Human FANCC is a noncatalytic constituent of the nuclear Fanconi anemia repair complex. The source evidence supports physical complex participation, interstrand cross-link repair, and contextual nonnuclear roles. It does not establish every molecular activity performed by the complex as a FANCC activity. This guide brings together target-specific original experiments, inherited phylogenetic assertions, localization and reaction models, and their distinct limits.
The final core retains repair-complex assembly and ICL repair, with nucleoplasm and FA nuclear-complex membership. Human nuclear immunoprecipitation and recombinant human CEF-module work are positive physical evidence. The latter uses Xenopus ID2 and does not isolate FANCC's particular contribution to ubiquitin transfer. Current GO:0030674 explicitly directs complex-scaffold roles to GO:0140378; that distinction does not itself prove that FANCC performs the more specific hold-together step. The inherited adaptor source remains UNDECIDED, and the core omits both adaptor MF and contributes-to ligase rather than silently retaining the old stronger mechanism. This does not deny a structural role for FANCC.
GO:0036297 ICL repair and GO:0065003 complex assembly are not ancestors of one another under the saved current is_a/part_of closure. Their inclusion represents the supported repair role and physical assembly contribution, not two independent catalytic activities. GO:0043240 is a protein complex and is represented separately from nucleoplasm. The exact C-specific chromatin IDA remains unresolved; nuclear-complex isolation alone does not resolve chromatin fractionation.
The inherited core quotations are preserved literally. The FANCE-binding and FAA/FAC-association statements support partner association; the E3-ligase quotation describes the complex. They are not newly interpreted as isolated FANCC catalysis or a directly demonstrated FANCC bridge to ID2. The same-role comparator checks and fixed-main GO-CAM index from the accepted direct review remain bounded negative searches, not proof of a universal convention or a missing annotation.
The reviewed target is human FANCC/Q00597, 558 residues. The source has no alternative-products field. Three NCBI NP records, 37 XP predictions and 35 Ensembl models are distinct locus annotations, not an automatic natural-product inventory. The HPA antigen and modeled full-length Reactome entities are not evidence that every such record has the same localization or activity.
The actual PANTHER v19 PTHR16798 tree and MSA place the exact 558-residue human target PTN002497666 below PTN000423656. The saved IBDs assert NER, cellular oxidative-stress response and FA nuclear-complex membership; there is no relevant target-path NOT. PANTHER family and GO_REF:0000033 describe the public framework. The current UniProt/source version is kept distinct from the saved v19 phylogeny. Human self-WITH for complex membership is legitimate experimental grounding. Neither donor count nor self-WITH is a weakness.
Mouse donor P50652 is explicitly linked to MGI:95480. Current experimental GOA traces NER to PMID:8704201 (IMP) and oxidative stress to PMID:24483844 (IGI); their biological scope was checked rather than inferred from the term labels.
PMID:8704201(https://pubmed.ncbi.nlm.nih.gov/8704201/) was recovered as the complete original from the OHSU Fanconi-anemia publication collection. Main Methods/Results describe exon-9 disruption in mice, primary embryonic fibroblast chromosome radials after MMC/DEB and splenocyte G2 accumulation after MMC. Printed page 52 Table 1 and Figure 3 were viewed. These positive lesion-response assays are kept distinct from a measured nucleotide-excision reaction. The paper also reports fertility and cytokine contexts; these are not new process proposals.
GO:0006289 specifies removal of a lesion-containing oligonucleotide and gap filling. GO:0036297 describes restoration of interstrand-crosslinked DNA. The proposed MODIFY is a lateral correction to the lesion/role actually supported, not an ontology-descendant refinement or a claim of universal NER loss. The original GOA evidence, term, IBD and inherited quotation are unchanged. Independent human FANCC-containing assembly and complementation evidence supports the positive ICL replacement.
PMID:20347428(https://pubmed.ncbi.nlm.nih.gov/20347428/) Results and Figure 1 explicitly identify FANCC in human HeLa nuclear FANCM immunoprecipitates. Quantitative depletion limits equating total FANCM/MHF pools with the FA core. PMID:22266823(https://pmc.ncbi.nlm.nih.gov/articles/PMC3280818/) Figure 2/Results recover FANCC with FAAP20; FANCA–FAAP20 and FAAP20–Rev1/ubiquitin roles remain distinct. The database review inspected their text; the direct-source review below records its separate figure and supplement scope.
PMID:27986592(https://pubmed.ncbi.nlm.nih.gov/27986592/) selected Results, Discussion and Methods resolve human BL100/CEF assemblies and Xenopus ID2. FANCC tagging and whole-CEF reconstitution support assembly membership; they do not isolate a C-specific catalytic or adaptor activity. FANCE contacts and FANCB/FAAP100 architecture are separately attributed. PMID:19965384(https://pubmed.ncbi.nlm.nih.gov/19965384/) executes Xenopus ID2 depletion/add-back and ICL repair, not a human FANCC incision assay. Its old quotation remains contextually interpreted and exact. No fixed whole-complex stoichiometry or isolated FANCC ligase activity is asserted.
PMID:24483844(https://pmc.ncbi.nlm.nih.gov/articles/PMC4186827/) includes both Fancc/Foxo3a and Fancd2/Foxo3a double-mutant mice. The selected complete main Results/Discussion and operative Methods were read. Fancc genetic/developmental observations are positive, but detailed ROS, neurosphere and antioxidant-rescue experiments in the main use Fancd2. Fancc Supplementary Figure S1 was not recovered after bounded failed routes and is not claimed read. There was no new figure-pixel inspection of this paper.
Independent PMID:27133164(https://pmc.ncbi.nlm.nih.gov/articles/PMC4881391/) directly supports a human FANCC stress-response contribution. Selected main Results/Figures 3–6 and Methods, actual Figure 5 pixels and the supplemental Methods were read. Patient R548X fibroblasts were SV40-immortalized and transduced with WT FANCC or vector. CCCP-associated mitochondrial ROS was assayed with MitoSOX flow cytometry; WT rescue reduced the signal. HeLa/Parkin and mouse macrophage experiments remain separately identified. The c.67delG experimental allele separates measured mitophagy from MMC/FANCD2 responses and is not treated as a newly established normal splice product. This supports contextual retention of the existing oxidative-stress term; no antioxidant-enzyme activity or new mitophagy process is inferred.
Inherited PMID:11520787(https://pubmed.ncbi.nlm.nih.gov/11520787/) STAT1 and PMID:9787138(https://pubmed.ncbi.nlm.nih.gov/9787138/) reductase quotations remain exact. Only their complete cached abstracts/identities were read here. They are context, not direct mitochondrial-ROS experiments.
HPA FANCC supports nucleoplasm with HPA030771. The 120-aa antigen exactly matches Q00597 residues 104–223. Selected A-431 and U-251MG merged images were viewed; the A-431 nuclear green signal is clearer, while U-251MG is weak and sparse. No U2OS pixel read, chromatin assay or exclusive localization is claimed. The GO_REF:0000052 method and source reliability are retained. Broad nucleus encompasses pools that nucleoplasm, which excludes chromosomes, does not exhaust. UniProt major/minor-form wording does not identify distinct natural isoforms.
The ten repair roots R-HSA-6785126, 6785342, 6785361, 6785732, 6785986, 6786155, 6786166, 6786171, 6788385 and 6788392 were traced through actual input/output/catalyst links to FANCC entity 419530, Q00597 1–558, with its own nucleoplasm compartment. These contexts are not independent microscopy experiments. UBE2T/FANCL perform ubiquitin transfer, named nucleases perform incision, POLN synthesis, USP1:WDR48 deubiquitination and ATR phosphorylation. A route through a composite catalytic complex does not confer each activity on FANCC. All assigned target routes are complete; eight unrelated off-target graph objects remain unexpanded.
Reactome R-HSA-6806425 has FANCC gene DNA input, FANCC protein output and separate TP53 regulation. The actual PMID:9063748(https://pubmed.ncbi.nlm.nih.gov/9063748/) abstract supports p53 transactivation; full Methods were unavailable here. It does not make FANCC the transcriptional performer or establish microscopy localization. Independent HPA supports the modeled output compartment.
Reactome R-HSA-9835411 reaches cytosolic FANCC entity 420801 through input/output HSP70/PKR complexes. The actual PMID:15299030(https://pubmed.ncbi.nlm.nih.gov/15299030/) abstract gives positive human FANCC PKR-response evidence, but its PDF-named publisher failure is not a main article. Cytosol is retained as a contextual pool; FANCC is not the kinase. Broader cytoplasm remains useful for other nonnuclear pools and is not uniformly narrowed to cytosol. PMID:9398857(https://pubmed.ncbi.nlm.nih.gov/9398857/) has positive nuclear/cytoplasmic complex evidence in the read abstract, with full Methods unavailable in that source assessment.
PMID:31666700(https://pmc.ncbi.nlm.nih.gov/articles/PMC6858856/) describes recombinant full-length chicken subunits expressed in insect cells. Selected Results, cloning/purification and ubiquitination Methods, and Extended Data Figures 1, 3 and 8 captions were independently read. Crosslinking places FANCC near FANCL and FANCE. Whole CEF omission/add-back is not a FANCC-only perturbation, and purified CEF did not readily reassociate with the symmetric subcomplex. This does not demonstrate a fixed human complex stoichiometry or isolated C-mediated recruitment.
PMID:32939280(https://pmc.ncbi.nlm.nih.gov/articles/PMC7467173/) Methods and Results §§3.3–3.4 model the prior chicken data, not a second independent human experiment. The later model assigns a region previously attributed to FANCC/FANCE to FANCG. It nevertheless supports a modeled C–E interface and maps a human residue-295 variant to that interface. The mapping predicts a possible defect; no human mutant assay was executed there. Crosslinks used during model building are not independent validation. No new figure pixels, raw maps, coordinates, deposited-model reanalysis or separate structural supplement are claimed here.
The old partner-unspecified PMID:24412244 record encompasses SMAD4 and FBXW7; PMID:35512704 expands to AKT1, SMAD4 and FBXW7. The positive AKT1 panel supports a specific binding refinement in the current-source audit, but the other primary target matrices remain unresolved. The old source is not rewritten to imply all partners are AKT1. MEOX2 interaction supports DNA-binding-transcription-factor binding without assigning transcription regulation. Supported generic FANCE coassociation remains non-core under the campaign's explicit binding exception. The following source accounts preserve the exact direct review's actual reading; numerical paragraph locators refer to its saved indexed originals, while linked papers, figures and tables provide public landmarks.
Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems.. Verified PubMed identity and complete cached abstract read. The abstract reports FANCE-region/FANCC binding and L554P loss, but attributes the stated yeast three-hybrid bridge to FANCG. Complete original Methods/Results were not recovered; failed publisher and repository routes are preserved. No target figure or supplement was inspected. Independent BioPlex/CEF support is labeled separately.
Cloning of cDNAs for Fanconi's anaemia by functional complementation.. Verified original identity and publisher Abstract read; the page explicitly supplies only a subscription preview. Functional complementation corrects human group-C cells and identifies FACC. Complete Methods/Results and figures remain unavailable. The linked correction is not treated as a replacement PMID or retraction. The ICL refinement uses separately named later evidence.
The Fanconi anaemia proteins, FAA and FAC, interact to form a nuclear complex.. Verified identity and publisher/cached abstract read. It positively reports FAA/FAC binding, L554P loss, predominantly cytoplasmic unbound proteins and a complex in nuclear and cytoplasmic fractions. The file named publisher-original is an abstract page, not complete operative Methods. No original figure pixels or complete Methods were recovered. Independent nuclear-complex and CEF assembly experiments are not represented as a reread of this historical paper.
Molecular chaperone GRP94 binds to the Fanconi anemia group C protein and regulates its intracellular expression.. Verified identity and full cached abstract read. Positive GRP94/FAC yeast-two-hybrid and co-IP, COS-1 cytosolic versus nuclear extracts, mouse liver and rat-cell expression experiments are explicit abstract claims. Complete target Methods/Results remain unavailable after saved publisher failures. The positive abstract and curator IPI attribution support keeping the generic GRP94 association as non-core; the unavailable detailed assays leave the GO:0051879 Hsp90 protein binding refinement deferred. This retains the reported interaction without asserting purified binary binding or FANCC chaperone activity. The study splice construct is not a new natural product.
The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair.. Official complete original main text was recovered as BioC and selected main passages 1–12 were actually read. The executed repair experiment uses Xenopus egg extracts, ID2 depletion/reconstitution and an ICL plasmid; it does not perturb human FANCC or assign incision chemistry to C. This is pathway context for the NAS, supplemented independently by human C-containing core and CEF reconstitution. No supplement or figure pixels were newly inspected.
A histone-fold complex and FANCM form a conserved DNA-remodeling complex to maintain genome stability.. Complete original BioC was available; selected Results 9–14, Methods 71–84, captions 87–100 and discussion 69 were read. Human HeLa nuclear-extract Figure 1C/E explicitly includes FANCC in the large FANCM/MHF-associated FA core. The separate smaller FANCM/MHF pool and non-C DNA-remodeling experiments are not transferred to FANCC. No new figure pixels or detailed online supplement were inspected.
Regulation of Rev1 by the Fanconi anemia core complex.. Complete main original was available; selected Results/captions 13–14,19,21,23,25,30,32,34,36–39 were read. Figure 2a and its accompanying Results explicitly identify FANCC in tagged FAAP20 immunoprecipitates from human 293T cells. The in vitro translated direct binding of Figure 2b is FANCA–FAAP20, not C. No new Figure 2 pixel or online detailed supplement read is claimed.
FAAP20: a novel ubiquitin-binding FA nuclear core-complex protein required for functional integrity of the FA-BRCA DNA repair pathway.. Complete official main and authentic supplemental PDF were available. Main Results/captions 21–31,34,36,40,61,63,66; supplemental Methods pp1–8 and S1–S7 captions were read. Main Figure 5 and supplement Figure S1 (PDF page 11) pixels were actually viewed. S1C explicitly shows FANCC in HeLa FAAP20 co-IP; S1B describes nuclear purification. Main Figure 5H labels A/G/FAAP20/H2A, not C. Thus core membership is supported while a separate C chromatin IDA remains unresolved, allowing possible complex-level projection rather than asserting a wrong-gene error. The supplement was newly recovered for this reassessment; earlier FANCA receipts are not retroactively changed. Official supplement: https://www.ebi.ac.uk/biostudies/files/S-EPMC3321854/supp_blood-2011-10-385963_blood-2011-10-385963-1.pdf .
Charting the molecular links between driver and susceptibility genes in colorectal cancer.. Official Europe PMC identity and cached abstract were verified. The DOI redirect establishes this exact publisher PII; its full main/target table remained inaccessible. An earlier unsuccessful guessed PII is retained only as a failed route, not treated as the original. No exact FANCC/SMAD4 or FANCC/FBXW7 primary measurements were inspected. Empty IntAct-query results are not evidence of absence or miscitation.
Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.. Complete original BioC and genuine Table S1/S2 workbooks were available. Main Results 18–25 and Experimental Procedures 48–64 were read; tables were programmatically extracted and exact target records manually inspected. Table S2A rows 181–182 map FANCC_1/KU178051 and FANCC_2/KU178052; S2B rows 104–105 pair each with MEOX2. S2C contains no FANCC target-specific PCA row. The assay is repeated human-ORF yeast two-hybrid, not a demonstrated transcriptional role. Literal Q6FHY5 remains the imported MEOX2 record; its sequence is not equated with curated P50222. Study clones remain separate from absent UniProt alternative_products. Table S2: https://www.ebi.ac.uk/biostudies/files/S-EPMC4882190/NIHMS754821-supplement-11.xlsx . The additional Procedures DOCX was captured but not read.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.. Complete original BioC was available; Methods 100–101,103,109–111,127–128,133–136 were read. Actual release tables were re-extracted: HCT116 network line 32947 is FANCC/FANCE and directed-edge line 38136 is FANCC bait/FANCE prey. The inspected 293T releases lack this pair; no biological absence claim follows. Human ORFeome FLAG–HA expression, anti-HA AP-MS and scoring support cellular coassociation, not purified binary interaction, reciprocity or exact natural-product equivalence. Public release downloads: https://bioplex.hms.harvard.edu/interactions.php (HCT116 5.5K December 2019 network and BioPlex3.0 HCT116 DirectedEdges).
Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.. Complete original BioC was available; selected main 13–17,19–22,25,27,30,48,64–76 were read. Actual Data S1 Figure iiiA (PDF page 3) pixels show tagged FANCC recovered with WT and E17K GST-AKT1, stronger for the mutant; no new quantification. The semi-endogenous MCF7 panel does not identify FANCC. Table S3B row 10 records AKT1-E17K/FANCC validation. Two genuine Table S2 downloads were unreadable ZIPs and are preserved as failures, not interpreted as negative measurements. IntAct positive SMAD4/FBXW7 BRET features are recorded with their mutation-with-no-effect labels, but their original target matrix remains uninspected, so those contexts remain U. No claim that all study interactions require mutants, or that proximity proves purified binary binding. Data S1 and Tables S1/S3 are available through https://www.ebi.ac.uk/biostudies/studies/S-EPMC9597701 ; XML provenance and exact EBI identifiers accompany the accompanying evidence record.
The FA Core Complex Contains a Homo-dimeric Catalytic Module for the Symmetric Mono-ubiquitination of FANCI-FANCD2.. Complete normal original already exists at fixed main; this is byte-exact reuse, not a new fetch. Selected Methods/Results/captions 20,23,26,29,33,34,37,38,46,49,50,52,56 were independently read. Human Sf9-expressed BL100 and CEF modules are tested with Xenopus ID2. CEF coexpression/purification and stimulation support physical assembly and pathway participation, while the proposed ID2-recognition mechanism is a module-level interpretation and the separately reported direct ID2 contact is FANCE. Neither an isolated FANCC catalytic/adaptor assay nor a human-ID2 experiment is claimed. No pixels or supplement were inspected.
Authored full_text_unavailable flags describe immutable selected normal-cache metadata. Complete external main/supplement availability, selected actual reading and viewed pixels are separate facts; a file capture is not a reading claim. The five shared references retain both complete source-review notes. PMID:9398857 has verified bibliographic identity and positive abstract claims, while its conservative UNVERIFIED assessment records unresolved operative experiment details. No rejection of those positive complexes follows from the access limit.
The supplemental Methods locator for PMID:27133164 was independently corrected in this synthesis to extracted lines 127–133 and 527–537, covering SV40 large-T immortalization, WT/vector rescue and MitoSOX flow cytometry. The public Methods account above is unchanged biologically. The earlier private ledger remains historical.
The original identities and term/evidence/reference/qualifier fields of the 37 historical records remain preserved, as do all 27 quotation/reference/path associations. The source-derived partner metadata and partner-resolved additions are described below. The full combined source set has 40 references, including two genuine existing structural sources. Four publications were fetched additively during the database review; the structural originals and PMID:27986592 were reused literally. No normal-cache content, original machine source or inherited quotation was rewritten. Failed access routes remain failures, and no provider research was fabricated. The 558-residue human target is not equated with experimental splice constructs, patient alleles or predicted transcript products.
The former authored GO:0030674 proposal is withdrawn from active assertions with retired: true; its complete UNDECIDED review, original source fields and quotations remain visible. This is our withdrawal of an unsupported proposal, not a claim that GO withdrew an imported annotation or that FANCC cannot have a structural role. At the initial withdrawal checkpoint, the 37 historical records comprised 36 active imported contexts and this one retired proposal, with 22 ACCEPT, 3 MODIFY, 6 KEEP_AS_NON_CORE and 5 UNDECIDED active decisions. The later partner-resolved checkpoint below supersedes those counts. The specific molecular activity remains unresolved and is not reassigned to another term merely to retain an active proposal.
The structured review now exposes all five current partner contexts from the two previously collapsed source groups. PMID:24412244 has separate SMAD4 and FBXW7 records, both UNDECIDED. PMID:35512704 has AKT1 MODIFY to GO:0043422 protein kinase B binding, plus separate SMAD4 and FBXW7 records, both UNDECIDED. The AKT1 decision follows the inspected Data S1 Figure iiiA and Table S3B row 10 described above; it does not transfer to the other partners. These source objects were generated by the repository seeder from the committed GOA file, then joined to their separately assessed evidence. The historical collapsed objects are retained in the appended notes.
Both cytosol records now retain a contextual non-core pool. The PMID:9596688 abstract explicitly reports cytosolic co-IP and corroborates the curator attribution; complete Methods and figures remain unavailable. This is a positive broad-location judgment, not a claim to have inspected the missing assay details. No publication quotation was added, replaced, reordered or removed.
The current review has 39 active imported contexts: 22 ACCEPT, 4 MODIFY, 8 KEEP_AS_NON_CORE and 5 UNDECIDED, plus the unchanged retired UNDECIDED adaptor proposal. It retains 40 references, one core unit and 27 inherited quotation paths. The earlier journal counts describe earlier checkpoints; they are not current totals.
All nine protein-binding contexts now carry the partner supplied by the committed GOA source. The remaining four fields identify FANCE/Q9HB96 for PMID:12649160 and PMID:33961781, MEOX2/Q6FHY5 for PMID:26871637, and GRP94/P14625 for PMID:9596688. These fields are copied from genuine repository-seeder output against the same unchanged GOA file; they add no interaction, assay, product equivalence or review decision. The two raw GRP94 records differ in assigner/date provenance and remain one shared context. The cytoplasm reason now agrees with the retained non-core cytosol judgment while preserving the unavailable detailed-Methods limit.
The comparator statement above concerns saved official annotations. Sibling FANCE/FANCF reviews are separate curatorial assertions, not independent primary evidence that FANCC performs the same molecular role. Deferring a contributes-to molecular function here does not require isolated-subunit catalysis: the evidence resolves C-containing assembly and repair participation more clearly than FANCC's particular contribution to the ligase mechanism. The existing question and experiment retain that mechanistic uncertainty, without adding a redundant knowledge-gap entry or changing the core.
Inherited quotation text, reference associations and order are preserved, including the title quotation and the contextual Xenopus ID2 quotation discussed by the reviewer. Their interpretation remains bounded by the accompanying reasons and this guide. No new publication quotation is introduced under the campaign curation instructions.