{"gene":"TG_276130","gene_symbol":"CPC2","run_date":"2026-09-08T14:08:30","timeline":{"discoveries":[{"year":2006,"finding":"TgCPC2 is a cathepsin C exopeptidase that removes dipeptides from unblocked N-terminal substrates of proteins or peptides, consistent with its papain-family cysteine protease classification.","method":"Enzymatic activity characterization with cathepsin C-specific inhibitor (Gly-Phe-dimethylketone) and substrate assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — enzymatic activity established with specific inhibitor and substrate assays in a single lab study with functional follow-up","pmids":["17164247"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2006,"finding":"TgCPC2 localizes to dense granules (constitutive secretory vesicles) of tachyzoites, as determined by subcellular localization experiments.","method":"Subcellular fractionation / localization assay identifying dense granule compartment","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — direct localization experiment reported in single lab study; functional link to secretory pathway inferred from compartment identity","pmids":["17164247"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2006,"finding":"TgCPC2 is required for peptide/protein degradation in the parasitophorous vacuole; cathepsin C inhibitor completely blocked degradation of E. coli beta-lactamase secreted into the parasitophorous vacuole of transgenic tachyzoites.","method":"Transgenic parasite expressing beta-lactamase as reporter in parasitophorous vacuole, treated with cathepsin C inhibitor Gly-Phe-dimethylketone","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional reporter assay with specific inhibitor in single lab; TgCPC2 implicated alongside TgCPC1 but not individually resolved by genetic KO","pmids":["17164247"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2006,"finding":"Upon targeted disruption of TgCPC1, TgCPC2 is up-regulated and compensates functionally, as TgCPC1 knockout parasites show no defect in invasion and growth; this epistatic compensation indicates TgCPC2 can substitute for TgCPC1 in tachyzoite growth.","method":"Targeted gene disruption of TgCPC1 followed by real-time PCR detection of TgCPC2 up-regulation and growth/invasion assays","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis via targeted disruption with phenotypic and expression readouts, single lab","pmids":["17164247"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2006,"finding":"TgCPC2 mRNA is undetectable in in vivo bradyzoites by real-time PCR, indicating stage-specific expression restricted to tachyzoites.","method":"Real-time PCR quantification of cathepsin mRNA in tachyzoites versus in vivo bradyzoites","journal":"The Journal of biological chemistry","confidence":"Low","confidence_rationale":"Tier 4 / Weak — expression-level measurement only, no direct mechanistic experiment on TgCPC2 function in bradyzoites","pmids":["17164247"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"current_model":"TgCPC2 is a dense-granule-localized cathepsin C exopeptidase in Toxoplasma gondii tachyzoites that removes dipeptides from unblocked N-terminal substrates, contributes to protein degradation in the parasitophorous vacuole, and can functionally substitute for TgCPC1 when the latter is genetically disrupted, collectively supporting a role for TgCPC2 in parasite intracellular growth and survival."},"narrative":{"mechanistic_narrative":"TgCPC2 is a papain-family cathepsin C cysteine exopeptidase of Toxoplasma gondii that removes dipeptides from the unblocked N-termini of proteins and peptides [PMID:17164247]. It localizes to the dense granules, the constitutive secretory vesicles of tachyzoites [PMID:17164247], and contributes to peptide/protein degradation within the parasitophorous vacuole, where cathepsin C inhibition completely blocks turnover of a secreted beta-lactamase reporter [PMID:17164247]. TgCPC2 functionally overlaps with the paralog TgCPC1: disruption of TgCPC1 up-regulates TgCPC2 and produces no invasion or growth defect, indicating TgCPC2 can substitute for TgCPC1 during tachyzoite growth [PMID:17164247]. Beyond this dense-granule/vacuolar degradative role in tachyzoites, no further mechanistic detail has been characterized in the available corpus.","teleology":[{"year":2006,"claim":"Established the biochemical identity of TgCPC2 as a cathepsin C exopeptidase, defining its mode of substrate processing as dipeptidyl removal from unblocked N-termini.","evidence":"Enzymatic activity assays with the cathepsin C-specific inhibitor Gly-Phe-dimethylketone and defined substrates","pmids":["17164247"],"confidence":"Medium","gaps":["No structural model or catalytic residue mapping","Substrate specificity beyond the dipeptidyl-N-terminal mode not detailed","Enzyme characterization from a single lab study"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2006,"claim":"Placed TgCPC2 in the dense granule secretory compartment, linking the enzyme to material delivered into the parasitophorous vacuole.","evidence":"Subcellular fractionation/localization in tachyzoites","pmids":["17164247"],"confidence":"Medium","gaps":["Trafficking route and processing/activation en route to dense granules unknown","Whether it is secreted into the vacuole versus retained in granules not resolved"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2006,"claim":"Connected cathepsin C activity to protein degradation inside the parasitophorous vacuole, implicating TgCPC2 in vacuolar proteolysis.","evidence":"Transgenic tachyzoites expressing a beta-lactamase reporter in the parasitophorous vacuole, with degradation blocked by cathepsin C inhibitor","pmids":["17164247"],"confidence":"Medium","gaps":["TgCPC2 contribution not resolved individually from TgCPC1 by genetic knockout","Physiological native substrates in the vacuole not identified","Inhibitor is not TgCPC2-specific across the two paralogs"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2006,"claim":"Demonstrated functional redundancy with TgCPC1, showing TgCPC2 is up-regulated and compensates when TgCPC1 is disrupted, so no growth or invasion defect results.","evidence":"Targeted gene disruption of TgCPC1 with real-time PCR of TgCPC2 and growth/invasion assays","pmids":["17164247"],"confidence":"Medium","gaps":["Phenotype of a direct TgCPC2 knockout not determined","Mechanism of transcriptional up-regulation upon TgCPC1 loss unknown","Whether double disruption is lethal not established"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":2006,"claim":"Defined TgCPC2 expression as stage-restricted to tachyzoites, absent in in vivo bradyzoites.","evidence":"Real-time PCR quantification of transcript across tachyzoites and in vivo bradyzoites","pmids":["17164247"],"confidence":"Low","gaps":["Expression-only measurement; no functional test of TgCPC2 in bradyzoites","Regulatory basis of stage-specific expression unknown"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]},{"year":null,"claim":"The individual, non-redundant contribution of TgCPC2 to vacuolar proteolysis and parasite fitness, its native substrates, and its structural basis of catalysis remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No direct TgCPC2 knockout phenotype","No endogenous substrate identified","No structural characterization"],"attribution":[{"species":"Toxoplasma gondii","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":[],"partners":["TGCPC1 (FUNCTIONAL PARALOG; COMPENSATED BY TGCPC2 UPON DISRUPTION)"],"other_free_text":["Expression restricted to tachyzoites; transcript undetectable in in vivo bradyzoites [#4]","Cathepsin C inhibitor Gly-Phe-dimethylketone blocks activity and vacuolar reporter degradation [#0, #2]"]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"17164247","id":"PMC_17164247","title":"Cathepsin Cs are key for the intracellular survival of the protozoan parasite, Toxoplasma gondii.","date":"2006","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/17164247","citation_count":46,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":3023,"output_tokens":1247,"usd":0.013887,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6262,"output_tokens":2401,"usd":0.045667,"stage2_stop_reason":"end_turn"},"total_usd":0.059554,"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\": 2006,\n      \"finding\": \"TgCPC2 is a cathepsin C exopeptidase that removes dipeptides from unblocked N-terminal substrates of proteins or peptides, consistent with its papain-family cysteine protease classification.\",\n      \"method\": \"Enzymatic activity characterization with cathepsin C-specific inhibitor (Gly-Phe-dimethylketone) and substrate assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — enzymatic activity established with specific inhibitor and substrate assays in a single lab study with functional follow-up\",\n      \"pmids\": [\"17164247\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"TgCPC2 localizes to dense granules (constitutive secretory vesicles) of tachyzoites, as determined by subcellular localization experiments.\",\n      \"method\": \"Subcellular fractionation / localization assay identifying dense granule compartment\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — direct localization experiment reported in single lab study; functional link to secretory pathway inferred from compartment identity\",\n      \"pmids\": [\"17164247\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"TgCPC2 is required for peptide/protein degradation in the parasitophorous vacuole; cathepsin C inhibitor completely blocked degradation of E. coli beta-lactamase secreted into the parasitophorous vacuole of transgenic tachyzoites.\",\n      \"method\": \"Transgenic parasite expressing beta-lactamase as reporter in parasitophorous vacuole, treated with cathepsin C inhibitor Gly-Phe-dimethylketone\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional reporter assay with specific inhibitor in single lab; TgCPC2 implicated alongside TgCPC1 but not individually resolved by genetic KO\",\n      \"pmids\": [\"17164247\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"Upon targeted disruption of TgCPC1, TgCPC2 is up-regulated and compensates functionally, as TgCPC1 knockout parasites show no defect in invasion and growth; this epistatic compensation indicates TgCPC2 can substitute for TgCPC1 in tachyzoite growth.\",\n      \"method\": \"Targeted gene disruption of TgCPC1 followed by real-time PCR detection of TgCPC2 up-regulation and growth/invasion assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis via targeted disruption with phenotypic and expression readouts, single lab\",\n      \"pmids\": [\"17164247\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"TgCPC2 mRNA is undetectable in in vivo bradyzoites by real-time PCR, indicating stage-specific expression restricted to tachyzoites.\",\n      \"method\": \"Real-time PCR quantification of cathepsin mRNA in tachyzoites versus in vivo bradyzoites\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — expression-level measurement only, no direct mechanistic experiment on TgCPC2 function in bradyzoites\",\n      \"pmids\": [\"17164247\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"TgCPC2 is a dense-granule-localized cathepsin C exopeptidase in Toxoplasma gondii tachyzoites that removes dipeptides from unblocked N-terminal substrates, contributes to protein degradation in the parasitophorous vacuole, and can functionally substitute for TgCPC1 when the latter is genetically disrupted, collectively supporting a role for TgCPC2 in parasite intracellular growth and survival.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TgCPC2 is a papain-family cathepsin C cysteine exopeptidase of Toxoplasma gondii that removes dipeptides from the unblocked N-termini of proteins and peptides [#0]. It localizes to the dense granules, the constitutive secretory vesicles of tachyzoites [#1], and contributes to peptide/protein degradation within the parasitophorous vacuole, where cathepsin C inhibition completely blocks turnover of a secreted beta-lactamase reporter [#2]. TgCPC2 functionally overlaps with the paralog TgCPC1: disruption of TgCPC1 up-regulates TgCPC2 and produces no invasion or growth defect, indicating TgCPC2 can substitute for TgCPC1 during tachyzoite growth [#3]. Beyond this dense-granule/vacuolar degradative role in tachyzoites, no further mechanistic detail has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"Established the biochemical identity of TgCPC2 as a cathepsin C exopeptidase, defining its mode of substrate processing as dipeptidyl removal from unblocked N-termini.\",\n      \"evidence\": \"Enzymatic activity assays with the cathepsin C-specific inhibitor Gly-Phe-dimethylketone and defined substrates\",\n      \"pmids\": [\"17164247\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"No structural model or catalytic residue mapping\",\n        \"Substrate specificity beyond the dipeptidyl-N-terminal mode not detailed\",\n        \"Enzyme characterization from a single lab study\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Placed TgCPC2 in the dense granule secretory compartment, linking the enzyme to material delivered into the parasitophorous vacuole.\",\n      \"evidence\": \"Subcellular fractionation/localization in tachyzoites\",\n      \"pmids\": [\"17164247\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Trafficking route and processing/activation en route to dense granules unknown\",\n        \"Whether it is secreted into the vacuole versus retained in granules not resolved\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Connected cathepsin C activity to protein degradation inside the parasitophorous vacuole, implicating TgCPC2 in vacuolar proteolysis.\",\n      \"evidence\": \"Transgenic tachyzoites expressing a beta-lactamase reporter in the parasitophorous vacuole, with degradation blocked by cathepsin C inhibitor\",\n      \"pmids\": [\"17164247\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"TgCPC2 contribution not resolved individually from TgCPC1 by genetic knockout\",\n        \"Physiological native substrates in the vacuole not identified\",\n        \"Inhibitor is not TgCPC2-specific across the two paralogs\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Demonstrated functional redundancy with TgCPC1, showing TgCPC2 is up-regulated and compensates when TgCPC1 is disrupted, so no growth or invasion defect results.\",\n      \"evidence\": \"Targeted gene disruption of TgCPC1 with real-time PCR of TgCPC2 and growth/invasion assays\",\n      \"pmids\": [\"17164247\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Phenotype of a direct TgCPC2 knockout not determined\",\n        \"Mechanism of transcriptional up-regulation upon TgCPC1 loss unknown\",\n        \"Whether double disruption is lethal not established\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2006,\n      \"claim\": \"Defined TgCPC2 expression as stage-restricted to tachyzoites, absent in in vivo bradyzoites.\",\n      \"evidence\": \"Real-time PCR quantification of transcript across tachyzoites and in vivo bradyzoites\",\n      \"pmids\": [\"17164247\"],\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\n        \"Expression-only measurement; no functional test of TgCPC2 in bradyzoites\",\n        \"Regulatory basis of stage-specific expression unknown\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The individual, non-redundant contribution of TgCPC2 to vacuolar proteolysis and parasite fitness, its native substrates, and its structural basis of catalysis remain undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No direct TgCPC2 knockout phenotype\",\n        \"No endogenous substrate identified\",\n        \"No structural characterization\"\n      ],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0004185\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]},\n      {\"term_id\": \"GO:0008234\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0020020\", \"supporting_discovery_ids\": [1], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006508\", \"supporting_discovery_ids\": [2], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"\"}]}\n    ],\n    \"complexes\": [],\n    \"partners\": [\"TgCPC1 (functional paralog; compensated by TgCPC2 upon disruption)\"],\n    \"other_free_text\": [\n      \"Expression restricted to tachyzoites; transcript undetectable in in vivo bradyzoites [#4]\",\n      \"Cathepsin C inhibitor Gly-Phe-dimethylketone blocks activity and vacuolar reporter degradation [#0, #2]\"\n    ]\n  },\n  \"strain_conflicts\": []\n}","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_276130","name":"CPC2","product":"cathepsin CPC2","uniprot_acc":"A0A125YLA1","chromosome":"TGME49_chrIII","start_pos":125876},{"strain":"GT1","gene_id":"TGGT1_276130","name":null,"product":"cathepsin CPC2","uniprot_acc":null,"chromosome":"TGGT1_chrIII","start_pos":114076},{"strain":"RH88","gene_id":"TGRH88_006050","name":null,"product":"cathepsin CPC2","uniprot_acc":null,"chromosome":"CM023084","start_pos":2476330},{"strain":"VEG","gene_id":"TGVEG_276130","name":null,"product":"cathepsin CPC2","uniprot_acc":"B9QIL3","chromosome":"TGVEG_chrIII","start_pos":136391}]}