UniProt: Q9HB96 (FANCE_HUMAN), 536 aa, chromosome 6. HGNC:3586. Gene ID 2178.
FANCE is one of the eight subunits of the Fanconi anemia (FA) core complex
(FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, plus associated FAAP
proteins). The FA core complex is a nuclear multisubunit E3 ubiquitin ligase
(the catalytic RING subunit is FANCL) that monoubiquitinates the FANCD2–FANCI
(ID2) heterodimer in response to replication-blocking DNA interstrand crosslinks
(ICLs), triggering downstream ICL repair by nucleolytic incision, translesion
synthesis and homologous recombination.
FANCE's specific, distinguishing role within the core complex is that of a
molecular bridge/adaptor: it directly binds FANCC and directly binds the
substrate FANCD2, thereby physically linking the assembled core complex to its
downstream substrate. FANCE is also required for the nuclear accumulation of
FANCC.
PMID:12093742
- PMID:12093742
- PMID:12093742
- PMID:12093742
PMID:12649160
- PMID:12649160
- PMID:12649160
- UniProt FT REGION 150..371 "Interaction with FANCC" (ECO:0000269|PubMed:12649160).
PMID:17296736
- PMID:17296736
- PMID:17296736
- Chk1 directly phosphorylates FANCE at Thr346 and Ser374; the non-phosphorylatable FANCE(T346A/S374A) still supports FANCD2 monoubiquitination and foci but fails to complement MMC hypersensitivity → phosphorylation has a function independent of FANCD2-Ub. PMID:17296736
- UniProt: MOD_RES 346 Phosphothreonine by CHEK1; MOD_RES 374 Phosphoserine by CHEK1.
PMID:19965384
- PMID:19965384
- Note: this NAS annotation on FANCE is a pathway-level attribution (the paper itself studies FANCI-FANCD2 in Xenopus egg extracts; FANCE participates as a core-complex subprovider upstream of FANCD2 monoubiquitination).
protein binding (GO:0005515) annotations: kept as non-core (uninformative term, but valid interaction evidence). The AKT1 neo-PPI is non-core cancer-context.FANCE recognizes the FANCD2 substrate within the Fanconi anaemia core machinery. Human interaction and complementation studies distinguish this recognition contribution from FANCL/UBE2T ubiquitin transfer. C-terminal FANCE recognition mutants retain the core associations that were tested but lose productive FANCD2 monoubiquitination and cross-link resistance; the inference of unchanged intrinsic catalytic competence remains qualified (PMID:12093742; PMID:24451376). The single core now uses GO:1990756 ubiquitin-like ligase-substrate adaptor activity, with interstrand cross-link repair, nucleoplasm and FA nuclear-complex membership as its process, location and assembly context. This is a refinement of the inherited adaptor claim, not an additional activity or a transfer of FANCL chemistry.
The inherited proposed annotation at position 25 originally cites PMID:12093742; PMID:12649160 is supporting evidence. Its five quotations and all other inherited quotation text, positions and reference associations remain unchanged. The integrated historical candidate contains 26 objects: 25 imported source contexts and one inherited proposed-source object, now reviewed as MODIFY. Current decisions are 20 ACCEPT, 3 KEEP_AS_NON_CORE, 2 MODIFY and 1 UNDECIDED. The inherited COMPLETE status has not been recomputed here. Generic FANCC/BioPlex associations remain supported non-core contexts, AKT1 binding is partner-specific, and the imported chromatin IDA remains unresolved without an absence claim.
Positive nuclear evidence includes human experiments and HPA nucleoplasmic imaging. Nucleoplasm is not used to erase broader nuclear or chromosome-associated observations. Reactome also models a cytosolic FANCE pool in a PKR-associated assembly; this does not establish an autonomous FANCE PKR mechanism. The 536-residue displayed protein, engineered constructs and external transcript/protein models remain distinct, with no natural alternative-products field invented.
The extra current nuclear-periphery IEA is retained as a separate source proposal. Its traced mouse donor PMID:27486799 measures Fancd2 with an anti-FANCD2 antibody and explicitly reports unsuccessful Fance immunohistology. Removal of that electronic transfer and an upstream attribution CHECK are proposed; the CHECK is NOT_REPORTED. This is not a negative localization claim about FANCE. Adopting the fresh source version and appending the new context require an explicit subsequent source integration.
Both complete assessments for PMID:12093742 and PMID:24451376 are preserved under labeled reading scopes. Immutable cache availability flags are separate from external original access and the passages or images actually inspected. The FANCE evidence and source guide records public article, figure, table, database and phylogenetic locators, including assay and access limits. No new publication quotation or provider-generated research file was created.
The current genuine GOA source version supplies seven previously absent supporting-entity lists at inherited positions 0–6 and the additional nuclear-periphery context at position 26. These fields are copied from the actual deterministic seeder output; the old source identifiers, evidence, terms, ordering and review text are retained. The UniProt source remains unchanged. The current GOA TSV is adopted byte-for-byte, without manual editing.
The nuclear-periphery source at 26 carries the accepted REMOVE decision and NOT_REPORTED attribution CHECK: its mouse donor paper measured Fancd2, not Fance. This does not assert FANCE absence or a NOT localization. The retired broad-adaptor proposal at 25 keeps its MODIFY recommendation and every original quotation. A specific GO:1990756 substrate-adaptor proposal at 27 uses bare PMID:12093742 and PMID:24451376 support and adds no quotation. This records the already-supported substrate-recognition specificity while avoiding two active broad/specific proposals for the same activity; FANCE remains distinct from FANCL/UBE2T ubiquitin-transfer chemistry.
There are now 28 total objects and 27 non-retired objects: 26 imported source contexts plus one active specific authored proposal, with the earlier broad proposal retained as retired history. Non-retired decisions are 20 ACCEPT, 3 KEEP_AS_NON_CORE, 1 MODIFY, 1 UNDECIDED, 1 REMOVE and 1 NEW. The retired object retains MODIFY. All 23 inherited quotation paths and reference associations, the 31 reference objects, core, biological description and inherited status remain unchanged. The earlier 26-object tally describes the preceding handoff, not this adopted source version. No new quotation or upstream report was added.
The specific GO:1990756 ubiquitin-like ligase-substrate adaptor proposal now occupies the original authored position 25 with action NEW. Its original PMID:12093742 attribution and all five quotation paths are retained. The earlier broad GO:0030674 term was an authored proposal, not an imported GOA assertion. The retired/MODIFY representation and the duplicate last proposal at 27 are therefore removed; the preceding journal entries remain a record of that superseded representation. The genuine imported nuclear-periphery context at 26 remains present and reviewed as REMOVE. No imported source object is altered.
The chromatin context at 8 is ACCEPT: human FANCE is identified in the FA nuclear core and the core has a chromatin-associated pool. The curator's component-level projection is retained while keeping the precise figure caveat: PMID:22343915 Figure 5H measures FANCA/FANCG/FAAP20/H2A, not a separately labeled FANCE band. This does not make every FANCE nuclear pool chromatin-bound or change the core's nucleoplasm location.
The standalone description restores CHEK1 phosphorylation of FANCE Thr346/Ser374 after checking the actual original Methods, Results, Figures 1–2 captions and Table 1 of PMID:17296736. Human full-length FANCE TS/AA complementation retains basal FANCD2 monoubiquitination and foci but fails normal damage-induced upregulation and mitomycin C resistance. Purified recombinant Chk1 phosphorylates bacterial human-FANCE preparations containing these sites. The detailed downstream role remains unresolved; no kinase activity or new process annotation is assigned to FANCE. The source guide records exact access and construct limits.
There are now 27 objects, all non-retired: 26 imported source contexts and one authored NEW proposal. Decisions are 21 ACCEPT, 3 KEEP_AS_NON_CORE, 1 MODIFY, 1 REMOVE and 1 NEW. All 23 inherited quotation text/reference/path associations, 31 complete reference objects, natural-product boundary, core and questions/experiments remain unchanged. The AKT1-specific binding refinement remains a contextual interaction outside the cross-link-repair core and does not establish an endogenous AKT1 repair mechanism. The MGI attribution query remains CHECK and NOT_REPORTED; a demonstrated mismatch in the inspected source does not authorize silently changing the upstream record.
The prior canonical DRAFT status reflected three advisories: supported generic-binding retentions at positions 4 and 5 and a present but uncited generated deep-research file. These are not inferred biological failures or caused by the chromatin UNDECIDED action. They are documented rather than used to manufacture quotations, duplicate cores or unsupported annotations. Canonical validation will recompute the status after this revision. No new publication quotations are added under the standing campaign instruction.