FANCF is a predominantly nuclear organizing subunit of the Fanconi anemia core complex. Its contacts with FANCG and the FANCC–FANCE module help assemble and stabilize the repair machinery, enabling coordinated activation of FANCD2–FANCI during interstrand cross-link repair and replication stress. FANCL and UBE2T perform ubiquitin transfer; FANCF supplies an integral structural contribution. Nuclear and chromatin-associated complex pools support this role, while a smaller cytosolic pool has a less clearly defined function. Defects in FANCF cause Fanconi anemia complementation group F and cellular hypersensitivity to DNA cross-linking agents.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006974 DNA damage response | IBA GO_REF:0000033 | ACCEPT | Summary: FANCF supports the FA damage-response machinery after cross-link damage and replication stress. Reason: The actual PANTHER v19 PTHR14449 tree and 374-residue target MSA place human PTN002494673 below PTN001426273, where the GO:0006974 IBD is grounded in mouse Fancf. The exact mouse E9Q5Z5/MGI:3689889 experimental annotation traces to PMID:21915857. Its accessible author dissertation chapter 5 directly tests Fancf-null MEFs: MMC causes chromosome breakage, G2 accumulation and reduced survival, and FANCD2 monoubiquitination is lost after either MMC or hydroxyurea (Figure 5.2D, printed dissertation page 84 / PDF page 85; HU 1 mM for 24 h; Methods and Results). Mouse and human FANCF also restore MMC resistance in human FA-F cells (Figure 5.1A). Retain DNA damage response because this measured activation response extends beyond the separately supported ICL-repair branch; it is not retained merely as a convenient parent term. FANCF organizes the core machinery rather than catalyzing ubiquitin transfer. The mouse tumor and gonadal phenotypes are not additional human process assertions. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001426273 SUPPORTS TRANSFER The actual v19 PTHR14449 target sequence and tree establish descent from this IBD node, with no target-path NOT. The GO:0006974 IBD cites mouse MGI:3689889; current experimental donor rows and the actual PMID:21915857 author chapter support the damage-response claim. The single donor is not a weakness; target self-WITH belongs to the separate complex-membership assertion, not this row. Supporting Evidence: PMID:17082180 At least eight FA proteins (FANCA, B, C, E, F, G, L, and M) form a nuclear core complex required for monoubiquitination of a downstream protein, FANCD2. PMID:21915857 they showed an aberrant response to DNA cross-linking agents as manifested by G(2) arrest, chromosomal aberrations, reduced survival, and an inability to monoubiquitinate FANCD2. |
| GO:0043240 Fanconi anaemia nuclear complex | IBA GO_REF:0000033 | ACCEPT | Summary: Verified ancestry and human target experiments support FA nuclear-complex membership. Reason: Human PTN002494673 is placed below PTN001426273 in the actual v19 PTHR14449 tree, with an exact 374-residue MSA match and no target-path NOT. The GO:0043240 IBD cites both mouse Fancf and human Q9NPI8; human self-WITH is legitimate experimental descendant evidence. PMID:11063725 demonstrates endogenous nuclear FANCF co-immunoprecipitation with FANCA, FANCC and FANCG in human lymphoblasts, and PMID:15262960 supplies controlled human assembly-mutant and three-hybrid experiments. Mouse PMID:21915857 functionally corroborates the conserved core role. These establish membership without assigning autonomous ligase activity, fixed complex stoichiometry or universal binary binding to FANCF. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001426273 SUPPORTS TRANSFER The actual v19 target path includes this experimentally grounded IBD node. Its mouse and human descendant sources support the complex claim; the target appearing in WITH is valid, not circular. Both current donor records and target-specific human nuclear-complex experiments were inspected. No path NOT or target-specific loss is established. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Retain the experimentally established nuclear compartment of human FANCF. Reason: The official UniProt SL-0191 mapping is to nucleus. Human PMID:11063725 directly demonstrates predominantly nuclear FANCF-GFP and endogenous nuclear FANCF in lymphoblast fractions, with marker controls and FA-F complementation of the tagged construct (Results and Figures 1–3, 6; construct and fractionation Methods). PMID:15262960 independently places human wild-type FANCF and the engineered N-terminal deletion in nuclear fractions (Figure 5B). These nuclear measurements do not restrict the protein to the chromosome-excluding nucleoplasm; the HPA and Reactome nucleoplasm records describe more specific source-scoped pools. Retain the encompassing nuclear claim without asserting exclusive nuclear residence, equal localization of engineered mutants, or an independently measured chromatin pool in these experiments. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus |
| GO:0036297 interstrand cross-link repair | IEA GO_REF:0000002 | ACCEPT | Summary: FANCF performs complex-assembly work required for interstrand cross-link repair. Reason: The actual IPR035428 family record matches human Q9NPI8 residues 1–362 and maps to GO:0036297 and GO:0043240. Human PMID:15262960 compares FANCF assembly mutants in FA-F cells: the N-terminal deletion remains nuclear but fails MMC complementation and weakens core contacts, while C-terminal variants have graded interaction and rescue effects (Figures 2–6; Experimental Procedures). Together with human FANCF rescue and nuclear complex recovery in PMID:11063725, this supports a performed assembly contribution to cross-link repair, not just a downstream disease phenotype. FANCL/UBE2T perform ubiquitin transfer and nucleases perform incisions; those activities are not transferred to FANCF. The inherited PMID:19965384 quotation concerns downstream ID2 and is preserved as pathway context, not relabeled as a human FANCF assay. Supporting Evidence: PMID:19965384 FANCI-FANCD2 is required for replication-coupled ICL repair in S phase. |
| GO:0043240 Fanconi anaemia nuclear complex | IEA GO_REF:0000120 | ACCEPT | Summary: The combined electronic methods correctly identify FANCF as an FA nuclear-complex component. Reason: The current combined source preserves ARBA00086467 and IPR035428. The exact InterPro family hit and GO mapping directly support complex membership. The actual ARBA rule requires Eukaryota and CATH FunFam 1.25.40.490:FF:000001; the independently saved InterPro CATH hit verifies the enclosing superfamily, not this exact FunFam condition, so that branch is not claimed to have been fully re-executed. Human nuclear complex recovery and assembly-mutant evidence in PMID:11063725 and PMID:15262960 independently establish the biological annotation. Retain membership without inferring enzymatic activity or treating overlapping source methods as independent experiments. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG. |
| GO:0005515 protein binding | IPI PMID:11063725 The Fanconi anemia protein FANCF forms a nuclear complex wit... | MODIFY | Summary: The FANCF–FANCG context supports FANCF as an integral scaffold of the repair core complex. Reason: FANCG (UniProtKB:O15287): PMID:11063725 demonstrates endogenous human FANCF co-immunoprecipitation with FANCG in lymphoblasts and restoration of FANCA–FANCG association after FANCF complementation. Its pairwise reticulocyte-translation experiments did not recover FANCF–FANCG binding under those conditions; they are not silently converted into positive binary binding. Independent human FANCF mutagenesis in PMID:15262960 resolves the structural function: C-terminal changes weaken FANCG interaction and stable FANCA-containing assembly, whereas the N-terminal 1–15 deletion prevents association with the FANCC/FANCE subcomplex and fails to restore MMC resistance despite nuclear localization. Some C-terminal deletions retain functional rescue despite weak co-immunoprecipitation, so a particular stable band is not treated as an absolute functional requirement. Current GO:0030674 explicitly directs integral complex scaffolds to GO:0140378. The latter captures FANCF holding the complex together; no ubiquitin-transfer chemistry or direct ligase–substrate-adaptor positioning is assigned. Proposed replacements: protein complex scaffold activity Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus, where it complexes with FANCA, FANCC and FANCG. PMID:17082180 The human FANCF protein reportedly functions as a molecular adaptor within the FA nuclear complex, bridging between the subcomplexes A:G and C:E. PMID:15262960 Our data demonstrate that FANCF acts as a flexible adaptor protein that plays a key role in the proper assembly of the FA core complex. |
| GO:0005515 protein binding | IPI PMID:12649160 Fanconi anemia protein complex: mapping protein interactions... | MODIFY | Summary: The FANCF–FANCG context supports FANCF as an integral scaffold of the repair core complex. Reason: FANCG (UniProtKB:O15287): The verified PMID:12649160 abstract explicitly reports yeast two-hybrid mapping between FANCG and the FANCF C-terminal region, including loss of interaction with FANCG Leu71Pro. Complete operative text was not recovered; no additional Methods or construct details are inferred from it. The replacement is a cross-source functional synthesis, independently grounded by the complete human FANCF experiments in PMID:15262960 rather than a claim that the inaccessible paper alone demonstrated every scaffold requirement. Independent human FANCF mutagenesis in PMID:15262960 resolves the structural function: C-terminal changes weaken FANCG interaction and stable FANCA-containing assembly, whereas the N-terminal 1–15 deletion prevents association with the FANCC/FANCE subcomplex and fails to restore MMC resistance despite nuclear localization. Some C-terminal deletions retain functional rescue despite weak co-immunoprecipitation, so a particular stable band is not treated as an absolute functional requirement. Current GO:0030674 explicitly directs integral complex scaffolds to GO:0140378. The latter captures FANCF holding the complex together; no ubiquitin-transfer chemistry or direct ligase–substrate-adaptor positioning is assigned. Proposed replacements: protein complex scaffold activity Supporting Evidence: PMID:12649160 FANCG was shown to interact with both the amino-terminus of FANCA and the carboxyl-terminal region of FANCF. PMID:12649160 FANCG was able to mediate interaction between FANCA and FANCF |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: The literal TCP11 isoform-7/FANCF HuRI interaction is supported as a screened binary association. Reason: The official HuRI dataset contains the exact Q8WWU5-7/Q9NPI8 pair, human ORFeome clones 100080789/55485, with N-terminal Gal4 fusion configuration and screen 1. Array, pooling and validated-two-hybrid records describe stages of the same pipeline rather than three independent physiological experiments. Main text reports quadruplicate retesting and sequence confirmation; study-wide MAPPIT/GPCA benchmarks are not individual validation of this pair. The literal TCP11 isoform identifier is preserved, without assuming all TCP11 products behave alike. A search for TCP11-specific binding and assessment of partner-class alternatives did not establish a more informative supported FANCF activity in this assay. Retain the positive association as non-core under the project’s supported-binding policy, without assigning a sperm, repair or scaffold role to this pair. Supporting Evidence: PMID:32296183 Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: The FANCF–HTT screen interaction is supported but does not establish a core FANCF function. Reason: NeuroNet Table S2 contains FANCF/HTT in NN1.0 (row 4403) and NN1.0ext (row 9678). The matching IntAct records identify human HTT residues 1–546, including mutation annotations at residues 18–38, tested with FANCF in yeast; this is not evidence for all native full-length huntingtin states. The read STAR Methods describe reporter autoactivation controls and growth/beta-galactosidase selection. No target-specific orthogonal mammalian validation or physiological FANCF–HTT mechanism was established by the inspected tables. Searches and partner-role assessment did not justify a huntingtin-specific binding term, enzyme-binding claim, or structural-scaffold activity for this fragment interaction. Retain the supported generic association as non-core. Supporting Evidence: PMID:32814053 systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Supported HPA images identify a nucleoplasmic FANCF pool. Reason: The current official Human Protein Atlas FANCF record reports supported nucleoplasm localization with HPA008899 in SH-SY5Y cells. Its 130-residue antigen matches displayed Q9NPI8 residues 231–360 exactly. Both linked merged images were inspected and show green signal within nuclear interiors. This supports the source localization, without quantitative colocalization, exclusive residence, a DNA-damage-focus assignment or transcript-model-specific localization. The inherited PMID:11063725 quotation is independent nuclear evidence, not an HPA image measurement. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus |
| GO:0000785 chromatin | IDA PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr... | ACCEPT | Summary: FANCF belongs to the FA core complex whose chromatin-associated pool is supported by this study. Reason: Retain the ComplexPortal-curated chromatin annotation as complex-level localization. The human HeLa nuclear complex purified in PMID:22343915 contains an explicitly identified FANCF band in Figure 1A/B, while Figure 5H and its accompanying Results show chromatin loading of FANCA/FANCG with FAAP20. These complementary observations support localization of FANCF as a constituent of the assembled repair complex. Figure 5H is not a separate FANCF immunoblot, and neither the main figure nor supplemental Figure S1 establishes isolated FANCF DNA binding. Lack of that individual measurement is not contrary localization evidence and does not justify rejecting the curator-supported complex projection. Supporting Evidence: PMID:22343915 is required for DNA-damage-induced chromatin loading of FANCA and the functional integrity of the FA pathway |
| GO:0036297 interstrand cross-link repair | NAS PMID:19965384 The Fanconi anemia pathway promotes replication-dependent DN... | ACCEPT | Summary: FANCF contributes to interstrand cross-link repair through its structural role in the FA core complex. Reason: The cited PMID:19965384 performs depletion and recombinant add-back of Xenopus FANCI–FANCD2 during repair of a plasmid cisplatin interstrand cross-link. It provides pathway-level mechanistic support, not an isolated human FANCF reaction. Independent human FANCF complementation in PMID:11063725 and domain/mutant assembly experiments in PMID:15262960 connect FANCF’s performed structural contribution to a functioning repair complex and MMC resistance. This supports the NAS ICL-repair annotation without assigning incision, DNA synthesis or ubiquitin-transfer catalysis to FANCF. Supporting Evidence: PMID:19965384 The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair. |
| GO:0043240 Fanconi anaemia nuclear complex | NAS PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr... | ACCEPT | Summary: FANCF is positively identified in the human FA nuclear core complex. Reason: PMID:22343915 reports two-step purification of the core from engineered HeLaS3 nuclear extracts, and Figure 1A/B explicitly labels FANCF among the identified polypeptides. This is sufficient positive support for the curated complex-membership assertion. The study chiefly analyzes FAAP20 and FANCA; membership does not assign FAAP20 ubiquitin recognition, FANCL catalysis or an isolated FANCF chromatin assay to FANCF. Supporting Evidence: PMID:22343915 Fanconi anemia (FA) nuclear core complex is a multiprotein complex |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835411 | KEEP AS NON CORE | Summary: Retain the modeled cytosolic FANCF pool as a contextual location. Reason: Reactome R-HSA-9835411 has input and output routes through FA-core:HSP70 assemblies to FANCF entity 420794, Q9NPI8 residues 1–374, with its own GO:0005829 compartment. The positive model should not be discarded because FANCF is predominantly nuclear. Its summation emphasizes FANCC binding to PKR and FANCA/FANCC/FANCG phenotypes, not a FANCF-specific PKR mechanism. Human fractionation in PMID:11063725 and PMID:15262960 detects smaller cytoplasmic FANCF signals, but the 2000 paper explicitly allows diffusion or cross-contamination and does not quantify a native cytosolic pool. Retain this non-core modeled context without calling it inactive or artifactual and without claiming direct FANCF-mediated PKR inhibition. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus Reactome:R-HSA-9835411 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785126 | ACCEPT | Summary: Reactome places the FANCF-containing repair assembly in nucleoplasm during FA core assembly. Reason: Reactome:R-HSA-6785126 was traced through its actual participant links to human FANCF entity 419537, Q9NPI8 residues 1–374, whose own compartment is GO:0005654. FANCF is a direct input and a component of the assembled output; the event separates nucleoplasmic assembly from FANCM/FAAP24-dependent DNA loading. Human nuclear co-association and complementation in PMID:11063725 and the assembly-mutant experiments in PMID:15262960 corroborate the nuclear core context. Retain this modeled participant location; related pathway records are not independent imaging experiments, and whole-complex participation does not prove every reaction-specific activity for FANCF. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus Reactome:R-HSA-6785126 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785342 | ACCEPT | Summary: Reactome places the FANCF-containing repair assembly in nucleoplasm during ID2 and UBE2T recruitment. Reason: Reactome:R-HSA-6785342 was traced through its actual participant links to human FANCF entity 419537, Q9NPI8 residues 1–374, whose own compartment is GO:0005654. FANCF remains in the core-containing input and output. FANCL-dependent recruitment of UBE2T is not autonomous FANCF ubiquitin-transfer activity. Human nuclear co-association and complementation in PMID:11063725 and the assembly-mutant experiments in PMID:15262960 corroborate the nuclear core context. Retain this modeled participant location; related pathway records are not independent imaging experiments, and whole-complex participation does not prove every reaction-specific activity for FANCF. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus Reactome:R-HSA-6785342 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785361 | ACCEPT | Summary: Reactome places the FANCF-containing repair assembly in nucleoplasm during ID2 monoubiquitination. Reason: Reactome:R-HSA-6785361 was traced through its actual participant links to human FANCF entity 419537, Q9NPI8 residues 1–374, whose own compartment is GO:0005654. FANCF occurs in input, output and a composite catalyst assembly. UBE2T and FANCL perform ubiquitin transfer; FANCF contributes complex organization. Human nuclear co-association and complementation in PMID:11063725 and the assembly-mutant experiments in PMID:15262960 corroborate the nuclear core context. Retain this modeled participant location; related pathway records are not independent imaging experiments, and whole-complex participation does not prove every reaction-specific activity for FANCF. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus Reactome:R-HSA-6785361 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785732 | ACCEPT | Summary: Reactome places the FANCF-containing repair assembly in nucleoplasm during nuclease recruitment. Reason: Reactome:R-HSA-6785732 was traced through its actual participant links to human FANCF entity 419537, Q9NPI8 residues 1–374, whose own compartment is GO:0005654. FANCF persists in core-containing input and output. The recruited FAN1 and SLX4-associated nucleases are distinct proteins; their DNA cleavage is not assigned to FANCF. Human nuclear co-association and complementation in PMID:11063725 and the assembly-mutant experiments in PMID:15262960 corroborate the nuclear core context. Retain this modeled participant location; related pathway records are not independent imaging experiments, and whole-complex participation does not prove every reaction-specific activity for FANCF. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus Reactome:R-HSA-6785732 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785986 | ACCEPT | Summary: Reactome places the FANCF-containing repair assembly in nucleoplasm during ICL unhooking. Reason: Reactome:R-HSA-6785986 was traced through its actual participant links to human FANCF entity 419537, Q9NPI8 residues 1–374, whose own compartment is GO:0005654. FANCF occurs in input, output and the composite catalytic assembly. The named nucleases make the incisions; this location record does not make FANCF a nuclease. Human nuclear co-association and complementation in PMID:11063725 and the assembly-mutant experiments in PMID:15262960 corroborate the nuclear core context. Retain this modeled participant location; related pathway records are not independent imaging experiments, and whole-complex participation does not prove every reaction-specific activity for FANCF. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus Reactome:R-HSA-6785986 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786155 | ACCEPT | Summary: Reactome places the FANCF-containing repair assembly in nucleoplasm during POLN recruitment. Reason: Reactome:R-HSA-6786155 was traced through its actual participant links to human FANCF entity 419537, Q9NPI8 residues 1–374, whose own compartment is GO:0005654. FANCF occurs in core-containing input and output. POLN recruitment and polymerase chemistry are separate from the FANCF component location. Human nuclear co-association and complementation in PMID:11063725 and the assembly-mutant experiments in PMID:15262960 corroborate the nuclear core context. Retain this modeled participant location; related pathway records are not independent imaging experiments, and whole-complex participation does not prove every reaction-specific activity for FANCF. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus Reactome:R-HSA-6786155 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786166 | ACCEPT | Summary: Reactome places the FANCF-containing repair assembly in nucleoplasm during POLN translesion synthesis. Reason: Reactome:R-HSA-6786166 was traced through its actual participant links to human FANCF entity 419537, Q9NPI8 residues 1–374, whose own compartment is GO:0005654. FANCF occurs in the input, released core output and composite catalyst route. POLN performs synthesis; FANCF is not assigned polymerase activity. Human nuclear co-association and complementation in PMID:11063725 and the assembly-mutant experiments in PMID:15262960 corroborate the nuclear core context. Retain this modeled participant location; related pathway records are not independent imaging experiments, and whole-complex participation does not prove every reaction-specific activity for FANCF. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus Reactome:R-HSA-6786166 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786171 | ACCEPT | Summary: Reactome places the FANCF-containing repair assembly in nucleoplasm during FANCD2 deubiquitination. Reason: Reactome:R-HSA-6786171 was traced through its actual participant links to human FANCF entity 419537, Q9NPI8 residues 1–374, whose own compartment is GO:0005654. FANCF is present in the substrate and output complexes. USP1:WDR48 is the separate catalyst; this does not assign deubiquitinase activity to FANCF. Human nuclear co-association and complementation in PMID:11063725 and the assembly-mutant experiments in PMID:15262960 corroborate the nuclear core context. Retain this modeled participant location; related pathway records are not independent imaging experiments, and whole-complex participation does not prove every reaction-specific activity for FANCF. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus Reactome:R-HSA-6786171 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6788385 | ACCEPT | Summary: Reactome places the FANCF-containing repair assembly in nucleoplasm during ATR–ATRIP recruitment. Reason: Reactome:R-HSA-6788385 was traced through its actual participant links to human FANCF entity 419537, Q9NPI8 residues 1–374, whose own compartment is GO:0005654. FANCF remains in core-containing input and output. The summation names other protein contacts, including FANCL–ATRIP; no binary FANCF–ATRIP contact is inferred. Human nuclear co-association and complementation in PMID:11063725 and the assembly-mutant experiments in PMID:15262960 corroborate the nuclear core context. Retain this modeled participant location; related pathway records are not independent imaging experiments, and whole-complex participation does not prove every reaction-specific activity for FANCF. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus Reactome:R-HSA-6788385 |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6788392 | ACCEPT | Summary: Reactome places the FANCF-containing repair assembly in nucleoplasm during ATR-dependent phosphorylation. Reason: Reactome:R-HSA-6788392 was traced through its actual participant links to human FANCF entity 419537, Q9NPI8 residues 1–374, whose own compartment is GO:0005654. FANCF occurs in input, output and a composite catalyst assembly. ATR performs phosphorylation of named substrates; no FANCF kinase activity is inferred. Human nuclear co-association and complementation in PMID:11063725 and the assembly-mutant experiments in PMID:15262960 corroborate the nuclear core context. Retain this modeled participant location; related pathway records are not independent imaging experiments, and whole-complex participation does not prove every reaction-specific activity for FANCF. Supporting Evidence: PMID:11063725 FANCF was found predominantly in the nucleus Reactome:R-HSA-6788392 |
| GO:0043240 Fanconi anaemia nuclear complex | IDA PMID:20347428 A histone-fold complex and FANCM form a conserved DNA-remode... | ACCEPT | Summary: Human FANCF is a component of the nuclear FA core complex isolated in the FANCM–MHF study. Reason: PMID:20347428 Results explicitly identifies FANC-F among the core proteins recovered after gel filtration of HeLa nuclear extract and FANCM immunoprecipitation, followed by silver staining, mass spectrometry and immunoblot analysis (Figure 1 and the purification Methods). This supports complex membership, not transfer of FANCM or MHF DNA-remodeling chemistry to FANCF. Most cellular FANCM/MHF is outside the FA core according to the separate depletion experiments; the annotation concerns the demonstrated FANCF-containing complex and does not make every FANCM complex a FANCF complex. Supporting Evidence: PMID:20347428 FANCM-MHF associates with the Fanconi anemia (FA) core complex, promotes FANCD2 monoubiquitination in response to DNA damage |
| GO:0005515 protein binding | IPI PMID:11063725 The Fanconi anemia protein FANCF forms a nuclear complex wit... | MODIFY | Summary: The FANCF–FANCA context supports FANCF as an integral scaffold of the repair core complex. Reason: PMID:11063725 shows reciprocal endogenous FANCA/FANCF co-immunoprecipitation, nuclear complex localization and FANCF-dependent restoration of nuclear FANCA and FANCA–FANCG assembly. Pairwise reticulocyte translation did not recover the FANCF–FANCA interaction, so association within the assembled complex is distinguished from a resolved direct interface. Independent human FANCF mutagenesis in PMID:15262960 resolves the structural function: C-terminal changes weaken FANCG interaction and stable FANCA-containing assembly, whereas the N-terminal 1–15 deletion prevents association with the FANCC/FANCE subcomplex and fails to restore MMC resistance despite nuclear localization. Some C-terminal deletions retain functional rescue despite weak co-immunoprecipitation, so a particular stable band is not treated as an absolute functional requirement. Current GO:0030674 explicitly directs integral complex scaffolds to GO:0140378. The latter captures FANCF holding the complex together; no ubiquitin-transfer chemistry or direct ligase–substrate-adaptor positioning is assigned. Proposed replacements: protein complex scaffold activity |
| GO:0005515 protein binding | IPI PMID:12649160 Fanconi anemia protein complex: mapping protein interactions... | MODIFY | Summary: The FANCF–FANCA context is retained within FANCF’s supported complex-scaffold activity. Reason: The positive PMID:12649160 abstract describes FANCG-mediated FANCA–FANCF association in a three-hybrid system: FANCG is the demonstrated bridge in that particular assay. It does not show FANCF itself bridging FANCA directly, and its complete Methods remain inaccessible. Independent PMID:11063725 assembly rescue and PMID:15262960 FANCF-specific mutant experiments establish the broader FANCF structural contribution. Independent human FANCF mutagenesis in PMID:15262960 resolves the structural function: C-terminal changes weaken FANCG interaction and stable FANCA-containing assembly, whereas the N-terminal 1–15 deletion prevents association with the FANCC/FANCE subcomplex and fails to restore MMC resistance despite nuclear localization. Some C-terminal deletions retain functional rescue despite weak co-immunoprecipitation, so a particular stable band is not treated as an absolute functional requirement. Current GO:0030674 explicitly directs integral complex scaffolds to GO:0140378. The latter captures FANCF holding the complex together; no ubiquitin-transfer chemistry or direct ligase–substrate-adaptor positioning is assigned. Proposed replacements: protein complex scaffold activity |
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Download this section (compressed HTML)Q: Which FANCF contacts determine productive core-complex assembly in cells when some mutants retain cross-link resistance despite weak stable co-immunoprecipitation?
Q: Does endogenous cytosolic FANCF participate functionally in the modeled FA-core:HSP70:PKR assembly, and how is that pool distinguished from nuclear protein redistributed during fractionation?
Experiment: Compare matched human FANCF interface variants at near-endogenous expression in FA-F complementation cells, measuring nuclear localization, several core contacts, FANCD2/FANCI monoubiquitination and cross-link survival. Include wild-type, empty-vector and N-terminal loss-of-function controls and quantify protein abundance to distinguish weakened association from destabilization.
Hypothesis: Complementary FANCF interfaces support repair through assembly dynamics that are not fully captured by a single stable co-immunoprecipitation measurement.
Experiment: Combine endogenous tagging and orthogonal live-cell/proximity measurements with controlled nuclear/cytosolic fractionation before and after DNA damage. Test FANCF association with HSP70/PKR and corresponding signaling only after confirming the relevant compartment; compare depletion and expression-matched rescue without assigning a role from colocalization alone.
Hypothesis: A distinct cytosolic FANCF-containing complex can be resolved from fractionation-associated redistribution.
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