C2CD3 is the reviewed human protein Q4AC94 (HGNC:24564), a C2-domain-rich organizer of the distal centriole. The normal source import contained 30 seeded assertions from 31 raw GOA rows; one otherwise matching assertion differed only in assignment/date provenance. This review preserves every seeded source object, partner, qualifier and reference identity. The five UniProt products retain their exact names and identifiers: name 5/Q4AC94-5, 1/Q4AC94-1, 2/Q4AC94-2, 3/Q4AC94-3 and 4/Q4AC94-4. These numeric names are not substituted for the accession suffixes, and their sequence notes are unchanged. Functional assays are not automatically attributed to every individual product.
The normal Falcon attempt and configured perplexity-lite fallback failed DNS and produced no provider report. The account below is manual literature reading; no provider-named output was fabricated. Existing source caches, two additional normal reference imports, raw UniProt/GOA and quarantined family exports remain unchanged.
PMID:24997988(https://pubmed.ncbi.nlm.nih.gov/24997988/) connects C2CD3 loss to shortened centrioles and gain of C2CD3 to long centriolar extensions. The inspected Results and relevant Methods distinguish low-level GFP-C2cd3 in mouse IMCD3 cells, mutant mouse fibroblasts, endogenous human RPE co-immunoprecipitation, and human-cell overexpression with correlative microscopy. The endogenous C2CD3–OFD1 association and capture of cell-expressed C2CD3 by OFD1 fragments support the exact OFD1 partner. They do not establish purified binary affinity. OFD1 antagonism is consistent with regulation of length; it does not make C2CD3 a tubulin polymerase or protein kinase.
The centriolar-satellite pool is retained as non-core. The mouse tagged-protein PCM1 colocalization is explicitly distinguished from a human localization image. Satellite localization does not imply that C2CD3 is needed for satellite integrity: the inspected perturbations did not establish that requirement. C2-domain calcium or lipid binding remains a mechanistic question, not an activity assigned from the domain name.
PMID:24469809(https://pubmed.ncbi.nlm.nih.gov/24469809/) independently summarizes C2cd3-dependent distal-appendage assembly, ciliogenic protein recruitment and ciliary-vesicle docking. Its normal cache is abstract-only despite an available PMCID. The complete abstract supports the stated mammalian mechanism; exact full-text constructs, Methods and images were not inspected. Recruitment of TTBK2, IFT factors and vesicle-associated proteins does not transfer their catalytic or transport activities to C2CD3.
PMID:41364719(https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003519) supplies newer primary evidence beyond a disease or knockout phenotype. Human U2OS expansion-microscopy epitope mapping places C2CD3 in a radial distal-centriolar organization, with different regions positioned toward the lumen and microtubule wall. Depletion disrupts the luminal protein network, distal-cap components and recruitment of the MNR/CEP90/OFD1 machinery. Initial procentriole formation persists; the result is not a universal absence of centriole duplication.
Mouse photoreceptor and tracheal cryo-electron tomography provides complementary architectural context. It does not identify each ring node or hook as a particular C2CD3 domain. The Discussion explicitly leaves the molecular composition of these structures open, including possible NA14 contributions. The MNR experiment is a cellular displacement/recruitment assay using expressed fluorescent fusions, not purified binary binding. C2CD3 alone did not decorate microtubules under those conditions; the paper does not claim this disproves every earlier construct-dependent observation.
Complete main Results and Discussion and relevant Methods were read from the primary publisher, and the matching normal XML cache supplies the exact quotation anchors. Original images, raw data and supplementary files were not independently analyzed. One C2CD3 siRNA was used in the inspected depletion experiments; centriolar fluorescence verified depletion, whereas a western-blot depletion measurement was unavailable because the control protein signal was not detectable. These limits constrain molecular detail without erasing the observed architectural phenotype.
One new molecular-function assertion is proposed: GO:0005200 structural constituent of cytoskeleton. Its official definition concerns contribution to the structural integrity of a cytoskeletal structure; it is a child of GO:0005198 structural molecule activity, part_of cytoskeleton organization and occurs_in cytoskeleton. The distal centriole is the mapped cytoskeletal structure, so this is more precise than the generic parent without requiring direct tubulin affinity. The basis here is the combination of physical C2CD3 occupancy within the distal architecture and disruption of that architecture after its loss. This is more specific evidence of structural work than ciliogenesis necessity alone. It does not assert an atomically identified C2CD3 ring, a finer adapter mechanism, direct microtubule affinity or calcium-dependent lipid binding.
The same function anchors one core unit covering the existing centriole-elongation, centrosomal protein-localization and non-motile-cilium-assembly assertions. GO:0071539 includes maintenance at the centrosome, so this role does not require a transport motor. GO:0061511 places elongation within centriole replication; the annotation does not imply that C2CD3 initiates every step of procentriole formation. No new process term is proposed, and no additional parent/child structural-function rows or redundant core units are added. No local C2CD3 GO-CAM index entry was found; this is a local observation, not a claim of global model absence. The new assertion is not inferred from other proteins having an annotation.
The proposal assesses all 30 unchanged source assertions: 17 ACCEPT and 13 KEEP_AS_NON_CORE, with one additional NEW molecular-function assertion and one core unit. Five products and all 16 original reference identities are preserved; two normal primary papers and the inspected UniProt record bring the reference list to 19. No source uncertainty is concealed: accepted claim-level biology may be independently established even where the original image or individual supplementary record was not inspected.
Seven short quotation instances are exact cache substrings. Aggregate quoted words, counting repeats, are 15 for PMID:24997988, eight for PMID:23769972 and ten for PMID:41364719. Reference-only supports retain the other evidence without copying long passages. Full normal candidate validation with term, reference and GOA checks enabled passed after the final term-specificity change (actualcb161f). The only two advisories concern the supported generic-binding policy dispositions. DRAFT records those advisories; all source assertions have been assessed. Independent whole-science review precedes any canonical application.
The exact candidate was applied after independent ROOT whole-science approval. Full normal candidate and canonical validation, status reporting, targeted rendering and standard codex/gpt-6 CREATE history validation passed. DRAFT retains two supported generic-binding policy advisories. All 30 source assertions and five product records are unchanged; the single added cytoskeletal structural function remains bounded by the stated primary-evidence limits. Existing sources, normal publication caches and earlier history were preserved. No remote publication is claimed by this local application record.