{"gene":"PF3D7_0306800","run_date":"2026-09-08T19:44:17","timeline":{"discoveries":[{"year":2017,"finding":"The Plasmodium falciparum TRiC chaperonin complex (which includes CCT2/PF3D7_0306800 as a subunit) localizes within the parasite cytosol and is not exported into the host red blood cell. Regulatable knockdown of the TRiC-θ subunit caused a severe asexual growth defect without altering protein export into the RBC, establishing that the complex is essential for parasite biology but its function is confined to within the parasite.","method":"Parasite-specific antibody, epitope-tagged transgenic parasites, regulatable knockdown (TRiC-θ subunit), growth assay, protein export assay","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — clean knockdown with defined cellular phenotype and localization data, single lab with two orthogonal methods; knockdown targets TRiC-θ, not CCT2 directly, so CCT2 membership in this complex is inferred","pmids":["28067475"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"The P. falciparum TRiC complex (PfTRiC, of which CCT2/PF3D7_0306800 is a component) binds and traffics Maurer's cleft membrane proteins (including PfSBP1) as soluble forms through the erythrocyte cytoplasm to the Maurer's clefts. The domain of interaction with PfTRiC was mapped to the amino-terminal domain of PfSBP1.","method":"Co-immunoprecipitation, domain-mapping experiments, localization studies in P. falciparum-infected erythrocytes","journal":"Traffic (Copenhagen, Denmark)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single Co-IP/pulldown study, single lab; CCT2 is a component of PfTRiC but the mechanistic findings are attributed to the complex, not CCT2 specifically","pmids":["25615740"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2022,"finding":"CCT2/PF3D7_0306800 is a subunit of the P. falciparum CCT (PfCCT) complex. Proteomic analysis of FLAG-tagged CCT8-purified PfCCT complexes from trophozoite-stage parasites identified CCT2 as part of the oligomeric chaperonin complex, whose clients include actin, tubulin, and WD40 propeller proteins.","method":"Affinity purification (FLAG-tag via SLI), mass spectrometry proteomics of synchronized trophozoite cultures","journal":"Frontiers in molecular biosciences","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single affinity purification/MS study establishing complex membership; no direct functional experiment on CCT2 subunit itself","pmids":["36567946"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"finding":"CCT2/PF3D7_0306800 (as part of the TRiC/CCT complex) was co-immunoprecipitated with the P. yoelii CAF1/CCR4/NOT complex (via PyCCR4-1::GFP) from synchronized schizonts, suggesting an association between TRiC subunits and the mRNA deadenylation/decay machinery at or below the threshold of high-confidence SAINT scoring.","method":"GFP immunoprecipitation followed by mass spectrometry (SAINT analysis) in P. yoelii transgenic parasites","journal":"PLoS pathogens","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single co-IP/MS experiment, CCT2 detected at low-confidence SAINT scores (0.1–0.35), single lab, no functional follow-up specific to CCT2","pmids":["30703164"],"is_preprint":false,"attribution":[{"species":"Plasmodium yoelii","strain":""}]}],"current_model":"CCT2/PF3D7_0306800 is a subunit of the oligomeric TRiC/CCT chaperonin complex in Plasmodium falciparum; the complex localizes within the parasite cytosol (not exported to the host erythrocyte), is essential for asexual parasite growth, and associates with client proteins including actin and tubulin as well as Maurer's cleft membrane proteins, but no mechanistic function has been demonstrated for the CCT2 subunit itself beyond its membership in this complex."},"narrative":{"mechanistic_narrative":"CCT2/PF3D7_0306800 is a subunit of the oligomeric TRiC/CCT chaperonin complex of Plasmodium falciparum, and its characterized biology in the available corpus is confined to its membership in this complex rather than any function demonstrated for the subunit itself [PMID:36567946]. Affinity purification of the parasite CCT complex from trophozoite-stage parasites identified CCT2 among the oligomeric subunits, with the complex engaging clients including actin, tubulin, and WD40 propeller proteins [PMID:36567946]. The complex localizes within the parasite cytosol and is not exported into the host erythrocyte; regulatable knockdown of a different subunit (TRiC-θ) causes a severe asexual growth defect without disrupting protein export, establishing that the complex is essential for intra-parasite biology [PMID:28067475]. The complex has additionally been co-immunoprecipitated with Maurer's cleft membrane proteins such as PfSBP1 [PMID:25615740] and, in P. yoelii, with the CAF1/CCR4/NOT mRNA-decay machinery [PMID:30703164], but these associations are attributed to the complex and no mechanistic role has been demonstrated for the CCT2 subunit specifically beyond its incorporation into PfCCT.","teleology":[{"year":2015,"claim":"To ask whether the parasite chaperonin machinery participates in trafficking exported host-cell remodeling proteins, the PfTRiC complex was tested for interaction with Maurer's cleft membrane cargo.","evidence":"Co-immunoprecipitation, domain mapping, and localization in P. falciparum-infected erythrocytes, identifying the PfSBP1 N-terminal domain as the interaction site","pmids":["25615740"],"confidence":"Low","gaps":["Single Co-IP/pulldown from one lab without reciprocal validation","Interaction attributed to the complex, not to the CCT2 subunit specifically","No functional test that CCT2 is required for PfSBP1 trafficking"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"To determine where the parasite TRiC complex acts and whether it is essential, its localization and the consequence of subunit depletion were assessed.","evidence":"Parasite-specific antibody, epitope-tagged transgenic parasites, and regulatable knockdown of the TRiC-θ subunit with growth and protein-export assays in P. falciparum","pmids":["28067475"],"confidence":"Medium","gaps":["Knockdown targeted TRiC-θ, not CCT2, so CCT2's individual essentiality is inferred from complex membership","Cytosolic confinement established for the complex, not shown for CCT2 in isolation","No molecular activity assigned to any single subunit"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2019,"claim":"To map protein networks around the CCR4/NOT deadenylation machinery, its interactors were profiled, incidentally detecting TRiC subunits including CCT2.","evidence":"GFP immunoprecipitation followed by mass spectrometry with SAINT scoring of PyCCR4-1::GFP from synchronized P. yoelii schizonts","pmids":["30703164"],"confidence":"Low","gaps":["CCT2 detected only at low-confidence SAINT scores (0.1–0.35)","No functional follow-up linking CCT2 to mRNA decay","Shown in P. yoelii, not P. falciparum"],"attribution":[{"species":"Plasmodium yoelii","strain":""}]},{"year":2022,"claim":"To define the composition and clients of the parasite CCT chaperonin, the complex was purified and its subunits and interactors catalogued, confirming CCT2 as a bona fide subunit.","evidence":"FLAG-tag affinity purification (via SLI) of CCT8-purified PfCCT complexes and mass spectrometry of synchronized trophozoites in P. falciparum","pmids":["36567946"],"confidence":"Low","gaps":["Single affinity-purification/MS study establishing membership only","No direct functional experiment on the CCT2 subunit","Client engagement (actin, tubulin, WD40 proteins) ascribed to the complex, not CCT2"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"What CCT2/PF3D7_0306800 contributes to the PfCCT/TRiC complex beyond membership — its individual essentiality, substrate specificity, and any subunit-specific function — remains uncharacterized.","evidence":"No discovery in the corpus tests CCT2 directly through knockdown, reconstitution, or structural analysis","pmids":[],"confidence":"Low","gaps":["No CCT2-specific loss-of-function or rescue experiment","No structural model of the CCT2 subunit within PfCCT","No demonstration that CCT2 selects any particular client"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TRiC/CCT chaperonin complex (PfCCT/PfTRiC)"],"partners":["CCT8 (CO-PURIFYING PFCCT SUBUNIT)","ACTIN (CLIENT)","TUBULIN (CLIENT)","WD40 PROPELLER PROTEINS (CLIENTS)","PFSBP1 / MAURER'S CLEFT MEMBRANE PROTEINS (COMPLEX-ASSOCIATED CARGO)","CAF1/CCR4/NOT COMPLEX (PYCCR4-1, LOW-CONFIDENCE, P. YOELII)"],"other_free_text":["The parasite chaperonin complex is essential for asexual growth and confined to the parasite cytosol, not exported to the host erythrocyte [#0].","All findings are attributed to the oligomeric complex; no mechanistic function has been demonstrated for the CCT2 subunit itself beyond its membership."]}},"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":"33184408","id":"","title":"Identification of a nuclear localization signal in the Plasmodium falciparum CTP: phosphocholine cytidylyltransferase enzyme.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/33184408","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["CCT2"],"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":["CCT2"],"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":["CCT2"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":7006,"output_tokens":1340,"usd":0.020559,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":6215,"output_tokens":2466,"usd":0.046363,"stage2_stop_reason":"end_turn"},"total_usd":0.066922,"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\": \"The Plasmodium falciparum TRiC chaperonin complex (which includes CCT2/PF3D7_0306800 as a subunit) localizes within the parasite cytosol and is not exported into the host red blood cell. Regulatable knockdown of the TRiC-θ subunit caused a severe asexual growth defect without altering protein export into the RBC, establishing that the complex is essential for parasite biology but its function is confined to within the parasite.\",\n      \"method\": \"Parasite-specific antibody, epitope-tagged transgenic parasites, regulatable knockdown (TRiC-θ subunit), growth assay, protein export assay\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — clean knockdown with defined cellular phenotype and localization data, single lab with two orthogonal methods; knockdown targets TRiC-θ, not CCT2 directly, so CCT2 membership in this complex is inferred\",\n      \"pmids\": [\"28067475\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The P. falciparum TRiC complex (PfTRiC, of which CCT2/PF3D7_0306800 is a component) binds and traffics Maurer's cleft membrane proteins (including PfSBP1) as soluble forms through the erythrocyte cytoplasm to the Maurer's clefts. The domain of interaction with PfTRiC was mapped to the amino-terminal domain of PfSBP1.\",\n      \"method\": \"Co-immunoprecipitation, domain-mapping experiments, localization studies in P. falciparum-infected erythrocytes\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single Co-IP/pulldown study, single lab; CCT2 is a component of PfTRiC but the mechanistic findings are attributed to the complex, not CCT2 specifically\",\n      \"pmids\": [\"25615740\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"CCT2/PF3D7_0306800 is a subunit of the P. falciparum CCT (PfCCT) complex. Proteomic analysis of FLAG-tagged CCT8-purified PfCCT complexes from trophozoite-stage parasites identified CCT2 as part of the oligomeric chaperonin complex, whose clients include actin, tubulin, and WD40 propeller proteins.\",\n      \"method\": \"Affinity purification (FLAG-tag via SLI), mass spectrometry proteomics of synchronized trophozoite cultures\",\n      \"journal\": \"Frontiers in molecular biosciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single affinity purification/MS study establishing complex membership; no direct functional experiment on CCT2 subunit itself\",\n      \"pmids\": [\"36567946\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"CCT2/PF3D7_0306800 (as part of the TRiC/CCT complex) was co-immunoprecipitated with the P. yoelii CAF1/CCR4/NOT complex (via PyCCR4-1::GFP) from synchronized schizonts, suggesting an association between TRiC subunits and the mRNA deadenylation/decay machinery at or below the threshold of high-confidence SAINT scoring.\",\n      \"method\": \"GFP immunoprecipitation followed by mass spectrometry (SAINT analysis) in P. yoelii transgenic parasites\",\n      \"journal\": \"PLoS pathogens\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single co-IP/MS experiment, CCT2 detected at low-confidence SAINT scores (0.1–0.35), single lab, no functional follow-up specific to CCT2\",\n      \"pmids\": [\"30703164\"],\n      \"is_preprint\": false,\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    }\n  ],\n  \"current_model\": \"CCT2/PF3D7_0306800 is a subunit of the oligomeric TRiC/CCT chaperonin complex in Plasmodium falciparum; the complex localizes within the parasite cytosol (not exported to the host erythrocyte), is essential for asexual parasite growth, and associates with client proteins including actin and tubulin as well as Maurer's cleft membrane proteins, but no mechanistic function has been demonstrated for the CCT2 subunit itself beyond its membership in this complex.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CCT2/PF3D7_0306800 is a subunit of the oligomeric TRiC/CCT chaperonin complex of Plasmodium falciparum, and its characterized biology in the available corpus is confined to its membership in this complex rather than any function demonstrated for the subunit itself [#2]. Affinity purification of the parasite CCT complex from trophozoite-stage parasites identified CCT2 among the oligomeric subunits, with the complex engaging clients including actin, tubulin, and WD40 propeller proteins [#2]. The complex localizes within the parasite cytosol and is not exported into the host erythrocyte; regulatable knockdown of a different subunit (TRiC-\\u03b8) causes a severe asexual growth defect without disrupting protein export, establishing that the complex is essential for intra-parasite biology [#0]. The complex has additionally been co-immunoprecipitated with Maurer's cleft membrane proteins such as PfSBP1 [#1] and, in P. yoelii, with the CAF1/CCR4/NOT mRNA-decay machinery [#3], but these associations are attributed to the complex and no mechanistic role has been demonstrated for the CCT2 subunit specifically beyond its incorporation into PfCCT.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"To ask whether the parasite chaperonin machinery participates in trafficking exported host-cell remodeling proteins, the PfTRiC complex was tested for interaction with Maurer's cleft membrane cargo.\",\n      \"evidence\": \"Co-immunoprecipitation, domain mapping, and localization in P. falciparum-infected erythrocytes, identifying the PfSBP1 N-terminal domain as the interaction site\",\n      \"pmids\": [\"25615740\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single Co-IP/pulldown from one lab without reciprocal validation\",\n        \"Interaction attributed to the complex, not to the CCT2 subunit specifically\",\n        \"No functional test that CCT2 is required for PfSBP1 trafficking\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"To determine where the parasite TRiC complex acts and whether it is essential, its localization and the consequence of subunit depletion were assessed.\",\n      \"evidence\": \"Parasite-specific antibody, epitope-tagged transgenic parasites, and regulatable knockdown of the TRiC-\\u03b8 subunit with growth and protein-export assays in P. falciparum\",\n      \"pmids\": [\"28067475\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Knockdown targeted TRiC-\\u03b8, not CCT2, so CCT2's individual essentiality is inferred from complex membership\",\n        \"Cytosolic confinement established for the complex, not shown for CCT2 in isolation\",\n        \"No molecular activity assigned to any single subunit\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"To map protein networks around the CCR4/NOT deadenylation machinery, its interactors were profiled, incidentally detecting TRiC subunits including CCT2.\",\n      \"evidence\": \"GFP immunoprecipitation followed by mass spectrometry with SAINT scoring of PyCCR4-1::GFP from synchronized P. yoelii schizonts\",\n      \"pmids\": [\"30703164\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"CCT2 detected only at low-confidence SAINT scores (0.1\\u20130.35)\",\n        \"No functional follow-up linking CCT2 to mRNA decay\",\n        \"Shown in P. yoelii, not P. falciparum\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium yoelii\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"To define the composition and clients of the parasite CCT chaperonin, the complex was purified and its subunits and interactors catalogued, confirming CCT2 as a bona fide subunit.\",\n      \"evidence\": \"FLAG-tag affinity purification (via SLI) of CCT8-purified PfCCT complexes and mass spectrometry of synchronized trophozoites in P. falciparum\",\n      \"pmids\": [\"36567946\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single affinity-purification/MS study establishing membership only\",\n        \"No direct functional experiment on the CCT2 subunit\",\n        \"Client engagement (actin, tubulin, WD40 proteins) ascribed to the complex, not CCT2\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"What CCT2/PF3D7_0306800 contributes to the PfCCT/TRiC complex beyond membership \\u2014 its individual essentiality, substrate specificity, and any subunit-specific function \\u2014 remains uncharacterized.\",\n      \"evidence\": \"No discovery in the corpus tests CCT2 directly through knockdown, reconstitution, or structural analysis\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No CCT2-specific loss-of-function or rescue experiment\",\n        \"No structural model of the CCT2 subunit within PfCCT\",\n        \"No demonstration that CCT2 selects any particular client\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0140662\", \"supporting_discovery_ids\": [2]},\n      {\"term_id\": \"GO:0051082\", \"supporting_discovery_ids\": [0, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006457\", \"supporting_discovery_ids\": [2]}\n    ],\n    \"complexes\": [\n      \"TRiC/CCT chaperonin complex (PfCCT/PfTRiC)\"\n    ],\n    \"partners\": [\n      \"CCT8 (co-purifying PfCCT subunit)\",\n      \"actin (client)\",\n      \"tubulin (client)\",\n      \"WD40 propeller proteins (clients)\",\n      \"PfSBP1 / Maurer's cleft membrane proteins (complex-associated cargo)\",\n      \"CAF1/CCR4/NOT complex (PyCCR4-1, low-confidence, P. yoelii)\"\n    ],\n    \"other_free_text\": [\n      \"The parasite chaperonin complex is essential for asexual growth and confined to the parasite cytosol, not exported to the host erythrocyte [#0].\",\n      \"All findings are attributed to the oligomeric complex; no mechanistic function has been demonstrated for the CCT2 subunit itself beyond its membership.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_0306800","name":null,"product":"T-complex protein 1 subunit beta","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0405200","name":null,"product":"T-complex protein 1 subunit beta, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0835900","name":null,"product":"T-complex protein 1 subunit beta, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"CCT2","evaluation":null}