"claim":"To test whether PGM2-dependent secretion is essential for the parasite life cycle, single and double (with PRP1) knockouts showed lytic cycle and acute virulence are unaffected, establishing this secretion branch as dispensable for those processes.","evidence":"Single and double gene deletion, plaque/lytic cycle assays, mouse acute infection model","pmids":["29202046"],"confidence":"Medium","gaps":["Whether PGM2 is required in chronic infection or other life-cycle stages was not tested","Functional redundancy with other paralogs not excluded"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2018,"claim":"To provide molecular and functional detail beyond genetics, the crystal structure was solved and antisense knockdown confirmed a role in parasite replication.","evidence":"X-ray crystallography and vivoPMO antisense knockdown with parasite replication assay","pmids":["30345257"],"confidence":"Medium","gaps":["No enzyme kinetics or in vitro demonstration of phosphoglucomutase catalysis reported","The structural features are not connected to the secretion phenotype"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"How PGM2's phosphoglucomutase activity mechanistically couples to high-Ca2+-triggered microneme exocytosis remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No substrate or metabolic product linked to the secretion defect","No identified interaction partners in the secretion machinery","Subcellular localization relative to micronemes not established in this corpus"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":["PGM2 is a phosphoglucomutase paralog; a related paralog PRP1 was co-deleted without additional lytic-cycle phenotype [#1]","Required specifically for high-Ca2+/ionophore-triggered microneme secretion, not constitutive or phosphatidic acid-triggered release [#0]","Dispensable for tachyzoite lytic cycle and acute mouse virulence [#1]","Crystal structure solved; antisense knockdown reduces parasite replication [#2]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"30345257","id":"PMC_30345257","title":"CSGID Solves Structures and Identifies Phenotypes for Five Enzymes in Toxoplasma gondii.","date":"2018","source":"Frontiers in cellular and infection microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/30345257","citation_count":12,"is_preprint":false},{"pmid":"29202046","id":"PMC_29202046","title":"Two Phosphoglucomutase Paralogs Facilitate Ionophore-Triggered Secretion of the Toxoplasma Micronemes.","date":"2017","source":"mSphere","url":"https://pubmed.ncbi.nlm.nih.gov/29202046","citation_count":10,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3602,"output_tokens":842,"usd":0.011718,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5670,"output_tokens":1758,"usd":0.03615,"stage2_stop_reason":"end_turn"},"total_usd":0.047868,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"Genetic deletion of PGM2 (a phosphoglucomutase paralog) abrogated high Ca2+-flux-mediated microneme secretion triggered by the ionophore A23187, but did not affect basal constitutive microneme release or phosphatidic acid-triggered microneme secretion, placing PGM2 specifically in the ionophore/high-Ca2+ branch of microneme exocytosis.\",\n      \"method\": \"Reverse genetics (gene deletion), microneme secretion assays with A23187 ionophore and phosphatidic acid, in vivo acute infection mouse model\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype and multiple secretion pathway readouts, single lab\",\n      \"pmids\": [\"29202046\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Deletion of PGM2 alone or combined deletion of PGM2 and PRP1 did not impair tachyzoite lytic cycle completion (host cell invasion and egress) or acute virulence in mice, demonstrating that high-Ca2+-mediated, PGM2-dependent microneme secretion is dispensable for these processes.\",\n      \"method\": \"Genetic deletion (single and double knockout), plaque/lytic cycle assays, mouse acute infection model\",\n      \"journal\": \"mSphere\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with multiple functional readouts, single lab\",\n      \"pmids\": [\"29202046\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"Crystal structure of Toxoplasma gondii PGMII (PGM2) was solved, revealing overall protein structure, oligomeric state, and active-site molecular details important for ligand recognition; antisense (vivoPMO)-mediated knockdown of PGM expression caused statistically significant reduction in parasite replication without host cell toxicity.\",\n      \"method\": \"X-ray crystallography, vivoPMO antisense knockdown, parasite replication assay\",\n      \"journal\": \"Frontiers in cellular and infection microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1-2 / Moderate — crystal structure combined with functional knockdown, single lab\",\n      \"pmids\": [\"30345257\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"Toxoplasma gondii PGM2 is a phosphoglucomutase paralog whose crystal structure has been solved; it functions specifically in high-Ca2+-flux-triggered microneme secretion (but not constitutive or phosphatidic acid-mediated release), and while its loss reduces ionophore-stimulated exocytosis, it is dispensable for lytic cycle completion and acute in vivo virulence.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"Toxoplasma gondii PGM2 is a phosphoglucomutase paralog that functions specifically in the high-Ca2+-flux branch of microneme exocytosis [#0]. Genetic deletion of PGM2 abrogates microneme secretion triggered by the calcium ionophore A23187 while leaving basal constitutive release and phosphatidic acid-triggered secretion intact, placing it selectively downstream of high-Ca2+ signaling [#0]. This PGM2-dependent secretion is nevertheless dispensable for tachyzoite lytic cycle completion—invasion and egress—and for acute virulence in mice, both alone and in combination with PRP1 deletion [#1]. The crystal structure of PGM2 has been solved, defining its oligomeric state and active-site features for ligand recognition, and antisense knockdown of PGM expression reduces parasite replication without host cell toxicity [#2]. Beyond these findings, the enzymatic substrates and the molecular link between PGM2 catalysis and the calcium-triggered secretion machinery have not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"To determine which branch of microneme exocytosis PGM2 acts in, deletion resolved that it is required specifically for high-Ca2+-triggered but not constitutive or phosphatidic acid-triggered secretion.\",\n      \"evidence\": \"Gene deletion with microneme secretion assays comparing A23187 ionophore and phosphatidic acid stimulation\",\n      \"pmids\": [\"29202046\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"The catalytic substrate and how phosphoglucomutase activity connects to calcium-triggered exocytosis are undefined\", \"Single-lab result\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"To test whether PGM2-dependent secretion is essential for the parasite life cycle, single and double (with PRP1) knockouts showed lytic cycle and acute virulence are unaffected, establishing this secretion branch as dispensable for those processes.\",\n      \"evidence\": \"Single and double gene deletion, plaque/lytic cycle assays, mouse acute infection model\",\n      \"pmids\": [\"29202046\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether PGM2 is required in chronic infection or other life-cycle stages was not tested\", \"Functional redundancy with other paralogs not excluded\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"To provide molecular and functional detail beyond genetics, the crystal structure was solved and antisense knockdown confirmed a role in parasite replication.\",\n      \"evidence\": \"X-ray crystallography and vivoPMO antisense knockdown with parasite replication assay\",\n      \"pmids\": [\"30345257\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No enzyme kinetics or in vitro demonstration of phosphoglucomutase catalysis reported\", \"The structural features are not connected to the secretion phenotype\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How PGM2's phosphoglucomutase activity mechanistically couples to high-Ca2+-triggered microneme exocytosis remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No substrate or metabolic product linked to the secretion defect\", \"No identified interaction partners in the secretion machinery\", \"Subcellular localization relative to micronemes not established in this corpus\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004614\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0002790\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": [\n      \"PGM2 is a phosphoglucomutase paralog; a related paralog PRP1 was co-deleted without additional lytic-cycle phenotype [#1]\",\n      \"Required specifically for high-Ca2+/ionophore-triggered microneme secretion, not constitutive or phosphatidic acid-triggered release [#0]\",\n      \"Dispensable for tachyzoite lytic cycle and acute mouse virulence [#1]\",\n      \"Crystal structure solved; antisense knockdown reduces parasite replication [#2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_297060","name":"PGM2","product":"phosphoglycerate mutase PGMII","uniprot_acc":"S8GJT7","chromosome":"TGME49_chrII","start_pos":1510431},{"strain":"GT1","gene_id":"TGGT1_297060","name":null,"product":"phosphoglycerate mutase PGMII","uniprot_acc":null,"chromosome":"TGGT1_chrII","start_pos":1486715},{"strain":"RH88","gene_id":"TGRH88_001910","name":null,"product":"phosphoglycerate mutase PGMII","uniprot_acc":null,"chromosome":"CM023083","start_pos":1686674},{"strain":"VEG","gene_id":"TGVEG_297060","name":null,"product":"phosphoglycerate mutase PGMII","uniprot_acc":"A0A125YK30","chromosome":"TGVEG_chrII","start_pos":1519703}]}