BRCA1 is a critical tumor suppressor protein that functions as a central hub for maintaining genomic stability. Its primary molecular function is as a RING-type E3 ubiquitin ligase (in complex with BARD1) that catalyzes K6-linked polyubiquitin chains. BRCA1 orchestrates the cellular response to DNA double-strand breaks through multiple mechanisms: promoting homologous recombination repair via DNA end resection and RAD51 loading, regulating cell cycle checkpoints (particularly S-phase and G2/M), and maintaining centrosome stability. The protein contains three key domains: an N-terminal RING domain mediating E3 ligase activity, a large central region with nuclear localization signals and protein interaction sites, and C-terminal BRCT domains that bind phosphoproteins. BRCA1 forms at least four major complexes (BRCA1-A through BRCA1-D) that execute distinct functions in the DNA damage response. Germline pathogenic variants in BRCA1 cause hereditary breast and ovarian cancer syndrome, with carriers having approximately 66% risk of breast cancer and 41% risk of ovarian cancer by age 70.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004842 ubiquitin-protein transferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA1 functions as a RING-type E3 ubiquitin ligase in complex with BARD1, catalyzing the formation of K6-linked polyubiquitin chains. This enzymatic activity is essential for multiple stages of homologous recombination repair and represents the only known enzymatic function of BRCA1. The IBA annotation is well-supported by extensive experimental evidence across multiple species. Reason: This annotation accurately captures BRCA1s core enzymatic function. Multiple studies have demonstrated that BRCA1-BARD1 heterodimer possesses E3 ubiquitin ligase activity, forming unconventional K6-linked polyubiquitin chains [PMID:12890688]. Recent work using ligase-null mutants (I26A/L63A/K65A) has definitively established this activity is required for homologous recombination [PMID:23007347]. The IBA annotation correctly identifies this conserved function across species. Supporting Evidence: PMID:12890688 The BRCA1/BARD1 heterodimer directs polymerization of ubiquitin primarily through an unconventional linkage involving lysine residue K6 file:human/BRCA1/BRCA1-deep-research-falcon.md See deep research file for comprehensive analysis |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | MODIFY | Summary: BRCA1 has DNA binding activity, though this is a general annotation that could be more specific. BRCA1 binds to damaged DNA at double-strand breaks and associates with chromatin during the DNA damage response. The central region contains DNA-binding capability. Reason: While BRCA1 does bind DNA, this annotation is too general and uninformative. BRCA1 specifically binds to damaged DNA and DNA structures at double-strand breaks. A more specific term like "damaged DNA binding" (GO:0003684) would better represent its actual function in the DNA damage response. Proposed replacements: damaged DNA binding |
| GO:0004842 ubiquitin-protein transferase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Duplicate annotation of BRCA1s E3 ubiquitin ligase activity, this time from InterPro domain prediction. The annotation is correct as BRCA1 contains a RING domain that mediates E3 ligase activity. Reason: This IEA annotation correctly identifies BRCA1s E3 ubiquitin ligase activity based on its RING domain. While redundant with the IBA annotation, it provides complementary evidence from protein domain analysis. The RING domain at the N-terminus is essential for BRCA1s E3 ligase function in complex with BARD1. Supporting Evidence: PMID:12890688 The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin |
| GO:0005515 protein binding | IPI PMID:10477523 Functional interaction of BRCA1-associated BARD1 with polyad... | REMOVE | Summary: Generic protein binding annotation from a study showing BRCA1 interaction with polyadenylation factor CstF-50. This is an uninformative annotation that should be replaced with more specific molecular function terms. Reason: The generic "protein binding" term provides no useful functional information about BRCA1. While BRCA1 does interact with many proteins including CstF-50 (as shown in PMID:10477523), this should be captured through more specific functional annotations like "RNA polymerase II C-terminal domain binding" or annotations related to its core functions in DNA repair and ubiquitination. Generic protein binding annotations should be avoided per curation guidelines. Supporting Evidence: PMID:10477523 Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50 |
| GO:0005515 protein binding | IPI PMID:11090615 Sequence-specific transcriptional corepressor function for B... | REMOVE | Summary: Generic protein binding annotation from BRCA1-ZBRK1 interaction study. ZBRK1 is a transcriptional corepressor that interacts with BRCA1. Reason: Generic protein binding annotation provides no functional information. The ZBRK1 interaction relates to transcriptional regulation, which is a peripheral function of BRCA1. If retained, should use more specific terms related to transcriptional regulation. Supporting Evidence: PMID:11090615 Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1 |
| GO:0005515 protein binding | IPI PMID:11739404 BRCA1-induced large-scale chromatin unfolding and allele-spe... | REMOVE | Summary: Generic protein binding annotation from chromatin unfolding study showing BRCA1 interaction with NELFB. Reason: Uninformative generic protein binding term. The study shows BRCA1 involvement in chromatin remodeling, which should be annotated with specific chromatin-related GO terms rather than generic protein binding. Supporting Evidence: PMID:11739404 BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations |
| GO:0005515 protein binding | IPI PMID:11836499 BRCA1 regulates the G2/M checkpoint by activating Chk1 kinas... | REMOVE | Summary: Generic protein binding from BRCA1-CHEK1 interaction study related to G2/M checkpoint control. Reason: Generic protein binding term is uninformative. This interaction with CHEK1 is specifically related to cell cycle checkpoint control, which is better captured by process annotations like "mitotic G2/M transition checkpoint" rather than generic binding. Supporting Evidence: PMID:11836499 BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage |
| GO:0005515 protein binding | IPI PMID:12419185 NBS1 localizes to gamma-H2AX foci through interaction with t... | REMOVE | Summary: Generic protein binding from study showing NBS1 localization to Ξ³-H2AX foci through BRCA1 BRCT domain interaction. Reason: Generic protein binding is uninformative. This interaction is specifically related to DNA damage response and double-strand break repair, which should be captured through more specific functional annotations. Supporting Evidence: PMID:12419185 NBS1 localizes to gamma-H2AX foci through interaction with the FHA/BRCT domain |
| GO:0005515 protein binding | IPI PMID:12607005 MDC1 is a mediator of the mammalian DNA damage checkpoint. | REMOVE | Summary: Generic protein binding from MDC1 interaction study. MDC1 is a key mediator of DNA damage checkpoint. Reason: Generic protein binding provides no functional insight. The MDC1 interaction is specifically important for DNA damage checkpoint signaling and should be captured through checkpoint-related process annotations. Supporting Evidence: PMID:12607005 MDC1 is a mediator of the mammalian DNA damage checkpoint |
| GO:0005515 protein binding | IPI PMID:14550570 BRCA1 interacts with FHL2 and enhances FHL2 transactivation ... | REMOVE | Summary: Generic protein binding from FHL2 interaction study. Reason: Uninformative generic protein binding annotation. FHL2 interaction relates to transcriptional activation, a peripheral function. Supporting Evidence: PMID:14550570 BRCA1 interacts with FHL2 and enhances FHL2 transactivation function |
| GO:0005515 protein binding | IPI PMID:14654789 A member of the Pyrin family, IFI16, is a novel BRCA1-associ... | REMOVE | Summary: Generic protein binding from IFI16 interaction study related to p53-mediated apoptosis. Reason: Generic protein binding is uninformative. The IFI16 interaction is specifically related to apoptotic signaling, which is captured by the separate apoptosis annotation from the same paper. Supporting Evidence: PMID:14654789 A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway |
| GO:0005515 protein binding | IPI PMID:15125843 Structure of the BRCT repeats of BRCA1 bound to a BACH1 phos... | REMOVE | Summary: Generic protein binding from structural study of BRCT-BACH1 phosphopeptide interaction. Reason: Generic protein binding provides no functional information. The BACH1/BRIP1 interaction through BRCT domains is critical for DNA repair, but this should be captured through specific DNA repair annotations rather than generic binding. Supporting Evidence: PMID:15125843 Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling |
| GO:0005515 protein binding | IPI PMID:15133502 Structure and mechanism of BRCA1 BRCT domain recognition of ... | REMOVE | Summary: Generic protein binding from BRCT-BACH1 structural study. Reason: Uninformative generic protein binding. The BACH1/BRIP1 interaction is important for DNA repair but should be captured through specific functional annotations. Supporting Evidence: PMID:15133502 Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer |
| GO:0005515 protein binding | IPI PMID:15674350 Structural determinants of the BRCA1 : estrogen receptor int... | REMOVE | Summary: Generic protein binding from BRCA1-estrogen receptor interaction study. Reason: Uninformative generic annotation. The estrogen receptor interaction may relate to hormone-responsive transcription but is not core to BRCA1 function. Supporting Evidence: PMID:15674350 Structural determinants of the BRCA1 : estrogen receptor interaction |
| GO:0005515 protein binding | IPI PMID:15965487 BRCA1 participates in DNA decatenation. | REMOVE | Summary: Generic protein binding from study on BRCA1 role in DNA decatenation. Reason: Generic protein binding provides no functional information. The DNA decatenation function should be captured through specific process annotations. Supporting Evidence: PMID:15965487 BRCA1 participates in DNA decatenation |
| GO:0005515 protein binding | IPI PMID:16326698 BRCA1 affects lipid synthesis through its interaction with a... | REMOVE | Summary: Generic protein binding from BRCA1-acetyl-CoA carboxylase interaction study. Reason: Uninformative generic annotation. The ACACA interaction relates to lipid metabolism, which is not a core BRCA1 function. Supporting Evidence: PMID:16326698 BRCA1 affects lipid synthesis through its interaction with acetyl-CoA carboxylase |
| GO:0005515 protein binding | IPI PMID:16452482 ATM activation by ionizing radiation requires BRCA1-associat... | REMOVE | Summary: Generic protein binding from BAAT1 interaction study related to ATM activation. Reason: Generic protein binding is uninformative. The BAAT1 interaction is important for ATM activation in DNA damage response but should be captured through checkpoint annotations. Supporting Evidence: PMID:16452482 ATM activation by ionizing radiation requires BRCA1-associated BAAT1 |
| GO:0005515 protein binding | IPI PMID:17334399 Functional consequences of cyclin D1/BRCA1 interaction in br... | REMOVE | Summary: Generic protein binding from cyclin D1-BRCA1 interaction study. Reason: Uninformative generic annotation. Cyclin D1 interaction relates to cell cycle regulation, which is captured by specific cell cycle annotations. Supporting Evidence: PMID:17334399 Functional consequences of cyclin D1/BRCA1 interaction in breast cancer cells |
| GO:0005515 protein binding | IPI PMID:17511879 The interaction of PP1 with BRCA1 and analysis of their expr... | REMOVE | Summary: Generic protein binding from PP1-BRCA1 interaction study. Reason: Uninformative generic annotation. PP1 phosphatase interaction may regulate BRCA1 phosphorylation status but is not core function. Supporting Evidence: PMID:17511879 The interaction of PP1 with BRCA1 and analysis of their expression in breast tumors |
| GO:0005515 protein binding | IPI PMID:17525332 ATM and ATR substrate analysis reveals extensive protein net... | REMOVE | Summary: Generic protein binding from ATM/ATR substrate analysis showing BRCA1 in DNA damage network. Reason: Generic protein binding is uninformative. This large-scale study identified BRCA1 in ATM/ATR response networks, which is better captured through DNA damage response annotations. Supporting Evidence: PMID:17525332 ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage |
| GO:0005515 protein binding | IPI PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | REMOVE | Summary: Generic protein binding from Abraxas-RAP80 complex study, key components of BRCA1-A complex. Reason: While this interaction is functionally important for BRCA1-A complex formation in DNA damage response, generic protein binding term is uninformative. The function is better captured through DNA repair process annotations. Supporting Evidence: PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response |
| GO:0005515 protein binding | IPI PMID:17581638 The FANCJ/MutLalpha interaction is required for correction o... | REMOVE | Summary: Generic protein binding from FANCJ/MutLalpha interaction study related to cross-link repair. Reason: Uninformative generic annotation. The FANCJ interaction is important for interstrand cross-link repair but should be captured through specific DNA repair annotations. Supporting Evidence: PMID:17581638 The FANCJ/MutLalpha interaction is required for correction of the cross-link response in FA-J cells |
| GO:0005515 protein binding | IPI PMID:17643121 CCDC98 targets BRCA1 to DNA damage sites. | REMOVE | Summary: Generic protein binding from CCDC98/Abraxas study targeting BRCA1 to DNA damage sites. Reason: Generic annotation. CCDC98/Abraxas is part of BRCA1-A complex crucial for DNA damage response, but this is captured by DNA repair annotations. Supporting Evidence: PMID:17643121 CCDC98 targets BRCA1 to DNA damage sites |
| GO:0005515 protein binding | IPI PMID:17873885 E2-BRCA1 RING interactions dictate synthesis of mono- or spe... | REMOVE | Summary: Generic protein binding from E2-BRCA1 RING interaction study on ubiquitin chain synthesis. Reason: Generic annotation. E2 enzyme interactions are captured by ubiquitin ligase activity annotations. Supporting Evidence: PMID:17873885 E2-BRCA1 RING interactions dictate synthesis of mono- or specific polyubiquitin chain linkages |
| GO:0005515 protein binding | IPI PMID:18001824 RNF8 ubiquitylates histones at DNA double-strand breaks and ... | REMOVE | Summary: Generic protein binding from RNF8 study on histone ubiquitylation at DSBs. Reason: Generic annotation. RNF8 interaction is important for DNA damage signaling but captured by DNA repair annotations. Supporting Evidence: PMID:18001824 RNF8 ubiquitylates histones at DNA double-strand breaks and promotes assembly of repair proteins |
| GO:0005515 protein binding | IPI PMID:18001825 RNF8 transduces the DNA-damage signal via histone ubiquityla... | REMOVE | Summary: Generic protein binding from RNF8 DNA damage signaling study. Reason: Duplicate generic annotation for RNF8 interaction. DNA damage response function captured elsewhere. Supporting Evidence: PMID:18001825 RNF8 transduces the DNA-damage signal via histone ubiquitylation and checkpoint protein assembly |
| GO:0005515 protein binding | IPI PMID:18285836 Pathogenicity of the BRCA1 missense variant M1775K is determ... | REMOVE | Summary: Generic protein binding from study of M1775K variant disrupting BRCT phosphopeptide binding. Reason: Generic annotation. Study demonstrates importance of BRCT domain interactions but this is captured by functional annotations. Supporting Evidence: PMID:18285836 Pathogenicity of the BRCA1 missense variant M1775K is determined by the disruption of the BRCT phosphopeptide-binding pocket |
| GO:0005515 protein binding | IPI PMID:19369211 PALB2 is an integral component of the BRCA complex required ... | REMOVE | Summary: Generic protein binding from PALB2 interaction study, critical for BRCA1-BRCA2 connection in HR. Reason: While PALB2 interaction is crucial for HR by bridging BRCA1 and BRCA2, generic protein binding is uninformative. This function is captured by HR repair annotations. Supporting Evidence: PMID:19369211 PALB2 is an integral component of the BRCA complex required for homologous recombination repair |
| GO:0005515 protein binding | IPI PMID:20016594 The SUMO modification pathway is involved in the BRCA1 respo... | REMOVE | Summary: Generic protein binding from SUMO pathway involvement in BRCA1 response to genotoxic stress. Reason: Generic annotation. SUMOylation pathway interactions are regulatory but not core to BRCA1 function. Supporting Evidence: PMID:20016594 The SUMO modification pathway is involved in the BRCA1 response to genotoxic stress |
| GO:0005515 protein binding | IPI PMID:20016603 Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses ... | REMOVE | Summary: Generic protein binding from PIAS1/PIAS4 SUMO E3 ligase interaction study. Reason: Generic annotation. SUMO E3 ligase interactions relate to post-translational regulation but are not core function. Supporting Evidence: PMID:20016603 Mammalian SUMO E3-ligases PIAS1 and PIAS4 promote responses to DNA double-strand breaks |
| GO:0005515 protein binding | IPI PMID:21240188 Interaction between the helicases genetically linked to Fanc... | REMOVE | Summary: Generic protein binding from FANCJ-BLM helicase interaction study. Reason: Generic annotation. Helicase interactions are important for DNA repair but captured by specific repair annotations. Supporting Evidence: PMID:21240188 interaction between the helicases genetically linked to Fanconi anemia group J and Bloom's syndrome |
| GO:0005515 protein binding | IPI PMID:21407215 Multifunctional transcription factor TFII-I is an activator ... | REMOVE | Summary: Generic protein binding from TFII-I transcription factor interaction study. Reason: Generic annotation. TFII-I interaction relates to transcriptional regulation, a peripheral function. Supporting Evidence: PMID:21407215 Multifunctional transcription factor TFII-I is an activator of BRCA1 function |
| GO:0005515 protein binding | IPI PMID:21951318 Ligand-dependent differences in estrogen receptor beta-inter... | REMOVE | Summary: Generic protein binding from estrogen receptor beta interaction in lung adenocarcinoma cells. Reason: Generic annotation. Estrogen receptor interactions are tissue-specific and not core to BRCA1 tumor suppressor function. Supporting Evidence: PMID:21951318 Ligand-dependent differences in estrogen receptor beta-interacting proteins identified in lung adenocarcinoma cells corresponds to estrogenic responses |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Generic protein binding from large-scale liver protein interaction network study. Reason: Generic annotation from proteomics screen provides no functional information. Supporting Evidence: PMID:21988832 Toward an understanding of the protein interaction network of the human liver |
| GO:0005515 protein binding | IPI PMID:22110403 Interplay between BRCA1 and RHAMM regulates epithelial apico... | REMOVE | Summary: Generic protein binding from RHAMM interaction study on epithelial polarization. Reason: Generic annotation. RHAMM interaction relates to cell polarization, not core BRCA1 function. Supporting Evidence: PMID:22110403 Interplay between BRCA1 and RHAMM regulates epithelial apicobasal polarization and may influence risk of breast cancer |
| GO:0005515 protein binding | IPI PMID:22193777 ChAM, a novel motif that mediates PALB2 intrinsic chromatin ... | REMOVE | Summary: Generic protein binding from PALB2 ChAM motif study on chromatin binding and DNA repair. Reason: Generic annotation. PALB2 interaction is crucial for HR but captured by DNA repair annotations. Supporting Evidence: PMID:22193777 ChAM, a novel motif that mediates PALB2 intrinsic chromatin binding and facilitates DNA repair |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:12890688 The BRCA1/BARD1 heterodimer assembles polyubiquitin chains t... | ACCEPT | Summary: Direct experimental evidence for BRCA1-BARD1 E3 ubiquitin ligase activity forming K6-linked polyubiquitin chains. This is a core molecular function of BRCA1. Reason: This IDA annotation provides direct experimental evidence for BRCA1s E3 ubiquitin ligase activity. The cited paper demonstrates that BRCA1-BARD1 heterodimer catalyzes formation of unconventional K6-linked polyubiquitin chains, distinguishing it from other E3 ligases. This enzymatic activity is essential for BRCA1s tumor suppressor function. Supporting Evidence: PMID:12890688 The BRCA1/BARD1 heterodimer directs polymerization of ubiquitin primarily through an unconventional linkage involving lysine residue K6 |
| GO:0000976 transcription cis-regulatory region binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Automated annotation for transcriptional regulatory region binding based on ortholog evidence. Reason: While BRCA1 does have transcriptional regulatory functions including binding to cis-regulatory regions, this is a peripheral function compared to its core role in DNA repair. The transcriptional activities are secondary to its primary tumor suppressor function through homologous recombination repair. Supporting Evidence: PMID:20820192 BRCA1 affects global DNA methylation through regulation of DNMT1 |
| GO:0003684 damaged DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: BRCA1 binds to damaged DNA at double-strand breaks as part of its DNA repair function. This is more specific than generic DNA binding. Reason: This annotation correctly captures BRCA1s ability to recognize and bind damaged DNA, particularly at double-strand breaks. BRCA1 is recruited to DSBs through multiple mechanisms including its BRCT domains binding to phosphorylated proteins and direct DNA interaction. This is a core function related to its role in homologous recombination repair. Supporting Evidence: PMID:15125843 Structure of the BRCT repeats of BRCA1 bound to a BACH1 phosphopeptide: implications for signaling |
| GO:0003713 transcription coactivator activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1 has transcription coactivator activity, demonstrated through interaction with RNA polymerase II and various transcription factors. Reason: While BRCA1 does function as a transcription coactivator through its C-terminal transactivation domain and interactions with RNA pol II, this is a peripheral function. The transcriptional role is secondary to its primary tumor suppressor function through DNA repair. Multiple studies confirm this activity but it is not essential for tumor suppression. Supporting Evidence: PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A PMID:20820192 BRCA1 affects global DNA methylation through regulation of DNMT1 |
| GO:0007098 centrosome cycle | IEA GO_REF:0000107 | ACCEPT | Summary: BRCA1 localizes to centrosomes and regulates centrosome duplication and function, preventing centrosome amplification and maintaining chromosomal stability. Reason: This annotation correctly identifies BRCA1s important role in centrosome regulation. BRCA1 localizes to centrosomes during mitosis, associates with gamma-tubulin, and prevents centrosome reduplication. Loss of BRCA1 leads to centrosome amplification and chromosomal instability. This is a core function contributing to genomic stability maintenance. Supporting Evidence: PMID:9789027 Our results indicate that BRCA1 localizes with the centrosome during mitosis and coimmunoprecipitates with gamma-tubulin, a centrosomal component essential for nucleation of microtubules PMID:21673012 KIAA0101 interacts with BRCA1 and regulates centrosome number |
| GO:0043009 chordate embryonic development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1 knockout mice show embryonic lethality, indicating a role in development. However, this is likely secondary to genomic instability. Reason: While BRCA1-null mice do show embryonic lethality around E7.5-8.5, this developmental role is likely secondary to severe genomic instability from loss of DNA repair function. The embryonic lethality results from accumulated DNA damage rather than a specific developmental program. This is a consequence of BRCA1 loss rather than a primary function. Supporting Evidence: PMID:10549283 We report here that Brca1-deficient mouse embryonic stem cells have impaired repair of chromosomal DSBs by homologous recombination |
| GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1 regulates DNA methylation through interaction with DNMT1, affecting global methylation patterns. Reason: BRCA1 does regulate DNA methylation and epigenetic silencing, particularly through DNMT1 regulation. However, this epigenetic function is peripheral to its core tumor suppressor role in DNA repair. The methylation effects may be secondary to transcriptional regulation or chromatin remodeling activities. Supporting Evidence: PMID:20820192 BRCA1 affects global DNA methylation through regulation of DNMT1 |
| GO:0044818 mitotic G2/M transition checkpoint | IEA GO_REF:0000107 | ACCEPT | Summary: BRCA1 is essential for G2/M checkpoint control, activating CHEK1 kinase upon DNA damage to prevent premature mitotic entry. Reason: This annotation correctly captures BRCA1s critical role in cell cycle checkpoint control. BRCA1 activates CHEK1 upon DNA damage, enforcing the G2/M checkpoint to prevent cells with damaged DNA from entering mitosis. Loss of BRCA1 leads to checkpoint defects and genomic instability. This is a core function essential for tumor suppression. Supporting Evidence: PMID:11836499 BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage |
| GO:0060816 random inactivation of X chromosome | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA1 supports XIST RNA concentration on the inactive X chromosome, contributing to X-inactivation. Reason: While BRCA1 does interact with XIST RNA and localizes to the inactive X chromosome, this is a specialized peripheral function not related to its core tumor suppressor role. The X-inactivation function is tissue and context-specific and not essential for BRCA1s primary DNA repair activities. Supporting Evidence: PMID:12419249 BRCA1 supports XIST RNA concentration on the inactive X chromosome |
| GO:0003713 transcription coactivator activity | IDA PMID:20820192 BRCA1 affects global DNA methylation through regulation of D... | KEEP AS NON CORE | Summary: Direct evidence for BRCA1 transcription coactivator activity in DNMT1 regulation and methylation control. Reason: This IDA annotation provides direct evidence for transcriptional coactivator function, specifically in regulating DNMT1. However, transcriptional regulation is a peripheral function compared to BRCA1s core role in DNA repair. The transcriptional activities contribute to but are not essential for tumor suppression. Supporting Evidence: PMID:20820192 BRCA1 affects global DNA methylation through regulation of DNMT1 |
| GO:0004842 ubiquitin-protein transferase activity | TAS Reactome:R-HSA-9701000 | ACCEPT | Summary: Reactome pathway annotation for BRCA1-BARD1 autoubiquitination activity. Reason: This TAS annotation from Reactome correctly identifies BRCA1s E3 ubiquitin ligase activity, specifically its autoubiquitination in complex with BARD1. This enzymatic activity is well-established and essential for BRCA1 function in DNA repair. Supporting Evidence: Reactome:R-HSA-9701000 BRCA1:BARD1 heterodimer autoubiquitinates |
| 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: Direct evidence showing BRCA1 regulates CpG methylation through DNMT1 control. Reason: This IMP annotation demonstrates BRCA1s role in epigenetic regulation through DNA methylation. While experimentally validated, this epigenetic function is peripheral to BRCA1s core tumor suppressor role in DNA repair. The methylation effects may be indirect consequences of transcriptional regulation. Supporting Evidence: PMID:20820192 BRCA1 affects global DNA methylation through regulation of DNMT1 |
| GO:0005515 protein binding | IPI PMID:16101277 Structural basis for cell cycle checkpoint control by the BR... | REMOVE | Summary: Generic protein binding from BRCA1-CtIP complex structural study for cell cycle checkpoint control. Reason: While CtIP interaction is crucial for DNA end resection in HR, generic protein binding is uninformative. Function captured by DNA repair annotations. Supporting Evidence: PMID:16101277 Structural basis for cell cycle checkpoint control by the BRCA1-CtIP complex |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:17349954 A critical role for the ubiquitin-conjugating enzyme Ubc13 i... | ACCEPT | Summary: Direct evidence showing BRCA1 E3 ligase activity is critical for initiating homologous recombination through Ubc13 interaction. Reason: This IDA annotation provides crucial evidence that BRCA1s E3 ubiquitin ligase activity, working with the E2 enzyme Ubc13, is required for initiating homologous recombination. This study demonstrates the functional importance of BRCA1s enzymatic activity in its core DNA repair function. Supporting Evidence: PMID:17349954 A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination |
| GO:0002039 p53 binding | IDA PMID:15571721 Characterization of segments from the central region of BRCA... | ACCEPT | Summary: BRCA1 central region contains intrinsically disordered segments that interact with p53 and other proteins involved in DNA damage response. Reason: The p53 binding annotation is specific and functionally relevant, unlike generic protein binding. BRCA1-p53 interaction is important for coordinating DNA damage response and apoptosis. The central region of BRCA1 forms an intrinsically disordered scaffold for multiple protein-protein interactions including p53. This interaction contributes to BRCA1s tumor suppressor function. Supporting Evidence: PMID:15571721 Characterization of segments from the central region of BRCA1: an intrinsically disordered scaffold for multiple protein-protein and protein-DNA interactions |
| GO:0005515 protein binding | IPI PMID:10518542 BRCA1-associated growth arrest is RB-dependent. | REMOVE | Summary: Generic protein binding from RB interaction study on growth arrest. Reason: Generic annotation. RB interaction relates to cell cycle control, captured by cell cycle annotations. Supporting Evidence: PMID:10518542 BRCA1-associated growth arrest is RB-dependent |
| GO:0005515 protein binding | IPI PMID:12354784 BRCA1 interacts directly with the Fanconi anemia protein FAN... | REMOVE | Summary: Generic protein binding from BRCA1-FANCA interaction in Fanconi anemia pathway. Reason: Generic annotation. FANCA interaction is important for interstrand cross-link repair, captured by DNA repair annotations. Supporting Evidence: PMID:12354784 BRCA1 interacts directly with the Fanconi anemia protein FANCA |
| GO:0051726 regulation of cell cycle | IDA PMID:21102443 Transcriptional regulation of BRCA1 expression by a metaboli... | ACCEPT | Summary: BRCA1 regulates cell cycle progression through multiple checkpoints and is subject to metabolic regulation. Reason: This annotation correctly captures BRCA1s broad role in cell cycle regulation. BRCA1 controls S-phase progression, G2/M checkpoint, and spindle checkpoint. It prevents premature cell cycle progression when DNA damage is present. This is a core function essential for maintaining genomic stability and tumor suppression. Supporting Evidence: PMID:21102443 Transcriptional regulation of BRCA1 expression by a metabolic switch PMID:11836499 BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage |
| GO:0003713 transcription coactivator activity | IMP PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme ... | KEEP AS NON CORE | Summary: BRCA1 links to RNA polymerase II holoenzyme complex via RNA helicase A, functioning as transcription coactivator. Reason: While this IMP annotation confirms BRCA1s transcription coactivator function through RNA pol II interaction, this is a peripheral function. The transcriptional role is secondary to BRCA1s primary tumor suppressor function through DNA repair mechanisms. Transcriptional defects do not fully explain BRCA1-associated cancer predisposition. Supporting Evidence: PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A |
| GO:0005515 protein binding | IPI PMID:20160719 Identification of DBC1 as a transcriptional repressor for BR... | REMOVE | Summary: Generic protein binding from DBC1 transcriptional repressor interaction study. Reason: Generic annotation. DBC1 interaction relates to transcriptional regulation, a peripheral function. Supporting Evidence: PMID:20160719 Identification of DBC1 as a transcriptional repressor for BRCA1 |
| GO:0005515 protein binding | IPI PMID:21673012 KIAA0101 interacts with BRCA1 and regulates centrosome numbe... | REMOVE | Summary: Generic protein binding from KIAA0101 interaction study on centrosome regulation. Reason: Generic annotation. KIAA0101 interaction relates to centrosome regulation, captured by centrosome cycle annotation. Supporting Evidence: PMID:21673012 KIAA0101 interacts with BRCA1 and regulates centrosome number |
| GO:0005515 protein binding | IPI PMID:11751867 The LIM domain protein LMO4 interacts with the cofactor CtIP... | REMOVE | Summary: Generic protein binding from LMO4-CtIP-BRCA1 interaction study. Reason: Generic annotation. LMO4 acts as a negative regulator of BRCA1 activity but generic binding is uninformative. Supporting Evidence: PMID:11751867 The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:20820192 BRCA1 affects global DNA methylation through regulation of D... | KEEP AS NON CORE | Summary: Direct evidence for BRCA1 binding to transcriptional regulatory regions in context of DNMT1 regulation. Reason: This IDA annotation demonstrates BRCA1 binding to cis-regulatory regions, but this transcriptional function is peripheral to its core DNA repair role. While BRCA1 does regulate transcription and epigenetic modifications, these activities are not the primary mechanism of tumor suppression. Supporting Evidence: PMID:20820192 BRCA1 affects global DNA methylation through regulation of DNMT1 |
| GO:0005515 protein binding | IPI PMID:18716619 CDK targets Sae2 to control DNA-end resection and homologous... | REMOVE | Summary: Generic protein binding from CDK-Sae2 study on DNA end resection control. Reason: Generic annotation. Study relates to DNA end resection regulation, captured by DNA repair annotations. Supporting Evidence: PMID:18716619 CDK targets Sae2 to control DNA-end resection and homologous recombination |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:20351172 The UBXN1 protein associates with autoubiquitinated forms of... | ACCEPT | Summary: Study showing UBXN1 associates with autoubiquitinated BRCA1 and inhibits its enzymatic function, confirming E3 ligase activity. Reason: This IDA annotation provides additional evidence for BRCA1s E3 ubiquitin ligase activity, specifically showing autoubiquitination. The study demonstrates negative regulation by UBXN1, further validating the functional importance of BRCA1s enzymatic activity. This is a core molecular function. Supporting Evidence: PMID:20351172 The UBXN1 protein associates with autoubiquitinated forms of the BRCA1 tumor suppressor and inhibits its enzymatic function |
| GO:0005515 protein binding | IPI PMID:20351172 The UBXN1 protein associates with autoubiquitinated forms of... | REMOVE | Summary: Generic protein binding from UBXN1 interaction study. Reason: Generic annotation. UBXN1 regulates BRCA1 E3 ligase activity, captured by ubiquitin ligase annotations. Supporting Evidence: PMID:20351172 The UBXN1 protein associates with autoubiquitinated forms of the BRCA1 tumor suppressor |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:19117993 BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING ... | ACCEPT | Summary: Study showing BAP1 interferes with BRCA1-BARD1 RING heterodimer E3 ligase activity, providing evidence through negative regulation. Reason: This IDA annotation confirms BRCA1s E3 ligase activity by demonstrating that BAP1 (BRCA1-associated protein 1) can interfere with the BRCA1-BARD1 heterodimer ubiquitin ligase function. This regulatory interaction validates the importance of BRCA1s enzymatic activity. Supporting Evidence: PMID:19117993 BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity |
| GO:0005515 protein binding | IPI PMID:19117993 BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING ... | REMOVE | Summary: Generic protein binding from BAP1 interference with BRCA1-BARD1 activity. Reason: Generic annotation. BAP1 interaction regulates E3 ligase activity, captured by ubiquitin ligase annotations. Supporting Evidence: PMID:19117993 BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity |
| GO:0003723 RNA binding | IDA PMID:12419249 BRCA1 supports XIST RNA concentration on the inactive X chro... | KEEP AS NON CORE | Summary: BRCA1 binds to XIST RNA and supports its concentration on the inactive X chromosome. Reason: While BRCA1 does bind RNA, specifically XIST RNA for X-inactivation, this is a specialized peripheral function. RNA binding is not central to BRCA1s tumor suppressor role. The X-inactivation function is context-specific and not required for DNA repair or genomic stability maintenance. Supporting Evidence: PMID:12419249 BRCA1 supports XIST RNA concentration on the inactive X chromosome |
| GO:0005515 protein binding | IPI PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | REMOVE | Summary: Generic protein binding from MERIT40 study facilitating BRCA1 localization. Reason: Generic annotation. MERIT40 is part of BRCA1-A complex for DNA damage repair, captured by repair annotations. Supporting Evidence: PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair |
| GO:0005515 protein binding | IPI PMID:12242698 Highlight: BRCA1 and BRCA2 proteins in breast cancer. | REMOVE | Summary: Generic protein binding from general BRCA1/BRCA2 protein review. Reason: Generic annotation from review article provides no specific functional information. Supporting Evidence: PMID:12242698 Highlight: BRCA1 and BRCA2 proteins in breast cancer |
| GO:0005515 protein binding | IPI PMID:15107825 BRCA1 cooperates with NUFIP and P-TEFb to activate transcrip... | REMOVE | Summary: Generic protein binding from NUFIP and P-TEFb interaction for transcription activation. Reason: Generic annotation. Relates to transcriptional function with RNA pol II, a peripheral activity. Supporting Evidence: PMID:15107825 BRCA1 cooperates with NUFIP and P-TEFb to activate transcription by RNA polymerase II |
| GO:0005515 protein binding | IPI PMID:10855792 VCP, a weak ATPase involved in multiple cellular events, int... | REMOVE | Summary: Generic protein binding from VCP ATPase interaction in nucleus. Reason: Generic annotation. VCP interaction function unclear, not core to BRCA1 tumor suppressor role. Supporting Evidence: PMID:10855792 VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells |
| GO:0005515 protein binding | IPI PMID:11301010 BACH1, a novel helicase-like protein, interacts directly wit... | REMOVE | Summary: Generic protein binding from BACH1/BRIP1 helicase interaction critical for DNA repair. Reason: While BACH1/BRIP1 interaction is crucial for DNA repair and forms BRCA1-B complex, generic protein binding is uninformative. Function captured by DNA repair annotations. Supporting Evidence: PMID:11301010 BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function |
| GO:0005515 protein binding | IPI PMID:14576433 The BRCT domain is a phospho-protein binding domain. | REMOVE | Summary: Generic protein binding from BRCT domain phospho-protein binding study. Reason: Generic annotation. BRCT domains bind phospho-proteins for DNA damage signaling, better captured by specific functional annotations. Supporting Evidence: PMID:14576433 The BRCT domain is a phospho-protein binding domain |
| GO:0005515 protein binding | IPI PMID:11877377 SMC1 is a downstream effector in the ATM/NBS1 branch of the ... | REMOVE | Summary: Generic protein binding from SMC1 S-phase checkpoint study. Reason: Generic annotation. SMC1 interaction relates to S-phase checkpoint, captured by cell cycle annotations. Supporting Evidence: PMID:11877377 SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpoint |
| GO:0005515 protein binding | IPI PMID:15265711 BARD1 regulates BRCA1 apoptotic function by a mechanism invo... | REMOVE | Summary: Generic protein binding from BARD1 nuclear retention study on apoptotic function. Reason: Generic annotation. BARD1 interaction is essential for E3 ligase activity, captured by ubiquitin ligase annotations. Supporting Evidence: PMID:15265711 BARD1 regulates BRCA1 apoptotic function by a mechanism involving nuclear retention |
| 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... | ACCEPT | Summary: BRCA1 participates in p53-mediated apoptosis through interaction with IFI16, contributing to DNA damage-induced cell death. Reason: This annotation correctly identifies BRCA1s role in DNA damage-induced apoptosis. BRCA1 interacts with IFI16 (a Pyrin family member) to promote p53-mediated apoptotic response to DNA damage. This apoptotic function complements BRCA1s DNA repair role by eliminating cells with irreparable damage, contributing to tumor suppression. Supporting Evidence: PMID:14654789 A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway |
| GO:0003677 DNA binding | TAS PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme ... | MODIFY | Summary: BRCA1 has DNA binding activity confirmed by author statement, though more specific terms would be preferable. Reason: While BRCA1 does bind DNA, this generic term is uninformative. BRCA1 specifically binds to damaged DNA at double-strand breaks and DNA structures during repair. The annotation should use more specific terms like "damaged DNA binding" (GO:0003684) to better represent its function. Proposed replacements: damaged DNA binding Supporting Evidence: PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A. |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA1 is a critical component of G2 DNA damage checkpoint signaling. It activates CHEK1 kinase upon DNA damage to prevent premature entry into mitosis. This IBA annotation reflects conserved checkpoint function across species. Reason: This annotation correctly identifies BRCA1s essential role in G2 checkpoint signaling, which is a core function of the protein. BRCA1 is required for CHEK1 activation and prevention of mitotic entry when DNA damage is present. Loss of this function leads to genomic instability. The IBA annotation captures this conserved function well. Supporting Evidence: PMID:11836499 BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage |
| 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. Supporting Evidence: PMID:10549283 We report here that Brca1-deficient mouse embryonic stem cells have impaired repair of chromosomal DSBs by homologous recombination PMID:32359443 BRCA1 counteracts 53BP1-RIF1-Shieldin activity, thereby activating DNA end resection. |
| GO:0043009 chordate embryonic development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: BRCA1 knockout mice exhibit early embryonic lethality around E7.5-8.5. However, this developmental requirement is likely secondary to genomic instability from loss of DNA repair function rather than a direct developmental role. Reason: While BRCA1 is indeed required for embryonic development (knockouts are lethal), this is most likely a consequence of genomic instability rather than a specific developmental function. The embryonic lethality results from accumulated DNA damage and chromosomal abnormalities. The annotation is technically correct but represents a secondary effect of BRCA1s core DNA repair function. Supporting Evidence: PMID:10549283 Brca1-deficient mouse embryonic stem cells have impaired repair of chromosomal DSBs by homologous recombination |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000003 | ACCEPT | Summary: BRCA1 forms a RING-type E3 ubiquitin ligase complex with BARD1. This enzymatic activity catalyzes K6-linked polyubiquitin chain formation and is essential for multiple stages of homologous recombination repair. Reason: This IEA annotation correctly identifies BRCA1s E3 ubiquitin ligase activity. The BRCA1-BARD1 heterodimer is a well-characterized RING-type E3 ligase that produces unconventional K6-linked polyubiquitin chains. This is the only known enzymatic activity of BRCA1 and is essential for its tumor suppressor function. While redundant with more specific annotations, it provides complementary evidence. Supporting Evidence: PMID:12890688 The BRCA1/BARD1 heterodimer directs polymerization of ubiquitin primarily through an unconventional linkage involving lysine residue K6 |
| GO:0006281 DNA repair | IEA GO_REF:0000120 | MODIFY | Summary: BRCA1 is a key DNA repair protein, particularly in homologous recombination. This general DNA repair annotation is correct but could be more specific. Reason: While BRCA1 does function in DNA repair, this general term is less informative than the more specific "double-strand break repair via homologous recombination" (GO:0000724) which better captures BRCA1s actual repair function. The generic DNA repair term obscures the specific mechanism. Should use the more specific HR term. Proposed replacements: double-strand break repair via homologous recombination |
| 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: PMID:10549283 Brca1-deficient mouse embryonic stem cells have impaired repair of chromosomal DSBs by homologous recombination |
| GO:0006629 lipid metabolic process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: BRCA1 interacts with acetyl-CoA carboxylase and affects lipid synthesis. However, this is a peripheral function not related to tumor suppression. Reason: While BRCA1 does interact with ACACA (acetyl-CoA carboxylase) and can affect lipid metabolism, this is not a core function of the protein. The lipid metabolic role is tangential to BRCA1s primary tumor suppressor function in DNA repair. This annotation likely represents an over-annotation based on protein interaction data. Supporting Evidence: PMID:16326698 BRCA1 affects lipid synthesis through its interaction with acetyl-CoA carboxylase |
| GO:0006631 fatty acid metabolic process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: BRCA1 has been linked to fatty acid metabolism through interaction with acetyl-CoA carboxylase, but this is not a core function. Reason: Similar to lipid metabolic process, this annotation reflects a peripheral function. BRCA1s interaction with acetyl-CoA carboxylase may affect fatty acid metabolism, but this is not related to its primary tumor suppressor function. This represents over-annotation based on interaction data rather than core biology. Supporting Evidence: PMID:16326698 BRCA1 affects lipid synthesis through its interaction with acetyl-CoA carboxylase |
| GO:0006633 fatty acid biosynthetic process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: BRCA1 negatively regulates fatty acid biosynthesis through interaction with acetyl-CoA carboxylase. This is a peripheral function. Reason: This is another metabolic annotation based on BRCA1-ACACA interaction. While BRCA1 may negatively regulate fatty acid biosynthesis, this is not a core tumor suppressor function. The annotation represents over-attribution based on protein interaction studies rather than central BRCA1 biology. Supporting Evidence: PMID:16326698 BRCA1 affects lipid synthesis through its interaction with acetyl-CoA carboxylase |
| 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: PMID:10724175 hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response |
| GO:0008270 zinc ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: BRCA1 contains a RING domain that coordinates zinc ions. This is structurally required for the domain fold and E3 ligase activity. Reason: BRCA1 contains an N-terminal RING finger domain that coordinates two zinc ions. This zinc binding is essential for maintaining the structural integrity of the RING domain, which mediates E3 ubiquitin ligase activity and BARD1 interaction. While a structural annotation, it correctly describes BRCA1 biochemistry. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 forms a heterodimeric RING-type E3 ubiquitin ligase complex with BARD1 through their N-terminal RING domains |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | ACCEPT | Summary: BRCA1 has E3 ubiquitin ligase (transferase) activity. This general term is correct but less specific than the ubiquitin ligase annotation. Reason: BRCA1 does have transferase activity specifically as an E3 ubiquitin ligase. While this parent term is less informative than the more specific ubiquitin ligase annotation, it is not incorrect and provides a valid higher-level classification of BRCA1 enzymatic function. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 forms a heterodimeric RING-type E3 ubiquitin ligase complex with BARD1 through their N-terminal RING domains |
| GO:0046872 metal ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: BRCA1 binds zinc ions through its RING finger domain. This is a parent term of zinc ion binding. Reason: BRCA1 binds metal ions (specifically zinc) through its RING finger domain. This general term is correct but less specific than the zinc ion binding annotation. It provides valid higher-level classification. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 forms a heterodimeric RING-type E3 ubiquitin ligase complex with BARD1 through their N-terminal RING domains |
| GO:0005515 protein binding | IPI PMID:22792074 FANCJ/BACH1 acetylation at lysine 1249 regulates the DNA dam... | REMOVE | Summary: Generic protein binding annotation from proteomics study. Reason: Generic protein binding term provides no functional information about BRCA1. Specific molecular interactions are better captured through more informative functional annotations. Supporting Evidence: PMID:22792074 2012 Jul 5. FANCJ/BACH1 acetylation at lysine 1249 regulates the DNA damage response. |
| GO:0005515 protein binding | IPI PMID:22884692 TRIP12 and UBR5 suppress spreading of chromatin ubiquitylati... | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Function should be captured by more specific molecular function or process annotations. Supporting Evidence: PMID:22884692 Aug 9. TRIP12 and UBR5 suppress spreading of chromatin ubiquitylation at damaged chromosomes. |
| GO:0005515 protein binding | IPI PMID:23624935 BRCA1 is a negative modulator of the PRC2 complex. | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative and should be replaced with more specific functional annotations. Supporting Evidence: PMID:23624935 BRCA1 is a negative modulator of the PRC2 complex. |
| GO:0005515 protein binding | IPI PMID:23680151 Function of BRCA1 in the DNA damage response is mediated by ... | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Supporting Evidence: PMID:23680151 Function of BRCA1 in the DNA damage response is mediated by ADP-ribosylation. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Supporting Evidence: PMID:24981860 2014 Jun 26. Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation. |
| GO:0005515 protein binding | IPI PMID:28319063 Compromised BRCA1-PALB2 interaction is associated with breas... | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Supporting Evidence: PMID:28319063 Mar 20. Compromised BRCA1-PALB2 interaction is associated with breast cancer risk. |
| GO:0005515 protein binding | IPI PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Supporting Evidence: PMID:29656893 2018 Apr 12. DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. |
| GO:0005515 protein binding | IPI PMID:31527615 The RNA-mediated estrogen receptor Ξ± interactome of hormone-... | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Supporting Evidence: PMID:31527615 The RNA-mediated estrogen receptor Ξ± interactome of hormone-dependent human breast cancer cell nuclei. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:34552057 ZGRF1 promotes end resection of DNA homologous recombination... | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Supporting Evidence: PMID:34552057 ZGRF1 promotes end resection of DNA homologous recombination via forming complex with BRCA1/EXO1. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Supporting Evidence: PMID:34591612 Oct 1. A protein interaction landscape of breast cancer. |
| GO:0005515 protein binding | IPI PMID:8944023 Identification of a RING protein that can interact in vivo w... | REMOVE | Summary: Generic protein binding from BAP1 interaction study. Reason: Generic protein binding term is uninformative. BAP1 interaction regulates E3 ligase activity, which is captured by ubiquitin ligase annotations. Supporting Evidence: PMID:8944023 Identification of a RING protein that can interact in vivo with the BRCA1 gene product. |
| GO:0005515 protein binding | IPI PMID:9497340 Identification of a novel cytoplasmic protein that specifica... | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Supporting Evidence: PMID:9497340 Identification of a novel cytoplasmic protein that specifically binds to nuclear localization signal motifs. |
| GO:0005515 protein binding | IPI PMID:9528852 BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 R... | REMOVE | Summary: Generic protein binding from BAP1 interaction study. Reason: Generic protein binding term is uninformative. BAP1 interaction is captured by E3 ligase annotations. Supporting Evidence: PMID:9528852 BAP1: a novel ubiquitin hydrolase which binds to the BRCA1 RING finger and enhances BRCA1-mediated cell growth suppression. |
| GO:0005515 protein binding | IPI PMID:9811458 Characterization of a carboxy-terminal BRCA1 interacting pro... | REMOVE | Summary: Generic protein binding from CtIP (RBBP8) interaction study. Reason: Generic protein binding term is uninformative. CtIP interaction is important for DNA end resection and is captured by DNA repair annotations. Supporting Evidence: PMID:9811458 Characterization of a carboxy-terminal BRCA1 interacting protein. |
| GO:0042802 identical protein binding | IPI PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | REMOVE | Summary: BRCA1 self-association or homodimerization annotation. Reason: This is a variant of protein binding that is not well-supported as a functional annotation for BRCA1. The primary BRCA1 interaction is heterodimerization with BARD1, not homodimerization. Supporting Evidence: PMID:29656893 2018 Apr 12. DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. |
| GO:0042802 identical protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | REMOVE | Summary: BRCA1 self-association annotation. Reason: Not a well-established functional annotation. BRCA1 primarily functions as a heterodimer with BARD1. Supporting Evidence: PMID:34591612 Oct 1. A protein interaction landscape of breast cancer. |
| GO:0042802 identical protein binding | IPI PMID:8944023 Identification of a RING protein that can interact in vivo w... | REMOVE | Summary: BRCA1 self-association annotation from BAP1 study. Reason: Not a core functional annotation. BRCA1 primarily forms heterodimers with BARD1 rather than homodimers. Supporting Evidence: PMID:8944023 Identification of a RING protein that can interact in vivo with the BRCA1 gene product. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response, homologous recombination repair, and cell cycle checkpoint control PMID:10910365 Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. |
| GO:0006281 DNA repair | NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. | MODIFY | Summary: BRCA1 is a key DNA repair protein. This general term is correct but less specific than the HR-specific annotation. Reason: While BRCA1 is a DNA repair protein, the more specific term "double-strand break repair via homologous recombination" (GO:0000724) is preferred as it captures BRCA1s actual repair mechanism. Proposed replacements: double-strand break repair via homologous recombination Supporting Evidence: PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. |
| 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. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 competes with the antagonistic protein 53BP1 to determine whether end resection occurs PMID:30704900 the RNF168-mediated chromatin ubiquitylation pathway acts redundantly with BRCA1 to promote PALB2- and RAD51-dependent HR PMID:20656689 2010 Jul 22. Differential regulation of JAMM domain deubiquitinating enzyme activity within the RAP80 complex. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 functions as a master regulator of homologous recombination (HR) through multiple mechanisms PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. |
| GO:0035825 homologous recombination | NAS PMID:30657944 CtIP-BRCA1 complex and MRE11 maintain replication forks in t... | ACCEPT | Summary: BRCA1 is essential for homologous recombination. Duplicate annotation from different source. Reason: Correct annotation for a core BRCA1 function. Homologous recombination is the primary mechanism of BRCA1 tumor suppression. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 functions as a master regulator of homologous recombination (HR) through multiple mechanisms PMID:30657944 CtIP-BRCA1 complex and MRE11 maintain replication forks in the presence of chain terminating nucleoside analogs. |
| GO:0044818 mitotic G2/M transition checkpoint | NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. | ACCEPT | Summary: BRCA1 is essential for G2/M checkpoint control, activating CHEK1 upon DNA damage. Reason: This annotation correctly identifies BRCA1s critical role in G2/M checkpoint control. BRCA1 activates CHEK1 to prevent premature mitotic entry when DNA damage is present. This is a core function. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 is involved in all phases of the cell cycle and regulates orderly progression PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. |
| 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. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response, homologous recombination repair |
| 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. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response, homologous recombination repair |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 functions as a master regulator of homologous recombination (HR) through multiple mechanisms PMID:28398198 Functional and mutational landscapes of BRCA1 for homology-directed repair and therapy resistance. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response PMID:16651405 DNA damage-induced BARD1 phosphorylation is critical for the inhibition of messenger RNA processing by BRCA1/BARD1 complex. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 is involved in all phases of the cell cycle and regulates orderly progression PMID:15159397 2004 May 24. BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage. |
| GO:0006338 chromatin remodeling | TAS PMID:35351360 BRCA1/BARD1 is a nucleosome reader and writer. | ACCEPT | Summary: BRCA1 promotes chromatin remodeling at DNA damage sites through its E3 ligase activity and interaction with remodeling complexes. Reason: BRCA1 plays an important role in chromatin remodeling at DNA damage sites. Its E3 ligase activity promotes chromatin remodeling through SMARCAD1 and other factors. This is part of the DNA damage response pathway. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md E3 ligase activity promotes chromatin remodeling and 53BP1 positioning through the remodeler SMARCAD1 PMID:35351360 Epub 2022 Mar 26. BRCA1/BARD1 is a nucleosome reader and writer. |
| GO:0061649 ubiquitin-modified histone reader activity | TAS PMID:35351360 BRCA1/BARD1 is a nucleosome reader and writer. | ACCEPT | Summary: BRCA1 recognizes ubiquitinated histones at DNA damage sites as part of its recruitment mechanism. Reason: BRCA1-BARD1 complex recognizes ubiquitinated histones, which is important for its recruitment to DNA damage sites and subsequent DNA repair. This activity links its E3 ligase function to chromatin recognition. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md Required for maintaining gene silencing in constitutive heterochromatin via histone H2A ubiquitination PMID:35351360 Epub 2022 Mar 26. BRCA1/BARD1 is a nucleosome reader and writer. |
| GO:0140863 histone H2AK127 ubiquitin ligase activity | TAS PMID:35351360 BRCA1/BARD1 is a nucleosome reader and writer. | ACCEPT | Summary: BRCA1-BARD1 complex ubiquitinates histone H2A at K127, a specific substrate of its E3 ligase activity. Reason: This specific annotation captures a defined substrate of BRCA1-BARD1 E3 ligase activity. H2A ubiquitination is important for DNA repair and chromatin dynamics at damage sites. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md Involved in histone modifications through ubiquitination PMID:35351360 Epub 2022 Mar 26. BRCA1/BARD1 is a nucleosome reader and writer. PMID:34321665 catalyse ubiquitin conjugation to H2AX at one site (K127) coincidental in H2A |
| GO:0140864 histone H2AK129 ubiquitin ligase activity | TAS PMID:35351360 BRCA1/BARD1 is a nucleosome reader and writer. | ACCEPT | Summary: BRCA1-BARD1 complex ubiquitinates histone H2A at K129, a specific substrate of its E3 ligase activity. Reason: This specific annotation captures a defined substrate of BRCA1-BARD1 E3 ligase activity. H2A ubiquitination at K129 is another site targeted by the BRCA1-BARD1 complex. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md Involved in histone modifications through ubiquitination PMID:35351360 Epub 2022 Mar 26. BRCA1/BARD1 is a nucleosome reader and writer. |
| 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. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 forms a heterodimeric RING-type E3 ubiquitin ligase complex with BARD1 |
| GO:0030308 negative regulation of cell growth | IMP PMID:10518542 BRCA1-associated growth arrest is RB-dependent. | KEEP AS NON CORE | Summary: BRCA1 negatively regulates cell growth through RB-dependent mechanisms. Reason: While BRCA1 does contribute to negative regulation of cell growth, this is likely a secondary effect of its checkpoint and DNA repair functions rather than a primary function. The growth suppression is RB-dependent and relates to cell cycle control. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 is involved in all phases of the cell cycle and regulates orderly progression PMID:10518542 BRCA1-associated growth arrest is RB-dependent. |
| 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 has transcriptional coactivator function through its C-terminal transactivation domain. Reason: BRCA1 does function as a transcriptional coactivator through interaction with RNA pol II and its C-terminal domain. However, this transcriptional function is peripheral to its core tumor suppressor role in DNA repair. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md The C-terminal region can transactivate heterologous promoters PMID:12080089 JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction. |
| GO:0005515 protein binding | IPI PMID:26833090 Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologo... | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Supporting Evidence: PMID:26833090 2016 Jan 28. Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous Recombination and Genome Stability. |
| GO:0005515 protein binding | IPI PMID:29899443 Structural basis for regulation of human acetyl-CoA carboxyl... | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Supporting Evidence: PMID:29899443 Jun 13. Structural basis for regulation of human acetyl-CoA carboxylase. |
| 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: file:human/BRCA1/BRCA1-deep-research.md Essential for G2/M checkpoint control; deficiency leads to premature mitotic entry despite DNA damage PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. |
| 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: file:human/BRCA1/BRCA1-deep-research.md Essential for G2/M checkpoint control; deficiency leads to premature mitotic entry despite DNA damage PMID:17643121 Jul 22. CCDC98 targets BRCA1 to DNA damage sites. |
| 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: file:human/BRCA1/BRCA1-deep-research.md Essential for G2/M checkpoint control; deficiency leads to premature mitotic entry despite DNA damage PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair. |
| GO:0005515 protein binding | IPI PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme ... | REMOVE | Summary: Generic protein binding from RNA helicase A (DHX9) interaction study. Reason: Generic protein binding term is uninformative. RNA pol II interaction is captured by transcription annotations. Supporting Evidence: PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A. |
| 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 regulates RNA pol II transcription through interaction with the holoenzyme complex via RNA helicase A. Reason: While BRCA1 does regulate transcription through RNA pol II interaction, this is a peripheral function. Transcriptional regulation is secondary to BRCA1s primary tumor suppressor role in DNA repair. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md The C-terminal region can transactivate heterologous promoters PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A. |
| GO:0070063 RNA polymerase binding | IDA PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme ... | KEEP AS NON CORE | Summary: BRCA1 binds RNA polymerase II holoenzyme through RNA helicase A. Reason: This is a more specific annotation than generic protein binding, correctly identifying BRCA1s interaction with RNA pol II. However, this transcriptional function is peripheral to its core DNA repair role. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md The C-terminal region can transactivate heterologous promoters PMID:9662397 BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A. |
| GO:0005515 protein binding | IPI PMID:26807646 EXD2 promotes homologous recombination by facilitating DNA e... | REMOVE | Summary: Generic protein binding annotation. Reason: Generic protein binding term is uninformative. Supporting Evidence: PMID:26807646 EXD2 promotes homologous recombination by facilitating DNA end resection. |
| 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: BRCA1 positively regulates transcription, identified through DBC1 transcriptional repressor study. Reason: BRCA1 does function as a transcriptional activator. However, transcriptional regulation is peripheral to its core tumor suppressor role in DNA repair. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md The C-terminal region can transactivate heterologous promoters PMID:20160719 Feb 16. Identification of DBC1 as a transcriptional repressor for BRCA1. |
| GO:0010575 positive regulation of vascular endothelial growth factor production | IMP PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction a... | MARK AS OVER ANNOTATED | Summary: BRCA1 positively regulates VEGF production. Reason: VEGF regulation is not a core function of BRCA1. This annotation likely reflects a downstream or indirect effect of BRCA1 activity rather than a primary function. The connection to angiogenesis is tangential to BRCA1s tumor suppressor role in DNA repair. Supporting Evidence: PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction and retard atherosclerosis. |
| 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 positively regulates gene expression. Reason: BRCA1 does have transcriptional coactivator function and can positively regulate gene expression. However, this general transcriptional function is peripheral to its core DNA repair role. Supporting Evidence: PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction and retard atherosclerosis. |
| GO:0045766 positive regulation of angiogenesis | IMP PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction a... | MARK AS OVER ANNOTATED | Summary: BRCA1 positively regulates angiogenesis. Reason: Angiogenesis regulation is not a core function of BRCA1. This annotation likely reflects an indirect or context-specific effect. The primary function of BRCA1 is DNA repair, not vascular biology. Supporting Evidence: PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction and retard atherosclerosis. |
| 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 negatively regulates estrogen receptor signaling. Reason: While BRCA1 does interact with estrogen receptor and may modulate its signaling, this is a tissue-specific peripheral function. It may contribute to breast cancer biology but is not the primary tumor suppressor mechanism. Supporting Evidence: PMID:17505062 May 15. Growth factor signaling pathways modulate BRCA1 repression of estrogen receptor-alpha activity. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response, homologous recombination repair PMID:22186889 BRCA1 is an essential regulator of heart function and survival following myocardial infarction. |
| GO:0031625 ubiquitin protein ligase binding | IPI PMID:17873885 E2-BRCA1 RING interactions dictate synthesis of mono- or spe... | ACCEPT | Summary: BRCA1 binds E2 ubiquitin-conjugating enzymes for its E3 ligase activity. Reason: BRCA1 interacts with E2 enzymes to catalyze ubiquitination. This annotation correctly captures the E2-E3 interaction essential for BRCA1 ubiquitin ligase function. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 forms a heterodimeric RING-type E3 ubiquitin ligase complex with BARD1 PMID:17873885 Sep 16. E2-BRCA1 RING interactions dictate synthesis of mono- or specific polyubiquitin chain linkages. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response, homologous recombination repair PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response, homologous recombination repair PMID:17643121 Jul 22. CCDC98 targets BRCA1 to DNA damage sites. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response, homologous recombination repair PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response PMID:17643121 Jul 22. CCDC98 targets BRCA1 to DNA damage sites. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 functions as a master regulator of homologous recombination (HR) through multiple mechanisms PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 functions as a master regulator of homologous recombination (HR) through multiple mechanisms PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair. |
| GO:0005515 protein binding | IPI PMID:9774970 Stable interaction between the products of the BRCA1 and BRC... | REMOVE | Summary: Generic protein binding annotation from meiotic chromosome study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:9774970 Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 functions as a master regulator of homologous recombination (HR) through multiple mechanisms PMID:17349954 A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination. |
| GO:0006301 DNA damage tolerance | IDA PMID:17349954 A critical role for the ubiquitin-conjugating enzyme Ubc13 i... | ACCEPT | Summary: BRCA1 involved in DNA damage tolerance through Ubc13-dependent ubiquitination. Reason: BRCA1 contributes to DNA damage tolerance through its ubiquitin ligase activity and role in promoting DNA repair. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response PMID:17349954 A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination. |
| 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: file:human/BRCA1/BRCA1-deep-research.md BRCA1 forms a heterodimeric RING-type E3 ubiquitin ligase complex with BARD1 PMID:17349954 A critical role for the ubiquitin-conjugating enzyme Ubc13 in initiating homologous recombination. |
| GO:0045717 negative regulation of fatty acid biosynthetic process | IMP PMID:16326698 BRCA1 affects lipid synthesis through its interaction with a... | MARK AS OVER ANNOTATED | Summary: BRCA1 negatively regulates fatty acid biosynthesis through ACACA interaction. Reason: This metabolic function is peripheral to BRCA1s core DNA repair role. Not a primary tumor suppressor function. Supporting Evidence: PMID:16326698 2005 Dec 2. BRCA1 affects lipid synthesis through its interaction with acetyl-CoA carboxylase. |
| GO:0007059 chromosome segregation | IMP PMID:15965487 BRCA1 participates in DNA decatenation. | KEEP AS NON CORE | Summary: BRCA1 participates in chromosome segregation through DNA decatenation function. Reason: BRCA1 participates in DNA decatenation which affects chromosome segregation. This is a secondary function related to genomic stability but not the primary tumor suppressor mechanism. Supporting Evidence: PMID:15965487 Jun 19. BRCA1 participates in DNA decatenation. |
| GO:0019899 enzyme binding | IPI PMID:15965487 BRCA1 participates in DNA decatenation. | KEEP AS NON CORE | Summary: BRCA1 binds topoisomerase II for DNA decatenation. Reason: More informative than generic protein binding. Topoisomerase II interaction contributes to decatenation function. Supporting Evidence: PMID:15965487 Jun 19. BRCA1 participates in DNA decatenation. |
| 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 negatively regulates transcription through ZBRK1 interaction. Reason: BRCA1 does have transcriptional repressor function, but this is peripheral to its core DNA repair role. Supporting Evidence: PMID:16288014 BRCA1 and c-Myc associate to transcriptionally repress psoriasin, a DNA damage-inducible gene. |
| 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 regulates RNA pol II transcription. Reason: BRCA1 does regulate transcription through interaction with RNA pol II. Peripheral function. Supporting Evidence: PMID:10910365 Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. |
| GO:0008270 zinc ion binding | TAS PMID:8944023 Identification of a RING protein that can interact in vivo w... | ACCEPT | Summary: BRCA1 RING domain binds zinc ions. Duplicate annotation. Reason: RING domain zinc binding is essential for E3 ligase function. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 forms a heterodimeric RING-type E3 ubiquitin ligase complex with BARD1 through their N-terminal RING domains PMID:8944023 Identification of a RING protein that can interact in vivo with the BRCA1 gene product. |
| GO:0015631 tubulin binding | NAS PMID:12214252 Roles of BRCA1 in centrosome duplication. | KEEP AS NON CORE | Summary: BRCA1 binds tubulin/gamma-TuRC for centrosome regulation. Reason: BRCA1 does interact with centrosomal components including gamma-tubulin ring complex. This may relate to centrosome duplication control but is peripheral to core DNA repair function. Supporting Evidence: PMID:12214252 Roles of BRCA1 in centrosome duplication. |
| GO:0031436 BRCA1-BARD1 complex | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA1 forms heterodimer with BARD1, the core E3 ligase complex. Essential annotation. Reason: The BRCA1-BARD1 complex is the functional E3 ubiquitin ligase. BRCA1 does not function independently; BARD1 is required for stability and activity. Core annotation. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 forms a heterodimeric RING-type E3 ubiquitin ligase complex with BARD1 through their N-terminal RING domains |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: BRCA1 positively regulates transcription. Conserved function from IBA. Reason: BRCA1 does have transcriptional coactivator function, but this is peripheral to its core DNA repair role. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md The C-terminal region can transactivate heterologous promoters |
| GO:0070531 BRCA1-A complex | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA1 forms BRCA1-A complex with Abraxas and RAP80 for DNA damage recognition. Reason: The BRCA1-A complex (containing Abraxas, RAP80, MERIT40, BRCC45, BRCC36) is essential for BRCA1 recruitment to DNA damage sites through ubiquitin recognition. Core annotation. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 functions in multiple distinct complexes, including BRCA1-A (Abraxas-RAP80) |
| 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: PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. |
| 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: PMID:18171670 2008 Jan 2. Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA double-strand break repair. |
| 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: PMID:20656689 2010 Jul 22. Differential regulation of JAMM domain deubiquitinating enzyme activity within the RAP80 complex. |
| 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: PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. |
| GO:0070531 BRCA1-A complex | NAS PMID:20656689 Differential regulation of JAMM domain deubiquitinating enzy... | ACCEPT | Summary: BRCA1-A complex annotation. Reason: Duplicate annotation. BRCA1-A complex is essential for DNA damage response. Supporting Evidence: PMID:20656689 2010 Jul 22. Differential regulation of JAMM domain deubiquitinating enzyme activity within the RAP80 complex. |
| GO:0070532 BRCA1-B complex | IPI PMID:16391231 Multifactorial contributions to an acute DNA damage response... | ACCEPT | Summary: BRCA1-B complex contains BRCA1 and BRIP1/FANCJ for replication fork protection. Reason: The BRCA1-B complex is important for S-phase checkpoint and replication-coupled DNA repair. Core annotation. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 functions in multiple distinct complexes, including BRCA1-B PMID:16391231 Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes. |
| GO:0070533 BRCA1-C complex | IPI PMID:16391231 Multifactorial contributions to an acute DNA damage response... | ACCEPT | Summary: BRCA1-C complex contains BRCA1 and CtIP for DNA end resection. Reason: The BRCA1-C complex is essential for DNA end resection, a critical step in homologous recombination. Core annotation. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 functions in multiple distinct complexes, including BRCA1-C PMID:16391231 Multifactorial contributions to an acute DNA damage response by BRCA1/BARD1-containing complexes. |
| GO:0110025 DNA strand resection involved in replication fork processing | NAS PMID:29709199 The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of D... | ACCEPT | Summary: BRCA1 promotes DNA strand resection at stalled replication forks. Reason: BRCA1 promotes DNA end resection, which is relevant for replication fork processing. Core function related to HR. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md Promotes DNA strand resection by recruiting RBBP8/CtIP and activating it PMID:29709199 The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair. |
| GO:0000152 nuclear ubiquitin ligase complex | IDA PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 an... | ACCEPT | Summary: BRCA1 forms nuclear ubiquitin ligase complex with BARD1. Reason: Core function. BRCA1-BARD1 is a nuclear E3 ubiquitin ligase. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 forms a heterodimeric RING-type E3 ubiquitin ligase complex with BARD1 PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. |
| GO:0005634 nucleus | IDA PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 an... | ACCEPT | Summary: BRCA1 nuclear localization. Reason: Duplicate annotation. Nuclear localization is essential. Supporting Evidence: PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. |
| GO:0071479 cellular response to ionizing radiation | IMP PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 an... | ACCEPT | Summary: BRCA1 mediates cellular response to ionizing radiation. Reason: Core DDR function. BRCA1 responds to IR-induced DNA damage. Supporting Evidence: PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. |
| GO:2000001 regulation of DNA damage checkpoint | NAS PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 an... | ACCEPT | Summary: BRCA1 regulates DNA damage checkpoints. Reason: Core function. Checkpoint regulation is essential for BRCA1 tumor suppression. Supporting Evidence: PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. |
| 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 positively regulates transcription. Duplicate IEA annotation. Reason: Transcriptional coactivator function is peripheral to core DNA repair role. |
| 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: PMID:19369211 PALB2 is an integral component of the BRCA complex required for homologous recombination repair. |
| GO:1990391 DNA repair complex | IPI PMID:19369211 PALB2 is an integral component of the BRCA complex required ... | ACCEPT | Summary: BRCA1 forms DNA repair complex with PALB2. Reason: BRCA1 functions in DNA repair complexes including with PALB2 for HR. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md PALB2 is an integral component of the BRCA complex required for homologous recombination repair PMID:19369211 PALB2 is an integral component of the BRCA complex required for homologous recombination repair. |
| 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: PMID:9342365 Cell cycle-dependent colocalization of BARD1 and BRCA1 proteins in discrete nuclear domains. |
| GO:0031436 BRCA1-BARD1 complex | IPI PMID:11573085 Structure of a BRCA1-BARD1 heterodimeric RING-RING complex. | ACCEPT | Summary: BRCA1-BARD1 heterodimer formation. Reason: Core complex. BRCA1-BARD1 is the functional E3 ligase unit. Supporting Evidence: PMID:11573085 Structure of a BRCA1-BARD1 heterodimeric RING-RING complex. |
| 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 positively regulates transcription by RNA polymerase II, acting as a transcriptional coactivator, here in the context of DNMT1 regulation. Reason: BRCA1 does have documented transcriptional coactivator activity, but this is peripheral to its core roles in DNA repair and E3 ligase activity. Marked non-core for consistency with the other annotations to this term (IBA, IEA, IDA), all of which treat BRCA1 transcriptional regulation as a secondary function. Supporting Evidence: PMID:20820192 BRCA1 affects global DNA methylation through regulation of DNMT1. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683735 | ACCEPT | Summary: BRCA1 localizes to nucleoplasm where it performs its DNA repair and checkpoint functions. Reason: Nucleoplasm localization is fundamental for BRCA1 function in DNA damage response and homologous recombination repair. Reactome pathway annotation is consistent with established localization data. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 serves as a central hub for maintaining genomic stability through its essential roles in DNA damage response, homologous recombination repair, and cell cycle checkpoint control |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683801 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684052 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684071 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684108 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684875 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684882 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684887 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685011 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685156 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685341 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685838 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685985 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685994 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686410 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686440 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686469 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686483 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686642 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686657 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686685 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693539 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693542 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693551 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693561 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693564 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693580 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693584 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693589 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693593 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693608 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693620 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6799332 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69891 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704330 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704408 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709571 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709601 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9853389 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2997709 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2997616 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| 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: PMID:26833090 2016 Jan 28. Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous Recombination and Genome Stability. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9701199 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683385 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5691411 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9701000 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9707051 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9663194 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:1990904 ribonucleoprotein complex | IDA PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chape... | UNDECIDED | Summary: BRCA1 association with ribonucleoprotein complex requires validation. While BRCA1 interacts with BRIP1/BACH1 which has RNA helicase activity, the evidence for direct RNP complex localization should be evaluated. Reason: Unable to access PMID:18809582 to verify the specific context of this annotation. BRCA1 has been reported to associate with RNA-related proteins but its presence in RNP complexes is not a core function. Supporting Evidence: PMID:18809582 Sep 22. Nucleophosmin serves as a rate-limiting nuclear export chaperone for the Mammalian ribosome. |
| GO:0032991 protein-containing complex | IDA PMID:9774970 Stable interaction between the products of the BRCA1 and BRC... | MODIFY | Summary: BRCA1 localization to a protein-containing complex is too generic. BRCA1 forms specific complexes like BRCA1-BARD1, BRCA1-A, BRCA1-B, and BRCA1-C. Reason: This term is too generic - BRCA1 forms well-characterized specific protein complexes. More informative annotations for BRCA1-BARD1, BRCA1-A, BRCA1-B, and BRCA1-C complexes already exist. Proposed replacements: BRCA1-BARD1 complex Supporting Evidence: PMID:9774970 Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. |
| GO:0000800 lateral element | IDA PMID:9774970 Stable interaction between the products of the BRCA1 and BRC... | KEEP AS NON CORE | Summary: BRCA1 localization to lateral elements of the synaptonemal complex during meiosis. This is consistent with its role in recombination. Reason: Lateral element localization is specific to meiotic cells and represents a specialized localization of BRCA1 related to its recombination function. This is a valid but context-specific annotation. Supporting Evidence: PMID:9774970 Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. |
| 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: PMID:20160719 Feb 16. Identification of DBC1 as a transcriptional repressor for BRCA1. |
| GO:0005737 cytoplasm | IDA PMID:20160719 Identification of DBC1 as a transcriptional repressor for BR... | KEEP AS NON CORE | Summary: BRCA1 cytoplasmic localization detected by direct assay. While BRCA1 is predominantly nuclear, cytoplasmic localization has been observed. Reason: BRCA1 is primarily nuclear but has been detected in cytoplasm. This is not a core localization but represents a minor pool of the protein and may be related to nuclear-cytoplasmic shuttling. Supporting Evidence: PMID:20160719 Feb 16. Identification of DBC1 as a transcriptional repressor for BRCA1. |
| GO:0071356 cellular response to tumor necrosis factor | IMP PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction a... | KEEP AS NON CORE | Summary: BRCA1 involvement in cellular response to TNF. This is a downstream effect rather than a core function. Reason: While BRCA1 may influence TNF responses through its effects on NF-kB signaling and cell survival pathways, this represents a secondary consequence of its core functions rather than a direct role in TNF signaling. Supporting Evidence: PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction and retard atherosclerosis. |
| 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... | MARK AS OVER ANNOTATED | Summary: BRCA1 role in regulating death receptor-mediated apoptosis. This is a downstream effect related to its tumor suppressor function. Reason: While BRCA1 loss may affect cell survival and death receptor signaling, this is likely an indirect effect of its core functions in DNA repair and genome stability rather than a direct mechanism. This term is highly specific and may represent over-annotation. Supporting Evidence: PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction and retard atherosclerosis. |
| GO:2000378 negative regulation of reactive oxygen species metabolic process | IMP PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction a... | MARK AS OVER ANNOTATED | Summary: BRCA1 involvement in ROS regulation. BRCA1 deficiency has been linked to oxidative stress. Reason: While BRCA1 loss may lead to increased ROS as a consequence of genome instability and metabolic changes, direct regulation of ROS metabolism is not a core function of BRCA1. This is likely an indirect downstream effect. Supporting Evidence: PMID:23415688 BRCA1 is a novel target to improve endothelial dysfunction and retard atherosclerosis. |
| 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: PMID:23855721 Localization of BRCA1 protein in breast cancer tissue and cell lines with mutations. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5659781 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-6797712 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9007605 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9699163 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9700998 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9701003 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9926521 | ACCEPT | Summary: BRCA1 nucleoplasm localization from Reactome pathway annotation. Reason: Nucleoplasm localization is well-established for BRCA1 DNA repair functions. |
| 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. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 functions in chromatin structure maintenance |
| GO:0005886 plasma membrane | IDA PMID:21282464 A novel role for BRCA1 in regulating breast cancer cell spre... | UNDECIDED | Summary: BRCA1 plasma membrane localization detected by direct assay. This is unexpected as BRCA1 is primarily a nuclear protein. Reason: Unable to access PMID:21282464 to verify this annotation. Plasma membrane localization for BRCA1 is unusual and not consistent with its known nuclear functions in DNA repair. This requires validation. Supporting Evidence: PMID:21282464 Jan 31. A novel role for BRCA1 in regulating breast cancer cell spreading and motility. |
| GO:0085020 protein K6-linked ubiquitination | IDA PMID:12890688 The BRCA1/BARD1 heterodimer assembles polyubiquitin chains t... | ACCEPT | Summary: BRCA1-BARD1 E3 ligase generates K6-linked ubiquitin chains. This is a characteristic activity of the BRCA1-BARD1 complex. Reason: K6-linked ubiquitination is a well-characterized enzymatic activity of the BRCA1-BARD1 E3 ligase complex, distinguishing it from other E3 ligases that typically generate K48 or K63 linkages. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 forms a heterodimeric RING-type E3 ubiquitin ligase complex with BARD1 through their N-terminal RING domains PMID:12890688 2003 Jul 30. The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin. |
| GO:0085020 protein K6-linked ubiquitination | IDA PMID:20351172 The UBXN1 protein associates with autoubiquitinated forms of... | ACCEPT | Summary: BRCA1-BARD1 E3 ligase generates K6-linked ubiquitin chains. Additional evidence for this core enzymatic activity. Reason: K6-linked ubiquitination is a well-characterized enzymatic activity of the BRCA1-BARD1 E3 ligase complex. Supporting Evidence: PMID:20351172 Mar 29. The UBXN1 protein associates with autoubiquitinated forms of the BRCA1 tumor suppressor and inhibits its enzymatic function. |
| GO:0031436 BRCA1-BARD1 complex | IDA PMID:12890688 The BRCA1/BARD1 heterodimer assembles polyubiquitin chains t... | ACCEPT | Summary: BRCA1 is a component of the BRCA1-BARD1 heterodimeric complex that possesses E3 ubiquitin ligase activity. Reason: The BRCA1-BARD1 complex is the essential functional unit for BRCA1 E3 ligase activity. This is a core annotation. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1 forms a heterodimeric RING-type E3 ubiquitin ligase complex with BARD1 through their N-terminal RING domains PMID:12890688 2003 Jul 30. The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin. |
| GO:0031436 BRCA1-BARD1 complex | IDA PMID:20351172 The UBXN1 protein associates with autoubiquitinated forms of... | ACCEPT | Summary: BRCA1 is a component of the BRCA1-BARD1 heterodimeric complex. Additional evidence for this core complex. Reason: The BRCA1-BARD1 complex is the essential functional unit for BRCA1 E3 ligase activity. This is a core annotation. Supporting Evidence: PMID:20351172 Mar 29. The UBXN1 protein associates with autoubiquitinated forms of the BRCA1 tumor suppressor and inhibits its enzymatic function. |
| 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: PMID:12890688 2003 Jul 30. The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin. |
| GO:0051865 protein autoubiquitination | IDA PMID:20351172 The UBXN1 protein associates with autoubiquitinated forms of... | ACCEPT | Summary: BRCA1-BARD1 complex undergoes autoubiquitination. Additional evidence for this E3 ligase property. Reason: Autoubiquitination is a common feature of E3 ligases and has been demonstrated for the BRCA1-BARD1 complex. Supporting Evidence: PMID:20351172 Mar 29. The UBXN1 protein associates with autoubiquitinated forms of the BRCA1 tumor suppressor and inhibits its enzymatic function. |
| 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: file:human/BRCA1/BRCA1-deep-research.md The C-terminal region can transactivate heterologous promoters PMID:16331276 BRCA1 and FOXA1 proteins coregulate the expression of the cell cycle-dependent kinase inhibitor p27(Kip1). |
| GO:0031436 BRCA1-BARD1 complex | IDA PMID:19117993 BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING ... | ACCEPT | Summary: BRCA1 is a component of the BRCA1-BARD1 heterodimeric complex. Additional evidence for this core complex. Reason: The BRCA1-BARD1 complex is the essential functional unit for BRCA1 E3 ligase activity. This is a core annotation. Supporting Evidence: PMID:19117993 BRCA1-associated protein 1 interferes with BRCA1/BARD1 RING heterodimer activity. |
| GO:0071681 cellular response to indole-3-methanol | IDA PMID:10868478 Suppression of breast cancer invasion and migration by indol... | MARK AS OVER ANNOTATED | Summary: BRCA1 involvement in cellular response to indole-3-methanol (I3C), a dietary compound. This is a highly specific experimental context. Reason: While this may represent a valid experimental observation, cellular response to a specific dietary compound is not a core function of BRCA1. This is likely a downstream or indirect effect and represents over-annotation. Supporting Evidence: PMID:10868478 Suppression of breast cancer invasion and migration by indole-3-carbinol: associated with up-regulation of BRCA1 and E-cadherin/catenin complexes. |
| 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: PMID:17643121 Jul 22. CCDC98 targets BRCA1 to DNA damage sites. |
| GO:0070531 BRCA1-A complex | IDA PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | ACCEPT | Summary: BRCA1 is a component of the BRCA1-A complex with RAP80 and Abraxas for DNA damage recognition. Reason: The BRCA1-A complex (containing RAP80, Abraxas, BRCC36, BRCC45) is a key BRCA1-containing complex involved in DNA damage response. This is a core annotation. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md BRCA1-A Complex (RAP80/Abraxas) PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. |
| GO:0070531 BRCA1-A complex | IDA PMID:17525341 RAP80 targets BRCA1 to specific ubiquitin structures at DNA ... | ACCEPT | Summary: BRCA1 is a component of the BRCA1-A complex. Additional evidence for this core complex. Reason: The BRCA1-A complex is a key BRCA1-containing complex involved in DNA damage response. This is a core annotation. Supporting Evidence: PMID:17525341 RAP80 targets BRCA1 to specific ubiquitin structures at DNA damage sites. |
| GO:0070531 BRCA1-A complex | IDA PMID:17525342 Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA... | ACCEPT | Summary: BRCA1 is a component of the BRCA1-A complex. Additional evidence for this core complex. Reason: The BRCA1-A complex is a key BRCA1-containing complex involved in DNA damage response. This is a core annotation. Supporting Evidence: PMID:17525342 Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response. |
| GO:0070531 BRCA1-A complex | IDA PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: BRCA1 is a component of the BRCA1-A complex. Additional evidence for this core complex. Reason: The BRCA1-A complex is a key BRCA1-containing complex involved in DNA damage response. This is a core annotation. Supporting Evidence: PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair. |
| GO:0070531 BRCA1-A complex | IDA PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | ACCEPT | Summary: BRCA1 is a component of the BRCA1-A complex. Additional evidence for this core complex. Reason: The BRCA1-A complex is a key BRCA1-containing complex involved in DNA damage response. This is a core annotation. Supporting Evidence: PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control. |
| GO:0031436 BRCA1-BARD1 complex | IDA PMID:15265711 BARD1 regulates BRCA1 apoptotic function by a mechanism invo... | ACCEPT | Summary: BRCA1 is a component of the BRCA1-BARD1 heterodimeric complex. Additional evidence for this core complex. Reason: The BRCA1-BARD1 complex is the essential functional unit for BRCA1 E3 ligase activity. This is a core annotation. Supporting Evidence: PMID:15265711 BARD1 regulates BRCA1 apoptotic function by a mechanism involving nuclear retention. |
| GO:0000151 ubiquitin ligase complex | NAS PMID:14976165 BRCA1 : BARD1 induces the formation of conjugated ubiquitin ... | ACCEPT | Summary: BRCA1 as part of a ubiquitin ligase complex. The term is somewhat generic but accurate. Reason: BRCA1-BARD1 is indeed a ubiquitin ligase complex. While the more specific term BRCA1-BARD1 complex exists, this general term is not incorrect. NAS evidence is appropriate for this well-established function. Supporting Evidence: PMID:14976165 Feb 19. BRCA1 : BARD1 induces the formation of conjugated ubiquitin structures, dependent on K6 of ubiquitin, in cells during DNA replication and repair. |
| GO:0000931 gamma-tubulin ring complex | NAS PMID:12214252 Roles of BRCA1 in centrosome duplication. | ACCEPT | Summary: BRCA1 association with gamma-tubulin ring complex at centrosomes. This is consistent with its centrosomal functions. Reason: BRCA1 associates with gamma-tubulin at centrosomes and plays a role in centrosome regulation. This is a validated localization. Supporting Evidence: file:human/BRCA1/BRCA1-deep-research.md Associates with gamma-tubulin at mother centrioles in unduplicated centrosomes PMID:12214252 Roles of BRCA1 in centrosome duplication. |
| 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: file:human/BRCA1/BRCA1-deep-research.md Blocks centrosome reduplication, preventing formation of multiple functional centrosomes PMID:12214252 Roles of BRCA1 in centrosome duplication. |
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