cct-1 encodes the alpha (TCP-1-alpha / CCT-alpha) subunit of the eukaryotic cytosolic chaperonin CCT (chaperonin-containing TCP-1), also known as TRiC. CCT/TRiC is an ATP-dependent, hetero-oligomeric double-ring chaperonin whose two stacked rings are each built from eight distinct but paralogous subunits (CCT1-CCT8 / alpha-theta); cct-1 is the alpha paralog. The assembled ~900 kDa complex, not any individual subunit, is the folding machine: it uses cycles of ATP binding and hydrolysis by its subunits to fold a subset of cytosolic proteins, most notably the obligate cytoskeletal substrates actin and tubulin, as well as WD40 beta-propeller proteins. The alpha subunit contributes an equatorial nucleotide-binding module and an apical substrate-binding surface and, unlike the low-ATPase subunits, retains a canonical ATP-binding/ATPase site. In C. elegans, cct-1 is a single-copy gene on chromosome II expressed constitutively throughout development, most prominently in neuronal and muscle tissues; the chaperonin acts in the cytoplasm and, together with the other seven CCT subunits, is essential for embryogenesis and for the in vivo biogenesis of actin and tubulin that underlies microtubule organization and microvillus formation.
Definition: A molecular function of a single subunit of a group II chaperonin (CCT/TRiC) that presents an apical-domain substrate-binding surface and contributes subunit-specific contacts to the ATP-dependent folding of client proteins by the assembled chaperonin, without itself folding a substrate independently of the complex.
Justification: Individual CCT subunits have no adequate GO molecular-function term and can only be annotated with the complex-level foldase activity or a generic catalytic term, obscuring subunit-specific substrate selectivity.
Parent term: molecular_function
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006457 protein folding | IBA GO_REF:0000033 | ACCEPT | Summary: cct-1 is the alpha subunit of the cytosolic chaperonin CCT/TRiC, which catalyzes ATP-dependent folding of actin, tubulin, and other cytosolic substrates. Protein folding is the core biological process for this subunit. Reason: The phylogenetic (IBA) inference is consistent with the conserved chaperonin family assignment (PANTHER PTHR11353; InterPro alpha-subunit signature IPR012715) and with direct evidence that the C. elegans CCT complex is required for actin and tubulin biogenesis in vivo. Protein folding is the correct core process annotation. 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 PMID:25143409 CCT depletion causes a reduction in the tubulin levels and disorganization of the microtubule network |
| GO:0005832 chaperonin-containing T-complex | IBA GO_REF:0000033 | ACCEPT | Summary: cct-1 is an integral subunit of the chaperonin-containing T-complex (CCT/TRiC), built from eight paralogous subunits per ring. Reason: Complex membership is the best-supported annotation for this gene. The phylogenetic inference agrees with direct biochemical purification of the C. elegans CCT complex, in which CCT-1 was identified as a subunit by antibody Western blot, and with yeast genetics showing the ring is built from eight distinct Cct subunits. Supporting Evidence: PMID:9434769 The chaperonin containing TCP-1 (CCT) from the free-living nematode Caenorhabditis elegans was purified and shown to contain at least seven subunit species ranging from 52-65 kDa PMID:15704212 stoichiometric array of eight different subunits, which are denoted Cct1p-Cct8p |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: Each CCT subunit binds ATP/ADP through the conserved equatorial nucleotide-binding site of the group II chaperonin fold; nucleotide binding drives the folding cycle. Reason: ATP binding is directly supported for the C. elegans protein: purified CCT-1/TCP-1 was shown to be a subunit of a high-molecular-mass complex that binds ATP. This is fully consistent with the InterPro chaperonin domains and the ATP-dependent mechanism of the complex. The alpha subunit retains a canonical nucleotide-binding site. Supporting Evidence: PMID:7758963 Ce TCP-1 is a 57-kDa protein subunit of a high-molecular-mass complex capable of binding ATP PMID:16762366 The eukaryotic cytosolic chaperonin CCT is an essential ATP-dependent protein folding machine |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: CCT/TRiC is a cytosolic chaperonin; cct-1 acts in the cytoplasm on cytosolic substrates. Reason: Cytoplasmic localization is consistent with the known biology of the cytosolic chaperonin and with the UniProt subcellular location. The more specific term cytosol (GO:0005829) would be preferable, but the broader cytoplasm annotation is not incorrect and is retained. Supporting Evidence: PMID:16762366 The eukaryotic cytosolic chaperonin CCT is an essential ATP-dependent protein folding machine |
| GO:0006457 protein folding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro domain-based annotation of protein folding, duplicating the IBA protein-folding annotation. Reason: Consistent electronic (InterPro) support for the core protein-folding process, in agreement with the IBA annotation and the conserved chaperonin mechanism. Supporting Evidence: PMID:16762366 Yeast CCT catalyses the folding of yeast ACT1p and human beta-actin with nearly identical rate constants and yields. |
| GO:0016887 ATP hydrolysis activity | IEA GO_REF:0000002 | ACCEPT | Summary: The CCT subunits are ATPases; ATP hydrolysis around the ring powers the substrate-folding cycle of the chaperonin. Reason: ATP hydrolysis is a conserved catalytic activity of the CCT/TRiC family, supported by the InterPro chaperonin domains and by the demonstration that the worm CCT-1 complex binds ATP. The alpha subunit retains a functional nucleotide-binding/ATPase site, so the term is appropriate. Supporting Evidence: PMID:16762366 The eukaryotic cytosolic chaperonin CCT is an essential ATP-dependent protein folding machine PMID:7758963 Ce TCP-1 is a 57-kDa protein subunit of a high-molecular-mass complex capable of binding ATP |
| GO:0140662 ATP-dependent protein folding chaperone | IEA GO_REF:0000002 | ACCEPT | Summary: ATP-dependent protein folding chaperone is the most informative molecular-function term for CCT/TRiC; cct-1 contributes to this activity as a subunit of the complex. Reason: This term precisely captures the activity of the CCT chaperonin. Strictly it is a complex-level activity to which the alpha subunit contributes rather than one it enables in isolation, but it is the best available molecular-function descriptor for this gene. 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 |
| GO:0005634 nucleus | IDA PMID:9434769 Subunit characterization of the Caenorhabditis elegans chape... | UNDECIDED | Summary: A nucleus located_in annotation attributed to the 1997 C. elegans CCT-1 paper. CCT/TRiC is canonically a cytoplasmic chaperonin, and the primary evidence for a nuclear location of CCT-1 cannot be verified from the available record. Reason: The cited paper is abstract-only in the cache (full text not accessible). Its abstract describes only a transcriptional promoter-reporter for cct-1 expression (tissue-level, neuronal and muscle), not protein immunolocalization; in C. elegans such reporters commonly carry a nuclear localization signal, which produces nuclear signal by construct design rather than reflecting endogenous protein location. CCT is a cytosolic chaperonin (UniProt subcellular location: cytoplasm). Because I cannot read the full text to establish the basis for a nucleus located_in call, and per curation guidance for annotations whose supporting publication is inaccessible, this is left UNDECIDED rather than removed; nuclear localization is at most a minor, non-core location for this cytosolic chaperonin subunit. Supporting Evidence: PMID:9434769 Expression of a reporter gene under the control of the C. elegans cct-1 promoter is found to be mainly restricted to neuronal and muscle tissues PMID:16762366 The eukaryotic cytosolic chaperonin CCT is an essential ATP-dependent protein folding machine |
| GO:0005832 chaperonin-containing T-complex | IDA PMID:9434769 Subunit characterization of the Caenorhabditis elegans chape... | ACCEPT | Summary: Direct experimental (IDA) demonstration that CCT-1 is a subunit of the purified C. elegans chaperonin-containing T-complex. Reason: This is the strongest annotation for the gene: the worm CCT complex was purified and CCT-1 identified as a subunit by anti-CCT-1 Western blot, with a subunit composition closely matching bovine CCT. Complex membership is experimentally established in the correct organism. Supporting Evidence: PMID:9434769 The chaperonin containing TCP-1 (CCT) from the free-living nematode Caenorhabditis elegans was purified and shown to contain at least seven subunit species ranging from 52-65 kDa PMID:7758963 Ce TCP-1 is a 57-kDa protein subunit of a high-molecular-mass complex capable of binding ATP |
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Download this section (compressed HTML)Q: Which native C. elegans clients depend specifically on the alpha (cct-1) subunit contacts, as opposed to the CCT/TRiC complex as a whole?
Q: Does CCT-1 have any genuine nuclear pool or function in C. elegans, or is the nucleus annotation an artifact of an NLS-tagged transcriptional reporter?
Experiment: Perform affinity purification/mass spectrometry of tagged cct-1 (or the assembled CCT/TRiC) from C. elegans to identify native clients and interactors.
Hypothesis: cct-1 engages a defined set of native C. elegans clients dominated by actin and tubulin but including additional cytosolic proteins.
Experiment: Determine the endogenous subcellular localization of CCT-1 by immunostaining or a tagged knock-in, comparing against an NLS-free transcriptional reporter, to test whether a genuine nuclear pool exists.
Hypothesis: Endogenous CCT-1 is predominantly cytoplasmic, and the nucleus annotation reflects reporter design rather than protein localization.
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: There is no GO molecular-function term that expresses "substrate-binding subunit of the CCT chaperonin". The alpha (CCT-1) subunit's own activity can therefore only be annotated as the complex-level foldase (GO:0140662) or as generic ATP binding/hydrolysis, leaving cct-1 molecular-function-dark at the subunit level, and its native C. elegans client repertoire (beyond actin and tubulin) is undefined.
OPEN ONTOLOGYBIOLOGY MF_DARK
What is known: It is firmly established that cct-1 is the alpha subunit of the eight-membered CCT/TRiC ring, that the assembled complex folds actin, tubulin, WD40 proteins and other cytosolic clients, that the worm CCT-1 protein is part of a high-molecular-mass ATP-binding complex, and that the eight subunits are functionally non-equivalent. What is missing is a term (and worm-specific data) that captures the alpha subunit's specific substrate-binding contribution.
Significance: CCT subunits are individually essential and non-redundant, so subunit-specific substrate engagement underlies the complex's client selectivity. Because no ontology term names a chaperonin substrate-binding subunit activity, the alpha subunit's characterized structural/regulatory role cannot be curated, and its native worm-specific clients remain unmapped.
What would resolve it: Affinity-proteomics of the C. elegans CCT/TRiC to define native clients that depend on the alpha subunit, plus crosslinking or cryo-EM mapping of alpha apical-domain contacts, would define the subunit contribution; a new GO molecular-function term for a chaperonin substrate-binding subunit activity would let the knowledge be expressed.
Provenance (the field's own admissions):
Proposed term (ontology gap):
Gap: Whether CCT-1 has any genuine, function-relevant nuclear localization in C. elegans is unresolved. A nucleus located_in annotation exists (from the 1997 CCT-1 paper) but its experimental basis cannot be verified, and the chaperonin is canonically cytoplasmic.
OPEN BIOLOGYCURATION RESIDUAL_SUBGAP
What is known: UniProt records the subcellular location of CCT-1 as cytoplasm, consistent with CCT being a cytosolic chaperonin. The cited primary paper's abstract describes only a transcriptional promoter-reporter (tissue-level expression), not protein immunolocalization, so it does not by itself establish an endogenous nuclear pool.
Significance: Some CCT/TRiC subunits have reported moonlighting roles outside the assembled chaperonin; distinguishing a genuine nuclear function of CCT-1 from a reporter-construct artifact would clarify whether the annotation should stand.
What would resolve it: Endogenous immunolocalization or a tagged CCT-1 knock-in in C. elegans, with and without an NLS-free transcriptional reporter as control, to test for a genuine nuclear pool and any nuclear function.
Provenance (the field's own admissions):
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