Brca1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000724 double-strand break repair via homologous recombination	IBA GO_REF:0000033	ACCEPT	Summary: BRCA1-BARD1 channels DSB repair toward homologous recombination by promoting end resection and PALB2-BRCA2-RAD51 loading at resected breaks. Reason: Central, defining biological role of BRCA1; broadly supported (IBA/ISO and mechanistic literature). Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0007095 mitotic G2 DNA damage checkpoint signaling	IBA GO_REF:0000033	ACCEPT	Summary: BRCA1 signals the G2 DNA-damage checkpoint, with BRCA1-mediated RBBP8 ubiquitination regulating CHEK1 activation after damage. Reason: Core checkpoint role tied to BRCA1's repair function; IBA/ISO support. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0004842 ubiquitin-protein transferase activity	IBA GO_REF:0000033	ACCEPT	Summary: Core catalytic activity: BRCA1, as the BRCA1-BARD1 RING heterodimer, accelerates ubiquitin transfer from charged E2~Ub onto substrate lysines (e.g. nucleosomal H2A, CtIP, PCNA) at sites of DNA damage. Reason: Defining molecular function of BRCA1 (EC 2.3.2.27); supported across IBA/ISO/ISS and the BRCA1-BARD1 mechanistic literature. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0031436 BRCA1-BARD1 complex	IBA GO_REF:0000033	ACCEPT	Summary: Obligate RING-RING heterodimer with BARD1 that constitutes the active E3 ligase; this assembly underlies essentially all BRCA1 catalytic and DNA-repair functions. Reason: Defining functional complex of BRCA1; documented in SUBUNIT and the core mechanistic literature. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0043009 chordate embryonic development	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Brca1 is required for embryonic development, with knockouts being embryonic lethal owing to defective proliferation and genome instability. Reason: Developmental phenotype downstream of BRCA1's essential genome-maintenance role.
GO:0045944 positive regulation of transcription by RNA polymerase II	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: Acts as a transcriptional activator at specific target genes, a regulatory output separable from its repair function. Reason: Activator role pleiotropic relative to core repair function.
GO:0070531 BRCA1-A complex	IBA GO_REF:0000033	ACCEPT	Summary: Component of the BRCA1-A complex (with RAP80/UIMC1, ABRAXAS1, BRCC36, BABAM1/2) that recognizes K63-ubiquitin chains and recruits BRCA1 to DNA double-strand-break sites. Reason: Bona fide repair-targeting complex central to BRCA1 recruitment; supported by SUBUNIT and IBA/ISO. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0003677 DNA binding	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Generic DNA-binding term; BRCA1 acts on damaged chromatin via complexes rather than as a sequence-specific DNA binder, so the bare term over-states a direct activity. Reason: Broad IEA MF; BRCA1's chromatin/damage engagement is captured by more specific terms.
GO:0004842 ubiquitin-protein transferase activity	IEA GO_REF:0000120	ACCEPT	Summary: Core catalytic activity: BRCA1, as the BRCA1-BARD1 RING heterodimer, accelerates ubiquitin transfer from charged E2~Ub onto substrate lysines (e.g. nucleosomal H2A, CtIP, PCNA) at sites of DNA damage. Reason: Defining molecular function of BRCA1 (EC 2.3.2.27); supported across IBA/ISO/ISS and the BRCA1-BARD1 mechanistic literature. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: BRCA1 acts predominantly in the nucleus, forming DNA-damage-induced foci on chromatin where it carries out repair and checkpoint functions. Reason: Primary site of BRCA1 action; UniProt SUBCELLULAR LOCATION and IDA support. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005694 chromosome	IEA GO_REF:0000044	ACCEPT	Summary: BRCA1 localizes to chromosomes/chromatin, where the BRCA1-BARD1 ligase modifies nucleosomal H2A at break sites. Reason: Direct chromatin association is core to BRCA1 function; IDA supported. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005737 cytoplasm	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Cytoplasmic pool seen e.g. on translocation during UV-induced apoptosis and ACACA binding; not the principal site of repair function. Reason: Secondary localization; BRCA1 acts mainly in the nucleus.
GO:0006281 DNA repair	IEA GO_REF:0000120	ACCEPT	Summary: BRCA1 facilitates cellular responses to DNA damage and is required for FANCD2 targeting and homology-directed repair, maintaining genome integrity. Reason: Core function captured directly in UniProt FUNCTION. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0006310 DNA recombination	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Broad recombination term encompassing BRCA1's HR role; the specific homologous-recombination/DSB terms capture the core activity more precisely. Reason: General parent process; specific HR terms are the core annotations.
GO:0006351 DNA-templated transcription	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Participation in DNA-templated transcription, reflecting BRCA1's accessory transcriptional roles rather than its repair core. Reason: Broad transcription process not tied to the core repair function.
GO:0006629 lipid metabolic process	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: General lipid-metabolism involvement stemming from BRCA1's inhibition of ACACA-driven lipogenesis. Reason: Very broad metabolic term secondary to the ACACA moonlighting role.
GO:0006631 fatty acid metabolic process	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Broadly impinges on fatty-acid metabolism via ACACA regulation, a moonlighting metabolic role. Reason: Broad metabolic term downstream of the ACACA-binding role.
GO:0006633 fatty acid biosynthetic process	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: Influences fatty-acid biosynthesis through its inhibitory ACACA interaction, a metabolic role peripheral to genome maintenance. Reason: Metabolic-pathway association secondary to core function.
GO:0006974 DNA damage response	IEA GO_REF:0000120	ACCEPT	Summary: BRCA1 coordinates the DNA-damage response, being phosphorylated by ATM/ATR and assembling repair/checkpoint complexes at break sites. Reason: Core DDR role; IMP-supported and central to BRCA1 biology. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0008270 zinc ion binding	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Zinc coordination by the N-terminal RING-type finger that structurally enables BARD1 heterodimerization and E3 activity. Reason: Structural cofactor binding underpinning, but not equivalent to, the core ligase MF.
GO:0016740 transferase activity	IEA GO_REF:0000043	MODIFY	Summary: Generic transferase parent; BRCA1's actual activity is the specific RING-type ubiquitin-protein transferase function of the BRCA1-BARD1 heterodimer. Reason: IEA parent term too broad; replace with the specific ubiquitin-protein transferase activity child. Proposed replacements: ubiquitin-protein transferase activity
GO:0046872 metal ion binding	IEA GO_REF:0000120	MARK AS OVER ANNOTATED	Summary: Generic metal-binding rollup of the RING zinc-coordination; the functionally meaningful aspect is the RING E3 activity, not metal binding per se. Reason: Keyword-derived broad MF superseded by the specific ligase and zinc-finger terms.
GO:0061630 ubiquitin protein ligase activity	IEA GO_REF:0000003	ACCEPT	Summary: BRCA1-BARD1 RING E3 ligase activity that promotes site-specific (mono)ubiquitination and K6-linked autoubiquitination, coupling enzymatic output to DNA-damage repair pathway choice. Reason: Synonymous core E3-ligase MF; mechanistically established for the BRCA1-BARD1 heterodimer. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0070013 intracellular organelle lumen	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: Very broad luminal compartment term that adds nothing beyond the specific nuclear/nucleoplasm localizations. Reason: Over-broad CC superseded by nucleus/nucleoplasm.
GO:0000724 double-strand break repair via homologous recombination	IEA GO_REF:0000107	ACCEPT	Summary: BRCA1-BARD1 channels DSB repair toward homologous recombination by promoting end resection and PALB2-BRCA2-RAD51 loading at resected breaks. Reason: Central, defining biological role of BRCA1; broadly supported (IBA/ISO and mechanistic literature). Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0000800 lateral element	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Meiotic synaptonemal-complex lateral-element localization tied to BRCA1's role in meiotic chromosome surveillance. Reason: Meiosis-specific localization, a specialized context of genome maintenance.
GO:0000976 transcription cis-regulatory region binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Binds cis-regulatory regions consistent with BRCA1's transcriptional-regulation activities at target promoters. Reason: Transcription-associated DNA binding, secondary to repair role.
GO:0002039 p53 binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Specific binding assertion that, alone, captures a partnership rather than a BRCA1 molecular function and is electronic-only here. Reason: Uninformative bare-binding MF; any p53-linked role is downstream and not the core function.
GO:0003713 transcription coactivator activity	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: BRCA1 can act as a transcriptional coactivator, a regulatory role secondary to and intertwined with its genome-maintenance function. Reason: Transcription role not the core repair/ligase function; keep as non-core.
GO:0003723 RNA binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Reported RNA-binding activity linked to transcription-coupled and RNA-associated functions rather than the core E3/repair role. Reason: Ancillary nucleic-acid binding; not the defining function.
GO:0005654 nucleoplasm	IEA GO_REF:0000107	ACCEPT	Summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities. Reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005886 plasma membrane	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Minor plasma-membrane-associated pool reported electronically; peripheral to BRCA1's nuclear repair activity. Reason: Non-core secondary localization with electronic support only.
GO:0006301 DNA damage tolerance	IEA GO_REF:0000107	ACCEPT	Summary: Via BRCA1-BARD1 ubiquitination of PCNA in unperturbed conditions, BRCA1 supports continuous DNA synthesis and suppresses ssDNA-gap accumulation, aiding tolerance of replication stress. Reason: Supported by recent PCNA-ubiquitination/fork-protection findings tied to BRCA1's E3 activity. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0006302 double-strand break repair	IEA GO_REF:0000107	ACCEPT	Summary: BRCA1 is a key effector of double-strand-break repair, biasing pathway choice away from NHEJ via H2A ubiquitination and 53BP1 repositioning. Reason: Core DSB-repair role; IMP plus electronic support. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0006357 regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Regulates Pol II transcription through coactivator and partner (LMO4/CCAR2) interactions, a pleiotropic role beyond DNA repair. Reason: Transcriptional regulation secondary to BRCA1's core repair/ligase role.
GO:0007059 chromosome segregation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Supports faithful chromosome segregation, a downstream consequence of BRCA1-maintained genome integrity and checkpoint control. Reason: Mitotic-fidelity outcome downstream of the core repair/checkpoint role.
GO:0007095 mitotic G2 DNA damage checkpoint signaling	IEA GO_REF:0000107	ACCEPT	Summary: BRCA1 signals the G2 DNA-damage checkpoint, with BRCA1-mediated RBBP8 ubiquitination regulating CHEK1 activation after damage. Reason: Core checkpoint role tied to BRCA1's repair function; IBA/ISO support. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0010212 response to ionizing radiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Responds to ionizing radiation as part of damage signaling, an upstream stimulus context of the repair function. Reason: Response-to-stimulus term contextual to the core DDR role.
GO:0010575 positive regulation of vascular endothelial growth factor production	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Linked to upregulating VEGF production, a downstream gene-expression output rather than a core activity. Reason: Growth-factor-production role pleiotropic to core function.
GO:0010628 positive regulation of gene expression	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Broadly upregulates expression of target genes via its transcriptional-activator activity. Reason: Generic expression-regulation role downstream of transcription activity.
GO:0016567 protein ubiquitination	IEA GO_REF:0000120	ACCEPT	Summary: BRCA1-BARD1 mediates protein ubiquitination of chromatin and repair substrates as its central biochemical activity. Reason: Core ubiquitination function; the specific K6/autoubiquitination children are also annotated. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0016604 nuclear body	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Localization to nuclear bodies, a sub-nuclear focus consistent with damage-induced assembly but not itself a defining site. Reason: Sub-nuclear localization secondary to the core nuclear/chromatin sites.
GO:0019899 enzyme binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Non-specific enzyme-binding term that conveys nothing about which enzyme or what BRCA1 does with it. Reason: Uninformative binding MF; specific partner roles are captured elsewhere.
GO:0030308 negative regulation of cell growth	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Tumor-suppressor-associated growth restraint, a downstream physiological consequence of intact BRCA1 genome maintenance. Reason: Growth-suppression phenotype downstream of the core repair role.
GO:0031436 BRCA1-BARD1 complex	IEA GO_REF:0000107	ACCEPT	Summary: Obligate RING-RING heterodimer with BARD1 that constitutes the active E3 ligase; this assembly underlies essentially all BRCA1 catalytic and DNA-repair functions. Reason: Defining functional complex of BRCA1; documented in SUBUNIT and the core mechanistic literature. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0031625 ubiquitin protein ligase binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic 'binds an E3 ligase' term that is uninformative for a protein that is itself the E3 ligase. Reason: Bare-binding MF adding no functional specificity beyond BRCA1's own catalytic terms.
GO:0032991 protein-containing complex	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Root-level complex term superseded by the specific BRCA1-BARD1 and BRCA1-A/B/C complex annotations. Reason: Uninformative generic CC; specific complexes are annotated.
GO:0033147 negative regulation of intracellular estrogen receptor signaling pathway	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Represses estrogen-receptor signaling, a hormone-pathway regulatory role pertinent to mammary biology but secondary to repair. Reason: Hormone-signaling regulation pleiotropic to core function.
GO:0042802 identical protein binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Generic self-association term that does not capture BRCA1's heterodimeric-with-BARD1 mode of action or any specific function. Reason: Uninformative bare-binding MF; BRCA1's functional partnerships are captured by specific complex terms.
GO:0045717 negative regulation of fatty acid biosynthetic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Inhibits fatty-acid synthesis by binding inactive phosphorylated ACACA and preventing its dephosphorylation, a distinct metabolic moonlighting role. Reason: Specific lipid-regulatory function via ACACA, separate from the core repair role.
GO:0045739 positive regulation of DNA repair	IEA GO_REF:0000107	ACCEPT	Summary: BRCA1 positively promotes homology-directed DNA repair by enabling resection and RAD51 loading at damage sites. Reason: Core pro-repair activity; consistent with FUNCTION. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0045766 positive regulation of angiogenesis	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Reported promotion of angiogenesis, a tissue-level role far downstream of BRCA1's molecular repair function. Reason: Angiogenic role pleiotropic and electronic-only.
GO:0045892 negative regulation of DNA-templated transcription	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Can repress transcription at certain targets (e.g. via LMO4/CCAR2-modulated activity), a context-specific regulatory role. Reason: Transcriptional repression not part of the core repair function.
GO:0045893 positive regulation of DNA-templated transcription	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Promotes transcription of subsets of target genes as a transcriptional activator, secondary to genome-maintenance roles. Reason: Activator output pleiotropic relative to core function.
GO:0045944 positive regulation of transcription by RNA polymerase II	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Acts as a transcriptional activator at specific target genes, a regulatory output separable from its repair function. Reason: Activator role pleiotropic relative to core repair function.
GO:0051865 protein autoubiquitination	IEA GO_REF:0000107	ACCEPT	Summary: BRCA1 undergoes K6-linked autoubiquitination that does not promote degradation, reflecting its intrinsic E3 ligase activity. Reason: Documented BRCA1 PTM/activity; core to its enzymatic characterization. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0070063 RNA polymerase binding	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Associates with the RNA polymerase II holoenzyme (via DHX9), underpinning BRCA1's transcriptional-regulation activity. Reason: Transcription-machinery interaction secondary to repair/ligase function.
GO:0070531 BRCA1-A complex	IEA GO_REF:0000107	ACCEPT	Summary: Component of the BRCA1-A complex (with RAP80/UIMC1, ABRAXAS1, BRCC36, BABAM1/2) that recognizes K63-ubiquitin chains and recruits BRCA1 to DNA double-strand-break sites. Reason: Bona fide repair-targeting complex central to BRCA1 recruitment; supported by SUBUNIT and IBA/ISO. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0071356 cellular response to tumor necrosis factor	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Participates in the cellular response to TNF, a signaling-context role distinct from BRCA1's repair catalysis. Reason: Cytokine-response context, not the core function.
GO:0071479 cellular response to ionizing radiation	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Mediates the cellular response to ionizing radiation, with BRCA1 phosphorylated and required for IR-induced S/G2 arrest. Reason: Stress-response context of BRCA1's core DDR/checkpoint role.
GO:0071681 cellular response to indole-3-methanol	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Reported response to indole-3-methanol, a chemical-stimulus context secondary to BRCA1's core activities. Reason: Specific chemical-response context, non-core.
GO:0085020 protein K6-linked ubiquitination	IEA GO_REF:0000107	ACCEPT	Summary: BRCA1-BARD1 specifically catalyzes 'Lys-6'-linked polyubiquitin chains, a hallmark non-degradative linkage of this E3 ligase. Reason: Signature catalytic output of BRCA1 stated explicitly in UniProt FUNCTION/PTM. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Modulates death-receptor extrinsic apoptotic signaling, a cell-fate role separable from direct repair catalysis. Reason: Apoptosis-modulation role pleiotropic to core function.
GO:1990904 ribonucleoprotein complex	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Association with RNP/RNA-containing complexes linked to BRCA1's reported RNA binding and transcription-coupled roles. Reason: Peripheral complex membership downstream of transcription-associated activity.
GO:2000378 negative regulation of reactive oxygen species metabolic process	IEA GO_REF:0000107	KEEP AS NON CORE	Summary: Limits ROS accumulation, an antioxidant/redox-protective role downstream of BRCA1-maintained genome and metabolic homeostasis. Reason: Redox-regulation role pleiotropic to the core repair function.
GO:0005634 nucleus	ISO GO_REF:0000119	ACCEPT	Summary: BRCA1 acts predominantly in the nucleus, forming DNA-damage-induced foci on chromatin where it carries out repair and checkpoint functions. Reason: Primary site of BRCA1 action; UniProt SUBCELLULAR LOCATION and IDA support. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0000152 nuclear ubiquitin ligase complex	ISO GO_REF:0000119	ACCEPT	Summary: BRCA1-BARD1 constitutes a nuclear ubiquitin ligase complex that ubiquitinates chromatin and repair-factor substrates at damage sites. Reason: Accurately captures the nuclear E3-ligase nature of the BRCA1-BARD1 heterodimer. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0000724 double-strand break repair via homologous recombination	ISO GO_REF:0000119	ACCEPT	Summary: BRCA1-BARD1 channels DSB repair toward homologous recombination by promoting end resection and PALB2-BRCA2-RAD51 loading at resected breaks. Reason: Central, defining biological role of BRCA1; broadly supported (IBA/ISO and mechanistic literature). Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0000976 transcription cis-regulatory region binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Binds cis-regulatory regions consistent with BRCA1's transcriptional-regulation activities at target promoters. Reason: Transcription-associated DNA binding, secondary to repair role.
GO:0002039 p53 binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Specific binding assertion that, alone, captures a partnership rather than a BRCA1 molecular function and is electronic-only here. Reason: Uninformative bare-binding MF; any p53-linked role is downstream and not the core function.
GO:0003682 chromatin binding	ISO GO_REF:0000096	ACCEPT	Summary: BRCA1-BARD1 engages chromatin (via BARD1 reading of H4K20me0 / H2AK15ub) to target its E3 activity to damaged nucleosomes. Reason: Chromatin engagement is mechanistically central to BRCA1's repair role. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0003713 transcription coactivator activity	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: BRCA1 can act as a transcriptional coactivator, a regulatory role secondary to and intertwined with its genome-maintenance function. Reason: Transcription role not the core repair/ligase function; keep as non-core.
GO:0004842 ubiquitin-protein transferase activity	ISO GO_REF:0000119	ACCEPT	Summary: Core catalytic activity: BRCA1, as the BRCA1-BARD1 RING heterodimer, accelerates ubiquitin transfer from charged E2~Ub onto substrate lysines (e.g. nucleosomal H2A, CtIP, PCNA) at sites of DNA damage. Reason: Defining molecular function of BRCA1 (EC 2.3.2.27); supported across IBA/ISO/ISS and the BRCA1-BARD1 mechanistic literature. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005654 nucleoplasm	ISO GO_REF:0000119	ACCEPT	Summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities. Reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005737 cytoplasm	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Cytoplasmic pool seen e.g. on translocation during UV-induced apoptosis and ACACA binding; not the principal site of repair function. Reason: Secondary localization; BRCA1 acts mainly in the nucleus.
GO:0005759 mitochondrial matrix	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: Reported mitochondrial-matrix pool implicated in mitochondrial genome maintenance, distinct from the dominant nuclear role. Reason: Secondary localization downstream of BRCA1's genome-maintenance function.
GO:0005886 plasma membrane	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Minor plasma-membrane-associated pool reported electronically; peripheral to BRCA1's nuclear repair activity. Reason: Non-core secondary localization with electronic support only.
GO:0006301 DNA damage tolerance	ISO GO_REF:0000119	ACCEPT	Summary: Via BRCA1-BARD1 ubiquitination of PCNA in unperturbed conditions, BRCA1 supports continuous DNA synthesis and suppresses ssDNA-gap accumulation, aiding tolerance of replication stress. Reason: Supported by recent PCNA-ubiquitination/fork-protection findings tied to BRCA1's E3 activity. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0006302 double-strand break repair	ISO GO_REF:0000119	ACCEPT	Summary: BRCA1 is a key effector of double-strand-break repair, biasing pathway choice away from NHEJ via H2A ubiquitination and 53BP1 repositioning. Reason: Core DSB-repair role; IMP plus electronic support. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0006357 regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Regulates Pol II transcription through coactivator and partner (LMO4/CCAR2) interactions, a pleiotropic role beyond DNA repair. Reason: Transcriptional regulation secondary to BRCA1's core repair/ligase role.
GO:0007059 chromosome segregation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Supports faithful chromosome segregation, a downstream consequence of BRCA1-maintained genome integrity and checkpoint control. Reason: Mitotic-fidelity outcome downstream of the core repair/checkpoint role.
GO:0007095 mitotic G2 DNA damage checkpoint signaling	ISO GO_REF:0000119	ACCEPT	Summary: BRCA1 signals the G2 DNA-damage checkpoint, with BRCA1-mediated RBBP8 ubiquitination regulating CHEK1 activation after damage. Reason: Core checkpoint role tied to BRCA1's repair function; IBA/ISO support. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0010212 response to ionizing radiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Responds to ionizing radiation as part of damage signaling, an upstream stimulus context of the repair function. Reason: Response-to-stimulus term contextual to the core DDR role.
GO:0010575 positive regulation of vascular endothelial growth factor production	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Linked to upregulating VEGF production, a downstream gene-expression output rather than a core activity. Reason: Growth-factor-production role pleiotropic to core function.
GO:0010628 positive regulation of gene expression	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Broadly upregulates expression of target genes via its transcriptional-activator activity. Reason: Generic expression-regulation role downstream of transcription activity.
GO:0016567 protein ubiquitination	ISO GO_REF:0000119	ACCEPT	Summary: BRCA1-BARD1 mediates protein ubiquitination of chromatin and repair substrates as its central biochemical activity. Reason: Core ubiquitination function; the specific K6/autoubiquitination children are also annotated. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0016604 nuclear body	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Localization to nuclear bodies, a sub-nuclear focus consistent with damage-induced assembly but not itself a defining site. Reason: Sub-nuclear localization secondary to the core nuclear/chromatin sites.
GO:0019899 enzyme binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Non-specific enzyme-binding term that conveys nothing about which enzyme or what BRCA1 does with it. Reason: Uninformative binding MF; specific partner roles are captured elsewhere.
GO:0030308 negative regulation of cell growth	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Tumor-suppressor-associated growth restraint, a downstream physiological consequence of intact BRCA1 genome maintenance. Reason: Growth-suppression phenotype downstream of the core repair role.
GO:0031436 BRCA1-BARD1 complex	ISO GO_REF:0000119	ACCEPT	Summary: Obligate RING-RING heterodimer with BARD1 that constitutes the active E3 ligase; this assembly underlies essentially all BRCA1 catalytic and DNA-repair functions. Reason: Defining functional complex of BRCA1; documented in SUBUNIT and the core mechanistic literature. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0031625 ubiquitin protein ligase binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Generic 'binds an E3 ligase' term that is uninformative for a protein that is itself the E3 ligase. Reason: Bare-binding MF adding no functional specificity beyond BRCA1's own catalytic terms.
GO:0032991 protein-containing complex	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Root-level complex term superseded by the specific BRCA1-BARD1 and BRCA1-A/B/C complex annotations. Reason: Uninformative generic CC; specific complexes are annotated.
GO:0033147 negative regulation of intracellular estrogen receptor signaling pathway	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Represses estrogen-receptor signaling, a hormone-pathway regulatory role pertinent to mammary biology but secondary to repair. Reason: Hormone-signaling regulation pleiotropic to core function.
GO:0042307 positive regulation of protein import into nucleus	ISO GO_REF:0000096	KEEP AS NON CORE	Summary: Promotes nuclear import of partner proteins, an ancillary trafficking role peripheral to repair catalysis. Reason: Partner-trafficking role not part of the core function.
GO:0042802 identical protein binding	ISO GO_REF:0000119	MARK AS OVER ANNOTATED	Summary: Generic self-association term that does not capture BRCA1's heterodimeric-with-BARD1 mode of action or any specific function. Reason: Uninformative bare-binding MF; BRCA1's functional partnerships are captured by specific complex terms.
GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Linked to silencing of genes via CpG-island methylation, an epigenetic regulatory role distinct from direct repair. Reason: Epigenetic gene-silencing role pleiotropic to core function.
GO:0045717 negative regulation of fatty acid biosynthetic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Inhibits fatty-acid synthesis by binding inactive phosphorylated ACACA and preventing its dephosphorylation, a distinct metabolic moonlighting role. Reason: Specific lipid-regulatory function via ACACA, separate from the core repair role.
GO:0045739 positive regulation of DNA repair	ISO GO_REF:0000119	ACCEPT	Summary: BRCA1 positively promotes homology-directed DNA repair by enabling resection and RAD51 loading at damage sites. Reason: Core pro-repair activity; consistent with FUNCTION. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0045766 positive regulation of angiogenesis	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Reported promotion of angiogenesis, a tissue-level role far downstream of BRCA1's molecular repair function. Reason: Angiogenic role pleiotropic and electronic-only.
GO:0045892 negative regulation of DNA-templated transcription	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Can repress transcription at certain targets (e.g. via LMO4/CCAR2-modulated activity), a context-specific regulatory role. Reason: Transcriptional repression not part of the core repair function.
GO:0045893 positive regulation of DNA-templated transcription	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Promotes transcription of subsets of target genes as a transcriptional activator, secondary to genome-maintenance roles. Reason: Activator output pleiotropic relative to core function.
GO:0045944 positive regulation of transcription by RNA polymerase II	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Acts as a transcriptional activator at specific target genes, a regulatory output separable from its repair function. Reason: Activator role pleiotropic relative to core repair function.
GO:0051726 regulation of cell cycle	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Broad cell-cycle regulation reflecting BRCA1's checkpoint-control activities after DNA damage. Reason: General cell-cycle regulation downstream of checkpoint signaling.
GO:0051865 protein autoubiquitination	ISO GO_REF:0000119	ACCEPT	Summary: BRCA1 undergoes K6-linked autoubiquitination that does not promote degradation, reflecting its intrinsic E3 ligase activity. Reason: Documented BRCA1 PTM/activity; core to its enzymatic characterization. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0070063 RNA polymerase binding	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Associates with the RNA polymerase II holoenzyme (via DHX9), underpinning BRCA1's transcriptional-regulation activity. Reason: Transcription-machinery interaction secondary to repair/ligase function.
GO:0070531 BRCA1-A complex	ISO GO_REF:0000119	ACCEPT	Summary: Component of the BRCA1-A complex (with RAP80/UIMC1, ABRAXAS1, BRCC36, BABAM1/2) that recognizes K63-ubiquitin chains and recruits BRCA1 to DNA double-strand-break sites. Reason: Bona fide repair-targeting complex central to BRCA1 recruitment; supported by SUBUNIT and IBA/ISO. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0070532 BRCA1-B complex	ISO GO_REF:0000119	ACCEPT	Summary: Component of the BRCA1-B complex (BRCA1-BARD1 with BACH1/BRIP1 and TOPBP1) linking BRCA1 to replication-associated DNA repair. Reason: Recognized BRCA1-defined repair complex; consistent with BRCT-BRIP1 interaction in SUBUNIT. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0070533 BRCA1-C complex	ISO GO_REF:0000119	ACCEPT	Summary: Component of the BRCA1-C complex (BRCA1-BARD1 with CtIP/RBBP8 and the MRN complex) that promotes DNA end resection committing breaks to homologous recombination. Reason: Established BRCA1 resection complex; consistent with BRCA1-RBBP8 interaction in SUBUNIT. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0071356 cellular response to tumor necrosis factor	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Participates in the cellular response to TNF, a signaling-context role distinct from BRCA1's repair catalysis. Reason: Cytokine-response context, not the core function.
GO:0071479 cellular response to ionizing radiation	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Mediates the cellular response to ionizing radiation, with BRCA1 phosphorylated and required for IR-induced S/G2 arrest. Reason: Stress-response context of BRCA1's core DDR/checkpoint role.
GO:0071681 cellular response to indole-3-methanol	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Reported response to indole-3-methanol, a chemical-stimulus context secondary to BRCA1's core activities. Reason: Specific chemical-response context, non-core.
GO:0085020 protein K6-linked ubiquitination	ISO GO_REF:0000119	ACCEPT	Summary: BRCA1-BARD1 specifically catalyzes 'Lys-6'-linked polyubiquitin chains, a hallmark non-degradative linkage of this E3 ligase. Reason: Signature catalytic output of BRCA1 stated explicitly in UniProt FUNCTION/PTM. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Modulates death-receptor extrinsic apoptotic signaling, a cell-fate role separable from direct repair catalysis. Reason: Apoptosis-modulation role pleiotropic to core function.
GO:1990391 DNA repair complex	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Generic membership in a DNA-repair complex; the specific BRCA1-defined complexes (BRCA1-BARD1/A/B/C) capture this more precisely. Reason: Broad complex term subordinate to the specific BRCA1 complexes already annotated.
GO:2000378 negative regulation of reactive oxygen species metabolic process	ISO GO_REF:0000119	KEEP AS NON CORE	Summary: Limits ROS accumulation, an antioxidant/redox-protective role downstream of BRCA1-maintained genome and metabolic homeostasis. Reason: Redox-regulation role pleiotropic to the core repair function.
GO:0005634 nucleus	NAS PMID:18171670 Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is ...	ACCEPT	Summary: BRCA1 acts predominantly in the nucleus, forming DNA-damage-induced foci on chromatin where it carries out repair and checkpoint functions. Reason: Primary site of BRCA1 action; UniProt SUBCELLULAR LOCATION and IDA support. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005634 nucleus	NAS PMID:20656689 Differential regulation of JAMM domain deubiquitinating enzy...	ACCEPT	Summary: BRCA1 acts predominantly in the nucleus, forming DNA-damage-induced foci on chromatin where it carries out repair and checkpoint functions. Reason: Primary site of BRCA1 action; UniProt SUBCELLULAR LOCATION and IDA support. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005634 nucleus	NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail.	ACCEPT	Summary: BRCA1 acts predominantly in the nucleus, forming DNA-damage-induced foci on chromatin where it carries out repair and checkpoint functions. Reason: Primary site of BRCA1 action; UniProt SUBCELLULAR LOCATION and IDA support. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0006281 DNA repair	NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail.	ACCEPT	Summary: BRCA1 facilitates cellular responses to DNA damage and is required for FANCD2 targeting and homology-directed repair, maintaining genome integrity. Reason: Core function captured directly in UniProt FUNCTION. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0006282 regulation of DNA repair	NAS PMID:20656689 Differential regulation of JAMM domain deubiquitinating enzy...	ACCEPT	Summary: BRCA1 regulates DNA repair by controlling pathway choice and the loading of downstream HR machinery at breaks. Reason: Core regulatory role over the repair process it executes. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0035825 homologous recombination	NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail.	ACCEPT	Summary: BRCA1 contributes to homologous recombination through its PALB2 interaction and modulation of RAD51 loading during recombinational repair. Reason: Core repair pathway; NAS support consistent with FUNCTION. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0035825 homologous recombination	NAS PMID:30657944 CtIP-BRCA1 complex and MRE11 maintain replication forks in t...	ACCEPT	Summary: BRCA1 contributes to homologous recombination through its PALB2 interaction and modulation of RAD51 loading during recombinational repair. Reason: Core repair pathway; NAS support consistent with FUNCTION. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0044818 mitotic G2/M transition checkpoint	NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail.	ACCEPT	Summary: Required for the DNA-damage-induced G2/M checkpoint arrest that prevents division of cells carrying unrepaired breaks. Reason: Core checkpoint function; IMP-supported and consistent with FUNCTION. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
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-BARD1 promotes nucleolytic end resection at breaks and protects/processes stalled replication forks, a step committing repair to homology-directed pathways. Reason: Resection is a core BRCA1-driven step (BRCA1-C/CtIP); NAS supported. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0003713 transcription coactivator activity	IDA PMID:20820192 BRCA1 affects global DNA methylation through regulation of D...	KEEP AS NON CORE	Summary: BRCA1 can act as a transcriptional coactivator, a regulatory role secondary to and intertwined with its genome-maintenance function. Reason: Transcription role not the core repair/ligase function; keep as non-core.
GO:0006974 DNA damage response	NAS PMID:16651405 DNA damage-induced BARD1 phosphorylation is critical for the...	ACCEPT	Summary: BRCA1 coordinates the DNA-damage response, being phosphorylated by ATM/ATR and assembling repair/checkpoint complexes at break sites. Reason: Core DDR role; IMP-supported and central to BRCA1 biology. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0045787 positive regulation of cell cycle	NAS PMID:15159397 BRCA1-BARD1 complexes are required for p53Ser-15 phosphoryla...	KEEP AS NON CORE	Summary: Reported positive cell-cycle regulation, a context-dependent role secondary to BRCA1's checkpoint function. Reason: Pleiotropic cell-cycle effect downstream of core checkpoint role.
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 checkpoint activation, controlling cell-cycle arrest in coordination with its repair complexes. Reason: Directly tied to BRCA1's checkpoint-control role; NAS supported. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0060816 random inactivation of X chromosome	IGI PMID:12419249 BRCA1 supports XIST RNA concentration on the inactive X chro...	KEEP AS NON CORE	Summary: Implicated in X-chromosome inactivation, a chromatin-level role related to BRCA1's chromosome-surveillance activity. Reason: Specialized chromatin role secondary to core repair function.
GO:0044027 negative regulation of gene expression via chromosomal CpG island methylation	IDA PMID:20820192 BRCA1 affects global DNA methylation through regulation of D...	KEEP AS NON CORE	Summary: Linked to silencing of genes via CpG-island methylation, an epigenetic regulatory role distinct from direct repair. Reason: Epigenetic gene-silencing role pleiotropic to core 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: Acts as a transcriptional activator at specific target genes, a regulatory output separable from its repair function. Reason: Activator role pleiotropic relative to core repair function.
GO:0001741 XY body	IDA PMID:31839538 GCNA Interacts with Spartan and Topoisomerase II to Regulate...	KEEP AS NON CORE	Summary: Localizes to the XY body (sex-body) during male meiosis, reflecting BRCA1's role in meiotic sex-chromosome inactivation/silencing. Reason: Meiosis-specific localization downstream of BRCA1's chromatin/genome-surveillance role.
GO:0005634 nucleus	IDA PMID:31839538 GCNA Interacts with Spartan and Topoisomerase II to Regulate...	ACCEPT	Summary: BRCA1 acts predominantly in the nucleus, forming DNA-damage-induced foci on chromatin where it carries out repair and checkpoint functions. Reason: Primary site of BRCA1 action; UniProt SUBCELLULAR LOCATION and IDA support.
GO:1990904 ribonucleoprotein complex	ISO PMID:18809582 Nucleophosmin serves as a rate-limiting nuclear export chape...	KEEP AS NON CORE	Summary: Association with RNP/RNA-containing complexes linked to BRCA1's reported RNA binding and transcription-coupled roles. Reason: Peripheral complex membership downstream of transcription-associated activity.
GO:0032991 protein-containing complex	ISO PMID:16951165 p27Kip1 repression of ErbB2-induced mammary tumor growth in ...	MARK AS OVER ANNOTATED	Summary: Root-level complex term superseded by the specific BRCA1-BARD1 and BRCA1-A/B/C complex annotations. Reason: Uninformative generic CC; specific complexes are annotated.
GO:0003713 transcription coactivator activity	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: BRCA1 can act as a transcriptional coactivator, a regulatory role secondary to and intertwined with its genome-maintenance function. Reason: Transcription role not the core repair/ligase function; keep as non-core.
GO:0006357 regulation of transcription by RNA polymerase II	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Regulates Pol II transcription through coactivator and partner (LMO4/CCAR2) interactions, a pleiotropic role beyond DNA repair. Reason: Transcriptional regulation secondary to BRCA1's core repair/ligase role.
GO:0070063 RNA polymerase binding	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Associates with the RNA polymerase II holoenzyme (via DHX9), underpinning BRCA1's transcriptional-regulation activity. Reason: Transcription-machinery interaction secondary to repair/ligase function.
GO:0044818 mitotic G2/M transition checkpoint	IMP PMID:15254237 BRCA1 is required for common-fragile-site stability via its ...	ACCEPT	Summary: Required for the DNA-damage-induced G2/M checkpoint arrest that prevents division of cells carrying unrepaired breaks. Reason: Core checkpoint function; IMP-supported and consistent with FUNCTION. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0000800 lateral element	ISO PMID:9774970 Stable interaction between the products of the BRCA1 and BRC...	KEEP AS NON CORE	Summary: Meiotic synaptonemal-complex lateral-element localization tied to BRCA1's role in meiotic chromosome surveillance. Reason: Meiosis-specific localization, a specialized context of genome maintenance.
GO:0000794 condensed nuclear chromosome	IDA PMID:26490168 FancJ (Brip1) loss-of-function allele results in spermatogon...	ACCEPT	Summary: Localizes to condensed nuclear chromosomes, reflecting chromatin association during mitotic/meiotic chromosome states. Reason: IDA-supported; keep experimental localization rather than removing. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0045893 positive regulation of DNA-templated transcription	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Promotes transcription of subsets of target genes as a transcriptional activator, secondary to genome-maintenance roles. Reason: Activator output pleiotropic relative to core function.
GO:0006974 DNA damage response	IMP PMID:23271346 BRCA1 deficiency in skin epidermis leads to selective loss o...	ACCEPT	Summary: BRCA1 coordinates the DNA-damage response, being phosphorylated by ATM/ATR and assembling repair/checkpoint complexes at break sites. Reason: Core DDR role; IMP-supported and central to BRCA1 biology. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005694 chromosome	IDA PMID:22549958 Meiotic DNA double-strand breaks and chromosome asynapsis in...	ACCEPT	Summary: BRCA1 localizes to chromosomes/chromatin, where the BRCA1-BARD1 ligase modifies nucleosomal H2A at break sites. Reason: Direct chromatin association is core to BRCA1 function; IDA supported. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005694 chromosome	IDA PMID:23039116 HORMAD2 is essential for synapsis surveillance during meioti...	ACCEPT	Summary: BRCA1 localizes to chromosomes/chromatin, where the BRCA1-BARD1 ligase modifies nucleosomal H2A at break sites. Reason: Direct chromatin association is core to BRCA1 function; IDA supported. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-912421	ACCEPT	Summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities. Reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-912423	ACCEPT	Summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities. Reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-912431	ACCEPT	Summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities. Reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-912449	ACCEPT	Summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities. Reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005654 nucleoplasm	TAS Reactome:R-MMU-912468	ACCEPT	Summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities. Reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0006302 double-strand break repair	IMP PMID:22186889 BRCA1 is an essential regulator of heart function and surviv...	ACCEPT	Summary: BRCA1 is a key effector of double-strand-break repair, biasing pathway choice away from NHEJ via H2A ubiquitination and 53BP1 repositioning. Reason: Core DSB-repair role; IMP plus electronic support. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0005737 cytoplasm	IDA PMID:11172592 Brca1 and Brca2 protein expression patterns in different tis...	KEEP AS NON CORE	Summary: Cytoplasmic pool seen e.g. on translocation during UV-induced apoptosis and ACACA binding; not the principal site of repair function. Reason: Secondary localization; BRCA1 acts mainly in the nucleus.
GO:0000976 transcription cis-regulatory region binding	IDA PMID:20820192 BRCA1 affects global DNA methylation through regulation of D...	KEEP AS NON CORE	Summary: Binds cis-regulatory regions consistent with BRCA1's transcriptional-regulation activities at target promoters. Reason: Transcription-associated DNA binding, secondary to repair role.
GO:0000794 condensed nuclear chromosome	IDA PMID:20551173 Functional conservation of Mei4 for meiotic DNA double-stran...	ACCEPT	Summary: Localizes to condensed nuclear chromosomes, reflecting chromatin association during mitotic/meiotic chromosome states. Reason: IDA-supported; keep experimental localization rather than removing.
GO:0085020 protein K6-linked ubiquitination	ISS GO_REF:0000024	ACCEPT	Summary: BRCA1-BARD1 specifically catalyzes 'Lys-6'-linked polyubiquitin chains, a hallmark non-degradative linkage of this E3 ligase. Reason: Signature catalytic output of BRCA1 stated explicitly in UniProt FUNCTION/PTM. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0051865 protein autoubiquitination	ISS GO_REF:0000024	ACCEPT	Summary: BRCA1 undergoes K6-linked autoubiquitination that does not promote degradation, reflecting its intrinsic E3 ligase activity. Reason: Documented BRCA1 PTM/activity; core to its enzymatic characterization. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0004842 ubiquitin-protein transferase activity	ISS GO_REF:0000024	ACCEPT	Summary: Core catalytic activity: BRCA1, as the BRCA1-BARD1 RING heterodimer, accelerates ubiquitin transfer from charged E2~Ub onto substrate lysines (e.g. nucleosomal H2A, CtIP, PCNA) at sites of DNA damage. Reason: Defining molecular function of BRCA1 (EC 2.3.2.27); supported across IBA/ISO/ISS and the BRCA1-BARD1 mechanistic literature. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0031436 BRCA1-BARD1 complex	ISS GO_REF:0000024	ACCEPT	Summary: Obligate RING-RING heterodimer with BARD1 that constitutes the active E3 ligase; this assembly underlies essentially all BRCA1 catalytic and DNA-repair functions. Reason: Defining functional complex of BRCA1; documented in SUBUNIT and the core mechanistic literature. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0003723 RNA binding	ISO PMID:12419249 BRCA1 supports XIST RNA concentration on the inactive X chro...	KEEP AS NON CORE	Summary: Reported RNA-binding activity linked to transcription-coupled and RNA-associated functions rather than the core E3/repair role. Reason: Ancillary nucleic-acid binding; not the defining function.
GO:0043009 chordate embryonic development	IMP PMID:9171368 Targeted mutations of breast cancer susceptibility gene homo...	KEEP AS NON CORE	Summary: Brca1 is required for embryonic development, with knockouts being embryonic lethal owing to defective proliferation and genome instability. Reason: Developmental phenotype downstream of BRCA1's essential genome-maintenance role.
GO:0045717 negative regulation of fatty acid biosynthetic process	ISS GO_REF:0000024	KEEP AS NON CORE	Summary: Inhibits fatty-acid synthesis by binding inactive phosphorylated ACACA and preventing its dephosphorylation, a distinct metabolic moonlighting role. Reason: Specific lipid-regulatory function via ACACA, separate from the core repair role.
GO:0005813 centrosome	TAS PMID:10855792 VCP, a weak ATPase involved in multiple cellular events, int...	KEEP AS NON CORE	Summary: Centrosomal pool linked to BRCA1's regulation of centrosomal microtubule nucleation, a function secondary to its nuclear repair role. Reason: Secondary localization downstream of BRCA1's broader genome-stability role.
GO:0051298 centrosome duplication	TAS PMID:10855792 VCP, a weak ATPase involved in multiple cellular events, int...	KEEP AS NON CORE	Summary: Regulates centrosome duplication, helping prevent centrosome amplification and aneuploidy. Reason: Centrosome control secondary to BRCA1's genome-stability function.
GO:0000793 condensed chromosome	IDA PMID:12913077 Targeted disruption of exons 1 to 6 of the Fanconi Anemia gr...	ACCEPT	Summary: Localizes to condensed chromosomes, consistent with BRCA1's role in genome maintenance through the cell cycle. Reason: IDA-supported localization; retain as observed nuclear/chromosomal site. Supporting Evidence: UniProt:P48754 E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. file:mouse/Brca1/Brca1-deep-research-falcon.md BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
GO:0007098 centrosome cycle	IGI PMID:15123655 Genetic interactions between Brca1 and Gadd45a in centrosome...	KEEP AS NON CORE	Summary: Participates in the centrosome cycle, consistent with AURKA-phosphorylation-regulated control of centrosomal microtubule nucleation. Reason: Centrosome-cycle role secondary to core repair/checkpoint function.
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage	ISO PMID:14654789 A member of the Pyrin family, IFI16, is a novel BRCA1-associ...	KEEP AS NON CORE	Summary: Engages DNA-damage-triggered intrinsic apoptosis when damage is irreparable, an outcome downstream of BRCA1 damage sensing. Reason: Apoptotic outcome downstream of the core DNA-damage-response role.
GO:0003684 damaged DNA binding	IDA PMID:11934988 Genomic instability in mice lacking histone H2AX.	MARK AS OVER ANNOTATED	Summary: BRCA1 is recruited to damaged DNA chiefly via ubiquitin/chromatin readers and partner complexes rather than as a direct damaged-DNA binder; the bare MF over-attributes a direct activity. Reason: Recruitment to damage is complex-mediated; specific complex/chromatin terms capture this better.

Core Functions

Functions with BARD1 as a RING E3 ubiquitin ligase that supports DNA damage signaling, repair-factor positioning, and genome stability.

Molecular Function:

ubiquitin-protein transferase activity

Directly Involved In:

protein ubiquitination protein K6-linked ubiquitination

Cellular Locations:

nucleus nucleoplasm

In Complex:

BRCA1-BARD1 complex

Supporting Evidence:

UniProt:P48754
E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
file:mouse/Brca1/Brca1-deep-research-falcon.md
BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.

References

GO_REF:0000003

Gene Ontology annotation based on Enzyme Commission mapping

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000043

Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

GO_REF:0000096

Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

GO_REF:0000117

Electronic Gene Ontology annotations created by ARBA machine learning models

GO_REF:0000119

Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:10855792

VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells.

PMID:11172592

Brca1 and Brca2 protein expression patterns in different tissues of murine origin.

PMID:11934988

Genomic instability in mice lacking histone H2AX.

PMID:12419249

BRCA1 supports XIST RNA concentration on the inactive X chromosome.

PMID:12913077

Targeted disruption of exons 1 to 6 of the Fanconi Anemia group A gene leads to growth retardation, strain-specific microphthalmia, meiotic defects and primordial germ cell hypoplasia.

PMID:14636569

Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair.

PMID:14654789

A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway.

PMID:15123655

Genetic interactions between Brca1 and Gadd45a in centrosome duplication, genetic stability, and neural tube closure.

PMID:15159397

BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage.

PMID:15254237

BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function.

PMID:16651405

DNA damage-induced BARD1 phosphorylation is critical for the inhibition of messenger RNA processing by BRCA1/BARD1 complex.

PMID:16951165

p27Kip1 repression of ErbB2-induced mammary tumor growth in transgenic mice involves Skp2 and Wnt/beta-catenin signaling.

PMID:18171670

Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA double-strand break repair.

PMID:18809582

Nucleophosmin serves as a rate-limiting nuclear export chaperone for the Mammalian ribosome.

PMID:20551173

Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice.

The cached publication supports MEI4 localization/function in meiotic double-strand break formation, not BRCA1 condensed nuclear chromosome localization

PMID:20656689

Differential regulation of JAMM domain deubiquitinating enzyme activity within the RAP80 complex.

PMID:20820192

BRCA1 affects global DNA methylation through regulation of DNMT1.

PMID:22186889

BRCA1 is an essential regulator of heart function and survival following myocardial infarction.

PMID:22369660

BRCA1 tumor suppressor network: focusing on its tail.

PMID:22549958

Meiotic DNA double-strand breaks and chromosome asynapsis in mice are monitored by distinct HORMAD2-independent and -dependent mechanisms.

PMID:23039116

HORMAD2 is essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity.

PMID:23271346

BRCA1 deficiency in skin epidermis leads to selective loss of hair follicle stem cells and their progeny.

PMID:26490168

FancJ (Brip1) loss-of-function allele results in spermatogonial cell depletion during embryogenesis and altered processing of crossover sites during meiotic prophase I in mice.

PMID:29709199

The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair.

PMID:30657944

CtIP-BRCA1 complex and MRE11 maintain replication forks in the presence of chain terminating nucleoside analogs.

PMID:31839538

GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome Stability.

The cached publication is a GCNA/Spartan genome-stability study and does not support BRCA1 nuclear localization

PMID:9171368

Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos.

PMID:9774970

Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells.

Reactome:R-MMU-912421

Formation of Meiotic Single-stranded Invasion Complex

Reactome:R-MMU-912423

Atr Phosphorylates Histone H2A.X at Unsynapsed Regions

Reactome:R-MMU-912431

Formation of Meiotic Heteroduplex

Reactome:R-MMU-912449

Recruitment of Atr Kinase to Unsynapsed Regions

Reactome:R-MMU-912468

Recruitment of Brca1 to Unsynapsed Regions

UniProt:P48754

UniProtKB record for mouse Brca1 (P48754)

file:mouse/Brca1/Brca1-deep-research-falcon.md

Falcon deep research synthesis for mouse Brca1

Deep Research

Falcon

(Brca1-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 32 citations 2026-05-03T20:45:25.121226

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research Report: Mouse Brca1 (UniProt P48754) — Functional Annotation (2023–2024 emphasis)

1) Target verification (gene/protein identity)

The research target corresponds to mouse (Mus musculus) Brca1/BRCA1, a ~1863 amino-acid nuclear protein with canonical BRCA1 architecture: N‑terminal RING domain (aa 1–109), a large central region (exon 11), a coiled-coil region, and a C‑terminal tandem BRCT repeat region. This domain organization matches the UniProt-provided BRCA1 description and is explicitly described in mouse-focused synthesis and in recent BRCA1–BARD1 mechanistic work. (durin2024mechanismsgoverningthe pages 49-54, wang2023crucialrolesof pages 23-26)

Note on accession mapping: In the retrieved full texts, the UniProt accession “P48754” was not explicitly stated; however, the protein described (mouse Brca1, ~1863 aa; RING/CC/BRCT; BRCA1–BARD1 E3 ligase) uniquely matches the UniProt identity provided in the prompt. (durin2024mechanismsgoverningthe pages 49-54, wang2023crucialrolesof pages 23-26)

2) Key concepts and definitions (current understanding)

BRCA1 as a genome-stability tumor suppressor

BRCA1/Brca1 is best understood as a central coordinator of genome maintenance, particularly homologous recombination (HR) and replication-associated genome stability, acting through multiple protein assemblies and post-translational modification pathways. (chauhan2024e3ligasesa pages 12-14, moser2025thirtyyearsof pages 3-4)

Core functional modules

(i) RING domain and E3 ubiquitin ligase activity. BRCA1 forms an obligate heterodimer with BARD1 via their RING domains; this heterodimer supplies BRCA1’s well-established enzymatic activity: a RING-type ubiquitin E3 ligase that promotes ubiquitin transfer from E2~Ub to substrates. (wang2023crucialrolesof pages 1-3, wang2023crucialrolesof pages 5-6)

(ii) BRCT repeats as interaction/scaffolding modules. BRCA1’s C-terminal BRCT domains are major determinants of BRCA1’s assembly into distinct multiprotein complexes at sites of DNA damage; these complexes modulate DNA repair pathway choice and HR steps. (chauhan2024e3ligasesa pages 12-14, wang2023crucialrolesof pages 21-23)

(iii) Coiled-coil region and HR effector axis. BRCA1 participates in a BRCA1–PALB2–BRCA2 axis that promotes RAD51 loading on resected ssDNA, a key step in HR. (chauhan2024e3ligasesa pages 12-14, moser2025thirtyyearsof pages 3-4)

3) Primary biochemical function (reaction, substrates, specificity)

Enzymatic reaction

BRCA1–BARD1 catalyzes E3-dependent ubiquitin transfer: it accelerates ubiquitin discharge from an E2~Ub conjugate onto defined substrates, a hallmark of RING E3 ligases. In biochemical assays, wild-type BRCA1–BARD1 robustly enhances E2~Ub discharge (e.g., with UBE2D3~Ub), whereas an engineered ligase-dead mutant lacking E2 interaction is devoid of this activity. (wang2023crucialrolesof pages 5-6)

Best-supported substrates and sites (2023–2024)

Nucleosomal histone H2A (C-terminal tail): A major, repeatedly supported substrate is nucleosomal histone H2A, which BRCA1–BARD1 mono-ubiquitylates at K125/K127/K129; mutation of these sites (3KR) greatly attenuates ubiquitylation. (wang2023crucialrolesof pages 1-3, wang2023crucialrolesof pages 3-5)

Phosphorylated CtIP (pCtIP): BRCA1–BARD1 also targets pCtIP, linking the ligase directly to DNA end resection (the step that commits breaks toward HR). (wang2023crucialrolesof pages 1-3)

Other substrates (reported/less consolidated): A mouse-focused synthesis collates additional reported substrates (e.g., Aurora B, cyclin B, Cdc25C, estrogen receptor α), emphasizing that the functional importance of many non-histone substrates remains context-dependent and sometimes disputed across studies. (durin2024mechanismsgoverningthe pages 49-54)

E2 usage and substrate context

Wang et al. (2023) report E2 specificity in reconstituted reactions: UBE2D3 is most efficient for H2A ubiquitylation, while UBE2W is most efficient for H3, and UBE2B is inactive in their assays. (wang2023crucialrolesof pages 3-5)

Ubiquitin linkage preferences (what is and is not settled)

Direct 2023–2024 evidence in the retrieved primary sources strongly supports site-specific mono-ubiquitylation of H2A at K125/K127/K129 in nucleosomal context. (wang2023crucialrolesof pages 1-3, wang2023crucialrolesof pages 3-5)

A mouse-focused synthesis additionally reports that BRCA1–BARD1 catalyzes autoubiquitination forming K6-linked polyubiquitin chains, but it also emphasizes that the functional role of such autoubiquitination and of H2A K125/127/129 ubiquitination has been interpreted differently across studies. (durin2024mechanismsgoverningthe pages 49-54)

4) Pathways and mechanistic roles

4.1 Homologous recombination and DSB repair pathway choice

A central, mechanistically grounded model is that BRCA1–BARD1 promotes end resection and channels repair toward HR. A key mechanism is BRCA1–BARD1-dependent H2A K125/127/129 ubiquitylation, which is required for 53BP1 repositioning to enable resection in S/G2, thus favoring HR over NHEJ. (chauhan2024e3ligasesa pages 12-14)

Wang et al. (2023) provide recent mechanistic support that BRCA1–BARD1 E3 ligase activity is critical for DNA end resection and contributes to later HR steps, linking enzymatic activity to HR functional endpoints (e.g., genotoxin sensitivity). (wang2023crucialrolesof pages 1-3)

4.2 Chromatin targeting and recruitment logic (damage-site specificity)

Recent synthesis emphasizes a targeting framework in which BRCA1 localization is controlled by ubiquitin-dependent recruitment pathways (e.g., Ubc13/RNF8-dependent signaling and BRCA1-A complex components such as RAP80/Abraxas) that position BRCA1 at damage-associated ubiquitin structures. (moser2025thirtyyearsof pages 24-25)

In parallel, BRCA1–BARD1 is targeted by BARD1 chromatin-reader functions that interpret damage-associated chromatin marks (e.g., H4K20me0 and H2A K15 ubiquitination), thereby coupling BRCA1–BARD1 enzymatic action to the correct chromatin context. (wang2023crucialrolesof pages 21-23)

4.3 Replication fork protection and replication-gap suppression (major 2024 development)

A key 2024 advance is expanded evidence that BRCA1–BARD1 E3 activity acts outside canonical DSB repair, supporting ongoing DNA synthesis and suppressing replication-associated damage.

PCNA ubiquitination in unperturbed conditions: Salas‑Lloret et al. (published May 2024, Nature Communications; https://doi.org/10.1038/s41467-024-48427-6) used a substrate-identification strategy (TULIP2) and identified PCNA as a direct BRCA1/BARD1 ubiquitination substrate in unperturbed conditions and independently of RAD18. Functionally, BRCA1/BARD1-mediated PCNA ubiquitination helps avoid ssDNA gap formation and promotes continuous DNA synthesis, linking BRCA1 E3 function to replication robustness. (salaslloret2024brca1bard1ubiquitinatespcna pages 1-2)

A mouse-focused synthesis further reports PCNA K164 as a BRCA1–BARD1 ubiquitination site in replication protection contexts, but residue-level site mapping is more explicitly presented in synthesis than in the extracted primary-paper snippet. (durin2024mechanismsgoverningthe pages 49-54)

5) Subcellular localization and where BRCA1 acts in the cell

BRCA1/Brca1 functions predominantly in the nucleus, forming DNA damage-induced nuclear foci and associating with damaged chromatin through ubiquitin-signaling scaffolds and BARD1-dependent chromatin recognition. (moser2025thirtyyearsof pages 23-24, moser2025thirtyyearsof pages 24-25)

Functionally distinct nuclear locales include:
- DSB-associated chromatin, where BRCA1–BARD1 E3 activity (H2A ubiquitination) supports 53BP1 repositioning and resection/HR commitment. (chauhan2024e3ligasesa pages 12-14)
- Stalled/perturbed replication forks, where BRCA1 supports RAD51 loading onto nascent DNA to prevent pathological nucleolytic degradation and promote fork restart; recent expert synthesis treats fork protection as mechanistically separable from canonical HR in some cases. (moser2025thirtyyearsof pages 3-4)

6) Current applications and real-world implementations (mouse-focused)

6.1 Preclinical breast cancer and therapy-response modeling

Conditional Brca1 loss in mammary epithelium—often combined with Trp53 loss—constitutes a widely used basal-like/TNBC preclinical platform for studying tumor evolution, DNA repair dependencies, and treatment responses in an immune-competent setting. A model-focused review summarizes that Brca1 conditional deletion alone yields long-latency tumorigenesis, while Brca1 plus Trp53 loss accelerates tumor formation and generates tumors resembling human basal-like disease. (ciringione2025facingthechallenge pages 11-12)

Minimal residual disease (MRD) imaging and treatment timing (quantitative): In a KB1P (K14cre;Brca1F/F;Trp53F/F)-derived organoid model, Steinbauer et al. (published July 2025, NPJ Breast Cancer; https://doi.org/10.1038/s41523-025-00795-y) report that AkaLuc bioluminescence imaging provides an in vivo detection threshold of ~1000 cells for MRD and is ~100-fold more sensitive than FLuc for their use case; they also report that a clinically relevant TAC(2×, q21) regimen yields a median relapse-free survival of 96 days. (steinbauer2025enhancedbioluminescenceimaging pages 1-2, steinbauer2025enhancedbioluminescenceimaging pages 7-7)

These workflows are “real-world” in the sense of being operationally deployed as standardized preclinical treatment and response-monitoring pipelines in mouse BRCA1-loss tumor models, including relapse and dormancy dynamics. (steinbauer2025enhancedbioluminescenceimaging pages 4-7)

6.2 Reproductive aging and fertility biology

Winship et al. (published Aug 2024, eBioMedicine; https://doi.org/10.1016/j.ebiom.2024.105262) implement an oocyte-specific conditional Brca1 knockout (Gdf9-Cre; Brca1fl/fl, exon 11 floxed) to model genome maintenance in reproductive aging. Quantitatively, in vitro oocyte maturation was reduced by 45% by PN300 in Brca1 cKO oocytes, consistent with compromised oocyte quality at advanced reproductive age. (winship2024conditionallossof pages 11-13, winship2024conditionallossof pages 2-3)

7) Expert opinions and analysis (authoritative interpretations)

A 2024 Biochemical Journal review frames BRCA1 as a paradigmatic ubiquitin E3 ligase controlling repair-factor localization and pathway routing, highlighting H2A K125/127/129 ubiquitylation as a mechanistic step enabling resection/HR and emphasizing that BRCA1 participates in multiple BRCT-defined multiprotein complexes (BRCA1-A/B/C). (chauhan2024e3ligasesa pages 12-14)

Recent synthesis also underscores a continuing debate: while 2023 mechanistic work supports a critical requirement for BRCA1–BARD1 E3 ligase activity in resection/HDR, some studies and contexts suggest partial dispensability of ligase activity for certain HR readouts, indicating context dependence and possible redundancy with other ubiquitin signaling pathways. (durin2024mechanismsgoverningthe pages 49-54, salaslloret2024brca1bard1ubiquitinatespcna pages 1-2)

8) Visual evidence (domain/function schematic)

Wang et al. (Molecular Cell, Oct 2023, https://doi.org/10.1016/j.molcel.2023.09.015) provide a graphical abstract and a Figure 1 schematic summarizing BRCA1/BARD1 domain organization (RING, coiled-coil, BRCT) and the coupling of E3 activity to H2A and pCtIP ubiquitylation across stages of homology-directed repair; these figures are useful for mapping domain-level annotations to functional steps. (wang2023crucialrolesof media 3ac94833, wang2023crucialrolesof media 2f74b539)

Summary table (compact functional annotation map)

Functional axis	Key molecular mechanism	Key substrates/modifications (sites if stated)	Evidence type (review/primary; mouse vs general)	Key 2023-2024 references (first author year journal)	Tool citation IDs to use in answer
HR / DSB repair	BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair	Nucleosomal histone H2A mono-ubiquitylation at K125/K127/K129; phosphorylated CtIP is also reported as a BRCA1-BARD1 substrate linked to resection	Primary mechanistic and review evidence; largely mammalian/general, but consistent with mouse Brca1 domain organization and function	Wang 2023 Molecular Cell; Chauhan 2024 Biochemical Journal	(wang2023crucialrolesof pages 1-3, wang2023crucialrolesof pages 21-23, wang2023crucialrolesof pages 23-26, chauhan2024e3ligasesa pages 12-14)
Chromatin ubiquitination / repair-pathway choice	BRCA1-BARD1-mediated H2A ubiquitylation remodels chromatin around DSBs, helps reposition/exclude 53BP1, and channels repair toward HR; requirement for ligase activity is supported by recent work but remains partly debated across studies	H2A K125/K127/K129 mono-ubiquitylation; BARD1 chromatin reading of H4K20me0 and H2A K15ub helps target the complex to appropriate chromatin	Primary and review; general DDR literature with direct BRCA1-BARD1 biochemical evidence	Wang 2023 Molecular Cell; Chauhan 2024 Biochemical Journal	(chauhan2024e3ligasesa pages 12-14, wang2023crucialrolesof pages 21-23, wang2023crucialrolesof pages 23-26)
Replication fork protection / continuous DNA synthesis	Beyond canonical HR, BRCA1-BARD1 E3 activity contributes to replication-fork integrity by suppressing ssDNA-gap accumulation and promoting continuous DNA synthesis in unperturbed conditions	PCNA ubiquitination, reported at K164 in a 2024 mechanistic synthesis; direct 2024 primary study identifies PCNA as a BRCA1/BARD1 substrate and shows RAD18-independent modification; established BRCA1-BARD1 H2A K127/K129 activity also noted	Strong 2024 primary evidence plus review/synthesis; mostly mammalian/general, highly relevant to Brca1 function	Salas-Lloret 2024 Nature Communications; Chauhan 2024 Biochemical Journal	(salaslloret2024brca1bard1ubiquitinatespcna pages 1-2, durin2024mechanismsgoverningthe pages 49-54, nguyen2025overviewofroles pages 6-8)
Complex assembly / domain architecture	Mouse BRCA1 is a ~1863-aa protein with N-terminal RING, long exon-11 region, coiled-coil domain, and tandem BRCT repeats; RING-RING binding to BARD1 stabilizes BRCA1 and creates the active E3 complex; BRCT domains scaffold phosphoprotein-dependent complexes; coiled-coil region supports PALB2 axis in HR	Structural/interaction features rather than single covalent sites; domains: RING, CC, BRCT	Mouse-specific descriptive evidence plus high-level mechanistic reviews	Wang 2023 Molecular Cell; Durin 2024 thesis/review-like synthesis	(durin2024mechanismsgoverningthe pages 49-54, wang2023crucialrolesof pages 23-26, wang2023crucialrolesof pages 1-3)
Localization to DNA damage sites / nuclear foci	BRCA1 localizes to nuclear foci and damaged chromatin through ubiquitin-dependent recruitment pathways (including RAP80/Abraxas/BRCA1-A) and BARD1 chromatin-reader functions; BRCA1-containing complexes assemble in S/G2 to promote resection and RAD51 focus formation	Damage-site recognition linked to H2A K15ub and H4K20me0 reading by BARD1; BRCA1 damage foci and RAD51 foci are common functional readouts	Review-heavy with cited primary work; mammalian/general but includes murine Brca1 nuclear-foci observations	Chauhan 2024 Biochemical Journal; Moser 2025 Cancer Discovery summarizing 2023-2024 work	(moser2025thirtyyearsof pages 24-25, wang2023crucialrolesof pages 21-23, moser2025thirtyyearsof pages 23-24, chauhan2024e3ligasesa pages 12-14)
Enzymatic activity / substrate scope	BRCA1-BARD1 is the sole well-established enzymatic activity of BRCA1: a RING E3 ubiquitin ligase whose substrate selectivity depends on E2 usage, substrate context, and intact heterodimerization; ligase-dead separation-of-function mutants impair repair phenotypes in some systems	H2A K125/K127/K129; pCtIP; PCNA; other reported substrates in broader literature include H3 and non-histone repair/cell-cycle proteins	Primary biochemical evidence with some controversy over which phenotypes strictly require ligase activity	Wang 2023 Molecular Cell; Salas-Lloret 2024 Nature Communications	(wang2023crucialrolesof pages 3-5, wang2023crucialrolesof pages 1-3, salaslloret2024brca1bard1ubiquitinatespcna pages 1-2)
Mouse mammary tumor modeling / translational use	Conditional Brca1 deletion in mammary epithelium yields long-latency tumors, while combined Brca1 and Trp53 loss accelerates basal-like mammary tumorigenesis and is widely used as a preclinical TNBC model; recent studies test modifiers such as WWOX, ITGA6, or imaging reporters in these backgrounds	Phenotypes rather than direct substrates; model genotypes include K14-Cre;Brca1fl/fl and Blg-Cre;Brca1F/F;Trp53F/F; imaging study reports minimal residual disease detection sensitivity of ~1000 cells	Primary mouse-model studies and model-focused reviews	Bidany-Mizrahi 2024 Cell Death Discovery; Faraldo 2024 Breast Cancer Research; Steinbauer 2025 NPJ Breast Cancer	(ciringione2025facingthechallenge pages 11-12, carbone2025druggablemolecularnetworks pages 13-15)
Mouse reproductive / oocyte biology	Oocyte-specific Brca1 loss compromises reproductive longevity, indicating a genome-maintenance role outside mammary epithelium; defects become prominent with advanced reproductive age	No specific substrate assigned; phenotype includes reduced litter size, ovarian reserve depletion, and impaired oocyte maturation; in vitro maturation reduced by 45% at PN300 in cKO oocytes	Primary mouse-specific evidence	Winship 2024 eBioMedicine	(winship2024conditionallossof pages 11-13, winship2024conditionallossof pages 2-3, winship2024conditionallossof pages 1-2)
Visual functional summary available	Figure 1A and graphical abstract summarize BRCA1/BARD1 domain organization and the coupling of E3 activity to HDR stages, useful for mapping annotation language to structural modules	Domains shown: RING, coiled-coil, BRCT; substrates include nucleosome/H2A and pCtIP	Figure extracted from primary paper	Wang 2023 Molecular Cell	(wang2023crucialrolesof media 3ac94833, wang2023crucialrolesof media e95b4c78, wang2023crucialrolesof media 352c1d81, wang2023crucialrolesof media 2f74b539)

Table: This table summarizes the main functional axes, mechanisms, substrates, and recent evidence relevant to mouse Brca1/BRCA1 in the UniProt P48754 context. It is designed as a compact reference for drafting a comprehensive, citation-rich annotation report.

Key recent sources (with dates and URLs)

Wang et al. “Crucial roles of the BRCA1-BARD1 E3 ubiquitin ligase activity in homology-directed DNA repair.” Molecular Cell (Oct 2023). https://doi.org/10.1016/j.molcel.2023.09.015 (wang2023crucialrolesof pages 1-3, wang2023crucialrolesof pages 3-5)
Salas‑Lloret et al. “BRCA1/BARD1 ubiquitinates PCNA in unperturbed conditions to promote continuous DNA synthesis.” Nature Communications (May 2024). https://doi.org/10.1038/s41467-024-48427-6 (salaslloret2024brca1bard1ubiquitinatespcna pages 1-2)
Chauhan et al. “E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease.” Biochemical Journal (Jul 2024). https://doi.org/10.1042/bcj20240124 (chauhan2024e3ligasesa pages 12-14)
Winship et al. “Conditional loss of Brca1 in oocytes…” eBioMedicine (Aug 2024). https://doi.org/10.1016/j.ebiom.2024.105262 (winship2024conditionallossof pages 11-13, winship2024conditionallossof pages 2-3)
Steinbauer et al. “Enhanced bioluminescence imaging…” NPJ Breast Cancer (Jul 2025). https://doi.org/10.1038/s41523-025-00795-y (steinbauer2025enhancedbioluminescenceimaging pages 1-2, steinbauer2025enhancedbioluminescenceimaging pages 7-7)

Limitations of the current evidence set

Some desired details (e.g., definitive ubiquitination site(s) on PCNA directly quoted from the primary 2024 paper snippet; explicit UniProt accession P48754 mapping text; absolute tumor-latency values for 2024 mammary conditional models) were not explicitly present in the extracted passages available in this run. Where residue-level claims come from synthesis rather than directly quoted primary text, this is indicated. (salaslloret2024brca1bard1ubiquitinatespcna pages 1-2, durin2024mechanismsgoverningthe pages 49-54)

References

(durin2024mechanismsgoverningthe pages 49-54): MA Durin. Mechanisms governing the functions of brca1-bard1 complexes during dna repair. Unknown journal, 2024.
(wang2023crucialrolesof pages 23-26): Meiling Wang, Wenjing Li, Nozomi Tomimatsu, Corey H. Yu, Jae-Hoon Ji, Salvador Alejo, Samuel R. Witus, Dauren Alimbetov, O’Taveon Fitzgerald, Bo Wu, Qijing Wang, Yuxin Huang, Yaqi Gan, Felix Dong, Youngho Kwon, Gangadhara R. Sareddy, Tyler J. Curiel, Amyn A. Habib, Robert Hromas, Carolina dos Santos Passos, Tingting Yao, Dmitri N. Ivanov, Peter S. Brzovic, Sandeep Burma, Rachel E. Klevit, and Weixing Zhao. Crucial roles of the brca1-bard1 e3 ubiquitin ligase activity in homology-directed dna repair. Molecular Cell, 83:3679-3691.e8, Oct 2023. URL: https://doi.org/10.1016/j.molcel.2023.09.015, doi:10.1016/j.molcel.2023.09.015. This article has 46 citations and is from a highest quality peer-reviewed journal.
(chauhan2024e3ligasesa pages 12-14): Anoop S. Chauhan, Satpal S. Jhujh, and Grant S. Stewart. E3 ligases: a ubiquitous link between dna repair, dna replication and human disease. Biochemical Journal, 481:923-944, Jul 2024. URL: https://doi.org/10.1042/bcj20240124, doi:10.1042/bcj20240124. This article has 18 citations and is from a domain leading peer-reviewed journal.
(moser2025thirtyyearsof pages 3-4): Sarah C. Moser and Jos Jonkers. Thirty years of brca1: mechanistic insights and their impact on mutation carriers. Cancer discovery, 15 3:461-480, Mar 2025. URL: https://doi.org/10.1158/2159-8290.cd-24-1326, doi:10.1158/2159-8290.cd-24-1326. This article has 9 citations and is from a highest quality peer-reviewed journal.
(wang2023crucialrolesof pages 1-3): Meiling Wang, Wenjing Li, Nozomi Tomimatsu, Corey H. Yu, Jae-Hoon Ji, Salvador Alejo, Samuel R. Witus, Dauren Alimbetov, O’Taveon Fitzgerald, Bo Wu, Qijing Wang, Yuxin Huang, Yaqi Gan, Felix Dong, Youngho Kwon, Gangadhara R. Sareddy, Tyler J. Curiel, Amyn A. Habib, Robert Hromas, Carolina dos Santos Passos, Tingting Yao, Dmitri N. Ivanov, Peter S. Brzovic, Sandeep Burma, Rachel E. Klevit, and Weixing Zhao. Crucial roles of the brca1-bard1 e3 ubiquitin ligase activity in homology-directed dna repair. Molecular Cell, 83:3679-3691.e8, Oct 2023. URL: https://doi.org/10.1016/j.molcel.2023.09.015, doi:10.1016/j.molcel.2023.09.015. This article has 46 citations and is from a highest quality peer-reviewed journal.
(wang2023crucialrolesof pages 5-6): Meiling Wang, Wenjing Li, Nozomi Tomimatsu, Corey H. Yu, Jae-Hoon Ji, Salvador Alejo, Samuel R. Witus, Dauren Alimbetov, O’Taveon Fitzgerald, Bo Wu, Qijing Wang, Yuxin Huang, Yaqi Gan, Felix Dong, Youngho Kwon, Gangadhara R. Sareddy, Tyler J. Curiel, Amyn A. Habib, Robert Hromas, Carolina dos Santos Passos, Tingting Yao, Dmitri N. Ivanov, Peter S. Brzovic, Sandeep Burma, Rachel E. Klevit, and Weixing Zhao. Crucial roles of the brca1-bard1 e3 ubiquitin ligase activity in homology-directed dna repair. Molecular Cell, 83:3679-3691.e8, Oct 2023. URL: https://doi.org/10.1016/j.molcel.2023.09.015, doi:10.1016/j.molcel.2023.09.015. This article has 46 citations and is from a highest quality peer-reviewed journal.
(wang2023crucialrolesof pages 21-23): Meiling Wang, Wenjing Li, Nozomi Tomimatsu, Corey H. Yu, Jae-Hoon Ji, Salvador Alejo, Samuel R. Witus, Dauren Alimbetov, O’Taveon Fitzgerald, Bo Wu, Qijing Wang, Yuxin Huang, Yaqi Gan, Felix Dong, Youngho Kwon, Gangadhara R. Sareddy, Tyler J. Curiel, Amyn A. Habib, Robert Hromas, Carolina dos Santos Passos, Tingting Yao, Dmitri N. Ivanov, Peter S. Brzovic, Sandeep Burma, Rachel E. Klevit, and Weixing Zhao. Crucial roles of the brca1-bard1 e3 ubiquitin ligase activity in homology-directed dna repair. Molecular Cell, 83:3679-3691.e8, Oct 2023. URL: https://doi.org/10.1016/j.molcel.2023.09.015, doi:10.1016/j.molcel.2023.09.015. This article has 46 citations and is from a highest quality peer-reviewed journal.
(wang2023crucialrolesof pages 3-5): Meiling Wang, Wenjing Li, Nozomi Tomimatsu, Corey H. Yu, Jae-Hoon Ji, Salvador Alejo, Samuel R. Witus, Dauren Alimbetov, O’Taveon Fitzgerald, Bo Wu, Qijing Wang, Yuxin Huang, Yaqi Gan, Felix Dong, Youngho Kwon, Gangadhara R. Sareddy, Tyler J. Curiel, Amyn A. Habib, Robert Hromas, Carolina dos Santos Passos, Tingting Yao, Dmitri N. Ivanov, Peter S. Brzovic, Sandeep Burma, Rachel E. Klevit, and Weixing Zhao. Crucial roles of the brca1-bard1 e3 ubiquitin ligase activity in homology-directed dna repair. Molecular Cell, 83:3679-3691.e8, Oct 2023. URL: https://doi.org/10.1016/j.molcel.2023.09.015, doi:10.1016/j.molcel.2023.09.015. This article has 46 citations and is from a highest quality peer-reviewed journal.
(moser2025thirtyyearsof pages 24-25): Sarah C. Moser and Jos Jonkers. Thirty years of brca1: mechanistic insights and their impact on mutation carriers. Cancer discovery, 15 3:461-480, Mar 2025. URL: https://doi.org/10.1158/2159-8290.cd-24-1326, doi:10.1158/2159-8290.cd-24-1326. This article has 9 citations and is from a highest quality peer-reviewed journal.
(salaslloret2024brca1bard1ubiquitinatespcna pages 1-2): Daniel Salas-Lloret, Néstor García-Rodríguez, Emily Soto-Hidalgo, Lourdes González-Vinceiro, Carmen Espejo-Serrano, Lisanne Giebel, María Luisa Mateos-Martín, Arnoud H. de Ru, Peter A. van Veelen, Pablo Huertas, Alfred C. O. Vertegaal, and Román González-Prieto. Brca1/bard1 ubiquitinates pcna in unperturbed conditions to promote continuous dna synthesis. Nature Communications, May 2024. URL: https://doi.org/10.1038/s41467-024-48427-6, doi:10.1038/s41467-024-48427-6. This article has 20 citations and is from a highest quality peer-reviewed journal.
(moser2025thirtyyearsof pages 23-24): Sarah C. Moser and Jos Jonkers. Thirty years of brca1: mechanistic insights and their impact on mutation carriers. Cancer discovery, 15 3:461-480, Mar 2025. URL: https://doi.org/10.1158/2159-8290.cd-24-1326, doi:10.1158/2159-8290.cd-24-1326. This article has 9 citations and is from a highest quality peer-reviewed journal.
(ciringione2025facingthechallenge pages 11-12): Alessia Ciringione and Federica Rizzi. Facing the challenge to mimic breast cancer heterogeneity: established and emerging experimental preclinical models integrated with omics technologies. International Journal of Molecular Sciences, 26:4572, May 2025. URL: https://doi.org/10.3390/ijms26104572, doi:10.3390/ijms26104572. This article has 7 citations.
(steinbauer2025enhancedbioluminescenceimaging pages 1-2): Silvia Steinbauer, Jamie D. Cowles, Mohammad Ali Sabbaghi, Marle Poppelaars, Azaz Hussain, Marina Wagesreither, Daniela Laimer-Gruber, Jozsef Tovari, Gergely Szakacs, and Agnes Csiszar. Enhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple-negative breast cancer. NPJ Breast Cancer, Jul 2025. URL: https://doi.org/10.1038/s41523-025-00795-y, doi:10.1038/s41523-025-00795-y. This article has 2 citations and is from a peer-reviewed journal.
(steinbauer2025enhancedbioluminescenceimaging pages 7-7): Silvia Steinbauer, Jamie D. Cowles, Mohammad Ali Sabbaghi, Marle Poppelaars, Azaz Hussain, Marina Wagesreither, Daniela Laimer-Gruber, Jozsef Tovari, Gergely Szakacs, and Agnes Csiszar. Enhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple-negative breast cancer. NPJ Breast Cancer, Jul 2025. URL: https://doi.org/10.1038/s41523-025-00795-y, doi:10.1038/s41523-025-00795-y. This article has 2 citations and is from a peer-reviewed journal.
(steinbauer2025enhancedbioluminescenceimaging pages 4-7): Silvia Steinbauer, Jamie D. Cowles, Mohammad Ali Sabbaghi, Marle Poppelaars, Azaz Hussain, Marina Wagesreither, Daniela Laimer-Gruber, Jozsef Tovari, Gergely Szakacs, and Agnes Csiszar. Enhanced bioluminescence imaging of tumor cells surviving chemotherapy in a murine model of triple-negative breast cancer. NPJ Breast Cancer, Jul 2025. URL: https://doi.org/10.1038/s41523-025-00795-y, doi:10.1038/s41523-025-00795-y. This article has 2 citations and is from a peer-reviewed journal.
(winship2024conditionallossof pages 11-13): Amy L. Winship, Lauren R. Alesi, Jessica M. Stringer, Yujie Cao, Yasmin M. Lewis, Lisa Tu, Elyse O.K. Swindells, Saranya Giridharan, Xuebi Cai, Meaghan J. Griffiths, Nadeen Zerafa, Leslie Gilham, Martha Hickey, and Karla J. Hutt. Conditional loss of brca1 in oocytes causes reduced litter size, ovarian reserve depletion and impaired oocyte in vitro maturation with advanced reproductive age in mice. eBioMedicine, 106:105262, Aug 2024. URL: https://doi.org/10.1016/j.ebiom.2024.105262, doi:10.1016/j.ebiom.2024.105262. This article has 8 citations and is from a peer-reviewed journal.
(winship2024conditionallossof pages 2-3): Amy L. Winship, Lauren R. Alesi, Jessica M. Stringer, Yujie Cao, Yasmin M. Lewis, Lisa Tu, Elyse O.K. Swindells, Saranya Giridharan, Xuebi Cai, Meaghan J. Griffiths, Nadeen Zerafa, Leslie Gilham, Martha Hickey, and Karla J. Hutt. Conditional loss of brca1 in oocytes causes reduced litter size, ovarian reserve depletion and impaired oocyte in vitro maturation with advanced reproductive age in mice. eBioMedicine, 106:105262, Aug 2024. URL: https://doi.org/10.1016/j.ebiom.2024.105262, doi:10.1016/j.ebiom.2024.105262. This article has 8 citations and is from a peer-reviewed journal.
(wang2023crucialrolesof media 3ac94833): Meiling Wang, Wenjing Li, Nozomi Tomimatsu, Corey H. Yu, Jae-Hoon Ji, Salvador Alejo, Samuel R. Witus, Dauren Alimbetov, O’Taveon Fitzgerald, Bo Wu, Qijing Wang, Yuxin Huang, Yaqi Gan, Felix Dong, Youngho Kwon, Gangadhara R. Sareddy, Tyler J. Curiel, Amyn A. Habib, Robert Hromas, Carolina dos Santos Passos, Tingting Yao, Dmitri N. Ivanov, Peter S. Brzovic, Sandeep Burma, Rachel E. Klevit, and Weixing Zhao. Crucial roles of the brca1-bard1 e3 ubiquitin ligase activity in homology-directed dna repair. Molecular Cell, 83:3679-3691.e8, Oct 2023. URL: https://doi.org/10.1016/j.molcel.2023.09.015, doi:10.1016/j.molcel.2023.09.015. This article has 46 citations and is from a highest quality peer-reviewed journal.
(wang2023crucialrolesof media 2f74b539): Meiling Wang, Wenjing Li, Nozomi Tomimatsu, Corey H. Yu, Jae-Hoon Ji, Salvador Alejo, Samuel R. Witus, Dauren Alimbetov, O’Taveon Fitzgerald, Bo Wu, Qijing Wang, Yuxin Huang, Yaqi Gan, Felix Dong, Youngho Kwon, Gangadhara R. Sareddy, Tyler J. Curiel, Amyn A. Habib, Robert Hromas, Carolina dos Santos Passos, Tingting Yao, Dmitri N. Ivanov, Peter S. Brzovic, Sandeep Burma, Rachel E. Klevit, and Weixing Zhao. Crucial roles of the brca1-bard1 e3 ubiquitin ligase activity in homology-directed dna repair. Molecular Cell, 83:3679-3691.e8, Oct 2023. URL: https://doi.org/10.1016/j.molcel.2023.09.015, doi:10.1016/j.molcel.2023.09.015. This article has 46 citations and is from a highest quality peer-reviewed journal.
(nguyen2025overviewofroles pages 6-8): Nhat Nguyen, Dominic Arris, and M. T. Tran. Overview of roles of novel components in the regulation of dna damage repair in brca1-deficient cancers: an update. DNA, Apr 2025. URL: https://doi.org/10.3390/dna5020017, doi:10.3390/dna5020017. This article has 1 citations.
(carbone2025druggablemolecularnetworks pages 13-15): Francesca Pia Carbone, Pietro Ancona, Stefano Volinia, Anna Terrazzan, and Nicoletta Bianchi. Druggable molecular networks in brca1/brca2-mutated breast cancer. Biology, 14:253, Mar 2025. URL: https://doi.org/10.3390/biology14030253, doi:10.3390/biology14030253. This article has 8 citations.
(winship2024conditionallossof pages 1-2): Amy L. Winship, Lauren R. Alesi, Jessica M. Stringer, Yujie Cao, Yasmin M. Lewis, Lisa Tu, Elyse O.K. Swindells, Saranya Giridharan, Xuebi Cai, Meaghan J. Griffiths, Nadeen Zerafa, Leslie Gilham, Martha Hickey, and Karla J. Hutt. Conditional loss of brca1 in oocytes causes reduced litter size, ovarian reserve depletion and impaired oocyte in vitro maturation with advanced reproductive age in mice. eBioMedicine, 106:105262, Aug 2024. URL: https://doi.org/10.1016/j.ebiom.2024.105262, doi:10.1016/j.ebiom.2024.105262. This article has 8 citations and is from a peer-reviewed journal.
(wang2023crucialrolesof media e95b4c78): Meiling Wang, Wenjing Li, Nozomi Tomimatsu, Corey H. Yu, Jae-Hoon Ji, Salvador Alejo, Samuel R. Witus, Dauren Alimbetov, O’Taveon Fitzgerald, Bo Wu, Qijing Wang, Yuxin Huang, Yaqi Gan, Felix Dong, Youngho Kwon, Gangadhara R. Sareddy, Tyler J. Curiel, Amyn A. Habib, Robert Hromas, Carolina dos Santos Passos, Tingting Yao, Dmitri N. Ivanov, Peter S. Brzovic, Sandeep Burma, Rachel E. Klevit, and Weixing Zhao. Crucial roles of the brca1-bard1 e3 ubiquitin ligase activity in homology-directed dna repair. Molecular Cell, 83:3679-3691.e8, Oct 2023. URL: https://doi.org/10.1016/j.molcel.2023.09.015, doi:10.1016/j.molcel.2023.09.015. This article has 46 citations and is from a highest quality peer-reviewed journal.
(wang2023crucialrolesof media 352c1d81): Meiling Wang, Wenjing Li, Nozomi Tomimatsu, Corey H. Yu, Jae-Hoon Ji, Salvador Alejo, Samuel R. Witus, Dauren Alimbetov, O’Taveon Fitzgerald, Bo Wu, Qijing Wang, Yuxin Huang, Yaqi Gan, Felix Dong, Youngho Kwon, Gangadhara R. Sareddy, Tyler J. Curiel, Amyn A. Habib, Robert Hromas, Carolina dos Santos Passos, Tingting Yao, Dmitri N. Ivanov, Peter S. Brzovic, Sandeep Burma, Rachel E. Klevit, and Weixing Zhao. Crucial roles of the brca1-bard1 e3 ubiquitin ligase activity in homology-directed dna repair. Molecular Cell, 83:3679-3691.e8, Oct 2023. URL: https://doi.org/10.1016/j.molcel.2023.09.015, doi:10.1016/j.molcel.2023.09.015. This article has 46 citations and is from a highest quality peer-reviewed journal.

Citations

wang2023crucialrolesof pages 5-6
wang2023crucialrolesof pages 1-3
durin2024mechanismsgoverningthe pages 49-54
wang2023crucialrolesof pages 3-5
moser2025thirtyyearsof pages 24-25
wang2023crucialrolesof pages 21-23
moser2025thirtyyearsof pages 3-4
ciringione2025facingthechallenge pages 11-12
steinbauer2025enhancedbioluminescenceimaging pages 4-7
wang2023crucialrolesof pages 23-26
moser2025thirtyyearsof pages 23-24
steinbauer2025enhancedbioluminescenceimaging pages 1-2
steinbauer2025enhancedbioluminescenceimaging pages 7-7
winship2024conditionallossof pages 11-13
winship2024conditionallossof pages 2-3
nguyen2025overviewofroles pages 6-8
carbone2025druggablemolecularnetworks pages 13-15
winship2024conditionallossof pages 1-2
https://doi.org/10.1038/s41467-024-48427-6
https://doi.org/10.1038/s41523-025-00795-y
https://doi.org/10.1016/j.ebiom.2024.105262
https://doi.org/10.1016/j.molcel.2023.09.015
https://doi.org/10.1042/bcj20240124
https://doi.org/10.1016/j.molcel.2023.09.015,
https://doi.org/10.1042/bcj20240124,
https://doi.org/10.1158/2159-8290.cd-24-1326,
https://doi.org/10.1038/s41467-024-48427-6,
https://doi.org/10.3390/ijms26104572,
https://doi.org/10.1038/s41523-025-00795-y,
https://doi.org/10.1016/j.ebiom.2024.105262,
https://doi.org/10.3390/dna5020017,
https://doi.org/10.3390/biology14030253,

📄 View Raw YAML

id: P48754
gene_symbol: Brca1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:10090
  label: Mus musculus
description: Brca1 encodes the mouse homolog of BRCA1, a nuclear genome-maintenance protein. Its primary roles are as a BARD1-associated RING E3 ubiquitin ligase and as a DNA-damage response scaffold that promotes homologous recombination, DNA end resection, repair-checkpoint control, and replication-associated genome stability. Transcriptional, metabolic, centrosomal, and developmental annotations are interpreted as secondary contexts unless directly tied to DNA repair or BRCA1-BARD1 ubiquitin ligase activity.
existing_annotations:
- term:
    id: GO:0000724
    label: double-strand break repair via homologous recombination
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: BRCA1-BARD1 channels DSB repair toward homologous recombination by promoting end resection and PALB2-BRCA2-RAD51 loading at resected breaks.
    action: ACCEPT
    reason: Central, defining biological role of BRCA1; broadly supported (IBA/ISO and mechanistic literature).
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0007095
    label: mitotic G2 DNA damage checkpoint signaling
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: BRCA1 signals the G2 DNA-damage checkpoint, with BRCA1-mediated RBBP8 ubiquitination regulating CHEK1 activation after damage.
    action: ACCEPT
    reason: Core checkpoint role tied to BRCA1's repair function; IBA/ISO support.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Core catalytic activity: BRCA1, as the BRCA1-BARD1 RING heterodimer, accelerates ubiquitin transfer from charged E2~Ub onto substrate lysines (e.g. nucleosomal H2A, CtIP, PCNA) at sites of DNA damage.'
    action: ACCEPT
    reason: Defining molecular function of BRCA1 (EC 2.3.2.27); supported across IBA/ISO/ISS and the BRCA1-BARD1 mechanistic literature.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0031436
    label: BRCA1-BARD1 complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Obligate RING-RING heterodimer with BARD1 that constitutes the active E3 ligase; this assembly underlies essentially all BRCA1 catalytic and DNA-repair functions.
    action: ACCEPT
    reason: Defining functional complex of BRCA1; documented in SUBUNIT and the core mechanistic literature.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0043009
    label: chordate embryonic development
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Brca1 is required for embryonic development, with knockouts being embryonic lethal owing to defective proliferation and genome instability.
    action: KEEP_AS_NON_CORE
    reason: Developmental phenotype downstream of BRCA1's essential genome-maintenance role.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Acts as a transcriptional activator at specific target genes, a regulatory output separable from its repair function.
    action: KEEP_AS_NON_CORE
    reason: Activator role pleiotropic relative to core repair function.
- term:
    id: GO:0070531
    label: BRCA1-A complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: Component of the BRCA1-A complex (with RAP80/UIMC1, ABRAXAS1, BRCC36, BABAM1/2) that recognizes K63-ubiquitin chains and recruits BRCA1 to DNA double-strand-break sites.
    action: ACCEPT
    reason: Bona fide repair-targeting complex central to BRCA1 recruitment; supported by SUBUNIT and IBA/ISO.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0003677
    label: DNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Generic DNA-binding term; BRCA1 acts on damaged chromatin via complexes rather than as a sequence-specific DNA binder, so the bare term over-states a direct activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: Broad IEA MF; BRCA1's chromatin/damage engagement is captured by more specific terms.
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: 'Core catalytic activity: BRCA1, as the BRCA1-BARD1 RING heterodimer, accelerates ubiquitin transfer from charged E2~Ub onto substrate lysines (e.g. nucleosomal H2A, CtIP, PCNA) at sites of DNA damage.'
    action: ACCEPT
    reason: Defining molecular function of BRCA1 (EC 2.3.2.27); supported across IBA/ISO/ISS and the BRCA1-BARD1 mechanistic literature.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: BRCA1 acts predominantly in the nucleus, forming DNA-damage-induced foci on chromatin where it carries out repair and checkpoint functions.
    action: ACCEPT
    reason: Primary site of BRCA1 action; UniProt SUBCELLULAR LOCATION and IDA support.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005694
    label: chromosome
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: BRCA1 localizes to chromosomes/chromatin, where the BRCA1-BARD1 ligase modifies nucleosomal H2A at break sites.
    action: ACCEPT
    reason: Direct chromatin association is core to BRCA1 function; IDA supported.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Cytoplasmic pool seen e.g. on translocation during UV-induced apoptosis and ACACA binding; not the principal site of repair function.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization; BRCA1 acts mainly in the nucleus.
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: BRCA1 facilitates cellular responses to DNA damage and is required for FANCD2 targeting and homology-directed repair, maintaining genome integrity.
    action: ACCEPT
    reason: Core function captured directly in UniProt FUNCTION.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0006310
    label: DNA recombination
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Broad recombination term encompassing BRCA1's HR role; the specific homologous-recombination/DSB terms capture the core activity more precisely.
    action: KEEP_AS_NON_CORE
    reason: General parent process; specific HR terms are the core annotations.
- term:
    id: GO:0006351
    label: DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Participation in DNA-templated transcription, reflecting BRCA1's accessory transcriptional roles rather than its repair core.
    action: KEEP_AS_NON_CORE
    reason: Broad transcription process not tied to the core repair function.
- term:
    id: GO:0006629
    label: lipid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: General lipid-metabolism involvement stemming from BRCA1's inhibition of ACACA-driven lipogenesis.
    action: KEEP_AS_NON_CORE
    reason: Very broad metabolic term secondary to the ACACA moonlighting role.
- term:
    id: GO:0006631
    label: fatty acid metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Broadly impinges on fatty-acid metabolism via ACACA regulation, a moonlighting metabolic role.
    action: KEEP_AS_NON_CORE
    reason: Broad metabolic term downstream of the ACACA-binding role.
- term:
    id: GO:0006633
    label: fatty acid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Influences fatty-acid biosynthesis through its inhibitory ACACA interaction, a metabolic role peripheral to genome maintenance.
    action: KEEP_AS_NON_CORE
    reason: Metabolic-pathway association secondary to core function.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: BRCA1 coordinates the DNA-damage response, being phosphorylated by ATM/ATR and assembling repair/checkpoint complexes at break sites.
    action: ACCEPT
    reason: Core DDR role; IMP-supported and central to BRCA1 biology.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0008270
    label: zinc ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Zinc coordination by the N-terminal RING-type finger that structurally enables BARD1 heterodimerization and E3 activity.
    action: KEEP_AS_NON_CORE
    reason: Structural cofactor binding underpinning, but not equivalent to, the core ligase MF.
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: Generic transferase parent; BRCA1's actual activity is the specific RING-type ubiquitin-protein transferase function of the BRCA1-BARD1 heterodimer.
    action: MODIFY
    reason: IEA parent term too broad; replace with the specific ubiquitin-protein transferase activity child.
    proposed_replacement_terms:
    - id: GO:0004842
      label: ubiquitin-protein transferase activity
- term:
    id: GO:0046872
    label: metal ion binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: Generic metal-binding rollup of the RING zinc-coordination; the functionally meaningful aspect is the RING E3 activity, not metal binding per se.
    action: MARK_AS_OVER_ANNOTATED
    reason: Keyword-derived broad MF superseded by the specific ligase and zinc-finger terms.
- term:
    id: GO:0061630
    label: ubiquitin protein ligase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000003
  review:
    summary: BRCA1-BARD1 RING E3 ligase activity that promotes site-specific (mono)ubiquitination and K6-linked autoubiquitination, coupling enzymatic output to DNA-damage repair pathway choice.
    action: ACCEPT
    reason: Synonymous core E3-ligase MF; mechanistically established for the BRCA1-BARD1 heterodimer.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0070013
    label: intracellular organelle lumen
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: Very broad luminal compartment term that adds nothing beyond the specific nuclear/nucleoplasm localizations.
    action: MARK_AS_OVER_ANNOTATED
    reason: Over-broad CC superseded by nucleus/nucleoplasm.
- term:
    id: GO:0000724
    label: double-strand break repair via homologous recombination
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: BRCA1-BARD1 channels DSB repair toward homologous recombination by promoting end resection and PALB2-BRCA2-RAD51 loading at resected breaks.
    action: ACCEPT
    reason: Central, defining biological role of BRCA1; broadly supported (IBA/ISO and mechanistic literature).
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0000800
    label: lateral element
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Meiotic synaptonemal-complex lateral-element localization tied to BRCA1's role in meiotic chromosome surveillance.
    action: KEEP_AS_NON_CORE
    reason: Meiosis-specific localization, a specialized context of genome maintenance.
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Binds cis-regulatory regions consistent with BRCA1's transcriptional-regulation activities at target promoters.
    action: KEEP_AS_NON_CORE
    reason: Transcription-associated DNA binding, secondary to repair role.
- term:
    id: GO:0002039
    label: p53 binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Specific binding assertion that, alone, captures a partnership rather than a BRCA1 molecular function and is electronic-only here.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative bare-binding MF; any p53-linked role is downstream and not the core function.
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: BRCA1 can act as a transcriptional coactivator, a regulatory role secondary to and intertwined with its genome-maintenance function.
    action: KEEP_AS_NON_CORE
    reason: Transcription role not the core repair/ligase function; keep as non-core.
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Reported RNA-binding activity linked to transcription-coupled and RNA-associated functions rather than the core E3/repair role.
    action: KEEP_AS_NON_CORE
    reason: Ancillary nucleic-acid binding; not the defining function.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities.
    action: ACCEPT
    reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Minor plasma-membrane-associated pool reported electronically; peripheral to BRCA1's nuclear repair activity.
    action: KEEP_AS_NON_CORE
    reason: Non-core secondary localization with electronic support only.
- term:
    id: GO:0006301
    label: DNA damage tolerance
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Via BRCA1-BARD1 ubiquitination of PCNA in unperturbed conditions, BRCA1 supports continuous DNA synthesis and suppresses ssDNA-gap accumulation, aiding tolerance of replication stress.
    action: ACCEPT
    reason: Supported by recent PCNA-ubiquitination/fork-protection findings tied to BRCA1's E3 activity.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0006302
    label: double-strand break repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: BRCA1 is a key effector of double-strand-break repair, biasing pathway choice away from NHEJ via H2A ubiquitination and 53BP1 repositioning.
    action: ACCEPT
    reason: Core DSB-repair role; IMP plus electronic support.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Regulates Pol II transcription through coactivator and partner (LMO4/CCAR2) interactions, a pleiotropic role beyond DNA repair.
    action: KEEP_AS_NON_CORE
    reason: Transcriptional regulation secondary to BRCA1's core repair/ligase role.
- term:
    id: GO:0007059
    label: chromosome segregation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Supports faithful chromosome segregation, a downstream consequence of BRCA1-maintained genome integrity and checkpoint control.
    action: KEEP_AS_NON_CORE
    reason: Mitotic-fidelity outcome downstream of the core repair/checkpoint role.
- term:
    id: GO:0007095
    label: mitotic G2 DNA damage checkpoint signaling
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: BRCA1 signals the G2 DNA-damage checkpoint, with BRCA1-mediated RBBP8 ubiquitination regulating CHEK1 activation after damage.
    action: ACCEPT
    reason: Core checkpoint role tied to BRCA1's repair function; IBA/ISO support.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0010212
    label: response to ionizing radiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Responds to ionizing radiation as part of damage signaling, an upstream stimulus context of the repair function.
    action: KEEP_AS_NON_CORE
    reason: Response-to-stimulus term contextual to the core DDR role.
- term:
    id: GO:0010575
    label: positive regulation of vascular endothelial growth factor production
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Linked to upregulating VEGF production, a downstream gene-expression output rather than a core activity.
    action: KEEP_AS_NON_CORE
    reason: Growth-factor-production role pleiotropic to core function.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Broadly upregulates expression of target genes via its transcriptional-activator activity.
    action: KEEP_AS_NON_CORE
    reason: Generic expression-regulation role downstream of transcription activity.
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: BRCA1-BARD1 mediates protein ubiquitination of chromatin and repair substrates as its central biochemical activity.
    action: ACCEPT
    reason: Core ubiquitination function; the specific K6/autoubiquitination children are also annotated.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0016604
    label: nuclear body
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Localization to nuclear bodies, a sub-nuclear focus consistent with damage-induced assembly but not itself a defining site.
    action: KEEP_AS_NON_CORE
    reason: Sub-nuclear localization secondary to the core nuclear/chromatin sites.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Non-specific enzyme-binding term that conveys nothing about which enzyme or what BRCA1 does with it.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative binding MF; specific partner roles are captured elsewhere.
- term:
    id: GO:0030308
    label: negative regulation of cell growth
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Tumor-suppressor-associated growth restraint, a downstream physiological consequence of intact BRCA1 genome maintenance.
    action: KEEP_AS_NON_CORE
    reason: Growth-suppression phenotype downstream of the core repair role.
- term:
    id: GO:0031436
    label: BRCA1-BARD1 complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Obligate RING-RING heterodimer with BARD1 that constitutes the active E3 ligase; this assembly underlies essentially all BRCA1 catalytic and DNA-repair functions.
    action: ACCEPT
    reason: Defining functional complex of BRCA1; documented in SUBUNIT and the core mechanistic literature.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Generic 'binds an E3 ligase' term that is uninformative for a protein that is itself the E3 ligase.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare-binding MF adding no functional specificity beyond BRCA1's own catalytic terms.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Root-level complex term superseded by the specific BRCA1-BARD1 and BRCA1-A/B/C complex annotations.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative generic CC; specific complexes are annotated.
- term:
    id: GO:0033147
    label: negative regulation of intracellular estrogen receptor signaling pathway
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Represses estrogen-receptor signaling, a hormone-pathway regulatory role pertinent to mammary biology but secondary to repair.
    action: KEEP_AS_NON_CORE
    reason: Hormone-signaling regulation pleiotropic to core function.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Generic self-association term that does not capture BRCA1's heterodimeric-with-BARD1 mode of action or any specific function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative bare-binding MF; BRCA1's functional partnerships are captured by specific complex terms.
- term:
    id: GO:0045717
    label: negative regulation of fatty acid biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Inhibits fatty-acid synthesis by binding inactive phosphorylated ACACA and preventing its dephosphorylation, a distinct metabolic moonlighting role.
    action: KEEP_AS_NON_CORE
    reason: Specific lipid-regulatory function via ACACA, separate from the core repair role.
- term:
    id: GO:0045739
    label: positive regulation of DNA repair
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: BRCA1 positively promotes homology-directed DNA repair by enabling resection and RAD51 loading at damage sites.
    action: ACCEPT
    reason: Core pro-repair activity; consistent with FUNCTION.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0045766
    label: positive regulation of angiogenesis
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Reported promotion of angiogenesis, a tissue-level role far downstream of BRCA1's molecular repair function.
    action: KEEP_AS_NON_CORE
    reason: Angiogenic role pleiotropic and electronic-only.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Can repress transcription at certain targets (e.g. via LMO4/CCAR2-modulated activity), a context-specific regulatory role.
    action: KEEP_AS_NON_CORE
    reason: Transcriptional repression not part of the core repair function.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Promotes transcription of subsets of target genes as a transcriptional activator, secondary to genome-maintenance roles.
    action: KEEP_AS_NON_CORE
    reason: Activator output pleiotropic relative to core function.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Acts as a transcriptional activator at specific target genes, a regulatory output separable from its repair function.
    action: KEEP_AS_NON_CORE
    reason: Activator role pleiotropic relative to core repair function.
- term:
    id: GO:0051865
    label: protein autoubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: BRCA1 undergoes K6-linked autoubiquitination that does not promote degradation, reflecting its intrinsic E3 ligase activity.
    action: ACCEPT
    reason: Documented BRCA1 PTM/activity; core to its enzymatic characterization.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0070063
    label: RNA polymerase binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Associates with the RNA polymerase II holoenzyme (via DHX9), underpinning BRCA1's transcriptional-regulation activity.
    action: KEEP_AS_NON_CORE
    reason: Transcription-machinery interaction secondary to repair/ligase function.
- term:
    id: GO:0070531
    label: BRCA1-A complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Component of the BRCA1-A complex (with RAP80/UIMC1, ABRAXAS1, BRCC36, BABAM1/2) that recognizes K63-ubiquitin chains and recruits BRCA1 to DNA double-strand-break sites.
    action: ACCEPT
    reason: Bona fide repair-targeting complex central to BRCA1 recruitment; supported by SUBUNIT and IBA/ISO.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0071356
    label: cellular response to tumor necrosis factor
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Participates in the cellular response to TNF, a signaling-context role distinct from BRCA1's repair catalysis.
    action: KEEP_AS_NON_CORE
    reason: Cytokine-response context, not the core function.
- term:
    id: GO:0071479
    label: cellular response to ionizing radiation
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Mediates the cellular response to ionizing radiation, with BRCA1 phosphorylated and required for IR-induced S/G2 arrest.
    action: KEEP_AS_NON_CORE
    reason: Stress-response context of BRCA1's core DDR/checkpoint role.
- term:
    id: GO:0071681
    label: cellular response to indole-3-methanol
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Reported response to indole-3-methanol, a chemical-stimulus context secondary to BRCA1's core activities.
    action: KEEP_AS_NON_CORE
    reason: Specific chemical-response context, non-core.
- term:
    id: GO:0085020
    label: protein K6-linked ubiquitination
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: BRCA1-BARD1 specifically catalyzes 'Lys-6'-linked polyubiquitin chains, a hallmark non-degradative linkage of this E3 ligase.
    action: ACCEPT
    reason: Signature catalytic output of BRCA1 stated explicitly in UniProt FUNCTION/PTM.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:1902042
    label: negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Modulates death-receptor extrinsic apoptotic signaling, a cell-fate role separable from direct repair catalysis.
    action: KEEP_AS_NON_CORE
    reason: Apoptosis-modulation role pleiotropic to core function.
- term:
    id: GO:1990904
    label: ribonucleoprotein complex
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Association with RNP/RNA-containing complexes linked to BRCA1's reported RNA binding and transcription-coupled roles.
    action: KEEP_AS_NON_CORE
    reason: Peripheral complex membership downstream of transcription-associated activity.
- term:
    id: GO:2000378
    label: negative regulation of reactive oxygen species metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: Limits ROS accumulation, an antioxidant/redox-protective role downstream of BRCA1-maintained genome and metabolic homeostasis.
    action: KEEP_AS_NON_CORE
    reason: Redox-regulation role pleiotropic to the core repair function.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: BRCA1 acts predominantly in the nucleus, forming DNA-damage-induced foci on chromatin where it carries out repair and checkpoint functions.
    action: ACCEPT
    reason: Primary site of BRCA1 action; UniProt SUBCELLULAR LOCATION and IDA support.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0000152
    label: nuclear ubiquitin ligase complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: BRCA1-BARD1 constitutes a nuclear ubiquitin ligase complex that ubiquitinates chromatin and repair-factor substrates at damage sites.
    action: ACCEPT
    reason: Accurately captures the nuclear E3-ligase nature of the BRCA1-BARD1 heterodimer.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0000724
    label: double-strand break repair via homologous recombination
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: BRCA1-BARD1 channels DSB repair toward homologous recombination by promoting end resection and PALB2-BRCA2-RAD51 loading at resected breaks.
    action: ACCEPT
    reason: Central, defining biological role of BRCA1; broadly supported (IBA/ISO and mechanistic literature).
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Binds cis-regulatory regions consistent with BRCA1's transcriptional-regulation activities at target promoters.
    action: KEEP_AS_NON_CORE
    reason: Transcription-associated DNA binding, secondary to repair role.
- term:
    id: GO:0002039
    label: p53 binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Specific binding assertion that, alone, captures a partnership rather than a BRCA1 molecular function and is electronic-only here.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative bare-binding MF; any p53-linked role is downstream and not the core function.
- term:
    id: GO:0003682
    label: chromatin binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: BRCA1-BARD1 engages chromatin (via BARD1 reading of H4K20me0 / H2AK15ub) to target its E3 activity to damaged nucleosomes.
    action: ACCEPT
    reason: Chromatin engagement is mechanistically central to BRCA1's repair role.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: BRCA1 can act as a transcriptional coactivator, a regulatory role secondary to and intertwined with its genome-maintenance function.
    action: KEEP_AS_NON_CORE
    reason: Transcription role not the core repair/ligase function; keep as non-core.
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: 'Core catalytic activity: BRCA1, as the BRCA1-BARD1 RING heterodimer, accelerates ubiquitin transfer from charged E2~Ub onto substrate lysines (e.g. nucleosomal H2A, CtIP, PCNA) at sites of DNA damage.'
    action: ACCEPT
    reason: Defining molecular function of BRCA1 (EC 2.3.2.27); supported across IBA/ISO/ISS and the BRCA1-BARD1 mechanistic literature.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities.
    action: ACCEPT
    reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Cytoplasmic pool seen e.g. on translocation during UV-induced apoptosis and ACACA binding; not the principal site of repair function.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization; BRCA1 acts mainly in the nucleus.
- term:
    id: GO:0005759
    label: mitochondrial matrix
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Reported mitochondrial-matrix pool implicated in mitochondrial genome maintenance, distinct from the dominant nuclear role.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization downstream of BRCA1's genome-maintenance function.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Minor plasma-membrane-associated pool reported electronically; peripheral to BRCA1's nuclear repair activity.
    action: KEEP_AS_NON_CORE
    reason: Non-core secondary localization with electronic support only.
- term:
    id: GO:0006301
    label: DNA damage tolerance
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Via BRCA1-BARD1 ubiquitination of PCNA in unperturbed conditions, BRCA1 supports continuous DNA synthesis and suppresses ssDNA-gap accumulation, aiding tolerance of replication stress.
    action: ACCEPT
    reason: Supported by recent PCNA-ubiquitination/fork-protection findings tied to BRCA1's E3 activity.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0006302
    label: double-strand break repair
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: BRCA1 is a key effector of double-strand-break repair, biasing pathway choice away from NHEJ via H2A ubiquitination and 53BP1 repositioning.
    action: ACCEPT
    reason: Core DSB-repair role; IMP plus electronic support.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Regulates Pol II transcription through coactivator and partner (LMO4/CCAR2) interactions, a pleiotropic role beyond DNA repair.
    action: KEEP_AS_NON_CORE
    reason: Transcriptional regulation secondary to BRCA1's core repair/ligase role.
- term:
    id: GO:0007059
    label: chromosome segregation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Supports faithful chromosome segregation, a downstream consequence of BRCA1-maintained genome integrity and checkpoint control.
    action: KEEP_AS_NON_CORE
    reason: Mitotic-fidelity outcome downstream of the core repair/checkpoint role.
- term:
    id: GO:0007095
    label: mitotic G2 DNA damage checkpoint signaling
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: BRCA1 signals the G2 DNA-damage checkpoint, with BRCA1-mediated RBBP8 ubiquitination regulating CHEK1 activation after damage.
    action: ACCEPT
    reason: Core checkpoint role tied to BRCA1's repair function; IBA/ISO support.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0010212
    label: response to ionizing radiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Responds to ionizing radiation as part of damage signaling, an upstream stimulus context of the repair function.
    action: KEEP_AS_NON_CORE
    reason: Response-to-stimulus term contextual to the core DDR role.
- term:
    id: GO:0010575
    label: positive regulation of vascular endothelial growth factor production
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Linked to upregulating VEGF production, a downstream gene-expression output rather than a core activity.
    action: KEEP_AS_NON_CORE
    reason: Growth-factor-production role pleiotropic to core function.
- term:
    id: GO:0010628
    label: positive regulation of gene expression
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Broadly upregulates expression of target genes via its transcriptional-activator activity.
    action: KEEP_AS_NON_CORE
    reason: Generic expression-regulation role downstream of transcription activity.
- term:
    id: GO:0016567
    label: protein ubiquitination
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: BRCA1-BARD1 mediates protein ubiquitination of chromatin and repair substrates as its central biochemical activity.
    action: ACCEPT
    reason: Core ubiquitination function; the specific K6/autoubiquitination children are also annotated.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0016604
    label: nuclear body
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Localization to nuclear bodies, a sub-nuclear focus consistent with damage-induced assembly but not itself a defining site.
    action: KEEP_AS_NON_CORE
    reason: Sub-nuclear localization secondary to the core nuclear/chromatin sites.
- term:
    id: GO:0019899
    label: enzyme binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Non-specific enzyme-binding term that conveys nothing about which enzyme or what BRCA1 does with it.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative binding MF; specific partner roles are captured elsewhere.
- term:
    id: GO:0030308
    label: negative regulation of cell growth
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Tumor-suppressor-associated growth restraint, a downstream physiological consequence of intact BRCA1 genome maintenance.
    action: KEEP_AS_NON_CORE
    reason: Growth-suppression phenotype downstream of the core repair role.
- term:
    id: GO:0031436
    label: BRCA1-BARD1 complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Obligate RING-RING heterodimer with BARD1 that constitutes the active E3 ligase; this assembly underlies essentially all BRCA1 catalytic and DNA-repair functions.
    action: ACCEPT
    reason: Defining functional complex of BRCA1; documented in SUBUNIT and the core mechanistic literature.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0031625
    label: ubiquitin protein ligase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic 'binds an E3 ligase' term that is uninformative for a protein that is itself the E3 ligase.
    action: MARK_AS_OVER_ANNOTATED
    reason: Bare-binding MF adding no functional specificity beyond BRCA1's own catalytic terms.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Root-level complex term superseded by the specific BRCA1-BARD1 and BRCA1-A/B/C complex annotations.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative generic CC; specific complexes are annotated.
- term:
    id: GO:0033147
    label: negative regulation of intracellular estrogen receptor signaling pathway
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Represses estrogen-receptor signaling, a hormone-pathway regulatory role pertinent to mammary biology but secondary to repair.
    action: KEEP_AS_NON_CORE
    reason: Hormone-signaling regulation pleiotropic to core function.
- term:
    id: GO:0042307
    label: positive regulation of protein import into nucleus
  evidence_type: ISO
  original_reference_id: GO_REF:0000096
  review:
    summary: Promotes nuclear import of partner proteins, an ancillary trafficking role peripheral to repair catalysis.
    action: KEEP_AS_NON_CORE
    reason: Partner-trafficking role not part of the core function.
- term:
    id: GO:0042802
    label: identical protein binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic self-association term that does not capture BRCA1's heterodimeric-with-BARD1 mode of action or any specific function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative bare-binding MF; BRCA1's functional partnerships are captured by specific complex terms.
- term:
    id: GO:0044027
    label: negative regulation of gene expression via chromosomal CpG island methylation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Linked to silencing of genes via CpG-island methylation, an epigenetic regulatory role distinct from direct repair.
    action: KEEP_AS_NON_CORE
    reason: Epigenetic gene-silencing role pleiotropic to core function.
- term:
    id: GO:0045717
    label: negative regulation of fatty acid biosynthetic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Inhibits fatty-acid synthesis by binding inactive phosphorylated ACACA and preventing its dephosphorylation, a distinct metabolic moonlighting role.
    action: KEEP_AS_NON_CORE
    reason: Specific lipid-regulatory function via ACACA, separate from the core repair role.
- term:
    id: GO:0045739
    label: positive regulation of DNA repair
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: BRCA1 positively promotes homology-directed DNA repair by enabling resection and RAD51 loading at damage sites.
    action: ACCEPT
    reason: Core pro-repair activity; consistent with FUNCTION.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0045766
    label: positive regulation of angiogenesis
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Reported promotion of angiogenesis, a tissue-level role far downstream of BRCA1's molecular repair function.
    action: KEEP_AS_NON_CORE
    reason: Angiogenic role pleiotropic and electronic-only.
- term:
    id: GO:0045892
    label: negative regulation of DNA-templated transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Can repress transcription at certain targets (e.g. via LMO4/CCAR2-modulated activity), a context-specific regulatory role.
    action: KEEP_AS_NON_CORE
    reason: Transcriptional repression not part of the core repair function.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Promotes transcription of subsets of target genes as a transcriptional activator, secondary to genome-maintenance roles.
    action: KEEP_AS_NON_CORE
    reason: Activator output pleiotropic relative to core function.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Acts as a transcriptional activator at specific target genes, a regulatory output separable from its repair function.
    action: KEEP_AS_NON_CORE
    reason: Activator role pleiotropic relative to core repair function.
- term:
    id: GO:0051726
    label: regulation of cell cycle
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Broad cell-cycle regulation reflecting BRCA1's checkpoint-control activities after DNA damage.
    action: KEEP_AS_NON_CORE
    reason: General cell-cycle regulation downstream of checkpoint signaling.
- term:
    id: GO:0051865
    label: protein autoubiquitination
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: BRCA1 undergoes K6-linked autoubiquitination that does not promote degradation, reflecting its intrinsic E3 ligase activity.
    action: ACCEPT
    reason: Documented BRCA1 PTM/activity; core to its enzymatic characterization.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0070063
    label: RNA polymerase binding
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Associates with the RNA polymerase II holoenzyme (via DHX9), underpinning BRCA1's transcriptional-regulation activity.
    action: KEEP_AS_NON_CORE
    reason: Transcription-machinery interaction secondary to repair/ligase function.
- term:
    id: GO:0070531
    label: BRCA1-A complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Component of the BRCA1-A complex (with RAP80/UIMC1, ABRAXAS1, BRCC36, BABAM1/2) that recognizes K63-ubiquitin chains and recruits BRCA1 to DNA double-strand-break sites.
    action: ACCEPT
    reason: Bona fide repair-targeting complex central to BRCA1 recruitment; supported by SUBUNIT and IBA/ISO.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0070532
    label: BRCA1-B complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Component of the BRCA1-B complex (BRCA1-BARD1 with BACH1/BRIP1 and TOPBP1) linking BRCA1 to replication-associated DNA repair.
    action: ACCEPT
    reason: Recognized BRCA1-defined repair complex; consistent with BRCT-BRIP1 interaction in SUBUNIT.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0070533
    label: BRCA1-C complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Component of the BRCA1-C complex (BRCA1-BARD1 with CtIP/RBBP8 and the MRN complex) that promotes DNA end resection committing breaks to homologous recombination.
    action: ACCEPT
    reason: Established BRCA1 resection complex; consistent with BRCA1-RBBP8 interaction in SUBUNIT.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0071356
    label: cellular response to tumor necrosis factor
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Participates in the cellular response to TNF, a signaling-context role distinct from BRCA1's repair catalysis.
    action: KEEP_AS_NON_CORE
    reason: Cytokine-response context, not the core function.
- term:
    id: GO:0071479
    label: cellular response to ionizing radiation
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Mediates the cellular response to ionizing radiation, with BRCA1 phosphorylated and required for IR-induced S/G2 arrest.
    action: KEEP_AS_NON_CORE
    reason: Stress-response context of BRCA1's core DDR/checkpoint role.
- term:
    id: GO:0071681
    label: cellular response to indole-3-methanol
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Reported response to indole-3-methanol, a chemical-stimulus context secondary to BRCA1's core activities.
    action: KEEP_AS_NON_CORE
    reason: Specific chemical-response context, non-core.
- term:
    id: GO:0085020
    label: protein K6-linked ubiquitination
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: BRCA1-BARD1 specifically catalyzes 'Lys-6'-linked polyubiquitin chains, a hallmark non-degradative linkage of this E3 ligase.
    action: ACCEPT
    reason: Signature catalytic output of BRCA1 stated explicitly in UniProt FUNCTION/PTM.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:1902042
    label: negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Modulates death-receptor extrinsic apoptotic signaling, a cell-fate role separable from direct repair catalysis.
    action: KEEP_AS_NON_CORE
    reason: Apoptosis-modulation role pleiotropic to core function.
- term:
    id: GO:1990391
    label: DNA repair complex
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Generic membership in a DNA-repair complex; the specific BRCA1-defined complexes (BRCA1-BARD1/A/B/C) capture this more precisely.
    action: KEEP_AS_NON_CORE
    reason: Broad complex term subordinate to the specific BRCA1 complexes already annotated.
- term:
    id: GO:2000378
    label: negative regulation of reactive oxygen species metabolic process
  evidence_type: ISO
  original_reference_id: GO_REF:0000119
  review:
    summary: Limits ROS accumulation, an antioxidant/redox-protective role downstream of BRCA1-maintained genome and metabolic homeostasis.
    action: KEEP_AS_NON_CORE
    reason: Redox-regulation role pleiotropic to the core repair function.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:18171670
  review:
    summary: BRCA1 acts predominantly in the nucleus, forming DNA-damage-induced foci on chromatin where it carries out repair and checkpoint functions.
    action: ACCEPT
    reason: Primary site of BRCA1 action; UniProt SUBCELLULAR LOCATION and IDA support.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:20656689
  review:
    summary: BRCA1 acts predominantly in the nucleus, forming DNA-damage-induced foci on chromatin where it carries out repair and checkpoint functions.
    action: ACCEPT
    reason: Primary site of BRCA1 action; UniProt SUBCELLULAR LOCATION and IDA support.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: NAS
  original_reference_id: PMID:22369660
  review:
    summary: BRCA1 acts predominantly in the nucleus, forming DNA-damage-induced foci on chromatin where it carries out repair and checkpoint functions.
    action: ACCEPT
    reason: Primary site of BRCA1 action; UniProt SUBCELLULAR LOCATION and IDA support.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0006281
    label: DNA repair
  evidence_type: NAS
  original_reference_id: PMID:22369660
  review:
    summary: BRCA1 facilitates cellular responses to DNA damage and is required for FANCD2 targeting and homology-directed repair, maintaining genome integrity.
    action: ACCEPT
    reason: Core function captured directly in UniProt FUNCTION.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0006282
    label: regulation of DNA repair
  evidence_type: NAS
  original_reference_id: PMID:20656689
  review:
    summary: BRCA1 regulates DNA repair by controlling pathway choice and the loading of downstream HR machinery at breaks.
    action: ACCEPT
    reason: Core regulatory role over the repair process it executes.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0035825
    label: homologous recombination
  evidence_type: NAS
  original_reference_id: PMID:22369660
  review:
    summary: BRCA1 contributes to homologous recombination through its PALB2 interaction and modulation of RAD51 loading during recombinational repair.
    action: ACCEPT
    reason: Core repair pathway; NAS support consistent with FUNCTION.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0035825
    label: homologous recombination
  evidence_type: NAS
  original_reference_id: PMID:30657944
  review:
    summary: BRCA1 contributes to homologous recombination through its PALB2 interaction and modulation of RAD51 loading during recombinational repair.
    action: ACCEPT
    reason: Core repair pathway; NAS support consistent with FUNCTION.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0044818
    label: mitotic G2/M transition checkpoint
  evidence_type: NAS
  original_reference_id: PMID:22369660
  review:
    summary: Required for the DNA-damage-induced G2/M checkpoint arrest that prevents division of cells carrying unrepaired breaks.
    action: ACCEPT
    reason: Core checkpoint function; IMP-supported and consistent with FUNCTION.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0110025
    label: DNA strand resection involved in replication fork processing
  evidence_type: NAS
  original_reference_id: PMID:29709199
  review:
    summary: BRCA1-BARD1 promotes nucleolytic end resection at breaks and protects/processes stalled replication forks, a step committing repair to homology-directed pathways.
    action: ACCEPT
    reason: Resection is a core BRCA1-driven step (BRCA1-C/CtIP); NAS supported.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: IDA
  original_reference_id: PMID:20820192
  review:
    summary: BRCA1 can act as a transcriptional coactivator, a regulatory role secondary to and intertwined with its genome-maintenance function.
    action: KEEP_AS_NON_CORE
    reason: Transcription role not the core repair/ligase function; keep as non-core.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: NAS
  original_reference_id: PMID:16651405
  review:
    summary: BRCA1 coordinates the DNA-damage response, being phosphorylated by ATM/ATR and assembling repair/checkpoint complexes at break sites.
    action: ACCEPT
    reason: Core DDR role; IMP-supported and central to BRCA1 biology.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0045787
    label: positive regulation of cell cycle
  evidence_type: NAS
  original_reference_id: PMID:15159397
  review:
    summary: Reported positive cell-cycle regulation, a context-dependent role secondary to BRCA1's checkpoint function.
    action: KEEP_AS_NON_CORE
    reason: Pleiotropic cell-cycle effect downstream of core checkpoint role.
- term:
    id: GO:2000001
    label: regulation of DNA damage checkpoint
  evidence_type: NAS
  original_reference_id: PMID:14636569
  review:
    summary: BRCA1 regulates DNA-damage checkpoint activation, controlling cell-cycle arrest in coordination with its repair complexes.
    action: ACCEPT
    reason: Directly tied to BRCA1's checkpoint-control role; NAS supported.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0060816
    label: random inactivation of X chromosome
  evidence_type: IGI
  original_reference_id: PMID:12419249
  review:
    summary: Implicated in X-chromosome inactivation, a chromatin-level role related to BRCA1's chromosome-surveillance activity.
    action: KEEP_AS_NON_CORE
    reason: Specialized chromatin role secondary to core repair function.
- term:
    id: GO:0044027
    label: negative regulation of gene expression via chromosomal CpG island methylation
  evidence_type: IDA
  original_reference_id: PMID:20820192
  review:
    summary: Linked to silencing of genes via CpG-island methylation, an epigenetic regulatory role distinct from direct repair.
    action: KEEP_AS_NON_CORE
    reason: Epigenetic gene-silencing role pleiotropic to core function.
- term:
    id: GO:0045944
    label: positive regulation of transcription by RNA polymerase II
  evidence_type: IMP
  original_reference_id: PMID:20820192
  review:
    summary: Acts as a transcriptional activator at specific target genes, a regulatory output separable from its repair function.
    action: KEEP_AS_NON_CORE
    reason: Activator role pleiotropic relative to core repair function.
- term:
    id: GO:0001741
    label: XY body
  evidence_type: IDA
  original_reference_id: PMID:31839538
  review:
    summary: Localizes to the XY body (sex-body) during male meiosis, reflecting BRCA1's role in meiotic sex-chromosome inactivation/silencing.
    action: KEEP_AS_NON_CORE
    reason: Meiosis-specific localization downstream of BRCA1's chromatin/genome-surveillance role.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:31839538
  review:
    summary: BRCA1 acts predominantly in the nucleus, forming DNA-damage-induced foci on chromatin where it carries out repair and checkpoint functions.
    action: ACCEPT
    reason: Primary site of BRCA1 action; UniProt SUBCELLULAR LOCATION and IDA support.
- term:
    id: GO:1990904
    label: ribonucleoprotein complex
  evidence_type: ISO
  original_reference_id: PMID:18809582
  review:
    summary: Association with RNP/RNA-containing complexes linked to BRCA1's reported RNA binding and transcription-coupled roles.
    action: KEEP_AS_NON_CORE
    reason: Peripheral complex membership downstream of transcription-associated activity.
- term:
    id: GO:0032991
    label: protein-containing complex
  evidence_type: ISO
  original_reference_id: PMID:16951165
  review:
    summary: Root-level complex term superseded by the specific BRCA1-BARD1 and BRCA1-A/B/C complex annotations.
    action: MARK_AS_OVER_ANNOTATED
    reason: Uninformative generic CC; specific complexes are annotated.
- term:
    id: GO:0003713
    label: transcription coactivator activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: BRCA1 can act as a transcriptional coactivator, a regulatory role secondary to and intertwined with its genome-maintenance function.
    action: KEEP_AS_NON_CORE
    reason: Transcription role not the core repair/ligase function; keep as non-core.
- term:
    id: GO:0006357
    label: regulation of transcription by RNA polymerase II
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Regulates Pol II transcription through coactivator and partner (LMO4/CCAR2) interactions, a pleiotropic role beyond DNA repair.
    action: KEEP_AS_NON_CORE
    reason: Transcriptional regulation secondary to BRCA1's core repair/ligase role.
- term:
    id: GO:0070063
    label: RNA polymerase binding
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Associates with the RNA polymerase II holoenzyme (via DHX9), underpinning BRCA1's transcriptional-regulation activity.
    action: KEEP_AS_NON_CORE
    reason: Transcription-machinery interaction secondary to repair/ligase function.
- term:
    id: GO:0044818
    label: mitotic G2/M transition checkpoint
  evidence_type: IMP
  original_reference_id: PMID:15254237
  review:
    summary: Required for the DNA-damage-induced G2/M checkpoint arrest that prevents division of cells carrying unrepaired breaks.
    action: ACCEPT
    reason: Core checkpoint function; IMP-supported and consistent with FUNCTION.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0000800
    label: lateral element
  evidence_type: ISO
  original_reference_id: PMID:9774970
  review:
    summary: Meiotic synaptonemal-complex lateral-element localization tied to BRCA1's role in meiotic chromosome surveillance.
    action: KEEP_AS_NON_CORE
    reason: Meiosis-specific localization, a specialized context of genome maintenance.
- term:
    id: GO:0000794
    label: condensed nuclear chromosome
  evidence_type: IDA
  original_reference_id: PMID:26490168
  review:
    summary: Localizes to condensed nuclear chromosomes, reflecting chromatin association during mitotic/meiotic chromosome states.
    action: ACCEPT
    reason: IDA-supported; keep experimental localization rather than removing.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0045893
    label: positive regulation of DNA-templated transcription
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Promotes transcription of subsets of target genes as a transcriptional activator, secondary to genome-maintenance roles.
    action: KEEP_AS_NON_CORE
    reason: Activator output pleiotropic relative to core function.
- term:
    id: GO:0006974
    label: DNA damage response
  evidence_type: IMP
  original_reference_id: PMID:23271346
  review:
    summary: BRCA1 coordinates the DNA-damage response, being phosphorylated by ATM/ATR and assembling repair/checkpoint complexes at break sites.
    action: ACCEPT
    reason: Core DDR role; IMP-supported and central to BRCA1 biology.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005694
    label: chromosome
  evidence_type: IDA
  original_reference_id: PMID:22549958
  review:
    summary: BRCA1 localizes to chromosomes/chromatin, where the BRCA1-BARD1 ligase modifies nucleosomal H2A at break sites.
    action: ACCEPT
    reason: Direct chromatin association is core to BRCA1 function; IDA supported.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005694
    label: chromosome
  evidence_type: IDA
  original_reference_id: PMID:23039116
  review:
    summary: BRCA1 localizes to chromosomes/chromatin, where the BRCA1-BARD1 ligase modifies nucleosomal H2A at break sites.
    action: ACCEPT
    reason: Direct chromatin association is core to BRCA1 function; IDA supported.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-912421
  review:
    summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities.
    action: ACCEPT
    reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-912423
  review:
    summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities.
    action: ACCEPT
    reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-912431
  review:
    summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities.
    action: ACCEPT
    reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-912449
  review:
    summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities.
    action: ACCEPT
    reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: TAS
  original_reference_id: Reactome:R-MMU-912468
  review:
    summary: Nucleoplasmic localization consistent with BRCA1's soluble nuclear and chromatin-associated repair/checkpoint activities.
    action: ACCEPT
    reason: Standard nuclear sublocation for BRCA1; TAS/Reactome supported, do not remove an experimentally consistent site.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0006302
    label: double-strand break repair
  evidence_type: IMP
  original_reference_id: PMID:22186889
  review:
    summary: BRCA1 is a key effector of double-strand-break repair, biasing pathway choice away from NHEJ via H2A ubiquitination and 53BP1 repositioning.
    action: ACCEPT
    reason: Core DSB-repair role; IMP plus electronic support.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:11172592
  review:
    summary: Cytoplasmic pool seen e.g. on translocation during UV-induced apoptosis and ACACA binding; not the principal site of repair function.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization; BRCA1 acts mainly in the nucleus.
- term:
    id: GO:0000976
    label: transcription cis-regulatory region binding
  evidence_type: IDA
  original_reference_id: PMID:20820192
  review:
    summary: Binds cis-regulatory regions consistent with BRCA1's transcriptional-regulation activities at target promoters.
    action: KEEP_AS_NON_CORE
    reason: Transcription-associated DNA binding, secondary to repair role.
- term:
    id: GO:0000794
    label: condensed nuclear chromosome
  evidence_type: IDA
  original_reference_id: PMID:20551173
  review:
    summary: Localizes to condensed nuclear chromosomes, reflecting chromatin association during mitotic/meiotic chromosome states.
    action: ACCEPT
    reason: IDA-supported; keep experimental localization rather than removing.
- term:
    id: GO:0085020
    label: protein K6-linked ubiquitination
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: BRCA1-BARD1 specifically catalyzes 'Lys-6'-linked polyubiquitin chains, a hallmark non-degradative linkage of this E3 ligase.
    action: ACCEPT
    reason: Signature catalytic output of BRCA1 stated explicitly in UniProt FUNCTION/PTM.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0051865
    label: protein autoubiquitination
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: BRCA1 undergoes K6-linked autoubiquitination that does not promote degradation, reflecting its intrinsic E3 ligase activity.
    action: ACCEPT
    reason: Documented BRCA1 PTM/activity; core to its enzymatic characterization.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: 'Core catalytic activity: BRCA1, as the BRCA1-BARD1 RING heterodimer, accelerates ubiquitin transfer from charged E2~Ub onto substrate lysines (e.g. nucleosomal H2A, CtIP, PCNA) at sites of DNA damage.'
    action: ACCEPT
    reason: Defining molecular function of BRCA1 (EC 2.3.2.27); supported across IBA/ISO/ISS and the BRCA1-BARD1 mechanistic literature.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0031436
    label: BRCA1-BARD1 complex
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Obligate RING-RING heterodimer with BARD1 that constitutes the active E3 ligase; this assembly underlies essentially all BRCA1 catalytic and DNA-repair functions.
    action: ACCEPT
    reason: Defining functional complex of BRCA1; documented in SUBUNIT and the core mechanistic literature.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: ISO
  original_reference_id: PMID:12419249
  review:
    summary: Reported RNA-binding activity linked to transcription-coupled and RNA-associated functions rather than the core E3/repair role.
    action: KEEP_AS_NON_CORE
    reason: Ancillary nucleic-acid binding; not the defining function.
- term:
    id: GO:0043009
    label: chordate embryonic development
  evidence_type: IMP
  original_reference_id: PMID:9171368
  review:
    summary: Brca1 is required for embryonic development, with knockouts being embryonic lethal owing to defective proliferation and genome instability.
    action: KEEP_AS_NON_CORE
    reason: Developmental phenotype downstream of BRCA1's essential genome-maintenance role.
- term:
    id: GO:0045717
    label: negative regulation of fatty acid biosynthetic process
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  review:
    summary: Inhibits fatty-acid synthesis by binding inactive phosphorylated ACACA and preventing its dephosphorylation, a distinct metabolic moonlighting role.
    action: KEEP_AS_NON_CORE
    reason: Specific lipid-regulatory function via ACACA, separate from the core repair role.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: TAS
  original_reference_id: PMID:10855792
  review:
    summary: Centrosomal pool linked to BRCA1's regulation of centrosomal microtubule nucleation, a function secondary to its nuclear repair role.
    action: KEEP_AS_NON_CORE
    reason: Secondary localization downstream of BRCA1's broader genome-stability role.
- term:
    id: GO:0051298
    label: centrosome duplication
  evidence_type: TAS
  original_reference_id: PMID:10855792
  review:
    summary: Regulates centrosome duplication, helping prevent centrosome amplification and aneuploidy.
    action: KEEP_AS_NON_CORE
    reason: Centrosome control secondary to BRCA1's genome-stability function.
- term:
    id: GO:0000793
    label: condensed chromosome
  evidence_type: IDA
  original_reference_id: PMID:12913077
  review:
    summary: Localizes to condensed chromosomes, consistent with BRCA1's role in genome maintenance through the cell cycle.
    action: ACCEPT
    reason: IDA-supported localization; retain as observed nuclear/chromosomal site.
    supported_by:
    - reference_id: UniProt:P48754
      supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
    - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
      supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.
- term:
    id: GO:0007098
    label: centrosome cycle
  evidence_type: IGI
  original_reference_id: PMID:15123655
  review:
    summary: Participates in the centrosome cycle, consistent with AURKA-phosphorylation-regulated control of centrosomal microtubule nucleation.
    action: KEEP_AS_NON_CORE
    reason: Centrosome-cycle role secondary to core repair/checkpoint function.
- term:
    id: GO:0008630
    label: intrinsic apoptotic signaling pathway in response to DNA damage
  evidence_type: ISO
  original_reference_id: PMID:14654789
  review:
    summary: Engages DNA-damage-triggered intrinsic apoptosis when damage is irreparable, an outcome downstream of BRCA1 damage sensing.
    action: KEEP_AS_NON_CORE
    reason: Apoptotic outcome downstream of the core DNA-damage-response role.
- term:
    id: GO:0003684
    label: damaged DNA binding
  evidence_type: IDA
  original_reference_id: PMID:11934988
  review:
    summary: BRCA1 is recruited to damaged DNA chiefly via ubiquitin/chromatin readers and partner complexes rather than as a direct damaged-DNA binder; the bare MF over-attributes a direct activity.
    action: MARK_AS_OVER_ANNOTATED
    reason: Recruitment to damage is complex-mediated; specific complex/chromatin terms capture this better.
references:
- id: GO_REF:0000003
  title: Gene Ontology annotation based on Enzyme Commission mapping
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: GO_REF:0000096
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-rat orthologs
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000119
  title: Automated transfer of experimentally-verified manual GO annotation data to mouse-human orthologs
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:10855792
  title: VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells.
  findings: []
- id: PMID:11172592
  title: Brca1 and Brca2 protein expression patterns in different tissues of murine origin.
  findings: []
- id: PMID:11934988
  title: Genomic instability in mice lacking histone H2AX.
  findings: []
- id: PMID:12419249
  title: BRCA1 supports XIST RNA concentration on the inactive X chromosome.
  findings: []
- id: PMID:12913077
  title: Targeted disruption of exons 1 to 6 of the Fanconi Anemia group A gene leads to growth retardation, strain-specific microphthalmia, meiotic defects and primordial germ cell hypoplasia.
  findings: []
- id: PMID:14636569
  title: Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair.
  findings: []
- id: PMID:14654789
  title: A member of the Pyrin family, IFI16, is a novel BRCA1-associated protein involved in the p53-mediated apoptosis pathway.
  findings: []
- id: PMID:15123655
  title: Genetic interactions between Brca1 and Gadd45a in centrosome duplication, genetic stability, and neural tube closure.
  findings: []
- id: PMID:15159397
  title: BRCA1-BARD1 complexes are required for p53Ser-15 phosphorylation and a G1/S arrest following ionizing radiation-induced DNA damage.
  findings: []
- id: PMID:15254237
  title: BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function.
  findings: []
- id: PMID:16651405
  title: DNA damage-induced BARD1 phosphorylation is critical for the inhibition of messenger RNA processing by BRCA1/BARD1 complex.
  findings: []
- id: PMID:16951165
  title: p27Kip1 repression of ErbB2-induced mammary tumor growth in transgenic mice involves Skp2 and Wnt/beta-catenin signaling.
  findings: []
- id: PMID:18171670
  title: Cell cycle-dependent complex formation of BRCA1.CtIP.MRN is important for DNA double-strand break repair.
  findings: []
- id: PMID:18809582
  title: Nucleophosmin serves as a rate-limiting nuclear export chaperone for the Mammalian ribosome.
  findings: []
- id: PMID:20551173
  title: Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice.
  findings:
  - statement: The cached publication supports MEI4 localization/function in meiotic double-strand break formation, not BRCA1 condensed nuclear chromosome localization
- id: PMID:20656689
  title: Differential regulation of JAMM domain deubiquitinating enzyme activity within the RAP80 complex.
  findings: []
- id: PMID:20820192
  title: BRCA1 affects global DNA methylation through regulation of DNMT1.
  findings: []
- id: PMID:22186889
  title: BRCA1 is an essential regulator of heart function and survival following myocardial infarction.
  findings: []
- id: PMID:22369660
  title: 'BRCA1 tumor suppressor network: focusing on its tail.'
  findings: []
- id: PMID:22549958
  title: Meiotic DNA double-strand breaks and chromosome asynapsis in mice are monitored by distinct HORMAD2-independent and -dependent mechanisms.
  findings: []
- id: PMID:23039116
  title: HORMAD2 is essential for synapsis surveillance during meiotic prophase via the recruitment of ATR activity.
  findings: []
- id: PMID:23271346
  title: BRCA1 deficiency in skin epidermis leads to selective loss of hair follicle stem cells and their progeny.
  findings: []
- id: PMID:26490168
  title: FancJ (Brip1) loss-of-function allele results in spermatogonial cell depletion during embryogenesis and altered processing of crossover sites during meiotic prophase I in mice.
  findings: []
- id: PMID:29709199
  title: The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair.
  findings: []
- id: PMID:30657944
  title: CtIP-BRCA1 complex and MRE11 maintain replication forks in the presence of chain terminating nucleoside analogs.
  findings: []
- id: PMID:31839538
  title: GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome Stability.
  findings:
  - statement: The cached publication is a GCNA/Spartan genome-stability study and does not support BRCA1 nuclear localization
- id: PMID:9171368
  title: 'Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos.'
  findings: []
- id: PMID:9774970
  title: Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells.
  findings: []
- id: Reactome:R-MMU-912421
  title: Formation of Meiotic Single-stranded Invasion Complex
  findings: []
- id: Reactome:R-MMU-912423
  title: Atr Phosphorylates Histone H2A.X at Unsynapsed Regions
  findings: []
- id: Reactome:R-MMU-912431
  title: Formation of Meiotic Heteroduplex
  findings: []
- id: Reactome:R-MMU-912449
  title: Recruitment of Atr Kinase to Unsynapsed Regions
  findings: []
- id: Reactome:R-MMU-912468
  title: Recruitment of Brca1 to Unsynapsed Regions
  findings: []
- id: UniProt:P48754
  title: UniProtKB record for mouse Brca1 (P48754)
  findings: []
- id: file:mouse/Brca1/Brca1-deep-research-falcon.md
  title: Falcon deep research synthesis for mouse Brca1
  findings: []
core_functions:
- molecular_function:
    id: GO:0004842
    label: ubiquitin-protein transferase activity
  description: Functions with BARD1 as a RING E3 ubiquitin ligase that supports DNA damage signaling, repair-factor positioning, and genome stability.
  in_complex:
    id: GO:0031436
    label: BRCA1-BARD1 complex
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005654
    label: nucleoplasm
  directly_involved_in:
  - id: GO:0016567
    label: protein ubiquitination
  - id: GO:0085020
    label: protein K6-linked ubiquitination
  supported_by:
  - reference_id: UniProt:P48754
    supporting_text: E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
  - reference_id: file:mouse/Brca1/Brca1-deep-research-falcon.md
    supporting_text: BRCA1 forms an obligate heterodimer with BARD1 through the N-terminal RING domains; the complex acts as an E3 ubiquitin ligase that promotes DNA end resection, antagonizes 53BP1 at breaks, and supports PALB2-BRCA2-RAD51 loading for homology-directed repair.

Gene Description

Existing Annotations Review

Core Functions

Functions with BARD1 as a RING E3 ubiquitin ligase that supports DNA damage signaling, repair-factor positioning, and genome stability.

References

Deep Research

Falcon

Research Report: Mouse Brca1 (UniProt P48754) — Functional Annotation (2023–2024 emphasis)

1) Target verification (gene/protein identity)

2) Key concepts and definitions (current understanding)

BRCA1 as a genome-stability tumor suppressor

Core functional modules

3) Primary biochemical function (reaction, substrates, specificity)

Enzymatic reaction

Best-supported substrates and sites (2023–2024)

E2 usage and substrate context

Ubiquitin linkage preferences (what is and is not settled)

4) Pathways and mechanistic roles

4.1 Homologous recombination and DSB repair pathway choice

4.2 Chromatin targeting and recruitment logic (damage-site specificity)

4.3 Replication fork protection and replication-gap suppression (major 2024 development)

5) Subcellular localization and where BRCA1 acts in the cell

6) Current applications and real-world implementations (mouse-focused)

6.1 Preclinical breast cancer and therapy-response modeling

6.2 Reproductive aging and fertility biology

7) Expert opinions and analysis (authoritative interpretations)

8) Visual evidence (domain/function schematic)

Summary table (compact functional annotation map)

Key recent sources (with dates and URLs)

Limitations of the current evidence set

Citations

📄 View Raw YAML