Gene: cct-8 / ORF Y55F3AR.3 / WormBase WBGene00021934
UniProt: Q9N358 (TCPQ_CAEEL), "T-complex protein 1 subunit theta" (CCT-theta / TCP-1-theta), 548 aa.
NCBI taxon: 6239.
This is a research journal. Provenance is recorded inline as [PMID:xxxx "verbatim quote"]
or [file:... "quote"]. KNOWN vs NOT-KNOWN are separated at the end.
cct-8 encodes the theta (θ) subunit of the eukaryotic cytosolic chaperonin CCT
(chaperonin-containing TCP-1), also called TRiC (TCP-1 ring complex). UniProt:
"Belongs to the TCP-1 chaperonin family." InterPro domains identify it specifically as the
theta paralog: IPR012721 Chap_CCT_theta, plus the pan-family IPR017998 Chaperone_TCP-1,
IPR002194 Chaperonin_TCP-1_CS, and the Cpn60/GroEL/TCP-1 fold (IPR002423). PANTHER family
PTHR11353 (CHAPERONIN). NCBIfam TIGR02346 chap_CCT_theta and CDD cd03341 TCP1_theta are
theta-subunit-specific, so the subunit assignment is unambiguous.
CCT/TRiC is a ~1 MDa double-ring machine; each ring is a hetero-octamer of eight distinct but
paralogous subunits (CCT1–CCT8 / alpha–theta), arranged in a fixed order. In C. elegans the
eight paralogs are cct-1..cct-8. The assembled complex, not any single subunit, is the folding
machine. PMID:15704212
CCT/TRiC is an ATP-dependent foldase. Each subunit is a member of the group II chaperonin
(GroEL/Cpn60-like) fold with an equatorial ATP-binding/hydrolysis domain, an intermediate
domain, and a substrate-binding apical domain. ATP binding and hydrolysis by the subunits drives
the folding cycle. PMID:16762366
The complex acts as a genuine catalyst of folding. PMID:16762366
The eight subunits are functionally non-equivalent — they have distinct substrate contacts and
distinct roles despite the shared fold. PMID:15704212 The conserved equatorial ATP-binding motif is required for the subunit-specific
activities. PMID:15704212
The GOA molecular-function annotations (ATP binding GO:0005524, ATP hydrolysis GO:0016887,
ATP-dependent protein folding chaperone GO:0140662) are all consistent with this conserved
mechanism and with the InterPro/PANTHER family assignment.
UniProt curates a worm-specific in-vivo role from a genome-wide RNAi screen: cct-8 is required
for correct localization of the germ-granule (P-granule) protein PGL-1.
[file:worm/cct-8/cct-8-uniprot.txt "Required for correct subcellular localization of pgl-1."]
Disruption phenotype: [file:worm/cct-8/cct-8-uniprot.txt "Low and diffuse subcellular
localization of pgl-1 in embryos rather than confined to granules in somatic cells."] The source
is the Updike & Strome genome-wide RNAi screen for P-granule genes; cct-8 was among 173 hits.
PMID:19805813 NOTE: the cached
PMID:19805813 record is abstract-only (full_text_available: false); the abstract does not name
cct-8 or pgl-1, so the specific pgl-1 phenotype is taken from the UniProt curation (which read
the full text), not quoted from the abstract.
The pgl-1 phenotype is most parsimoniously explained by cct-8's canonical chaperonin role: PGL-1
condensation into P granules likely depends on CCT/TRiC-assisted folding of PGL-1 itself or of a
partner. Whether PGL-1 (or actin, which scaffolds germ granules) is the direct CCT substrate has
not been established.
Protein-level evidence: the mature protein was directly sequenced by Edman/MS (UniProt
"Direct protein sequencing" keyword; PE:1 evidence at protein level), confirming expression.
Subcellular location: cytoplasm (UniProt SUBCELLULAR LOCATION "Cytoplasm"; by similarity to
human CCT-theta P50990). Consistent with the cytosolic role of CCT/TRiC. GOA has GO:0005737
cytoplasm (IEA). The more precise term would be cytosol (GO:0005829), but cytoplasm is not wrong.
There is no unfolded protein binding (GO:0051082) annotation in the C. elegans GOA (unlike the
yeast/human orthologs), so no MODIFY is needed for that term here.
Deep research (cct-8-deep-research-falcon.md, Edison, 32 citations) surfaced two key
C. elegans functional papers and subunit-level structural detail:
Noormohammadi et al. 2016, Nat Commun PMID:27892468: cct-8/CCT8 is rate-limiting for
TRiC/CCT assembly and its somatic increase boosts proteostasis and longevity.
PMID:27892468; PMID:27892468; PMID:27892468; PMID:27892468. cct-8 is required for lifespan extension in daf-2, eat-2, and glp-1
long-lived backgrounds (from the paper's body / deep-research synthesis), and its protective
effect can be partly HSF-1-independent.
Calculli et al. 2021, Sci Adv PMID:34172445: cct-8 acts cell-autonomously in neurons to
prevent polyglutamine aggregation. PMID:34172445.
Subunit-specific properties (from CCT/TRiC structural reviews via deep research): the theta
subunit is a LOW-ATPase subunit (the "CCT6 hemisphere": CCT1/3/6/8), retains bound ADP, and
contributes to substrate binding, allostery, and complex assembly rather than bulk ATP
consumption. [file:worm/cct-8/cct-8-deep-research-falcon.md "CCT-8 occupies a defined position
in the low-ATPase hemisphere and plays a specialized role in substrate binding, allosteric
regulation, and complex assembly"]; [file:worm/cct-8/cct-8-deep-research-falcon.md "Both actin
and tubulin make specific contacts with CCT-8-containing apical domains during folding"].
Impact on the review:
- Core-function molecular_function set to GO:0005524 (ATP binding) rather than ATP hydrolysis,
because theta is a low-ATPase subunit; contributes_to_molecular_function = GO:0140662.
- GO:0016887 (ATP hydrolysis) existing annotation kept as ACCEPT (family-level InterPro; theta
retains the catalytic P-loop/aspartate) with the low-ATPase nuance recorded.
- Knowledge gap #1 reframed: theta substrate contacts ARE structurally characterized, so the gap
is now primarily the ONTOLOGY gap (no MF term for a chaperonin substrate-binding subunit) plus
the residual BIOLOGY gap of the native worm client set.