Fanconi anemia group B protein (FANCB, also FAAP95) is a non-catalytic subunit of the Fanconi anemia (FA) core complex, a nuclear multisubunit ubiquitin ligase that, in response to DNA replication stress and interstrand crosslinks (ICLs), monoubiquitinates the FANCD2-FANCI (ID2) heterodimer to activate the FA/BRCA DNA repair pathway. FANCB assembles with the RING E3 ligase FANCL and with FAAP100 into the FANCB-FANCL-FAAP100 (BL100) catalytic module, where it serves as the central scaffold and dimerization factor: two BL100 heterotrimers associate through FANCB to form the symmetric "dimer of trimers" that gives the core complex its architecture and positions the two FANCL RING domains to ubiquitinate FANCD2 and FANCI. FANCB is required for the stability and coordinated nuclear import of the module (chaperoned by FANCA and FANCM) and for chromatin loading of the complex at sites of damage; in its absence FANCD2 monoubiquitination fails. The gene is X-linked (Xp22.31) and subject to X-inactivation, so a single active copy is functional, making FANCB a dosage-sensitive node whose loss causes Fanconi anemia complementation group B, frequently a severe VACTERL-with-hydrocephalus phenotype, with cellular hypersensitivity to crosslinking agents and chromosomal instability.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0043240 Fanconi anaemia nuclear complex | IBA GO_REF:0000033 | ACCEPT | Summary: FANCB is a core structural subunit of the Fanconi anemia nuclear (core) complex. Reason: This is the defining, best-supported complex-membership annotation for FANCB and is corroborated experimentally (IDA, NAS below) and structurally. FANCB is one of the eight stably associated subunits of the FA core complex and, with FANCL and FAAP100, forms its central catalytic module. Supporting Evidence: PMID:15502827 essential component of the nuclear protein PMID:31666700 A dimer of FANCB-FAAP100 heterodimers is located in the middle region of the structure |
| GO:1905168 positive regulation of double-strand break repair via homologous recombination | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) inference that the FA pathway promotes homologous-recombination repair of double-strand breaks. Reason: Promotion of HR is a genuine but downstream, pathway-level consequence of FA-core-complex activity rather than FANCB's direct molecular function. FANCB's core role is architectural scaffolding of the BL100 module that enables FANCD2-FANCI monoubiquitination; effects on HR are indirect and shared across FA proteins. Retained as non-core. Supporting Evidence: PMID:21458466 Gene targeting efficiency was 16.2% (6/37) for control cells and 0% (0/96) for fancbΞex2 |
| GO:1990414 replication-born double-strand break repair via sister chromatid exchange | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) inference linking FANCB to repair of replication-associated double-strand breaks via sister-chromatid exchange. Reason: The FA core complex modulates sister-chromatid-exchange outcomes at stalled/blocked replication forks, but this is a downstream pathway-level role rather than FANCB's direct scaffolding activity. Retained as non-core. Supporting Evidence: PMID:20347428 FANCM-MHF associates with the Fanconi anemia (FA) core complex PMID:21458466 Decreased Homologous RecombinationThe fancbΞex2 cells were tested for spontaneous sister chromatid exchanges (SCEs) |
| GO:2000042 negative regulation of double-strand break repair via homologous recombination | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic (IBA) inference that the FA pathway also restrains homologous recombination. Reason: The FA pathway both promotes and limits HR/crossover outcomes (fork protection, suppression of aberrant recombination and sister-chromatid exchange). This regulatory role is downstream and pathway-level, not FANCB's direct molecular function. Retained as non-core. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: FANCB localizes to the nucleus, where the FA core complex acts on chromatin. Reason: Consistent with UniProt subcellular location (Nucleus) and with the more specific nucleoplasm and Fanconi anaemia nuclear complex annotations. Nuclear import of the BL100 module is chaperoned by FANCA/FANCM. Broad but correct. Supporting Evidence: PMID:17396147 each member of the L-B-P100 subcomplex has a disturbed nuclear localization in FA-A cells |
| GO:0036297 interstrand cross-link repair | IEA GO_REF:0000002 | ACCEPT | Summary: FANCB participates in DNA interstrand crosslink repair as part of the FA core complex. Reason: This is the central biological process of the FA pathway. FANCB is required for the FANCD2-FANCI monoubiquitination step that activates replication-coupled ICL repair. Correct and specific. Supporting Evidence: PMID:19965384 FANCI-FANCD2 is required for replication-coupled ICL repair in S phase PMID:32106311 the indispensable role of FANCB protein in the enzymatic activation of FANCD2 monoubiquitination, an essential step in the repair of DNA interstrand crosslinks |
| GO:0043240 Fanconi anaemia nuclear complex | IEA GO_REF:0000002 | ACCEPT | Summary: FANCB is a subunit of the Fanconi anemia nuclear (core) complex (InterPro-based). Reason: Consistent with the experimental IDA/NAS and phylogenetic IBA annotations of the same term; FANCB (IPR033333) is a defining FA core complex component. |
| GO:0005515 protein binding | IPI PMID:17396147 FAAP100 is essential for activation of the Fanconi anemia-as... | MODIFY | Summary: Binary interaction evidence (with FAAP100, Q0VG06). "Protein binding" is uninformative; the underlying, well-supported molecular function is a protein-macromolecule adaptor / scaffold activity. Reason: The IPI captures the direct FANCB-FAAP100 interaction, but GO:0005515 conveys no specific function. Structural and biochemical work shows FANCB is the dimerization/scaffold factor that bridges FANCL and FAAP100 into the BL100 module and templates core-complex assembly, stimulating FANCL ligase activity. This is best represented as protein-macromolecule adaptor activity (GO:0030674). Proposed replacements: protein-macromolecule adaptor activity Supporting Evidence: PMID:17396147 directly interacts with FANCB and FANCL to form a stable subcomplex PMID:27986592 FANCB plays a key structural function, being the dimerization factor |
| GO:0000785 chromatin | IDA PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr... | ACCEPT | Summary: FANCB, as part of the FA core complex, is loaded onto chromatin upon DNA damage. Reason: Experimental (IDA) chromatin localization is consistent with the DNA-damage-induced chromatin loading of the FA core complex, which delivers the FANCD2-FANCI substrate to damaged chromatin. Defer to the curator's experimental assessment. Supporting Evidence: PMID:22343915 required for DNA-damage-induced chromatin loading of FANCA |
| GO:0036297 interstrand cross-link repair | NAS PMID:19965384 The Fanconi anemia pathway promotes replication-dependent DN... | ACCEPT | Summary: FANCB contributes to interstrand crosslink repair via the FA pathway. Reason: Duplicate of the ICL-repair process term (also IEA) supported by an authoritative statement that the FA pathway (FANCI-FANCD2 monoubiquitination, which FANCB enables) drives replication-coupled ICL repair. Correct and central. Supporting Evidence: PMID:19965384 FANCI-FANCD2 is required for replication-coupled ICL repair in S phase |
| GO:0043240 Fanconi anaemia nuclear complex | NAS PMID:22343915 FAAP20: a novel ubiquitin-binding FA nuclear core-complex pr... | ACCEPT | Summary: FANCB is an integral component of the FA nuclear core complex. Reason: Consistent with the IDA/IEA/IBA annotations of the same term. The FAAP20 study treats FANCB as an established FA nuclear core-complex subunit. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9835411 | ACCEPT | Summary: A cytosolic pool of FANCB exists as the assembled BL100 module prior to chaperoned nuclear import (and in the FA-core-complex:HSP70 assembly implicated in PKR signaling). Reason: The BL100 (L-B-P100) module is the major cytosolic form of FANCL/FANCB/FAAP100 and moves to the nucleus only when associated with FANCA and FANCM. Cytosolic localization is thus biologically accurate for an assembly/storage pool, though FANCB's functional site is nuclear. Supporting Evidence: PMID:17396147 each member of the L-B-P100 subcomplex has a disturbed nuclear localization in FA-A cells |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785126 | ACCEPT | Summary: FANCB acts in the nucleoplasm as part of the FA core complex during ICL repair. Reason: Nucleoplasm is the functional compartment of the assembled FA core complex; consistent with the nucleus and Fanconi anaemia nuclear complex annotations. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785342 | ACCEPT | Summary: FANCB acts in the nucleoplasm as part of the FA core complex during ICL repair. Reason: Redundant Reactome nucleoplasm localization; correct functional compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785361 | ACCEPT | Summary: FANCB acts in the nucleoplasm as part of the FA core complex during ICL repair. Reason: Redundant Reactome nucleoplasm localization; correct functional compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785732 | ACCEPT | Summary: FANCB acts in the nucleoplasm as part of the FA core complex during ICL repair. Reason: Redundant Reactome nucleoplasm localization; correct functional compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6785986 | ACCEPT | Summary: FANCB acts in the nucleoplasm as part of the FA core complex during ICL repair. Reason: Redundant Reactome nucleoplasm localization; correct functional compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786155 | ACCEPT | Summary: FANCB acts in the nucleoplasm as part of the FA core complex during ICL repair. Reason: Redundant Reactome nucleoplasm localization; correct functional compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786166 | ACCEPT | Summary: FANCB acts in the nucleoplasm as part of the FA core complex during ICL repair. Reason: Redundant Reactome nucleoplasm localization; correct functional compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6786171 | ACCEPT | Summary: FANCB acts in the nucleoplasm as part of the FA core complex during ICL repair. Reason: Redundant Reactome nucleoplasm localization; correct functional compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6788385 | ACCEPT | Summary: FANCB acts in the nucleoplasm as part of the FA core complex during ICL repair. Reason: Redundant Reactome nucleoplasm localization; correct functional compartment. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6788392 | ACCEPT | Summary: FANCB acts in the nucleoplasm as part of the FA core complex during ICL repair. Reason: Redundant Reactome nucleoplasm localization; correct functional compartment. |
| GO:0043240 Fanconi anaemia nuclear complex | IDA PMID:20347428 A histone-fold complex and FANCM form a conserved DNA-remode... | ACCEPT | Summary: Experimental (IDA) evidence places FANCB in the FA nuclear core complex, which the FANCM-MHF DNA-remodeling complex associates with. Reason: Direct experimental complex-membership annotation consistent with all other GO:0043240 annotations. The full study biochemically purified the FA core complex (of which FANCB is a subunit); defer to the curator's experimental determination. Supporting Evidence: PMID:20347428 FANCM-MHF associates with the Fanconi anemia (FA) core complex |
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Download this section (compressed HTML)Q: Does FANCB self-associate to form the dimerization interface directly, or is the "dimer of trimers" bridged through FANCB-FAAP100 contacts (isolated FANCB self-association has not been demonstrated)?
Q: How does hemizygous/X-inactivation dosage of the single active FANCB allele set the threshold for FA core complex assembly and FANCD2 monoubiquitination?
Experiment: Structure-guided mutagenesis of the FANCB dimerization interface to test whether disrupting BL100 dimerization abolishes FANCD2-FANCI monoubiquitination while preserving individual subunit stability.
Experiment: Quantitative reconstitution of FANCL ubiquitin-ligase activity with and without FANCB to dissect its architectural (adaptor) versus allosteric stimulation of catalysis.
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