BRCA1 is a nuclear tumor-suppressor protein that organizes DNA damage responses and homologous-recombination repair through several distinct molecular activities. Its N-terminal RING domain engages ubiquitin-conjugating enzymes in a ligase heterodimer with BARD1, modifying nucleosomal histones and other substrates; ubiquitin linkage and substrate specificity depend on the E2 and biochemical context. Tandem C-terminal BRCT repeats recognize phosphorylated protein motifs, while a central DNA-binding region and protein-interaction interfaces cooperate with BARD1 to promote DNA-end resection and recruitment of repair factors. BRCA1-containing assemblies also influence damage checkpoints, transcriptional regulation and context-dependent centrosome and metabolic responses. Pathogenic germline variants cause hereditary breast and ovarian cancer predisposition.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004842 ubiquitin-protein transferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA1 is the E2-engaging subunit of the BRCA1βBARD1 RING ubiquitin ligase. Reason: The phylogenetic assertion agrees with direct biochemical and structural evidence on human BRCA1βBARD1. Purified heterodimer produces K6-linked autoubiquitin in the conditions tested by Wu-Baer and colleagues; other E2 partners support different products. Acceptance does not depend on the erroneous unrelated PMID previously cited in this rationale, and does not claim that the PAINT tree or all donor experiments were independently reread. |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: BRCA1 has experimentally demonstrated DNA-binding activity in its central region. Reason: Purified central BRCA1 fragments bind DNA, and the BRCA1 DNA-binding module contributes to resection stimulation by the intact BRCA1βBARD1 complex. Generic DNA binding is a sound description of these assays. Recruitment through BRCT phosphoprotein recognition is a separate mechanism and does not by itself justify replacing every DNA-binding assertion with damaged DNA binding. |
| GO:0004842 ubiquitin-protein transferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: The BRCA1 RING domain supports ubiquitin ligase activity with BARD1. Reason: The InterPro-derived activity agrees with direct human heterodimer biochemistry and the structure positioning an E2 enzyme through the BRCA1 RING. It is retained as a distinct source assertion, without treating agreement with another annotation as independent experimental replication. |
| GO:0005515 protein binding | IPI PMID:10477523 Functional interaction of BRCA1-associated BARD1 with polyad... | KEEP AS NON CORE | Summary: BRCA1 association with BARD1 is supported; the recorded partner is BARD1, not CstF-50. Reason: The GOA partner is Q99728. The original abstract directly studies BARD1-CstF-50 and does not expose the BRCA1-BARD1 assay. Independent PMID:8944023 explicitly identifies BARD1 binding to the BRCA1 N terminus and its disruption by BRCA1 variants. Retain the correct interaction as non-core with that corroboration, without attributing direct CstF-50 binding or the polyadenylation-inhibitory mechanism to BRCA1. |
| GO:0005515 protein binding | IPI PMID:11090615 Sequence-specific transcriptional corepressor function for B... | KEEP AS NON CORE | Summary: BRCA1 binds the transcriptional corepressor ZBRK1. Reason: The abstract explicitly reports BRCA1-ZBRK1 interaction in vitro and in vivo and a nuclear complex at a GADD45 intronic recognition sequence. This supports the recorded Q9GZX5 interaction. Keep the supported binding as non-core; ZBRK1 sequence recognition and repression do not by themselves make BRCA1 a sequence-specific DNA-binding factor. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11739404 BRCA1-induced large-scale chromatin unfolding and allele-spe... | KEEP AS NON CORE | Summary: BRCA1 BRCT fragments bind COBRA1 and CtIP with distinct responses to cancer-associated variants. Reason: The cached Results and Figure 5 text report endogenous BRCA1 coimmunoprecipitation with FLAG-COBRA1 in HEK293T cells and GST-fragment pull-downs of both in-vitro-translated COBRA1 and CtIP. M1775R enhances COBRA1 association but abolishes CtIP association in that assay. Both GOA partners are supported; retain the interactions without turning the engineered lac-operator chromatin-unfolding assay into an intrinsic ATPase assertion. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11836499 BRCA1 regulates the G2/M checkpoint by activating Chk1 kinas... | UNDECIDED | Summary: BRCA1-dependent CHK1 activation is established, but the recorded BRCA1-CHK1 binding assay is not exposed in the available abstract. Reason: The abstract describes CHK1 activation and regulation of G2/M effectors. It does not identify the assay establishing physical binding to the GOA partner O14757. Functional activation alone cannot settle this interaction record. Preserve the curator IPI assertion as UNDECIDED pending its target-specific assay; do not remove it or call it misattributed. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12419185 NBS1 localizes to gamma-H2AX foci through interaction with t... | UNDECIDED | Summary: The BRCA1-H2AX interaction requires inspection of the target-specific experiment. Reason: The recorded partner is P16104/H2AX. The abstract establishes direct binding of the NBS1 FHA/BRCT region to gamma-H2AX and notes that this can occur without NBS1 association with BRCA1. That does not establish that the BRCA1-H2AX IPI row is false, nor does it demonstrate this pair. Keep the assertion unresolved; do not relabel the NBS1 domain experiment as a BRCA1 domain experiment. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12607005 MDC1 is a mediator of the mammalian DNA damage checkpoint. | UNDECIDED | Summary: MDC1-dependent BRCA1 recruitment does not by itself resolve the BRCA1-MDC1 physical interaction. Reason: The abstract reports MDC1 interaction with phosphorylated H2AX and effects on BRCA1 focus formation, but does not describe the BRCA1-Q14676 binding experiment. The relevant full assay is not in this cache. Preserve the source assertion as UNDECIDED rather than infer binding from recruitment or remove it on the basis of the paper focus. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:14550570 BRCA1 interacts with FHL2 and enhances FHL2 transactivation ... | KEEP AS NON CORE | Summary: BRCA1 physically associates with FHL2 in the transcriptional assays described. Reason: The abstract reports yeast two-hybrid identification, association in vitro, yeast and human cells, and mapping to the second BRCT repeat and FHL2 LIM domains. The Q14192 interaction is directly supported. Retain non-core binding with its transcriptional context rather than remove it for generic terminology. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:14654789 A member of the Pyrin family, IFI16, is a novel BRCA1-associ... | KEEP AS NON CORE | Summary: BRCA1 binds IFI16 through mapped regions in the DNA-damage/apoptosis study. Reason: The abstract maps BRCA1 residues 502-802 to the IFI16 Pyrin region and distinguishes a binding-deficient IFI16 mutant in cellular apoptosis assays. This supports Q16666 binding. Keep the molecular association without treating every apoptosis effect as an intrinsic enzymatic or universal process function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15125843 Structure of the BRCT repeats of BRCA1 bound to a BACH1 phos... | MODIFY | Summary: The BRCA1 tandem BRCT domain recognizes a phosphoserine-containing BACH1/BRIP1 peptide. Reason: The abstract explicitly describes the human BRCA1 BRCT-phosphopeptide crystal structure, with BACH1 Ser990 phosphorylation and Phe993 anchoring the interface. GO:0050815 is a more informative description of the measured recognition than generic protein binding. The structural construct is a domain-peptide complex, not proof of every interaction of full-length proteins in cells. Proposed replacements: phosphoserine residue binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15133502 Structure and mechanism of BRCA1 BRCT domain recognition of ... | MODIFY | Summary: BRCA1 BRCT recognition of the phosphorylated BACH1/BRIP1 interaction segment is supported structurally. Reason: The abstract reports the human tandem-BRCT complex with the minimal phosphorylated BACH1 peptide and selective disruption of phospho-dependent interactions by variants. Together with the directly mapped Ser990 anchor in PMID:15125843, this supports phosphoserine residue binding. Keep the construct and phospho-dependent recognition limits explicit. Proposed replacements: phosphoserine residue binding |
| GO:0005515 protein binding | IPI PMID:15674350 Structural determinants of the BRCA1 : estrogen receptor int... | KEEP AS NON CORE | Summary: BRCA1 binds ER-alpha through mapped N-terminal interaction regions. Reason: The abstract describes contact mapping and in-vitro/cellular interaction and repression assays for the P03372 partner. Retain the documented interaction as non-core. Do not substitute ER-beta, and do not infer that BRCA1 itself has estrogen receptor activity from regulation of receptor transcription. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15965487 BRCA1 participates in DNA decatenation. | KEEP AS NON CORE | Summary: BRCA1 associates with topoisomerase II-alpha in S-phase cells. Reason: The abstract explicitly reports interaction and colocalization with P11388, BRCA1-dependent topoisomerase ubiquitination and DNA-decatenation effects. Retain the interaction without attributing topoisomerase catalysis to BRCA1; the separate enzyme-binding annotation can carry that broader partner class. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16326698 BRCA1 affects lipid synthesis through its interaction with a... | MODIFY | Summary: BRCA1 binds phosphorylated inactive acetyl-CoA carboxylase alpha. Reason: The abstract states that BRCA1 binds only the phosphorylated inactive ACCA form and prevents its dephosphorylation. GO:0051219 captures the observed phosphoprotein recognition without adding an unsupported catalytic claim or guessing the residue from this abstract. The two GOA entries with Q13085 are retained as original source evidence. Proposed replacements: phosphoprotein binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16452482 ATM activation by ionizing radiation requires BRCA1-associat... | KEEP AS NON CORE | Summary: BRCA1 associates with BRAT1, originally called BAAT1, in the reported DNA-damage study. Reason: The abstract describes recovery of BAAT1 as a BRCA1-associated protein by yeast two-hybrid screening and its association with ATM. Retain Q6PJG6 binding as non-core. The functional ATM phosphorylation and phosphatase experiments concern BAAT1/BRAT1 and do not establish BRCA1 kinase activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17334399 Functional consequences of cyclin D1/BRCA1 interaction in br... | UNDECIDED | Summary: The cyclin-D1-specific binding experiment remains unverified from the available abstract. Reason: The abstract reports phosphorylation of BRCA1 by a cyclin D1-CDK4 complex and ensuing promoter-occupancy effects. The recorded GOA partner is P24385/cyclin D1, not CDK4. Those substrate/complex experiments do not alone expose the physical interaction assay underlying this IPI record. Keep UNDECIDED until that assay is inspected, without calling the annotation wrong. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17511879 The interaction of PP1 with BRCA1 and analysis of their expr... | MODIFY | Summary: BRCA1 binds the alpha, beta and gamma catalytic subunits of protein phosphatase 1. Reason: The actual cached Results and Figure 1-2 text show a yeast two-hybrid PP1beta hit, mapping of a KVTF-containing BRCA1 region by GST pull-down, reduced binding after motif substitutions, and reciprocal coimmunoprecipitation with all three PP1 variants in HEK293T cells. GO:0008157 describes all three recorded partners more precisely. It does not assert BRCA1 phosphatase catalysis. Proposed replacements: protein phosphatase 1 binding Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17525332 ATM and ATR substrate analysis reveals extensive protein net... | UNDECIDED | Summary: The four BRCA1 interaction edges in the ATM/ATR network study need target-row inspection. Reason: The abstract describes a large phosphorylation network but does not expose the binding tests for P24864, Q12888, Q14676 or Q6NZY4. Phosphorylation enrichment and network membership are not substitutes for inspecting these IPI edges. Preserve the curator assertions as unresolved rather than remove a screen annotation merely because it is generic. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | KEEP AS NON CORE | Summary: BRCA1 binds phospho-Abraxas and participates in distinct Abraxas-RAP80, BACH1 and CtIP complexes. Reason: The abstract directly establishes phospho-motif binding of Abraxas and its bridging of RAP80 to BRCA1, with Abraxas mutually exclusive with BACH1 or CtIP. Retain this multi-partner source row as non-core binding; do not treat all recorded partners as one simultaneous complex or generalize direct phosphopeptide recognition to RAP80. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17581638 The FANCJ/MutLalpha interaction is required for correction o... | KEEP AS NON CORE | Summary: The BRCA1-FANCJ interaction is retained although it is dispensable for the specific cross-link response tested. Reason: The cached abstract and Introduction/Discussion distinguish FANCJ-BRCA1 association from FANCJ-MLH1 binding and show that eliminating BRCA1 binding does not abolish correction of the tested FA-J ICL response. That functional dispensability does not negate the physical interaction. Independent PMID:11301010 directly supports BRCA1-BACH1 binding. Results/Methods are absent from this partial cache, so no claim is made to have read their assay panels. |
| GO:0005515 protein binding | IPI PMID:17643121 CCDC98 targets BRCA1 to DNA damage sites. | KEEP AS NON CORE | Summary: CCDC98/Abraxas mediates association between BRCA1 and RAP80. Reason: The abstract explicitly identifies CCDC98 as a BRCA1 partner and the mediator of its association with RAP80. Keep both the Q6UWZ7 and Q96RL1-1 GOA assertions in this context without claiming a direct binary BRCA1-RAP80 interface or deleting the partner isoform designation. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:17873885 E2-BRCA1 RING interactions dictate synthesis of mono- or spe... | KEEP AS NON CORE | Summary: This generic-binding source row records BARD1 association with BRCA1. Reason: The GOA partner here is Q99728/BARD1. The abstract uses the human heterodimeric BRCA1-BARD1 E3 to study six E2 interactions with BRCA1; those E2 results must not replace the partner on this row. Retain supported heterodimer association, also corroborated by PMID:8944023. The separately seeded E2-related row can be assessed on its own partner. |
| GO:0005515 protein binding | IPI PMID:18001824 RNF8 ubiquitylates histones at DNA double-strand breaks and ... | UNDECIDED | Summary: BRCA1 interaction with H2AX or 53BP1 cannot be established from recruitment evidence alone. Reason: The GOA partners are P16104 and Q12888, not RNF8. The abstract describes RNF8-dependent histone ubiquitylation and BRCA1/53BP1 retention at breaks; it does not expose the assays for the two recorded BRCA1 interactions. Preserve these experimental assertions as UNDECIDED rather than infer direct binding or remove them because of the RNF8-focused title. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18001825 RNF8 transduces the DNA-damage signal via histone ubiquityla... | UNDECIDED | Summary: The BRCA1-H2AX binding experiment remains unresolved in this partial cache. Reason: Although marked full_text_available, the cached body contains Introduction and Discussion, without the Results/Methods supporting the P16104 interaction. It establishes RNF8-dependent ubiquitylation and recruitment of BRCA1, and explicitly distinguishes these from BRCA1-dependent H2AX ubiquitylation. This does not adjudicate the IPI pair; retain UNDECIDED. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18285836 Pathogenicity of the BRCA1 missense variant M1775K is determ... | MODIFY | Summary: The BRCA1 BRCT phosphopeptide-binding pocket mediates recognition of BRIP1 and CtIP. Reason: The abstract and Discussion report that M1775K obstructs the phosphopeptide-binding pocket and interferes with both partners. Independent structures in PMID:15125843 and PMID:16101277 identify the relevant BRIP1 and CtIP phosphoserine anchors. Refine to GO:0050815 while keeping the original variant study as evidence and avoiding a claim that every functional Results subsection was available in this partial cache. Proposed replacements: phosphoserine residue binding |
| GO:0005515 protein binding | IPI PMID:19369211 PALB2 is an integral component of the BRCA complex required ... | KEEP AS NON CORE | Summary: BRCA1 binds PALB2 and associates with repair complexes containing CtIP, BARD1 and BRIP1. Reason: The abstract and cached Discussion describe direct coiled-coil-mediated PALB2-BRCA1 association and PALB2 precipitates containing CtIP or BACH1. This establishes the generic interaction assertion even though the complete Results/Methods and every partner-specific assay are not cached. Keep all original partner records; distinguish direct PALB2 binding from co-complex evidence and do not claim one obligatory four-partner assembly. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20016594 The SUMO modification pathway is involved in the BRCA1 respo... | UNDECIDED | Summary: SUMO modification of BRCA1 is not by itself evidence for noncovalent SUMO binding. Reason: The abstract establishes stress-dependent SUMO conjugation and colocalization with SUMO1 and SUMO2/3. The GOA partners are P61956 and P63165. The assay underlying their IPI interpretation is not exposed, so retain UNDECIDED rather than equate covalent modification or colocalization with a SUMO-binding activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20016603 Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses ... | UNDECIDED | Summary: The BRCA1-SUMO2 interaction needs the underlying immunoprecipitation/conjugation experiment. Reason: The cached abstract plus short Methods summary describe coordinated SUMOylation and ubiquitylation and mention immunoprecipitation of BRCA1 and SUMOylated proteins, but omit the actual results needed to distinguish covalent conjugation from noncovalent binding to P61956. Preserve the source assertion as unresolved; no SUMO-binding replacement is justified from these passages. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21240188 Interaction between the helicases genetically linked to Fanc... | KEEP AS NON CORE | Summary: BRCA1 binding to FANCJ is retained with independent direct evidence and a source-access qualification. Reason: The available Introduction/Discussion treats BRCA1 as an established FANCJ partner, while the new experiments summarized focus on BLM-FANCJ binding independent of BRCA1. PMID:11301010 directly supports the same Q9BX63 interaction. Retain non-core binding using that corroboration, while recording that the target assay from PMID:21240188 was not available; BLM independence does not disprove BRCA1-FANCJ binding. |
| GO:0005515 protein binding | IPI PMID:21407215 Multifunctional transcription factor TFII-I is an activator ... | KEEP AS NON CORE | Summary: BRCA1 associates with TFII-I through its BRCT domain in nuclear complexes. Reason: The cached Results describe BRCT affinity capture and reciprocal endogenous coimmunoprecipitation in HeLa cells, with deletion analysis in COS7 cells. These directly support P78347 association. Keep as non-core binding without assigning TFII-I DNA-sequence recognition to BRCA1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21951318 Ligand-dependent differences in estrogen receptor beta-inter... | KEEP AS NON CORE | Summary: BRCA1 coassociates with ER-beta in a cell- and ligand-dependent context. Reason: The actual Results and Figure 5 text report coimmunoprecipitation with endogenous ER-beta in treated A549/H1944 cells and in tumor samples, with absence in tested H1793/H1792 or normal-tissue conditions. Retain Q92731 association, bounded to co-complex evidence rather than a universally present direct binary interaction or an ER-alpha result. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | UNDECIDED | Summary: The BRCA1 edges to HSPD1 and FHL2 in the liver interaction screen remain uninspected. Reason: The cached paper describes the large yeast two-hybrid screen, but searches of the actual body find no BRCA1, FHL2 or HSPD1 target record; the supplementary interaction tables have not been inspected. A global validation percentage cannot validate P10809 and Q14192 individually. Preserve the source-specific IPI assertion as UNDECIDED, notwithstanding independently supported FHL2 binding in another paper. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22110403 Interplay between BRCA1 and RHAMM regulates epithelial apico... | KEEP AS NON CORE | Summary: BRCA1 associates with RHAMM-containing complexes during cell-cycle-dependent microtubule regulation. Reason: The actual Results/Figure 5 text reports RHAMM species in BRCA1 immunoprecipitates and interprets a mobility shift as suggestive of phosphorylation. Retain O75330 association without claiming direct phospho-RHAMM recognition. Q99728/BARD1 is the other GOA partner and has direct independent support in PMID:8944023; not every original supplementary panel was inspected here. |
| GO:0005515 protein binding | IPI PMID:22193777 ChAM, a novel motif that mediates PALB2 intrinsic chromatin ... | KEEP AS NON CORE | Summary: BRCA1-PALB2 complex association is retained; the histone partner remains less resolved. Reason: The partial cached Introduction/Discussion states that the PALB2 ChAM deletion retains known binding partners and discusses BRCA1-mediated recruitment. Independent PMID:19369211 directly establishes Q86YC2/PALB2 binding. Retain the generic binding assertion on that evidence while preserving P16104/H2AX as an unverified partner-specific edge; PALB2 nucleosome binding is not proof of a direct BRCA1-H2AX interface. |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:12890688 The BRCA1/BARD1 heterodimer assembles polyubiquitin chains t... | ACCEPT | Summary: Purified full-length BRCA1βBARD1 assembles predominantly K6-linked chains in the reported assay. Reason: The source directly tests linkage specificity and BRCA1 autoubiquitination, supporting ubiquitin transferase activity. It does not itself establish that K6 is the only linkage BRCA1βBARD1 can produce, or prove a universal requirement for this activity in tumor suppression. Supporting Evidence: |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1 associates with the DNMT1 regulatory region. Reason: The DNMT1 study reports promoter occupancy involving OCT1 and BRCA1-dependent DNMT1 regulation. Retain the transcriptional regulatory-region association with that cellular context; promoter occupancy is not recast as autonomous sequence-specific DNA recognition by BRCA1. Supporting Evidence: |
| GO:0003684 damaged DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: BRCA1βBARD1 binds DNA-break substrates and its BRCA1 DNA-binding module supports resection. Reason: The orthology-derived assertion is consistent with biochemical and single-molecule analysis of the heterodimer on DNA-end substrates and with the BRCA1 DNA-binding module. The previously supplied BACH1 phosphopeptide structure is not evidence of direct DNA binding. That BRCT-mediated protein-recognition mechanism is kept separate from DNA binding; the exact ortholog-transfer provenance has not been independently reconstructed. |
| GO:0003713 transcription coactivator activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1 contributes to transcriptional activation in defined promoter and reporter contexts. Reason: BRCA1-containing transcriptional complexes and promoter/reporter assays support this function. RHA links BRCA1 to RNA polymerase II, and BRCA1 regulates DNMT1 through a promoter complex. The annotation is retained outside the principal repair-focused synthesis; the available evidence does not establish that transcriptional regulation is dispensable for tumor suppression. |
| GO:0007098 centrosome cycle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1 has a centrosomal role in controlling duplication. Reason: Centrosomal localization, gamma-tubulin association and centrosome-amplification phenotypes support this cell-cycle role. It is retained as a contextual function alongside the central DNA repair mechanisms, without implying that BRCA1 catalyses microtubule nucleation. |
| GO:0043009 chordate embryonic development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1 is implicated in chordate embryonic development. Reason: Retain the existing comparative developmental assertion as a contextual role. Loss of genome-maintenance functions can affect development, but lethality alone neither identifies a dedicated developmental reaction nor proves that all developmental effects are secondary. The complete ortholog experiments and PAINT ancestral-node placement were not independently reconstructed. Supporting Evidence: file:human/BRCA1/BRCA1-uniprot.txt |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1-dependent DNMT1 expression contributes to CpG-associated gene regulation. Reason: The source connects BRCA1-dependent DNMT1 regulation with DNA methylation and expression effects. This is a supported regulatory relationship, not methyltransferase catalysis by BRCA1. Its non-core designation does not imply that the measured phenotype is false. Supporting Evidence: |
| GO:0044818 mitotic G2/M transition checkpoint | IEA GO_REF:0000107 | ACCEPT | Summary: BRCA1 contributes to DNA damage-dependent G2/M checkpoint signaling. Reason: BRCA1-containing repair/checkpoint assemblies and perturbation studies support inhibition of mitotic entry after damage. BRCA1 acts as an assembly and signaling factor; ATM/ATR and downstream kinases perform the phosphorylation reactions. Acceptance of the broad checkpoint function does not claim a freshly reconstructed PAINT tree or a direct kinase activity for BRCA1. |
| GO:0060816 random inactivation of X chromosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1 is associated with XIST-dependent inactive-X chromatin in the source experiments. Reason: The source reports association with XIST RNA, localization to inactive-X chromatin and effects on XIST localization. Retain the specific regulatory context without inferring a direct binary RNA contact or claiming that this role is universally required in every tissue. Supporting Evidence: |
| GO:0003713 transcription coactivator activity | IDA PMID:20820192 BRCA1 affects global DNA methylation through regulation of D... | KEEP AS NON CORE | Summary: BRCA1 contributes to transcriptional activation in defined promoter and reporter contexts. Reason: BRCA1-containing transcriptional complexes and promoter/reporter assays support this function. RHA links BRCA1 to RNA polymerase II, and BRCA1 regulates DNMT1 through a promoter complex. The annotation is retained outside the principal repair-focused synthesis; the available evidence does not establish that transcriptional regulation is dispensable for tumor suppression. Supporting Evidence: |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-9701000 | ACCEPT | Summary: Reactome pathway annotation for BRCA1-BARD1 autoubiquitination activity. Reason: The curated Reactome event describes BRCA1βBARD1 autoubiquitination. Independent purified-heterodimer and E2-interaction studies support the ubiquitin-transferase activity, with products dependent on the biochemical conditions. This event supports the activity assertion; it does not by itself establish that autoubiquitination or every ligase product is universally required for DNA repair. Supporting Evidence: Reactome:R-HSA-9701000 |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IMP PMID:20820192 BRCA1 affects global DNA methylation through regulation of D... | KEEP AS NON CORE | Summary: BRCA1-dependent DNMT1 expression contributes to CpG-associated gene regulation. Reason: The source connects BRCA1-dependent DNMT1 regulation with DNA methylation and expression effects. This is a supported regulatory relationship, not methyltransferase catalysis by BRCA1. Its non-core designation does not imply that the measured phenotype is false. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:16101277 Structural basis for cell cycle checkpoint control by the BR... | MODIFY | Summary: BRCA1 tandem BRCT repeats recognize phosphorylated CtIP at Ser327. Reason: The abstract explicitly reports a human CtIP phosphopeptide-BRCT crystal structure and thermodynamic comparison with BACH1, including the phospho-Ser327 anchor and perturbation by M1775R. GO:0050815 is an evidence-matched refinement of this Q99708 interaction. Do not infer CtIP nuclease or checkpoint catalysis for BRCA1. Proposed replacements: phosphoserine residue binding Supporting Evidence: |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:17349954 A critical role for the ubiquitin-conjugating enzyme Ubc13 i... | ACCEPT | Summary: BRCA1 ubiquitin ligase activation is coupled to Ubc13-dependent DNA damage responses. Reason: The source reports loss of BRCA1 recruitment and E3 activation in Ubc13-deficient cells. This supports the curated activity together with independent purified BRCA1βBARD1 assays. Ubc13 depletion is not the same experiment as a BRCA1-specific ligase-null separation-of-function mutant and is not presented as such. |
| GO:0002039 p53 binding | IDA PMID:15571721 Characterization of segments from the central region of BRCA... | KEEP AS NON CORE | Summary: Central BRCA1 polypeptides bind p53 in biophysical assays. Reason: The source describes binding of purified BRCA1 central-region fragments to p53 and DNA at low-micromolar affinities. This is a supported specific interaction, retained outside the principal core-function synthesis. Binding alone does not establish every downstream p53-dependent response or make p53 binding the single defining mechanism of BRCA1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:10518542 BRCA1-associated growth arrest is RB-dependent. | KEEP AS NON CORE | Summary: BRCA1 complexes with hypophosphorylated RB in the reported growth-suppression experiments. Reason: The abstract maps BRCA1 residues 304-394 and the pRb ABC region in binding. The cached Discussion cautions that RB dependence alone is not proof that direct binding causes growth suppression. Retain P06400 association while preserving that causal distinction and without redefining the interaction as generic phosphoprotein recognition. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12354784 BRCA1 interacts directly with the Fanconi anemia protein FAN... | KEEP AS NON CORE | Summary: BRCA1 directly interacts with FANCA through mapped regions. Reason: The abstract reports yeast two-hybrid, in-vitro-synthesis coimmunoprecipitation and cell-extract coimmunoprecipitation, with BRCA1 residues 740-1083 and the FANCA N terminus implicated. Retain O15360 binding; interaction with FANCA is not evidence that BRCA1 possesses every activity of the FA core complex. Supporting Evidence: |
| GO:0051726 regulation of cell cycle | IDA PMID:21102443 Transcriptional regulation of BRCA1 expression by a metaboli... | ACCEPT | Summary: BRCA1 participates in DNA damage-dependent cell-cycle control. Reason: The broad activity is well supported by BRCA1 checkpoint studies. The original metabolic-switch paper primarily manipulates CtBP and BRCA1 promoter regulation; its G2-block observation follows CtBP depletion and is not recast as a purified BRCA1 activity. Independent BRCA1βBARD1 depletion and p53/p21 checkpoint results corroborate the curated broad function. |
| GO:0003713 transcription coactivator activity | IMP PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme ... | KEEP AS NON CORE | Summary: BRCA1 contributes to transcriptional activation in defined promoter and reporter contexts. Reason: BRCA1-containing transcriptional complexes and promoter/reporter assays support this function. RHA links BRCA1 to RNA polymerase II, and BRCA1 regulates DNMT1 through a promoter complex. The annotation is retained outside the principal repair-focused synthesis; the available evidence does not establish that transcriptional regulation is dispensable for tumor suppression. |
| GO:0005515 protein binding | IPI PMID:20160719 Identification of DBC1 as a transcriptional repressor for BR... | KEEP AS NON CORE | Summary: DBC1 binds the BRCA1 BRCT region and modulates its transcriptional readouts. Reason: The actual cached Results describe coimmunoprecipitation, GST-BRCT binding to in-vitro-translated DBC1, domain mapping and mammalian two-hybrid assays. These support Q8N163 association. Retain as non-core; repression of BRCA1 reporter activity by DBC1 does not justify an unrelated BRCA1 inhibitory enzyme annotation. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21673012 KIAA0101 interacts with BRCA1 and regulates centrosome numbe... | KEEP AS NON CORE | Summary: BRCA1 associates with KIAA0101/PAF15 in the centrosome-regulation study. Reason: The abstract and cached Discussion explicitly report KIAA0101 in a BRCA1 complex and distinguish centrosome effects from an absent effect on homologous recombination in their assay. The partial Results mainly cover candidate discovery; the binding panel and Methods are not present. Retain Q15004 association on the explicit source report, with no claim of having inspected that missing assay or of direct purified-protein binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11751867 The LIM domain protein LMO4 interacts with the cofactor CtIP... | KEEP AS NON CORE | Summary: BRCA1 associates with LMO4 and CtIP in a transcription-regulatory complex. Reason: The abstract reports BRCT-mediated LMO4 association, differential effects of BRCA1 variants on LMO4 versus CtIP binding, and an in-vivo complex. Retain P61969/LMO4 binding. The molecular-adaptor description in this abstract concerns LMO4; it does not by itself establish an adaptor-function replacement for BRCA1. Supporting Evidence: |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:20820192 BRCA1 affects global DNA methylation through regulation of D... | KEEP AS NON CORE | Summary: BRCA1 associates with the DNMT1 regulatory region. Reason: The DNMT1 study reports promoter occupancy involving OCT1 and BRCA1-dependent DNMT1 regulation. Retain the transcriptional regulatory-region association with that cellular context; promoter occupancy is not recast as autonomous sequence-specific DNA recognition by BRCA1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:18716619 CDK targets Sae2 to control DNA-end resection and homologous... | KEEP AS NON CORE | Summary: BRCA1-CtIP binding is retained with direct independent evidence and a limit on this citation. Reason: The available original paper contains the yeast Sae2 abstract and a Methods summary mentioning CtIP downregulation; the specific human BRCA1-CtIP binding experiment is not exposed. PMID:16101277 directly establishes the same Q99708 interaction. Retain non-core binding using that corroboration without asserting that the yeast-focused abstract proves the human pair or that the original annotation is erroneous. |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:20351172 The UBXN1 protein associates with autoubiquitinated forms of... | ACCEPT | Summary: The UBXN1 study supports ubiquitin-protein transferase activity by BRCA1βBARD1. Reason: The source measures the heterodimer, autoubiquitinated BRCA1 and inhibition of ligase function by UBXN1. Its K6-chain observations concern the reported conditions, not a universal exclusion of other ubiquitin linkages. The established activity and complex remain core even though the upstream inhibitor is another protein. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:20351172 The UBXN1 protein associates with autoubiquitinated forms of... | KEEP AS NON CORE | Summary: UBXN1 associates with autoubiquitinated BRCA1-BARD1 through two interaction modes. Reason: The abstract and full cached Discussion distinguish UBXN1 UBA recognition of BRCA1-conjugated K6 chains from ubiquitin-independent interaction with the heterodimer. Retain Q04323 association; do not transfer UBXN1 ubiquitin-recognition activity or its inhibitory action to BRCA1 itself. The detailed Results/Methods are absent from this partial cache. Supporting Evidence: |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:19117993 BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING ... | ACCEPT | Summary: The BAP1 study directly measures the BRCA1βBARD1 ligase complex. Reason: The source reports that BAP1 interacts with BARD1, perturbs BRCA1βBARD1 association and inhibits BRCA1 autoubiquitination and NPM1 ubiquitination. These are measurements of the annotated complex and its activity; they do not assign BAP1 hydrolase activity to BRCA1 or imply every BAP1 association is a direct BRCA1 contact. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19117993 BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING ... | KEEP AS NON CORE | Summary: BAP1 associates with and perturbs the BRCA1-BARD1 complex. Reason: The original abstract maps the new direct contact to BARD1 and describes interference with the BRCA1-BARD1 association; it does not demonstrate that this newer assay maps a direct BAP1-BRCA1 interface. Independent PMID:9528852 directly reports BAP1 binding the BRCA1 RING region. Keep Q92560 binding with both contexts and no claim that BRCA1 has BAP1 deubiquitinase activity. |
| GO:0003723 RNA binding | IDA PMID:12419249 BRCA1 supports XIST RNA concentration on the inactive X chro... | KEEP AS NON CORE | Summary: BRCA1 associates with XIST RNA in the inspected source. Reason: RNA association and XIST localization experiments support the curated RNA-binding assertion with curator deference. The accessible evidence does not distinguish purified direct RNA contact from association in a ribonucleoprotein complex; this narrower mechanistic uncertainty is not evidence that the interaction is false. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | KEEP AS NON CORE | Summary: BRCA1 recruitment through CCDC98/Abraxas is supported in the RAP80-complex context. Reason: The actual partner is Q6UWZ7/Abraxas, not MERIT40. The cached Discussion describes the Abraxas C-terminal phospho-dependent BRCA1 connection and MERIT40-mediated stabilization of a five-subunit recruitment complex; PMID:17525340 provides direct Abraxas-binding evidence. Retain this association without inventing a direct BRCA1-MERIT40 interface. |
| GO:0005515 protein binding | IPI PMID:12242698 Highlight: BRCA1 and BRCA2 proteins in breast cancer. | UNDECIDED | Summary: The BRCA1-BRCA2/RAD51 IPI assertions cannot be adjudicated from this review abstract. Reason: PMID:12242698 is a review summarizing several functions and protein partnerships, not an exposed primary assay for P51587 and Q06609. The relevant cited experiments and their exact linkage to these GOA records are not available in this cache. Preserve both records as unresolved rather than call the biology false or convert a general review summary into a direct binding experiment. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15107825 BRCA1 cooperates with NUFIP and P-TEFb to activate transcrip... | KEEP AS NON CORE | Summary: BRCA1 associates with NUFIP in the transcriptional system studied. Reason: The abstract explicitly reports a human NUFIP yeast two-hybrid interaction with BRCA1 and separates NUFIP-P-TEFb/Cyclin T1 association from BRCA1-dependent transcriptional synergy. Retain Q9UHK0 binding; no BRCA1 ATPase or direct Cyclin T1 interface is inferred from the NUFIP experiments. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:10855792 VCP, a weak ATPase involved in multiple cellular events, int... | KEEP AS NON CORE | Summary: BRCA1 physically associates with VCP through a mapped region. Reason: The abstract reports binding of the VCP N-terminal region to BRCA1 residues 303-625 in vitro and association in living cells. Retain P55072 binding. Its proposed ATP-transporter model is an interpretation, not evidence that BRCA1 transports ATP or has VCP ATPase activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:11301010 BACH1, a novel helicase-like protein, interacts directly wit... | KEEP AS NON CORE | Summary: BACH1/BRIP1 directly binds the BRCA1 BRCT repeats. Reason: The abstract directly establishes Q9BX63 binding and a BRCA1-binding-dependent effect of a BACH1 helicase mutant on repair. Retain this source-specific interaction without transferring helicase catalysis to BRCA1. The later phosphoserine-specific refinement is assigned to the rows whose evidence explicitly establishes that recognition mechanism. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:14576433 The BRCT domain is a phospho-protein binding domain. | MODIFY | Summary: BRCA1 BRCT recognition of phosphorylated BACH1 is a regulated molecular interaction. Reason: The original abstract explicitly establishes direct phospho-dependent BRCA1-BACH1 interaction and its cell-cycle regulation. The Ser990-contact structure in PMID:15125843 provides residue-specific corroboration, supporting GO:0050815. This is binding of a phosphorylated protein segment, not binding free phosphoserine or kinase activity. Proposed replacements: phosphoserine residue binding |
| GO:0005515 protein binding | IPI PMID:11877377 SMC1 is a downstream effector in the ATM/NBS1 branch of the ... | KEEP AS NON CORE | Summary: BRCA1 associates with SMC1 in the DNA-damage response study. Reason: The abstract explicitly states SMC1 association with BRCA1, while the limited cached Discussion concentrates on ATM/NBS1-dependent SMC1 phosphorylation. Retain Q14683 binding; do not infer that BRCA1 is the SMC1 kinase or that phosphorylation dependence of the binding itself was demonstrated. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15265711 BARD1 regulates BRCA1 apoptotic function by a mechanism invo... | KEEP AS NON CORE | Summary: BRCA1-BARD1 association influences nuclear retention and the studied apoptotic response. Reason: The abstract describes perturbation of cellular BRCA1-BARD1 interaction by N-terminal peptides, nuclear retention and apoptosis in transfected MCF-7 cells. Retain Q99728 binding with this context; the source does not make every BRCA1-BARD1 complex a universal apoptosis-inhibitory mechanism. Supporting Evidence: |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IDA PMID:14654789 A member of the Pyrin family, IFI16, is a novel BRCA1-associ... | KEEP AS NON CORE | Summary: BRCA1 and IFI16 can promote p53-dependent apoptosis after DNA damage. Reason: The source reports BRCA1βIFI16 association and enhanced DNA damage-induced apoptosis on coexpression, with loss of the effect for an IFI16 mutant deficient in BRCA1 binding. This experimentally supported signaling outcome is retained with its cellular and expression context; BRCA1 is not assigned an apoptotic protease or p53 kinase activity. Supporting Evidence: |
| GO:0003677 DNA binding | TAS PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme ... | ACCEPT | Summary: BRCA1 DNA binding is independently supported, while this early source emphasizes transcriptional association. Reason: The RNA-helicase-A paper supports the original author statement in a transcriptional context; its accessible abstract does not measure damaged-DNA specificity. Independent direct BRCA1 fragment and heterodimer DNA-binding work supports retention of the broad term. The earlier replacement was unjustifiably narrower than this source assertion. |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA1 contributes to DNA damage-dependent G2/M checkpoint signaling. Reason: BRCA1-containing repair/checkpoint assemblies and perturbation studies support inhibition of mitotic entry after damage. BRCA1 acts as an assembly and signaling factor; ATM/ATR and downstream kinases perform the phosphorylation reactions. Acceptance of the broad checkpoint function does not claim a freshly reconstructed PAINT tree or a direct kinase activity for BRCA1. |
| GO:0000724 double-strand break repair via homologous recombination | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA1 is essential for homologous recombination-mediated repair of DNA double-strand breaks. This is the primary tumor suppressor function of BRCA1. The IBA annotation correctly identifies this conserved core function. Reason: This is the most critical annotation for BRCA1. The protein orchestrates HR through multiple mechanisms including DNA end resection, competition with 53BP1 for repair pathway choice, and facilitation of RAD51 loading. Deficiency in HR repair is the primary mechanism of BRCA1-associated cancer predisposition. This IBA annotation appropriately captures the conserved and central function. |
| GO:0043009 chordate embryonic development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: BRCA1 is implicated in chordate embryonic development. Reason: Retain the existing comparative developmental assertion as a contextual role. Loss of genome-maintenance functions can affect development, but lethality alone neither identifies a dedicated developmental reaction nor proves that all developmental effects are secondary. The complete ortholog experiments and PAINT ancestral-node placement were not independently reconstructed. Supporting Evidence: file:human/BRCA1/BRCA1-uniprot.txt |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000003 | ACCEPT | Summary: BRCA1βBARD1 is a RING E3 ubiquitin ligase. Reason: The EC-derived assertion agrees with purified heterodimer biochemistry and nucleosome structures. Product linkage depends on the E2 and assay context: K6-linked autoubiquitination and histone substrate ubiquitination are established, while other E2 partners support other chain products. This source alone does not establish an unconditional ligase requirement for every tumor-suppressive function. |
| GO:0006281 DNA repair | IEA GO_REF:0000120 | ACCEPT | Summary: BRCA1 participates in multiple DNA repair mechanisms. Reason: The broad DNA-repair assertion is biologically correct. Homologous recombination is well established, but BRCA1 also supports DNA-end processing and single-strand annealing in the reported assays. Restricting this general source assertion to homologous recombination alone would unnecessarily narrow the evidence; the core synthesis provides the mechanistic detail. |
| GO:0006310 DNA recombination | IEA GO_REF:0000043 | ACCEPT | Summary: BRCA1 participates in DNA recombination through its role in homologous recombination. This general term is less specific than the HR-specific annotation. Reason: BRCA1 is indeed involved in DNA recombination, specifically through homologous recombination. While the more specific HR annotation is preferred, this general recombination term is not incorrect and captures a broad aspect of BRCA1 function. The annotation is acceptable as it provides a higher-level grouping of BRCA1s function. Supporting Evidence: |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000043 | MODIFY | Summary: BRCA1 restrains fatty-acid synthesis through phosphorylated acetyl-CoA carboxylase. Reason: The inspected source supports a regulatory role: BRCA1 binds phosphorylated inactive ACCA and impedes its dephosphorylation, while BRCA1 silencing increases fatty-acid synthesis. It does not assign BRCA1 a fatty-acid-synthesis enzyme reaction. Refine the broad electronic metabolic assertion to the evidenced negative regulation, already represented by another source row, rather than dismissing the biology because it is non-core. Proposed replacements: negative regulation of fatty acid biosynthetic process Supporting Evidence: |
| GO:0006631 fatty acid metabolic process | IEA GO_REF:0000043 | MODIFY | Summary: BRCA1 restrains fatty-acid synthesis through phosphorylated acetyl-CoA carboxylase. Reason: The inspected source supports a regulatory role: BRCA1 binds phosphorylated inactive ACCA and impedes its dephosphorylation, while BRCA1 silencing increases fatty-acid synthesis. It does not assign BRCA1 a fatty-acid-synthesis enzyme reaction. Refine the broad electronic metabolic assertion to the evidenced negative regulation, already represented by another source row, rather than dismissing the biology because it is non-core. Proposed replacements: negative regulation of fatty acid biosynthetic process Supporting Evidence: |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000043 | MODIFY | Summary: BRCA1 restrains fatty-acid synthesis through phosphorylated acetyl-CoA carboxylase. Reason: The inspected source supports a regulatory role: BRCA1 binds phosphorylated inactive ACCA and impedes its dephosphorylation, while BRCA1 silencing increases fatty-acid synthesis. It does not assign BRCA1 a fatty-acid-synthesis enzyme reaction. Refine the broad electronic metabolic assertion to the evidenced negative regulation, already represented by another source row, rather than dismissing the biology because it is non-core. Proposed replacements: negative regulation of fatty acid biosynthetic process Supporting Evidence: |
| GO:0006974 DNA damage response | IEA GO_REF:0000120 | ACCEPT | Summary: BRCA1 is a central hub in the DNA damage response, coordinating checkpoint activation, DNA repair pathway choice, and chromatin remodeling at damage sites. Reason: This annotation correctly identifies BRCA1s critical role in the DNA damage response. BRCA1 functions as a master coordinator of the DDR, being recruited to damage sites, activating checkpoints, promoting DNA end resection, and facilitating repair. This is a core function of BRCA1. Supporting Evidence: |
| GO:0008270 zinc ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: Zinc coordination supports the BRCA1 RING fold. Reason: The RING domain is a zinc-coordinating structural module in the BRCA1βBARD1 heterodimer. Structural work corroborates the existing annotation. This is a structural requirement of the ligase machinery, not a separate zinc-transport or metal-metabolism function. |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | ACCEPT | Summary: BRCA1βBARD1 has ubiquitin transferase activity. Reason: The broad electronic transferase term is consistent with the established RING E3 activity. The specific ubiquitin ligase activity is used in the core synthesis; no unrelated transfer reaction is inferred. |
| GO:0046872 metal ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: Zinc coordination supports the BRCA1 RING fold. Reason: The RING domain is a zinc-coordinating structural module in the BRCA1βBARD1 heterodimer. Structural work corroborates the existing annotation. This is a structural requirement of the ligase machinery, not a separate zinc-transport or metal-metabolism function. |
| GO:0005515 protein binding | IPI PMID:22792074 FANCJ/BACH1 acetylation at lysine 1249 regulates the DNA dam... | KEEP AS NON CORE | Summary: BRCA1 associates with FANCJ/BRIP1 in the DNA damage response; FANCJ acetylation-site mutants retain this association. Reason: The cached Results describe FANCJ immunoprecipitation recovering BRCA1 in FA-J cells, including wild-type and K1249R/K1249Q FANCJ (Figure 4B), and endogenous association during damage-response experiments (Figure 3A). This is supported interaction evidence. Retain the broad binding annotation with this context; FANCJ helicase activity is not an activity of BRCA1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22884692 TRIP12 and UBR5 suppress spreading of chromatin ubiquitylati... | UNDECIDED | Summary: GOA records BRCA1 binding with TP53BP1 for the TRIP12/UBR5 study, but the available abstract does not resolve that interaction. Reason: The abstract reports altered chromatin ubiquitination and accumulation of both BRCA1 and 53BP1 after ligase depletion. Shared recruitment is not itself a binding assay. The BRCA1-TP53BP1 experiment underlying this IPI row is unavailable here, so defer the decision without asserting the curator used the wrong gene or that the interaction is false. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23624935 BRCA1 is a negative modulator of the PRC2 complex. | KEEP AS NON CORE | Summary: BRCA1 associates with EZH2 in the PRC2 regulatory context. Reason: The available abstract and Discussion explicitly report BRCA1-EZH2 interaction and describe in vitro binding and co-immunoprecipitation supporting an N-terminal BRCA1 association with PRC2. This supports retention of protein binding as non-core. GOA specifically preserves Q61188, labeled Ezh2 and Xeno in the BRCA1 UniProt interaction record; do not silently replace it with a human EZH2 accession. The cached source discusses both mouse ES and human breast cancer models, but does not expose the complete construct-level Results. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23680151 Function of BRCA1 in the DNA damage response is mediated by ... | KEEP AS NON CORE | Summary: BRCA1 forms a complex with BARD1 in the reported recruitment mechanism at DNA lesions. Reason: The abstract explicitly identifies the BRCA1-BARD1 RING-domain heterodimer and the Discussion describes its recruitment. Retain the supported interaction as non-core at this broad term. The PAR-recognition mechanism in this study is assigned to the BARD1 BRCT domains, so it does not justify replacing BRCA1 protein binding with an intrinsic PAR-binding activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | UNDECIDED | Summary: The chromatin interaction screen is the source of a GOA BRCA1-BARD1 binding row, but the target-specific result is absent from the cache. Reason: The abstract describes tagged-protein affinity purification and mass spectrometry across many chromatin proteins. It does not identify the BRCA1-BARD1 measurement. The specific interaction table or experiment is required to adjudicate this source-specific row; the absence from this abstract does not contradict BARD1 binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28319063 Compromised BRCA1-PALB2 interaction is associated with breas... | KEEP AS NON CORE | Summary: BRCA1 binds PALB2, and selected PALB2 N-terminal variants disrupt the association. Reason: The available Results explicitly compare co-immunoprecipitation of endogenous BRCA1 with ectopically expressed PALB2 variants in human 293T cells. Y28C and L35P disrupt the association whereas other tested variants retain it. This supports the interaction; retain protein binding as non-core while leaving the homologous-recombination interpretation to the corresponding process annotations. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | UNDECIDED | Summary: GOA links BRCA1 to eight protein partners from a proximity-labeling DNA repair network study. Reason: The available abstract and Discussion establish APEX-based mapping of protein neighborhoods around endogenous BRCA1, 53BP1, and MDC1. They do not expose the individual BRCA1-partner records or follow-up assays for the eight GOA partners. Proximity labeling can include transient or indirect neighbors; it cannot by itself establish a particular direct interaction. Defer this source-specific binding row pending the Results and interaction data, without inferring that the GOA associations are false. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31527615 The RNA-mediated estrogen receptor Ξ± interactome of hormone-... | UNDECIDED | Summary: GOA records a BRCA1-ESR1 association from the nuclear estrogen-receptor interaction dataset. Reason: The source describes tandem affinity purification and mass spectrometry in MCF7 cells before and after RNase treatment. The cached body does not name BRCA1 and provides no BRCA1-specific measurement, while directing the interaction data to external deposits. The target pair and its RNase sensitivity therefore cannot be adjudicated here. Do not infer either direct binding or RNA dependence for BRCA1 from the study title. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | UNDECIDED | Summary: GOA records BRCA1-BARD1 binding from BioPlex interaction profiling. Reason: The abstract and cached Introduction/Discussion describe AP-MS networks in 293T and HCT116 cells, but do not include the BRCA1-BARD1 experiment or interaction record. The established biology of this pair does not substitute for inspecting the cited screen result. Keep this source-specific row undecided pending the relevant data; no removal or misattribution is supported. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:34552057 ZGRF1 promotes end resection of DNA homologous recombination... | KEEP AS NON CORE | Summary: BRCA1 associates with ZGRF1 in a DNA damage-responsive complex that also includes EXO1. Reason: The Results describe reciprocal co-immunoprecipitation using ZGRF1, BRCA1, and EXO1 antibodies in human cell extracts, with increased association after irradiation. The study describes the complex as independent of chromatin. Retain the interaction as non-core; this does not assign ZGRF1 helicase or EXO1 nuclease activity to BRCA1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | KEEP AS NON CORE | Summary: The breast cancer interaction study explicitly supports BRCA1 binding to spinophilin/PPP1R9B. Reason: The abstract and Discussion explicitly identify spinophilin as a BRCA1 interactor and discuss regulation of BRCA1 phosphorylation. That source-specific interaction supports the collapsed protein-binding assertion, retained as non-core. GOA also records ABRAXAS1/Q6UWZ7, UIMC1/Q96RL1, RBBP8/Q99708, BARD1/Q99728, and BRIP1/Q9BX63; those five individual partner measurements remain unverified because the available cache lacks their Results and interaction data. Retention does not validate all six edges or assign phosphatase activity to BRCA1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:8944023 Identification of a RING protein that can interact in vivo w... | KEEP AS NON CORE | Summary: BRCA1 interacts with the RING-domain protein BARD1 through its N-terminal region. Reason: The abstract explicitly identifies BARD1 and describes disruption of the interaction by breast-cancer-associated BRCA1 missense variants. GOA partner Q99728 also corresponds to BARD1 in the local UniProt record. Retain this supported interaction as non-core and correct the previous review text, which mistakenly described this paper as a BAP1 study. The paper does not support that prior BAP1-specific narrative. Supporting Evidence: PMID:8944023 interacts in vivo with the N-terminal region of BRCA1 |
| GO:0005515 protein binding | IPI PMID:9497340 Identification of a novel cytoplasmic protein that specifica... | KEEP AS NON CORE | Summary: BRCA1 nuclear-localization sequences interact with BRAP2/BRAP and importin alpha. Reason: The abstract describes a BRCA1-NLS yeast two-hybrid screen, identification of importin alpha, and BRAP2 binding assessed by two-hybrid and GST pull-down assays. The GOA partners are KPNA2 and BRAP in the local UniProt interaction record. Retain these supported interactions as non-core. Recognition of BRCA1 localization signals by its partners does not establish an NLS-recognition or transport-receptor activity of BRCA1 itself. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9528852 BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 R... | KEEP AS NON CORE | Summary: BAP1 associates with the BRCA1 RING region. Reason: The abstract explicitly reports BAP1 binding to wild-type BRCA1 and impaired binding to the tested germline RING-region variants. Retain the supported binding annotation as non-core. The ubiquitin-hydrolase activity discussed in this source belongs to BAP1, and the accessible text does not justify replacing the interaction with a BRCA1 enzymatic activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9811458 Characterization of a carboxy-terminal BRCA1 interacting pro... | KEEP AS NON CORE | Summary: CtIP/RBBP8 binds the C-terminal region of human BRCA1. Reason: The abstract explicitly describes yeast two-hybrid and in vitro biochemical assays showing CtIP interaction with BRCA1 residues 1602-1863 and loss of the interaction with the Y1853ter truncation. Retain the interaction as non-core. This early source does not by itself establish the detailed DNA-end-resection mechanism asserted in the previous review reason. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | UNDECIDED | Summary: The source-specific BRCA1 self-association assertion remains unverified. Reason: The entire available cache was read, but it lacks the Results and target interaction table needed to assess the BRCA1 self-edge. Its full-text flag does not supply those missing sections. Predominant BRCA1βBARD1 heterodimerization is not evidence against BRCA1 self-association; the experimental source assertion and all partner fields remain unchanged pending the relevant assay. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | UNDECIDED | Summary: The source-specific BRCA1 self-association assertion remains unverified. Reason: The entire available cache was read, but it lacks the Results and target interaction table needed to assess the BRCA1 self-edge. Its full-text flag does not supply those missing sections. Predominant BRCA1βBARD1 heterodimerization is not evidence against BRCA1 self-association; the experimental source assertion and all partner fields remain unchanged pending the relevant assay. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:8944023 Identification of a RING protein that can interact in vivo w... | UNDECIDED | Summary: The original BRCA1 self-association assay needs verification. Reason: The accessible abstract describes discovery of BARD1 and its interaction with BRCA1; this is not a BAP1 paper. It does not expose the assay underlying the separately curated BRCA1 self-binding assertion. Heterodimer formation does not refute self-association, so the previous removal is withdrawn without claiming the uninspected self-binding assay is validated. Supporting Evidence: |
| GO:0006974 DNA damage response | TAS PMID:10910365 Functional link of BRCA1 and ataxia telangiectasia gene prod... | ACCEPT | Summary: BRCA1 is a central component of the DNA damage response, coordinating repair and checkpoint functions. Reason: This annotation correctly identifies BRCA1s critical role in the DNA damage response. BRCA1 is phosphorylated by ATM/ATR kinases and coordinates checkpoint activation, DNA repair pathway choice, and chromatin remodeling. This is a core function. Supporting Evidence: |
| GO:0006281 DNA repair | NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. | ACCEPT | Summary: BRCA1 participates in multiple DNA repair mechanisms. Reason: The broad DNA-repair assertion is biologically correct. Homologous recombination is well established, but BRCA1 also supports DNA-end processing and single-strand annealing in the reported assays. Restricting this general source assertion to homologous recombination alone would unnecessarily narrow the evidence; the core synthesis provides the mechanistic detail. |
| GO:0006282 regulation of DNA repair | NAS PMID:20656689 Differential regulation of JAMM domain deubiquitinating enzy... | ACCEPT | Summary: BRCA1 regulates DNA repair pathway choice between homologous recombination and non-homologous end joining. Reason: BRCA1 does regulate DNA repair by promoting homologous recombination over NHEJ through competition with 53BP1 and DNA end resection. This regulatory function is distinct from and complementary to its direct role in HR. |
| GO:0035825 homologous recombination | NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. | ACCEPT | Summary: BRCA1 is essential for homologous recombination. This is a core function. Reason: Homologous recombination is the primary mechanism by which BRCA1 maintains genomic stability and suppresses tumorigenesis. This annotation is correct and represents a core function. Supporting Evidence: |
| GO:0035825 homologous recombination | NAS PMID:30657944 CtIP-BRCA1 complex and MRE11 maintain replication forks in t... | ACCEPT | Summary: BRCA1 contributes to recombinational repair and damaged-fork processing with CtIP. Reason: The source directly addresses BRCA1βCtIP-dependent tolerance and processing of chain-terminating nucleoside analogues during replication. The broad author-statement annotation to homologous recombination is retained with independent BRCA1 HR evidence; the source is not misrepresented as assigning BRCA1 the nuclease reaction performed by MRE11. |
| GO:0044818 mitotic G2/M transition checkpoint | NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. | ACCEPT | Summary: BRCA1 contributes to DNA damage-dependent G2/M checkpoint signaling. Reason: BRCA1-containing repair/checkpoint assemblies and perturbation studies support inhibition of mitotic entry after damage. BRCA1 acts as an assembly and signaling factor; ATM/ATR and downstream kinases perform the phosphorylation reactions. Acceptance of the broad checkpoint function does not claim a freshly reconstructed PAINT tree or a direct kinase activity for BRCA1. |
| GO:0006302 double-strand break repair | TAS Reactome:R-HSA-5693606 | ACCEPT | Summary: BRCA1 is essential for DNA double-strand break repair via homologous recombination. Reason: This annotation correctly identifies BRCA1s role in DSB repair. While the more specific HR term is preferred, DSB repair is accurate and represents a core function. |
| GO:0006302 double-strand break repair | IEA GO_REF:0000107 | ACCEPT | Summary: BRCA1 is essential for DSB repair. Duplicate annotation from ortholog transfer. Reason: Correct annotation for a core BRCA1 function. DSB repair is central to BRCA1 tumor suppression. |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:28398198 Functional and mutational landscapes of BRCA1 for homology-d... | ACCEPT | Summary: Direct experimental evidence for BRCA1 role in homologous recombination repair. This is the most specific and accurate annotation for BRCA1s primary tumor suppressor function. Reason: This IDA annotation with direct experimental evidence correctly identifies BRCA1s essential role in HR. This is the core tumor suppressor function. Supporting Evidence: |
| GO:0006974 DNA damage response | NAS PMID:16651405 DNA damage-induced BARD1 phosphorylation is critical for the... | ACCEPT | Summary: BRCA1 is central to the DNA damage response. Duplicate annotation. Reason: Core function of BRCA1. DNA damage response is essential for tumor suppression. Supporting Evidence: |
| GO:0045786 negative regulation of cell cycle | NAS PMID:15159397 BRCA1-BARD1 complexes are required for p53Ser-15 phosphoryla... | ACCEPT | Summary: BRCA1 negatively regulates cell cycle by enforcing checkpoints upon DNA damage. Reason: BRCA1 enforces cell cycle checkpoints (S-phase and G2/M) upon DNA damage, preventing progression of cells with damaged DNA. This checkpoint function is a core tumor suppressor mechanism. Supporting Evidence: |
| GO:0006338 chromatin remodeling | TAS PMID:35351360 BRCA1/BARD1 is a nucleosome reader and writer. | ACCEPT | Summary: BRCA1βBARD1-dependent histone ubiquitination supports repair-associated chromatin remodeling. Reason: The reader/writer review and primary structural work connect H2A C-terminal ubiquitination to recruitment of the remodeler SMARCAD1 and rearrangement of 53BP1-associated chromatin. BRCA1 contributes by writing the histone mark with BARD1, not by acquiring the ATPase activity of the downstream remodeler. |
| GO:0061649 ubiquitin-modified histone reader activity | TAS PMID:35351360 BRCA1/BARD1 is a nucleosome reader and writer. | MARK AS OVER ANNOTATED | Summary: Modified-histone recognition resides in BARD1 within the BRCA1βBARD1 reader/writer complex. Reason: The original unqualified enables assertion overstates BRCA1-specific reader activity. Primary structures and binding mutations place H2AK13/15-ubiquitin recognition in BARD1 ankyrin/BRCT domains. BRCA1 RING contacts the nucleosome acidic patch and E2 and contributes to the genuine reader/writer heterodimer, but this does not establish an intrinsic ubiquitin-modified-histone reader site in BRCA1. No source qualifier or term is rewritten, and the complex-level biology is retained in the synthesis. |
| GO:0140863 histone H2AK127 ubiquitin ligase activity | TAS PMID:35351360 BRCA1/BARD1 is a nucleosome reader and writer. | ACCEPT | Summary: BRCA1βBARD1 catalyses nucleosomal H2A K127 ubiquitination. Reason: The original review is corroborated by direct NMR monitoring and mutagenesis of nucleosomal H2A in purified RING-heterodimer/E2 assays. The evidence distinguishes H2A C-terminal acceptor sites from the K6 linkage in ubiquitin chains, and assigns catalytic activity to BRCA1 working with BARD1 and E2 rather than to a histone-reader domain. |
| GO:0140864 histone H2AK129 ubiquitin ligase activity | TAS PMID:35351360 BRCA1/BARD1 is a nucleosome reader and writer. | ACCEPT | Summary: BRCA1βBARD1 catalyses nucleosomal H2A K129 ubiquitination. Reason: The original review is corroborated by direct NMR monitoring and mutagenesis of nucleosomal H2A in purified RING-heterodimer/E2 assays. The evidence distinguishes H2A C-terminal acceptor sites from the K6 linkage in ubiquitin chains, and assigns catalytic activity to BRCA1 working with BARD1 and E2 rather than to a histone-reader domain. |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000041 | ACCEPT | Summary: BRCA1 catalyzes protein ubiquitination as an E3 ubiquitin ligase in complex with BARD1. Reason: This annotation correctly identifies BRCA1s role in protein ubiquitination. As an E3 ubiquitin ligase, BRCA1-BARD1 catalyzes ubiquitination of multiple substrates including histones and itself. |
| GO:0030308 negative regulation of cell growth | IMP PMID:10518542 BRCA1-associated growth arrest is RB-dependent. | MODIFY | Summary: BRCA1 overexpression suppresses DNA synthesis and colony outgrowth in an RB-dependent context. Reason: The inspected abstract and Discussion describe proliferation and DNA-synthesis endpoints, not a measurement of individual cell size. GO cell growth means an increase in cellular size; negative regulation of cell population proliferation better represents the documented assay. This correction is bounded to the available source sections and does not claim all omitted Results were inspected. Proposed replacements: negative regulation of cell population proliferation Supporting Evidence: |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:12080089 JunB potentiates function of BRCA1 activation domain 1 (AD1)... | KEEP AS NON CORE | Summary: BRCA1 AD1 transcriptional activation is potentiated by JunB. Reason: The source tests the BRCA1 AD1 coiled-coil interaction with Jun proteins and transcriptional reporters, with dependence on cellular JunB levels. Retain this activation phenotype with its domain and cellular context; it is not evidence that BRCA1 is a sequence-specific transcription factor. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26833090 Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologo... | KEEP AS NON CORE | Summary: BRCA1 interacts with XPG in a homologous-recombination repair context. Reason: The abstract explicitly reports a direct XPG-BRCA1 interaction, and the available Discussion reiterates the interaction while distinguishing BRCA1 regulation from XPG associations with BRCA2/PALB2/RAD51. Retain the supported binding assertion as non-core. XPG nuclease activity and putative scaffolding properties are not molecular functions of BRCA1. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:29899443 Structural basis for regulation of human acetyl-CoA carboxyl... | KEEP AS NON CORE | Summary: BRCA1 BRCT domains bind acetyl-CoA carboxylase 1 in an inhibited filament state. Reason: The abstract describes a cryo-EM structure of an inactive ACC1 filament associated with BRCA1 BRCT domains, providing explicit physical interaction evidence. Retain the interaction as non-core with this metabolic regulatory context. A finer molecular-function replacement would require a separate ontology and mechanistic adjudication; no ACC1 catalytic activity is attributed to BRCA1. Supporting Evidence: |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IMP PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | ACCEPT | Summary: BRCA1 is essential for G2 DNA damage checkpoint signaling, demonstrated through BRCA1-A complex (Abraxas-RAP80) studies. Reason: Core function of BRCA1. G2 checkpoint control is essential for tumor suppression by preventing mitotic entry with damaged DNA. Supporting Evidence: |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IMP PMID:17643121 CCDC98 targets BRCA1 to DNA damage sites. | ACCEPT | Summary: BRCA1 is essential for G2 checkpoint signaling. Duplicate annotation from CCDC98/Abraxas study. Reason: Core function of BRCA1. CCDC98 targets BRCA1 to DNA damage sites for checkpoint signaling. Supporting Evidence: |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IMP PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: BRCA1 is essential for G2 checkpoint signaling. Duplicate annotation from MERIT40 study. Reason: Core function of BRCA1. MERIT40 facilitates BRCA1 localization for checkpoint function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme ... | KEEP AS NON CORE | Summary: RNA helicase A connects BRCA1 to the RNA polymerase II holoenzyme. Reason: The abstract maps the RHA interaction to portions of the BRCA1 BRCT region, reports interaction in yeast nuclei, and describes inhibition of BRCA1-dependent transcription by a binding-competent truncated RHA in human cells. Retain this supported interaction as non-core. Neither RNA-helicase activity nor a detailed mechanism of transcriptional activation should be assigned to BRCA1 from binding alone. Supporting Evidence: |
| GO:0006357 regulation of transcription by RNA polymerase II | IMP PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme ... | KEEP AS NON CORE | Summary: BRCA1 contributes to transcriptional activation in defined promoter and reporter contexts. Reason: BRCA1-containing transcriptional complexes and promoter/reporter assays support this function. RHA links BRCA1 to RNA polymerase II, and BRCA1 regulates DNMT1 through a promoter complex. The annotation is retained outside the principal repair-focused synthesis; the available evidence does not establish that transcriptional regulation is dispensable for tumor suppression. |
| GO:0070063 RNA polymerase binding | IDA PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme ... | KEEP AS NON CORE | Summary: BRCA1 associates with the RNA polymerase II holoenzyme through RHA. Reason: The source explicitly places RHA between BRCA1 and the holoenzyme and tests inhibition of BRCA1-mediated transcription by a truncated RHA construct. Retain the curated polymerase-binding association without misrepresenting these data as purified binary BRCA1βpolymerase binding. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:26807646 EXD2 promotes homologous recombination by facilitating DNA e... | KEEP AS NON CORE | Summary: BRCA1 co-purifies with EXD2, CtIP, and MRE11 in a DNA-repair complex. Reason: The Results report BRCA1, CtIP, and MRE11 in FLAG-EXD2 immunoprecipitates from human extracts treated with benzonase to limit DNA bridging. This supports a protein-complex association involving the GOA partner group. Retain the broad interaction annotation as non-core; co-purification does not establish three independent direct binary contacts or confer EXD2/MRE11 nuclease activity on BRCA1. Supporting Evidence: |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:20160719 Identification of DBC1 as a transcriptional repressor for BR... | KEEP AS NON CORE | Summary: Full-length BRCA1 activates a SIRT1 promoter reporter in the source experiments. Reason: DBC1 represses BRCA1 BRCT-dependent transactivation and the SIRT1 promoter response mediated by full-length BRCA1. Retain the positive transcriptional regulation in that assay; distinguish inhibition of BRCA1 activity from regulation of BRCA1 expression. Supporting Evidence: |
| GO:0010575 positive regulation of vascular endothelial growth factor production | IMP PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction a... | KEEP AS NON CORE | Summary: BRCA1 influences VEGFA production in the tested endothelial context. Reason: The source reports loss- and gain-of-function analyses in endothelial cells and increased VEGFA expression with BRCA1 overexpression. This supports the curated regulation as a contextual outcome. It is not rejected merely because vascular regulation lies outside the principal repair mechanism, and no direct promoter-binding mechanism is invented. Supporting Evidence: |
| GO:0010628 positive regulation of gene expression | IMP PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction a... | KEEP AS NON CORE | Summary: BRCA1 gain and loss of function alter endothelial gene-expression outputs. Reason: The source reports expression and signaling changes in endothelial cells, including VEGFA-related effects. The broad regulation term is supported with this experimental context; no direct promoter contact or general transcription-factor activity is inferred. Supporting Evidence: |
| GO:0045766 positive regulation of angiogenesis | IMP PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction a... | KEEP AS NON CORE | Summary: BRCA1 promotes angiogenic outcomes in the source endothelial and ischemia experiments. Reason: BRCA1 gain of function improved angiogenesis and hindlimb reperfusion in the reported experiments, alongside endothelial signaling changes. Retain the experimentally supported regulatory annotation with its model context. The result does not establish that BRCA1 is an extracellular angiogenic ligand or a dedicated angiogenesis enzyme. Supporting Evidence: |
| GO:0033147 negative regulation of intracellular estrogen receptor signaling pathway | IMP PMID:17505062 Growth factor signaling pathways modulate BRCA1 repression o... | KEEP AS NON CORE | Summary: BRCA1 restrains estrogen-receptor activity in a PI3K/Akt-dependent cellular context. Reason: BRCA1 underexpression increases ER-alpha activity, while perturbation of PI3K/Akt signaling and ER phosphorylation sites modifies the response. This supports the negative regulation actually asserted, not a direct kinase or phosphatase reaction by BRCA1. Supporting Evidence: |
| GO:0006302 double-strand break repair | IDA PMID:22186889 BRCA1 is an essential regulator of heart function and surviv... | ACCEPT | Summary: Direct experimental evidence for BRCA1 role in DSB repair. Reason: Core function of BRCA1. DSB repair is central to its tumor suppressor role. Supporting Evidence: |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:17873885 E2-BRCA1 RING interactions dictate synthesis of mono- or spe... | MODIFY | Summary: BRCA1 binds the E2 ubiquitin-conjugating enzyme UBE2K. Reason: The exact GOA partner P61086 is UBE2K, independently verified in official identity records. The cited biochemical study tests E2 binding to the BRCA1 RING. GO:0031625 specifies binding an E3 ligase; GO:0031624 specifies binding an E2 conjugating enzyme and is the correct partner-class refinement. This row is distinct from the same-paper generic-binding row whose source partner is BARD1. Proposed replacements: ubiquitin conjugating enzyme binding Supporting Evidence: PMID:17873885 All six E2s bind directly to the BRCA1 RING motif |
| GO:0006302 double-strand break repair | IMP PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | ACCEPT | Summary: BRCA1 is essential for DSB repair. IMP annotation from BRCA1-A complex study. Reason: Core function of BRCA1. Supporting Evidence: |
| GO:0006302 double-strand break repair | IMP PMID:17643121 CCDC98 targets BRCA1 to DNA damage sites. | ACCEPT | Summary: BRCA1 is essential for DSB repair. IMP annotation from CCDC98 study. Reason: Core function of BRCA1. Supporting Evidence: |
| GO:0006302 double-strand break repair | IMP PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: BRCA1 is essential for DSB repair. IMP annotation from MERIT40 study. Reason: Core function of BRCA1. Supporting Evidence: |
| GO:0010212 response to ionizing radiation | IMP PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | ACCEPT | Summary: BRCA1 responds to ionizing radiation-induced DNA damage. Reason: BRCA1 is recruited to DNA damage sites induced by ionizing radiation to mediate repair. This is consistent with its core DDR function. Supporting Evidence: |
| GO:0010212 response to ionizing radiation | IMP PMID:17643121 CCDC98 targets BRCA1 to DNA damage sites. | ACCEPT | Summary: BRCA1 responds to ionizing radiation. Duplicate annotation. Reason: Core DDR function. Supporting Evidence: |
| GO:0010212 response to ionizing radiation | IMP PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: BRCA1 responds to ionizing radiation. Duplicate annotation. Reason: Core DDR function. Supporting Evidence: |
| GO:0045739 positive regulation of DNA repair | IMP PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | ACCEPT | Summary: BRCA1 positively regulates DNA repair through its role in HR. Reason: BRCA1 promotes HR repair through multiple mechanisms. Core function. Supporting Evidence: |
| GO:0045739 positive regulation of DNA repair | IMP PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: BRCA1 positively regulates DNA repair. Duplicate annotation. Reason: Core function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9774970 Stable interaction between the products of the BRCA1 and BRC... | KEEP AS NON CORE | Summary: BRCA1 and BRCA2 coexist in a biochemical complex in the reported mitotic and meiotic contexts. Reason: The abstract explicitly reports a BRCA1-BRCA2 biochemical complex together with localization observations. This supports retaining protein binding as non-core at the level of complex association. Colocalization alone would not establish binding, and the available text does not prove a direct binary contact or identify its bridging components. Supporting Evidence: |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:17349954 A critical role for the ubiquitin-conjugating enzyme Ubc13 i... | ACCEPT | Summary: Direct experimental evidence for BRCA1 role in HR through Ubc13 study. Reason: Core tumor suppressor function. Supporting Evidence: |
| GO:0006301 DNA damage tolerance | IDA PMID:17349954 A critical role for the ubiquitin-conjugating enzyme Ubc13 i... | UNDECIDED | Summary: The BRCA1-specific lesion-bypass assertion requires the original assay context. Reason: GO DNA damage tolerance concerns replication past lesions without removing them, which is distinct from repair by homologous recombination. The accessible abstract clearly reports Ubc13 requirements in postreplication repair and BRCA1 recruitment/E3 activation in HR, but does not expose the target-specific lesion-bypass assay. Neither the paper title nor BRCA1βs established repair function resolves that distinction; retain the source assertion as uncertain rather than alleging misattribution. Supporting Evidence: |
| GO:0016567 protein ubiquitination | IDA PMID:17349954 A critical role for the ubiquitin-conjugating enzyme Ubc13 i... | ACCEPT | Summary: BRCA1 catalyzes ubiquitination through Ubc13. Reason: Core E3 ligase function. Supporting Evidence: |
| GO:0045717 negative regulation of fatty acid biosynthetic process | IMP PMID:16326698 BRCA1 affects lipid synthesis through its interaction with a... | KEEP AS NON CORE | Summary: BRCA1 negatively regulates fatty-acid synthesis through ACCA. Reason: The source reports preferential binding to phosphorylated inactive ACCA, inhibition of its dephosphorylation, and increased fatty-acid synthesis after BRCA1 silencing. These support the regulation actually asserted. Non-core metabolic context is not grounds for labeling a supported regulation over-annotated. Supporting Evidence: PMID:16326698 BRCA1 affects lipid synthesis by preventing P-ACCA dephosphorylation |
| GO:0007059 chromosome segregation | IMP PMID:15965487 BRCA1 participates in DNA decatenation. | KEEP AS NON CORE | Summary: BRCA1 supports chromosome decatenation and segregation in the source experiments. Reason: The study connects BRCA1, topoisomerase II association and decatenation-dependent segregation. Retain the contextual genome-maintenance role while assigning DNA topoisomerase catalysis to TOP2 rather than BRCA1. Supporting Evidence: |
| GO:0019899 enzyme binding | IPI PMID:15965487 BRCA1 participates in DNA decatenation. | KEEP AS NON CORE | Summary: BRCA1 associates with topoisomerase II in a decatenation-related context. Reason: The source supports the enzyme association and its functional context. Binding to an enzyme does not establish that BRCA1 performs the enzyme reaction, and no more specific binding term is guessed from the partner name. Supporting Evidence: |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:16288014 BRCA1 and c-Myc associate to transcriptionally repress psori... | KEEP AS NON CORE | Summary: BRCA1 participates in repression of S100A genes with c-Myc. Reason: The source reports BRCA1/c-Myc occupancy at the psoriasin promoter, dependence on functional c-Myc and loss of BRCA1-mediated repression with a disease-associated BRCA1 mutation. Retain this promoter-specific regulatory role without generalizing every BRCA1 interaction to repression. Supporting Evidence: |
| GO:0006357 regulation of transcription by RNA polymerase II | TAS PMID:10910365 Functional link of BRCA1 and ataxia telangiectasia gene prod... | KEEP AS NON CORE | Summary: BRCA1 contributes to transcriptional activation in defined promoter and reporter contexts. Reason: BRCA1-containing transcriptional complexes and promoter/reporter assays support this function. RHA links BRCA1 to RNA polymerase II, and BRCA1 regulates DNMT1 through a promoter complex. The annotation is retained outside the principal repair-focused synthesis; the available evidence does not establish that transcriptional regulation is dispensable for tumor suppression. |
| GO:0008270 zinc ion binding | TAS PMID:8944023 Identification of a RING protein that can interact in vivo w... | ACCEPT | Summary: Zinc coordination supports the BRCA1 RING fold. Reason: The RING domain is a zinc-coordinating structural module in the BRCA1βBARD1 heterodimer. Structural work corroborates the existing annotation. This is a structural requirement of the ligase machinery, not a separate zinc-transport or metal-metabolism function. |
| GO:0015631 tubulin binding | NAS PMID:12214252 Roles of BRCA1 in centrosome duplication. | KEEP AS NON CORE | Summary: BRCA1 associates with centrosomal gamma-tubulin. Reason: The review abstract and independent localization study support the gamma-tubulin association. This does not by itself establish stable membership in the gamma-tubulin ring complex, which is assessed separately, or a tubulin polymerase activity. |
| GO:0031436 BRCA1-BARD1 complex | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA1 forms the functional RING ubiquitin-ligase heterodimer with BARD1. Reason: Structural and biochemical evidence establishes the heterodimer and its ubiquitin-ligase function. This core complex assignment does not imply that every isolated BRCA1 domain lacks an independently measurable activity or that BRCA1 belongs to only one assembly. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: BRCA1 contributes to transcriptional activation in defined promoter and reporter contexts. Reason: BRCA1-containing transcriptional complexes and promoter/reporter assays support this function. RHA links BRCA1 to RNA polymerase II, and BRCA1 regulates DNMT1 through a promoter complex. The annotation is retained outside the principal repair-focused synthesis; the available evidence does not establish that transcriptional regulation is dispensable for tumor suppression. |
| GO:0070531 BRCA1-A complex | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA1 participates in the BRCA1-A DNA damage-response assembly. Reason: The source context and independent interaction studies support a BRCA1 assembly involving Abraxas, RAP80 and associated BRCC components at damaged chromatin. Their ubiquitin-recognition and deubiquitination functions are not all intrinsic BRCA1 activities. The annotation describes complex membership, not a claim that every subunit was independently assayed in each cited paper. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: BRCA1 localizes to nucleus. Core cellular component. Reason: BRCA1 is primarily a nuclear protein. Nuclear localization is essential for its DNA repair function. |
| GO:0005654 nucleoplasm | IEA GO_REF:0000117 | ACCEPT | Summary: BRCA1 localizes to nucleoplasm. Reason: BRCA1 is found in the nucleoplasm where it performs DNA repair functions. |
| GO:0005694 chromosome | IEA GO_REF:0000120 | ACCEPT | Summary: BRCA1 localizes to chromosomes, particularly at DNA damage sites. Reason: BRCA1 associates with chromatin and chromosomes for DNA repair. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: BRCA1 also found in cytoplasm though primarily nuclear. Reason: BRCA1 can be found in the cytoplasm, especially in certain splice variants. Some studies show cytoplasmic localization in certain contexts. This is a minor, non-core pool of a predominantly nuclear protein; marked non-core for consistency with the IDA cytoplasm annotation. |
| GO:0005634 nucleus | IDA PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | ACCEPT | Summary: BRCA1 nuclear localization confirmed experimentally. Reason: Nuclear localization is essential for BRCA1 function. Supporting Evidence: |
| GO:0005634 nucleus | NAS PMID:18171670 Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is ... | ACCEPT | Summary: BRCA1 nuclear localization. Reason: Duplicate annotation. Nuclear localization is essential. Supporting Evidence: |
| GO:0005634 nucleus | NAS PMID:20656689 Differential regulation of JAMM domain deubiquitinating enzy... | ACCEPT | Summary: BRCA1 nuclear localization. Reason: Duplicate annotation. Nuclear localization is essential. Supporting Evidence: |
| GO:0005634 nucleus | NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. | ACCEPT | Summary: BRCA1 nuclear localization. Reason: Duplicate annotation. Nuclear localization is essential. Supporting Evidence: |
| GO:0070531 BRCA1-A complex | NAS PMID:20656689 Differential regulation of JAMM domain deubiquitinating enzy... | ACCEPT | Summary: BRCA1 participates in the BRCA1-A DNA damage-response assembly. Reason: The source context and independent interaction studies support a BRCA1 assembly involving Abraxas, RAP80 and associated BRCC components at damaged chromatin. Their ubiquitin-recognition and deubiquitination functions are not all intrinsic BRCA1 activities. The annotation describes complex membership, not a claim that every subunit was independently assayed in each cited paper. |
| GO:0070532 BRCA1-B complex | IPI PMID:16391231 Multifactorial contributions to an acute DNA damage response... | ACCEPT | Summary: BRCA1βBARD1 enters distinct damage-responsive protein assemblies. Reason: The source reports damage-dependent BRCA1βBARD1 supercomplexes involving TopBP1 and MRE11βRAD50βNBS1, with distinct contributions to the damage response. Retain the curator-assigned complex identity without converting the nuclease/helicase activities of partners into BRCA1 catalysis or claiming permanent membership across cell states. Supporting Evidence: |
| GO:0070533 BRCA1-C complex | IPI PMID:16391231 Multifactorial contributions to an acute DNA damage response... | ACCEPT | Summary: BRCA1βBARD1 enters distinct damage-responsive protein assemblies. Reason: The source reports damage-dependent BRCA1βBARD1 supercomplexes involving TopBP1 and MRE11βRAD50βNBS1, with distinct contributions to the damage response. Retain the curator-assigned complex identity without converting the nuclease/helicase activities of partners into BRCA1 catalysis or claiming permanent membership across cell states. Supporting Evidence: |
| GO:0110025 DNA strand resection involved in replication fork processing | NAS PMID:29709199 The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of D... | UNDECIDED | Summary: The precise stalled-fork resection context remains unresolved from the available source. Reason: The available review cache contains an abstract and Introduction rather than the BRCA1-specific fork-processing section. GO:0110025 specifically describes resection at a stalled fork; evidence for DSB-end resection does not automatically establish that assertion, and BRCA1-dependent fork protection must be distinguished from productive processing. Preserve the source NAS assertion pending its relevant section; the MRN-focused title is not evidence of a wrong-gene annotation. Supporting Evidence: |
| GO:0000152 nuclear ubiquitin ligase complex | IDA PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 an... | ACCEPT | Summary: The BRCC source establishes a nuclear BRCA1-containing ubiquitin-ligase and damage-response assembly. Reason: BRCC isolation and recombinant BRCA1/BARD1/BRCC45/BRCC36 experiments support the complex and ligase context. The reported radiosensitivity and G2/M effects followed depletion of BRCC36 or BRCC45; those partner perturbations are not mislabeled as isolated BRCA1 experiments. Independent BRCA1 checkpoint evidence supports the retained broad source assertion. |
| GO:0005634 nucleus | IDA PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 an... | ACCEPT | Summary: The BRCC source establishes a nuclear BRCA1-containing ubiquitin-ligase and damage-response assembly. Reason: BRCC isolation and recombinant BRCA1/BARD1/BRCC45/BRCC36 experiments support the complex and ligase context. The reported radiosensitivity and G2/M effects followed depletion of BRCC36 or BRCC45; those partner perturbations are not mislabeled as isolated BRCA1 experiments. Independent BRCA1 checkpoint evidence supports the retained broad source assertion. |
| GO:0071479 cellular response to ionizing radiation | IMP PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 an... | ACCEPT | Summary: The BRCC source establishes a nuclear BRCA1-containing ubiquitin-ligase and damage-response assembly. Reason: BRCC isolation and recombinant BRCA1/BARD1/BRCC45/BRCC36 experiments support the complex and ligase context. The reported radiosensitivity and G2/M effects followed depletion of BRCC36 or BRCC45; those partner perturbations are not mislabeled as isolated BRCA1 experiments. Independent BRCA1 checkpoint evidence supports the retained broad source assertion. |
| GO:2000001 regulation of DNA damage checkpoint | NAS PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 an... | ACCEPT | Summary: The BRCC source establishes a nuclear BRCA1-containing ubiquitin-ligase and damage-response assembly. Reason: BRCC isolation and recombinant BRCA1/BARD1/BRCC45/BRCC36 experiments support the complex and ligase context. The reported radiosensitivity and G2/M effects followed depletion of BRCC36 or BRCC45; those partner perturbations are not mislabeled as isolated BRCA1 experiments. Independent BRCA1 checkpoint evidence supports the retained broad source assertion. |
| GO:0000793 condensed chromosome | IEA GO_REF:0000107 | ACCEPT | Summary: BRCA1 associates with condensed chromosomes. Reason: BRCA1 localizes to chromosomes including during mitosis. |
| GO:0000794 condensed nuclear chromosome | IEA GO_REF:0000107 | ACCEPT | Summary: BRCA1 localizes to condensed nuclear chromosomes. Reason: Duplicate of condensed chromosome annotation. |
| GO:0001673 male germ cell nucleus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1 localizes to male germ cell nucleus (meiosis). Reason: BRCA1 is expressed in male germ cells and may function in meiotic recombination. Tissue-specific localization. |
| GO:0001741 XY body | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1 localizes to XY body during male meiosis. Reason: BRCA1 localizes to XY body and participates in meiotic sex chromosome inactivation. Germline-specific function. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1 contributes to transcriptional activation in defined promoter and reporter contexts. Reason: BRCA1-containing transcriptional complexes and promoter/reporter assays support this function. RHA links BRCA1 to RNA polymerase II, and BRCA1 regulates DNMT1 through a promoter complex. The annotation is retained outside the principal repair-focused synthesis; the available evidence does not establish that transcriptional regulation is dispensable for tumor suppression. |
| GO:0005634 nucleus | NAS PMID:19369211 PALB2 is an integral component of the BRCA complex required ... | ACCEPT | Summary: BRCA1 nuclear localization. Reason: Nuclear localization is essential for function. Supporting Evidence: |
| GO:1990391 DNA repair complex | IPI PMID:19369211 PALB2 is an integral component of the BRCA complex required ... | ACCEPT | Summary: BRCA1 is a constituent of the PALB2βBRCA2 homologous-recombination assembly. Reason: The source identifies direct BRCA1βPALB2 coiled-coil interaction and links disruption of that interaction to defective HR. PALB2 connects BRCA1 to BRCA2/RAD51 machinery; this supports DNA-repair-complex membership without transferring BRCA2 or RAD51 catalytic roles. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:9342365 Cell cycle-dependent colocalization of BARD1 and BRCA1 prote... | ACCEPT | Summary: BRCA1 nuclear localization. Reason: Core localization. Nuclear is essential for function. Supporting Evidence: |
| GO:0031436 BRCA1-BARD1 complex | IPI PMID:11573085 Structure of a BRCA1-BARD1 heterodimeric RING-RING complex. | ACCEPT | Summary: BRCA1 forms the functional RING ubiquitin-ligase heterodimer with BARD1. Reason: Structural and biochemical evidence establishes the heterodimer and its ubiquitin-ligase function. This core complex assignment does not imply that every isolated BRCA1 domain lacks an independently measurable activity or that BRCA1 belongs to only one assembly. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: BRCA1 nucleoplasm localization. Reason: Nucleoplasm localization is essential for BRCA1 function. |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | ACCEPT | Summary: BRCA1 localizes to nuclear bodies including BRCA1 foci. Reason: BRCA1 forms nuclear foci at DNA damage sites. This is consistent with its repair function. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:20820192 BRCA1 affects global DNA methylation through regulation of D... | KEEP AS NON CORE | Summary: BRCA1 contributes to transcriptional activation in defined promoter and reporter contexts. Reason: BRCA1-containing transcriptional complexes and promoter/reporter assays support this function. RHA links BRCA1 to RNA polymerase II, and BRCA1 regulates DNMT1 through a promoter complex. The annotation is retained outside the principal repair-focused synthesis; the available evidence does not establish that transcriptional regulation is dispensable for tumor suppression. Supporting Evidence: |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683735 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5683735 (CHEK2 is recruited to DNA DSBs). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683801 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5683801 (CHEK2 phosphorylates BRCA1). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684052 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5684052 (PIAS4 SUMOylates MDC1). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684071 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5684071 (RNF4 ubiquitinates MDC1). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684108 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5684108 (BRCA1 binds phosphorylated RBBP8). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684875 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5684875 (Binding of ATR:ATRIP to RPA at resected DNA DSBs). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684882 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5684882 (CHEK1 is recruited to resected DNA DSBs). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684887 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5684887 (Activation of CHEK1 at resected DNA DSBs). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685011 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5685011 (ATR activation at DNA DSBs). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685156 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5685156 (ATR phosphorylates RPA2). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685341 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5685341 (BCDX2 complex stabilizes RAD51 filament). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685838 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5685838 (CX3 complex binds D-loop structures). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685985 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5685985 (EXO1 or DNA2 in complex with BLM or WRN binds initially resected DNA DSBs along with BRIP1 recruitment). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685994 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5685994 (Long-range resection of DNA DSBs by EXO1 or DNA2). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686410 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5686410 (BLM mediates dissolution of double Holliday junction). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686440 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5686440 (MUS81:EME1,EME2 cleaves D-loop). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686469 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5686469 (Resolution of D-loops cleaved by MUS81:EME1 or MUS81:EME2). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686483 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5686483 (Resolution of Holliday junctions cleaved by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2)). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686642 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5686642 (RAD52 promotes single strand annealing at resected DNA DSBs). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686657 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5686657 (ERCC1:XPF cleaves flaps generated by SSA). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686685 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5686685 (RIF1 and PAX1IP bind TP53BP1 at DNA DSBs). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693539 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5693539 (Ligation of DNA and formation of Holliday structures following repair synthesis). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693542 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5693542 (Association of RPA complexes with ssDNA at resected DNA DSBs). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693551 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5693551 (Phosphorylation of BRCA1-A complex at multiple sites by ATM). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693561 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5693561 (RAD51 binds BRCA2 at resected DNA DSBs). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693564 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5693564 (Association of RAD51 with RAD52:DNA double-strand break ends). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693580 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5693580 (Association of RAD52 with the RPA complex at resected DNA DSBs). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693584 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5693584 (Cleavage of Holliday junctions by GEN1 or SLX1A:SLX4:MUS81:EME1,(MUS81:EME2)). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693589 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5693589 (D-loop dissociation and strand annealing). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693593 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5693593 (D-loop extension by DNA polymerases). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693608 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5693608 (Initial resection of double-strand break ends). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693620 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5693620 (D-loop formation mediated by PALB2, BRCA2 and RAD51). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6799332 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-6799332 (ATR phosphorylates TP53). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69891 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-69891 (Phosphorylation and activation of CHEK2 by ATM). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704330 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9704330 (Defective D-loop formation mediated by PALB2, BRCA2 and RAD51 due to loss-of-function of PALB2 in BRCA1 binding). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704408 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9704408 (Defective D-loop formation mediated by PALB2, BRCA2 and RAD51 due to loss-of-function of PALB2 in binding to BRCA2/RAD51/RAD51C). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709571 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9709571 (BRCA2 mutants with BRC defects or a defect in the C-terminal RAD51 binding site do not bind RAD51). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709601 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9709601 (Defective recruitment of BRCA2 and RAD51 due to loss of BRCA2 function in PALB2 binding). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9853389 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9853389 (FIGNL1 binds RAD51). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2997709 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-2997709 (PIAS1,4 SUMOylates BRCA1 with SUMO1). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2997616 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-2997616 (PIAS1,4 SUMOylates BRCA1 with SUMO2,3). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005634 nucleus | IDA PMID:26833090 Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologo... | ACCEPT | Summary: BRCA1 nuclear localization confirmed by direct assay. Reason: Nuclear localization is fundamental to BRCA1 function in DNA repair and transcriptional regulation. BRCA1 contains nuclear localization sequences and IDA evidence is appropriate for this annotation. Supporting Evidence: |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9701199 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9701199 (Defective D-loop formation mediated by PALB2, BRCA2 and RAD51 due to loss-of-function of BRCA1 in PALB2 binding). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683385 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5683385 (Formation of BRCA1-A complex at DNA DSBs). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5691411 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5691411 (BRCA1-A complex deubiquitinates K63polyUb-histone H2A). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9701000 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9701000 (BRCA1:BARD1 heterodimer autoubiquitinates). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9707051 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9707051 (UBXN1 binds BRCA1:BARD1 heterodimer). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9663194 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9663194 (Some pathogenic BRCA1 mutants do not bind BARD1). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:1990904 ribonucleoprotein complex | IDA PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chape... | UNDECIDED | Summary: The BRCA1 ribonucleoprotein-complex assertion remains source-limited. Reason: The entire available cache contains the NPM abstract and Discussion, but omits the Results and target complex inventory underlying this IDA assertion. Those accessible sections do not independently establish the BRCA1-containing complex. This is an access limitation, not proof of curator error or a reason to transfer NPMβs ribosome-export activity to BRCA1. Supporting Evidence: |
| GO:0032991 protein-containing complex | IDA PMID:9774970 Stable interaction between the products of the BRCA1 and BRC... | KEEP AS NON CORE | Summary: BRCA1 was detected in a BRCA1βBRCA2-containing protein complex. Reason: The cited source reports stable BRCA1βBRCA2 association in mitotic and meiotic cells. The broad complex annotation is sound. The earlier proposed substitution with BRCA1βBARD1 did not match the specific complex described by this source and is withdrawn; distinct named repair-complex annotations remain elsewhere. Supporting Evidence: |
| GO:0000800 lateral element | IDA PMID:9774970 Stable interaction between the products of the BRCA1 and BRC... | KEEP AS NON CORE | Summary: BRCA1 localizes to meiotic chromosome axial elements in the source study. Reason: The source describes mitotic and meiotic BRCA1βBRCA2 association and colocalization along developing synaptonemal-complex axial elements. Retain the curator-assigned lateral-element localization with its meiotic context, without asserting that this is its only germ-cell location. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:20160719 Identification of DBC1 as a transcriptional repressor for BR... | ACCEPT | Summary: BRCA1 nuclear localization confirmed by direct assay. Reason: Nuclear localization is fundamental to BRCA1 function in DNA repair and transcriptional regulation. BRCA1 contains two nuclear localization sequences in its central region. Supporting Evidence: |
| GO:0005737 cytoplasm | IDA PMID:20160719 Identification of DBC1 as a transcriptional repressor for BR... | KEEP AS NON CORE | Summary: The BRCA1βDBC1 complex can redistribute to the cytoplasm during ultraviolet-induced apoptosis. Reason: The source detects the endogenous complex in nuclei and its export during the tested apoptotic response. A context-dependent cytoplasmic pool is compatible with the major nuclear repair function; no cytoplasmic catalytic role is inferred. Supporting Evidence: |
| GO:0071356 cellular response to tumor necrosis factor | IMP PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction a... | UNDECIDED | Summary: The exact BRCA1-dependent TNF response assay is not exposed in the available abstract. Reason: The abstract supports endothelial inflammatory and survival effects but does not identify the specific TNF challenge and readout used for this annotation. Preserve the experimental assertion without inventing an NF-kB mechanism or treating the unavailable full assay as an absence result. Supporting Evidence: |
| GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors | IMP PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction a... | UNDECIDED | Summary: The death-domain-receptor specificity requires the original experimental details. Reason: BRCA1-dependent endothelial survival is supported, but the accessible abstract does not resolve the death-receptor pathway specified by this term. Context dependence and non-core status do not make an IMP annotation false. The prior confident over-annotation judgment is replaced by uncertainty about the uninspected pathway-specific assay. Supporting Evidence: |
| GO:2000378 negative regulation of reactive oxygen species metabolic process | IMP PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction a... | KEEP AS NON CORE | Summary: BRCA1 gain of function reduces reactive-oxygen-species readouts in endothelial cells. Reason: The reported loss- and gain-of-function experiments support the direction of the curated regulatory effect. Retain this cellular regulation outside the primary core functions, without assigning BRCA1 a ROS-detoxifying catalytic activity or an unmeasured direct metabolic mechanism. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:23855721 Localization of BRCA1 protein in breast cancer tissue and ce... | ACCEPT | Summary: BRCA1 nuclear localization confirmed by direct assay. Reason: Nuclear localization is fundamental to BRCA1 function in DNA repair and transcriptional regulation. Supporting Evidence: |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5659781 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-5659781 (BRCA1 forms a heterodimer with BARD1). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6797712 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-6797712 (CDK12 stimulates expression of DNA repair genes). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9007605 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9007605 (BRCA1 gene expression is inhibited by E2F6). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9699163 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9699163 (Defective BARD1 does not bind BRCA1). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9700998 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9700998 (BAP1 disrupts the BRCA1:BARD1 heterodimer). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9701003 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9701003 (BAP1 binds BRCA1:BARD1 heterodimer). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926521 | ACCEPT | Summary: BRCA1 has a curated nucleoplasmic localization in a Reactome source context. Reason: The retained TAS source is R-HSA-9926521 (MITF-M-dependent BRCA1 gene expression). Nucleoplasmic BRCA1 is independently established by direct localization studies. The cached event summary was read, but its full entity hierarchy and every underlying experiment were not re-curated. This location assertion does not transfer another participantβs catalytic activity or a mutant-specific defect to wild-type BRCA1. |
| GO:0005694 chromosome | ISS GO_REF:0000024 | ACCEPT | Summary: BRCA1 association with chromosomes, consistent with its role in DNA repair and chromatin functions. Reason: BRCA1 localizes to chromatin and DNA damage sites on chromosomes as part of its core DNA repair function. ISS evidence from sequence similarity supports this localization. |
| GO:0005886 plasma membrane | IDA PMID:21282464 A novel role for BRCA1 in regulating breast cancer cell spre... | KEEP AS NON CORE | Summary: A fraction of endogenous BRCA1 localizes at the plasma membrane in the studied cells. Reason: The inspected Results distinguish endogenous full-length BRCA1 microscopy and FRET from experiments using an EGFP-tagged BRCT fragment. They report endogenous BRCA1 at the plasma membrane by light and electron cryomicroscopy and proximity to ERM proteins. Predominantly nuclear localization does not contradict this documented contextual pool; no transmembrane or integral-membrane role is inferred. Supporting Evidence: |
| GO:0085020 protein K6-linked ubiquitination | IDA PMID:12890688 The BRCA1/BARD1 heterodimer assembles polyubiquitin chains t... | ACCEPT | Summary: BRCA1βBARD1 assembles K6-linked ubiquitin chains in the source biochemical assay. Reason: The purified full-length heterodimer produces preferential K6-linked autoubiquitin chains under the reported conditions. This is a positive specificity result, not evidence against the different products obtained with other E2 enzymes. |
| GO:0085020 protein K6-linked ubiquitination | IDA PMID:20351172 The UBXN1 protein associates with autoubiquitinated forms of... | ACCEPT | Summary: The UBXN1 study supports protein K6-linked ubiquitination by BRCA1βBARD1. Reason: The source measures the heterodimer, autoubiquitinated BRCA1 and inhibition of ligase function by UBXN1. Its K6-chain observations concern the reported conditions, not a universal exclusion of other ubiquitin linkages. The established activity and complex remain core even though the upstream inhibitor is another protein. Supporting Evidence: |
| GO:0031436 BRCA1-BARD1 complex | IDA PMID:12890688 The BRCA1/BARD1 heterodimer assembles polyubiquitin chains t... | ACCEPT | Summary: BRCA1 forms the functional RING ubiquitin-ligase heterodimer with BARD1. Reason: Structural and biochemical evidence establishes the heterodimer and its ubiquitin-ligase function. This core complex assignment does not imply that every isolated BRCA1 domain lacks an independently measurable activity or that BRCA1 belongs to only one assembly. |
| GO:0031436 BRCA1-BARD1 complex | IDA PMID:20351172 The UBXN1 protein associates with autoubiquitinated forms of... | ACCEPT | Summary: The UBXN1 study supports BRCA1-BARD1 complex by BRCA1βBARD1. Reason: The source measures the heterodimer, autoubiquitinated BRCA1 and inhibition of ligase function by UBXN1. Its K6-chain observations concern the reported conditions, not a universal exclusion of other ubiquitin linkages. The established activity and complex remain core even though the upstream inhibitor is another protein. Supporting Evidence: |
| GO:0051865 protein autoubiquitination | IDA PMID:12890688 The BRCA1/BARD1 heterodimer assembles polyubiquitin chains t... | ACCEPT | Summary: BRCA1-BARD1 complex undergoes autoubiquitination. This is a characteristic property of E3 ubiquitin ligases. Reason: Autoubiquitination is a common feature of E3 ligases and has been demonstrated for the BRCA1-BARD1 complex. This is consistent with its E3 ligase activity. Supporting Evidence: |
| GO:0051865 protein autoubiquitination | IDA PMID:20351172 The UBXN1 protein associates with autoubiquitinated forms of... | ACCEPT | Summary: The UBXN1 study supports protein autoubiquitination by BRCA1βBARD1. Reason: The source measures the heterodimer, autoubiquitinated BRCA1 and inhibition of ligase function by UBXN1. Its K6-chain observations concern the reported conditions, not a universal exclusion of other ubiquitin linkages. The established activity and complex remain core even though the upstream inhibitor is another protein. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:16331276 BRCA1 and FOXA1 proteins coregulate the expression of the ce... | KEEP AS NON CORE | Summary: BRCA1 has transcriptional activation activity, particularly through its C-terminal region. Reason: While BRCA1 has documented transcriptional regulatory functions and the C-terminal region can transactivate heterologous promoters, this is considered a secondary function compared to its core roles in DNA repair and E3 ligase activity. Supporting Evidence: |
| GO:0031436 BRCA1-BARD1 complex | IDA PMID:19117993 BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING ... | ACCEPT | Summary: The BAP1 study directly measures the BRCA1βBARD1 ligase complex. Reason: The source reports that BAP1 interacts with BARD1, perturbs BRCA1βBARD1 association and inhibits BRCA1 autoubiquitination and NPM1 ubiquitination. These are measurements of the annotated complex and its activity; they do not assign BAP1 hydrolase activity to BRCA1 or imply every BAP1 association is a direct BRCA1 contact. Supporting Evidence: |
| GO:0071681 cellular response to indole-3-methanol | IDA PMID:10868478 Suppression of breast cancer invasion and migration by indol... | UNDECIDED | Summary: The source associates indole-3-carbinol exposure with increased BRCA1 expression. Reason: The accessible abstract reports BRCA1 upregulation alongside reduced invasion and migration. It does not independently establish which BRCA1-dependent step mediates the cellular response, and the full experiment underlying the curated IDA assertion was not accessible. The prior rationale based solely on a non-core dietary-compound context is insufficient for confident over-annotation. Supporting Evidence: |
| GO:0005634 nucleus | IDA PMID:17643121 CCDC98 targets BRCA1 to DNA damage sites. | ACCEPT | Summary: BRCA1 nuclear localization confirmed by direct assay. Reason: Nuclear localization is fundamental to BRCA1 function in DNA repair and transcriptional regulation. Supporting Evidence: |
| GO:0070531 BRCA1-A complex | IDA PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | ACCEPT | Summary: BRCA1 participates in the BRCA1-A DNA damage-response assembly. Reason: The source context and independent interaction studies support a BRCA1 assembly involving Abraxas, RAP80 and associated BRCC components at damaged chromatin. Their ubiquitin-recognition and deubiquitination functions are not all intrinsic BRCA1 activities. The annotation describes complex membership, not a claim that every subunit was independently assayed in each cited paper. |
| GO:0070531 BRCA1-A complex | IDA PMID:17525341 RAP80 targets BRCA1 to specific ubiquitin structures at DNA ... | ACCEPT | Summary: BRCA1 participates in the BRCA1-A DNA damage-response assembly. Reason: The source context and independent interaction studies support a BRCA1 assembly involving Abraxas, RAP80 and associated BRCC components at damaged chromatin. Their ubiquitin-recognition and deubiquitination functions are not all intrinsic BRCA1 activities. The annotation describes complex membership, not a claim that every subunit was independently assayed in each cited paper. |
| GO:0070531 BRCA1-A complex | IDA PMID:17525342 Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA... | ACCEPT | Summary: BRCA1 participates in the BRCA1-A DNA damage-response assembly. Reason: The source context and independent interaction studies support a BRCA1 assembly involving Abraxas, RAP80 and associated BRCC components at damaged chromatin. Their ubiquitin-recognition and deubiquitination functions are not all intrinsic BRCA1 activities. The annotation describes complex membership, not a claim that every subunit was independently assayed in each cited paper. |
| GO:0070531 BRCA1-A complex | IDA PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: BRCA1 participates in the BRCA1-A DNA damage-response assembly. Reason: The source context and independent interaction studies support a BRCA1 assembly involving Abraxas, RAP80 and associated BRCC components at damaged chromatin. Their ubiquitin-recognition and deubiquitination functions are not all intrinsic BRCA1 activities. The annotation describes complex membership, not a claim that every subunit was independently assayed in each cited paper. |
| GO:0070531 BRCA1-A complex | IDA PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | ACCEPT | Summary: BRCA1 participates in the BRCA1-A DNA damage-response assembly. Reason: The source context and independent interaction studies support a BRCA1 assembly involving Abraxas, RAP80 and associated BRCC components at damaged chromatin. Their ubiquitin-recognition and deubiquitination functions are not all intrinsic BRCA1 activities. The annotation describes complex membership, not a claim that every subunit was independently assayed in each cited paper. |
| GO:0031436 BRCA1-BARD1 complex | IDA PMID:15265711 BARD1 regulates BRCA1 apoptotic function by a mechanism invo... | ACCEPT | Summary: BRCA1 forms the functional RING ubiquitin-ligase heterodimer with BARD1. Reason: Structural and biochemical evidence establishes the heterodimer and its ubiquitin-ligase function. This core complex assignment does not imply that every isolated BRCA1 domain lacks an independently measurable activity or that BRCA1 belongs to only one assembly. |
| GO:0000151 ubiquitin ligase complex | NAS PMID:14976165 BRCA1 : BARD1 induces the formation of conjugated ubiquitin ... | ACCEPT | Summary: BRCA1 forms the functional RING ubiquitin-ligase heterodimer with BARD1. Reason: Structural and biochemical evidence establishes the heterodimer and its ubiquitin-ligase function. This core complex assignment does not imply that every isolated BRCA1 domain lacks an independently measurable activity or that BRCA1 belongs to only one assembly. |
| GO:0000931 gamma-tubulin ring complex | NAS PMID:12214252 Roles of BRCA1 in centrosome duplication. | UNDECIDED | Summary: Centrosomal gamma-tubulin association does not by itself establish gamma-tubulin-ring-complex membership. Reason: The accessible review abstract and independent localization paper support centrosomal BRCA1 and gamma-tubulin coassociation. GO:0000931 denotes the gamma-tubulin ring complex, a more specific assembly than the centrosome. Its exact BRCA1 membership evidence was not available in the inspected review abstract, so the original NAS assertion is preserved as uncertain rather than converted into an unsupported permanent-complex claim. |
| GO:0046600 negative regulation of centriole replication | NAS PMID:12214252 Roles of BRCA1 in centrosome duplication. | KEEP AS NON CORE | Summary: BRCA1 blocks centrosome reduplication, preventing formation of multiple functional centrosomes. Reason: BRCA1 has documented roles in centrosome regulation and blocks centrosome reduplication. While this is a real function, it is secondary to the core DNA repair and E3 ligase functions. Supporting Evidence: |
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Download this section (compressed HTML)Q: Which endogenous substrates and E2-dependent ubiquitin products explain the separable repair and tumor-suppressive activities of full-length BRCA1βBARD1, and how do ligase-defective mutants compare with mutants that retain DNA binding and partner assembly?
Q: Can the original interaction tables and self-association assays resolve the source-specific UNDECIDED rows, including whether recorded screen partners represent direct contacts, co-complex associations or proximity measurements?
Q: Which of the eight named UniProt alternative products retain each DNA-binding, RING and BRCT activity? Existing unqualified GOA objects do not demonstrate functional equivalence of all products.
Q: Does the available evidence justify a BRCA1 contributes_to relationship for the BRCA1βBARD1 histone-reader function, while retaining the direct modified-histone recognition site on BARD1?
Q: Which assays distinguish BRCA1 participation in productive stalled-fork resection from fork protection, general DSB-end resection and downstream phenotypes?
Q: Which molecular-function term would best capture the experimentally observed stimulation of EXO1 and BLMβDNA2/WRNβDNA2 resection by BRCA1βBARD1 and the isolated BRCA1 467β696 module, while distinguishing fragment concentration-dependent effects from the intact complex and retaining helicase/nuclease catalysis on the partner enzymes?
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