FANCI (FANCI) — AIGR vs Affinage
Affinage record: run 2026-06-09 · 43 discoveries · self-eval win (faith 100%) · gates passed.
Agreement (brief)
Both sources converge on FANCI's core biology and the AIGR review already captures it:
- FANCI is the obligate ID2-clamp partner of FANCD2, monoubiquitinated on Lys523 by
FANCL/UBE2T, mutually interdependent with FANCD2 monoubiquitination (AIGR
GO:0031398, GO:1990391; core_functions).
- DNA binding with preference for branched structures; the monoubiquitinated ID2
complex becomes a closed sliding clamp encircling dsDNA (AIGR NEW GO:0003677;
PMID:32269332).
- ATR S/TQ-cluster phosphorylation acts as the activating molecular switch (AIGR
description + GO:0031398; PMID:18931676).
- Interstrand cross-link repair as the defining process; nucleoplasm/chromatin
localization (AIGR GO:0036297, GO:0000785, GO:0005654).
- Downstream partners FAN1 and POLN captured as non-core interactions.
Affinage's PMID-dense narrative (43 citations) is a strong, accurate literature scan and
matches the curated picture on all central mechanistic points.
Disagreements
| Topic | Affinage says | AIGR review says | Verdict (who is right + why) |
|---|---|---|---|
| GO grounding layer | mechanism_profile lists coarse parents: GO:0140096 catalytic activity acting on a protein, GO:0098772 molecular function regulator, GO:0060090 molecular adaptor, GO:0003723 RNA binding |
Specific curated terms: GO:0003677 DNA binding (MF), GO:0031398, GO:0036297, GO:1990391 |
AIGR right. Affinage's own note flags this layer as coarse/contradictory. FANCI is not a catalytic protein-modifying enzyme (it is the substrate/co-factor for FANCL/UBE2T); "catalytic activity acting on a protein" is wrong-branch. AIGR's DNA-binding MF is the correct defining activity. |
| Cytoplasm / membrane localization | Not asserted by Affinage (narrative is nuclear) | AIGR carries and down-scores them: cytoplasm MARK_AS_OVER_ANNOTATED (PMID:18445686 EML3 spindle proteomics), membrane REMOVE (PMID:19946888 NK membrane fraction) |
AIGR right and more rigorous — it adjudicates GOA-inherited noise Affinage never surfaced. |
| RNA binding / R-loop, nucleolar rRNA | Included as discoveries (PMID:30650351, PMID:30692263) with GO:0003723 RNA binding |
Not annotated | AIGR defensibly conservative. These are real but largely FANCD2-independent, secondary functions; importing GO:0003723 at FANCI's core level would over-annotate. Documented, not adopted. |
| RAD51 filament stabilization / fork protection | Discovery (PMID:27694619): ID complex binds RAD51, stabilizes RAD51-DNA filament, protects 5' end from FAN1 | Was absent | Partially incorporated. Well-evidenced, and FANCI's (not FANCD2's) DNA binding is explicitly required — so PMID:27694619 was added as supporting evidence for the DNA-binding MF. No clean GO BP term exists ("replication fork protection" resolves only to CC complex GO:0031298 or the ill-fitting GO:0031297 processing), so no new BP annotation was created. |
| PIDD1/caspase-2 apoptotic switch; dormant-origin firing; meiosis/spermatogenesis; Akt/PHLPP1; PARP1; IMPDH2 | Included as discoveries (PMID:34256011, 25843623, 34373449/31219578, 27097374, 39037758, 32021289) | Not annotated | AIGR right to exclude from core. These are context-specific or single-study over-reaches (several are cancer-cell or mouse-specific); appropriate as narrative, not as curated core GO. |
Papers incorporated into the review
| PMID | Supports | How used |
|---|---|---|
| PMID:19589784 | FANCI intrinsic DNA binding (branched-structure preference); K523 monoub by UBE2T-FANCL | Added verbatim supported_by to the DNA-binding NEW GO:0003677 annotation (independent primary biochemistry alongside structural PMID:32269332); reference + reference_review (HIGH/VERIFIED) |
| PMID:22287633 | DNA-binding-dependent stimulation of FANCD2 monoubiquitination by FANCI | Added verbatim supported_by to GO:0031398 positive regulation of protein ubiquitination (IDA); reference + reference_review (HIGH/VERIFIED) |
| PMID:27694619 | FANCI's DNA binding explicitly required for ID2-mediated RAD51-DNA filament stabilization / fork-end protection | Added verbatim supported_by to the DNA-binding NEW GO:0003677 annotation; reference + reference_review (MEDIUM/VERIFIED, notes no clean BP term) |
No new GO annotations (terms/qualifiers) were created; the three papers strengthen existing
core annotations. Validation remains ✓ Valid (single expected deep-research-file warning).
Net assessment
The AIGR review was already accurate and complete on FANCI's core biology, and is more
rigorous than Affinage on GOA-inherited localization noise (cytoplasm/membrane) and on GO
branch precision (Affinage's coarse mechanism_profile mislabels FANCI as a protein-acting
catalytic enzyme). Affinage's value here was surfacing well-cited primary biochemistry that
the curated review carried on a single structural reference; three of those papers were
incorporated as independent verbatim support for the DNA-binding molecular function and the
positive-regulation-of-ubiquitination process. Affinage's remaining "discoveries" (RNA/R-loop,
nucleolar rRNA, meiosis, PIDD1 apoptosis, dormant origins, cancer-cell partnerships) are
genuine literature but are secondary/context-specific and were correctly left out of core GO —
several would be over-annotations if imported at FANCI's core level.