{"gene":"TG_238390","gene_symbol":"UGO","run_date":"2026-09-08T12:58:24","timeline":{"discoveries":[{"year":2019,"finding":"UGO (unique GC organizer) is a cofactor required for assembly of the atypical guanylate cyclase (GC) complex at the plasma membrane of Toxoplasma gondii. The GC complex is composed of a P4-ATPase fused to two GC catalytic domains, and its membrane assembly depends on UGO together with CDC50.1.","method":"Conditional depletion/genetic approaches combined with functional assays for egress and signaling platform characterization","journal":"Nature microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic loss-of-function with defined molecular complex characterization in a single study; complex composition established but structural/biochemical reconstitution not reported in the abstract","pmids":["30742070"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"finding":"UGO is confirmed as a component of the GC complex (alongside CDC50.1 and SLF) that governs cGMP-dependent signaling; the complex integrates signals (phosphatidic acid, pH, ionic changes) to trigger microneme exocytosis, conoid extrusion, motility, invasion, and egress in both tachyzoites and bradyzoites.","method":"Conditional depletion of complex components (SLF, GC) with phenotypic readouts of microneme secretion, conoid extrusion, motility, invasion, egress, and cyst burden in mice","journal":"mBio","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic depletion with multiple orthogonal phenotypic readouts in a single lab study; UGO role inferred from complex membership, not directly depleted in this paper","pmids":["36200777"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"UGO (unique GC organizer) is an essential cofactor of the Toxoplasma gondii guanylate cyclase (GC) signaling complex at the plasma membrane, where it cooperates with CDC50.1 and SLF to assemble an atypical P4-ATPase/GC platform that integrates lipid (phosphatidic acid) and environmental signals to drive cGMP production, microneme exocytosis, and timely host-cell egress and invasion during both acute and chronic infection."},"narrative":{"mechanistic_narrative":"UGO (unique GC organizer) is an essential assembly cofactor of the atypical guanylate cyclase (GC) signaling complex at the plasma membrane of Toxoplasma gondii [PMID:30742070]. Together with CDC50.1, UGO is required for membrane assembly of the GC complex, which is built around a P4-ATPase fused to two GC catalytic domains [PMID:30742070]. As a component of this complex alongside CDC50.1 and SLF, UGO participates in a cGMP-dependent signaling platform that integrates lipid (phosphatidic acid), pH, and ionic cues to drive microneme exocytosis, conoid extrusion, motility, invasion, and egress in both tachyzoites and bradyzoites [PMID:36200777]. Beyond its role in complex assembly and this signaling output, the structural and biochemical basis of UGO's cofactor function has not been characterized in the available corpus.","teleology":[{"year":2019,"claim":"Establishing how the atypical GC platform is built at the parasite plasma membrane, this work identified UGO as a cofactor required, together with CDC50.1, for membrane assembly of the P4-ATPase/dual-GC complex.","evidence":"Conditional depletion/genetic loss-of-function combined with egress and signaling platform characterization in Toxoplasma gondii","pmids":["30742070"],"confidence":"Medium","gaps":["No structural or biochemical reconstitution of the UGO-containing complex","Mechanism by which UGO promotes membrane assembly is undefined","Direct binding partners of UGO within the complex not mapped"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2022,"claim":"Extending the complex to a full signaling module, this study placed UGO alongside CDC50.1 and SLF in a cGMP-dependent platform that transduces lipid and environmental cues into microneme secretion, motility, invasion, and egress across life stages.","evidence":"Conditional depletion of complex components (SLF, GC) with phenotypic readouts of microneme secretion, conoid extrusion, motility, invasion, egress, and cyst burden in mice","pmids":["36200777"],"confidence":"Medium","gaps":["UGO's role here is inferred from complex membership; UGO itself was not directly depleted in this study","How UGO contributes to signal integration versus scaffolding is not resolved","Direct molecular interactions of UGO with SLF and CDC50.1 not biochemically demonstrated"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The precise molecular function of UGO within the GC complex — whether it acts purely as an assembly scaffold or contributes to catalytic regulation — and its structural interactions remain unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model of UGO or the assembled complex","No direct biochemical demonstration of UGO's binding interfaces","Whether UGO influences cGMP catalysis directly versus indirectly is unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Atypical guanylate cyclase (GC) complex (P4-ATPase/dual-GC with CDC50.1, SLF, UGO)"],"partners":["CDC50.1","SLF","GUANYLATE CYCLASE (P4-ATPASE-FUSED DUAL GC)"],"other_free_text":["UGO = 'unique GC organizer'; required for membrane assembly of the GC signaling platform in Toxoplasma gondii.","Complex integrates phosphatidic acid, pH, and ionic signals to drive cGMP-dependent microneme exocytosis, conoid extrusion, motility, invasion, and egress in both tachyzoites and bradyzoites."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"30742070","id":"PMC_30742070","title":"Phosphatidic acid governs natural egress in Toxoplasma gondii via a guanylate cyclase receptor platform.","date":"2019","source":"Nature microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/30742070","citation_count":81,"is_preprint":false},{"pmid":"36200777","id":"PMC_36200777","title":"A Signaling Factor Linked to Toxoplasma gondii Guanylate Cyclase Complex Controls Invasion and Egress during Acute and Chronic Infection.","date":"2022","source":"mBio","url":"https://pubmed.ncbi.nlm.nih.gov/36200777","citation_count":13,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3529,"output_tokens":694,"usd":0.010498,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5404,"output_tokens":1644,"usd":0.03406,"stage2_stop_reason":"end_turn"},"total_usd":0.044558,"stage1_batch_id":"msgbatch_01TEPNZ4MCzJ7xtsNwosiDRk","stage2_batch_id":"msgbatch_01FQShM7n1sfCr4pWTDShmki","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2019,\n      \"finding\": \"UGO (unique GC organizer) is a cofactor required for assembly of the atypical guanylate cyclase (GC) complex at the plasma membrane of Toxoplasma gondii. The GC complex is composed of a P4-ATPase fused to two GC catalytic domains, and its membrane assembly depends on UGO together with CDC50.1.\",\n      \"method\": \"Conditional depletion/genetic approaches combined with functional assays for egress and signaling platform characterization\",\n      \"journal\": \"Nature microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic loss-of-function with defined molecular complex characterization in a single study; complex composition established but structural/biochemical reconstitution not reported in the abstract\",\n      \"pmids\": [\"30742070\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"UGO is confirmed as a component of the GC complex (alongside CDC50.1 and SLF) that governs cGMP-dependent signaling; the complex integrates signals (phosphatidic acid, pH, ionic changes) to trigger microneme exocytosis, conoid extrusion, motility, invasion, and egress in both tachyzoites and bradyzoites.\",\n      \"method\": \"Conditional depletion of complex components (SLF, GC) with phenotypic readouts of microneme secretion, conoid extrusion, motility, invasion, egress, and cyst burden in mice\",\n      \"journal\": \"mBio\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic depletion with multiple orthogonal phenotypic readouts in a single lab study; UGO role inferred from complex membership, not directly depleted in this paper\",\n      \"pmids\": [\"36200777\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"UGO (unique GC organizer) is an essential cofactor of the Toxoplasma gondii guanylate cyclase (GC) signaling complex at the plasma membrane, where it cooperates with CDC50.1 and SLF to assemble an atypical P4-ATPase/GC platform that integrates lipid (phosphatidic acid) and environmental signals to drive cGMP production, microneme exocytosis, and timely host-cell egress and invasion during both acute and chronic infection.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"UGO (unique GC organizer) is an essential assembly cofactor of the atypical guanylate cyclase (GC) signaling complex at the plasma membrane of Toxoplasma gondii [#0]. Together with CDC50.1, UGO is required for membrane assembly of the GC complex, which is built around a P4-ATPase fused to two GC catalytic domains [#0]. As a component of this complex alongside CDC50.1 and SLF, UGO participates in a cGMP-dependent signaling platform that integrates lipid (phosphatidic acid), pH, and ionic cues to drive microneme exocytosis, conoid extrusion, motility, invasion, and egress in both tachyzoites and bradyzoites [#1]. Beyond its role in complex assembly and this signaling output, the structural and biochemical basis of UGO's cofactor function has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2019,\n      \"claim\": \"Establishing how the atypical GC platform is built at the parasite plasma membrane, this work identified UGO as a cofactor required, together with CDC50.1, for membrane assembly of the P4-ATPase/dual-GC complex.\",\n      \"evidence\": \"Conditional depletion/genetic loss-of-function combined with egress and signaling platform characterization in Toxoplasma gondii\",\n      \"pmids\": [\"30742070\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural or biochemical reconstitution of the UGO-containing complex\",\n        \"Mechanism by which UGO promotes membrane assembly is undefined\",\n        \"Direct binding partners of UGO within the complex not mapped\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Extending the complex to a full signaling module, this study placed UGO alongside CDC50.1 and SLF in a cGMP-dependent platform that transduces lipid and environmental cues into microneme secretion, motility, invasion, and egress across life stages.\",\n      \"evidence\": \"Conditional depletion of complex components (SLF, GC) with phenotypic readouts of microneme secretion, conoid extrusion, motility, invasion, egress, and cyst burden in mice\",\n      \"pmids\": [\"36200777\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"UGO's role here is inferred from complex membership; UGO itself was not directly depleted in this study\",\n        \"How UGO contributes to signal integration versus scaffolding is not resolved\",\n        \"Direct molecular interactions of UGO with SLF and CDC50.1 not biochemically demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The precise molecular function of UGO within the GC complex — whether it acts purely as an assembly scaffold or contributes to catalytic regulation — and its structural interactions remain unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No structural model of UGO or the assembled complex\",\n        \"No direct biochemical demonstration of UGO's binding interfaces\",\n        \"Whether UGO influences cGMP catalysis directly versus indirectly is unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006182\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [\"Atypical guanylate cyclase (GC) complex (P4-ATPase/dual-GC with CDC50.1, SLF, UGO)\"],\n    \"partners\": [\"CDC50.1\", \"SLF\", \"guanylate cyclase (P4-ATPase-fused dual GC)\"],\n    \"other_free_text\": [\n      \"UGO = 'unique GC organizer'; required for membrane assembly of the GC signaling platform in Toxoplasma gondii.\",\n      \"Complex integrates phosphatidic acid, pH, and ionic signals to drive cGMP-dependent microneme exocytosis, conoid extrusion, motility, invasion, and egress in both tachyzoites and bradyzoites.\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_238390","name":"UGO","product":"guanylate cyclase organizer UGO","uniprot_acc":"S8GQN5","chromosome":"TGME49_chrVI","start_pos":179006},{"strain":"GT1","gene_id":"TGGT1_238390","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrVI","start_pos":181213},{"strain":"RH88","gene_id":"TGRH88_032150","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023087","start_pos":3527099},{"strain":"VEG","gene_id":"TGVEG_238390","name":null,"product":"putative transmembrane protein","uniprot_acc":"B9QQU3","chromosome":"TGVEG_chrVI","start_pos":187237}]}