Human Fanconi anemia group F protein. 374 aa, chromosome 11p14.3. HGNC:3587.
FANCF is a subunit of the Fanconi anemia (FA) nuclear core complex (FANCA, FANCB,
FANCC, FANCE, FANCF, FANCG, FANCL, FANCM + associated FAAP proteins). The core complex is
a multisubunit ubiquitin ligase (FANCL is the RING E3, UBE2T the E2) whose essential job is
monoubiquitination of the FANCD2-FANCI (ID2) complex in response to DNA damage
(especially interstrand cross-links, ICLs) and replication stress. Monoubiquitinated ID2 is
loaded onto chromatin and coordinates the downstream ICL-repair steps (nucleolytic
unhooking, translesion synthesis, homologous recombination).
FANCF itself has no catalytic activity and no recognizable sequence motif; its function is
structural — a flexible molecular adaptor/scaffold that bridges the FANCA:FANCG and
FANCC:FANCE subcomplexes and is required for assembly/stability of the intact core complex
and hence for FANCD2 monoubiquitination.
Biallelic FANCF loss → Fanconi anemia complementation group F (MIM:603467): bone marrow
failure, congenital malformations, cancer predisposition, cellular ICL hypersensitivity and
chromosomal instability [PMID:10615118, de Winter 2000 Nat Genet, FANCF cloning].
Human FANCF assembly and complementation evidence supports an integral protein-complex scaffold (GO:0140378), refining the historical adaptor terminology without assigning FANCL/UBE2T chemistry or FANCE substrate recognition to FANCF. The more specific ubiquitin ligase complex scaffold term requires an organization not established by these assays. The core keeps one ICL-repair process facet, with independently measured hydroxyurea response described as additional breadth. Nuclear location encompasses the nucleoplasmic and chromatin-associated complex pools; the smaller cytosolic pool remains contextual and does not establish a FANCF-specific PKR mechanism.
The final current source version has 27 imported contexts: 20 ACCEPT, four MODIFY and three KEEP_AS_NON_CORE decisions. All 25 inherited reviews and all 42 inherited quotation paths/texts/reference associations remain exact, including five core supporting objects. No authored NEW annotation or publication quotation is introduced. All 26 reference identities/findings remain; shared historical notes appear once with both current reading scopes labeled. Availability flags follow actual selected cache metadata and are separated from externally recovered originals and the passages/figures actually inspected.
The independently fetched GOA is adopted through genuine seeding: nine supporting-entity lists are backfilled exactly, and the two grouped binding records resolve into FANCA/FANCG partner contexts. The deterministic first match, FANCG, remains at each old position (5 and 6); FANCA contexts are appended at 25 and 26 with their accepted partner-specific reviews and bare reference IDs. Every inherited quote stays at its old index and association. The genuine refreshed GOA replaces its older machine source version; the inherited UniProt bytes remain exact. The inherited COMPLETE status here is historical and has not been recomputed.
See the FANCF source guide for public paper, figure, database and PAINT locators, assay species/construct limits, and the distinction between available originals and actual reading. The 374-residue displayed product has no UniProt ALTPROD record; engineered deletions are not natural splice products.
All six canonical checks pass, including term labels, ontology components, current source matching and rendering of all 60 narratives. Computed status is DRAFT with three advisories: two supported generic-binding screen associations retained as non-core under the standing campaign instruction, and the unused inherited Affinage file. The final 27 imported contexts have 20 ACCEPT, four MODIFY and three KEEP_AS_NON_CORE decisions, with no UNDECIDED or authored NEW entries. All 42 inherited quotation paths, 26 reference identities and one scaffold core are retained. The genuine refreshed GOA is adopted; existing UniProt and all normal sources remain unchanged. External original-paper access remains distinct from abstract-only cache metadata.
The 11 Reactome location contexts now cite their own event records, with direct FANCF participant links and complete representative routes in the source guide. The two ICL-repair rows explicitly cite FANCF-specific PMID:15262960 and PMID:17082180; FA-complex rows also expose the existing curated UniProt SUBUNIT provenance. Nuclear-localization text is not used as direct evidence for cytosol.
The independently inspected mouse HU result remains supported by the genuine Bakker author-dissertation chapter: Figure 5.2, printed page 84 / PDF page 85, with a compact provenance record and the complete dissertation linked in the guide. The measured output is FANCD2 monoubiquitination in Fancf-null versus wild-type MEFs, not FANCF ubiquitin-transfer chemistry. The abstract-only normal cache is unchanged.
FANCG-specific binding reasons no longer repeat the separate FANCA paragraphs; inherited quotations remain exactly where they were. PMID:21915857's former MEDIUM sentence is explicitly historical and superseded by the current HIGH assessment. PMID:17082180 is HIGH relevance because it directly addresses human FANCF, while its independently checked scope remains the original abstract rather than newly recovered full Methods or figures.
All 27 imported source objects, actions (20 ACCEPT, four MODIFY, three KEEP_AS_NON_CORE), 26 reference identities/findings, the core, product boundary and 42 quotation paths/text/reference associations are retained. No new quotation or annotation is added.
Canonical validation of this evidence-link successor passed all six checks and all 60 rendered narratives. DRAFT and the three existing advisories remain: two supported generic-binding screen associations and the unused inherited research file. The public page and provenance are additional evidence artifacts; normal sources and all inherited quotations remain exact.
