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
|
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):
UniProt: P41988 (TCPA_CAEEL). Gene: cct-1 (synonym tcp-1; ORF T05C12.7);
WormBase WBGene00000377. Chromosome II. 549 aa, ~58.8 kDa.
cct-1 encodes the alpha (TCP-1-alpha / CCT-alpha) subunit of the eukaryotic
cytosolic chaperonin CCT (chaperonin-containing TCP-1), also called TRiC. CCT/TRiC
is an ATP-dependent, hetero-oligomeric double-ring chaperonin; each ring is built
from eight distinct but paralogous subunits (CCT1-CCT8 / alpha-theta). cct-1 is the
alpha paralog. The assembled complex — not any single subunit — is the folding
machine; it folds actin, tubulin, and a subset of other cytosolic proteins.
ATP-agarose) that the C. elegans TCP-1/CCT-1 protein is a subunit of a large
ATP-binding complex. Also: single-copy gene on chromosome II, transcript
constant through development PMID:7758963, and unlike Hsp60 it is not heat-inducible ("tcp-1 is not upregulated
at elevated temperatures, but instead appears to be down-regulated").
The C. elegans CCT complex contains CCT-1 as a subunit (experimental IDA).
PMID:9434769 with Western blots using anti-CCT-1 and
anti-CCT-5 antibodies; the worm CCT subunit composition closely matches bovine
CCT. This paper is the basis for the WormBase IDA annotations
(GO:0005832 chaperonin-containing T-complex; GO:0005634 nucleus).
CCT/TRiC is an ATP-dependent foldase for actin and tubulin (conserved
mechanism).
PMID:16762366;
purified yeast CCT catalyses actin folding PMID:16762366.
The eight subunits are non-equivalent and form a stoichiometric ring.
PMID:15704212 and "These results provide evidence for
functional differences among Cct subunits and for physiological properties of
unassembled subunits."
In C. elegans the CCT subunits (cct-1..cct-8) are ubiquitously expressed,
essential for embryogenesis, and required in vivo for actin/tubulin biogenesis.
PMID:25143409;
PMID:25143409; loss of CCT causes actin/tubulin
biogenesis failure and PMID:25143409. IFB-2 intermediate filament is unaffected —
substrate specificity for actin/tubulin.
Subcellular localization: predominantly cytoplasmic.
PMID:25143409. Consistent with
UniProt SUBCELLULAR LOCATION: Cytoplasm.
cct-1 promoter drives expression in neuronal and muscle tissues (transcriptional
reporter), consistent with actin/tubulin-rich tissues PMID:9434769.
Nucleus localization (GO:0005634, IDA, PMID:9434769): The 1997 paper's
abstract (full text not accessible; full_text_available: false) describes only a
transcriptional promoter-reporter for expression (tissue level: neuron/muscle),
not protein subcellular immunolocalization. C. elegans transcriptional reporters
commonly carry an NLS, giving nuclear signal by design. Independent immunostaining
of the assembled worm CCT complex shows it is predominantly cytoplasmic ("less in
the nucleus", PMID:25143409). I cannot verify from the cached abstract what
evidence underlies a nucleus located_in call for CCT-1. Per repo guidance
(cannot access the relevant publication's full text), this annotation is marked
UNDECIDED rather than removed; it is at most a minor / non-core localization.
Subunit-specific (alpha) native client repertoire in C. elegans is undefined;
there is no GO molecular-function term expressing "substrate-binding CCT subunit",
so the alpha subunit's own MF can only be annotated as the complex-level foldase
(GO:0140662) or generic ATP binding/hydrolysis (ontology-level gap; shared across
the CCT family, cf. cct-8 review).
Automated deep research was unavailable for this gene: the falcon provider
(just deep-research-falcon worm cct-1 --fallback perplexity-lite) hung/timed out on
repeated attempts and produced no output, so there is intentionally no
cct-1-deep-research-falcon.md file (a fabricated one must never be created). This
review is instead grounded in the UniProt record (P41988 / TCPA_CAEEL), the QuickGO GOA
export, and the cached primary literature listed above (PMID:7758963, PMID:9434769,
PMID:7576182 — C. elegans-specific; PMID:16762366, PMID:15704212 — yeast mechanism;
PMID:25143409 — C. elegans in vivo). Every supporting_text in the review is a verbatim
substring of one of these cached publications.
Following the cct-8 review pattern: core_functions models the subunit as
molecular_function = ATP binding (GO:0005524, the concrete per-subunit MF),
contributes_to_molecular_function = ATP-dependent protein folding chaperone
(GO:0140662, the complex-level activity), directly_involved_in = protein folding
(GO:0006457), in_complex = chaperonin-containing T-complex (GO:0005832),
locations = cytoplasm (GO:0005737). Unlike theta (a low-ATPase subunit), alpha
retains a canonical nucleotide-binding/ATPase site.
id: P41988
gene_symbol: cct-1
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:6239
label: Caenorhabditis elegans
description: >-
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.
existing_annotations:
- term:
id: GO:0006457
label: protein folding
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
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.
action: ACCEPT
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.
supported_by:
- reference_id: PMID:16762366
supporting_text: >-
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
- reference_id: PMID:25143409
supporting_text: >-
CCT depletion causes a reduction in the tubulin levels and disorganization
of the microtubule network
- term:
id: GO:0005832
label: chaperonin-containing T-complex
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: part_of
review:
summary: >-
cct-1 is an integral subunit of the chaperonin-containing T-complex
(CCT/TRiC), built from eight paralogous subunits per ring.
action: ACCEPT
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.
supported_by:
- reference_id: PMID:9434769
supporting_text: >-
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
- reference_id: PMID:15704212
supporting_text: >-
stoichiometric array of eight different subunits, which are denoted
Cct1p-Cct8p
- term:
id: GO:0005524
label: ATP binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
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.
action: ACCEPT
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.
supported_by:
- reference_id: PMID:7758963
supporting_text: >-
Ce TCP-1 is a 57-kDa protein subunit of a high-molecular-mass complex
capable of binding ATP
- reference_id: PMID:16762366
supporting_text: >-
The eukaryotic cytosolic chaperonin CCT is an essential ATP-dependent
protein folding machine
- term:
id: GO:0005737
label: cytoplasm
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: >-
CCT/TRiC is a cytosolic chaperonin; cct-1 acts in the cytoplasm on cytosolic
substrates.
action: ACCEPT
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.
supported_by:
- reference_id: PMID:16762366
supporting_text: >-
The eukaryotic cytosolic chaperonin CCT is an essential ATP-dependent
protein folding machine
- term:
id: GO:0006457
label: protein folding
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: involved_in
review:
summary: >-
InterPro domain-based annotation of protein folding, duplicating the IBA
protein-folding annotation.
action: ACCEPT
reason: >-
Consistent electronic (InterPro) support for the core protein-folding
process, in agreement with the IBA annotation and the conserved chaperonin
mechanism.
supported_by:
- reference_id: PMID:16762366
supporting_text: >-
Yeast CCT catalyses the folding of yeast ACT1p and human beta-actin with
nearly identical rate constants and yields.
- term:
id: GO:0016887
label: ATP hydrolysis activity
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: >-
The CCT subunits are ATPases; ATP hydrolysis around the ring powers the
substrate-folding cycle of the chaperonin.
action: ACCEPT
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.
supported_by:
- reference_id: PMID:16762366
supporting_text: >-
The eukaryotic cytosolic chaperonin CCT is an essential ATP-dependent
protein folding machine
- reference_id: PMID:7758963
supporting_text: >-
Ce TCP-1 is a 57-kDa protein subunit of a high-molecular-mass complex
capable of binding ATP
- term:
id: GO:0140662
label: ATP-dependent protein folding chaperone
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
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.
action: ACCEPT
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.
supported_by:
- reference_id: PMID:16762366
supporting_text: >-
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
- term:
id: GO:0005634
label: nucleus
evidence_type: IDA
original_reference_id: PMID:9434769
qualifier: located_in
review:
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.
action: UNDECIDED
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.
supported_by:
- reference_id: PMID:9434769
supporting_text: >-
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
- reference_id: PMID:16762366
supporting_text: >-
The eukaryotic cytosolic chaperonin CCT is an essential ATP-dependent
protein folding machine
- term:
id: GO:0005832
label: chaperonin-containing T-complex
evidence_type: IDA
original_reference_id: PMID:9434769
qualifier: part_of
review:
summary: >-
Direct experimental (IDA) demonstration that CCT-1 is a subunit of the
purified C. elegans chaperonin-containing T-complex.
action: ACCEPT
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.
supported_by:
- reference_id: PMID:9434769
supporting_text: >-
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
- reference_id: PMID:7758963
supporting_text: >-
Ce TCP-1 is a 57-kDa protein subunit of a high-molecular-mass complex
capable of binding ATP
core_functions:
- description: >-
cct-1 is the alpha subunit of the cytosolic chaperonin CCT/TRiC. As part of the
hetero-oligomeric double-ring complex it binds nucleotide through its equatorial
domain and presents an apical substrate-binding surface, contributing to the
ATP-dependent folding of actin, tubulin, and other cytosolic clients. The
foldase activity is a property of the assembled complex, to which the alpha
subunit contributes; unlike the low-ATPase subunits, alpha retains a canonical
nucleotide-binding/ATPase site.
molecular_function:
id: GO:0005524
label: ATP binding
contributes_to_molecular_function:
id: GO:0140662
label: ATP-dependent protein folding chaperone
directly_involved_in:
- id: GO:0006457
label: protein folding
locations:
- id: GO:0005737
label: cytoplasm
in_complex:
id: GO:0005832
label: chaperonin-containing T-complex
supported_by:
- reference_id: PMID:7758963
supporting_text: >-
Ce TCP-1 is a 57-kDa protein subunit of a high-molecular-mass complex
capable of binding ATP
- reference_id: PMID:16762366
supporting_text: >-
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
- reference_id: PMID:25143409
supporting_text: >-
is essential for proper formation of microvilli in intestinal cells
knowledge_gaps:
- gap_statement: >-
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.
boundary: >-
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.
gap_kind:
- ONTOLOGY
- BIOLOGY
dark_aspect: MF_DARK
status: OPEN
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.
resolution: >-
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:
- reference_id: PMID:15704212
supporting_text: >-
These results provide evidence for functional differences among Cct subunits
and for physiological properties of unassembled subunits
- reference_id: PMID:7758963
supporting_text: >-
Ce TCP-1 is a 57-kDa protein subunit of a high-molecular-mass complex
capable of binding ATP
proposed_terms:
- proposed_name: chaperonin substrate-binding subunit activity
proposed_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 such as cct-1/alpha have no adequate GO
molecular-function term: they can currently be annotated only with the
complex-level foldase activity (GO:0140662) or a generic catalytic term,
neither of which captures the subunit-specific substrate-binding
contribution that distinguishes the eight paralogous subunits.
proposed_parent:
id: GO:0003674
label: molecular_function
- gap_statement: >-
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.
boundary: >-
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.
gap_kind:
- BIOLOGY
- CURATION
dark_aspect: RESIDUAL_SUBGAP
status: OPEN
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.
resolution: >-
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:
- reference_id: PMID:9434769
supporting_text: >-
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
- reference_id: PMID:16762366
supporting_text: >-
The eukaryotic cytosolic chaperonin CCT is an essential ATP-dependent
protein folding machine
proposed_new_terms:
- proposed_name: chaperonin substrate-binding subunit activity
proposed_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.
proposed_parent:
id: GO:0003674
label: molecular_function
suggested_questions:
- question: >-
Which native C. elegans clients depend specifically on the alpha (cct-1) subunit
contacts, as opposed to the CCT/TRiC complex as a whole?
- question: >-
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?
suggested_experiments:
- description: >-
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.
- description: >-
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.
references:
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000044
title: >-
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
vocabulary mapping, accompanied by conservative changes to GO terms applied by
UniProt
findings: []
- id: PMID:9434769
title: >-
Subunit characterization of the Caenorhabditis elegans chaperonin containing
TCP-1 and expression pattern of the gene encoding CCT-1.
findings:
- statement: >-
The C. elegans CCT complex was purified and shown to contain CCT-1 among at
least seven subunit species, with a composition like bovine CCT.
supporting_text: >-
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
- statement: >-
A cct-1 promoter reporter is expressed mainly in neuronal and muscle
tissues, consistent with a role in actin and tubulin folding.
supporting_text: >-
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
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: >-
PubMed-verified C. elegans-specific primary paper; basis for the WormBase IDA
complex-membership annotation. Abstract-only in cache, so the nucleus IDA it
also underlies cannot be independently verified (see the nucleus annotation
review).
- id: PMID:7758963
title: Molecular analysis of Caenorhabditis elegans tcp-1, a gene encoding a chaperonin protein.
findings:
- statement: >-
The C. elegans TCP-1/CCT-1 protein is a 57-kDa subunit of a
high-molecular-mass ATP-binding complex; tcp-1 is single-copy on chromosome
II and constitutively expressed.
supporting_text: >-
Ce TCP-1 is a 57-kDa protein subunit of a high-molecular-mass complex
capable of binding ATP
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: >-
PubMed-verified. Direct biochemical evidence in C. elegans that CCT-1 is a
subunit of a large ATP-binding complex; anchors the ATP binding and
complex-membership annotations.
- id: PMID:7576182
title: Characterization of four new tcp-1-related cct genes from the nematode Caenorhabditis elegans.
findings:
- statement: >-
cct-1 (tcp-1) belongs to a C. elegans CCT multigene family whose members are
expressed in all life stages.
supporting_text: >-
The five C. elegans cct genes are expressed in all life stages
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: >-
PubMed-verified. Establishes the C. elegans cct gene family and constitutive
expression; background/context for cct-1.
- id: PMID:16762366
title: >-
Quantitative actin folding reactions using yeast CCT purified via an internal tag
in the CCT3/gamma subunit.
findings:
- statement: CCT/TRiC is an ATP-dependent folding machine for actin and tubulin.
supporting_text: >-
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
- statement: Purified yeast CCT catalyzes actin folding.
supporting_text: >-
Yeast CCT catalyses the folding of yeast ACT1p and human beta-actin with
nearly identical rate constants and yields.
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: >-
PubMed-verified. A yeast-based study establishing the conserved ATP-dependent
foldase mechanism and actin/tubulin/WD40 substrate scope of CCT/TRiC that
applies to the C. elegans alpha subunit. Used for mechanism, not a
worm-specific claim.
- id: PMID:15704212
title: Physiological effects of unassembled chaperonin Cct subunits in the yeast Saccharomyces cerevisiae.
findings:
- statement: CCT is built from eight distinct subunits Cct1p-Cct8p per ring that are functionally non-equivalent.
supporting_text: >-
stoichiometric array of eight different subunits, which are denoted
Cct1p-Cct8p
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: >-
PubMed-verified. Yeast genetics showing the eight Cct subunits are distinct and
non-redundant; supports the subunit-level knowledge gap framing.
- id: PMID:25143409
title: >-
Caenorhabditis elegans chaperonin CCT/TRiC is required for actin and tubulin
biogenesis and microvillus formation in intestinal epithelial cells.
findings:
- statement: >-
C. elegans CCT is required in vivo for microvillus formation in intestinal
cells.
supporting_text: >-
is essential for proper formation of microvilli in intestinal cells
- statement: CCT depletion reduces tubulin levels and disorganizes the microtubule network.
supporting_text: >-
CCT depletion causes a reduction in the tubulin levels and disorganization of
the microtubule network
- statement: CCT acts specifically on actin and tubulin among the filamentous cytoskeletons.
supporting_text: >-
suggesting substrate specificity of CCT in the folding of filamentous
cytoskeletons in vivo
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: >-
PubMed-verified C. elegans primary paper. Direct in vivo evidence for CCT
function in actin/tubulin biogenesis; strongly informs the protein-folding
annotations. (Validator sees abstract only; quotes drawn from the abstract.)