FANCB

Summary: The verified ancestral assertion and human experiments support FANCB membership in the FA nuclear complex.

Reason: The saved PANTHER v19 tree places the exact human Q8NB91 859-residue sequence at PTN002523840 beneath PTN002408105. The actual IBD for GO:0043240 cites the human target itself, correctly preserving experimental descendant grounding rather than circular propagation. Human HeLa purification and recombinant human BL100 assembly independently support the membership (PMID:17396147; PMID:20347428; PMID:27986592). The inherited PMID:15502827 abstract is positive for the nuclear core, while PMID:31666700 resolves a Gallus gallus complex expressed in Sf9 cells and is conserved structural corroboration, not a human preparation. Retain GO:0043240 without assigning FANCL catalytic chemistry, an isolated FANCB homodimer, or one invariant whole-complex stoichiometry.

Summary: Conserved promotion of homologous-recombination repair is retained as a context-dependent regulatory role.

Reason: The actual PTN002408105 IBD and target path are verified, with experimental mouse Fancb grounding rather than a weak pairwise transfer. Current mouse donor GOA traces this term to PMID:25520194: Fancb exon-2 deletion was combined with Recql5 deletion or a strong Blm hypomorph in mouse embryonic stem cells, revealing lesion- and background-dependent chromosome, RAD51-loading, nascent-strand and restart phenotypes. Independently, PMID:21458466 measured reduced spontaneous SCE, gene targeting and MMC-induced RAD51 foci after mouse Fancb deletion. These positive data support a conserved role promoting productive repair; they do not establish FANCB as the strand-exchange catalyst or a universal effect in every cell type. Retain this specific regulatory facet as non-core relative to FANCB’s structural FA-core function, without rejecting the valid ancestral placement or treating a single donor as insufficient.

Summary: The inherited sister-chromatid repair role is retained with the mouse assay and cellular-context limits.

Reason: The target inherits the actual GO:1990414 IBD at PTN002408105, with mouse Fancb MGI:2448558 as experimental grounding. PMID:25520194 links FANCB/BLM/RECQL5 genetic interactions to replication-associated chromosome damage, fork protection and restart, while PMID:21458466 directly measured spontaneous SCE by BrdU-labelled metaphase analysis and found reduced SCE in Fancb-deficient mouse embryonic stem cells. The latter explicitly reports species/cell-type differences in prior FA studies. Preserve the sound inherited repair role as a contextual non-core facet; the 2015 fork and chromosome endpoints are not relabeled as a new direct SCE measurement, and the inherited PMID:20347428 complex-association quotation is not a FANCB-specific SCE assay. Neither donor count nor self-WITH is used as a weakness, and no biochemical recombinase activity is inferred.

Summary: The inherited negative-HR assertion has verified ancestry, but its FANCB-specific negative direction remains unresolved.

Reason: The GO:2000042 IBD at PTN002408105 lies on the verified human target path and traces to mouse Fancb evidence in PMID:25520194; neither that placement nor the experimental donor identity is disputed. However, the term requires a reduction in the frequency, rate or extent of homologous-recombination DSB repair. In the mouse embryonic-stem-cell experiments, Fancb exon-2 deletion reduced RAD51 recovered at nascent DNA under both HU conditions, and additional Recql5 deletion restored RAD51 (Results and Figure 7A/E). Suppression of RAD51 in the Fancb-deficient background is therefore attributed to RECQL5, not demonstrated FANCB inhibition of HR. BLM deficiency suppressing MMC-induced chromosome defects in that background and the proposed avoidance of harmful repair intermediates are relevant genetic observations, but they do not resolve the target-specific negative-HR claim; the Discussion labels its mechanistic model speculative. Retain UNDECIDED pending evidence that distinguishes FANCB-dependent suppression of HR from fork protection and the actions of its genetic partners. This does not assert loss of the function, an incorrect ancestral node, or absence of FANCB involvement in repair.

Summary: The nucleus is an established compartment for human FANCB-containing complexes.

Reason: The actual UniProt Q8NB91 subcellular-location assertion maps SL-0191 to GO:0005634 through GO_REF:0000044. Human HeLa nuclear-extract purification independently recovers FANCB with FANCL and FAAP100, and FANCM immunoprecipitation identifies FANCB in the nuclear FA core (PMID:17396147, Figure 2 and fractionation Methods; PMID:20347428, initial Results and Figure 1). Retain the encompassing nuclear location. The separate Reactome nucleoplasm assignments describe modeled pools; they do not prove that every nuclear FANCB molecule occupies only that narrower compartment, whose definition excludes chromosomes. No chromatin resolution, exclusive nuclear residence, or localization of a separately established natural splice product is inferred here.

Summary: FANCB contributes the structure of the FA repair-activating core to interstrand cross-link repair.

Reason: The current InterPro record IPR033333 maps specifically to GO:0036297 and GO:0043240 and matches human Q8NB91 residues 7–858. Its ICL assignment is coherent with experimentally supported FANCB assembly work: human FANCB organizes the FANCL–FAAP100 module in cellular and reconstituted-complex experiments (PMID:17396147; PMID:27986592). This structural contribution is participation in the repair machinery, not merely the product being consumed or processed. PMID:19965384 establishes the downstream requirement for ubiquitinated ID2 in Xenopus replication-coupled ICL repair; its inherited quotation is not a direct human FANCB incision assay. PMID:32106311 provides additional clinical/variant context in the accessible abstract and Discussion, but its cached extraction omits operative Methods/Results. Retain ICL repair without assigning FANCL ubiquitin-transfer, nuclease incision or POLN synthesis to FANCB.

Summary: The FANCB family mapping correctly identifies a component of the FA nuclear complex.

Reason: The actual IPR033333 entry and target match establish this specific family-to-GO:0043240 mapping. Human nuclear-core purification and human FANCB–FANCL–FAAP100 reconstitution corroborate it independently (PMID:17396147; PMID:20347428; PMID:27986592). Membership is retained as a central structural role. The electronic mapping does not itself establish binary contacts, stoichiometry or ubiquitin-ligase chemistry, and no such additional activity is inferred.

Summary: FANCB is an integral structural scaffold of the FANCL–FAAP100 module.

Reason: The imported WITH partner Q0VG06 is FAAP100. In PMID:17396147, human HEK293 mammalian two-hybrid assays support FANCB–FAAP100 association, while stable FLAG-FANCB permits a strong FAAP100–FANCL three-hybrid signal (Figure 2A/B; mammalian hybrid Methods). Human HeLa FLAG/His-FANCL purifications recover the stable FANCB–FANCL–FAAP100 module from nuclear and cytosolic extracts (Figure 2C/D). These cellular and purified-complex results should not be described as a purified binary binding measurement. Independently, recombinant human BL100 expressed in Sf9 cells retains its dimer interface after FANCL dropout, and crosslinking MS connects FANCB to both FANCL and FAAP100 (PMID:27986592, Results on FANCB-mediated assembly and the subunit-dropout experiments, Figures 2/3 and XL/MS Methods). That paper could not demonstrate self-association of isolated FANCB; its evidence concerns FANCB within the assembled module. Together these data support FANCB as an integral component holding the BL100 protein complex together, matching GO:0140378 protein complex scaffold activity. The current GO:0030674 comment explicitly directs protein-complex scaffold roles to GO:0140378; the stable assembled-module role here therefore supports the scaffold term rather than the broad adaptor term. They do not assign FANCL ubiquitin-ligase chemistry, the FANCE–ID2 substrate bridge, an autonomous FANCB homodimer, or an invariant whole-core stoichiometry to FANCB. Exact equivalence of the historical constructs to the current 859-residue sequence was not established. The informative structural scaffold activity is supported independently of generic binding; a substrate-specific adaptor term is not justified.

Proposed replacements: protein complex scaffold activity

Summary: The inspected chromatin experiment does not resolve the imported FANCB-specific localization claim.

Reason: PMID:22343915 establishes FANCB membership of the human nuclear FA core, including the FANCB-labelled bands in Figure 1A/B. That membership is distinct from localization to chromatin, an organized DNA-protein chromosome component under the current GO:0000785 definition. The actual Figure 5H panel, caption and accompanying chromatin-loading Results identify FANCA, FANCG and FAAP20 in HeLa fractions, with H2A as the chromatin control; they do not directly identify FANCB in that experiment. The authentic supplemental PDF was subsequently recovered through BioStudies and read in full as extracted text, with Figure S1 pixels also inspected. Its cellular-fraction Methods cite an earlier protocol, while Figure S1C independently shows FANCB in a FAAP20 co-immunoprecipitate; that is positive complex membership rather than a FANCB-labelled chromatin fraction. No verified FANCB-specific chromatin readout was identified in the inspected main and supplement. This does not establish that FANCB is excluded from chromatin or that the curator used the wrong gene. The inherited supporting quotation specifically concerns FANCA and remains unchanged as historical source context; it is not direct FANCB localization evidence. Without verified target-specific operative evidence for this source claim, retain UNDECIDED rather than rejecting the experimental annotation.

Summary: FANCB contributes structurally to the FA core required for interstrand cross-link repair.

Reason: The current GO:0036297 definition covers removal of a DNA interstrand cross-link and restoration of DNA. PMID:19965384 is pathway-level support: the inspected main experiments use Xenopus egg extracts and recombinant Xenopus FANCI–FANCD2 to establish replication-coupled incision and lesion-bypass requirements, rather than directly measuring human FANCB catalysis. Independent human FANCB evidence places it in the FA core and establishes its organizing role in the FANCL–FAAP100 module (PMID:17396147, Figure 2; PMID:27986592, human BL100 assembly, dropout and crosslinking experiments). This is structural participation in the repair machinery, not merely being a substrate or an incidental damage-response correlate. Retain the broad ICL-repair annotation because the actual FANCB work supports assembly of the repair-activating core but does not identify FANCB as the enzyme executing a narrower incision, translesion-synthesis or ubiquitin-transfer step. The inherited ID2 quotation is preserved with its Xenopus target scope, and no human FANCB incision assay is inferred from it.

Summary: Independent human nuclear-core purification supports FANCB complex membership.

Reason: PMID:22343915 uses tandem affinity purification from HeLa S3 nuclear extracts expressing tagged FANCA/FAAP100 or tagged FAAP20. FANCB is explicitly labelled in the actual core-purification Figure 1A/B, supporting its inclusion in the FA nuclear complex alongside the other recovered subunits. The main purification Methods and figure caption were read, and the figure pixels were inspected. The recovered supplemental Methods specify the tagged constructs/cell lines, and actual Figure S1C pixels independently show FANCB in the FAAP20 immunoprecipitate; no current FANCB sequence-equivalence claim is made. This positive target-specific membership evidence supports GO:0043240 without assigning FAAP20 ubiquitin binding, FANCA-specific chromatin loading, or catalytic ligase activity to FANCB. The unresolved FANCB chromatin annotation from the same publication is a different claim and does not negate the directly visible complex membership.

Summary: A positive cytosolic FANCB pool is retained with a bounded PKR-pathway context.

Reason: Reactome R-HSA-9835411 has explicit input/output paths through the cytosolic FA-core:HSP70 assembly to human FANCB entity 420791, Q8NB91 residues 1–859, with its own GO:0005829 compartment. The source summation emphasizes FANCC-dependent PKR regulation and FANCA/FANCC/FANCG phenotypes. The actual PMID:15299030 abstract likewise identifies those three proteins; complete operative Methods were not recovered, so it is not used to assert either a FANCB-specific PKR mechanism or FANCB absence from the experiment. Independently, PMID:17396147 directly recovered human FANCB–FANCL–FAAP100 from HeLa cytosolic extracts (Figure 2C and Results), as well as a nuclear pool. Keep the genuine location as a contextual, non-core facet of this signaling-model assertion; this does not label cytosolic FANCB an artifact or an inactive protein, nor negate its assembly function.

Summary: Reactome places the FANCB-containing core in nucleoplasm during core assembly.

Reason: Reactome:R-HSA-6785126 was traced through its actual participant links to human FANCB entity 419528, Q8NB91 residues 1–859, whose own compartment is GO:0005654. FANCB is a direct input and a component of the assembled output. The source explicitly models the core assembling in nucleoplasm before DNA loading. Independent human nuclear-core purification supports the biological setting (PMID:17396147 and PMID:20347428). Retain the source-specific nucleoplasm location without treating ten pathway contexts as ten independent localization experiments.

Summary: Reactome places the FANCB-containing core in nucleoplasm during ID2 and UBE2T recruitment.

Reason: Reactome:R-HSA-6785342 was traced through its actual participant links to human FANCB entity 419528, Q8NB91 residues 1–859, whose own compartment is GO:0005654. FANCB remains within the core in both input and output. The source assigns E2 recruitment to FANCL and describes ID2 association; it does not make FANCB the E2 enzyme. Independent human nuclear-core purification supports the biological setting (PMID:17396147 and PMID:20347428). Retain the source-specific nucleoplasm location without treating ten pathway contexts as ten independent localization experiments.

Summary: Reactome places the FANCB-containing core in nucleoplasm during ID2 monoubiquitination.

Reason: Reactome:R-HSA-6785361 was traced through its actual participant links to human FANCB entity 419528, Q8NB91 residues 1–859, whose own compartment is GO:0005654. FANCB is present in input, output and the composite catalytic assembly. The event summation assigns ubiquitin transfer to UBE2T and FANCL; FANCB provides an organizing component, not autonomous ligase chemistry. Independent human nuclear-core purification supports the biological setting (PMID:17396147 and PMID:20347428). Retain the source-specific nucleoplasm location without treating ten pathway contexts as ten independent localization experiments.

Summary: Reactome places the FANCB-containing core in nucleoplasm during nuclease recruitment.

Reason: Reactome:R-HSA-6785732 was traced through its actual participant links to human FANCB entity 419528, Q8NB91 residues 1–859, whose own compartment is GO:0005654. FANCB remains in the core-containing input and output. The newly recruited nucleases and their docking proteins are distinct from FANCB; membership does not confer their DNA-binding or nuclease activities. Independent human nuclear-core purification supports the biological setting (PMID:17396147 and PMID:20347428). Retain the source-specific nucleoplasm location without treating ten pathway contexts as ten independent localization experiments.

Summary: Reactome places the FANCB-containing core in nucleoplasm during ICL unhooking.

Reason: Reactome:R-HSA-6785986 was traced through its actual participant links to human FANCB entity 419528, Q8NB91 residues 1–859, whose own compartment is GO:0005654. FANCB occurs in input, output and the composite catalytic assembly, but the event identifies FAN1 and other nucleases as the incision performers. A target route through that assembly supports location without assigning nuclease chemistry to FANCB. Independent human nuclear-core purification supports the biological setting (PMID:17396147 and PMID:20347428). Retain the source-specific nucleoplasm location without treating ten pathway contexts as ten independent localization experiments.

Summary: Reactome places the FANCB-containing core in nucleoplasm during POLN recruitment.

Reason: Reactome:R-HSA-6786155 was traced through its actual participant links to human FANCB entity 419528, Q8NB91 residues 1–859, whose own compartment is GO:0005654. The target occurs in core-containing input and output complexes. The recruited POLN polymerase is a distinct performer; FANCB is not treated as the polymerase or its DNA substrate. Independent human nuclear-core purification supports the biological setting (PMID:17396147 and PMID:20347428). Retain the source-specific nucleoplasm location without treating ten pathway contexts as ten independent localization experiments.

Summary: Reactome places the FANCB-containing core in nucleoplasm during POLN translesion synthesis.

Reason: Reactome:R-HSA-6786166 was traced through its actual participant links to human FANCB entity 419528, Q8NB91 residues 1–859, whose own compartment is GO:0005654. FANCB remains in the input complex and is released with a core-complex output; a composite catalyst path also contains it. POLN performs synthesis. This source establishes a modeled FANCB location, not DNA-polymerase activity. Independent human nuclear-core purification supports the biological setting (PMID:17396147 and PMID:20347428). Retain the source-specific nucleoplasm location without treating ten pathway contexts as ten independent localization experiments.

Summary: Reactome places the FANCB-containing core in nucleoplasm during ID2 deubiquitination.

Reason: Reactome:R-HSA-6786171 was traced through its actual participant links to human FANCB entity 419528, Q8NB91 residues 1–859, whose own compartment is GO:0005654. The FANCB-containing core is in the substrate complex and output. The actual catalyst is the separate USP1:WDR48 complex, so deubiquitinase activity is not transferred to FANCB. Independent human nuclear-core purification supports the biological setting (PMID:17396147 and PMID:20347428). Retain the source-specific nucleoplasm location without treating ten pathway contexts as ten independent localization experiments.

Summary: Reactome places the FANCB-containing core in nucleoplasm during ATR–ATRIP recruitment.

Reason: Reactome:R-HSA-6788385 was traced through its actual participant links to human FANCB entity 419528, Q8NB91 residues 1–859, whose own compartment is GO:0005654. FANCB remains within core-containing input and output complexes. The source assigns specific recruitment contacts to other components, including FANCL and ATRIP; it does not demonstrate a binary FANCB–ATRIP interaction. Independent human nuclear-core purification supports the biological setting (PMID:17396147 and PMID:20347428). Retain the source-specific nucleoplasm location without treating ten pathway contexts as ten independent localization experiments.

Summary: Reactome places the FANCB-containing core in nucleoplasm during ATR-dependent phosphorylation.

Reason: Reactome:R-HSA-6788392 was traced through its actual participant links to human FANCB entity 419528, Q8NB91 residues 1–859, whose own compartment is GO:0005654. The target occurs in input, output and the composite catalyst assembly. ATR is the kinase and the named phosphorylated proteins are other components; this is not evidence for FANCB kinase activity. Independent human nuclear-core purification supports the biological setting (PMID:17396147 and PMID:20347428). Retain the source-specific nucleoplasm location without treating ten pathway contexts as ten independent localization experiments.

Summary: Human FANCB is recovered as a member of the nuclear FA core complex.

Reason: PMID:20347428 explicitly reports FANCB among the known FA core proteins identified by mass spectrometry and immunoblotting after immunoprecipitation of the FANCM peak from gel-filtered HeLa nuclear extracts (initial Results and Figure 1). Main Methods describe nuclear-extract chromatography and immunoprecipitation; detailed supplementary Methods were not read. This is positive human FANCB complex-membership evidence, although the paper focuses its mechanistic experiments on FANCM and MHF. Retain GO:0043240 for membership; do not transfer the DNA-remodeling, DNA-binding or branch-migration activities of those other proteins to FANCB, or interpret co-purification as a binary contact or a measured native subunit stoichiometry.