{"gene":"TG_212820","gene_symbol":"","run_date":"2026-09-08T11:06:24","timeline":{"discoveries":[{"year":2020,"finding":"Toxoplasma gondii DSK2 (TGGT1_223680, ubiquitin family protein), along with DDI1 and RAD23, are UBL-UBA shuttle proteins that localize to the cytoplasm and nucleus and escort ubiquitinylated proteins to the proteasome for degradation; deletion of these shuttle proteins caused accumulation of ubiquitinylated proteins and asynchronous cell division.","method":"Gene knockout (triple-gene deletion), localization by imaging (cytoplasm/nucleus), accumulation of ubiquitinylated proteins assayed upon deletion, cell division phenotype analysis","journal":"FASEB Journal","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean KO with defined cellular phenotype (ubiquitin accumulation, asynchronous division) and direct localization experiment, single lab, multiple orthogonal readouts","pmids":["32808330"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"GT1"}]}],"current_model":"DSK2 (ubiquitin family protein, TGGT1_223680) is a UBL-UBA shuttle protein that localizes to the cytoplasm and nucleus of Toxoplasma gondii, where it escorts ubiquitinylated proteins to the proteasome for degradation and is required for synchronous parasite cell division."},"narrative":{"mechanistic_narrative":"The Toxoplasma gondii ubiquitin family protein DSK2 (TGGT1_223680) is a UBL-UBA shuttle protein that, together with DDI1 and RAD23, escorts ubiquitinylated proteins to the proteasome for degradation [PMID:32808330]. It localizes to both the cytoplasm and the nucleus, and combined deletion of these shuttle factors causes accumulation of ubiquitinylated proteins and asynchronous parasite cell division, linking DSK2-dependent proteasomal targeting to synchronous division [PMID:32808330]. Beyond [PMID:32808330], no further mechanistic detail — including substrate specificity, direct proteasome contacts, or the individual contribution of DSK2 relative to DDI1 and RAD23 — has been characterized in the available corpus.","teleology":[{"year":2020,"claim":"It was unknown whether Toxoplasma encodes UBL-UBA shuttle proteins linking ubiquitinylation to proteasomal degradation; knockout showed DSK2 (with DDI1 and RAD23) is required to clear ubiquitinylated proteins and maintain synchronous division, establishing a shuttle-to-proteasome role tied to cell-cycle fidelity.","evidence":"Triple-gene deletion, imaging-based localization, and assays of ubiquitinylated-protein accumulation and cell-division phenotype in T. gondii GT1","pmids":["32808330"],"confidence":"Medium","gaps":["The individual contribution of DSK2 versus DDI1 and RAD23 is not resolved by the combined deletion","No specific ubiquitinylated substrates or direct proteasome contacts were identified","The mechanistic link between shuttle-protein loss and asynchronous division was not defined"],"attribution":[{"species":"Toxoplasma gondii","strain":"GT1"}]},{"year":null,"claim":"The substrate repertoire, binding partners at the proteasome, and the mechanism by which DSK2 loss disrupts division synchrony remain undefined.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No substrate identified for DSK2","No structural or biochemical characterization of UBL/UBA-mediated proteasome docking","DSK2-specific phenotype uncoupled from DDI1/RAD23 not established"],"attribution":[{"species":"Toxoplasma gondii","strain":"GT1"}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["DDI1","RAD23"],"other_free_text":["Deletion of DSK2 together with DDI1 and RAD23 causes accumulation of ubiquitinylated proteins and asynchronous parasite cell division [#0]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"32808330","id":"PMC_32808330","title":"Toxoplasma gondii UBL-UBA shuttle proteins contribute to the degradation of ubiquitinylated proteins and are important for synchronous cell division and virulence.","date":"2020","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/32808330","citation_count":24,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2891,"output_tokens":398,"usd":0.007321,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5032,"output_tokens":1358,"usd":0.029555,"stage2_stop_reason":"end_turn"},"total_usd":0.036876,"stage1_batch_id":"msgbatch_01WokvBYTB6JLnYrpD4rXnyV","stage2_batch_id":"msgbatch_01M7hsQDvz6AqVC9DLVjQzzc","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2020,\n      \"finding\": \"Toxoplasma gondii DSK2 (TGGT1_223680, ubiquitin family protein), along with DDI1 and RAD23, are UBL-UBA shuttle proteins that localize to the cytoplasm and nucleus and escort ubiquitinylated proteins to the proteasome for degradation; deletion of these shuttle proteins caused accumulation of ubiquitinylated proteins and asynchronous cell division.\",\n      \"method\": \"Gene knockout (triple-gene deletion), localization by imaging (cytoplasm/nucleus), accumulation of ubiquitinylated proteins assayed upon deletion, cell division phenotype analysis\",\n      \"journal\": \"FASEB Journal\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean KO with defined cellular phenotype (ubiquitin accumulation, asynchronous division) and direct localization experiment, single lab, multiple orthogonal readouts\",\n      \"pmids\": [\"32808330\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}\n      ]\n    }\n  ],\n  \"current_model\": \"DSK2 (ubiquitin family protein, TGGT1_223680) is a UBL-UBA shuttle protein that localizes to the cytoplasm and nucleus of Toxoplasma gondii, where it escorts ubiquitinylated proteins to the proteasome for degradation and is required for synchronous parasite cell division.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"The Toxoplasma gondii ubiquitin family protein DSK2 (TGGT1_223680) is a UBL-UBA shuttle protein that, together with DDI1 and RAD23, escorts ubiquitinylated proteins to the proteasome for degradation [#0]. It localizes to both the cytoplasm and the nucleus, and combined deletion of these shuttle factors causes accumulation of ubiquitinylated proteins and asynchronous parasite cell division, linking DSK2-dependent proteasomal targeting to synchronous division [#0]. Beyond [#0], no further mechanistic detail — including substrate specificity, direct proteasome contacts, or the individual contribution of DSK2 relative to DDI1 and RAD23 — has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2020,\n      \"claim\": \"It was unknown whether Toxoplasma encodes UBL-UBA shuttle proteins linking ubiquitinylation to proteasomal degradation; knockout showed DSK2 (with DDI1 and RAD23) is required to clear ubiquitinylated proteins and maintain synchronous division, establishing a shuttle-to-proteasome role tied to cell-cycle fidelity.\",\n      \"evidence\": \"Triple-gene deletion, imaging-based localization, and assays of ubiquitinylated-protein accumulation and cell-division phenotype in T. gondii GT1\",\n      \"pmids\": [\"32808330\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The individual contribution of DSK2 versus DDI1 and RAD23 is not resolved by the combined deletion\",\n        \"No specific ubiquitinylated substrates or direct proteasome contacts were identified\",\n        \"The mechanistic link between shuttle-protein loss and asynchronous division was not defined\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The substrate repertoire, binding partners at the proteasome, and the mechanism by which DSK2 loss disrupts division synchrony remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No substrate identified for DSK2\",\n        \"No structural or biochemical characterization of UBL/UBA-mediated proteasome docking\",\n        \"DSK2-specific phenotype uncoupled from DDI1/RAD23 not established\"\n      ],\n      \"attribution\": [\n        {\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0031593\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0043161\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"GT1\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"DDI1\", \"RAD23\"],\n    \"other_free_text\": [\n      \"Deletion of DSK2 together with DDI1 and RAD23 causes accumulation of ubiquitinylated proteins and asynchronous parasite cell division [#0]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_212820","name":null,"product":"ubiquitin family protein","uniprot_acc":"S8GH27","chromosome":"TGME49_chrV","start_pos":632259},{"strain":"GT1","gene_id":"TGGT1_212820","name":null,"product":"ubiquitin family protein","uniprot_acc":null,"chromosome":"TGGT1_chrV","start_pos":502016},{"strain":"RH88","gene_id":"TGRH88_024210","name":null,"product":"ubiquitin family protein","uniprot_acc":null,"chromosome":"CM023086","start_pos":668162},{"strain":"VEG","gene_id":"TGVEG_212820","name":null,"product":"ubiquitin family protein","uniprot_acc":"B9QGK9","chromosome":"TGVEG_chrV","start_pos":597787}]}