TCP1 (CCT1, CCT-alpha) is the alpha subunit of the cytosolic chaperonin CCT/TRiC. This group II chaperonin is a hexadecamer of two stacked rings, each containing one copy of each of eight paralogous subunits (CCT1-CCT8), enclosing a folding chamber. Each subunit has an equatorial ATP-binding/ATPase domain, an intermediate hinge domain and an apical substrate-binding domain. CCT1 is one of the higher-affinity ATP-binding subunits. ATP binding and hydrolysis around the ring close the chamber and drive folding. TRiC folds newly synthesized cytoskeletal proteins (actin and alpha/beta-tubulin), G-protein beta subunits, WD40-repeat proteins such as the telomerase cofactor TCAB1, and other cytosolic clients. It cooperates with the co-chaperone prefoldin. A centrosomal pool of CCT, together with the chaperonin-like proteins BBS6, BBS10 and BBS12, assembles the BBSome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000242 pericentriolar material | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Orthology-based annotation of TCP1 to pericentriolar material. Reason: Some CCT is found at the centrosome, where CCT and the BBS chaperonin-like proteins assemble the BBSome. Most TCP1 is cytosolic, so this specific location transferred by orthology adds little and is not core. Supporting Evidence: PMID:20080638 a novel complex composed of three chaperonin-like BBS proteins (BBS6, BBS10, and BBS12) and CCT/TRiC family chaperonins mediates BBSome assembly |
| GO:0000792 heterochromatin | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Orthology-based annotation of TCP1 to heterochromatin. Reason: No human evidence places the cytosolic chaperonin subunit on heterochromatin. TCP1 acts in the cytosol, and this orthology transfer most likely reflects a peripheral or isolated observation. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0001669 acrosomal vesicle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology-based annotation of TCP1 to the acrosomal vesicle. Reason: CCT subunits have been reported on the sperm surface and acrosomal region in rodents, where they are proposed to take part in zona pellucida recognition. This is a specialized location in a specific cell type and is kept as non-core. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0002199 zona pellucida receptor complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology-based annotation of TCP1 as part of the zona pellucida receptor complex. Reason: This is a moonlighting association reported for rodent sperm, separate from the cytosolic folding role. It is kept as non-core and deferred to the source curators. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | MARK AS OVER ANNOTATED | Summary: TCP1 was recovered in a proteome-wide mRNA interactome capture (HDA). Reason: High-throughput mRNA-crosslinking capture often recovers abundant cytosolic proteins. There is no evidence that CCT1 has a sequence-specific or functional RNA-binding activity. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005515 protein binding | IPI PMID:14532270 A product of the human gene adjacent to parkin is a componen... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with PACRG. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. PACRG (Glup) forms a large chaperone complex that contains Hsp70/90 and chaperonin components. The partner is a likely CCT client or co-chaperone. The chaperone activity of the complex is captured by the ATP-dependent protein folding chaperone term. |
| GO:0005515 protein binding | IPI PMID:16085932 A novel, evolutionarily conserved protein phosphatase comple... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CCT8. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. From a protein phosphatase complex paper. This is a binding between subunits of the CCT/TRiC hetero-oligomer. Complex membership is captured by GO:0005832 chaperonin-containing T-complex. |
| GO:0005515 protein binding | IPI PMID:16085932 A novel, evolutionarily conserved protein phosphatase comple... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CCT4. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. This is a binding between subunits of the CCT/TRiC hetero-oligomer. Complex membership is captured by GO:0005832 chaperonin-containing T-complex. |
| GO:0005515 protein binding | IPI PMID:16085932 A novel, evolutionarily conserved protein phosphatase comple... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CCT2. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. This is a binding between subunits of the CCT/TRiC hetero-oligomer. Complex membership is captured by GO:0005832 chaperonin-containing T-complex. |
| GO:0005515 protein binding | IPI PMID:16097032 Subproteomic analysis of metal-interacting proteins in human... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CCT2. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. From a metal-interacting protein proteomics study. This is a binding between subunits of the CCT/TRiC hetero-oligomer. Complex membership is captured by GO:0005832 chaperonin-containing T-complex. |
| GO:0005515 protein binding | IPI PMID:21098288 Decreased glucocerebrosidase activity in Gaucher disease par... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with GBA1 (glucocerebrosidase). Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. Reduced binding of GCase to TRiC is proposed to impair GCase maturation. The partner is a likely CCT client or co-chaperone. The chaperone activity of the complex is captured by the ATP-dependent protein folding chaperone term. |
| GO:0005515 protein binding | IPI PMID:24846140 Chaperonin-containing TCP-1 complex directly binds to the cy... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with OLR1 (LOX-1). Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. CCT binds the cytoplasmic domain of LOX-1. The partner is a likely CCT client or co-chaperone. The chaperone activity of the complex is captured by the ATP-dependent protein folding chaperone term. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CBFA2T2. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. From a proteome-scale binary interactome map. This interaction comes from a high-throughput interaction screen and defines no specific activity. |
| GO:0005515 protein binding | IPI PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with WRAP53 (TCAB1). Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. TCAB1 is a folding client of TRiC, and this is the informative relationship. The partner is a likely CCT client or co-chaperone. The chaperone activity of the complex is captured by the ATP-dependent protein folding chaperone term. |
| GO:0005515 protein binding | IPI PMID:29477555 HtrA3 is a cellular partner of cytoskeleton proteins and TCP... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with HTRA3. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. Active HtrA3 binds TCP1alpha but does not cleave it. The role of the interaction is unknown. |
| GO:0005515 protein binding | IPI PMID:29477555 HtrA3 is a cellular partner of cytoskeleton proteins and TCP... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with HTRA3 isoform. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. This is the same HtrA3 study with a specific isoform. |
| GO:0005515 protein binding | IPI PMID:29477555 HtrA3 is a cellular partner of cytoskeleton proteins and TCP... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with HTRA3 isoform. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. This is the same HtrA3 study with a specific isoform. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CCT8. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. From histone crosslinking mass spectrometry. This is a binding between subunits of the CCT/TRiC hetero-oligomer. Complex membership is captured by GO:0005832 chaperonin-containing T-complex. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CCT4. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. This is a binding between subunits of the CCT/TRiC hetero-oligomer. Complex membership is captured by GO:0005832 chaperonin-containing T-complex. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CCT2. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. This is a binding between subunits of the CCT/TRiC hetero-oligomer. Complex membership is captured by GO:0005832 chaperonin-containing T-complex. |
| GO:0005515 protein binding | IPI PMID:31470122 Cellular substrates and pro-apoptotic function of the human ... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with HTRA4. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. A substrate-identification screen for the HtrA4 protease. This interaction comes from a high-throughput interaction screen and defines no specific activity. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with HTT (huntingtin). Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. From a neurodegenerative-disease interactome map. TRiC is known to engage polyglutamine huntingtin. The partner is a likely CCT client or co-chaperone. The chaperone activity of the complex is captured by the ATP-dependent protein folding chaperone term. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with BRPF3. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. From a neurodegenerative-disease interactome map. This interaction comes from a high-throughput interaction screen and defines no specific activity. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with ARL2BP. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. From a neurodegenerative-disease interactome map. This interaction comes from a high-throughput interaction screen and defines no specific activity. |
| GO:0005515 protein binding | IPI PMID:33144677 Dlec1 is required for spermatogenesis and male fertility in ... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with DLEC1. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. DLEC1 associates with TCP1 in mouse testis. The partner is a likely CCT client or co-chaperone. The chaperone activity of the complex is captured by the ATP-dependent protein folding chaperone term. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CCT2. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. From a proteome-scale interaction network. This is a binding between subunits of the CCT/TRiC hetero-oligomer. Complex membership is captured by GO:0005832 chaperonin-containing T-complex. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CCT8. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. From OpenCell endogenous-tag interaction proteomics. This is a binding between subunits of the CCT/TRiC hetero-oligomer. Complex membership is captured by GO:0005832 chaperonin-containing T-complex. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CCT4. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. This is a binding between subunits of the CCT/TRiC hetero-oligomer. Complex membership is captured by GO:0005832 chaperonin-containing T-complex. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CCT2. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. This is a binding between subunits of the CCT/TRiC hetero-oligomer. Complex membership is captured by GO:0005832 chaperonin-containing T-complex. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Reported physical association of TCP1 (CCT1) with CCT2. Reason: GO:0005515 protein binding is uninformative about the molecular activity of TCP1. The interaction itself is not disputed. From multimodal cell-map proteomics. This is a binding between subunits of the CCT/TRiC hetero-oligomer. Complex membership is captured by GO:0005832 chaperonin-containing T-complex. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based annotation of ATP binding. Reason: Each CCT subunit has the conserved group II chaperonin equatorial nucleotide-binding site. CCT1 is one of the higher-affinity ATP-binding subunits of TRiC: it crosslinks to ATP at intermediate nucleotide concentrations, and ATP binding to the high-affinity subunits is required for viability. Supporting Evidence: PMID:23041314 We conclude that a gradient of affinities governs ATP binding to TRiC subunits: CCT5 and CCT4 have the highest affinities and thus are occupied at the lowest ATP concentrations, followed by CCT1 and CCT2. PMID:23041314 Whereas ATP binding to these high-affinity subunits is required for viability, ATP binding to the four low-affinity subunits is dispensable for TRiC activity. |
| GO:0005794 Golgi apparatus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Orthology-based annotation of TCP1 to the Golgi apparatus. Reason: TCP1 is a cytosolic chaperonin subunit. Golgi association is not part of its established biology in human cells. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005813 centrosome | IDA PMID:20080638 BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family c... | KEEP AS NON CORE | Summary: CCT subunits localize to the centrosome, where they act with BBS6/BBS10/BBS12 to assemble the BBSome. Reason: The experimental localization is accepted. A centrosomal pool of CCT supports BBSome assembly, but the main location of TCP1 is the cytosol. Supporting Evidence: PMID:20080638 CCT activity is essential for BBSome assembly, and knockdown of CCT chaperonins in zebrafish results in BBS phenotypes. PMID:20080638 a novel complex composed of three chaperonin-like BBS proteins (BBS6, BBS10, and BBS12) and CCT/TRiC family chaperonins mediates BBSome assembly |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: UniProt mapping of TCP1 to the centrosome. Reason: This is consistent with the experimental centrosome data and is non-core. Supporting Evidence: PMID:20080638 a novel complex composed of three chaperonin-like BBS proteins (BBS6, BBS10, and BBS12) and CCT/TRiC family chaperonins mediates BBSome assembly |
| GO:0005815 microtubule organizing center | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Orthology-based annotation of TCP1 to the microtubule organizing center. Reason: This is a broader parent of the centrosome location and is non-core. Supporting Evidence: PMID:20080638 a novel complex composed of three chaperonin-like BBS proteins (BBS6, BBS10, and BBS12) and CCT/TRiC family chaperonins mediates BBSome assembly |
| GO:0005829 cytosol | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt mapping of TCP1 to the cytosol. Reason: The cytosol is the main site of CCT/TRiC folding. Supporting Evidence: PMID:1630491 We conclude that TCP1 functions as a cytosolic chaperone in the biogenesis of tubulin. PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005829 cytosol | TAS PMID:1630491 TCP1 complex is a molecular chaperone in tubulin biogenesis. | ACCEPT | Summary: TCP1 acts as a cytosolic chaperone in tubulin biogenesis. Reason: This is correct and is the core location. Supporting Evidence: PMID:1630491 We conclude that TCP1 functions as a cytosolic chaperone in the biogenesis of tubulin. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-391266 | ACCEPT | Summary: Reactome places TCP1 in the cytosol for CCT/TRiC association with sphingosine kinase 1. Reason: Cytosol is correct. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6814119 | ACCEPT | Summary: Reactome places TCP1 in the cytosol for TRiC binding of unfolded G-protein beta. Reason: Cytosol is correct. G-beta is a well-established TRiC client. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6814120 | ACCEPT | Summary: Reactome places TCP1 in the cytosol for ATP hydrolysis-driven folding of G-beta by TRiC. Reason: Cytosol is correct. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6814121 | ACCEPT | Summary: Reactome places TCP1 in the cytosol for PDCL binding to G-beta and TRiC. Reason: Cytosol is correct. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-6814124 | ACCEPT | Summary: Reactome places TCP1 in the cytosol for ATP binding to G-beta-associated TRiC. Reason: Cytosol is correct. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8850527 | ACCEPT | Summary: Reactome places TCP1 in the cytosol for PDCL release of folded G-beta. Reason: Cytosol is correct. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8850529 | ACCEPT | Summary: Reactome places TCP1 in the cytosol for RGS protein and GNB5 binding to TRiC. Reason: Cytosol is correct. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8850534 | ACCEPT | Summary: Reactome places TCP1 in the cytosol for PDCL-promoted folding of GNB5. Reason: Cytosol is correct. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8850539 | ACCEPT | Summary: Reactome places TCP1 in the cytosol for release of GNB5:RGS dimers. Reason: Cytosol is correct. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8950718 | ACCEPT | Summary: Reactome places TCP1 in the cytosol for TCP1 expression. Reason: Cytosol is correct. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0005832 chaperonin-containing T-complex | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT inference that TCP1 is part of the CCT complex. Reason: This is the defining complex membership of TCP1/CCT1 and is directly supported in human cells. Supporting Evidence: PMID:23011926 This purified human TRiC contained all eight CCT subunits organized into double-barrel rings, consistent with what has been found for bovine and yeast TRiC. PMID:23011926 has eight different subunits, chaperone containing TCP-1 (CCT1–8), that are arranged so that there is one of each subunit per ring. |
| GO:0005832 chaperonin-containing T-complex | IDA PMID:23011926 Human TRiC complex purified from HeLa cells contains all eig... | ACCEPT | Summary: Human TRiC purified from HeLa cells contains all eight CCT subunits, including CCT1. Reason: This is direct biochemical evidence. Supporting Evidence: PMID:23011926 This purified human TRiC contained all eight CCT subunits organized into double-barrel rings, consistent with what has been found for bovine and yeast TRiC. |
| GO:0005832 chaperonin-containing T-complex | IDA PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | ACCEPT | Summary: TRiC containing CCT1 was characterized as the folding chaperone for TCAB1. Reason: This is correct. Supporting Evidence: PMID:25467444 We find that TRiC is required for folding the telomerase cofactor TCAB1, which controls trafficking of telomerase and small Cajal body RNAs (scaRNAs). |
| GO:0005832 chaperonin-containing T-complex | IDA PMID:30955883 The Chaperonin TRiC/CCT Associates with Prefoldin through a ... | ACCEPT | Summary: Structural and crosslinking analysis of TRiC with prefoldin. Reason: This is correct and consistent with the other evidence. Supporting Evidence: PMID:30955883 PFD can act after TRiC bound its substrates to enhance the rate and yield of the folding reaction, suppressing non-productive reaction cycles. |
| GO:0005832 chaperonin-containing T-complex | IEA GO_REF:0000107 | ACCEPT | Summary: Orthology-based annotation of TCP1 to the CCT complex. Reason: This is correct. Supporting Evidence: PMID:23011926 This purified human TRiC contained all eight CCT subunits organized into double-barrel rings, consistent with what has been found for bovine and yeast TRiC. |
| GO:0005832 chaperonin-containing T-complex | IPI PMID:22133715 Reconstitution of the human chaperonin CCT by co-expression ... | ACCEPT | Summary: Recombinant human CCT was reconstituted by co-expressing all eight subunits, with a tag placed in CCT1. Reason: This is direct evidence that CCT1 is incorporated into a functional complex. Supporting Evidence: PMID:22133715 The CCT1 subunit was engineered to carry a hexa-histidine tag or FLAG tag in the internal loop region. PMID:22133715 The purified recombinant CCT complexes were indistinguishable from the endogenous CCT purified from HeLa cells in terms of morphology and function. |
| GO:0005874 microtubule | IDA PMID:21525035 PEX14 is required for microtubule-based peroxisome motility ... | UNDECIDED | Summary: TCP1 was annotated to microtubule (IDA) from a study of PEX14 complexes and peroxisome motility. Reason: The cached abstract describes PEX14-tubulin binding and does not mention TCP1. The basis for a TCP1-microtubule localization cannot be checked here, possibly co-purification of CCT with its tubulin client. A stable association of CCT1 with polymerized microtubules is not established in the literature reviewed. Supporting Evidence: PMID:21525035 Unexpectedly, tubulin was discovered to be the major PEX14-associated protein, and direct binding of the proteins was demonstrated. |
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT inference that TCP1 acts in protein folding. Reason: This is the core process of the CCT/TRiC chaperonin. Supporting Evidence: PMID:1630491 We conclude that TCP1 functions as a cytosolic chaperone in the biogenesis of tubulin. PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0006457 protein folding | IDA PMID:22133715 Reconstitution of the human chaperonin CCT by co-expression ... | ACCEPT | Summary: Reconstituted recombinant human CCT containing tagged CCT1 is functionally equivalent to endogenous CCT. Reason: This is accepted. Supporting Evidence: PMID:22133715 The purified recombinant CCT complexes were indistinguishable from the endogenous CCT purified from HeLa cells in terms of morphology and function. |
| GO:0006457 protein folding | IDA PMID:30955883 The Chaperonin TRiC/CCT Associates with Prefoldin through a ... | ACCEPT | Summary: Prefoldin enhances the rate and yield of TRiC-mediated folding. Reason: This is accepted. Supporting Evidence: PMID:30955883 PFD can act after TRiC bound its substrates to enhance the rate and yield of the folding reaction, suppressing non-productive reaction cycles. |
| GO:0006457 protein folding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based annotation of protein folding. Reason: This is correct. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0006457 protein folding | IMP PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | ACCEPT | Summary: Depletion of TRiC subunits abolishes TCAB1 folding and accumulation. Reason: This is accepted. The paper shows that TRiC folds TCAB1 and that DC-associated TCAB1 mutants are impaired in TRiC folding. Supporting Evidence: PMID:25467444 We find that TRiC is required for folding the telomerase cofactor TCAB1, which controls trafficking of telomerase and small Cajal body RNAs (scaRNAs). |
| GO:0006457 protein folding | TAS PMID:1630491 TCP1 complex is a molecular chaperone in tubulin biogenesis. | ACCEPT | Summary: TCP1 is a cytosolic chaperone in tubulin biogenesis. Tubulin is released in an assembly-competent form only on Mg-ATP hydrolysis. Reason: This is a classic finding and is accepted. Supporting Evidence: PMID:1630491 We conclude that TCP1 functions as a cytosolic chaperone in the biogenesis of tubulin. PMID:1630491 Addition of Mg-ATP, but not nonhydrolysable analogues, released the tubulin subunits as assembly-competent protein |
| GO:0007021 tubulin complex assembly | NAS PMID:11532003 Cytosolic chaperonin-containing t-complex polypeptide 1 chan... | KEEP AS NON CORE | Summary: A curator statement that CCT takes part in tubulin complex assembly, based on cell-cycle changes in CCT subunit content and tubulin binding. Reason: CCT folds alpha- and beta-tubulin monomers into assembly-competent forms, and tubulin-specific cofactors then assemble the heterodimer. CCT supplies the folded monomers rather than performing heterodimer assembly, so this is a downstream contribution and is kept as non-core. Supporting Evidence: PMID:1630491 We conclude that TCP1 functions as a cytosolic chaperone in the biogenesis of tubulin. PMID:11532003 the alpha and delta subunit content in the 700- to 900-kDa CCT complex was appreciably lower in the M phase cells than in asynchronous cells |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based annotation of ATP hydrolysis activity. Reason: CCT1 retains the canonical nucleotide-binding and hydrolysis site and is among the higher-affinity ATP-binding TRiC subunits. ATP hydrolysis drives the folding cycle. Supporting Evidence: PMID:23041314 We conclude that a gradient of affinities governs ATP binding to TRiC subunits: CCT5 and CCT4 have the highest affinities and thus are occupied at the lowest ATP concentrations, followed by CCT1 and CCT2. PMID:1630491 Addition of Mg-ATP, but not nonhydrolysable analogues, released the tubulin subunits as assembly-competent protein |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:21753002 Parkin interacts with Ambra1 to induce mitophagy. | KEEP AS NON CORE | Summary: TCP1 was recovered among Parkin-associated proteins. Reason: This is consistent with CCT engaging the E3 ligase Parkin as a client or partner. The functional meaning is not established, and it is not part of the core chaperonin function. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0032212 positive regulation of telomere maintenance via telomerase | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Automated (ARBA) annotation of positive regulation of telomere maintenance via telomerase. Reason: The telomerase link is indirect but experimentally supported in human cells. TRiC folds TCAB1, which is needed for telomerase trafficking and telomere elongation. This is kept as a non-core, client-specific consequence, consistent with the IMP row. Supporting Evidence: PMID:25467444 We find that TRiC is required for folding the telomerase cofactor TCAB1, which controls trafficking of telomerase and small Cajal body RNAs (scaRNAs). PMID:25467444 Depletion of TRiC causes loss of TCAB1 protein, mislocalization of telomerase and scaRNAs to nucleoli, and failure of telomere elongation. |
| GO:0032212 positive regulation of telomere maintenance via telomerase | IMP PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | KEEP AS NON CORE | Summary: TRiC depletion causes failure of telomere elongation through loss of folded TCAB1 (annotated as acts upstream of). Reason: This is a genuine experimental consequence of TRiC-mediated folding of TCAB1. It is a downstream, client-specific effect and is non-core. Supporting Evidence: PMID:25467444 Depletion of TRiC causes loss of TCAB1 protein, mislocalization of telomerase and scaRNAs to nucleoli, and failure of telomere elongation. PMID:25467444 Our findings establish a critical role for TRiC-mediated protein folding in the telomerase pathway and link proteostasis, telomere maintenance, and human disease. |
| GO:0044183 protein folding chaperone | IDA PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | MODIFY | Summary: TRiC folds TCAB1. CCT1 is a subunit of the folding machine. Reason: The activity is correctly a protein folding chaperone. It is ATP-dependent and is a property of the hetero-oligomeric complex to which CCT1 contributes. The more specific GO:0140662 ATP-dependent protein folding chaperone is more accurate. Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: PMID:25467444 We find that TRiC is required for folding the telomerase cofactor TCAB1, which controls trafficking of telomerase and small Cajal body RNAs (scaRNAs). PMID:1630491 Addition of Mg-ATP, but not nonhydrolysable analogues, released the tubulin subunits as assembly-competent protein |
| GO:0044183 protein folding chaperone | IDA PMID:30955883 The Chaperonin TRiC/CCT Associates with Prefoldin through a ... | MODIFY | Summary: TRiC with prefoldin folds substrates. CCT1 is a subunit of the folding machine. Reason: As above, the more specific ATP-dependent protein folding chaperone term applies. Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: PMID:30955883 PFD can act after TRiC bound its substrates to enhance the rate and yield of the folding reaction, suppressing non-productive reaction cycles. PMID:1630491 Addition of Mg-ATP, but not nonhydrolysable analogues, released the tubulin subunits as assembly-competent protein |
| GO:0044183 protein folding chaperone | IEA GO_REF:0000117 | MODIFY | Summary: Automated annotation of protein folding chaperone. Reason: This is correct but less specific than the ATP-dependent chaperonin activity. Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: PMID:1630491 Addition of Mg-ATP, but not nonhydrolysable analogues, released the tubulin subunits as assembly-competent protein |
| GO:0044297 cell body | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Orthology-based annotation of TCP1 to the cell body. Reason: TCP1 is a ubiquitous cytosolic protein. A neuronal cell-body location adds no specific information beyond cytosol. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0050821 protein stabilization | IMP PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | KEEP AS NON CORE | Summary: TRiC depletion causes loss of TCAB1 protein, read as protein stabilization. Reason: TRiC folds TCAB1, and unfolded TCAB1 is degraded. The stabilization follows from folding, so this is kept as a non-core, client-specific consequence. Supporting Evidence: PMID:25467444 Depletion of TRiC causes loss of TCAB1 protein, mislocalization of telomerase and scaRNAs to nucleoli, and failure of telomere elongation. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: TCP1 was detected in urinary exosome proteomics. Reason: Abundant cytosolic proteins are often found in exosome proteomes. This is not a functional location. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: TCP1 was detected in B-cell exosome proteomics. Reason: As above. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: TCP1 was detected in prostatic-secretion exosome proteomics. Reason: As above. Supporting Evidence: PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:0090666 scaRNA localization to Cajal body | IMP PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | KEEP AS NON CORE | Summary: TRiC is required for scaRNA localization to Cajal bodies, through TCAB1 folding (annotated as acts upstream of, positive effect). Reason: This is a correct experimental observation. It is an indirect consequence of folding the TCAB1 client and is non-core. Supporting Evidence: PMID:25467444 We find that TRiC is required for folding the telomerase cofactor TCAB1, which controls trafficking of telomerase and small Cajal body RNAs (scaRNAs). PMID:25467444 Depletion of TRiC causes loss of TCAB1 protein, mislocalization of telomerase and scaRNAs to nucleoli, and failure of telomere elongation. |
| GO:0140662 ATP-dependent protein folding chaperone | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based annotation of ATP-dependent protein folding chaperone. Reason: This is the most informative activity term for CCT/TRiC. Strictly, CCT1 contributes to this activity of the hetero-oligomer rather than having it alone. Supporting Evidence: PMID:1630491 Addition of Mg-ATP, but not nonhydrolysable analogues, released the tubulin subunits as assembly-competent protein PMID:11532003 The chaperonin-containing t-complex polypeptide 1 (CCT) is a cytosolic molecular chaperone composed of eight subunits that assists in the folding of actin, tubulin and other cytosolic proteins. |
| GO:1904851 positive regulation of establishment of protein localization to telomere | IMP PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | KEEP AS NON CORE | Summary: TRiC depletion impairs telomerase localization to telomeres (annotated as acts upstream of). Reason: This is an indirect consequence of TCAB1 folding and is non-core. Supporting Evidence: PMID:25467444 Depletion of TRiC causes loss of TCAB1 protein, mislocalization of telomerase and scaRNAs to nucleoli, and failure of telomere elongation. |
| GO:1904871 positive regulation of protein localization to Cajal body | HMP PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | KEEP AS NON CORE | Summary: TRiC depletion impairs protein localization to Cajal bodies (TCAB1). Reason: This is an indirect, client-specific consequence of folding and is non-core. Supporting Evidence: PMID:25467444 We find that TRiC is required for folding the telomerase cofactor TCAB1, which controls trafficking of telomerase and small Cajal body RNAs (scaRNAs). PMID:25467444 Depletion of TRiC causes loss of TCAB1 protein, mislocalization of telomerase and scaRNAs to nucleoli, and failure of telomere elongation. |
| GO:1904874 positive regulation of telomerase RNA localization to Cajal body | IMP PMID:25467444 Proteostatic control of telomerase function through TRiC-med... | KEEP AS NON CORE | Summary: TRiC depletion causes telomerase RNA (TERC) to mislocalize from Cajal bodies to nucleoli. Reason: This is an indirect consequence of TCAB1 folding and is non-core. Supporting Evidence: PMID:25467444 Depletion of TRiC causes loss of TCAB1 protein, mislocalization of telomerase and scaRNAs to nucleoli, and failure of telomere elongation. |
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Download this section (compressed HTML)Q: Which clients depend specifically on CCT1's apical domain, and does the M-phase loss of CCT1 from the complex regulate folding capacity physiologically?
Experiment: Use crosslinking mass spectrometry and cryo-EM of human TRiC-client complexes (for example TCAB1 or tubulin) to map contacts with CCT1, then test apical-domain point mutants of CCT1 for client-specific folding defects in human cells.
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