{"gene":"TG_269260","gene_symbol":"SCE1","run_date":"2026-09-08T14:08:29","timeline":{"discoveries":[{"year":2017,"finding":"SCE1 (Suppressor of Ca2+-dependent Egress 1) was identified as a negative regulator of rapid Ca2+-dependent cell egress in Toxoplasma gondii through a forward genetic screen; gain-of-function mutations in SCE1 rescued egress in a cdpk3 knockout background, placing SCE1 downstream of CDPK3 in the Ca2+ signaling pathway.","method":"Forward genetic screen (gain-of-function mutants in Δcdpk3 background), genetic epistasis","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis via forward screen with phosphoproteomic validation, single lab, two orthogonal methods","pmids":["28258212"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"finding":"CDPK3-dependent phosphorylation of SCE1 is required to relieve SCE1's suppressive activity on Ca2+-dependent egress; global phosphoproteomic analysis showed that SCE1 deletion restored many Δcdpk3-dependent phosphorylation events to near wild-type levels.","method":"Global phosphoproteomic analysis, genetic deletion (ΔSCE1 in Δcdpk3 background)","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — phosphoproteomics combined with genetic epistasis, single lab, two orthogonal methods","pmids":["28258212"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"SCE1 functions as a negative regulator (suppressor) of Ca2+-dependent host cell egress in Toxoplasma gondii; CDPK3 phosphorylates SCE1 to relieve its suppressive activity, thereby potentiating egress downstream of cytosolic Ca2+ flux."},"narrative":{"mechanistic_narrative":"SCE1 (Suppressor of Ca2+-dependent Egress 1) is a negative regulator of rapid Ca2+-dependent host cell egress in Toxoplasma gondii, acting downstream of the calcium-dependent protein kinase CDPK3 [PMID:28258212]. It was identified in a forward genetic screen in which gain-of-function mutations in SCE1 restored egress in a Δcdpk3 background, genetically placing SCE1 within the Ca2+ signaling pathway that controls egress [PMID:28258212]. CDPK3-dependent phosphorylation of SCE1 relieves its suppressive activity, and deletion of SCE1 restores many Δcdpk3-dependent phosphorylation events toward wild-type levels, establishing SCE1 as the physiological brake on egress that CDPK3 antagonizes [PMID:28258212]. Beyond this genetic and phosphoproteomic placement, no biochemical mechanism, direct substrates, or structural detail for SCE1 has been characterized in the available corpus.","teleology":[{"year":2017,"claim":"Identifying a downstream effector of CDPK3 in egress signaling: SCE1 was found as a negative regulator whose gain-of-function mutations bypass the loss of CDPK3, defining a genetic brake on Ca2+-dependent egress.","evidence":"Forward genetic screen for gain-of-function suppressors in a Δcdpk3 background with genetic epistasis, in Toxoplasma gondii","pmids":["28258212"],"confidence":"Medium","gaps":["The molecular identity of the process SCE1 suppresses (e.g. direct effectors) is not defined","Whether SCE1 acts on egress machinery directly or through intermediaries is unknown","No biochemical or structural characterization of SCE1"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2017,"claim":"Establishing the regulatory logic: CDPK3-dependent phosphorylation of SCE1 relieves its suppression, since SCE1 deletion restores Δcdpk3-dependent phosphorylation events, positioning SCE1 as the target through which CDPK3 potentiates egress.","evidence":"Global phosphoproteomic analysis combined with genetic deletion of SCE1 in a Δcdpk3 background, in Toxoplasma gondii","pmids":["28258212"],"confidence":"Medium","gaps":["Direct phosphorylation of SCE1 by CDPK3 not demonstrated in vitro","The specific phosphosites and their functional consequences are not mapped","Downstream substrates whose phosphorylation SCE1 controls are unidentified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The biochemical activity of SCE1, its direct interaction partners, and the molecular mechanism by which it suppresses Ca2+-dependent egress remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No molecular function or enzymatic activity assigned to SCE1","No subcellular localization established","No structural model or direct binding partners identified"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["CDPK3 (UPSTREAM KINASE RELIEVING SCE1 SUPPRESSION VIA PHOSPHORYLATION)"],"other_free_text":["SCE1 acts downstream of CDPK3 in the Ca2+ signaling pathway controlling rapid egress [#0].","CDPK3-dependent phosphorylation relieves SCE1's suppressive activity; SCE1 deletion restores Δcdpk3-dependent phosphorylation events toward wild-type levels [#1]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"28258212","id":"PMC_28258212","title":"A forward genetic screen identifies a negative regulator of rapid Ca2+-dependent cell egress (MS1) in the intracellular parasite Toxoplasma gondii.","date":"2017","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/28258212","citation_count":21,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2867,"output_tokens":579,"usd":0.008643,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5316,"output_tokens":1567,"usd":0.032877,"stage2_stop_reason":"end_turn"},"total_usd":0.04152,"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\": 2017,\n      \"finding\": \"SCE1 (Suppressor of Ca2+-dependent Egress 1) was identified as a negative regulator of rapid Ca2+-dependent cell egress in Toxoplasma gondii through a forward genetic screen; gain-of-function mutations in SCE1 rescued egress in a cdpk3 knockout background, placing SCE1 downstream of CDPK3 in the Ca2+ signaling pathway.\",\n      \"method\": \"Forward genetic screen (gain-of-function mutants in Δcdpk3 background), genetic epistasis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis via forward screen with phosphoproteomic validation, single lab, two orthogonal methods\",\n      \"pmids\": [\"28258212\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"CDPK3-dependent phosphorylation of SCE1 is required to relieve SCE1's suppressive activity on Ca2+-dependent egress; global phosphoproteomic analysis showed that SCE1 deletion restored many Δcdpk3-dependent phosphorylation events to near wild-type levels.\",\n      \"method\": \"Global phosphoproteomic analysis, genetic deletion (ΔSCE1 in Δcdpk3 background)\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — phosphoproteomics combined with genetic epistasis, single lab, two orthogonal methods\",\n      \"pmids\": [\"28258212\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"SCE1 functions as a negative regulator (suppressor) of Ca2+-dependent host cell egress in Toxoplasma gondii; CDPK3 phosphorylates SCE1 to relieve its suppressive activity, thereby potentiating egress downstream of cytosolic Ca2+ flux.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SCE1 (Suppressor of Ca2+-dependent Egress 1) is a negative regulator of rapid Ca2+-dependent host cell egress in Toxoplasma gondii, acting downstream of the calcium-dependent protein kinase CDPK3 [#0]. It was identified in a forward genetic screen in which gain-of-function mutations in SCE1 restored egress in a Δcdpk3 background, genetically placing SCE1 within the Ca2+ signaling pathway that controls egress [#0]. CDPK3-dependent phosphorylation of SCE1 relieves its suppressive activity, and deletion of SCE1 restores many Δcdpk3-dependent phosphorylation events toward wild-type levels, establishing SCE1 as the physiological brake on egress that CDPK3 antagonizes [#1]. Beyond this genetic and phosphoproteomic placement, no biochemical mechanism, direct substrates, or structural detail for SCE1 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2017,\n      \"claim\": \"Identifying a downstream effector of CDPK3 in egress signaling: SCE1 was found as a negative regulator whose gain-of-function mutations bypass the loss of CDPK3, defining a genetic brake on Ca2+-dependent egress.\",\n      \"evidence\": \"Forward genetic screen for gain-of-function suppressors in a Δcdpk3 background with genetic epistasis, in Toxoplasma gondii\",\n      \"pmids\": [\"28258212\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The molecular identity of the process SCE1 suppresses (e.g. direct effectors) is not defined\",\n        \"Whether SCE1 acts on egress machinery directly or through intermediaries is unknown\",\n        \"No biochemical or structural characterization of SCE1\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Establishing the regulatory logic: CDPK3-dependent phosphorylation of SCE1 relieves its suppression, since SCE1 deletion restores Δcdpk3-dependent phosphorylation events, positioning SCE1 as the target through which CDPK3 potentiates egress.\",\n      \"evidence\": \"Global phosphoproteomic analysis combined with genetic deletion of SCE1 in a Δcdpk3 background, in Toxoplasma gondii\",\n      \"pmids\": [\"28258212\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Direct phosphorylation of SCE1 by CDPK3 not demonstrated in vitro\",\n        \"The specific phosphosites and their functional consequences are not mapped\",\n        \"Downstream substrates whose phosphorylation SCE1 controls are unidentified\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The biochemical activity of SCE1, its direct interaction partners, and the molecular mechanism by which it suppresses Ca2+-dependent egress remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No molecular function or enzymatic activity assigned to SCE1\",\n        \"No subcellular localization established\",\n        \"No structural model or direct binding partners identified\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"Ca2+-dependent host cell egress (negative regulation)\", \"supporting_discovery_ids\": [0, 1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"CDPK3 (upstream kinase relieving SCE1 suppression via phosphorylation)\"],\n    \"other_free_text\": [\n      \"SCE1 acts downstream of CDPK3 in the Ca2+ signaling pathway controlling rapid egress [#0].\",\n      \"CDPK3-dependent phosphorylation relieves SCE1's suppressive activity; SCE1 deletion restores Δcdpk3-dependent phosphorylation events toward wild-type levels [#1].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_269260","name":"SCE1","product":"suppressor of calcium-dependent egress SCE1","uniprot_acc":"S8EY50","chromosome":"TGME49_chrVIII","start_pos":5955886},{"strain":"GT1","gene_id":"TGGT1_269260","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrVIII","start_pos":5955672},{"strain":"RH88","gene_id":"TGRH88_082000","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023089","start_pos":11075705},{"strain":"VEG","gene_id":"TGVEG_269260","name":null,"product":"putative transmembrane protein","uniprot_acc":"V4ZSA9","chromosome":"TGVEG_chrVIII","start_pos":5972576}]}