{"gene":"TG_319930","gene_symbol":"PP6R","run_date":"2026-09-10T21:09:19","timeline":{"discoveries":[{"year":2023,"finding":"TgPP6C (catalytic subunit) and TgPP6R (regulatory subunit) likely form a complex, as indicated by co-assembly studies; the predicted structural subunit TgPP6S does not coassemble with TgPP6C and TgPP6R.","method":"Co-assembly/complex formation assay (pulldown/co-immunoprecipitation implied by subunit interaction characterization)","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — single-lab study using co-assembly data with negative result for TgPP6S providing orthogonal support, but abstract does not detail the precise co-IP method","pmids":["38091362"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2023,"finding":"TgPP6R is essential for parasite growth and replication, as its ablation impairs these processes.","method":"Conditional knockdown/ablation with growth and replication phenotypic readout","journal":"PLoS pathogens","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — clean loss-of-function with defined cellular phenotype (growth/replication defect), single lab","pmids":["38091362"],"is_preprint":false,"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]}],"current_model":"TgPP6R (regulatory subunit) forms a complex with the catalytic subunit TgPP6C as part of a PP6 phosphatase holoenzyme; TgPP6R is essential for parasite growth and replication, and together with TgPP6C controls cell cycle progression by regulating the phosphorylation of cell cycle-associated proteins during endodyogeny in Toxoplasma gondii."},"narrative":{"mechanistic_narrative":"TgPP6R is the regulatory subunit of a PP6-type protein phosphatase holoenzyme in Toxoplasma gondii, where it co-assembles with the catalytic subunit TgPP6C, while the predicted structural subunit TgPP6S does not join this complex [PMID:38091362]. TgPP6R is essential for parasite growth and replication, its ablation impairing both processes [PMID:38091362]. Beyond its assignment as the PP6 regulatory subunit and its essentiality, the specific substrate recognition or regulatory function contributed by TgPP6R itself has not been characterized in the available corpus.","teleology":[{"year":2023,"claim":"Establishing the composition of the Toxoplasma PP6 phosphatase was needed to define which subunits form a functional holoenzyme; co-assembly studies showed TgPP6R and the catalytic TgPP6C associate while the predicted structural TgPP6S does not.","evidence":"Co-assembly/complex formation assay in T. gondii RH, with a negative result for TgPP6S as orthogonal support","pmids":["38091362"],"confidence":"Medium","gaps":["Precise co-IP method and stoichiometry not detailed","Direct interaction interface between TgPP6R and TgPP6C not mapped","Role of TgPP6S in the pathway left undefined"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2023,"claim":"Whether the regulatory subunit is dispensable was unknown; conditional ablation demonstrated TgPP6R is essential for parasite growth and replication.","evidence":"Conditional knockdown/ablation with growth and replication readout in T. gondii RH","pmids":["38091362"],"confidence":"Medium","gaps":["The specific step of replication blocked by TgPP6R loss not resolved","Whether essentiality reflects holoenzyme assembly versus an independent function is unclear"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2023,"claim":"To connect the phosphatase to a cellular process, ablation and motif mutagenesis of the catalytic subunit TgPP6C showed it is required for synchronous daughter-cell division during endodyogeny and for ordered rosette formation.","evidence":"Conditional ablation, microscopy of endodyogeny, and mutagenesis of six conserved catalytic motifs in T. gondii RH","pmids":["38091362"],"confidence":"High","gaps":["Findings concern TgPP6C, not TgPP6R directly","How endodyogeny synchrony is mechanistically enforced by the phosphatase is unresolved"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]},{"year":2023,"claim":"To identify the molecular targets of the phosphatase, phosphoproteomics after TgPP6C ablation showed it predominantly controls phosphorylation of cell cycle regulatory proteins, defining PP6 as a dephosphorylase of cell cycle regulators.","evidence":"Mass spectrometry-based phosphoproteomics following conditional knockdown of TgPP6C in T. gondii RH","pmids":["38091362"],"confidence":"Medium","gaps":["No direct substrate validated by reconstitution","Substrates were mapped via the catalytic subunit, not through TgPP6R"],"attribution":[{"species":"Toxoplasma gondii","strain":"RH"}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["PP6 phosphatase holoenzyme (TgPP6C catalytic + TgPP6R regulatory subunit)"],"partners":["TGPP6C (CATALYTIC SUBUNIT)"],"other_free_text":["TgPP6R is essential for parasite growth and replication in T. gondii RH [#1].","TgPP6S, a predicted structural subunit, does not co-assemble with TgPP6C/TgPP6R [#0].","PP6 holoenzyme controls synchronous endodyogeny and dephosphorylation of cell cycle regulators, evidence derived via the catalytic subunit TgPP6C [#2, #3]."]},"strain_conflicts":[]},"prefetch_data":{},"corpus_meta":[{"pmid":"38091362","id":"PMC_38091362","title":"The Toxoplasma protein phosphatase 6 catalytic subunit (TgPP6C) is essential for cell cycle progression and virulence.","date":"2023","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/38091362","citation_count":11,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":2973,"output_tokens":1021,"usd":0.012117,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5912,"output_tokens":2195,"usd":0.042217,"stage2_stop_reason":"end_turn"},"total_usd":0.056692,"stage1_batch_id":"msgbatch_01S6GjoYQm8LTPUsdhASdqag","stage2_batch_id":"msgbatch_01VX63RTMdBJqsG6gQMqoCjz","note":"batch pricing = 50% of standard","corrective_rerun":"2026-09-10 wrong-gene rerun (round-4 rules)","corrective_reason":"summary amended"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"TgPP6C (catalytic subunit) and TgPP6R (regulatory subunit) likely form a complex, as indicated by co-assembly studies; the predicted structural subunit TgPP6S does not coassemble with TgPP6C and TgPP6R.\",\n      \"method\": \"Co-assembly/complex formation assay (pulldown/co-immunoprecipitation implied by subunit interaction characterization)\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — single-lab study using co-assembly data with negative result for TgPP6S providing orthogonal support, but abstract does not detail the precise co-IP method\",\n      \"pmids\": [\"38091362\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TgPP6R is essential for parasite growth and replication, as its ablation impairs these processes.\",\n      \"method\": \"Conditional knockdown/ablation with growth and replication phenotypic readout\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — clean loss-of-function with defined cellular phenotype (growth/replication defect), single lab\",\n      \"pmids\": [\"38091362\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"TgPP6C ablation significantly reduced synchronous division of daughter cells during endodyogeny, resulting in disordered rosettes, and the six conserved motifs of TgPP6C were required for efficient endodyogeny, establishing a direct role in cell cycle progression.\",\n      \"method\": \"Conditional knockdown/ablation, phenotypic analysis of endodyogeny by microscopy, mutagenesis of conserved motifs\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined cellular phenotype plus mutagenesis of catalytic motifs, two orthogonal approaches in a single rigorous study\",\n      \"pmids\": [\"38091362\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Phosphoproteomic analysis following TgPP6C ablation revealed that TgPP6C predominantly controls the phosphorylation status of proteins involved in regulation of the parasite cell cycle, placing TgPP6C as a phosphatase that dephosphorylates cell cycle regulators.\",\n      \"method\": \"Phosphoproteomics (mass spectrometry-based) after conditional knockdown of TgPP6C\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — quantitative phosphoproteomics with loss-of-function, single lab, no direct substrate validation by reconstitution\",\n      \"pmids\": [\"38091362\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    }\n  ],\n  \"current_model\": \"TgPP6R (regulatory subunit) forms a complex with the catalytic subunit TgPP6C as part of a PP6 phosphatase holoenzyme; TgPP6R is essential for parasite growth and replication, and together with TgPP6C controls cell cycle progression by regulating the phosphorylation of cell cycle-associated proteins during endodyogeny in Toxoplasma gondii.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TgPP6R is the regulatory subunit of a PP6-type protein phosphatase holoenzyme in Toxoplasma gondii, where it co-assembles with the catalytic subunit TgPP6C, while the predicted structural subunit TgPP6S does not join this complex [#0]. TgPP6R is essential for parasite growth and replication, its ablation impairing both processes [#1]. As part of this holoenzyme, the PP6 phosphatase governs cell cycle progression during endodyogeny: TgPP6C loss reduces synchronous daughter-cell division and disrupts rosette organization [#2], and phosphoproteomic analysis places the catalytic subunit as a dephosphorylase acting predominantly on cell cycle regulatory proteins [#3]. Beyond its assignment as the PP6 regulatory subunit and its essentiality, the specific substrate recognition or regulatory function contributed by TgPP6R itself has not been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Establishing the composition of the Toxoplasma PP6 phosphatase was needed to define which subunits form a functional holoenzyme; co-assembly studies showed TgPP6R and the catalytic TgPP6C associate while the predicted structural TgPP6S does not.\",\n      \"evidence\": \"Co-assembly/complex formation assay in T. gondii RH, with a negative result for TgPP6S as orthogonal support\",\n      \"pmids\": [\"38091362\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Precise co-IP method and stoichiometry not detailed\", \"Direct interaction interface between TgPP6R and TgPP6C not mapped\", \"Role of TgPP6S in the pathway left undefined\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Whether the regulatory subunit is dispensable was unknown; conditional ablation demonstrated TgPP6R is essential for parasite growth and replication.\",\n      \"evidence\": \"Conditional knockdown/ablation with growth and replication readout in T. gondii RH\",\n      \"pmids\": [\"38091362\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"The specific step of replication blocked by TgPP6R loss not resolved\", \"Whether essentiality reflects holoenzyme assembly versus an independent function is unclear\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"To connect the phosphatase to a cellular process, ablation and motif mutagenesis of the catalytic subunit TgPP6C showed it is required for synchronous daughter-cell division during endodyogeny and for ordered rosette formation.\",\n      \"evidence\": \"Conditional ablation, microscopy of endodyogeny, and mutagenesis of six conserved catalytic motifs in T. gondii RH\",\n      \"pmids\": [\"38091362\"],\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"Findings concern TgPP6C, not TgPP6R directly\", \"How endodyogeny synchrony is mechanistically enforced by the phosphatase is unresolved\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"To identify the molecular targets of the phosphatase, phosphoproteomics after TgPP6C ablation showed it predominantly controls phosphorylation of cell cycle regulatory proteins, defining PP6 as a dephosphorylase of cell cycle regulators.\",\n      \"evidence\": \"Mass spectrometry-based phosphoproteomics following conditional knockdown of TgPP6C in T. gondii RH\",\n      \"pmids\": [\"38091362\"],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No direct substrate validated by reconstitution\", \"Substrates were mapped via the catalytic subunit, not through TgPP6R\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific mechanistic contribution of TgPP6R itself — how it directs substrate recognition, subcellular targeting, or timing of the PP6 holoenzyme during the cell cycle — remains undefined.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"\",\n      \"gaps\": [\"No TgPP6R-specific substrate or interaction beyond TgPP6C characterized\", \"No structural model of the holoenzyme\", \"Regulatory role of TgPP6R distinct from catalytic subunit not dissected\"],\n      \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0019888\", \"supporting_discovery_ids\": [0], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]}\n    ],\n    \"localization\": [],\n    \"pathway\": [\n      {\"term_id\": \"GO:0007049\", \"supporting_discovery_ids\": [2, 3], \"attribution\": [{\"species\": \"Toxoplasma gondii\", \"strain\": \"RH\"}]}\n    ],\n    \"complexes\": [\"PP6 phosphatase holoenzyme (TgPP6C catalytic + TgPP6R regulatory subunit)\"],\n    \"partners\": [\"TgPP6C (catalytic subunit)\"],\n    \"other_free_text\": [\n      \"TgPP6R is essential for parasite growth and replication in T. gondii RH [#1].\",\n      \"TgPP6S, a predicted structural subunit, does not co-assemble with TgPP6C/TgPP6R [#0].\",\n      \"PP6 holoenzyme controls synchronous endodyogeny and dephosphorylation of cell cycle regulators, evidence derived via the catalytic subunit TgPP6C [#2, #3].\"\n    ]\n  },\n  \"strain_conflicts\": []\n}\n```","audit_flag":null,"strains":[{"strain":"ME49","gene_id":"TGME49_319930","name":"PP6R","product":"serine/threonine protein phosphatase 6 regulatory subunit PP6R","uniprot_acc":"S8GI39","chromosome":"TGME49_chrIV","start_pos":647104},{"strain":"GT1","gene_id":"TGGT1_319930","name":null,"product":"hypothetical protein","uniprot_acc":null,"chromosome":"TGGT1_chrIV","start_pos":591656},{"strain":"RH88","gene_id":"TGRH88_007260","name":null,"product":"unspecified product","uniprot_acc":null,"chromosome":"CM023085","start_pos":658034},{"strain":"VEG","gene_id":"TGVEG_319930","name":null,"product":"SIT4 phosphatase-associated protein","uniprot_acc":"V5B1M1","chromosome":"TGVEG_chrIV","start_pos":646695}]}