{"gene":"PF3D7_0214000","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2017,"finding":"Knockdown of the TRiC-θ subunit (CCT8) in P. falciparum caused a severe growth defect during asexual development but did not alter protein export into the red blood cell, establishing that CCT8 is essential for parasite growth but its function is unrelated to protein trafficking in the RBC compartment. Additionally, using parasite-specific antibody and epitope-tagged transgenic parasites, no export of the TRiC complex (including CCT8) into the RBC was detected, contradicting a prior claim of TRiC export.","method":"Regulatable knockdown (conditional knockdown line) of CCT8 with growth phenotype readout; parasite-specific antibody and epitope-tagged transgenic parasite imaging/fractionation","journal":"Cellular microbiology","confidence":"High","confidence_rationale":"Tier 2 / Moderate — conditional knockdown with specific phenotypic readout (growth defect, no export change) plus orthogonal antibody/tagged-parasite localization, single lab but two complementary methods","pmids":["28067475"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"CCT8 (PF3D7_0214000) was successfully C-terminally FLAG-tagged via Selection Linked Integration (SLI) in P. falciparum trophozoites and used as the handle for affinity purification of the intact PfCCT complex, demonstrating that CCT8 is a bona fide subunit of the P. falciparum chaperonin CCT complex. Proteomic analysis of the purified complex identified its interactome at the trophozoite stage.","method":"SLI-mediated endogenous C-terminal FLAG tagging; anti-FLAG immunoprecipitation followed by mass spectrometry proteomics (CCT8-FLAG parasite line)","journal":"Frontiers in molecular biosciences","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal pull-down and MS proteomics from endogenously tagged line, single lab, single study","pmids":["36567946"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"Multiple sequence alignment of all PfCCT subunits revealed that CCT8 (PfCCT8) carries the most divergent ATP-hydrolysis motif among P. falciparum CCT subunits: the canonical GDGTT motif is replaced by GDFTN, suggesting heterogeneity in ATP hydrolysis potential within the PfCCT complex and a possibly distinct catalytic contribution of CCT8 to substrate folding.","method":"Comparative multiple sequence alignment of all PfCCT subunit sequences; in silico characterization of the ATP-hydrolysis catalytic site","journal":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational/bioinformatic analysis only, no biochemical validation of CCT8 ATP hydrolysis activity reported","pmids":["26443825"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"CCT8, as part of the TRiC/CCT complex, was detected as an associating protein in an immunoprecipitation of PyCCR4-1 (a CAF1/CCR4/NOT deadenylase complex component) from P. yoelii schizonts by mass spectrometry, suggesting the TRiC complex (including CCT8) associates with the CAF1/CCR4/NOT complex, consistent with a role in inhibiting stress granule formation during active translation.","method":"GFP-tagged PyCCR4-1 immunoprecipitation followed by mass spectrometry (SAINT scoring) in P. yoelii schizonts","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-IP/MS experiment with low SAINT score for CCT8, indirect association cannot be distinguished from bridging interaction, single lab","pmids":["30703164"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2023,"finding":"In proximity-labeling (TurboID) experiments using PTP4 as bait in P. falciparum-infected erythrocytes, CCT8 (host CCT8 noted; however the body text references 'host chaperone CCT8' in proximity to parasite chaperones near PTP4/J-dots) was detected as enriched near PTP4 rather than KAHRP, consistent with CCT8's localization in the J-dot/chaperone-enriched compartment in the infected red blood cell.","method":"PerTurboID proximity biotinylation with site-specific quantification of biotinylated peptides; comparison between PTP4-TurboID and KAHRP-TurboID fusions","journal":"eLife","confidence":"Low","confidence_rationale":"Tier 3 / Weak — proximity labeling detects association but cannot distinguish direct from indirect; single study, and attribution to Plasmodium vs. host CCT8 is ambiguous in the abstract","pmids":["37737226"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_0214000 (CCT8) is the theta subunit of the P. falciparum chaperonin CCT/TRiC complex, is essential for asexual parasite growth (its knockdown causes severe growth defects), is not exported into the host red blood cell and is not involved in RBC protein trafficking, carries a divergent ATP-hydrolysis motif (GDFTN) suggesting heterogeneous catalytic contributions within the complex, and its FLAG-tagged form can affinity-purify the intact PfCCT complex for interactome analysis."},"narrative":{"mechanistic_narrative":"PF3D7_0214000 (CCT8) is the theta subunit of the P. falciparum chaperonin CCT/TRiC complex and is essential for asexual blood-stage growth, as its conditional knockdown produces a severe growth defect [PMID:28067475]. Endogenous C-terminal FLAG tagging confirms CCT8 as a bona fide subunit of the intact PfCCT complex and allows affinity purification of the complex for trophozoite-stage interactome analysis [PMID:36567946]. CCT8 is not exported into the host red blood cell and does not participate in protein trafficking into the RBC compartment, contradicting a prior claim of TRiC export [PMID:28067475]. Sequence analysis shows CCT8 carries the most divergent ATP-hydrolysis motif among PfCCT subunits (canonical GDGTT replaced by GDFTN), implying a distinct or reduced catalytic contribution to substrate folding within the complex [PMID:26443825]. Beyond its role as an essential CCT/TRiC subunit, no substrate-level folding mechanism specific to CCT8 has been characterized in the available corpus.","teleology":[{"year":2015,"claim":"The question of whether all PfCCT subunits contribute equally to ATP-driven folding was addressed by comparing catalytic motifs, revealing CCT8 as the most divergent subunit.","evidence":"Comparative multiple sequence alignment and in silico characterization of the ATP-hydrolysis site across all PfCCT subunits","pmids":["26443825"],"confidence":"Low","gaps":["Computational only; no biochemical validation of CCT8 ATP hydrolysis or its consequence for folding","Does not establish whether the GDFTN substitution abolishes or merely alters activity"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Whether CCT8 is functionally required in parasites and whether the TRiC complex is exported to remodel the host cell was tested, establishing essentiality for growth and ruling out an RBC-trafficking role.","evidence":"Regulatable conditional knockdown of CCT8 with growth readout, plus parasite-specific antibody and epitope-tagged parasite localization/fractionation","pmids":["28067475"],"confidence":"High","gaps":["The specific intracellular substrates folded by CCT8/PfCCT are not identified","Does not resolve which parasite processes fail upon CCT8 loss beyond a general growth defect"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"A possible link between the CCT/TRiC complex and translational/stress-granule regulation was raised by detecting CCT8 as an associating protein of the CAF1/CCR4/NOT deadenylase machinery.","evidence":"GFP-tagged PyCCR4-1 immunoprecipitation followed by mass spectrometry (SAINT scoring) in P. yoelii schizonts","pmids":["30703164"],"confidence":"Low","gaps":["Single co-IP/MS with low SAINT score for CCT8; direct versus bridged association not distinguished","Shown in P. yoelii, not P. falciparum; functional relevance to CCT8 untested"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2022,"claim":"Confirmation that CCT8 is an integral subunit of the assembled PfCCT complex, and a route to its interactome, was provided by endogenous tagging and pulldown.","evidence":"SLI-mediated endogenous C-terminal FLAG tagging and anti-FLAG immunoprecipitation with mass spectrometry from CCT8-FLAG parasites","pmids":["36567946"],"confidence":"Medium","gaps":["Interactome is stage-restricted (trophozoite); functional substrates not validated","Single lab, single study without reciprocal validation of individual partners"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2023,"claim":"Proximity labeling placed a CCT8 signal in the J-dot/chaperone-enriched compartment near PTP4 in infected erythrocytes, though the parasite-versus-host origin of the CCT8 was ambiguous.","evidence":"PerTurboID proximity biotinylation with PTP4 versus KAHRP baits in P. falciparum-infected erythrocytes","pmids":["37737226"],"confidence":"Low","gaps":["Attribution to parasite CCT8 versus host CCT8 is ambiguous in the source","Proximity labeling cannot distinguish direct from indirect association","Conflicts with the established finding that parasite CCT8 is not exported"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"The specific substrates folded by CCT8 and the functional consequence of its divergent GDFTN ATP-hydrolysis motif within the PfCCT complex remain unresolved.","evidence":"No direct biochemical or substrate-level characterization of CCT8 in the available corpus","pmids":[],"confidence":"Low","gaps":["No CCT8-specific folding substrate identified","No biochemical test of the GDFTN motif's effect on complex catalysis","No structural model of PfCCT with CCT8 positioned"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["Chaperonin-containing T-complex (CCT/TRiC), P. falciparum PfCCT"],"partners":["PFCCT COMPLEX SUBUNITS (CO-PURIFIED VIA CCT8-FLAG)","CAF1/CCR4/NOT COMPLEX VIA PYCCR4-1 (P. YOELII, LOW CONFIDENCE)","PTP4-PROXIMAL J-DOT COMPARTMENT (LOW CONFIDENCE, ATTRIBUTION AMBIGUOUS)"],"other_free_text":["Essential for P. falciparum asexual blood-stage growth (conditional knockdown gives severe growth defect).","Not exported into the host red blood cell and not involved in RBC protein trafficking, contradicting a prior TRiC-export claim.","Carries the most divergent ATP-hydrolysis motif among PfCCT subunits (GDGTT replaced by GDFTN), implying heterogeneous catalytic contribution."]}},"prefetch_data":{},"corpus_meta":[{"pmid":"28067475","id":"PMC_28067475","title":"The chaperonin TRiC forms an oligomeric complex in the malaria parasite cytosol.","date":"2017","source":"Cellular microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/28067475","citation_count":51,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"25615740","id":"PMC_25615740","title":"New Export Pathway in Plasmodium falciparum-Infected Erythrocytes: Role of the Parasite Group II Chaperonin, PfTRiC.","date":"2015","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/25615740","citation_count":15,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["curated_ref"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"37737226","id":"","title":"PerTurboID, a targeted in situ method reveals the impact of kinase deletion on its local protein environment in the cytoadhesion complex of malaria-causing parasites.","date":"2023","source":"eLife","url":"https://pubmed.ncbi.nlm.nih.gov/37737226","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCT8"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"36567946","id":"","title":"The malaria parasite chaperonin containing TCP-1 (CCT) complex: Data integration with other CCT proteomes.","date":"2022","source":"Frontiers in molecular biosciences","url":"https://pubmed.ncbi.nlm.nih.gov/36567946","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCT8"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"30703164","id":"","title":"Plasmodium male gametocyte development and transmission are critically regulated by the two putative deadenylases of the CAF1/CCR4/NOT complex.","date":"2019","source":"PLoS pathogens","url":"https://pubmed.ncbi.nlm.nih.gov/30703164","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCT8"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false},{"pmid":"26443825","id":"","title":"Plasmodium actin is incompletely folded by heterologous protein-folding machinery and likely requires the native Plasmodium chaperonin complex to enter a mature functional state.","date":"2015","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/26443825","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCT8"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":8578,"output_tokens":1689,"usd":0.025535,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6748,"output_tokens":2574,"usd":0.049045,"stage2_stop_reason":"end_turn"},"total_usd":0.07458,"stage1_batch_id":"msgbatch_01SRp5hyRc82zNjddxyCCXGk","stage2_batch_id":"msgbatch_01K3BTmBazRo3pRrMvyaPMTY","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"Knockdown of the TRiC-θ subunit (CCT8) in P. falciparum caused a severe growth defect during asexual development but did not alter protein export into the red blood cell, establishing that CCT8 is essential for parasite growth but its function is unrelated to protein trafficking in the RBC compartment. Additionally, using parasite-specific antibody and epitope-tagged transgenic parasites, no export of the TRiC complex (including CCT8) into the RBC was detected, contradicting a prior claim of TRiC export.\",\n      \"method\": \"Regulatable knockdown (conditional knockdown line) of CCT8 with growth phenotype readout; parasite-specific antibody and epitope-tagged transgenic parasite imaging/fractionation\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — conditional knockdown with specific phenotypic readout (growth defect, no export change) plus orthogonal antibody/tagged-parasite localization, single lab but two complementary methods\",\n      \"pmids\": [\"28067475\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CCT8 (PF3D7_0214000) was successfully C-terminally FLAG-tagged via Selection Linked Integration (SLI) in P. falciparum trophozoites and used as the handle for affinity purification of the intact PfCCT complex, demonstrating that CCT8 is a bona fide subunit of the P. falciparum chaperonin CCT complex. Proteomic analysis of the purified complex identified its interactome at the trophozoite stage.\",\n      \"method\": \"SLI-mediated endogenous C-terminal FLAG tagging; anti-FLAG immunoprecipitation followed by mass spectrometry proteomics (CCT8-FLAG parasite line)\",\n      \"journal\": \"Frontiers in molecular biosciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal pull-down and MS proteomics from endogenously tagged line, single lab, single study\",\n      \"pmids\": [\"36567946\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Multiple sequence alignment of all PfCCT subunits revealed that CCT8 (PfCCT8) carries the most divergent ATP-hydrolysis motif among P. falciparum CCT subunits: the canonical GDGTT motif is replaced by GDFTN, suggesting heterogeneity in ATP hydrolysis potential within the PfCCT complex and a possibly distinct catalytic contribution of CCT8 to substrate folding.\",\n      \"method\": \"Comparative multiple sequence alignment of all PfCCT subunit sequences; in silico characterization of the ATP-hydrolysis catalytic site\",\n      \"journal\": \"FASEB journal : official publication of the Federation of American Societies for Experimental Biology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational/bioinformatic analysis only, no biochemical validation of CCT8 ATP hydrolysis activity reported\",\n      \"pmids\": [\"26443825\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CCT8, as part of the TRiC/CCT complex, was detected as an associating protein in an immunoprecipitation of PyCCR4-1 (a CAF1/CCR4/NOT deadenylase complex component) from P. yoelii schizonts by mass spectrometry, suggesting the TRiC complex (including CCT8) associates with the CAF1/CCR4/NOT complex, consistent with a role in inhibiting stress granule formation during active translation.\",\n      \"method\": \"GFP-tagged PyCCR4-1 immunoprecipitation followed by mass spectrometry (SAINT scoring) in P. yoelii schizonts\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-IP/MS experiment with low SAINT score for CCT8, indirect association cannot be distinguished from bridging interaction, single lab\",\n      \"pmids\": [\"30703164\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"In proximity-labeling (TurboID) experiments using PTP4 as bait in P. falciparum-infected erythrocytes, CCT8 (host CCT8 noted; however the body text references 'host chaperone CCT8' in proximity to parasite chaperones near PTP4/J-dots) was detected as enriched near PTP4 rather than KAHRP, consistent with CCT8's localization in the J-dot/chaperone-enriched compartment in the infected red blood cell.\",\n      \"method\": \"PerTurboID proximity biotinylation with site-specific quantification of biotinylated peptides; comparison between PTP4-TurboID and KAHRP-TurboID fusions\",\n      \"journal\": \"eLife\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — proximity labeling detects association but cannot distinguish direct from indirect; single study, and attribution to Plasmodium vs. host CCT8 is ambiguous in the abstract\",\n      \"pmids\": [\"37737226\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"PF3D7_0214000 (CCT8) is the theta subunit of the P. falciparum chaperonin CCT/TRiC complex, is essential for asexual parasite growth (its knockdown causes severe growth defects), is not exported into the host red blood cell and is not involved in RBC protein trafficking, carries a divergent ATP-hydrolysis motif (GDFTN) suggesting heterogeneous catalytic contributions within the complex, and its FLAG-tagged form can affinity-purify the intact PfCCT complex for interactome analysis.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_0214000 (CCT8) is the theta subunit of the P. falciparum chaperonin CCT/TRiC complex and is essential for asexual blood-stage growth, as its conditional knockdown produces a severe growth defect [#0]. Endogenous C-terminal FLAG tagging confirms CCT8 as a bona fide subunit of the intact PfCCT complex and allows affinity purification of the complex for trophozoite-stage interactome analysis [#1]. CCT8 is not exported into the host red blood cell and does not participate in protein trafficking into the RBC compartment, contradicting a prior claim of TRiC export [#0]. Sequence analysis shows CCT8 carries the most divergent ATP-hydrolysis motif among PfCCT subunits (canonical GDGTT replaced by GDFTN), implying a distinct or reduced catalytic contribution to substrate folding within the complex [#2]. Beyond its role as an essential CCT/TRiC subunit, no substrate-level folding mechanism specific to CCT8 has been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"The question of whether all PfCCT subunits contribute equally to ATP-driven folding was addressed by comparing catalytic motifs, revealing CCT8 as the most divergent subunit.\",\n      \"evidence\": \"Comparative multiple sequence alignment and in silico characterization of the ATP-hydrolysis site across all PfCCT subunits\",\n      \"pmids\": [\"26443825\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Computational only; no biochemical validation of CCT8 ATP hydrolysis or its consequence for folding\",\n        \"Does not establish whether the GDFTN substitution abolishes or merely alters activity\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Whether CCT8 is functionally required in parasites and whether the TRiC complex is exported to remodel the host cell was tested, establishing essentiality for growth and ruling out an RBC-trafficking role.\",\n      \"evidence\": \"Regulatable conditional knockdown of CCT8 with growth readout, plus parasite-specific antibody and epitope-tagged parasite localization/fractionation\",\n      \"pmids\": [\"28067475\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"The specific intracellular substrates folded by CCT8/PfCCT are not identified\",\n        \"Does not resolve which parasite processes fail upon CCT8 loss beyond a general growth defect\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"A possible link between the CCT/TRiC complex and translational/stress-granule regulation was raised by detecting CCT8 as an associating protein of the CAF1/CCR4/NOT deadenylase machinery.\",\n      \"evidence\": \"GFP-tagged PyCCR4-1 immunoprecipitation followed by mass spectrometry (SAINT scoring) in P. yoelii schizonts\",\n      \"pmids\": [\"30703164\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single co-IP/MS with low SAINT score for CCT8; direct versus bridged association not distinguished\",\n        \"Shown in P. yoelii, not P. falciparum; functional relevance to CCT8 untested\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Confirmation that CCT8 is an integral subunit of the assembled PfCCT complex, and a route to its interactome, was provided by endogenous tagging and pulldown.\",\n      \"evidence\": \"SLI-mediated endogenous C-terminal FLAG tagging and anti-FLAG immunoprecipitation with mass spectrometry from CCT8-FLAG parasites\",\n      \"pmids\": [\"36567946\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Interactome is stage-restricted (trophozoite); functional substrates not validated\",\n        \"Single lab, single study without reciprocal validation of individual partners\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Proximity labeling placed a CCT8 signal in the J-dot/chaperone-enriched compartment near PTP4 in infected erythrocytes, though the parasite-versus-host origin of the CCT8 was ambiguous.\",\n      \"evidence\": \"PerTurboID proximity biotinylation with PTP4 versus KAHRP baits in P. falciparum-infected erythrocytes\",\n      \"pmids\": [\"37737226\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Attribution to parasite CCT8 versus host CCT8 is ambiguous in the source\",\n        \"Proximity labeling cannot distinguish direct from indirect association\",\n        \"Conflicts with the established finding that parasite CCT8 is not exported\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific substrates folded by CCT8 and the functional consequence of its divergent GDFTN ATP-hydrolysis motif within the PfCCT complex remain unresolved.\",\n      \"evidence\": \"No direct biochemical or substrate-level characterization of CCT8 in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No CCT8-specific folding substrate identified\",\n        \"No biochemical test of the GDFTN motif's effect on complex catalysis\",\n        \"No structural model of PfCCT with CCT8 positioned\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140662\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005737\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006457\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [\"Chaperonin-containing T-complex (CCT/TRiC), P. falciparum PfCCT\"],\n    \"partners\": [\"PfCCT complex subunits (co-purified via CCT8-FLAG)\", \"CAF1/CCR4/NOT complex via PyCCR4-1 (P. yoelii, low confidence)\", \"PTP4-proximal J-dot compartment (low confidence, attribution ambiguous)\"],\n    \"other_free_text\": [\n      \"Essential for P. falciparum asexual blood-stage growth (conditional knockdown gives severe growth defect).\",\n      \"Not exported into the host red blood cell and not involved in RBC protein trafficking, contradicting a prior TRiC-export claim.\",\n      \"Carries the most divergent ATP-hydrolysis motif among PfCCT subunits (GDGTT replaced by GDFTN), implying heterogeneous catalytic contribution.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0214000","name":null,"product":"T-complex protein 1 subunit theta","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0310900","name":null,"product":"T-complex protein 1 subunit theta, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0406800","name":null,"product":"T-complex protein 1 subunit theta, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CCT8","evaluation":null}