{"gene":"PF3D7_1132200","run_date":"2026-09-08T12:51:28","timeline":{"discoveries":[{"year":2017,"finding":"P. falciparum TRiC (which includes the TCP1/TRiC-α subunit, PF3D7_1132200) forms an oligomeric complex that localizes within the parasite cytosol and is not exported into the red blood cell. Knockdown of the TRiC-θ subunit caused a severe asexual growth defect without altering protein export, establishing that the complex is essential for parasite viability but functions within the parasite rather than in host-cell protein trafficking.","method":"Parasite-specific antibody staining, epitope-tagged transgenic parasites (localization), and regulatable knockdown of TRiC-θ subunit with growth phenotype readout","journal":"Cellular microbiology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct localization by antibody and tagged lines plus genetic knockdown with defined phenotype, but findings are about TRiC complex broadly; PF3D7_1132200 inferred as complex member, single lab","pmids":["28067475"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"finding":"The antihistamine clemastine binds to and destabilizes the P. falciparum TRiC/CCT complex (which includes TCP1/PF3D7_1132200 as a subunit), as shown by thermal proteome profiling (TPP) destabilizing all eight TRiC subunits. Clemastine treatment reduced tubulin levels in P. falciparum and caused mitotic spindle disorientation and aberrant tubulin morphology, establishing that the TRiC complex is required for de novo folding of cytoskeletal proteins including tubulin.","method":"Parallel chemoproteomic platforms: thermal proteome profiling (TPP) and stability of proteins from rates of oxidation (SPROX); phenotypic analysis of tubulin levels and spindle morphology after clemastine treatment","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — two orthogonal chemoproteomic methods in single lab; PF3D7_1132200 is one of eight destabilized subunits, so finding is complex-level with TCP1 implicated as member","pmids":["32127489"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2015,"finding":"The P. falciparum TRiC complex (PfTRiC, which includes TCP1/PF3D7_1132200) associates with Maurer's cleft resident proteins (including PfSBP1) in the red blood cell cytoplasm and was proposed to traffic these proteins to the Maurer's cleft membrane. The domain of interaction with PfTRiC was mapped to the N-terminal domain of PfSBP1.","method":"Co-immunoprecipitation/association experiments identifying PfTRiC–PfSBP1 interaction; domain-mapping of the PfSBP1 N-terminal interaction region","journal":"Traffic (Copenhagen, Denmark)","confidence":"Low","confidence_rationale":"Tier 3 / Weak — single lab, single co-IP/association method; PF3D7_1132200 implicated as part of PfTRiC complex but its specific role not individually dissected; contradicted by Spillman et al. 2017 regarding export","pmids":["25615740"],"is_preprint":false,"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"current_model":"PF3D7_1132200 (TCP1) is a subunit of the essential P. falciparum TRiC/CCT chaperonin complex that resides in the parasite cytosol, is required for asexual parasite growth (likely through de novo folding of cytoskeletal substrates such as tubulin), and is targeted by the antimalarial compound clemastine; its function is intrinsic to the parasite rather than related to protein export into the host red blood cell."},"narrative":{"mechanistic_narrative":"PF3D7_1132200 (TCP1) is a subunit of the essential P. falciparum TRiC/CCT chaperonin, an oligomeric complex that resides in the parasite cytosol and is required for asexual parasite viability [PMID:28067475]. The complex functions within the parasite rather than in host-cell protein export: regulatable knockdown of the TRiC-θ subunit caused a severe asexual growth defect without altering protein trafficking into the red blood cell [PMID:28067475]. The chaperonin mediates de novo folding of cytoskeletal substrates, and its pharmacological destabilization by the antihistamine clemastine—which destabilizes all eight TRiC subunits—reduces tubulin levels and produces mitotic spindle disorientation and aberrant tubulin morphology [PMID:32127489]. All available evidence addresses the TRiC/CCT complex as a whole with PF3D7_1132200 inferred as a constituent subunit; no function has been dissected for the TCP1 subunit individually in the available corpus.","teleology":[{"year":2015,"claim":"An early question was whether PfTRiC participates in trafficking parasite proteins into the host red blood cell; this study mapped an association between the complex and Maurer's cleft cargo.","evidence":"Co-immunoprecipitation identifying a PfTRiC–PfSBP1 association and domain-mapping to the N-terminal region of PfSBP1","pmids":["25615740"],"confidence":"Low","gaps":["Single lab, single co-IP/association method without reciprocal validation; contradicted regarding export by later work","Specific contribution of the TCP1 subunit not dissected from the complex","No functional demonstration that PfTRiC actually delivers cargo to the Maurer's cleft"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2017,"claim":"The competing question of where PfTRiC acts was resolved by showing the complex is cytosolic, non-exported, and essential for parasite growth intrinsically rather than for host-cell trafficking.","evidence":"Parasite-specific antibody staining and epitope-tagged transgenic lines for localization, plus regulatable knockdown of the TRiC-θ subunit with a growth phenotype readout","pmids":["28067475"],"confidence":"Medium","gaps":["PF3D7_1132200 inferred as a complex member; the knockdown targeted the θ subunit, not TCP1","Substrate repertoire of the complex not defined in this study","Single lab"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":2020,"claim":"To define both the substrate specificity and a druggable liability of the complex, chemoproteomics showed clemastine destabilizes all eight TRiC subunits and that the complex is required for folding cytoskeletal proteins including tubulin.","evidence":"Thermal proteome profiling (TPP) and SPROX chemoproteomics identifying clemastine binding/destabilization, with phenotypic analysis of tubulin levels and spindle morphology after treatment","pmids":["32127489"],"confidence":"Medium","gaps":["TCP1 is one of eight destabilized subunits, so the finding is complex-level with PF3D7_1132200 implicated as a member","Clemastine binding site on the complex not localized to a specific subunit","Full substrate range beyond tubulin not enumerated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]},{"year":null,"claim":"Whether PF3D7_1132200 (TCP1) has any subunit-specific function, binding role, or non-redundant contribution distinct from the intact TRiC/CCT complex remains unaddressed.","evidence":"","pmids":[],"confidence":"Low","gaps":["No genetic or biochemical study isolating the TCP1 subunit's individual role","No structural model of PfTRiC or of the TCP1 subunit","Direct substrate-binding by TCP1 not demonstrated"],"attribution":[{"species":"Plasmodium falciparum","strain":""}]}],"mechanism_profile":{"molecular_activity":[],"localization":[],"pathway":[],"complexes":["TRiC/CCT chaperonin complex (PfTRiC)"],"partners":["TRIC-Θ SUBUNIT (COMPLEX CO-MEMBER)","PFSBP1 (LOW-CONFIDENCE ASSOCIATION)"],"other_free_text":["PF3D7_1132200 (TCP1/TRiC-α) is characterized only as a subunit of the P. falciparum TRiC/CCT chaperonin; the corpus establishes no function for the subunit independent of the complex.","The complex is required for asexual parasite viability and for de novo folding of cytoskeletal substrates such as tubulin.","The complex is destabilized by the antimalarial compound clemastine."]}},"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":"32127489","id":"PMC_32127489","title":"Plasmodium chaperonin TRiC/CCT identified as a target of the antihistamine clemastine using parallel chemoproteomic strategy.","date":"2020","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/32127489","citation_count":41,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["TCP1"],"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":"33272134","id":"PMC_33272134","title":"Comparative structural insight into prefoldin subunints of archaea and eukaryotes with special emphasis on unexplored prefoldin of Plasmodium falciparum.","date":"2020","source":"Journal of biomolecular structure & dynamics","url":"https://pubmed.ncbi.nlm.nih.gov/33272134","citation_count":0,"is_preprint":false,"source_species":["Pf"],"role":"primary","match_terms":["TCP1"],"competing_organism_flag":false,"competing_organism_match":"","competing_organism_only":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":4859,"output_tokens":1153,"usd":0.015936,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":5939,"output_tokens":1986,"usd":0.039672,"stage2_stop_reason":"end_turn"},"total_usd":0.055608,"stage1_batch_id":"msgbatch_01DisAaTypwmC8QwdMBuePHo","stage2_batch_id":"msgbatch_0184zxZTqxiEfdYYfPMfkqjb","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2017,\n      \"finding\": \"P. falciparum TRiC (which includes the TCP1/TRiC-α subunit, PF3D7_1132200) forms an oligomeric complex that localizes within the parasite cytosol and is not exported into the red blood cell. Knockdown of the TRiC-θ subunit caused a severe asexual growth defect without altering protein export, establishing that the complex is essential for parasite viability but functions within the parasite rather than in host-cell protein trafficking.\",\n      \"method\": \"Parasite-specific antibody staining, epitope-tagged transgenic parasites (localization), and regulatable knockdown of TRiC-θ subunit with growth phenotype readout\",\n      \"journal\": \"Cellular microbiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct localization by antibody and tagged lines plus genetic knockdown with defined phenotype, but findings are about TRiC complex broadly; PF3D7_1132200 inferred as complex member, single lab\",\n      \"pmids\": [\"28067475\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The antihistamine clemastine binds to and destabilizes the P. falciparum TRiC/CCT complex (which includes TCP1/PF3D7_1132200 as a subunit), as shown by thermal proteome profiling (TPP) destabilizing all eight TRiC subunits. Clemastine treatment reduced tubulin levels in P. falciparum and caused mitotic spindle disorientation and aberrant tubulin morphology, establishing that the TRiC complex is required for de novo folding of cytoskeletal proteins including tubulin.\",\n      \"method\": \"Parallel chemoproteomic platforms: thermal proteome profiling (TPP) and stability of proteins from rates of oxidation (SPROX); phenotypic analysis of tubulin levels and spindle morphology after clemastine treatment\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — two orthogonal chemoproteomic methods in single lab; PF3D7_1132200 is one of eight destabilized subunits, so finding is complex-level with TCP1 implicated as member\",\n      \"pmids\": [\"32127489\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"The P. falciparum TRiC complex (PfTRiC, which includes TCP1/PF3D7_1132200) associates with Maurer's cleft resident proteins (including PfSBP1) in the red blood cell cytoplasm and was proposed to traffic these proteins to the Maurer's cleft membrane. The domain of interaction with PfTRiC was mapped to the N-terminal domain of PfSBP1.\",\n      \"method\": \"Co-immunoprecipitation/association experiments identifying PfTRiC–PfSBP1 interaction; domain-mapping of the PfSBP1 N-terminal interaction region\",\n      \"journal\": \"Traffic (Copenhagen, Denmark)\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — single lab, single co-IP/association method; PF3D7_1132200 implicated as part of PfTRiC complex but its specific role not individually dissected; contradicted by Spillman et al. 2017 regarding export\",\n      \"pmids\": [\"25615740\"],\n      \"is_preprint\": false,\n      \"attribution\": [\n        {\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}\n      ]\n    }\n  ],\n  \"current_model\": \"PF3D7_1132200 (TCP1) is a subunit of the essential P. falciparum TRiC/CCT chaperonin complex that resides in the parasite cytosol, is required for asexual parasite growth (likely through de novo folding of cytoskeletal substrates such as tubulin), and is targeted by the antimalarial compound clemastine; its function is intrinsic to the parasite rather than related to protein export into the host red blood cell.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"PF3D7_1132200 (TCP1) is a subunit of the essential P. falciparum TRiC/CCT chaperonin, an oligomeric complex that resides in the parasite cytosol and is required for asexual parasite viability [#0]. The complex functions within the parasite rather than in host-cell protein export: regulatable knockdown of the TRiC-\\u03b8 subunit caused a severe asexual growth defect without altering protein trafficking into the red blood cell [#0]. The chaperonin mediates de novo folding of cytoskeletal substrates, and its pharmacological destabilization by the antihistamine clemastine\\u2014which destabilizes all eight TRiC subunits\\u2014reduces tubulin levels and produces mitotic spindle disorientation and aberrant tubulin morphology [#1]. All available evidence addresses the TRiC/CCT complex as a whole with PF3D7_1132200 inferred as a constituent subunit; no function has been dissected for the TCP1 subunit individually in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2015,\n      \"claim\": \"An early question was whether PfTRiC participates in trafficking parasite proteins into the host red blood cell; this study mapped an association between the complex and Maurer's cleft cargo.\",\n      \"evidence\": \"Co-immunoprecipitation identifying a PfTRiC\\u2013PfSBP1 association and domain-mapping to the N-terminal region of PfSBP1\",\n      \"pmids\": [\"25615740\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Single lab, single co-IP/association method without reciprocal validation; contradicted regarding export by later work\",\n        \"Specific contribution of the TCP1 subunit not dissected from the complex\",\n        \"No functional demonstration that PfTRiC actually delivers cargo to the Maurer's cleft\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"The competing question of where PfTRiC acts was resolved by showing the complex is cytosolic, non-exported, and essential for parasite growth intrinsically rather than for host-cell trafficking.\",\n      \"evidence\": \"Parasite-specific antibody staining and epitope-tagged transgenic lines for localization, plus regulatable knockdown of the TRiC-\\u03b8 subunit with a growth phenotype readout\",\n      \"pmids\": [\"28067475\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"PF3D7_1132200 inferred as a complex member; the knockdown targeted the \\u03b8 subunit, not TCP1\",\n        \"Substrate repertoire of the complex not defined in this study\",\n        \"Single lab\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"To define both the substrate specificity and a druggable liability of the complex, chemoproteomics showed clemastine destabilizes all eight TRiC subunits and that the complex is required for folding cytoskeletal proteins including tubulin.\",\n      \"evidence\": \"Thermal proteome profiling (TPP) and SPROX chemoproteomics identifying clemastine binding/destabilization, with phenotypic analysis of tubulin levels and spindle morphology after treatment\",\n      \"pmids\": [\"32127489\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"TCP1 is one of eight destabilized subunits, so the finding is complex-level with PF3D7_1132200 implicated as a member\",\n        \"Clemastine binding site on the complex not localized to a specific subunit\",\n        \"Full substrate range beyond tubulin not enumerated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Whether PF3D7_1132200 (TCP1) has any subunit-specific function, binding role, or non-redundant contribution distinct from the intact TRiC/CCT complex remains unaddressed.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No genetic or biochemical study isolating the TCP1 subunit's individual role\",\n        \"No structural model of PfTRiC or of the TCP1 subunit\",\n        \"Direct substrate-binding by TCP1 not demonstrated\"\n      ],\n      \"attribution\": [{\"species\": \"Plasmodium falciparum\", \"strain\": \"\"}]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0051082\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0006457\", \"supporting_discovery_ids\": [1]}\n    ],\n    \"complexes\": [\"TRiC/CCT chaperonin complex (PfTRiC)\"],\n    \"partners\": [\"TRiC-\\u03b8 subunit (complex co-member)\", \"PfSBP1 (Low-confidence association)\"],\n    \"other_free_text\": [\n      \"PF3D7_1132200 (TCP1/TRiC-\\u03b1) is characterized only as a subunit of the P. falciparum TRiC/CCT chaperonin; the corpus establishes no function for the subunit independent of the complex.\",\n      \"The complex is required for asexual parasite viability and for de novo folding of cytoskeletal substrates such as tubulin.\",\n      \"The complex is destabilized by the antimalarial compound clemastine.\"\n    ]\n  }\n}","audit_flag":null,"strains":[{"strain":"Pf3D7","gene_id":"PF3D7_1132200","name":null,"product":"T-complex protein 1 subunit alpha","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PbANKA","gene_id":"PBANKA_0916200","name":null,"product":"T-complex protein 1 subunit alpha, putative","uniprot_acc":null,"chromosome":null,"start_pos":null},{"strain":"PkH","gene_id":"PKNH_0930400","name":null,"product":"T-complex protein 1 subunit alpha, putative","uniprot_acc":null,"chromosome":null,"start_pos":null}],"gene_symbol":"TCP1","evaluation":null}