FANCI is a DNA-binding component of the FANCI–FANCD2 (ID2) repair complex. Purified human FANCI binds DNA, and ubiquitination changes the architecture and substrate preference of human ID2. FANCI also promotes FANCD2 monoubiquitination through a regulatory and structural contribution. FANCL and UBE2T perform ubiquitin transfer; FAN1 and POLN supply nuclease and polymerase activities, respectively.
PMID:19589784(https://pmc.ncbi.nlm.nih.gov/articles/PMC2749091/) directly tests purified human FANCI and C-terminal fragments. Methods specify a 1328-residue protein, historically called isoform 1. Figure 2 and the accompanying competition Results show binding to branched substrates, including Holliday-junction and Y DNA. This historical name does not identify today’s 1268-residue Q9NVI1-1. The normal cache declares full text available but contains selected material; the official external main supplied the operative Methods and Results read here. Figure 2 pixels were independently viewed.
PMID:32269332(https://pmc.ncbi.nlm.nih.gov/articles/PMC7398534/) tests full-length human FANCI/FANCD2 purified from insect cells. Main Results, expression/purification and binding Methods, Figures 2 and 4, and Extended Data 6 distinguish unmodified ID2 from ubiquitinated clamps. Unmodified ID2 has a modest preference for branched substrates. Ubiquitination stabilizes a DNA-encircling complex that also binds ordinary duplex DNA and loses much of that preference. Circular-versus-linear DNA experiments support sliding; they do not measure stimulation of DNA polymerase processivity. No coordinate reanalysis, supplementary-video reading or universal natural-product equivalence is claimed.
The inherited DNA secondary structure binding proposal is retained with these limits. The actual term includes junction and other secondary structures. Its child four-way junction DNA binding covers only part of the tested substrate set. Current RAD51C and XRCC2 annotations provide role-matched junction-binding comparators; the current FANCD2 query did not verify the inherited claim that FANCD2 carries GO:0003697. The fixed GO-CAM index contains no FANCI/Q9NVI1 entry, which is not evidence of curator omission. No additional DNA-binding annotation is proposed.
PMID:19965384(https://pmc.ncbi.nlm.nih.gov/articles/PMC2909596/) measures replication-coupled ICL repair in Xenopus egg extracts. Depletion, recombinant ID2 rescue, ubiquitination-site controls, chromatin loading, incision and bypass experiments are distinguished from direct human FANCI assays. Human FANCI supplies independently demonstrated DNA-binding and clamp structure; it is not assigned the incision or synthesis chemistry. The main operative text was read; figure pixels and supplemental Methods were not.
PMID:18931676(https://pmc.ncbi.nlm.nih.gov/articles/PMC3293454/) separates chicken DT40 experiments from human U2OS Figure 6 and its Methods. Human FANCI phosphosite substitutions reduce FANCD2 monoubiquitination and foci. Figure 6 pixels were viewed. This supports the specific positive regulation of protein monoubiquitination, an ontology descendant of the imported broad ubiquitination-regulation term.
PMID:22287633(https://pmc.ncbi.nlm.nih.gov/articles/PMC3378891/) uses chicken FANCI/FANCD2/FANCL and human E1/UBE2T. The Ex6 mutant retains FANCD2-binding proficiency/basal stimulation without DNA but loses efficient DNA-stimulated modification. FANCI K525R, which cannot receive its normal ubiquitin modification, still promotes FANCD2 modification. This distinguishes FANCI’s performed regulatory contribution from simply being a substrate. Chicken R1288Q alone remains DNA-binding proficient, whereas its ID complex is impaired; the paper explicitly contrasts it with reported human R1285Q. The selected main Methods/Results and captions were read, without figure pixels or a whole-supplement claim.
PMID:27694619(https://pmc.ncbi.nlm.nih.gov/articles/PMC5159555/) separates human HeLa interaction evidence from purified chicken FANCI/FANCD2/RAD51 assays. The latter support FANCI DNA binding in filament stabilization and DNA-end protection. These assays are corroborating conserved evidence, not human mutant tests or FANCI nuclease chemistry. The selected main Methods/Results/captions were read; no pixels were inspected.
The imported cytoplasm annotation from PMID:18445686(https://pubmed.ncbi.nlm.nih.gov/18445686/) cannot be rejected from its EML3-focused title or FANCI’s nuclear enrichment. Its target-level operative original was not recovered: publisher/author requests failed, and the Max Planck repository describes an institutional-access PDF. Independent current Human Protein Atlas FANCI data report HPA040379 nucleoplasm and cytosol in A-431 and U-251MG cells. The actual XML and those two selected images were independently inspected. They support a cytosolic pool, not exclusive residence, a product-specific location, or retrospective reading of the 2008 experiment. Enhanced antibody validation is not absolute specificity: the separate HeLa BAC-GFP validation is mainly nuclear and the source notes additional antibody locations. No HeLa image or quantitative colocalization analysis was performed here.
The membrane HDA source, PMID:19946888(https://pubmed.ncbi.nlm.nih.gov/19946888/), remains UNDECIDED. Its abstract describes a positive NK-cell membrane-fraction proteome, but the original FANCI target table and fraction controls were unavailable in the retained finite requests. The membrane term does not require a transmembrane segment. Possible carryover is not demonstrated contamination. The earlier confident artifact assertion is superseded without asserting either membrane residence or absence.
PMID:17412408(https://pmc.ncbi.nlm.nih.gov/articles/PMC2175179/) supplies independent human evidence beyond ICL repair: FANCI depletion reduces I-SceI-induced repair in the integrated DR-U2OS homologous-recombination reporter and affects G2/M and intra-S checkpoint responses. Results on repair, localization and complementation and the corresponding siRNA, reporter, checkpoint, cDNA and cell-assay Methods were read. These establish repair participation, not FANCI recombinase activity. No supplement or figure pixels were inspected for this paper. The core uses the specific interstrand cross-link repair facet. Broader human repair evidence remains in the imported annotation review and biological account without adding the redundant DNA-repair parent to the core. The separate monoubiquitination-regulatory facet is retained.
PMID:19465922(https://pubmed.ncbi.nlm.nih.gov/19465922/) contributes the positive human mitotic fragile-site/ultrafine-bridge context in the complete cached abstract and curated UniProt location note. Its full operative Methods and pixels were not inspected. Together with chromatin-associated material and HPA nucleoplasm, it supports retaining nuclear breadth: nucleoplasm alone excludes chromosomes.
The database evidence assessment independently read PMID:19763158(https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1000645), including strain generation, colony-survival Methods, Results and Figure 2. Dictyostelium Ax2-derived fncI deletion, confirmed by Southern analysis, reduces colony survival after one-hour cisplatin exposure. This is positive ancestral donor evidence despite the paper emphasizing Xpf's larger contribution. Those pixels were read in the database assessment, not newly reread in this synthesis; no supplement or independent curve analysis is claimed.
The literal products remain Q9NVI1-3 (displayed 1328 residues), Q9NVI1-2 (1267), Q9NVI1-1 (1268) and Q9NVI1-4 (252), in their inherited order. The 2007 cDNA paper describes a 1328-residue isoform 3; the 2009 biochemical paper's historical 1328-residue “isoform 1” is not today's Q9NVI1-1. Engineered phosphosite/DNA-binding mutants, fragments and modification states are not natural products. Equivalent activity and localization across the four products remain unestablished; the 252-residue product is not inferred to be a processed chain.
The single core unit combines DNA secondary-structure binding with the structural and regulatory work of ID2. A human ID2 ring bearing ubiquitin on FANCD2 alone can close; the description does not make FANCI Lys523 ubiquitination an absolute prerequisite for every closed ring. Nucleoplasm and chromatin are separate, non-ancestral anatomical locations, while DNA repair complex occupies the complex slot. The observed cytosolic pool has no assigned biochemical core role, and the unresolved membrane-fraction observation is not converted into a membrane core. The three inherited core quotation objects are preserved, with the current prose correcting overbroad historical shorthand.
The actual PANTHER v19 PTHR21818 tree and MSA place human PTN002502899 below PTN000497925, and the ungapped target equals the displayed 1328-residue sequence. The GO PAINT IBD source contains four matching assertions on that path (GO:0006974, GO:0031398, GO:0005654 and GO:1990391), with no target-path NOT. The derived path is PTN000497925 → PTN001094789 → PTN000497926 → PTN000497927 → PTN000497928 → PTN008371700 → PTN002730006 → PTN000461674 → PTN000497931 → PTN000497932 → PTN000497933 → PTN000497934 → PTN000497935 → PTN001094793 → PTN002730007 → PTN000497936 → PTN002502899.
The target's presence in its own WITH list is legitimate experimental grounding. The DNA-response donor DDB_G0293476 resolves to Q54BR4 and the actual cisplatin experiment above. The regulation assertion names human Q9NVI1 and chicken A0A8V0YNA7. Current chicken identity is verified, but its retrieved GOA export lacks the historical experimental regulation row; that export-lineage gap does not overturn the inspected human and chicken experiments. No judgment rests on donor count.
InterPro IPR026171 matches FANCI residues 1–1328 and maps to DNA repair. Independent human ICL and HR evidence supports retaining that breadth. Official UniProt location mappings SL-0191 and SL-0086 remain source records; independent evidence supports nucleus and a cytosolic pool. The precise repair-complex child search did not identify a named ID2 term, so no identifier is invented.
Eleven event records yield 25 target-reaching routes. The three native human target states are FANCI 419529, p-4S-FANCI 6788480 and MonoUb-K523,p-4S-FANCI 6785321. Each explicitly covers residues 1–1328 and has its own nucleoplasm compartment. They are modification states, not different splice products. Event membership is a curated model, not eleven independent imaging experiments.
FANCL/UBE2T catalyze ubiquitin transfer; ATR phosphorylates FANCI; the named nucleases perform incision; POLN performs synthesis; USP1:WDR48 performs deubiquitination. FANCI contributes DNA binding and assembly/regulation or is the modified substrate, as appropriate. Membership in a composite catalyst does not transfer those enzyme activities to FANCI. The following public paths identify the actual participant trace; edge labels preserve input/output versus catalyst membership.
| Event (stored review index) | Actual participant route | Edges |
|---|---|---|
| R-HSA-6785342 (25) | 6785342 → 420764 → 419529 | input → hasComponent |
| R-HSA-6785342 (25) | 6785342 → 6785340 → 420764 → 419529 | output → hasComponent → hasComponent |
| R-HSA-6785361 (16) | 6785361 → 6785363 → 6788398 → 6788402 → 6788480 | catalystActivity → physicalEntity → hasComponent → hasComponent |
| R-HSA-6785361 (16) | 6785361 → 6785367 → 420757 → 420750 → 6785321 | output → hasComponent → hasComponent → hasComponent |
| R-HSA-6785361 (16) | 6785361 → 6788398 → 6788402 → 6788480 | input → hasComponent → hasComponent |
| R-HSA-6785594 (26) | 6785594 → 419529 | input |
| R-HSA-6785594 (26) | 6785594 → 420764 → 419529 | output → hasComponent |
| R-HSA-6785732 (17) | 6785732 → 6785367 → 420757 → 420750 → 6785321 | input → hasComponent → hasComponent → hasComponent |
| R-HSA-6785732 (17) | 6785732 → 6785734 → 6785367 → 420757 → 420750 → 6785321 | output → hasComponent → hasComponent → hasComponent → hasComponent |
| R-HSA-6785986 (18) | 6785986 → 6785734 → 6785367 → 420757 → 420750 → 6785321 | input → hasComponent → hasComponent → hasComponent → hasComponent |
| R-HSA-6785986 (18) | 6785986 → 6785992 → 6785734 → 6785367 → 420757 → 420750 → 6785321 | catalystActivity → physicalEntity → hasComponent → hasComponent → hasComponent → hasComponent |
| R-HSA-6785986 (18) | 6785986 → 6786151 → 420757 → 420750 → 6785321 | output → hasComponent → hasComponent → hasComponent |
| R-HSA-6786155 (19) | 6786155 → 6786151 → 420757 → 420750 → 6785321 | input → hasComponent → hasComponent → hasComponent |
| R-HSA-6786155 (19) | 6786155 → 6786156 → 6786151 → 420757 → 420750 → 6785321 | output → hasComponent → hasComponent → hasComponent → hasComponent |
| R-HSA-6786166 (20) | 6786166 → 420757 → 420750 → 6785321 | output → hasComponent → hasComponent |
| R-HSA-6786166 (20) | 6786166 → 6786156 → 6786151 → 420757 → 420750 → 6785321 | input → hasComponent → hasComponent → hasComponent → hasComponent |
| R-HSA-6786166 (20) | 6786166 → 6786167 → 6786156 → 6786151 → 420757 → 420750 → 6785321 | catalystActivity → physicalEntity → hasComponent → hasComponent → hasComponent → hasComponent |
| R-HSA-6786171 (21) | 6786171 → 6785367 → 420757 → 420750 → 6785321 | input → hasComponent → hasComponent → hasComponent |
| R-HSA-6786171 (21) | 6786171 → 6788402 → 6788480 | output → hasComponent |
| R-HSA-6788385 (27) | 6788385 → 6785340 → 420764 → 419529 | input → hasComponent → hasComponent |
| R-HSA-6788385 (27) | 6788385 → 6788386 → 6785340 → 420764 → 419529 | output → hasComponent → hasComponent → hasComponent |
| R-HSA-6788392 (22) | 6788392 → 6788386 → 6785340 → 420764 → 419529 | input → hasComponent → hasComponent → hasComponent |
| R-HSA-6788392 (22) | 6788392 → 6788394 → 6788386 → 6785340 → 420764 → 419529 | catalystActivity → physicalEntity → hasComponent → hasComponent → hasComponent |
| R-HSA-6788392 (22) | 6788392 → 6788398 → 6788402 → 6788480 | output → hasComponent → hasComponent |
| R-HSA-6797712 (28) | 6797712 → 6797713 → 419529 | output → hasMember |
The current genuine GOA contributes 30 imported contexts. Together with the retained inherited authored DNA-binding proposal at position 29, the file contains 31 objects. All 30 old positions and all 23 inherited quotation paths/text/reference associations remain. Eleven supporting-entity fields are backfilled from the genuine seeder; the historical PMID:20603015 object at position 8 now explicitly represents FANCD2, and its separate FAN1 context is appended at position 30. The old position-8 quotation remains contextual evidence from the same source, while the current reason distinguishes the FANCD2 partner and independent human ID2 support. The imported source term/evidence/reference/qualifier is unchanged. No additional authored assertion or new quotation field is introduced. The genuine current GOA is explicitly adopted; the old UniProt machine file stays byte-identical.
The final actions are 20 ACCEPT, 5 MODIFY, 4 KEEP_AS_NON_CORE, 1 UNDECIDED and 1 retained NEW. The membrane HDA is the unresolved context. The generic-binding non-core contexts follow the standing supported-binding convention. Thirty reference identities include the three added supporting sources PMID:17412408, PMID:19465922 and PMID:19763158. Five overlapping reference assessments preserve historical notes once and both complete labeled current reading scopes. The old chicken-mutant shorthand is explicitly superseded by the Ex6/R1288Q distinctions.
All 15 selected publication flags match immutable cache metadata. A cache flag does not mean the complete original, supplement or all figures were read, nor does abstract-only cache metadata preclude separately obtained original text. The source-specific limits above and the full reference assessments distinguish these. The evidence union has 45 immutable normal files; 29 are selected (15 publications, 11 Reactome records and 3 PANTHER files), and the 16 unused files remain private. These are agent-authored notes and guide; no provider research file is manufactured.
The current core uses GO:0036297 interstrand cross-link repair in place of its GO:0006281 DNA-repair ancestor. The accepted human structural contribution and conserved extract repair experiments support this specific process; the independent HR reporter remains valid context. No additional HR process is proposed merely to balance coverage. The core also retains positive regulation of FANCD2 monoubiquitination: FANCI performs regulatory/structural work rather than only receiving ubiquitin.
The inherited Affinage research file was used to locate the following originals. Its biological leads were evaluated rather than copied into annotations.
Only selected original Methods/Results and captions were read for these additions, as recorded per reference. Supplemental pixels were not independently inspected. PMID:30692263 remains an abstract-only normal cache; its additional reading came from the original PMC page and separately retained, discontinuous indexed original text. No cache header or body was rewritten to simulate full availability.
Directly demonstrated human nucleolar localization is represented by a NEW IDA cellular-component assertion, GO:0005730, citing PMID:30692263. Nucleus does not entail nucleolus: the specific location adds experimental information while preserving the broader imported location contexts. The assertion is appended after all 31 existing positions, introduces no new quotation, and remains outside the repair core. It does not establish exclusive localization or ribosome-biogenesis chemistry.
The eleven Reactome rows are separate curated event contexts, not eleven independent localization experiments. Their target-specific routes and chemistry limits remain in the individual reasons. All model FANCI states use residues 1–1328 in nucleoplasm; modification states are not natural splice isoforms. Event-cited primary papers were not all independently reread, and the models are distinguished from direct imaging/reconstitution. No behavior is generalized to all four natural products. The historical 1328-residue constructs and engineered fragments differ from the current 1268-residue Q9NVI1-1 product; detailed identities above remain operative.
The three supported generic-binding rows remain KEEP_AS_NON_CORE under the explicit CLINGEN_MENDELIAN project exception (canonical policy, lines 2975–2988). The membrane HDA remains UNDECIDED because the operative target table is unavailable. Cytosol refinement retains its independent HPA support and the original PMID:18445686 access limit. None of these judgments is changed by incomplete evidence or a generic binding-policy preference.
The accepted follow-up contains 32 active records (30 imported contexts and two authored proposals), 39 references and four unchanged natural products. The current normal-source union is 36 files, including seven genuinely fetched primary publications. All 23 inherited quotation associations are unchanged. 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. The Affinage citation documents discovery, not primary experimental support for an individual annotation.