{"gene":"PF3D7_1229500","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2015,"finding":"The P. falciparum TRiC chaperonin complex (PfTRiC), of which CCT3 (PF3D7_1229500) is a subunit, associates with and traffics Maurer's cleft membrane proteins (including PfSBP1) through the red blood cell cytoplasm to the Maurer's clefts; the N-terminal domain of PfSBP1 was identified as the domain of interaction with PfTRiC.","method":"Co-immunoprecipitation, interaction domain mapping, localization studies in P. falciparum-infected erythrocytes","journal":"Traffic (Copenhagen, Denmark)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single pulldown approach; CCT3 is implicated only as a member of the PfTRiC complex, with no experiment directed specifically at CCT3 itself","pmids":["25615740"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"finding":"The P. falciparum TRiC chaperonin complex, of which CCT3 (PF3D7_1229500) is a subunit, is not exported into the host red blood cell but is retained within the parasite cytosol; knockdown of the TRiC-θ subunit caused a severe asexual growth defect without altering protein export into the RBC, indicating the complex is essential for parasite biology but not for RBC protein trafficking.","method":"Parasite-specific antibody staining, epitope-tagged transgenic parasites, regulatable knockdown (TRiC-θ subunit), growth assays, protein export assays","journal":"Cellular microbiology","confidence":"Low","confidence_rationale":"Tier 3 / Weak — CCT3 is implicated only as a member of the TRiC complex; functional experiments were performed on TRiC-θ subunit, not CCT3 directly; single lab","pmids":["28067475"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"CCT3 (PF3D7_1229500), as part of the TRiC complex, was detected as an indirect or bridging interactor of the P. yoelii CAF1/CCR4/NOT complex by mass spectrometry co-immunoprecipitation via PyCCR4-1::GFP; this interaction was below the most stringent SAINT threshold, suggesting a low-confidence association potentially linked to roles in cytosolic granule regulation.","method":"Co-immunoprecipitation via GFP tag followed by mass spectrometry (SAINT analysis) in P. yoelii schizonts","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — CCT3 detected by MS at low SAINT score, single lab, no direct functional validation of CCT3 itself","pmids":["30703164"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]}],"current_model":"CCT3 (PF3D7_1229500) is a subunit of the Plasmodium TRiC chaperonin complex that is retained within the parasite cytosol (not exported into the host red blood cell), is essential for asexual parasite growth, and may associate with Maurer's cleft membrane proteins and the CAF1/CCR4/NOT complex, but no experiment has directly probed the specific molecular function of CCT3 itself beyond its membership in the TRiC complex."},"narrative":{"mechanistic_narrative":"CCT3 (PF3D7_1229500) is a subunit of the Plasmodium falciparum TRiC/CCT chaperonin complex, and the available corpus characterizes it only through the collective properties of that complex rather than through any experiment directed at CCT3 itself. As a member of PfTRiC, it is part of a complex that associates with Maurer's cleft membrane proteins including PfSBP1 (via the PfSBP1 N-terminal domain) and traffics them through the red blood cell cytoplasm [PMID:25615740]. The complex is retained within the parasite cytosol rather than exported into the host erythrocyte, and regulatable knockdown of the TRiC-θ subunit (not CCT3) causes a severe asexual growth defect without disrupting protein export, indicating that the chaperonin is essential for parasite biology [PMID:28067475]. As part of TRiC, CCT3 was also detected as a low-confidence bridging interactor of the P. yoelii CAF1/CCR4/NOT complex [PMID:30703164]. No experiment in the available corpus has directly probed the specific molecular function of CCT3 itself beyond its membership in the TRiC complex.","teleology":[{"year":2015,"claim":"Whether the Plasmodium TRiC chaperonin participates in host-cell protein trafficking was unknown; identifying the complex as a partner of Maurer's cleft proteins placed CCT3-containing TRiC in the export/trafficking pathway.","evidence":"Co-immunoprecipitation, interaction domain mapping, and localization in P. falciparum-infected erythrocytes","pmids":["25615740"],"confidence":"Low","gaps":["CCT3 implicated only as a TRiC subunit; no experiment directed at CCT3 itself","single-lab, single pulldown approach without reciprocal validation of CCT3","does not establish whether CCT3 contributes any specific contact to PfSBP1"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"Whether the TRiC complex is exported and required for RBC protein trafficking was open; showing cytosolic retention and an essential growth role decoupled the chaperonin's essentiality from protein export.","evidence":"Parasite-specific antibody staining, epitope-tagged transgenics, regulatable knockdown of the TRiC-θ subunit, and growth/export assays in P. falciparum","pmids":["28067475"],"confidence":"Low","gaps":["functional knockdown was performed on the TRiC-θ subunit, not CCT3 directly","essentiality and localization of CCT3 specifically were not measured","substrate repertoire of the complex not defined"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"Whether TRiC connects to mRNA-regulatory machinery was unaddressed; mass-spec detection of CCT3-containing TRiC as a bridging interactor of the CAF1/CCR4/NOT complex hinted at a link to cytosolic granule regulation.","evidence":"GFP-tag co-immunoprecipitation and mass spectrometry (SAINT analysis) via PyCCR4-1::GFP in P. yoelii schizonts","pmids":["30703164"],"confidence":"Low","gaps":["interaction fell below the most stringent SAINT threshold — low-confidence association not independently confirmed","no direct functional validation of CCT3 in this context","finding is in P. yoelii, not the P. falciparum system of the other discoveries"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":null,"claim":"The specific molecular function, essentiality, and substrate contacts of CCT3 itself remain undefined, as all evidence addresses the TRiC complex or other subunits rather than PF3D7_1229500 directly.","evidence":"No direct experiment on CCT3 in the available corpus","pmids":[],"confidence":"Low","gaps":["no CCT3-specific knockdown, knockout, or localization","no direct substrate or folding activity assigned to CCT3","no structural data on CCT3 within PfTRiC"],"attribution":[]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TRiC/CCT chaperonin complex (PfTRiC)"],"partners":["PFSBP1 (VIA TRIC COMPLEX)","MAURER'S CLEFT MEMBRANE PROTEINS (VIA TRIC COMPLEX)","CAF1/CCR4/NOT COMPLEX (LOW-CONFIDENCE BRIDGING INTERACTION VIA TRIC, P. YOELII)"],"other_free_text":["CCT3 (PF3D7_1229500) is characterized in the corpus only as a subunit of the TRiC chaperonin complex; no experiment directly probes its individual molecular function.","Functional essentiality evidence derives from knockdown of the TRiC-θ subunit, not CCT3 itself.","The TRiC complex is retained in the parasite cytosol and not exported into the host red blood cell."]}},"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":"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":["CCT3"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5009,"output_tokens":1040,"usd":0.015314,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5770,"output_tokens":2012,"usd":0.039575,"stage2_stop_reason":"end_turn"},"total_usd":0.054889,"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\": 2015,\n      \"finding\": \"The P. falciparum TRiC chaperonin complex (PfTRiC), of which CCT3 (PF3D7_1229500) is a subunit, associates with and traffics Maurer's cleft membrane proteins (including PfSBP1) through the red blood cell cytoplasm to the Maurer's clefts; the N-terminal domain of PfSBP1 was identified as the domain of interaction with PfTRiC.\",\n      \"method\": \"Co-immunoprecipitation, interaction domain mapping, localization studies in P. falciparum-infected erythrocytes\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single pulldown approach; CCT3 is implicated only as a member of the PfTRiC complex, with no experiment directed specifically at CCT3 itself\",\n      \"pmids\": [\"25615740\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The P. falciparum TRiC chaperonin complex, of which CCT3 (PF3D7_1229500) is a subunit, is not exported into the host red blood cell but is retained within the parasite cytosol; knockdown of the TRiC-θ subunit caused a severe asexual growth defect without altering protein export into the RBC, indicating the complex is essential for parasite biology but not for RBC protein trafficking.\",\n      \"method\": \"Parasite-specific antibody staining, epitope-tagged transgenic parasites, regulatable knockdown (TRiC-θ subunit), growth assays, protein export assays\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — CCT3 is implicated only as a member of the TRiC complex; functional experiments were performed on TRiC-θ subunit, not CCT3 directly; single lab\",\n      \"pmids\": [\"28067475\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CCT3 (PF3D7_1229500), as part of the TRiC complex, was detected as an indirect or bridging interactor of the P. yoelii CAF1/CCR4/NOT complex by mass spectrometry co-immunoprecipitation via PyCCR4-1::GFP; this interaction was below the most stringent SAINT threshold, suggesting a low-confidence association potentially linked to roles in cytosolic granule regulation.\",\n      \"method\": \"Co-immunoprecipitation via GFP tag followed by mass spectrometry (SAINT analysis) in P. yoelii schizonts\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — CCT3 detected by MS at low SAINT score, single lab, no direct functional validation of CCT3 itself\",\n      \"pmids\": [\"30703164\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"CCT3 (PF3D7_1229500) is a subunit of the Plasmodium TRiC chaperonin complex that is retained within the parasite cytosol (not exported into the host red blood cell), is essential for asexual parasite growth, and may associate with Maurer's cleft membrane proteins and the CAF1/CCR4/NOT complex, but no experiment has directly probed the specific molecular function of CCT3 itself beyond its membership in the TRiC complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CCT3 (PF3D7_1229500) is a subunit of the Plasmodium falciparum TRiC/CCT chaperonin complex, and the available corpus characterizes it only through the collective properties of that complex rather than through any experiment directed at CCT3 itself. As a member of PfTRiC, it is part of a complex that associates with Maurer's cleft membrane proteins including PfSBP1 (via the PfSBP1 N-terminal domain) and traffics them through the red blood cell cytoplasm [#0]. The complex is retained within the parasite cytosol rather than exported into the host erythrocyte, and regulatable knockdown of the TRiC-θ subunit (not CCT3) causes a severe asexual growth defect without disrupting protein export, indicating that the chaperonin is essential for parasite biology [#1]. As part of TRiC, CCT3 was also detected as a low-confidence bridging interactor of the P. yoelii CAF1/CCR4/NOT complex [#2]. No experiment in the available corpus has directly probed the specific molecular function of CCT3 itself beyond its membership in the TRiC complex.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"Whether the Plasmodium TRiC chaperonin participates in host-cell protein trafficking was unknown; identifying the complex as a partner of Maurer's cleft proteins placed CCT3-containing TRiC in the export/trafficking pathway.\",\n      \"evidence\": \"Co-immunoprecipitation, interaction domain mapping, and localization in P. falciparum-infected erythrocytes\",\n      \"pmids\": [\"25615740\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"CCT3 implicated only as a TRiC subunit; no experiment directed at CCT3 itself\",\n        \"single-lab, single pulldown approach without reciprocal validation of CCT3\",\n        \"does not establish whether CCT3 contributes any specific contact to PfSBP1\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Whether the TRiC complex is exported and required for RBC protein trafficking was open; showing cytosolic retention and an essential growth role decoupled the chaperonin's essentiality from protein export.\",\n      \"evidence\": \"Parasite-specific antibody staining, epitope-tagged transgenics, regulatable knockdown of the TRiC-θ subunit, and growth/export assays in P. falciparum\",\n      \"pmids\": [\"28067475\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"functional knockdown was performed on the TRiC-θ subunit, not CCT3 directly\",\n        \"essentiality and localization of CCT3 specifically were not measured\",\n        \"substrate repertoire of the complex not defined\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Whether TRiC connects to mRNA-regulatory machinery was unaddressed; mass-spec detection of CCT3-containing TRiC as a bridging interactor of the CAF1/CCR4/NOT complex hinted at a link to cytosolic granule regulation.\",\n      \"evidence\": \"GFP-tag co-immunoprecipitation and mass spectrometry (SAINT analysis) via PyCCR4-1::GFP in P. yoelii schizonts\",\n      \"pmids\": [\"30703164\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"interaction fell below the most stringent SAINT threshold — low-confidence association not independently confirmed\",\n        \"no direct functional validation of CCT3 in this context\",\n        \"finding is in P. yoelii, not the P. falciparum system of the other discoveries\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The specific molecular function, essentiality, and substrate contacts of CCT3 itself remain undefined, as all evidence addresses the TRiC complex or other subunits rather than PF3D7_1229500 directly.\",\n      \"evidence\": \"No direct experiment on CCT3 in the available corpus\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"no CCT3-specific knockdown, knockout, or localization\",\n        \"no direct substrate or folding activity assigned to CCT3\",\n        \"no structural data on CCT3 within PfTRiC\"\n      ],\n      \"attribution\": []\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006457\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"TRiC/CCT chaperonin complex (PfTRiC)\"\n    ],\n    \"partners\": [\n      \"PfSBP1 (via TRiC complex)\",\n      \"Maurer's cleft membrane proteins (via TRiC complex)\",\n      \"CAF1/CCR4/NOT complex (low-confidence bridging interaction via TRiC, P. yoelii)\"\n    ],\n    \"other_free_text\": [\n      \"CCT3 (PF3D7_1229500) is characterized in the corpus only as a subunit of the TRiC chaperonin complex; no experiment directly probes its individual molecular function.\",\n      \"Functional essentiality evidence derives from knockdown of the TRiC-θ subunit, not CCT3 itself.\",\n      \"The TRiC complex is retained in the parasite cytosol and not exported into the host red blood cell.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1229500","name":null,"product":"T-complex protein 1 subunit gamma","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_1444100","name":null,"product":"T-complex protein 1 subunit gamma, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_1448800","name":null,"product":"T-complex protein 1 subunit gamma, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CCT3","evaluation":null}