BICRA

Summary: BICRA associates with chromatin as a GBAF subunit.

Reason: PMID:29374058 reports sequential salt extraction showing that GLTSCR1 associates with bulk chromatin, together with stable GBAF-complex membership. This supports the cellular-component assertion without implying direct sequence-specific DNA binding.

Summary: The BICRA–NCK1 interaction is corroborated; its functional refinement awaits the study-specific assay record.

Reason: UniProt Q9NZM4 lists NCK1 with NbExp=3 and an IntAct identifier, corroborating the physical interaction. PMID:17474147 reports SH3-domain peptide-array screening including NCK1; its abstract was read, but the BICRA peptide and supplementary assay entry were inaccessible. The missing study-specific record prevents assessment of the BICRA residues, partner domain and assay context needed to decide whether a more informative molecular-function term is supported. UniProt experiment counts do not identify which assays underlie this source row, and the linked IntAct record was inaccessible. UNDECIDED records that unresolved functional assessment. It does not dispute the interaction or infer a native signaling role merely from the partner identity.

Summary: The BICRA–CRK interaction is corroborated; its functional refinement awaits the study-specific assay record.

Reason: UniProt Q9NZM4 lists CRK with NbExp=2 and an IntAct identifier, corroborating the physical interaction. PMID:17474147 reports SH3-domain peptide-array screening including CRK; its abstract was read, but the BICRA peptide and supplementary assay entry were inaccessible. The missing study-specific record prevents assessment of the BICRA residues, partner domain and assay context needed to decide whether a more informative molecular-function term is supported. UniProt experiment counts do not identify which assays underlie this source row, and the linked IntAct record was inaccessible. UNDECIDED records that unresolved functional assessment. It does not dispute the interaction or infer a native signaling role merely from the partner identity.

Summary: Refine BRD4 association to BICRA-mediated coupling of BRD4 and chromatin-remodeling machinery.

Reason: The Results section of PMID:21555454, inspected through the indexed PMC3133372 full text, describes human 293T assays that show tagged GLTSCR1 co-immunoprecipitating endogenous BRD4 and a GLTSCR1 interactome linking BRD4 to chromatin-remodeling components. Together, these experiments and the UniProt subunit annotation support BICRA bridging BRD4 to GBAF. GO:0030674 describes bringing macromolecules together for coordinated function and is more informative than generic binding. This refinement concerns the BRD4-to-complex connection, not merely scaffolding the internal complex or assigning ATPase chemistry to BICRA. The studies do not establish every contact through a purified binary or ternary reconstitution, and the replacement does not assert that stronger assay claim.

Proposed replacements: protein-macromolecule adaptor activity

Summary: Refine BRD4 association to BICRA-mediated coupling of BRD4 and chromatin-remodeling machinery.

Reason: PMID:29374058 identifies BICRA as a stable GBAF component, establishes effects on complex composition, and shows BRD4 associated with GLTSCR1 and other GBAF subunits. Together, these experiments and the UniProt subunit annotation support BICRA bridging BRD4 to GBAF. GO:0030674 describes bringing macromolecules together for coordinated function and is more informative than generic binding. This refinement concerns the BRD4-to-complex connection, not merely scaffolding the internal complex or assigning ATPase chemistry to BICRA. The studies do not establish every contact through a purified binary or ternary reconstitution, and the replacement does not assert that stronger assay claim.

Proposed replacements: protein-macromolecule adaptor activity

Summary: The BICRA–CRK interaction is corroborated; its functional refinement awaits the study-specific assay record.

Reason: UniProt Q9NZM4 lists CRK with NbExp=2 and an IntAct identifier, corroborating the physical interaction. PMID:35044719 reports human domain–peptide mapping; its abstract and selected CRK bait/Results passages were read, but the exact BICRA peptide and supplementary assay record were not inspected. The missing study-specific record prevents assessment of the BICRA residues, partner domain and assay context needed to decide whether a more informative molecular-function term is supported. UniProt experiment counts do not identify which assays underlie this source row, and the linked IntAct record was inaccessible. UNDECIDED records that unresolved functional assessment. It does not dispute the interaction or infer a native signaling role merely from the partner identity.

Summary: Nuclear localization is consistent with BICRA chromatin-complex function.

Reason: The automated nucleus assertion agrees with the nuclear location in the UniProt record, the human GBAF/chromatin experiments in PMID:29374058 and the nucleoplasmic Reactome assembly records. No cytoplasmic or isoform-wide relocation claim is needed.

Summary: Retain the experimentally curated nuclear location.

Reason: PMID:21555454 places GLTSCR1 in a BRD4-associated transcriptional setting; the inspected experiments use nuclear-targeted BRD4 constructs and do not establish endogenous localization of every BICRA isoform. Independent GBAF chromatin-association evidence in PMID:29374058 and the UniProt location support nucleus, so the existing IMP annotation is retained without inventing a new localization assay.

Summary: The BICRA-containing assembly reaction is nucleoplasmic.

Reason: The official Reactome R-HSA-9932443 record explicitly lists nucleoplasm as its compartment and places BICRA/BICRAL and the assembled complex in that compartment. Its cached summary describes recruitment of one of the mutually exclusive paralogs with BRD9. This supports the stated location; it does not require both paralogs in one complex.

Summary: The ATPase-module assembly event supports nucleoplasmic location.

Reason: Reactome R-HSA-9933236 explicitly places the input and output ncBAF assemblies in the human nucleoplasm. BICRA is a constituent of the accepting complex. The compartment, rather than assembly alone, supports the location assertion.

Summary: BICRA participates in chromatin remodeling through GBAF.

Reason: PMID:29374058 establishes stable GBAF membership, effects on complex assembly, chromatin association and DNA-stimulated ATPase activity of GLTSCR1 immunoprecipitates containing BRG1. BICRA contributes to the remodeling machinery as a subunit; the associated SMARCA2/SMARCA4 proteins provide the ATPase, so this process annotation is not an assertion that isolated BICRA is an enzyme.

Summary: Transcription regulation is a central consequence of BICRA chromatin-complex function.

Reason: PMID:29374058 connects BICRA-containing GBAF to BRD4 and reports context-dependent control of the BRD4 target MYC. PMID:21555454 separately shows effects on selected cellular BRD4 target transcripts. Retain the direction-neutral RNA polymerase II regulation term: BICRA does not universally activate every target.

Summary: BICRA supports proliferation in a defined prostate-cancer context.

Reason: PMID:29374058 reports reduced proliferation and colony formation after GLTSCR1 knockout in PC3 cells. Several other tested lines, including LNCaP, did not show an equivalent viability requirement. Keep the positive proliferation annotation as a context-dependent downstream role, not the core molecular function or a universal growth-promoting effect.

Summary: GBAF is the complex that specifically describes BICRA membership.

Reason: The source IBA asserts inherited SWI/SNF-complex membership. Independent human evidence in PMID:29374058 identifies GLTSCR1 in the compositionally distinct GBAF complex. GO:0140288 names that assembly explicitly; current ontology records place GBAF and GO:0016514 under the SWI/SNF superfamily, so this is not described as a strict child-term substitution. No PAINT node-placement error, donor-count weakness or target-self circularity is asserted.

Proposed replacements: GBAF complex

Summary: Refine experimentally demonstrated complex membership to GBAF.

Reason: PMID:29374058 uses gradients and immunoprecipitation to distinguish the GLTSCR1-containing GBAF assembly from canonical BAF and PBAF. GO:0140288 matches this particular complex and avoids a blanket claim of membership in all mammalian SWI/SNF assemblies. Preserve the original IDA source and refine its reviewed interpretation.

Proposed replacements: GBAF complex

Summary: Human BICRA evidence supports the GBAF complex refinement.

Reason: The original Ensembl-based transfer is preserved, including its donor identifiers. Independently inspected human experiments in PMID:29374058 identify BICRA in GBAF, making GO:0140288 the informative complex assignment. This refinement does not diagnose an orthology failure or claim that the donor experiments were re-reviewed.

Proposed replacements: GBAF complex

Summary: Retain a qualified GBAF-associated role in the undifferentiated stem-cell state.

Reason: PMID:30510198 identifies BICRA/BICRAL as GBAF components and links the complex to naive mouse embryonic stem-cell identity. The decisive functional perturbations are mainly BRD9 inhibition/depletion, and the Discussion notes that Gltscr1 deletion alone did not impair pluripotency, plausibly because BICRAL can compensate. Retain this NAS process assertion as a context-limited complex-associated role, not an independently demonstrated BICRA requirement in human stem cells or a general block to differentiation. PMID:33232675 establishes human neurodevelopmental phenotypes and model-organism developmental relevance; it does not test the stem-cell mechanism asserted here and therefore does not supply independent support for that mechanism.

Summary: Positive transcriptional regulation has experimental grounding on BICRA.

Reason: The PAINT IBA is consistent with human GLTSCR1 depletion experiments in PMID:21555454 showing reduced expression of selected BRD4 target genes. Q9NZM4 in its own supporting set is expected when target experiments support the ancestral inference; it is not circular. The full PTN000399987 phylogeny was not independently re-curated. Opposite effects at other genes or in other cells do not negate this positive context.

Summary: GLTSCR1 supports transcription of selected BRD4 target genes.

Reason: PMID:21555454 reports reduced PIM2, CCND1 and DCPS transcripts after GLTSCR1 depletion in human C33A cells, while the RPL13A control was unaffected. Its viral reporter also decreased, although a small reduction in E2 protein complicates that assay alone. Together with BRD4 association, the cellular-transcript result supports positive transcriptional regulation in the tested context.

Summary: GBAF membership is the defining complex assignment.

Reason: PMID:29374058 establishes stable BICRA-containing GBAF assemblies, their separation from canonical BAF/PBAF, and mutually exclusive occupancy by BICRA or BICRAL. This is the central complex-level interpretation of BICRA function.

Summary: Positive transcription is established, but the precise regulator-activator mechanism is unresolved.

Reason: PMID:21555454 positively supports BRD4 association and activation of selected target-gene transcription. The current official GO:0140537 definition concerns increasing a transcription regulator's activity, and its usage comment explicitly excludes activity at the promoter; GO:0003713 instead concerns coactivation at a genomic locus. The selected BICRA experiments do not distinguish these spatial mechanisms. Positive transcript changes therefore support GO:0045893 without by themselves settling GO:0140537. The paper's NSD3/JMJD6 promoter ChIP is not a BICRA experiment. Retain UNDECIDED for the specific IMP molecular-function assertion; neither removal nor a GO:0003713 replacement is justified by the inspected evidence.

Summary: The stem-cell-maintenance role is a qualified GBAF-level developmental context.

Reason: PMID:30510198 provides mouse ESC evidence for a BRD9-containing GBAF complex that supports the naive pluripotent state. BICRA is a component, but the perturbation evidence is principally BRD9-directed and paralog compensation limits the interpretation of Gltscr1 deletion. Retain the NAS annotation as non-core with this explicit complex/species boundary, rather than assert a unique human BICRA stem-cell-maintenance activity. PMID:33232675 establishes human neurodevelopmental phenotypes and model-organism developmental relevance; it does not test the stem-cell mechanism asserted here and therefore does not supply independent support for that mechanism.