FANCA

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0043240 Fanconi anaemia nuclear complex	IBA GO_REF:0000033	ACCEPT	Summary: Retain experimentally grounded PAINT inheritance of FA nuclear-complex membership. Reason: The saved PANTHER v19 PTHR12047 tree places the exact 1455-residue human target PTN002486031 beneath ancestral PTN001382355. The matching IBD explicitly asserts GO:0043240 with experimental human O15360 evidence; no relevant NOT occurs on the saved target path. A self-WITH source is valid experimental grounding, not circularity. Human nuclear-extract affinity purification, endogenous coimmunoprecipitation and FANCA-dependent FAAP20/core assembly in PMID:22343915 independently support membership. The inherited PMID:12649160 quotation is preserved; its accessible abstract maps FANCG-mediated contacts rather than demonstrating that FANCA itself bridges every pair. This membership does not assign the complex catalytic activity to FANCA or to all its natural products. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001382355 · PTN001382355 SUPPORTS TRANSFER Verified source node on the exact human target path, with matching GO:0043240 IBD and valid human self-source; target experiments independently support complex membership. Supporting Evidence: PMID:12649160 proteins form a nuclear complex required for the monoubiquination of the
GO:0045589 regulation of regulatory T cell differentiation	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Retain the valid inherited Treg differentiation role as a contextual, non-core process. Reason: The exact human PANTHER v19 target lies beneath PTN000248169, whose GO:0045589 IBD is grounded in mouse Fanca MGI:1341823. Current mouse Q9JL70 GOA traces the experimental IMP to PMID:24501220. Its Fanca-null mice have impaired Treg suppressive function and altered Foxp3 target-gene expression, with deficient control of effector-cell proliferation and graft-versus-host disease; comparable Treg numbers and Foxp3 expression delimit the phenotype. Current GO differentiation definitions include acquisition of specialized functional features and development to the mature state, so unchanged counts alone do not refute the curated functional-maturation inference. Retain the valid propagation as contextual immune regulation rather than the principal FANCA repair unit. The study does not directly assay human Treg differentiation, establish a precursor-to-mature trajectory, or resolve a direct FANCA–Foxp3 mechanism. Neither donor number nor orthology is treated as evidence of failure. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000248169 · PTN000248169 SUPPORTS TRANSFER Verified target-path IBD and mouse experimental donor. The supported immune functional-maturation context remains non-core; no target-specific loss or invalid node placement was established.
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Retain nucleus as the encompassing location of independently observed nucleoplasmic and chromatin-associated FANCA. Reason: The UniProt SL-0191 mapping and the inherited PMID:9398857 quotation correctly assert nuclear FANCA. Independent HPA063236 imaging supports a nucleoplasmic pool, while human PMID:22343915 directly demonstrates chromatin-associated FANCA and its damage-induced loading. GO:0005654 excludes chromosomes, so replacing nucleus solely with nucleoplasm would lose supported spatial breadth. The encompassing nuclear annotation is therefore retained alongside the separately supported finer locations, without assigning all nuclear FANCA to one pool or declaring cytoplasmic FANCA inactive. HPA's 80-residue antigen maps to residues 1056–1135 of the 1455- and 1424-residue products and is absent from the 297-residue product; these images do not establish equivalent localization of all three products. The original source fields and inherited quotation remain unchanged. Supporting Evidence: PMID:9398857 is found in similar abundance in both cytoplasm and nucleus
GO:0005737 cytoplasm	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: Retain the cytoplasmic FANCA pool as contextual without calling it uniformly inactive. Reason: UniProt SL-0086 maps to cytoplasm and the inherited PMID:9398857 abstract explicitly reports unbound FAA/FAC predominantly cytoplasmic and their complex in both cytoplasm and nucleus. Human HSC93 fractionation in PMID:22343915 also detects FANCA in cytosolic and nuclear fractions, with predominance in the nuclear fraction. The separate PKR-associated context in Reactome and the positive human-bone-marrow abstract of PMID:15299030 argue against describing every cytoplasmic pool as inactive or solely awaiting import. Retain the location as contextual relative to the established nuclear repair unit; neither the fractionation nor the broad source resolves all natural products. Supporting Evidence: PMID:9398857 unbound FAA and FAC localize predominantly to the cytoplasm, the FAA-FAC complex
GO:0036297 interstrand cross-link repair	IEA GO_REF:0000002	ACCEPT	Summary: Retain the FANCA-family mapping to interstrand cross-link repair. Reason: The current IPR003516 family entry maps explicitly to GO:0036297 and covers residues 23–1447 of human O15360. Independent human experiments in PMID:22343915 identify FANCA in nuclear FA-core preparations and show that full-length FANCA restores FANCD2 monoubiquitination in FANCA-deficient cells whereas the tested terminal deletion constructs fail. Its depletion also destabilizes FAAP20 and affects the repair assembly. These observations support FANCA performing an assembly/stability contribution to ICL repair, without assigning the FANCL ubiquitin-transfer reaction or nuclease chemistry to FANCA. The unchanged inherited PMID:19965384 quotation is general pathway corroboration: that paper experimentally depletes and restores Xenopus FANCI–FANCD2, not human FANCA. The family match and engineered constructs do not establish functional equivalence of all natural products. Supporting Evidence: PMID:19965384 central event in the activation of the Fanconi anemia pathway is the
GO:0043240 Fanconi anaemia nuclear complex	IEA GO_REF:0000002	ACCEPT	Summary: Retain the explicit InterPro FANCA-family mapping to the FA nuclear complex. Reason: IPR003516 is the FANCA family and currently maps to GO:0043240; its human O15360 match spans residues 23–1447. Human nuclear FA-core purification and endogenous association in PMID:22343915 corroborate the family inference. FANCA also stabilizes FAAP20 and permits its association with the broader complex in the tested human cells. Membership is a structural/assembly role, not independent ubiquitin-ligase catalysis, and the full-length family match does not determine the behavior of the 297- or 1424-residue natural products.
GO:0005515 protein binding	IPI PMID:10627486 Strong FANCA/FANCG but weak FANCA/FANCC interaction in the y...	KEEP AS NON CORE	Summary: FANCA–FANCG association is supported; the original yeast assay remains incompletely accessible. Reason: The PMID:10627486 abstract explicitly reports strong FANCA/FANCG interaction using full-length cDNAs in yeast two-hybrid assays. Complete operative text was not recovered. Independently inspected human FANCA immunoprecipitation and selective N-terminal deletion experiments in PMID:22343915 Figures 2–3 substantiate this partner association, but do not retrospectively verify the old constructs. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:10627486 found a strong interaction between FANCA and FANCG proteins
GO:0005515 protein binding	IPI PMID:10652215 Investigation of Fanconi anemia protein interactions by yeas...	KEEP AS NON CORE	Summary: FANCA–FANCG interaction is supported without extending the older assay to every product. Reason: PMID:10652215 reports strong FANCA–FANCG yeast two-hybrid interaction and fragment mapping in its accessible abstract; the complete main article was not recovered. Human complex association and FANCA domain-selective binding in PMID:22343915 independently support the pair. The older paper reports weak FANCA self-interaction, which is not conflated with the different self-interaction result in PMID:10627486. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:10652215 indicating strong, direct interaction between these proteins
GO:0005515 protein binding	IPI PMID:11063725 The Fanconi anemia protein FANCF forms a nuclear complex wit...	KEEP AS NON CORE	Summary: The expanded current partner contexts retain supported core-complex association as non-core. Reason: FANCG context: The accessible PMID:11063725 abstract identifies a human lymphoblast nuclear FANCF/FANCA/FANCC/FANCG complex. Full operative Methods and Results were not recovered. Independently read human complex and FANCA–FANCG experiments in PMID:22343915 support the imported FANCG context; they do not establish the exact historical tagged product. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. FANCF context: PMID:11063725 reports a FANCF-containing nuclear complex with FANCA, FANCC and FANCG in its accessible abstract. Independently inspected FANCA immunoprecipitates from human HeLa nuclear extract contain FANCF by mass spectrometry in PMID:22705371 Figure 1. This supports coassociation without establishing a purified binary FANCA–FANCF interface; full Methods and Results of the older paper remain unavailable. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:11063725 where it complexes with FANCA, FANCC and
GO:0005515 protein binding	IPI PMID:12649160 Fanconi anemia protein complex: mapping protein interactions...	KEEP AS NON CORE	Summary: The expanded current partner contexts retain supported core-complex association as non-core. Reason: FANCG context: PMID:12649160 reports yeast two- and three-hybrid mapping in its accessible abstract; full operative text was not recovered. The stated bridge from FANCA to FANCF is mediated by FANCG, so that bridge must not be assigned to FANCA merely by association. Independently inspected PMID:22343915 Figure 3 supports FANCA–FANCG binding and its N-terminal dependence. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. FANCF context: The PMID:12649160 abstract describes FANCG-mediated bridging of FANCA to FANCF in yeast hybrid assays. Its complete operative text remains unavailable. Human FANCA immunopurification with FANCF detected in PMID:22705371 independently supports complex coassociation, while leaving binary contact and the old constructs unresolved. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:12649160 FANCG was shown to interact with both
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	KEEP AS NON CORE	Summary: The human ORF two-hybrid record supports FANCA–FANCG association. Reason: The original PMID:16189514 Supplementary Table S2 contains FANCA–FANCG with a positive Y2H field and an independently catalogued literature interaction; its co-affinity-purification field is blank. The recovered Supplementary Methods describe human ORFeome v1.1 fusions in yeast, exclusion of autoactivators, sequence-tag checks and pairwise retesting. The main article remains a subscription preview. The gene-level table collapses splice/polymorphic variants and does not identify an exact current natural FANCA product. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:16189514
GO:0005515 protein binding	IPI PMID:17289582 Identification of FAAP24, a Fanconi anemia core complex prot...	KEEP AS NON CORE	Summary: FANCA–FANCG core association is supported independently of the inaccessible FAAP24 study. Reason: PMID:17289582 chiefly addresses FANCM–FAAP24 in the accessible abstract; its complete main article was not recovered. That emphasis is not evidence of a wrong FANCA annotation. Independent human FANCA–FANCG binding and core-complex association in PMID:22343915 substantiate the imported pair, without assigning FANCM remodeling or FAAP24 DNA recognition to FANCA. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:17289582 PMID:22343915
GO:0005515 protein binding	IPI PMID:17396147 FAAP100 is essential for activation of the Fanconi anemia-as...	KEEP AS NON CORE	Summary: The expanded current partner contexts retain supported core-complex association as non-core. Reason: FANCG context: PMID:17396147 Figure 1 and its purification Results show overlapping FANCA/FANCG fractionation and their participation in the human FA core complex. The source separates this module from the FANCB–FANCL–FAAP100 subcomplex. Together with the independently inspected selective FANCA interaction mapping in PMID:22343915, this supports FANCG association without treating the whole core as one binary interface. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. FAAP100 context: PMID:17396147 Figures 1–2 and the HeLa purification Methods show FANCA/FAAP100 coimmunoprecipitation and nuclear complex association. In contrast, FAAP100–FANCA two-/three-hybrid testing was negative, and the stable FANCB–FANCL–FAAP100 module can separate from FANCA under high-salt conditions. Retain the positive complex association without upgrading it to purified binary binding. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:17396147 FAAP100 is essential for activation of the Fanconi anemia-associated DNA damage
GO:0005515 protein binding	IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote...	UNDECIDED	Summary: The GRB2 peptide-array result is traced but the operative original remains inaccessible. Reason: The PMID:17474147 abstract describes an in vitro SH3-domain peptide-array screen, and the current IntAct records identify GRB2 residues 156–215 with FANCA peptide regions 493–506 and 1404–1417. These curated records do not substitute for the unavailable original target array and controls. SH3-domain binding is a plausible more specific term, but no replacement is asserted without verifying those experiments. The reported peptide interaction is not treated as false or as a full-length cellular signaling mechanism. Supporting Evidence: PMID:17474147
GO:0005515 protein binding	IPI PMID:22266823 Regulation of Rev1 by the Fanconi anemia core complex.	KEEP AS NON CORE	Summary: FANCA associates with FAAP20 in the explicitly imported partner-product context. Reason: PMID:22266823 Figure 2 shows FANCA–FAAP20 coimmunoprecipitation, including an in vitro translated preparation, and separates the FAAP20 N-terminal FANCA-binding region from its C-terminal UBZ function. The displayed partner source is Q6NZ36-1 and remains literal; the assay does not establish equivalence among FANCA natural products. FAAP20 supplies the demonstrated Rev1/ubiquitin bridge, which is not transferred to FANCA. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:22266823 multisubunit Fanconi anemia core complex. FAAP20 binds to FANCA subunit and is
GO:0005515 protein binding	IPI PMID:28514442 Architecture of the human interactome defines protein commun...	KEEP AS NON CORE	Summary: BioPlex 2.0 records FANCG bait recovering FANCA. Reason: The actual BioPlex 2.0 directed-edge file contains FANCG as bait and FANCA as prey. The separately saved undirected interaction-list file lacks this pair, so the positive claim is explicitly tied to the directed file rather than treating releases as interchangeable. PMID:28514442 Online Methods describe sequence-validated human ORFeome C-terminal HA–FLAG constructs, HEK293T expression, anti-HA capture and mass-spectrometry scoring. This is cellular coassociation, not purified binary binding or a verified current FANCA isoform. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:28514442
GO:0005515 protein binding	IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ...	KEEP AS NON CORE	Summary: The original validation table records a positive FANCA–FANCG assay. Reason: PMID:32814053 Table S4, hsPRS-v1 sheet, records FANCA–FANCG as POS, while Table S2 also includes the pair in the extended network. The author-version Methods describe DULIP luminescence-based coprecipitation in HEK293 cells with fusion-expression and background controls; the exact IntAct record identifies this mammalian luminescence assay. This paper is not HuRI, and its positive-reference-set result is not misrepresented as an independently discovered disease mechanism or current-product sequence proof. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:32814053
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: BioPlex 3.0 supports FANCA–FANCG coassociation in both profiled cell lines. Reason: The original saved 293T and HCT116 network tables contain the FANCA–FANCG pair, and their directed files identify FANCG bait recovering FANCA. PMID:33961781 Methods describe human ORFeome constructs, cellular affinity purification and technical-duplicate mass spectrometry. Detection in both contexts supports association; it does not prove a purified interface, equal physiological abundance, or activity of all three natural FANCA products. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:33961781
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	KEEP AS NON CORE	Summary: Endogenously tagged FANCA copurifies with FAAP100 in OpenCell. Reason: The actual OpenCell interaction table records FANCA bait with FAAP100;C17ORF70, including Q0VG06 among the reported peptide/protein identifiers. PMID:35271311 describes split-mNeonGreen endogenous tagging of HEK293T polyclonal pools and biological-triplicate affinity-enrichment mass spectrometry. The association is supported, while neither the table’s protein-group identifiers nor generic tagging information resolve the natural FANCA product or a binary FANCA–FAAP100 interface. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:35271311
GO:0005515 protein binding	IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc...	KEEP AS NON CORE	Summary: The valid preprint-associated record supports tagged FANCA–FANCG proximity and coassociation. Reason: PMID:37398436 is the 2023 preprint, with PubMed explicitly linking the later journal version PMID:38467836; it is not a wrong identifier merely because the MED-indexed Europe PMC query omits it. The preserved cache and current IntAct records describe LuTHy BRET/proximity and luminescence coprecipitation with several tag orientations for FANCA–FANCG. The cache’s hosted article has a version boundary, and no preprint/final byte identity or target clone-sequence equivalence is claimed. Independent original FANCA–FANCG experiments corroborate the association. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:37398436 PMID:22343915
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	KEEP AS NON CORE	Summary: The U2OS AP-MS map contains the FANCA–FANCG edge. Reason: PMID:40205054 Methods describe C-terminal HA–FLAG human ORFeome baits expressed in U2OS cells, anti-HA capture, peptide identification and CompPASS/CompPASS-Plus filtering. The actual NDEx source contains the FANCA–FANCG edge and literal participant attributes. Edge order and bait inventory are not taken as proof of a particular IP direction, reciprocal individual experiments, binary binding or exact natural-product identity. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:40205054
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: Retain supported HPA nucleoplasmic localization with the antibody and product boundary explicit. Reason: The current HPA record for ENSG00000187741 reports supported nucleoplasm with antibody HPA063236 in MCF7, SiHa and U2OS. Actual MCF7 and SiHa image inspection is consistent with green staining in the nuclear interior and spared nucleolar regions. The antigen is the same 80-residue sequence at positions 1056–1135 in both long natural products; it is absent from the 297-residue product. This supports a gene-level nucleoplasmic pool without resolving the long products, measuring DNA-damage recruitment or assigning the short product this localization. Supporting Evidence: GO_REF:0000052
GO:0000785 chromatin	IDA PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr...	ACCEPT	Summary: FANCA associates with chromatin in human cells. Reason: PMID:22343915 demonstrates FANCA in the chromatin-enriched fraction after MMC or hydroxyurea and the dependence of its loading on FAAP20 (Figure 5 and the chromatin-association Results). FAAP20 depletion and complementation distinguish chromatin recruitment from merely restoring FANCA abundance. This supports the observed FANCA location without transferring FAAP20 ubiquitin recognition or claiming that every natural FANCA product was localized. Supporting Evidence: PMID:22343915 but is required for DNA-damage-induced chromatin loading of FANCA and the
GO:0036297 interstrand cross-link repair	NAS PMID:19965384 The Fanconi anemia pathway promotes replication-dependent DN...	ACCEPT	Summary: FANCA participates in interstrand cross-link repair through its demonstrated core-complex role. Reason: The imported evidence is NAS. The fully inspected PMID:19965384 main and captions experimentally reconstitute Xenopus FANCI/FANCD2-dependent repair, not direct human FANCA cleavage. Its pathway context is compatible with FANCA participation, which is independently grounded by the human FANCA assembly and ICL recruitment/survival evidence in PMID:22343915 and PMID:22705371. FANCA supplies complex organization; the incision/TLS chemistry measured on ID2-depleted extracts is not relabeled as FANCA catalysis. Supporting Evidence: PMID:19965384 hypersensitivity to chemicals that generate DNA interstrand cross-links (ICLs)
GO:0043240 Fanconi anaemia nuclear complex	NAS PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr...	ACCEPT	Summary: The non-traceable membership assertion is independently supported by the cited original. Reason: Although this imported row carries NAS, the inspected human purification and interaction data in PMID:22343915 directly establish FANCA core membership. This evidence-code context is preserved rather than rewritten; the claim does not depend on treating all FA proteins as interchangeable or making FANCA the ubiquitin-transfer catalyst. Supporting Evidence: PMID:22343915 that FAAP20 is an integral component of the FA nuclear core complex. We identify
GO:0005829 cytosol	TAS Reactome:R-HSA-9835411	KEEP AS NON CORE	Summary: Retain the modeled cytosolic FA-core–HSP70–PKR context as non-core localization. Reason: Reaction R-HSA-9835411 contains the explicit input route R-HSA-9835411 → R-HSA-9835414 → R-HSA-9835415 → R-HSA-420796, and an output route through R-HSA-9835398. The terminal FANCA entity is O15360 residues 1–1455 with its own cytosol compartment, GO:0005829. The reaction describes FANCC-mediated PKR association in a larger FA-core/HSP70 assembly; the PMID:15299030 abstract separately reports functional interactions of FANCA/FANCC/FANCG with PKR and altered PKR activation in human FA bone-marrow cells. Complete PKR-paper Methods were not recovered, so no binary FANCA–PKR interface or new FANCA catalytic activity is claimed. This positive contextual pool is not dismissed as inactive preassembly.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6785126	ACCEPT	Summary: Retain the nucleoplasmic FANCA pool modeled during assembly at an interstrand crosslink. Reason: Current reaction R-HSA-6785126 has a verified target route (R-HSA-6785126 → R-HSA-419541) to FANCA R-HSA-419541, whose own compartment is GO:0005654 and whose reference is UniProt O15360, residues 1–1455. FANCA is an explicit input and a component of the assembled output. The annotation is supported as a cellular location even where the enclosing complex contains another enzyme. It does not localize all three natural products or establish every modeled molecular contact. The broader graph has eight recorded off-target retrieval failures; the cited FANCA path is complete.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6785342	ACCEPT	Summary: Retain the nucleoplasmic FANCA pool modeled during recruitment of the ID2 complex and UBE2T. Reason: Current reaction R-HSA-6785342 has a verified target route (R-HSA-6785342 → R-HSA-6785124 → R-HSA-6785123 → R-HSA-419541) to FANCA R-HSA-419541, whose own compartment is GO:0005654 and whose reference is UniProt O15360, residues 1–1455. FANCA occurs inside the input and output FA-core assemblies; FANCL and UBE2T perform the ubiquitin-ligase functions. The annotation is supported as a cellular location even where the enclosing complex contains another enzyme. It does not localize all three natural products or establish every modeled molecular contact. The broader graph has eight recorded off-target retrieval failures; the cited FANCA path is complete.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6785361	ACCEPT	Summary: Retain the nucleoplasmic FANCA pool modeled during ID2 monoubiquitination. Reason: Current reaction R-HSA-6785361 has a verified target route (R-HSA-6785361 → R-HSA-6788398 → R-HSA-6788397 → R-HSA-6788399 → R-HSA-419541) to FANCA R-HSA-419541, whose own compartment is GO:0005654 and whose reference is UniProt O15360, residues 1–1455. FANCA occurs inside the input, output and catalyst-containing assembly. This does not make FANCA the FANCL/UBE2T catalytic subunit. The annotation is supported as a cellular location even where the enclosing complex contains another enzyme. It does not localize all three natural products or establish every modeled molecular contact. The broader graph has eight recorded off-target retrieval failures; the cited FANCA path is complete.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6785732	ACCEPT	Summary: Retain the nucleoplasmic FANCA pool modeled during nuclease recruitment to monoubiquitinated ID2. Reason: Current reaction R-HSA-6785732 has a verified target route (R-HSA-6785732 → R-HSA-6785367 → R-HSA-6788397 → R-HSA-6788399 → R-HSA-419541) to FANCA R-HSA-419541, whose own compartment is GO:0005654 and whose reference is UniProt O15360, residues 1–1455. FANCA is a component of the input and output assemblies, while FAN1 and the other named nucleases supply their own activities. The annotation is supported as a cellular location even where the enclosing complex contains another enzyme. It does not localize all three natural products or establish every modeled molecular contact. The broader graph has eight recorded off-target retrieval failures; the cited FANCA path is complete.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6785986	ACCEPT	Summary: Retain the nucleoplasmic FANCA pool modeled during interstrand-crosslink unhooking. Reason: Current reaction R-HSA-6785986 has a verified target route (R-HSA-6785986 → R-HSA-6786151 → R-HSA-419526 → R-HSA-419541) to FANCA R-HSA-419541, whose own compartment is GO:0005654 and whose reference is UniProt O15360, residues 1–1455. FANCA is present in the input, output and catalyst-containing repair assemblies; nuclease activity belongs to the modeled nucleases, not to every component. The annotation is supported as a cellular location even where the enclosing complex contains another enzyme. It does not localize all three natural products or establish every modeled molecular contact. The broader graph has eight recorded off-target retrieval failures; the cited FANCA path is complete.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6786155	ACCEPT	Summary: Retain the nucleoplasmic FANCA pool modeled during POLN recruitment. Reason: Current reaction R-HSA-6786155 has a verified target route (R-HSA-6786155 → R-HSA-6786151 → R-HSA-419526 → R-HSA-419541) to FANCA R-HSA-419541, whose own compartment is GO:0005654 and whose reference is UniProt O15360, residues 1–1455. FANCA occurs in both the input and output complexes. The recruited polymerase is POLN; this location record does not assign polymerase activity to FANCA. The annotation is supported as a cellular location even where the enclosing complex contains another enzyme. It does not localize all three natural products or establish every modeled molecular contact. The broader graph has eight recorded off-target retrieval failures; the cited FANCA path is complete.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6786166	ACCEPT	Summary: Retain the nucleoplasmic FANCA pool modeled during POLN translesion synthesis. Reason: Current reaction R-HSA-6786166 has a verified target route (R-HSA-6786166 → R-HSA-6788399 → R-HSA-419541) to FANCA R-HSA-419541, whose own compartment is GO:0005654 and whose reference is UniProt O15360, residues 1–1455. FANCA is included in the input, output and catalyst-containing assemblies. POLN performs the DNA synthesis; FANCA membership supports location rather than polymerase chemistry. The annotation is supported as a cellular location even where the enclosing complex contains another enzyme. It does not localize all three natural products or establish every modeled molecular contact. The broader graph has eight recorded off-target retrieval failures; the cited FANCA path is complete.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6786171	ACCEPT	Summary: Retain the nucleoplasmic FANCA pool modeled during FANCD2 deubiquitination. Reason: Current reaction R-HSA-6786171 has a verified target route (R-HSA-6786171 → R-HSA-6788397 → R-HSA-6788399 → R-HSA-419541) to FANCA R-HSA-419541, whose own compartment is GO:0005654 and whose reference is UniProt O15360, residues 1–1455. FANCA is included in the input and output assemblies; the deubiquitinase is USP1 with WDR48, not FANCA. The annotation is supported as a cellular location even where the enclosing complex contains another enzyme. It does not localize all three natural products or establish every modeled molecular contact. The broader graph has eight recorded off-target retrieval failures; the cited FANCA path is complete.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6788385	ACCEPT	Summary: Retain the nucleoplasmic FANCA pool modeled during ATR–ATRIP recruitment. Reason: Current reaction R-HSA-6788385 has a verified target route (R-HSA-6788385 → R-HSA-6785340 → R-HSA-6785124 → R-HSA-6785123 → R-HSA-419541) to FANCA R-HSA-419541, whose own compartment is GO:0005654 and whose reference is UniProt O15360, residues 1–1455. FANCA is present inside both input and output repair complexes; it is not thereby assigned ATR kinase activity. The annotation is supported as a cellular location even where the enclosing complex contains another enzyme. It does not localize all three natural products or establish every modeled molecular contact. The broader graph has eight recorded off-target retrieval failures; the cited FANCA path is complete.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6788392	ACCEPT	Summary: Retain the nucleoplasmic FANCA pool modeled during ATR-dependent phosphorylation. Reason: Current reaction R-HSA-6788392 has a verified target route (R-HSA-6788392 → R-HSA-6788398 → R-HSA-6788397 → R-HSA-6788399 → R-HSA-419541) to FANCA R-HSA-419541, whose own compartment is GO:0005654 and whose reference is UniProt O15360, residues 1–1455. FANCA is a component of the input, output and catalyst-containing assemblies. ATR supplies the kinase activity, while FANCA retains its complex role. The annotation is supported as a cellular location even where the enclosing complex contains another enzyme. It does not localize all three natural products or establish every modeled molecular contact. The broader graph has eight recorded off-target retrieval failures; the cited FANCA path is complete.
GO:0005515 protein binding	IPI PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr...	KEEP AS NON CORE	Summary: FANCA directly anchors the mapped FAAP20 interaction region. Reason: PMID:22343915 Figures 2–3 combine human cell coimmunoprecipitation, FANCA deletion mapping and recombinant fragment assays. The FANCA C-terminal region around residues 1095–1200 binds FAAP20, while the FANCG-associated region is different. This supports the imported association; the separately reassessed inherited scaffold proposal depends on the additional assembly experiments, not merely on this one IPI row. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:22343915 a region on FANCA that physically interacts with FAAP20, and show that FANCA
GO:0005515 protein binding	IPI PMID:22705371 A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubi...	KEEP AS NON CORE	Summary: FANCA–FAAP20 complex association is supported in human cells. Reason: PMID:22705371 Figure 1 and purification Methods identify FAAP20 in human FANCA immunoprecipitates and reciprocal tagged FAAP20 preparations. FANCA patient-cell complementation restores FAAP20 stability. The paper also distinguishes FAAP20 N-terminal core association from its UBZ-dependent recruitment function; FANCA is not thereby assigned ubiquitin binding or RNF8 catalytic activity. The supported generic binding assertion is retained as non-core under the campaign exception. Partner identity or coassociation alone does not assign FANCA an adaptor, enzyme-regulator or stoichiometric heterodimer function. Supporting Evidence: PMID:22705371 by RNF8 and its partner, UBC13, and mediated by FAAP20, a component of the FA
GO:0043240 Fanconi anaemia nuclear complex	IDA PMID:22266823 Regulation of Rev1 by the Fanconi anemia core complex.	ACCEPT	Summary: Human FANCA is present in the FAAP20-containing FA core complex. Reason: PMID:22266823 Figure 2 identifies FANCA in cellular FAAP20 immunoprecipitates and tests the interaction region. Core membership is distinct from the FAAP20 UBZ/Rev1 bridge and from FANCA being the core’s ubiquitin-ligase catalyst. The recovered main/captions were read; online detailed Methods and supplement were not recovered. Supporting Evidence: PMID:22266823 multisubunit Fanconi anemia core complex. FAAP20 binds to FANCA subunit and is
GO:0043240 Fanconi anaemia nuclear complex	IDA PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr...	ACCEPT	Summary: FANCA participates in the experimentally isolated human nuclear core complex. Reason: PMID:22343915 Figures 1–3 and the human purification/interaction Results establish FANCA-containing FA complexes, partner stability and assembly dependence. These are positive membership data rather than an inference from disease alone. The FANCA deletion/fragment results do not establish equivalent assembly by each natural product. Supporting Evidence: PMID:22343915 that FAAP20 is an integral component of the FA nuclear core complex. We identify
GO:0043240 Fanconi anaemia nuclear complex	IDA PMID:22705371 A ubiquitin-binding protein, FAAP20, links RNF8-mediated ubi...	ACCEPT	Summary: Human FANCA belongs to the FAAP20-associated FA nuclear core complex. Reason: PMID:22705371 Figure 1 and its gel-filtration/immunopurification Methods identify the complex in HeLa nuclear extract and reciprocal FAAP20 preparations. The independently described damage-recruitment function is consistent with that membership. Chicken DT40 functional experiments are kept separate from the human biochemical complex evidence. Supporting Evidence: PMID:22705371
GO:0043240 Fanconi anaemia nuclear complex	IDA PMID:20347428 A histone-fold complex and FANCM form a conserved DNA-remode...	ACCEPT	Summary: FANCA is a constituent of the human FA nuclear complex. Reason: PMID:20347428 Figure 1 and main purification Methods show FANCA immunoprecipitation from human HeLa nuclear extract containing FA core proteins and MHF partners. Quantitative immunodepletion also shows that much FANCM/MHF exists outside the FANCA-containing complex. This supports FANCA complex membership without asserting that every associated partner is exclusively in that complex or transferring FANCM fork-remodeling activity. Supporting Evidence: PMID:20347428
GO:0005515 protein binding	IPI PMID:11726552 Fanconi anemia protein, FANCA, associates with BRG1, a compo...	UNDECIDED	Summary: The BRG1-associated experimental context remains incompletely verified. Reason: The PMID:11726552 abstract positively reports FANCA–BRG1 coassociation and transfected nuclear colocalization, while saying FANCA was not absolutely required for the tested in vitro chromatin-remodeling reaction. Full operative Methods, Results and target controls were not recovered. The ATPase-binding and adaptor alternatives were considered, but the available scope does not justify replacing this context with BRG1 activation, remodeling or a recruitment mechanism. UNDECIDED records that access limit, not absence of the reported interaction. Supporting Evidence: PMID:11726552 FANCA was demonstrated to associate with the endogenous SWI/SNF
GO:0005634 nucleus	IDA PMID:11726552 Fanconi anemia protein, FANCA, associates with BRG1, a compo...	ACCEPT	Summary: Retain the supported nuclear location without excluding chromatin-associated FANCA. Reason: The PMID:11726552 abstract reports nuclear colocalization of transfected FANCA and BRG1, but its operative Methods and Results remain inaccessible. Independent HPA063236 images from MCF7 and SiHa cells show nuclear-interior signal with spared nucleolar regions, supporting a nucleoplasmic pool. The antigen is present in the two longer FANCA products and absent from the 297-residue product; these images do not distinguish the longer products. PMID:22343915 also demonstrates chromatin-associated FANCA. Because nucleoplasm excludes chromosomes, it would not replace the full supported nuclear breadth. Nuclear residence is not exclusive of the positive cytoplasmic pool. Supporting Evidence: PMID:11726552 between transfected FANCA and BRG1
GO:0005515 protein binding	IPI PMID:12571280 Nonerythroid alphaII spectrin is required for recruitment of...	UNDECIDED	Summary: The FANCA–XPF experimental context requires the unavailable operative source. Reason: The PMID:12571280 abstract reports FANCA/XPF damage-induced foci and association with nonerythroid alphaII spectrin. Its proposed scaffold is spectrin, not automatically FANCA. Complete operative evidence and the exact target interaction controls were not recovered; therefore neither an adaptor-function replacement nor experimental removal is justified. This access-limited decision preserves the positive reported association. Supporting Evidence: PMID:12571280 alphaSpIISigma*, FANCA and XPF co-immunoprecipitate with each other from normal
GO:0005634 nucleus	TAS PMID:9398857 The Fanconi anaemia proteins, FAA and FAC, interact to form ...	ACCEPT	Summary: Retain nuclear localization alongside the independently resolved nucleoplasmic and chromatin pools. Reason: The PMID:9398857 abstract reports the FAA–FAC complex in both nuclear and cytoplasmic fractions; its full operative original was not recovered. Independent HPA063236 images from MCF7 and SiHa cells show nuclear-interior signal with spared nucleolar regions, supporting a nucleoplasmic pool. The antigen is present in the two longer FANCA products and absent from the 297-residue product; these images do not distinguish the longer products. PMID:22343915 also demonstrates chromatin-associated FANCA. Because nucleoplasm excludes chromosomes, it would not replace the full supported nuclear breadth. Nuclear residence is not exclusive of the positive cytoplasmic pool. Supporting Evidence: PMID:9398857 is found in similar abundance in both cytoplasm and nucleus
GO:0005737 cytoplasm	TAS PMID:9398857 The Fanconi anaemia proteins, FAA and FAC, interact to form ...	KEEP AS NON CORE	Summary: A genuine cytoplasmic FANCA pool is retained as contextual localization. Reason: The PMID:9398857 abstract positively reports cytoplasmic free FAA and a FAA–FAC complex in both compartments. Independently inspected human fractionation and complex studies in PMID:17396147 Figures 2 and 4 and PMID:22343915 Figure 2 corroborate a cytoplasmic pool. The available evidence does not support the inherited blanket claim that every cytoplasmic FANCA molecule is inactive. This contextual residence is retained without substituting cytoplasm for the nuclear repair location. Supporting Evidence: PMID:9398857 unbound FAA and FAC localize predominantly to the cytoplasm, the FAA-FAC complex
GO:0006281 DNA repair	TAS PMID:8896564 Positional cloning of the Fanconi anaemia group A gene.	MODIFY	Summary: Refine broad DNA repair to the independently supported interstrand cross-link and single-strand annealing repair roles. Reason: PMID:8896564 identifies human FANCA and crosslink-sensitive disease in its accessible abstract, but its full original remains unavailable. Independently inspected human core assembly and ICL recruitment/survival experiments support interstrand cross-link repair (PMID:22343915; PMID:22705371). Purified FANCA annealing and human U2OS reporter perturbation/complementation in PMID:30057198 independently support double-strand break repair via single-strand annealing. Both replacements are typed descendants of DNA repair and are mutually non-ancestral. This is a cross-source gene-level refinement: the imported TAS source object and its historical quotation are preserved, and the 1996 paper is not claimed to have assayed SSA. The existing specific SSA proposal provides its experimental context rather than a second biological function. No partner nuclease, polymerase or ubiquitin-transfer activity is assigned to FANCA. Proposed replacements: interstrand cross-link repair double-strand break repair via single-strand annealing Supporting Evidence: PMID:8896564 new class of genes associated with the prevention or repair of DNA damage PMID:22343915 PMID:22705371 PMID:30057198
GO:0065003 protein-containing complex assembly	TAS PMID:9398857 The Fanconi anaemia proteins, FAA and FAC, interact to form ...	ACCEPT	Summary: FANCA contributes physical organization to assembly of the FA core complex. Reason: The older PMID:9398857 abstract reports complex formation correlated with function, while its complete operative original remains unavailable. Independent human patient-cell reconstitution and selective FANCA interaction-domain experiments in PMID:22343915 Figures 2–3 provide more than necessity alone: FANCA connects the FANCG-associated and FAAP20-associated parts of the complex, and deleting the mapped regions disrupts assembly/function. The term describes the arrangement and bonding of complex components, not the catalytic role of FANCL. No verified narrower FA-complex-assembly term was found. Supporting Evidence: PMID:9398857 the FAA and FAC bind each other and form a complex
GO:0140378 protein complex scaffold activity	IPI PMID:22266823 Regulation of Rev1 by the Fanconi anemia core complex.	NEW	Summary: Refine the inherited proposal to integral protein-complex scaffold activity. Reason: The current GO:0030674 annotation comment explicitly directs protein-complex scaffolds to GO:0140378. The latter describes an integral complex component that holds the complex together. FANCA supplies this structural organization in the human FA core: in PMID:22343915 Figure 2I, restoring FAAP20 abundance in FANCA-deficient cells does not restore its coassociation with FANCG/FANCM; Figure 3 maps separable FANCA regions supporting FANCG and FAAP20 contacts, and recombinant fragments localize the FAAP20 contact. These target experiments establish more than complex membership or two unrelated binding observations. They do not establish a purified ternary stoichiometry or direct FANCA–FANCF interface. PMID:22266823 and its preserved quotation support FANCA–FAAP20 association; the ubiquitin/Rev1 bridge measured there belongs to FAAP20. The inherited IPI evidence code and primary identifier remain intact, with PMID:22343915 supplying the decisive independent physical-assembly evidence. Official QuickGO records rechecked on 2026-10-25 confirm exact human scaffold IDA annotations for CCDC6 (UniProtKB:Q16204) and CHIC2 (UniProtKB:Q9UKJ5), documented with record identifiers, references and response provenance in FANCA-scaffold-comparators.json. These establish convention examples, not an identical FANCA mechanism or a universal inference from absence among selected FA proteins. The earlier adaptor interpretation is superseded by the explicit ontology distinction. No new supplement or figure pixels were read for this reassessment; detailed mammalian constructs and equivalence of the natural 297- and 1424-residue products remain unresolved. Supporting Evidence: PMID:22266823 multisubunit Fanconi anemia core complex. FAAP20 binds to FANCA subunit and is PMID:22343915 a region on FANCA that physically interacts with FAAP20, and show that FANCA
GO:1990814 DNA/DNA annealing activity	IDA PMID:30057198 FANCA Promotes DNA Double-Strand Break Repair by Catalyzing ...	NEW	Summary: Refine the inherited ssDNA-binding proposal to directly measured DNA/DNA annealing activity. Reason: PMID:30057198 Results, Figures 1–4 and STAR Methods directly assay purified human FANCA-mediated formation of duplex products from complementary DNA strands, including partially duplex substrates. The defined reaction contains no added ATP; protein concentration, no-protein controls and disease-associated or engineered mutants distinguish annealing from binding alone. Some mutants retain DNA binding while losing annealing. FANCA performs the measured reaction. GO:1990814 matches that activity and is a typed is_a descendant of GO:0003697, so this authored NEW proposal is refined rather than retaining a redundant ancestor or adding a row. The primary source becomes PMID:30057198 with IDA. Both inherited PMID:22194614 quotations remain at their exact original paths and reference associations solely as nucleic-acid-binding context; neither quotation is presented as evidence of annealing. The new annealing support is an unquoted citation. Actual exact-term human IDA comparators include RECQL, RECQL4 and BLM; target experiments, not their presence or absence, establish the FANCA reaction. Strand exchange remains measured breadth of the same biochemical unit, without asserting ATPase, nuclease or equivalent activity of all natural products. Supporting Evidence: PMID:22194614 Using purified protein, we report that human FANCA has intrinsic affinity for nucleic acids. PMID:22194614 its affinity for ssDNA is significantly higher than for dsDNA in an electrophoretic mobility shift assay PMID:30057198
GO:0045002 double-strand break repair via single-strand annealing	IMP PMID:30057198 FANCA Promotes DNA Double-Strand Break Repair by Catalyzing ...	NEW	Summary: Retain a source-bounded role in double-strand break repair via single-strand annealing. Reason: PMID:30057198 combines purified human FANCA-mediated annealing/strand-exchange reactions with human U2OS SSA reporter knockdown, knockout and complementation assays. The biochemical experiments establish that FANCA itself performs annealing rather than merely being required for another enzyme’s reaction. Separation-of-function mutants, including the D598N comparison, distinguish the observed SSA role from FANCD2 monoubiquitination; RAD52 perturbation provides a comparator within the tested system. These results support GO:0045002 at that cellular and construct scope, without making all repair contexts RAD52-independent or assigning an ATPase or nuclease activity. The broad imported DNA-repair row is refined to the independently supported ICL and SSA roles; this inherited specific proposal preserves the SSA experimental context, rather than adding another biological function. ICL repair and SSA repair are mutually non-ancestral in the captured typed closure. The three natural FANCA products were not compared for functional equivalence. Supporting Evidence: PMID:30057198 The SA and SE activities of FANCA directly explain its role in homology-directed DSB repair. PMID:30057198 Our cell-based DSB repair assay further demonstrates that FANCA contributes to the repair of DNA double strand breaks independently of the FA pathway and RAD52 in human cells.

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