FANCB (Q8NB91) — Gene Review Notes

Human Fanconi anemia group B protein / FAAP95. Gene at Xp22.31; X-linked. 859 aa. HGNC:3583.

Summary of function

FANCB is a non-catalytic structural subunit of the Fanconi anemia (FA) core complex, the
multisubunit E3 ubiquitin ligase (FANCA/B/C/E/F/G/L/M + FAAPs) that monoubiquitinates the
FANCD2–FANCI (ID2) heterodimer during replication-coupled DNA interstrand crosslink (ICL)
repair. Within the complex FANCB forms, together with the RING E3 ligase FANCL and FAAP100,
the FANCB–FANCL–FAAP100 (BL100) catalytic module. FANCB is the dimerization/scaffold factor:
two BL100 heterotrimers associate through FANCB to give the symmetric "dimer of trimers" that
templates assembly of the whole core complex and positions the two FANCL RING domains to
ubiquitinate both FANCD2 and FANCI. Loss of FANCB abolishes FANCD2 monoubiquitination, causes
crosslinker hypersensitivity, chromosomal instability, and the FA-B clinical phenotype (often
severe VACTERL-H).

Key provenance

Identity, X-linkage, essentiality for FANCD2 ubiquitination

• PMID:15502827 — Meetei 2004, Nat Genet; identified FANCB (=FAAP95) as FA core complex subunit.
• PMID:15502827 — X-linked inheritance; single active copy makes FANCB a uniquely vulnerable node.
• UniProt FUNCTION: [file:human/FANCB/FANCB-uniprot.txt "DNA repair protein required for FANCD2 ubiquitination"].
• UniProt SUBUNIT: multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM; "The complex is not found in FA patients." Nucleus (ECO:0000269|PubMed:15502827).

FANCB is the scaffold / dimerization factor of the BL100 catalytic module

• PMID:27986592 — Swuec 2017, cryo-EM of the dimeric catalytic module.
• PMID:27986592.
• PMID:27986592 — FANCL activity architecturally stimulated by FANCB/FAAP100.
• PMID:31666700 — Shakeel 2019, Nature, full FA core complex structure.
• PMID:31666700.
• Note FANCB is the only BL100 protomer carrying disease-associated missense mutations (Swuec 2017), underscoring its structural role.

Direct interaction with FANCL and FAAP100; subcomplex protects members; nuclear localization

• PMID:17396147 — Ling 2007; FAAP100 + FANCB + FANCL = L-B-P100 subcomplex.
• PMID:17396147 — nuclear import of the module is FANCA/FANCM-dependent; the module is cytosolic until chaperoned to the nucleus.

Chromatin loading and ICL repair context

• PMID:22343915 — FAAP20 paper; FA core complex (incl. FANCB, IDA chromatin) loads onto chromatin upon damage.
• PMID:19965384 — Knipscheer 2009; places the FANCD2 monoubiquitination output (which FANCB enables) in replication-coupled ICL repair.
• PMID:20347428 — Yan 2010; FA core complex (of which FANCB is a subunit) purified; suppresses sister-chromatid exchanges, promotes FANCD2 monoubiquitination.

Curation reasoning highlights

• MF "protein binding" (GO:0005515, IPI with FAAP100): uninformative; the real, well-supported MF is a protein-macromolecule adaptor/scaffold activity (GO:0030674) — FANCB bridges/dimerizes FANCL and FAAP100 and templates core-complex assembly. MODIFY.
• HR/SCE regulation IBA terms (GO:1905168, GO:2000042, GO:1990414) are phylogenetic (mouse Fancb) and reflect broad FA-pathway roles downstream of FANCB's direct scaffolding function → KEEP_AS_NON_CORE.
• Multiple redundant Reactome nucleoplasm TAS lines and cytosol TAS: locations are correct (cytosolic assembly pool + nuclear function) → ACCEPT.
• Structural PDBs: 7KZP/7KZQ etc. (human FA core complex, PMID:32939280); 6SRI (chicken, PMID:31666700).