FANCI (Q9NVI1) review notes

Human Fanconi anemia group I protein. HGNC:25568. 1328 aa. Chromosome 15.

Core biology (synthesized)

FANCI is the obligate heterodimeric partner of FANCD2, forming the FANCI-FANCD2
(ID2) complex, the central effector of the Fanconi anemia (FA) DNA-repair pathway.
Both proteins are monoubiquitinated (FANCI on Lys523) by the FANCL/UBE2T ligase
acting downstream of the multi-subunit FA core complex. Monoubiquitination is
mutually interdependent, and FANCI is required to promote FANCD2 monoubiquitination.
The ID2 complex binds and scans dsDNA with preference for branched structures
(Holliday junctions, overhangs, replication forks); upon monoubiquitination it
rearranges into a closed sliding clamp that encircles duplex DNA to coordinate ICL
repair (nucleolytic incision/unhooking, translesion synthesis, homologous
recombination). FANCI phosphorylation by ATR (S/TQ cluster) acts as a molecular
switch turning the pathway on. Disease: Fanconi anemia complementation group I
(biallelic FANCI mutations).

Provenance

Localization caveats

MF gap

GOA export lacks a DNA-binding MF term for FANCI even though UniProt carries the
DNA-binding keyword and DNA binding is FANCI's defining biochemical activity
(branched/duplex DNA binding; clamp). Added GO:0003677 as NEW.

2026-10-25 — Integrated evidence, core and current source contexts

The current biological assessment distinguishes FANCI's DNA-binding and ID2 structural/regulatory contribution from FANCL/UBE2T ubiquitin-transfer chemistry. Human ID2 can close with ubiquitin on FANCD2 alone; the old shorthand that FANCI Lys523 ubiquitination always drives closure is not a universal prerequisite. The core retains DNA secondary-structure binding, with broader DNA repair supported independently by the human I-SceI HR-reporter experiments in PMID:17412408. The ICL descendant is not redundantly listed beside that broader process. Human phosphosite and purified chicken K525R/Ex6 experiments support performed promotion of FANCD2 monoubiquitination rather than merely substrate necessity. Chicken Ex6 is the DNA-binding-defective charge-reversal mutant; R1288Q alone retains DNA binding and is not equated to the reported human R1285Q behavior.

Four natural products remain distinct from historical 1328-residue “isoform 1,” fragments and engineered mutants. HPA supports a cytosolic pool without resolving every product or its function. The NK-cell membrane-fraction annotation remains UNDECIDED because its original target table and fraction controls were not recovered; possible carryover is not proven contamination.

The genuine current GOA now has 30 imported contexts, plus retained authored proposal 29: 31 stored objects. Eleven genuine supporting-entity backfills preserve the original source identities. Position 8 takes the seeder's FANCD2 representative, and the separate FAN1 context is appended at 30, leaving every inherited position and all 23 quotation associations intact. No new quotation fields or authored annotations were added. Current actions are 20 ACCEPT / 5 MODIFY / 4 KEEP_AS_NON_CORE / 1 UNDECIDED / 1 retained NEW. The old UniProt machine record remains exact; GOA adoption is explicit. Historical description/status and earlier journal assertions above remain historical, not simultaneous current conclusions.

Five whole reference unions retain the historical note once and both complete labeled current source-reading scopes. All selected publication availability flags were reconciled against immutable cache headers, separately from external availability and actual reading. See the consolidated FANCI evidence and source guide for primary Methods/Results/figure locators, the 25 Reactome target paths and three modification states, PAINT ancestry, and access limits. This entry is agent-authored; no provider output is synthesized.

2026-10-25 — Canonical validation

All six canonical checks pass, including current GOA matching, term/component validation and rendering of 68 narratives. Computed status is DRAFT with 4 advisories: 3 supported generic-binding advisories retained under the standing campaign instruction and one advisory for the unused inherited research file. Review all 30 current imported contexts and the retained inherited DNA-secondary-structure-binding proposal: 20 ACCEPT, five MODIFY, four KEEP_AS_NON_CORE, one UNDECIDED and one NEW. Retain four natural products without assuming functional equivalence. Keep the membrane-fraction claim UNDECIDED because target-level original evidence remains unavailable. Adopt genuine current GOA with eleven supporting-entity backfills and one appended FAN1 context; retain FANCD2 at old position 8. Preserve all 30 inherited positions, 23 quotation associations, 27 original reference identities and three original core quotation objects; add three supporting references. Existing UniProt, publication/Reactome/family caches, provider outputs, prior history, generated HTML and unrelated work remain exact. New publication files are genuine additive fetches; no new quotation field is authored.

2026-10-26 — PR 5548 feedback follow-up

Replace the core DNA-repair parent with the specific ICL-repair term; retain the accepted broad imported annotation and human HR-reporter evidence. The current biological description now includes nucleolar, RNA and FANCD2-independent functions with primary-source scope documented in the source guide. Product/reagent equivalence limits belong in these notes and that guide rather than in the standalone description. The four natural products remain unchanged and are not assumed functionally equivalent.

The earlier integration choice of the broad core process is superseded by this specific-core decision. Seven genuine additional primary caches support the bounded literature audit; the immutable Affinage file was used for discovery and is now explicitly referenced. No new process annotation is added. The separately reviewed human nucleolus IDA assertion is appended at position 31, leaving all earlier positions intact. The three supported generic-binding decisions and membrane UNDECIDED are retained. Shared Reactome provenance is consolidated in the source guide, and spacing artifacts in reviewer-authored reference notes are corrected. All 31 annotation positions, machine source fields and 23 inherited quotation paths/text/reference associations are preserved. No publication quotations were added.

Canonical validation of the accepted successor: All six canonical checks pass and all 70 narratives render. Computed status remains DRAFT with four advisories: three supported generic-binding records under the explicit project instruction and one annotation-level unused-research-file advisory. There are now 32 active objects: 30 imported contexts, the inherited DNA-binding proposal and the appended human nucleolus IDA proposal. All 23 inherited quotation/path/reference associations and four natural products remain unchanged. Nine reference entries are added, yielding 39; seven missing primary publications are genuine additive fetches. The Affinage file is used for discovery and cited at reference level, which does not suppress the annotation-level advisory. No new process annotation or publication quotation is authored.