FANCE

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0043240 Fanconi anaemia nuclear complex	IBA GO_REF:0000033	ACCEPT	Summary: Verified ancestral placement and human experiments support FANCE membership in the FA nuclear complex. Reason: The actual v19 PTHR32094 tree places the exact displayed Q9HB96 sequence at PTN002528904 below PTN001280497. Its GO:0043240 IBD cites the human target itself, correctly preserving experimental grounding rather than circularity. PMID:12093742 demonstrates endogenous nuclear FANCE, co-purification of FANCA/FANCF/FANCG and complement-group-dependent core association (Figures 1–2). These data support the defined complex membership. They do not make FANCE the FANCL/UBE2T catalytic machinery, establish a fixed stoichiometry in every cell, or demonstrate equivalent activity of every external transcript model. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN001280497 SUPPORTS TRANSFER The actual PANTHER v19 PTHR32094 tree and exact 536-residue target MSA place human PTN002528904 beneath this IBD node. The one target-path IBD for GO:0043240 is experimentally grounded in human Q9HB96, and no NOT occurs on that path. Self-WITH is legitimate descendant evidence. Human nuclear immunopurification in PMID:12093742 corroborates the complex membership. Supporting Evidence: PMID:12093742 FANCE protein is part of this nuclear complex, binding both FANCC and FANCD2 PMID:17296736 form a core enzyme complex, required for the monoubiquitination of FANCD2
GO:0005634 nucleus	IEA GO_REF:0000044	ACCEPT	Summary: Retain the encompassing nuclear location of human FANCE. Reason: The current UniProt Q9HB96 location and official SL-0191 mapping support GO:0005634. PMID:12093742 demonstrates endogenous and tagged FANCE in HeLa nuclear foci and nuclear-core immunoprecipitates (Results and Figures 1–2; expression, antibody and microscopy Methods). Current Human Protein Atlas data independently identify nucleoplasm with two antibodies and also report a mitotic-chromosome pool. Because nucleoplasm excludes chromosomes, substituting it for every nuclear assertion would lose that breadth. Retain nucleus alongside the more specific source-scoped nucleoplasm records, without asserting exclusive nuclear residence or identity of all transcript-derived protein models. Supporting Evidence: PMID:12093742 FANCE protein is part of this nuclear complex, binding both FANCC and FANCD2
GO:0036297 interstrand cross-link repair	IEA GO_REF:0000002	ACCEPT	Summary: FANCE participates in interstrand cross-link repair through the FA core and FANCD2 recruitment. Reason: The actual InterPro IPR039685 family record matches Q9HB96 and maps to GO:0036297 and GO:0043240. Human PMID:24451376 supplies target-specific functional grounding: full-length FANCE and engineered C-terminal/Phe522 variants were compared in FA-E cells; variants that lose FANCD2 recruitment fail to restore ID2 monoubiquitination, mitomycin-C resistance and chromosome protection despite retaining measured core associations (Figures 1–3; Experimental Procedures). FANCE therefore performs recruitment/assembly work used by repair, rather than being merely a processed substrate. This does not assign ubiquitin-transfer or incision chemistry to FANCE. The inherited PMID:19965384 quote concerns downstream ID2 in Xenopus and is retained as contextual evidence, not relabeled as a direct human FANCE assay. Supporting Evidence: PMID:19965384 FANCI-FANCD2 is required for replication-coupled ICL repair in S phase PMID:17296736 form a core enzyme complex, required for the monoubiquitination of FANCD2
GO:0043240 Fanconi anaemia nuclear complex	IEA GO_REF:0000002	ACCEPT	Summary: The FANCE family mapping correctly identifies FA nuclear-complex membership. Reason: The current IPR039685 target match and official InterPro-to-GO mapping explicitly assign GO:0043240. Human FANCE nuclear immunoprecipitation and interaction experiments independently establish the membership (PMID:12093742, Figures 1–2 and Methods). Retain this structural component claim without importing partner enzyme activities or treating the family mapping alone as a direct binding assay. Supporting Evidence: PMID:12093742 FANCE protein is part of this nuclear complex, binding both FANCC and FANCD2
GO:0005515 protein binding	IPI PMID:12649160 Fanconi anemia protein complex: mapping protein interactions...	KEEP AS NON CORE	Summary: Retain the FANCC interaction with explicit historical-source and independent-assay boundaries. Reason: The PMID:12649160 abstract positively reports mapping of the FANCC–FANCE interaction and failure of FANCC L554P to bind FANCE; its complete operative original was not recovered. Independently inspected PMID:12093742 Results and Figure 4 describe mammalian two-hybrid and insect-cell coimmunoprecipitation of FANCE with wild-type FANCC, with disease-associated FANCC mutants impaired. Actual PMID:33961781 BioPlex tables also recover FANCE with FANCC bait in HCT116 cells. These support the association without retrospectively verifying the old assay details. The FANCC-facing interaction alone does not establish the separately assessed FANCD2 substrate-recruitment activity, a transport mechanism, or autonomous FANCE scaffold activity. Retain supported generic binding as non-core under the campaign exception. Supporting Evidence: PMID:12649160 A central region of FANCE was sufficient for FANCC binding
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: BioPlex records FANCC bait recovering FANCE in human HCT116 cells. Reason: The actual BioPlex HCT116 network contains Q00597/FANCC–Q9HB96/FANCE at line 32947; its directed-edge table identifies FANCC bait and FANCE prey at line 38136. The two separately inspected 293T release tables do not contain this pair, which is not evidence of biological nonbinding. PMID:33961781 Methods describe tagged human ORFeome constructs, anti-HA affinity purification and mass spectrometry. This supports cellular coassociation rather than a purified binary interface, reciprocal recovery or exact equivalence of all current protein models. No more informative molecular role follows from this pair alone; the supported interaction is retained as non-core under the campaign exception. Supporting Evidence: PMID:33961781
GO:0005515 protein binding	IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei...	MODIFY	Summary: Refine the directly observed AKT1 association to protein kinase B binding. Reason: PMID:35512704 Data S1, Figure iiiA, displays FLAG-tagged FANCE recovered with GST-AKT1 wild type and the E17K mutant in transfected HEK293T cells. The FANCE panel was visually inspected; the mutant band is stronger, without new densitometry. Table S3B row 22 separately records positive AKT1-E17K/FANCE GST pull-down in HEK293T and NanoPCA in MCF7, with semi-endogenous IP and endogenous co-IP marked N/A. The main Methods describe tagged proximity, complementation and lysate pull-down assays. GO:0043422 precisely names binding to protein kinase B/AKT without assigning FANCE kinase activity, kinase regulation, phosphorylation-substrate status or a demonstrated endogenous repair mechanism. The unreadable Table S2 download remains an explicit source limitation. Proposed replacements: protein kinase B binding Supporting Evidence: PMID:35512704
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: Human Protein Atlas evidence supports nucleoplasmic FANCE. Reason: The current official HPA FANCE XML and subcellular page retain supported nucleoplasm localization with HPA013343 in HEL, THP-1 and U2OS cells and CAB014893 in A-431, U-251MG and U2OS cells. The inspected HEL and A-431 merged images show green signal within nuclear interiors, with dark nucleolar regions most evident in A-431; the THP-1 image and record also include mitotic cells. HPA013343 antigen matches displayed Q9HB96 residues 112–252 exactly; CAB014893 antigen sequence is not supplied. These are localization observations, not a product-specific functional assay, direct quantification or proof of a particular damage-site complex. The inherited PMID:12093742 quotation remains separate corroborating nuclear evidence, not an HPA measurement. Supporting Evidence: PMID:12093742 FANCE protein is part of this nuclear complex, binding both FANCC and FANCD2
GO:0000785 chromatin	IDA PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr...	ACCEPT	Summary: FANCE associates with chromatin as a constituent of the Fanconi anaemia core complex. Reason: PMID:22343915 identifies FANCE in affinity-purified human HeLaS3 nuclear core material (main Figure 1A/B) and measures DNA-damage-induced chromatin association of core components (Figure 5H). The latter panel measures FANCA, FANCG, FAAP20 and H2A, and supplemental Figure S1C does not display FANCE; neither panel is claimed as an isolated FANCE chromatin-fraction readout. Accept the curator's component-level localization of FANCE within this chromatin-associated repair complex. Independent human nuclear-core and FANCD2-recruitment experiments in PMID:12093742 and PMID:24451376 corroborate its membership and functional role in that machinery, without themselves being direct FANCE chromatin-fraction measurements. The absence of a separately labeled FANCE band is insufficient to reject this legitimate complex-level projection. This does not imply that every nuclear FANCE pool is chromatin-bound or equate nucleoplasm with chromatin. Supporting Evidence: PMID:22343915 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: FANCE participates in interstrand cross-link repair through substrate recruitment by the FA core machinery. Reason: The imported assertion is NAS. PMID:19965384 directly tests replication-coupled repair of a defined cisplatin ICL in Xenopus extracts using FANCI/FANCD2 depletion and reconstitution; it is pathway context rather than a human FANCE-specific assay. Independently inspected human FANCE experiments in PMID:12093742 establish core membership and FANCD2 binding, and PMID:24451376 tests FANCE complementation, C-terminal mutations, FANCD2/FANCI monoubiquitination, cross-linker sensitivity and chromosome aberrations. The substrate-recognition contribution supports FANCE participation in the repair pathway; incision, DNA synthesis and FANCL/UBE2T ubiquitin-transfer chemistry are not reassigned to FANCE. Supporting Evidence: PMID:19965384 FANCI-FANCD2 is required for replication-coupled ICL repair in S phase
GO:0043240 Fanconi anaemia nuclear complex	NAS PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr...	ACCEPT	Summary: FANCE is identified in purified human nuclear FA core material. Reason: PMID:22343915 Methods and Figure 1A/B describe two-step affinity purification from HeLaS3 nuclear extracts and label FANCE among the mass-spectrometry-identified core polypeptides. The actual Figure 1 pixels were inspected. The authentic supplement identifies the FANCE expression construct and distinguishes nuclear-extract purification from chromatin fractionation. Retain the imported NAS context and core membership, without promoting it to an independently resolved FANCE chromatin assay or an autonomous ubiquitin-ligase activity. Supporting Evidence: PMID:22343915 FAAP20 is an integral component of the FA nuclear core complex
GO:0005829 cytosol	TAS Reactome:R-HSA-9835411	KEEP AS NON CORE	Summary: Retain the explicitly modeled cytosolic FANCE pool as a contextual location. Reason: Reactome R-HSA-9835411 has input and output paths through the cytosolic FA-core:HSP70 complex to FANCE entity 420786, Q9HB96 residues 1–536, with its own GO:0005829 compartment. This is a positive target-specific source assertion. The event summation emphasizes FANCC binding to PKR and FANCA/FANCC/FANCG cellular phenotypes; it is not an independently inspected FANCE-specific PKR assay. Retain this non-core modeled pool without calling it an artifact or inactive protein, and without converting whole-complex membership into FANCE-mediated PKR inhibition. The directly characterized nuclear repair role remains distinct.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6785126	ACCEPT	Summary: Reactome places the FANCE-containing repair assembly in nucleoplasm during FA core assembly. Reason: Reactome:R-HSA-6785126 was independently traced through actual participant links to human FANCE entity 419543, Q9HB96 residues 1–536, whose own compartment is GO:0005654. FANCE is a direct input and a member of the assembled output. The event distinguishes nucleoplasmic assembly from FANCM/FAAP24-dependent DNA loading. Human nuclear localization and core association are corroborated by PMID:12093742, Figures 1–2. Retain this source-specific modeled pool; ten related pathway records are not ten independent imaging experiments, and their shared location does not establish every reaction-specific activity for FANCE.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6785342	ACCEPT	Summary: Reactome places the FANCE-containing repair assembly in nucleoplasm during ID2 and UBE2T recruitment. Reason: Reactome:R-HSA-6785342 was independently traced through actual participant links to human FANCE entity 419543, Q9HB96 residues 1–536, whose own compartment is GO:0005654. FANCE remains within the input and output core complexes. The event describes FANCL-dependent E2 recruitment; independent human FANCE–FANCD2 binding and recruitment experiments support FANCE participation without making it UBE2T. Human nuclear localization and core association are corroborated by PMID:12093742, Figures 1–2. Retain this source-specific modeled pool; ten related pathway records are not ten independent imaging experiments, and their shared location does not establish every reaction-specific activity for FANCE.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6785361	ACCEPT	Summary: Reactome places the FANCE-containing repair assembly in nucleoplasm during ID2 monoubiquitination. Reason: Reactome:R-HSA-6785361 was independently traced through actual participant links to human FANCE entity 419543, Q9HB96 residues 1–536, whose own compartment is GO:0005654. FANCE is present in input, output and a composite catalyst assembly. The event assigns ubiquitin-transfer chemistry to UBE2T and FANCL; membership does not establish autonomous FANCE ligase activity. Human nuclear localization and core association are corroborated by PMID:12093742, Figures 1–2. Retain this source-specific modeled pool; ten related pathway records are not ten independent imaging experiments, and their shared location does not establish every reaction-specific activity for FANCE.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6785732	ACCEPT	Summary: Reactome places the FANCE-containing repair assembly in nucleoplasm during nuclease recruitment. Reason: Reactome:R-HSA-6785732 was independently traced through actual participant links to human FANCE entity 419543, Q9HB96 residues 1–536, whose own compartment is GO:0005654. FANCE persists in core-containing input and output complexes. FAN1 and the SLX4-associated nucleases are separate proteins; their binding and cleavage activities are not assigned to FANCE. Human nuclear localization and core association are corroborated by PMID:12093742, Figures 1–2. Retain this source-specific modeled pool; ten related pathway records are not ten independent imaging experiments, and their shared location does not establish every reaction-specific activity for FANCE.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6785986	ACCEPT	Summary: Reactome places the FANCE-containing repair assembly in nucleoplasm during ICL unhooking. Reason: Reactome:R-HSA-6785986 was independently traced through actual participant links to human FANCE entity 419543, Q9HB96 residues 1–536, whose own compartment is GO:0005654. FANCE is present in input, output and the composite catalytic assembly. The named nucleases perform incisions; the location assertion does not mean FANCE cuts DNA. Human nuclear localization and core association are corroborated by PMID:12093742, Figures 1–2. Retain this source-specific modeled pool; ten related pathway records are not ten independent imaging experiments, and their shared location does not establish every reaction-specific activity for FANCE.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6786155	ACCEPT	Summary: Reactome places the FANCE-containing repair assembly in nucleoplasm during POLN recruitment. Reason: Reactome:R-HSA-6786155 was independently traced through actual participant links to human FANCE entity 419543, Q9HB96 residues 1–536, whose own compartment is GO:0005654. FANCE is within core-containing input and output complexes. POLN recruitment and polymerase activity are distinct from the FANCE component location. Human nuclear localization and core association are corroborated by PMID:12093742, Figures 1–2. Retain this source-specific modeled pool; ten related pathway records are not ten independent imaging experiments, and their shared location does not establish every reaction-specific activity for FANCE.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6786166	ACCEPT	Summary: Reactome places the FANCE-containing repair assembly in nucleoplasm during POLN translesion synthesis. Reason: Reactome:R-HSA-6786166 was independently traced through actual participant links to human FANCE entity 419543, Q9HB96 residues 1–536, whose own compartment is GO:0005654. FANCE is present in the input complex and a released core output; a composite catalyst route also contains it. POLN performs synthesis, so no FANCE DNA-polymerase activity follows. Human nuclear localization and core association are corroborated by PMID:12093742, Figures 1–2. Retain this source-specific modeled pool; ten related pathway records are not ten independent imaging experiments, and their shared location does not establish every reaction-specific activity for FANCE.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6786171	ACCEPT	Summary: Reactome places the FANCE-containing repair assembly in nucleoplasm during FANCD2 deubiquitination. Reason: Reactome:R-HSA-6786171 was independently traced through actual participant links to human FANCE entity 419543, Q9HB96 residues 1–536, whose own compartment is GO:0005654. FANCE occurs in the substrate and output complexes. USP1:WDR48 is the separate catalyst; FANCE is not assigned deubiquitinase activity. Human nuclear localization and core association are corroborated by PMID:12093742, Figures 1–2. Retain this source-specific modeled pool; ten related pathway records are not ten independent imaging experiments, and their shared location does not establish every reaction-specific activity for FANCE.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6788385	ACCEPT	Summary: Reactome places the FANCE-containing repair assembly in nucleoplasm during ATR–ATRIP recruitment. Reason: Reactome:R-HSA-6788385 was independently traced through actual participant links to human FANCE entity 419543, Q9HB96 residues 1–536, whose own compartment is GO:0005654. FANCE remains in core-containing input and output complexes. The named recruitment contacts involve other proteins, including FANCL and ATRIP; no binary FANCE–ATRIP interaction is inferred. Human nuclear localization and core association are corroborated by PMID:12093742, Figures 1–2. Retain this source-specific modeled pool; ten related pathway records are not ten independent imaging experiments, and their shared location does not establish every reaction-specific activity for FANCE.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-6788392	ACCEPT	Summary: Reactome places the FANCE-containing repair assembly in nucleoplasm during ATR-dependent phosphorylation. Reason: Reactome:R-HSA-6788392 was independently traced through actual participant links to human FANCE entity 419543, Q9HB96 residues 1–536, whose own compartment is GO:0005654. FANCE occurs in input, output and the composite catalyst assembly. ATR performs phosphorylation and the named substrates are other proteins; no FANCE kinase activity follows. Human nuclear localization and core association are corroborated by PMID:12093742, Figures 1–2. Retain this source-specific modeled pool; ten related pathway records are not ten independent imaging experiments, and their shared location does not establish every reaction-specific activity for FANCE.
GO:0043240 Fanconi anaemia nuclear complex	IDA PMID:22266823 Regulation of Rev1 by the Fanconi anemia core complex.	ACCEPT	Summary: Human FANCE coassociates with the FAAP20-containing FA core complex. Reason: PMID:22266823 Results and Figure 2a explicitly identify FANCE, FANCC and FANCA in anti-FLAG immunoprecipitates of FLAG-FAAP20-expressing human 293T cells. Figure 2e separately assays FANCE levels after FAAP20 depletion and proteasome inhibition in HeLa cells. The in vitro translated direct-binding test in Figure 2b concerns FANCA–FAAP20, not FANCE–FAAP20. The positive cellular complex association supports this term without implying purified binary binding or transferring FAAP20 ubiquitin-binding activity. Supporting Evidence: PMID:22266823 with FANCA, FANCE, and FANCC, indicating that FAAP20 associates with the FA core complex
GO:0043240 Fanconi anaemia nuclear complex	IDA PMID:20347428 A histone-fold complex and FANCM form a conserved DNA-remode...	ACCEPT	Summary: FANCE is a constituent of the human nuclear FA core complex. Reason: PMID:20347428 Results explicitly identify FANC-E together with the other known core components in FANCM immunoprecipitates from fractionated human HeLa nuclear extract, using silver staining, mass spectrometry and immunoblotting (Figure 1B/C). The Methods describe gel filtration and complex identification. The same paper resolves a separate smaller FANCM–MHF complex, so its DNA binding and remodeling assays do not establish those activities for FANCE. Accept the demonstrated complex membership without transferring the enzymatic functions of other subunits. Supporting Evidence: PMID:20347428 FANCM-MHF associates with the Fanconi anemia (FA) core complex
GO:0005634 nucleus	NAS PMID:11001585 Isolation of a cDNA representing the Fanconi anemia compleme...	ACCEPT	Summary: Human FANCE is a nuclear protein. Reason: The original PMID:11001585 establishes the human 536-residue FANCE cDNA by rescue of MMC hypersensitivity in FA-E cells; its nuclear-location statement is based on predicted nuclear localization signals, not direct imaging. Independently inspected PMID:12093742 Results, Figure 1C and microscopy Methods directly detect endogenous FANCE and transfected FANCE–YFP in HeLa nuclear foci, with antibody controls. This supports the broad nucleus annotation while preserving its original NAS code and separating the two evidence levels. Nuclear foci are not equated with a distinct organelle or an exclusively chromatin-bound pool, and the engineered tags are not natural alternative products. Supporting Evidence: PMID:11001585 PMID:12093742
GO:1990756 ubiquitin-like ligase-substrate adaptor activity	IDA PMID:12093742 FANCE: the link between Fanconi anaemia complex assembly and...	NEW	Summary: Recognizes and recruits FANCD2 to the Fanconi anaemia core machinery. Reason: Human FANCE interaction experiments in PMID:12093742, particularly Results and Figure 6, establish FANCD2 recognition alongside association with the FA core. Independent human complementation and C-terminal mutant experiments in PMID:24451376, Figures 1–2, distinguish loss of substrate recognition and productive monoubiquitination from the measured core associations that remain. The authors qualify their assumption of retained intrinsic catalytic competence; additional mutant effects cannot be excluded. GO:1990756 names the supported ligase–substrate recruitment contribution. FANCL and UBE2T perform ubiquitin transfer. This refines the existing authored proposal in place, retaining its original PMID:12093742 attribution and all five inherited quotation associations. It does not add a second activity, a hold-together scaffold claim or a new process. The accepted official definition, typed ancestry, same-role comparator and GO-CAM checks support the specificity; no curator-omission argument is made. Supporting Evidence: PMID:12093742 provides a critical bridge between the FA complex and FANCD2 PMID:12093742 FANCE protein is part of this nuclear complex, binding both FANCC and FANCD2 PMID:12649160 Direct interaction between FANCE and FANCD2 was also demonstrated in the yeast 2-hybrid system PMID:16513431 FANCE is predominantly localized in the nucleus and acts as a molecular bridge between the FA core complex and FANCD2, through direct binding of both FANCC and FANCD2 PMID:16127171 FANCE is shown to be a key mediator of protein interactions both in the architecture of the FA protein complex and in the connection of complex components to the putative downstream targets of complex activity
GO:0034399 nuclear periphery	IEA GO_REF:0000107	REMOVE	Summary: Do not transfer a Fancd2 localization measurement to human FANCE. Reason: The exact current Ensembl-Compara donor B8JJD3/ENSMUSP00000110451 is mouse Fance, and its GO:0034399 IDA traces to PMID:27486799. The full original Methods, Table 1, Results subsection Fancd2 and Figure 8 were inspected, including Figure 8 pixels. The measured perinuclear protein is Fancd2; the authors explicitly report unsuccessful Fance immunohistology. GO:0034399 describes the nuclear-lumen region proximal to the inner membrane, so a Fance-dependent change in Fancd2 staining does not establish that Fance itself occupies that compartment. Remove this electronic transfer because its traced experimental grounding concerns another gene product, while retaining the literal source and a precise upstream query. This is not a claim that human FANCE is absent from the nuclear periphery, an inference from an abstract omission, or a challenge based merely on species or donor count.

Gene Description

Existing Annotations Review

Core Functions

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Affinage

📚 Additional Documentation

Notes

Source Guide

📄 View Raw YAML