Human CC2D1A is Q6P1N0 (HGNC:30237). The normal seed contains 21 source assertions and two UniProt alternative products. The frozen ClinGen association is autosomal recessive complex neurodevelopmental disorder, classified Definitive. Disease validity establishes a gene–disease relationship, not a particular molecular activity.
ROOT reports prior normal Falcon and perplexity-lite research attempts failing because the offline environment lacked deep-research-client[cyberian] 0.2.7rc1. This is a prior-session attestation identifying native chunk f3ddc6; its complete native envelope was not retained and is not independently reconstructed here. The research was not rerun solely to recreate provenance. These are manual notes, and no provider research file was authored. Existing UniProt, GOA and publication caches remain unchanged. Four additional references were obtained through the normal publication fetcher and imported with exact source bytes.
PMID:12917378(https://pmc.ncbi.nlm.nih.gov/articles/PMC6740452/) originally characterized a mouse-brain 595-residue Freud-1 clone with rat Htr1a reporters and rat L6/RN46A cells. Recombinant-protein DNA-binding and reporter controls support rodent sequence recognition and repression. The human sequence comparison does not itself identify an experimentally tested current human product. Selected Methods, cloning results and captions were read from a primary-paper reproduction after official access failed; the normal cache is abstract-only. The curator's historical product mapping remains unresolved. This warrants a provenance question, not a claim of paralog misattribution. Htr1a and SV40 reporter experiments also do not positively establish the snRNA specificity of GO:1905381; this does not establish that CC2D1A cannot regulate snRNA.
Separate human evidence comes from PMID:27914010(https://pmc.ncbi.nlm.nih.gov/articles/PMC5479700/). Selected official Methods, Results and captions describe endogenous and tagged Freud-1 in HEK-293 and SK-N-SH cells, Brg1 interaction, promoter ChIP and depletion experiments. In HEK-293 cells, Freud-1 depletion reduces Brg1 recruitment, while substantial HTR1A derepression requires combined depletion. In SK-N-SH cells, recruitment is mutually dependent and either depletion increases HTR1A expression. These support human nuclear transcriptional repression with cell-dependent partners. ChIP alone does not prove direct DNA contact, and Brg1 ATPase or HDAC chemistry must not be assigned to CC2D1A. The antibody recognizes multiple products; no isoform-specific core function is inferred.
PAINT IBA assertions are ancestral-node judgments. Target self-inclusion in WITH/FROM is expected when its experimental annotations helped seed that judgment. Neither self-inclusion nor a short donor list establishes circularity. The nuclear transcriptional role is independently corroborated; historical human IDA provenance and snRNA specificity are separate questions.
PMID:18662999(https://pmc.ncbi.nlm.nih.gov/articles/PMC2546995/) tests full-length human Aki1 with human PDK1/Akt constructs. Selected official Methods, Results and captions were inspected. Sequential immunoprecipitation with mock/S6K controls supports a ternary complex; translated, immunopurified Aki1 binds recombinant partners. Depletion weakens PDK1–Akt association and Akt Thr308 phosphorylation, without a comparable effect on Ser473 or intrinsic PDK1 activity. PIP3 production and Akt membrane-recruitment controls distinguish coordination from upstream PI3K activation. EGF versus IGF-1/PDGF controls and concentration-dependent reversal limit generalization. The evidence supports noncatalytic signaling-adaptor activity, not kinase activity or universal growth-factor regulation. The separately accessed primary Results report that immunoprecipitated Aki1 accelerates recombinant PDK1-mediated Akt phosphorylation in the presence of PIP3. This is a biochemical kinase assay, not a CC2D1A depletion-rescue experiment or fully purified binary binding reconstitution. The normal PMID:18662999 cache remains abstract-only; its brief evidence anchor does not substitute for the separately accessed Methods and Results.
GO:0035591 signaling adaptor activity concerns bringing signaling molecules together to coordinate their functions and is a child of protein–macromolecule adaptor activity. This is a candidate core molecular function supported by the mechanism above. A new process annotation is not inferred merely from apoptosis, viability or disease phenotypes.
The original NF-kappaB source, PMID:12761501, is a human cDNA overexpression screen. Its cached abstract does not expose the CC2D1A-specific table. PMID:20529849(https://pmc.ncbi.nlm.nih.gov/articles/PMC2915672/) independently identifies the screened clone and tests human CC2D1A expression, reporter activity, IKK immunoprecipitate activity and target-gene expression. Selected Methods/Results include expression and pathway-knockdown controls. Ubc13 depletion/rescue tests dependence on Ubc13, not endogenous CC2D1A necessity. The evidence supports a context-dependent positive canonical-pathway effect. It does not establish CC2D1A kinase or ubiquitin-ligase activity, direct TRAF2/TAK1 recruitment, or a universal physiological stimulus. The normal PMID:20529849 cache contains XML-derived text. Its complete available nonduplicated Methods, Results, main figure captions and Discussion were read; no figure pixels or supplementary experiments were independently inspected. The authors did not resolve a physiological activating stimulus in the cell systems examined.
The normal UniProt record independently names CHMP4B/Q9H444 as an interaction partner. Three source IPI assertions describe this interaction at different levels of experimental coverage. Supported generic binding can remain non-core under the standing ClinGen project instruction; lack of a more specific justified term does not require removal. Neither generic binding nor association with an ESCRT component establishes a catalytic activity or makes every ESCRT process a core CC2D1A function.
Cytoplasmic and nuclear localization agree with human fractionation and the transcription/signaling experiments. The centrosomal electronic mapping cites PMID:20171170(https://doi.org/10.1016/j.bbrc.2010.02.103), whose abstract explicitly reports centrosomal localization. Selected publisher Methods confirm human HeLa/293T cells. This supports retaining the conservative location mapping independently of the PDK1–Akt mechanism. Its inhibitor/association results do not by themselves prove all site-specific recruitment mechanisms, and no new cohesion process is proposed here.
Membrane, cadherin-binding and extracellular-exosome source rows need tissue/assay-specific care. The E-cadherin study uses proximity proteomics; proximity alone does not demonstrate direct cadherin binding. Exosome proteome detection does not establish a secreted signaling role. Missing target tables are an access limitation, not evidence that the protein was absent from the experiment.
The normal products Q6P1N0-1 and Q6P1N0-2 are preserved. Historical construct lengths, apparent molecular weights and UniProt sequence cautions do not suffice to map a functional experiment to a current isoform without a sequence comparison.
The normal source assertions and alternative products are preserved, with one evidence-based signaling-adaptor molecular function added. Seven existing source assertions remain unresolved. Canonical application, standard CREATE history, final rendering and publication require normal candidate checks, distinct whole-science review and ROOT acceptance.
The 21 machine assertions and two products are preserved exactly. The review retains 10 ACCEPT, 4 KEEP_AS_NON_CORE and 7 UNDECIDED decisions and proposes one NEW molecular function, GO:0035591 signaling adaptor activity. No new process annotation is proposed. This activity is supported by actual partner coordination, not only a necessity phenotype; it is distinct from the three existing CHMP4B generic-binding assertions. No redundant broader adaptor term is added. The local GO-CAM index did not supply a target match during the bounded consultation; this is not a claim about live model absence.
Two mechanistic core summaries describe nuclear repression and cytosolic PDK1–Akt coordination. Accepted centrosomal localization is an independent experimentally supported property. It is intentionally not assigned to the Akt adaptor core because location alone does not establish that mechanism at the centrosome; no extra centrosomal process or molecular activity is manufactured to fill that gap.
The standing project binding instruction supports qualified non-core retention of corroborated generic interactions, superseding the general skill removal preference. The exact UniProt Q6P1N0–Q9H444 edge corroborates the three CHMP4B rows, but an interaction count is not a substitute for original target-level controls. The individual screen tables remain uninspected.
Reference correctness distinguishes actual independent primary/metadata checks from cached-only historical screens. Normal full-text flags are preserved as cache-access facts; selected external primary reading is separately identified. The four added normal caches contain three abstract-only records (PMID:20171170, PMID:27914010 and PMID:18662999) and one full XML record (PMID:20529849). PMID or PMCID availability does not imply full cached access. Selected external reading remains separately documented.
These are curation/access tasks and are kept outside the biological questions in the review. The adaptor mechanism does not depend on claiming a CC2D1A depletion-rescue experiment; the biochemical assay wording above comes from the separately accessed primary Results, while the normal abstract is quoted only for its reported complex formation.
The two PMID:12917378 IDA molecular-function rows now receive ACCEPT with curator deference and independent human corroboration from PMID:27914010. Retaining the supported human function does not turn the original mouse-brain 595-residue clone or rat reporters into a human-isoform experiment. The historical construct mapping remains a provenance task. The conserved DNA-binding interpretation combines the original specificity controls and the human promoter/repression evidence; ChIP alone is not a direct-contact assay. This supersedes the earlier action-level uncertainty for these two rows while preserving its factual caveat.
The snRNA-specific row receives MODIFY to GO:0000122 negative regulation of transcription by RNA polymerase II. The official source term and its parents distinguish snRNA regulation from the broader process. Selected Methods and Results in the primary-paper reproduction explicitly identify Htr1a promoter-luciferase and FRE/SV40 reporters with sequence-mutation controls. The positive assay identity, together with independent human HTR1A repression, supports generalization; neither an abstract omission nor rarity in the repository establishes absence of snRNA regulation. The existing nuclear core uses the same supported negative process specialization. No additional annotation or process is added.
Cadherin binding remains UNDECIDED after a fresh source check. The official definition requires binding, so proximity or colocalization is insufficient on its own. The newly opened PMC author manuscript was read through its complete main Results, Discussion and Methods. It describes BioID, GFP localization and predicted interaction networks. Its reported counts differ from the published cached abstract, which also includes adhesion-plaque proteomics. The final publisher body and target supplements were not obtained. Thus the target's full experimental basis cannot be reduced to the proximity assay alone. The requested automatic OVER action is declined on this concrete access/provenance boundary, not on a claim that proximity proves binding. Corpus vote counts are not biological evidence, and no universal requirement for purified binary binding is imposed. The source-specific annotation may be reassessed when its target record and final assay context are available.
This bounded response preserves all 21 machine assertions, the pre-existing authored adaptor NEW, two products, 18 references and all source caches. Final decisions are 12 ACCEPT, four KEEP_AS_NON_CORE, four UNDECIDED, one MODIFY and the unchanged one NEW. Four unresolved source assertions concern membrane, cadherin binding and two exosome datasets. Prior notes remain verbatim; this dated appendix supersedes their earlier action counts and source-access state. The optional centrosomal-mechanism and broader literature expansions are deferred; the existing independent centrosome location and explicit biological question remain intact. Normal validation, distinct focused peer and ROOT acceptance precede any canonical application or new standard EDIT history.