CCT4 encodes the delta subunit of the cytosolic chaperonin-containing T-complex (CCT/TRiC). CCT/TRiC is an ATP-dependent hetero-oligomeric chaperonin with two stacked rings built from eight related subunits. The complex assists folding of actin, tubulin, and other cytosolic substrates. CCT4 contributes as an integral subunit of the assembled CCT complex rather than as a free general protein-binding factor.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: CCT4 is a subunit of the CCT/TRiC chaperonin, which catalyzes ATP-dependent folding of actin and other cytosolic substrates. Reason: Yeast CCT purified from cells folds yeast ACT1p and human beta-actin in vitro, and the CCT family assignment supports conserved chaperonin function. Supporting Evidence: PMID:16762366 Yeast CCT catalyses the folding of yeast ACT1p and human beta-actin with nearly identical rate constants and yields. file:interpro/panther/PTHR11353/PTHR11353-metadata.yaml PANTHER PTHR11353 classifies CCT4 in the chaperonin family. file:yeast/CCT4/CCT4-deep-research-falcon.md Falcon synthesis supports CCT4 as the CCT/TRiC delta subunit with conserved ATP-dependent chaperonin function. |
| GO:0005832 chaperonin-containing T-complex | IBA GO_REF:0000033 | ACCEPT | Summary: CCT4 is an integral CCT/TRiC subunit and the complex term is appropriate. Reason: The chaperonin-containing T-complex is composed of a stoichiometric array of Cct1p-Cct8p subunits, including Cct4p. 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, which are denoted Cct1p-Cct8p. |
| GO:0051082 unfolded protein binding | IBA GO_REF:0000033 | MODIFY | Summary: The broad unfolded-protein binding term should be replaced by a chaperone term that captures CCT/TRiC activity. Reason: CCT4 acts through an ATP-dependent chaperonin complex; GO:0140662 is more informative than generic unfolded protein binding. Proposed replacements: ATP-dependent protein folding chaperone |
| GO:0000166 nucleotide binding | IEA GO_REF:0000043 | ACCEPT | Summary: CCT4 is a TCP-1 family chaperonin subunit with conserved nucleotide-binding machinery. Reason: ATP binding and hydrolysis are part of the CCT chaperonin cycle, but this broad keyword-derived term is retained as a valid molecular feature. Supporting Evidence: file:interpro/panther/PTHR11353/PTHR11353-metadata.yaml PTHR11353 is the conserved chaperonin family that includes TCP-1/CCT proteins. |
| GO:0005524 ATP binding | IEA GO_REF:0000120 | ACCEPT | Summary: ATP binding is consistent with the ATP-dependent CCT/TRiC chaperonin cycle. Reason: The complex is explicitly described as an ATP-dependent folding machine and CCT4 belongs to the ATPase-containing TCP-1 chaperonin family. Supporting Evidence: PMID:16762366 The eukaryotic cytosolic chaperonin CCT is an essential ATP-dependent protein folding machine. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: CCT4 functions in the cytosolic CCT/TRiC complex. Reason: UniProt and CCT chaperone literature place this chaperonin in the cytoplasm, where it folds cytosolic substrates such as actin and tubulin. |
| GO:0005832 chaperonin-containing T-complex | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA annotation to the CCT complex is supported by the known subunit composition. Reason: CCT4/Cct4p is one of the Cct1p-Cct8p subunits of the chaperonin-containing T-complex. |
| GO:0006457 protein folding | IEA GO_REF:0000120 | ACCEPT | Summary: Protein folding is the core biological process of the CCT/TRiC complex. Reason: The term is broad but correct for this subunit because the assembled CCT complex catalyzes folding of actin and other substrates. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: ATP hydrolysis activity is consistent with CCT/TRiC chaperonin mechanism. Reason: CCT is an ATP-dependent folding machine and the InterPro/PANTHER family supports the conserved chaperonin ATPase fold. |
| GO:0051082 unfolded protein binding | IEA GO_REF:0000120 | MODIFY | Summary: Generic unfolded-protein binding is less specific than the chaperonin activity supported for CCT4. Reason: The molecular role is ATP-dependent chaperonin-mediated folding, so GO:0140662 is a better replacement. Proposed replacements: ATP-dependent protein folding chaperone |
| GO:0140662 ATP-dependent protein folding chaperone | IEA GO_REF:0000002 | ACCEPT | Summary: ATP-dependent protein folding chaperone is the best available MF term for CCT4-containing CCT/TRiC. Reason: CCT/TRiC is an ATP-dependent folding machine, and CCT4 contributes as one subunit of this complex. Supporting Evidence: PMID:16762366 The eukaryotic cytosolic chaperonin CCT is an essential ATP-dependent protein folding machine. |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | MARK AS OVER ANNOTATED | Summary: Generic protein binding from complex-scale data is not informative for CCT4. Reason: PMID:16554755 is a large-scale complex map; CCT4's functional binding role is better represented by CCT complex membership and chaperone activity. |
| GO:0005515 protein binding | IPI PMID:19536198 An atlas of chaperone-protein interactions in Saccharomyces ... | MARK AS OVER ANNOTATED | Summary: Chaperone interactome data do not justify retaining generic protein binding as a core annotation. Reason: PMID:19536198 reports broad TAP-tag chaperone interactions that are often indirect; the specific function is CCT/TRiC chaperonin activity. Supporting Evidence: PMID:19536198 The interactions presented are indirect TAP-tag based interactions and not direct binary interactions. |
| GO:0005515 protein binding | IPI PMID:27107014 An inter-species protein-protein interaction network across ... | MARK AS OVER ANNOTATED | Summary: Inter-species interaction evidence is too generic for a useful GO MF annotation. Reason: The annotation does not identify a specific binding activity beyond the already curated chaperonin complex and ATP-dependent folding function. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | MARK AS OVER ANNOTATED | Summary: Recent interactome evidence should not be elevated to a core protein-binding function. Reason: The core function is ATP-dependent chaperonin-mediated folding, and generic protein binding would obscure that more precise annotation. |
| GO:0006457 protein folding | IDA PMID:16762366 Quantitative actin folding reactions using yeast CCT purifie... | ACCEPT | Summary: Direct biochemical evidence supports CCT-mediated protein folding. Reason: Yeast CCT purified through an internal tag catalyzes actin folding in vitro; because CCT4 is a required complex subunit, the process annotation is retained. Supporting Evidence: PMID:16762366 Yeast CCT catalyses the folding of yeast ACT1p and human beta-actin with nearly identical rate constants and yields. |
| GO:0005832 chaperonin-containing T-complex | IPI PMID:15704212 Physiological effects of unassembled chaperonin Cct subunits... | ACCEPT | Summary: Protein-interaction evidence supports CCT4 as part of the CCT complex. Reason: The study describes the CCT complex as two rings containing the Cct1p-Cct8p subunits, consistent with CCT4 complex membership. |
| GO:0005832 chaperonin-containing T-complex | IDA PMID:16762366 Quantitative actin folding reactions using yeast CCT purifie... | ACCEPT | Summary: Direct analysis of purified yeast CCT supports CCT4 complex membership. Reason: The IDA evidence derives from purified yeast CCT; the cellular component term is accurate for the assembled complex. |
| GO:0051082 unfolded protein binding | IDA PMID:16762366 Quantitative actin folding reactions using yeast CCT purifie... | MODIFY | Summary: The IDA evidence supports chaperonin-mediated folding rather than generic unfolded-protein binding. Reason: Replace with GO:0140662 because CCT4's substrate engagement occurs as part of an ATP-dependent folding chaperonin. Proposed replacements: ATP-dependent protein folding chaperone |
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Experiment: Compare substrate folding outcomes after CCT4-specific conditional depletion against depletion of other CCT subunits to identify any subunit-biased substrate effects.
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