Human Fanconi anemia group B protein / FAAP95. Gene at Xp22.31; X-linked. 859 aa. HGNC:3583.
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).
FANCB supplies an integral structural scaffold in the FANCL–FANCB–FAAP100 module. Human cellular association and reconstituted-complex experiments support this organizing role (PMID:17396147, Figure 2 and hybrid/purification Methods; PMID:27986592, assembled-module/dropout Results and XL-MS Methods). FANCL and UBE2T supply ubiquitin-transfer chemistry. Isolated FANCB self-association was not demonstrated, and human BL100, Xenopus ID2 and conserved chicken structures must remain separate experimental contexts. The core retains ICL repair participation, nucleoplasm and FA nuclear-complex membership, without asserting FANCB nuclease, polymerase, kinase or ligase activity.
The scaffold term is now GO:0140378. The earlier use of GO:0030674 overlooked its explicit usage comment directing integral protein-complex scaffolds to GO:0140378. This corrects the molecular-function representation without changing the underlying assembly evidence. The three inherited core quotations remain exact and refer to assembled-module or conserved structural evidence; they do not establish an autonomous FANCB homodimer. The 2016 study used both BL100 cryo-EM and negative-stain EM, with negative-stain ID2 reconstruction; the retained historical Cryo-EM shorthand does not describe every preparation. The 2019 conserved chicken core-complex cryo-EM study is separate.
The final annotation assessment is 17 ACCEPT, 4 KEEP_AS_NON_CORE, 1 MODIFY and 1 UNDECIDED across the 23 inherited source objects. The unresolved chromatin context is separate from positively supported core membership: the inspected PMID:22343915 main Figure 5H labels FANCA, FANCG and FAAP20, while Figure 1 and authentic supplemental Figure S1C establish FANCB membership. All supplemental extracted Methods/captions and Figure S1 pixels were inspected; no FANCB-specific chromatin readout was identified. This does not establish absence from chromatin. Cytosolic BL100 recovery is positive, and the bounded PKR model is retained non-core without calling cytosolic FANCB inactive.
Verified PANTHER v19 ancestry and actual mouse Fancb experiments support the three context-dependent repair-regulatory annotations. PMID:25520194 and PMID:21458466 address different genetic, lesion and cellular settings; their results do not grant FANCB recombinase or helicase chemistry. Current Q8NB91 has 859 residues and no alternative-products comment. Processing and external transcript models are kept distinct from natural-product or construct equivalence.
All 17 inherited quotation paths, texts and reference associations remain unchanged. The 25 original reference identities/findings are retained, with PMID:25520194 and PMID:15299030 added from genuine existing sources. Four shared manual assessments retain both complete labeled reading scopes. Cache metadata, external original availability and actual reading are distinct; the source guide gives public paper, figure and database locators. No new publication quotation or NEW annotation is introduced. Earlier counts and biological shorthand in this journal describe the historical review. Its inherited COMPLETE status is preserved in this private synthesis for subsequent canonical recomputation, not a new status determination.
The biological summary now states FANCB's structural role, nuclear repair-associated and cytosolic assemblies, X-linked inheritance and disease spectrum without using evidence-acquisition commentary. Human BL100 reconstitution supports a dimeric assembly, not an autonomous isolated FANCB homodimer or one invariant stoichiometry of every full core complex (PMID:27986592, Results and Figures 2–3). The founding abstract and clinical abstract/Introduction support X-linkage, X-inactivation and severe VACTERL-H disease context (PMID:15502827; PMID:32106311); no new claim of whole-paper clinical review is made.
GO:2000042 is now UNDECIDED. The actual mouse PMID:25520194 Results and Figure 7A/E report reduced RAD51 at nascent DNA after Fancb deletion; additional Recql5 deletion restores it. Thus the review suggestion that FANCB deletion itself elevates RAD51 reverses this comparison. The Results and Discussion attribute RAD51 suppression in the FANCB-defective background to RECQL5. BLM-dependent chromosome outcomes and the speculative remodeling model do not independently establish FANCB-specific suppression of homologous-recombination DSB repair. Positive fork protection, valid PAINT ancestry and the separately supported positive-repair/SCE annotations remain intact. The new total is 17 ACCEPT, 3 KEEP_AS_NON_CORE, 1 MODIFY and 2 UNDECIDED across the unchanged 23 imported contexts.
Correction to the inherited structural shorthand above: PMID:32939280 models the chicken FA core complex from the PMID:31666700 chicken map and crosslinking data, using deep-learning predictions and Rosetta. The earlier line associating it with a human structure and the listed PDB identifiers is not reliable support for those identifiers or species. No replacement PDB identifier is asserted here. The original journal entry remains historical; the current source guide and reference assessment provide the corrected species/model scope.
All 17 inherited quotation paths and reference associations remain unchanged, including the complex-association, nuclear-localization, FANCA-chromatin and normalized section-heading excerpts flagged in feedback. Their limitations remain explicit; preservation is not fresh endorsement of those snippets as target-specific proof. Under the campaign instructions, no publication quotation is added, replaced, moved or deleted. A verified reference-only support entry links the unresolved negative-HR review to the actual paper. The generated provider file is not newly cited solely to change status or clear an advisory. Source caches, core functions and product boundaries are unchanged.