TCP1 (also known as CCT1) encodes the alpha subunit of the chaperonin-containing T-complex (TRiC/CCT) in S. cerevisiae. TRiC/CCT is an essential, hetero-oligomeric, group II chaperonin composed of eight paralogous subunits (CCT1-8) arranged in two stacked rings of eight subunits each, forming a ~1 MDa complex. The complex functions as an ATP-dependent protein folding machine that assists the folding of actin, tubulin, and a small number of other substrates including WD40-repeat proteins. Each subunit contributes to the overall ATP-dependent protein folding chaperone activity of the complex; individual subunits do not independently fold substrates. TCP1/CCT1 is essential for viability and plays roles in mitotic spindle formation in yeast. The crystal structure of yeast CCT (PMID:21701561) reveals intrinsic asymmetry among the eight subunits, with each displaying unique configurations and substrate-binding properties.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: TCP1 is part of the TRiC/CCT complex that assists protein folding. IBA annotation is consistent with IDA evidence from PMID:16762366 demonstrating that purified yeast CCT catalyses actin folding in vitro. Reason: Core biological process. The TRiC/CCT complex is an essential protein folding machine, and TCP1 is a required subunit. IBA is well supported by experimental data. Supporting Evidence: PMID:16762366 The eukaryotic cytosolic chaperonin CCT is an essential ATP-dependent protein folding machine whose action is required for folding the cytoskeletal proteins actin and tubulin file:yeast/TCP1/TCP1-deep-research-falcon.md TCP1/CCT1 encodes CCT1 (TCP-1; CCT-alpha), one of eight paralogous subunits that assemble into the eukaryotic cytosolic chaperonin TRiC/CCT. |
| GO:0005832 chaperonin-containing T-complex | IBA GO_REF:0000033 | ACCEPT | Summary: TCP1 is the alpha subunit of the chaperonin-containing T-complex (TRiC/CCT). IBA is consistent with IDA and IPI evidence from PMID:16762366 and PMID:15704212. Reason: Core complex membership. TCP1 is an integral, essential subunit of TRiC/CCT. Well supported by multiple experimental methods. |
| GO:0051082 unfolded protein binding | IBA GO_REF:0000033 | MODIFY | Summary: GO:0051082 (unfolded protein binding) is now formally obsolete. TCP1, as a subunit of TRiC/CCT, does interact with unfolded substrates (actin, tubulin), but this occurs in the context of the ATP-dependent chaperonin folding cycle, not as a standalone binding function. The correct replacement is GO:0140662 (ATP-dependent protein folding chaperone), with the qualifier contributes_to since TCP1 is a subunit of the complex. Reason: GO:0051082 is now formally obsolete. TCP1 binds unfolded proteins only as part of the TRiC/CCT complex's ATP-dependent folding cycle. The appropriate replacement is GO:0140662 (ATP-dependent protein folding chaperone). This IEA-level annotation via InterPro already exists for this gene. Proposed replacements: ATP-dependent protein folding chaperone |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: TCP1 binds ATP as part of its chaperonin function. This is a parent term of ATP binding and is correct but general. Reason: Correct. All TRiC/CCT subunits bind nucleotides (ATP/ADP). The more specific term ATP binding (GO:0005524) is also annotated. This broader IEA is acceptable. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: TCP1 binds ATP through its equatorial domain. Each CCT subunit has an ATP-binding site that is essential for the allosteric chaperonin cycle. Reason: Correct and fundamental. ATP binding is essential for the TRiC/CCT folding mechanism. UniProt keywords confirm ATP-binding. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: TCP1 is a cytoplasmic protein. UniProt subcellular location annotation confirms cytoplasmic localization. Reason: Correct. TRiC/CCT is a cytoplasmic/cytosolic complex. |
| GO:0005832 chaperonin-containing T-complex | IEA GO_REF:0000117 | ACCEPT | Summary: Redundant with the IBA and IDA annotations for TRiC/CCT membership. Correct ARBA-based annotation. Reason: Correct. Redundant with experimental evidence but acceptable. |
| GO:0006457 protein folding | IEA GO_REF:0000120 | ACCEPT | Summary: Redundant with IBA and IDA annotations for protein folding. Correct. Reason: Correct. Consistent with IBA and IDA evidence. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: Each TRiC/CCT subunit has ATPase activity. The crystal structure (PMID:21701561) reveals ATP-binding heterogeneity among subunits, and the complex uses a sequential ATP hydrolysis mechanism. Reason: Correct. Each CCT subunit contributes ATPase activity to the chaperonin cycle. InterPro-based annotation is well supported. |
| GO:0051082 unfolded protein binding | IEA GO_REF:0000120 | MODIFY | Summary: GO:0051082 is now formally obsolete. Same rationale as the IBA annotation above. Reason: GO:0051082 is now formally obsolete. Should be replaced with GO:0140662 (ATP-dependent protein folding chaperone), which is already annotated via InterPro. Proposed replacements: ATP-dependent protein folding chaperone |
| GO:0140662 ATP-dependent protein folding chaperone | IEA GO_REF:0000002 | ACCEPT | Summary: This is the correct molecular function term for TRiC/CCT subunits. InterPro-based annotation via IPR017998 (Chaperone TCP-1). TCP1 contributes to this activity as part of the hetero-oligomeric complex. Reason: Correct and the most appropriate MF term. GO:0140662 is the proper replacement for the obsoleting GO:0051082. As a complex subunit, the qualifier should ideally be contributes_to rather than enables, but the IEA annotation is correct in substance. |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | MARK AS OVER ANNOTATED | Summary: IPI evidence from the global landscape of protein complexes study (Krogan et al. 2006). TCP1 interacts with POP2 (P39008) and YPP1 (P46951) in TAP-MS experiments. Reason: Protein binding is uninformative for a chaperonin subunit. Interactions detected in large-scale complex purification studies likely reflect chaperone-substrate or complex-subunit interactions already captured by the TRiC/CCT complex membership annotation. These are better described by the chaperonin complex annotation. |
| GO:0005515 protein binding | IPI PMID:19536198 An atlas of chaperone-protein interactions in Saccharomyces ... | MARK AS OVER ANNOTATED | Summary: IPI evidence from the chaperone-protein interactions atlas (Gong et al. 2009). TCP1 interacts with SIT4 (P20604), POP2 (P39008), and YPP1 (P46951). Reason: Protein binding is uninformative for a chaperonin subunit. These interactions represent chaperonin-substrate relationships that are an inherent part of TRiC/CCT function. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | MARK AS OVER ANNOTATED | Summary: IPI evidence from a global protein kinase and phosphatase interaction network. TCP1 interacts with SIT4 (P20604). Reason: Protein binding is uninformative for a chaperonin subunit. |
| GO:0005515 protein binding | IPI PMID:21701561 The crystal structure of yeast CCT reveals intrinsic asymmet... | MARK AS OVER ANNOTATED | Summary: IPI evidence from the crystal structure study of yeast CCT. TCP1 interacts with ACT1 (P60010) in the CCT-actin co-crystal structure. This is a well-characterized chaperonin-substrate interaction. Reason: Protein binding is uninformative. The TCP1-actin interaction is a direct chaperonin-substrate relationship, which is the core function of TRiC/CCT already captured by the protein folding and complex membership annotations. Supporting Evidence: PMID:21701561 We have solved the crystal structure of yeast CCT in complex with actin at 3.8 Å resolution, revealing the subunit organisation and the location of discrete patches of co-evolving 'signature residues' that mediate specific interactions between CCT and its substrates. |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | MARK AS OVER ANNOTATED | Summary: IPI evidence from an inter-species protein-protein interaction network. TCP1 interacts with several human proteins (cross-species interactions). Reason: Protein binding is uninformative. Cross-species interactions in this context likely reflect conserved chaperonin-substrate relationships. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | MARK AS OVER ANNOTATED | Summary: IPI evidence from the social and structural architecture of the yeast protein interactome. TCP1 interacts with SIT4 (P20604). Reason: Protein binding is uninformative for a chaperonin subunit. |
| GO:0005515 protein binding | IPI PMID:9878052 Compartmentation of protein folding in vivo: sequestration o... | MARK AS OVER ANNOTATED | Summary: IPI evidence from the chaperonin-GimC system study (Siegers et al. 1999). TCP1 interacts with ACT1 (P60010). This study demonstrated that TRiC and GimC form an integrated folding compartment that sequesters newly synthesized actin. Reason: Protein binding is uninformative. The TCP1-actin interaction is a core chaperonin-substrate relationship already captured by the protein folding and complex annotations. The study supports the chaperonin function annotation. Supporting Evidence: PMID:9878052 We propose that TRiC and GimC form an integrated 'folding compartment' which functions in cooperation with the translation machinery. |
| GO:0006457 protein folding | IDA PMID:16762366 Quantitative actin folding reactions using yeast CCT purifie... | ACCEPT | Summary: PMID:16762366 demonstrated quantitative actin folding using purified yeast CCT. The purified complex catalyses folding of both yeast ACT1p and human beta-actin with nearly identical rate constants. Reason: Core biological process. Direct experimental demonstration of TRiC/CCT-mediated protein folding in vitro using the purified complex containing TCP1. Supporting Evidence: PMID:16762366 Yeast CCT catalyses the folding of yeast ACT1p and human beta-actin with nearly identical rate constants and yields. |
| GO:0005886 plasma membrane | HDA PMID:16622836 The plasma membrane proteome of Saccharomyces cerevisiae and... | KEEP AS NON CORE | Summary: HDA evidence from the plasma membrane proteome study. TCP1 was detected in the plasma membrane fraction, though this may reflect co-purification rather than true membrane localization. Reason: TCP1 was detected in the plasma membrane proteome, but TRiC/CCT is primarily a cytosolic complex. The plasma membrane association may be a minor or artifact localization. Not a core localization. |
| GO:0005832 chaperonin-containing T-complex | IPI PMID:15704212 Physiological effects of unassembled chaperonin Cct subunits... | ACCEPT | Summary: PMID:15704212 studied physiological effects of unassembled Cct subunits. TCP1 was shown to be part of the complex through interaction with other subunits (with CCT6/S000002596 as supporting entity). Reason: Core complex membership with experimental IPI evidence. Supporting Evidence: PMID:15704212 Eukaryotic chaperonins, the Cct complexes, are assembled into two rings, each of which is composed of a stoichiometric array of eight different subunits |
| GO:0005832 chaperonin-containing T-complex | IDA PMID:16762366 Quantitative actin folding reactions using yeast CCT purifie... | ACCEPT | Summary: PMID:16762366 purified the intact yeast CCT complex, confirming TCP1 as a constituent subunit. Reason: Core complex membership with direct experimental evidence from purified complex. |
| GO:0051082 unfolded protein binding | IDA PMID:16762366 Quantitative actin folding reactions using yeast CCT purifie... | MODIFY | Summary: GO:0051082 is now formally obsolete. PMID:16762366 demonstrated that the purified CCT complex binds actin folding intermediates (Ac(I)) and processes them to native actin in an ATP-dependent manner. This is chaperonin-mediated folding, not passive unfolded protein binding. Reason: GO:0051082 is now formally obsolete. The experimental evidence from PMID:16762366 actually demonstrates ATP-dependent protein folding chaperone activity. The CCT complex binds actin intermediates in a pre-equilibrium step followed by ATP-driven processing to native actin. This is GO:0140662 (ATP-dependent protein folding chaperone). Proposed replacements: ATP-dependent protein folding chaperone Supporting Evidence: PMID:16762366 The results from this controlled CCT-actin folding assay are consistent with a model where CCT and Ac(I) are in a binding pre-equilibrium with a rate-limiting binding step, followed by a faster ATP-driven processing to native actin. |
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Download this section (compressed HTML)Q: Which yeast TRiC/CCT substrates require CCT1-specific apical or chamber-facing contacts rather than generic complex-level chaperonin activity?
Q: Should the emerging nuclear TRiC/CCT RNA polymerase II role be curated for TCP1 after peer-reviewed confirmation, or treated as a non-core complex phenotype?
Experiment: Combine CCT1 apical/chamber-surface mutants with purified yeast TRiC folding assays and in vivo client abundance/activity readouts for ACT1, tubulins, Cdh1, and Cdc20.
Hypothesis: CCT1 contributes substrate-specific contacts that are required for efficient folding of selected actin, tubulin, or WD40-repeat clients.
Type: client-specific folding assay
Experiment: Validate nuclear TRiC occupancy and RNAPII/RNA phenotypes using independently tagged CCT subunits, acute degron or anchor-away perturbations, and rescue with cytoplasm-restricted versus nucleus-permissive CCT1 variants.
Hypothesis: The nuclear RNA polymerase II phenotype of cct1-2 reflects assembled TRiC/CCT function rather than indirect cytoplasmic proteostasis stress.
Type: nuclear TRiC validation
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