BRCA2 (Breast cancer type 2 susceptibility protein) is a critical tumor suppressor that functions as a mediator of homologous recombination (HR) DNA repair. The protein contains multiple functional domains: BRC repeats that bind RAD51 recombinase, a DNA-binding domain (DBD) with OB folds and tower domain that binds ssDNA, and a C-terminal recombinase-binding region (CTRB) that engages both DNA and RAD51. BRCA2 loads and stabilizes RAD51 onto RPA-coated single-stranded DNA to form the presynaptic filament required for strand invasion during HR. Additionally, BRCA2 protects stalled and reversed replication forks from MRE11-mediated nucleolytic degradation, a function genetically separable from but coordinated with HR. Key partners include RAD51, PALB2, BRCA1-BARD1, and DSS1. Loss of BRCA2 function causes homologous recombination deficiency (HRD), conferring sensitivity to PARP inhibitors and platinum agents. Biallelic mutations cause Fanconi anemia (complementation group D1/FANCD1). BRCA2 localizes predominantly to the nucleus at DNA damage sites.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0003697 single-stranded DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA2 binds single-stranded DNA through its DNA-binding domain (DBD) containing OB folds and through its C-terminal region (CTRB). This is essential for its function in loading RAD51 onto ssDNA during homologous recombination. Reason: Core molecular function. The DBD with OB folds directly binds ssDNA to facilitate RAD51 loading. This is well-supported by structural and biochemical studies (PMID:20729832, Kwon et al. 2023 Nature Comm). Supporting Evidence: file:human/BRCA2/BRCA2-deep-research-falcon.md The canonical DBD comprises a helical domain (HD), three OB folds (OB1-OB3), and a tower domain appendage. It binds DNA with high affinity and preferentially engages ssDNA in concert with DSS1 PMID:20729832 Purified human BRCA2 stimulates RAD51-mediated recombination PMID:12228710 demonstrate that this BRCA2 domain binds single-stranded DNA |
| GO:0000724 double-strand break repair via homologous recombination | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA2 is the central mediator of homologous recombination repair, loading RAD51 onto resected ssDNA to form the presynaptic filament required for strand invasion. Reason: Core biological process. BRCA2's primary function is mediating HR by facilitating RAD51 nucleoprotein filament formation. This is the defining function of BRCA2 and is well-established across multiple lines of evidence. Supporting Evidence: file:human/BRCA2/BRCA2-deep-research-falcon.md BRCA2 is a genome maintenance factor that mediates homologous recombination (HR) by loading and stabilizing the recombinase RAD51 on resected single-stranded DNA (ssDNA) to form the presynaptic filament required for homology search and strand exchange |
| GO:0000724 double-strand break repair via homologous recombination | IEA GO_REF:0000120 | ACCEPT | Summary: Computational annotation consistent with BRCA2's established role in HR repair. Reason: This IEA annotation is correctly capturing BRCA2's core function in HR repair. Redundant with IBA but valid. |
| GO:0003677 DNA binding | IEA GO_REF:0000043 | ACCEPT | Summary: BRCA2 binds DNA through its DNA-binding domain containing OB folds. This is a parent term of ssDNA binding. Reason: Valid but less specific than GO:0003697 (ssDNA binding). BRCA2 does bind DNA through its DBD and CTRB regions. |
| GO:0006281 DNA repair | IEA GO_REF:0000120 | ACCEPT | Summary: BRCA2 functions in DNA repair, specifically homologous recombination repair. Reason: Valid parent term of the more specific GO:0000724. BRCA2 is fundamentally a DNA repair protein. |
| GO:0005515 protein binding | IPI PMID:10373512 Interaction between the product of the breast cancer suscept... | REMOVE | Summary: This paper describes the interaction between BRCA2 and DSS1 (SEM1), a functionally conserved protein. DSS1 binding is important for BRCA2 stability and function. Reason: Generic protein binding is uninformative. The specific interaction (BRCA2-DSS1) is important but should be annotated with a more specific term if available. Supporting Evidence: PMID:10373512 Interaction between the product of the breast cancer susceptibility gene BRCA2 and DSS1, a protein functionally conserved from yeast to mammals. |
| GO:0005515 protein binding | IPI PMID:10551859 Expression of BRC repeats in breast cancer cells disrupts th... | REMOVE | Summary: Paper describes BRC repeats binding to RAD51 and disruption of this interaction leading to radiation hypersensitivity. Reason: Generic protein binding is uninformative. The functionally relevant interaction is RAD51 binding via BRC repeats. Supporting Evidence: PMID:10551859 Expression of BRC repeats in breast cancer cells disrupts the BRCA2-Rad51 complex and leads to radiation hypersensitivity and loss of G(2)/M checkpoint control. |
| GO:0005515 protein binding | IPI PMID:12442171 Insights into DNA recombination from the structure of a RAD5... | REMOVE | Summary: Structural study of RAD51-BRCA2 complex revealing molecular basis of their interaction. Reason: Generic protein binding is uninformative. This important structural work reveals RAD51 binding mechanism. Supporting Evidence: PMID:12442171 Insights into DNA recombination from the structure of a RAD51-BRCA2 complex. |
| GO:0005515 protein binding | IPI PMID:15115758 Direct interaction of FANCD2 with BRCA2 in DNA damage respon... | REMOVE | Summary: Paper describes direct interaction between FANCD2 and BRCA2 in DNA damage response. Reason: Generic protein binding is uninformative. FANCD2 interaction is relevant to Fanconi anemia pathway. Supporting Evidence: PMID:15115758 Apr 28. Direct interaction of FANCD2 with BRCA2 in DNA damage response pathways. |
| GO:0005515 protein binding | IPI PMID:15800615 CDK-dependent phosphorylation of BRCA2 as a regulatory mecha... | REMOVE | Summary: CDK-dependent phosphorylation of BRCA2 regulates RAD51 binding and recombinational repair. Reason: Generic protein binding is uninformative. The key finding is regulated RAD51 interaction. Supporting Evidence: PMID:15800615 CDK-dependent phosphorylation of BRCA2 as a regulatory mechanism for recombinational repair. |
| GO:0005515 protein binding | IPI PMID:16205630 DSS1 is required for the stability of BRCA2. | REMOVE | Summary: DSS1 is required for BRCA2 stability. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:16205630 DSS1 is required for the stability of BRCA2. |
| GO:0005515 protein binding | IPI PMID:17420451 Analysis of PALB2/FANCN-associated breast cancer families. | REMOVE | Summary: Analysis of PALB2/FANCN-associated breast cancer families, describing PALB2 interaction. Reason: Generic protein binding is uninformative. PALB2 interaction is critical for BRCA2 function. Supporting Evidence: PMID:17420451 Analysis of PALB2/FANCN-associated breast cancer families. |
| GO:0005515 protein binding | IPI PMID:17515903 Interaction with the BRCA2 C terminus protects RAD51-DNA fil... | REMOVE | Summary: Interaction with BRCA2 C terminus protects RAD51-DNA filaments from BRC repeat-mediated disassembly. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:17515903 Interaction with the BRCA2 C terminus protects RAD51-DNA filaments from disassembly by BRC repeats. |
| GO:0005515 protein binding | IPI PMID:17515904 Stabilization of RAD51 nucleoprotein filaments by the C-term... | REMOVE | Summary: Stabilization of RAD51 nucleoprotein filaments by BRCA2 C-terminal region. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:17515904 May 21. Stabilization of RAD51 nucleoprotein filaments by the C-terminal region of BRCA2. |
| GO:0005515 protein binding | IPI PMID:17541404 Interactions between human BRCA2 protein and the meiosis-spe... | REMOVE | Summary: Interactions between BRCA2 and meiosis-specific recombinase DMC1. Reason: Generic protein binding is uninformative. DMC1 binding is relevant for meiotic recombination. Supporting Evidence: PMID:17541404 May 31. Interactions between human BRCA2 protein and the meiosis-specific recombinase DMC1. |
| GO:0005515 protein binding | IPI PMID:18212739 FANCG promotes formation of a newly identified protein compl... | REMOVE | Summary: FANCG promotes formation of complex containing BRCA2, FANCD2 and XRCC3. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:18212739 Jan 21. FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3. |
| GO:0005515 protein binding | IPI PMID:18264088 Resistance to therapy caused by intragenic deletion in BRCA2... | REMOVE | Summary: Resistance to therapy caused by intragenic deletion in BRCA2. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:18264088 Resistance to therapy caused by intragenic deletion in BRCA2. |
| GO:0005515 protein binding | IPI PMID:19303847 The BRC repeats of BRCA2 modulate the DNA-binding selectivit... | REMOVE | Summary: BRC repeats modulate DNA-binding selectivity of RAD51. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:19303847 The BRC repeats of BRCA2 modulate the DNA-binding selectivity of RAD51. |
| GO:0005515 protein binding | IPI PMID:19369211 PALB2 is an integral component of the BRCA complex required ... | REMOVE | Summary: PALB2 is integral component of BRCA complex required for HR repair. With BRCA1 and PALB2. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:19369211 PALB2 is an integral component of the BRCA complex required for homologous recombination repair. |
| GO:0005515 protein binding | IPI PMID:19609323 Structural basis for recruitment of BRCA2 by PALB2. | REMOVE | Summary: Structural basis for BRCA2 recruitment by PALB2. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:19609323 Structural basis for recruitment of BRCA2 by PALB2. |
| GO:0005515 protein binding | IPI PMID:19628690 The BRC repeats of human BRCA2 differentially regulate RAD51... | REMOVE | Summary: BRC repeats differentially regulate RAD51 binding on ssDNA vs dsDNA. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:19628690 The BRC repeats of human BRCA2 differentially regulate RAD51 binding on single- versus double-stranded DNA to stimulate strand exchange. |
| GO:0005515 protein binding | IPI PMID:20421506 Mapping the physical and functional interactions between the... | REMOVE | Summary: Physical and functional interactions between p53 and BRCA2. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:20421506 Mapping the physical and functional interactions between the tumor suppressors p53 and BRCA2. |
| GO:0005515 protein binding | IPI PMID:20729832 Purified human BRCA2 stimulates RAD51-mediated recombination... | REMOVE | Summary: Purified BRCA2 stimulates RAD51-mediated recombination. Key mechanistic study. Reason: Generic protein binding is uninformative. The important finding is RAD51 regulation. Supporting Evidence: PMID:20729832 Purified human BRCA2 stimulates RAD51-mediated recombination. |
| GO:0005515 protein binding | IPI PMID:20729859 Human BRCA2 protein promotes RAD51 filament formation on RPA... | REMOVE | Summary: BRCA2 promotes RAD51 filament formation on RPA-covered ssDNA. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:20729859 Aug 22. Human BRCA2 protein promotes RAD51 filament formation on RPA-covered single-stranded DNA. |
| GO:0005515 protein binding | IPI PMID:21399666 A mitotic function for the high-mobility group protein HMG20... | REMOVE | Summary: HMG20b interaction with BRC repeats of BRCA2 has mitotic function. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:21399666 A mitotic function for the high-mobility group protein HMG20b regulated by its interaction with the BRC repeats of the BRCA2 tumor suppressor. |
| GO:0005515 protein binding | IPI PMID:21601571 Valine 1532 of human BRC repeat 4 plays an important role in... | REMOVE | Summary: Valine 1532 of BRC repeat 4 important for BRCA2-RAD51 interaction. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:21601571 Epub 2011 May 17. Valine 1532 of human BRC repeat 4 plays an important role in the interaction between BRCA2 and RAD51. |
| GO:0005515 protein binding | IPI PMID:22116401 Synaptonemal complex protein SYCP3 impairs mitotic recombina... | REMOVE | Summary: Synaptonemal complex protein SYCP3 impairs mitotic recombination by interfering with BRCA2. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:22116401 Synaptonemal complex protein SYCP3 impairs mitotic recombination by interfering with BRCA2. |
| GO:0005515 protein binding | IPI PMID:22193777 ChAM, a novel motif that mediates PALB2 intrinsic chromatin ... | REMOVE | Summary: ChAM motif mediates PALB2 chromatin binding and facilitates DNA repair. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:22193777 ChAM, a novel motif that mediates PALB2 intrinsic chromatin binding and facilitates DNA repair. |
| GO:0005515 protein binding | IPI PMID:22293751 APRIN is a cell cycle specific BRCA2-interacting protein req... | REMOVE | Summary: APRIN is cell cycle specific BRCA2-interacting protein required for genome integrity. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:22293751 APRIN is a cell cycle specific BRCA2-interacting protein required for genome integrity and a predictor of outcome after chemotherapy in breast cancer. |
| GO:0005515 protein binding | IPI PMID:24013206 A cancer-associated BRCA2 mutation reveals masked nuclear ex... | REMOVE | Summary: Cancer-associated BRCA2 mutation reveals masked nuclear export signals. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:24013206 Sep 8. A cancer-associated BRCA2 mutation reveals masked nuclear export signals controlling localization. |
| GO:0005515 protein binding | IPI PMID:24141787 Breast cancer-associated missense mutants of the PALB2 WD40 ... | REMOVE | Summary: PALB2 WD40 domain directly binds RAD51C, RAD51 and BRCA2. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:24141787 Breast cancer-associated missense mutants of the PALB2 WD40 domain, which directly binds RAD51C, RAD51 and BRCA2, disrupt DNA repair. |
| GO:0005515 protein binding | IPI PMID:24485656 Breast cancer proteins PALB2 and BRCA2 stimulate polymerase ... | REMOVE | Summary: PALB2 and BRCA2 stimulate polymerase eta at blocked replication forks. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:24485656 2014 Jan 30. Breast cancer proteins PALB2 and BRCA2 stimulate polymerase Ξ· in recombination-associated DNA synthesis at blocked replication forks. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | REMOVE | Summary: Human chromatin-related protein interactions. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:24981860 2014 Jun 26. Human-chromatin-related protein interactions identify a demethylase complex required for chromosome segregation. |
| GO:0005515 protein binding | IPI PMID:25282148 Structure and mechanism of action of the BRCA2 breast cancer... | REMOVE | Summary: Structure and mechanism of action of BRCA2 breast cancer tumor suppressor. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:25282148 2014 Oct 5. Structure and mechanism of action of the BRCA2 breast cancer tumor suppressor. |
| GO:0005515 protein binding | IPI PMID:28319063 Compromised BRCA1-PALB2 interaction is associated with breas... | REMOVE | Summary: Compromised BRCA1-PALB2 interaction associated with breast cancer risk. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:28319063 Mar 20. Compromised BRCA1-PALB2 interaction is associated with breast cancer risk. |
| GO:0005515 protein binding | IPI PMID:30410870 Two Missense Variants Detected in Breast Cancer Probands Pre... | REMOVE | Summary: Two missense variants preventing BRCA2-PALB2 interaction. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:30410870 Two Missense Variants Detected in Breast Cancer Probands Preventing BRCA2-PALB2 Protein Interaction. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Dual proteome-scale networks reveal cell-specific remodeling of human interactome. Reason: Generic protein binding is uninformative. High-throughput study. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | REMOVE | Summary: Protein interaction landscape of breast cancer. Reason: Generic protein binding is uninformative. High-throughput study. Supporting Evidence: PMID:34591612 Oct 1. A protein interaction landscape of breast cancer. |
| GO:0005515 protein binding | IPI PMID:39009827 Proteome-scale characterisation of motif-based interactome r... | REMOVE | Summary: Proteome-scale characterisation of motif-based interactome rewiring by disease mutations. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:39009827 2024 Jul 15. Proteome-scale characterisation of motif-based interactome rewiring by disease mutations. |
| GO:0005515 protein binding | IPI PMID:9560268 The BRC repeats in BRCA2 are critical for RAD51 binding and ... | REMOVE | Summary: BRC repeats critical for RAD51 binding and resistance to methyl methanesulfonate. Reason: Generic protein binding is uninformative. The important finding is RAD51 binding via BRC repeats. Supporting Evidence: PMID:9560268 The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment. |
| GO:0042802 identical protein binding | IPI PMID:21601571 Valine 1532 of human BRC repeat 4 plays an important role in... | KEEP AS NON CORE | Summary: BRCA2 can form homodimers or oligomers. Reason: BRCA2 oligomerization has been reported but is not central to its primary function in HR repair. Supporting Evidence: PMID:21601571 Epub 2011 May 17. Valine 1532 of human BRC repeat 4 plays an important role in the interaction between BRCA2 and RAD51. |
| GO:0042802 identical protein binding | IPI PMID:25282148 Structure and mechanism of action of the BRCA2 breast cancer... | KEEP AS NON CORE | Summary: BRCA2 homodimerization. Reason: Oligomerization is a secondary property, not core function. Supporting Evidence: PMID:25282148 2014 Oct 5. Structure and mechanism of action of the BRCA2 breast cancer tumor suppressor. |
| GO:0000722 telomere maintenance via recombination | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA2 has been shown to localize to telomeres and facilitate telomere replication and capping through RAD51 loading (PMID:21076401). Reason: BRCA2 does function at telomeres via its general HR function, but this is not the primary cellular role. Supported by PMID:21076401. |
| GO:0001556 oocyte maturation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Developmental process in which oocytes develop. BRCA2 is required for proper meiotic recombination. Reason: Downstream developmental consequence of BRCA2's role in meiotic HR. Not a direct molecular function. |
| GO:0001833 inner cell mass cell proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Embryonic developmental process. BRCA2 knockout is embryonic lethal. Reason: This is a distal phenotypic consequence of loss of genome maintenance, not a specific function of BRCA2. |
| GO:0006302 double-strand break repair | IEA GO_REF:0000107 | ACCEPT | Summary: Parent term of HR repair. BRCA2 specifically functions in HR, not NHEJ. Reason: Valid parent term. BRCA2 functions specifically in the HR subtype of DSB repair. |
| GO:0007283 spermatogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA2 is required for meiotic recombination during spermatogenesis. HSF2BP interaction is required for spermatogenesis (PMID:31242413). Reason: BRCA2 is essential for meiosis, and loss causes infertility. This is a consequence of its meiotic HR function. |
| GO:0007420 brain development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: BRCA2 loss leads to developmental defects including in brain. This is pleiotropic. Reason: Distal phenotypic effect of genome instability, not a specific BRCA2 function. |
| GO:0008283 cell population proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Generic cell proliferation term. Reason: Too generic. BRCA2 loss affects proliferation due to genome instability, not via direct regulation of proliferation. |
| GO:0008585 female gonad development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA2 required for meiosis which is essential for gonad development. Reason: Downstream consequence of meiotic HR function. |
| GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: BRCA2 loss leads to activation of apoptosis due to unrepaired DNA damage. Reason: BRCA2 does not directly regulate apoptosis. Apoptosis is a downstream consequence of HR deficiency. |
| GO:0010165 response to X-ray | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA2-deficient cells are hypersensitive to X-rays due to defective HR repair. Reason: Valid but represents the phenotypic response rather than BRCA2's direct function. |
| GO:0010225 response to UV-C | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Response to UV damage. Reason: Phenotypic response to DNA damage. BRCA2 participates in repair of UV-induced lesions via HR. |
| GO:0010332 response to gamma radiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA2 is essential for repair of gamma-radiation induced DSBs. Reason: Phenotypic response. BRCA2 repairs radiation-induced DSBs via HR. |
| GO:0030097 hemopoiesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Biallelic BRCA2 mutations cause Fanconi anemia with bone marrow failure. Reason: Downstream phenotype of BRCA2/FANCD1 deficiency. Not a direct function. |
| GO:0030330 DNA damage response, signal transduction by p53 class mediator | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: p53 activation occurs when BRCA2-mediated repair fails. Reason: BRCA2 does not directly regulate p53 signaling. This is an indirect consequence. |
| GO:0031297 replication fork processing | IEA GO_REF:0000107 | ACCEPT | Summary: BRCA2 protects stalled and reversed replication forks from nucleolytic degradation by MRE11. Reason: Core function. BRCA2 stabilizes RAD51 on reversed forks to prevent degradation. This is mechanistically separable from but related to HR function. Supporting Evidence: file:human/BRCA2/BRCA2-deep-research-falcon.md Beyond DSB repair, BRCA2 stabilizes RAD51 on stalled/reversed replication forks to prevent nucleolytic degradation (e.g., by MRE11) and to promote restart, a function genetically and biochemically separable but coordinated with HR PMID:29038466 protects stalled replication forks from nucleolytic degradation |
| GO:0032465 regulation of cytokinesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA2 has been implicated in centrosome and cytokinesis regulation. Reason: BRCA2 localizes to centrosomes and affects mitotic fidelity, but this is secondary to HR function. |
| GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Apoptosis induction when BRCA2-mediated repair fails. Reason: Indirect consequence of HR deficiency, not a direct BRCA2 function. |
| GO:0043009 chordate embryonic development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: BRCA2 knockout is embryonic lethal. Reason: Distal phenotypic effect of genome instability. |
| GO:0045931 positive regulation of mitotic cell cycle | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: BRCA2 loss causes cell cycle arrest. Reason: BRCA2 does not directly regulate cell cycle. Cell cycle effects are consequence of checkpoint activation. |
| GO:0051276 chromosome organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA2 affects chromosome stability through HR repair. Reason: Valid but vague. BRCA2 contributes to chromosome stability via its repair function. |
| GO:0071425 hematopoietic stem cell proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: BRCA2/FANCD1 deficiency causes bone marrow failure. Reason: Phenotypic consequence of Fanconi anemia, not direct function. |
| GO:0072089 stem cell proliferation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Generic stem cell term. Reason: Too generic and represents phenotypic consequence. |
| GO:0090398 cellular senescence | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: BRCA2 loss can trigger senescence. Reason: Senescence is a downstream response to DNA damage, not a BRCA2 function. |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:28398198 Functional and mutational landscapes of BRCA1 for homology-d... | ACCEPT | Summary: Functional and mutational landscapes of BRCA1 for HR and therapy resistance. Reason: Direct experimental evidence for BRCA2's role in HR repair. Supporting Evidence: PMID:28398198 Functional and mutational landscapes of BRCA1 for homology-directed repair and therapy resistance. |
| GO:0005515 protein binding | IPI PMID:26833090 Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologo... | REMOVE | Summary: Non-catalytic roles for XPG with BRCA1 and BRCA2 in HR and genome stability. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:26833090 2016 Jan 28. Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous Recombination and Genome Stability. |
| GO:0005515 protein binding | IPI PMID:31242413 HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Req... | REMOVE | Summary: HSF2BP interacts with conserved domain of BRCA2 for spermatogenesis. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:31242413 HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for Mouse Spermatogenesis. |
| GO:0005515 protein binding | IDA PMID:9774970 Stable interaction between the products of the BRCA1 and BRC... | REMOVE | Summary: Stable interaction between BRCA1 and BRCA2 in mitotic and meiotic cells. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:9774970 Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. |
| GO:0000724 double-strand break repair via homologous recombination | IMP PMID:21719596 A comprehensive functional characterization of BRCA2 variant... | ACCEPT | Summary: Comprehensive functional characterization of BRCA2 variants associated with Fanconi anemia. Reason: Mutant phenotype analysis confirms BRCA2's role in HR. Supporting Evidence: PMID:21719596 Jun 30. A comprehensive functional characterization of BRCA2 variants associated with Fanconi anemia using mouse ES cell-based assay. |
| GO:0005515 protein binding | IPI PMID:21719596 A comprehensive functional characterization of BRCA2 variant... | REMOVE | Summary: BRCA2 variants characterized for functional interactions. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:21719596 Jun 30. A comprehensive functional characterization of BRCA2 variants associated with Fanconi anemia using mouse ES cell-based assay. |
| GO:0005515 protein binding | IPI PMID:25585578 FBH1 influences DNA replication fork stability and homologou... | REMOVE | Summary: FBH1 influences DNA replication fork stability through RAD51 ubiquitylation. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:25585578 FBH1 influences DNA replication fork stability and homologous recombination through ubiquitylation of RAD51. |
| GO:0010484 histone H3 acetyltransferase activity | IDA PMID:9619837 The BRCA2 is a histone acetyltransferase. | UNDECIDED | Summary: Original 1998 paper claimed BRCA2 has intrinsic HAT activity. However, this finding is controversial and has not been widely replicated. A 1998 study (PMID:9824164) showed that BRCA2 associates with acetyltransferase activity when bound to P/CAF, suggesting the HAT activity is from associated P/CAF, not intrinsic to BRCA2. Reason: The claim of intrinsic HAT activity is contested. PMID:9824164 indicates the activity comes from P/CAF association. This needs expert review. Supporting Evidence: PMID:9619837 The BRCA2 is a histone acetyltransferase. |
| GO:0010485 histone H4 acetyltransferase activity | IDA PMID:9619837 The BRCA2 is a histone acetyltransferase. | UNDECIDED | Summary: Same controversial claim as H3 HAT activity. Reason: Intrinsic HAT activity claim is contested. Needs expert review. Supporting Evidence: PMID:9619837 The BRCA2 is a histone acetyltransferase. |
| GO:0005515 protein binding | IPI PMID:19423707 PALB2 regulates recombinational repair through chromatin ass... | REMOVE | Summary: PALB2 regulates recombinational repair through chromatin association and oligomerization. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:19423707 2009 May 7. PALB2 regulates recombinational repair through chromatin association and oligomerization. |
| GO:0000724 double-strand break repair via homologous recombination | IDA PMID:20729832 Purified human BRCA2 stimulates RAD51-mediated recombination... | ACCEPT | Summary: Purified human BRCA2 stimulates RAD51-mediated recombination. Key biochemical study demonstrating BRCA2's direct role in HR. Reason: High-quality direct assay evidence confirming BRCA2's role in stimulating RAD51-dependent recombination. Supporting Evidence: PMID:20729832 Purified human BRCA2 stimulates RAD51-mediated recombination. |
| GO:0003697 single-stranded DNA binding | IDA PMID:20729832 Purified human BRCA2 stimulates RAD51-mediated recombination... | ACCEPT | Summary: Biochemical demonstration that purified BRCA2 binds ssDNA directly. Reason: Direct biochemical evidence for ssDNA binding activity. Supporting Evidence: PMID:20729832 Purified human BRCA2 stimulates RAD51-mediated recombination. |
| GO:0002020 protease binding | IPI PMID:15314155 BRCA2 is ubiquitinated in vivo and interacts with USP11, a d... | KEEP AS NON CORE | Summary: BRCA2 interacts with USP11, a deubiquitinating enzyme. Reason: USP11 is a DUB that regulates BRCA2 stability. This is a regulatory interaction, not core function. Supporting Evidence: PMID:15314155 BRCA2 is ubiquitinated in vivo and interacts with USP11, a deubiquitinating enzyme that exhibits prosurvival function in the cellular response to DNA damage. |
| GO:0005515 protein binding | IPI PMID:12242698 Highlight: BRCA1 and BRCA2 proteins in breast cancer. | REMOVE | Summary: BRCA1 and BRCA2 proteins in breast cancer. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:12242698 Highlight: BRCA1 and BRCA2 proteins in breast cancer. |
| GO:0005515 protein binding | IPI PMID:15967112 WDRPUH, a novel WD-repeat-containing protein, is highly expr... | REMOVE | Summary: WDRPUH interaction with BRCA2. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:15967112 WDRPUH, a novel WD-repeat-containing protein, is highly expressed in human hepatocellular carcinoma and involved in cell proliferation. |
| GO:0005515 protein binding | IPI PMID:11597317 BRCA2 and homologous recombination. | REMOVE | Summary: BRCA2 and homologous recombination review. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:11597317 BRCA2 and homologous recombination. |
| GO:0005515 protein binding | IPI PMID:15930293 BRCA2 suppresses cell proliferation via stabilizing MAGE-D1. | REMOVE | Summary: BRCA2 suppresses cell proliferation via stabilizing MAGE-D1. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:15930293 BRCA2 suppresses cell proliferation via stabilizing MAGE-D1. |
| GO:0005515 protein binding | IPI PMID:16099937 Analysis of albumin-associated peptides and proteins from ov... | REMOVE | Summary: Analysis of albumin-associated peptides from ovarian cancer patients. Reason: Generic protein binding is uninformative. Low relevance study. Supporting Evidence: PMID:16099937 2005 Aug 11. Analysis of albumin-associated peptides and proteins from ovarian cancer patients. |
| GO:0005515 protein binding | IPI PMID:16275750 Centrobin: a novel daughter centriole-associated protein tha... | REMOVE | Summary: Centrobin centriole duplication study. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:16275750 Centrobin: a novel daughter centriole-associated protein that is required for centriole duplication. |
| GO:0005515 protein binding | IPI PMID:9774970 Stable interaction between the products of the BRCA1 and BRC... | REMOVE | Summary: BRCA1-BRCA2 interaction in mitotic and meiotic cells. Reason: Generic protein binding is uninformative. Supporting Evidence: PMID:9774970 Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. |
| GO:0043015 gamma-tubulin binding | IPI PMID:17286961 Interference with BRCA2, which localizes to the centrosome d... | KEEP AS NON CORE | Summary: BRCA2 localizes to centrosome and interacts with gamma-tubulin. Interference leads to abnormal nuclear division. Reason: BRCA2 does localize to centrosomes and binds gamma-tubulin, but this is secondary to its HR function. Supporting Evidence: PMID:17286961 Interference with BRCA2, which localizes to the centrosome during S and early M phase, leads to abnormal nuclear division. |
| GO:0004402 histone acetyltransferase activity | IDA NOT PMID:9824164 BRCA2 associates with acetyltransferase activity when bound ... | ACCEPT | Summary: BRCA2 associates with acetyltransferase activity when bound to P/CAF. This study shows HAT activity comes from P/CAF, not BRCA2 itself. Reason: This is a NOT (negated) annotation correctly asserting that BRCA2 does NOT have intrinsic histone acetyltransferase activity - the observed activity comes from associated P/CAF (PMID:9824164). This is an accurate, well-supported negative annotation and should be RETAINED, not removed - it documents the absence of a dubious/unreproduced activity and guards against the positive HAT claims (GO:0010484/GO:0010485) being taken at face value. REMOVE would wrongly discard correct curated negative information; the annotation is right, so ACCEPT. Supporting Evidence: PMID:9824164 BRCA2 associates with acetyltransferase activity when bound to P/CAF. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: BRCA2 is predominantly nuclear where it functions in DNA repair. Reason: Core localization. BRCA2 must be nuclear to perform its DNA repair function. |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: BRCA2 has been reported to have transcriptional activation activity in its N-terminal domain. Reason: BRCA2 contains a transcriptional activation domain and has been shown to activate transcription (PMID:9126734), but this is not its primary function. |
| GO:0006338 chromatin remodeling | IEA GO_REF:0000108 | UNDECIDED | Summary: Inferred from claimed HAT activity. Reason: This inference depends on the contested HAT activity claim. Needs expert review. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear localization. Reason: Consistent with known nuclear function. |
| GO:0005813 centrosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: BRCA2 localizes to centrosomes during S and early M phase. Reason: BRCA2 does localize to centrosomes (PMID:17286961, PMID:21276791) but this is secondary to its nuclear DNA repair function. |
| GO:0006310 DNA recombination | IEA GO_REF:0000120 | ACCEPT | Summary: Parent term of HR. Reason: Valid. BRCA2 is a key recombination mediator. |
| GO:0006974 DNA damage response | IEA GO_REF:0000120 | ACCEPT | Summary: BRCA2 is part of the DNA damage response. Reason: BRCA2 is recruited to and functions at DNA damage sites. |
| GO:0000152 nuclear ubiquitin ligase complex | IDA PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 an... | ACCEPT | Summary: BRCA2 is part of the BRCC holoenzyme complex which contains BRCA1 and has ubiquitin ligase activity. Reason: BRCA2 is part of multi-protein DNA repair complexes with ubiquitin ligase activity. Supporting Evidence: PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. |
| GO:0005634 nucleus | IDA PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 an... | ACCEPT | Summary: Nuclear localization is essential for BRCA2's role in homologous recombination DNA repair. Reason: Nuclear localization is core to BRCA2 function in DNA repair, directly demonstrated by IDA evidence. Supporting Evidence: file:human/BRCA2/BRCA2-deep-research-falcon.md BRCA2 is predominantly nuclear and accumulates at DNA double-strand breaks, ssDNA gaps, and stressed/reversed replication forks PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. |
| GO:0071479 cellular response to ionizing radiation | IMP PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 an... | ACCEPT | Summary: BRCA2 is required for proper response to ionizing radiation. Reason: BRCA2 is essential for repair of radiation-induced DSBs via HR. Supporting Evidence: PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. |
| GO:2000001 regulation of DNA damage checkpoint | NAS PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 an... | KEEP AS NON CORE | Summary: BRCA2 participates in checkpoint regulation. Reason: BRCA2 affects checkpoint signaling but is not a direct checkpoint regulator. Supporting Evidence: PMID:14636569 Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair. |
| GO:0005694 chromosome | IEA GO_REF:0000107 | ACCEPT | Summary: BRCA2 associates with chromosomes at DNA damage sites. Reason: BRCA2 is recruited to chromosomal DNA damage sites. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Some BRCA2 is cytoplasmic before nuclear import. Reason: BRCA2 is predominantly nuclear but some cytoplasmic localization exists. |
| GO:0007141 male meiosis I | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA2 is required for meiotic recombination. Reason: BRCA2 functions in meiotic HR, essential for meiosis I. |
| GO:0070200 establishment of protein localization to telomere | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BRCA2 facilitates RAD51 localization to telomeres. Reason: BRCA2 loads RAD51 at telomeres for replication (PMID:21076401). |
| GO:0005634 nucleus | NAS PMID:19369211 PALB2 is an integral component of the BRCA complex required ... | ACCEPT | Summary: Nuclear localization in BRCA complex. Reason: Consistent with established nuclear function. Supporting Evidence: PMID:19369211 PALB2 is an integral component of the BRCA complex required for homologous recombination repair. |
| GO:1990391 DNA repair complex | IPI PMID:19369211 PALB2 is an integral component of the BRCA complex required ... | ACCEPT | Summary: BRCA2 is part of the BRCA complex with BRCA1 and PALB2 required for HR repair. Reason: Core component of DNA repair complex. Supporting Evidence: PMID:19369211 PALB2 is an integral component of the BRCA complex required for homologous recombination repair. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: BRCA2 localizes to the nucleoplasm where it participates in DNA repair processes. Reason: Nucleoplasm localization is consistent with BRCA2's role in nuclear DNA repair machinery. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Some BRCA2 is present in cytosol. Reason: BRCA2 is predominantly nuclear; cytosolic localization is secondary. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9763200 | KEEP AS NON CORE | Summary: Reactome pathway annotation for cytosolic BRCA2. Reason: Secondary localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709571 | ACCEPT | Summary: Reactome pathway annotation. Reason: Consistent with nuclear function. |
| GO:0005634 nucleus | IDA PMID:26833090 Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologo... | ACCEPT | Summary: Nuclear localization with XPG in HR complex. Reason: Consistent with nuclear DNA repair function. Supporting Evidence: PMID:26833090 2016 Jan 28. Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous Recombination and Genome Stability. |
| GO:0032991 protein-containing complex | IDA PMID:26833090 Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologo... | ACCEPT | Summary: BRCA2 is part of HR protein complex. Reason: BRCA2 functions in multi-protein complexes. Supporting Evidence: PMID:26833090 2016 Jan 28. Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous Recombination and Genome Stability. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709601 | ACCEPT | Summary: Reactome pathway annotation. Reason: Nucleoplasm localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9709268 | KEEP AS NON CORE | Summary: Reactome pathway annotation. Reason: Secondary localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9709273 | KEEP AS NON CORE | Summary: Reactome pathway annotation. Reason: Secondary localization. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9763137 | KEEP AS NON CORE | Summary: Reactome pathway - BRCA2 binds SEM1(DSS1). Reason: Secondary localization. |
| GO:0032991 protein-containing complex | IDA PMID:9774970 Stable interaction between the products of the BRCA1 and BRC... | ACCEPT | Summary: BRCA1-BRCA2 complex in mitotic and meiotic cells. Reason: BRCA2 forms complexes with BRCA1 and other HR proteins. Supporting Evidence: PMID:9774970 Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. |
| GO:0000800 lateral element | IDA PMID:9774970 Stable interaction between the products of the BRCA1 and BRC... | KEEP AS NON CORE | Summary: BRCA2 localizes to synaptonemal complex lateral elements during meiosis. Reason: Meiosis-specific localization for meiotic HR function. Supporting Evidence: PMID:9774970 Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. |
| GO:0000781 chromosome, telomeric region | IDA PMID:21076401 BRCA2 acts as a RAD51 loader to facilitate telomere replicat... | KEEP AS NON CORE | Summary: BRCA2 acts as RAD51 loader at telomeres for telomere replication and capping. Reason: Telomeric localization for HR-dependent telomere maintenance. Supporting Evidence: PMID:21076401 Nov 14. BRCA2 acts as a RAD51 loader to facilitate telomere replication and capping. |
| GO:0070200 establishment of protein localization to telomere | IDA PMID:21076401 BRCA2 acts as a RAD51 loader to facilitate telomere replicat... | KEEP AS NON CORE | Summary: BRCA2 localizes RAD51 to telomeres. Reason: Extension of BRCA2's RAD51 loading function to telomeres. Supporting Evidence: PMID:21076401 Nov 14. BRCA2 acts as a RAD51 loader to facilitate telomere replication and capping. |
| GO:1990426 mitotic recombination-dependent replication fork processing | IMP PMID:21076401 BRCA2 acts as a RAD51 loader to facilitate telomere replicat... | ACCEPT | Summary: BRCA2 required for recombination-dependent fork processing at telomeres. Reason: Core function - BRCA2's role in replication fork processing is well-established. Supporting Evidence: PMID:21076401 Nov 14. BRCA2 acts as a RAD51 loader to facilitate telomere replication and capping. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685242 | ACCEPT | Summary: Reactome - CHEK1 phosphorylates BRCA2. Reason: Nucleoplasm localization during checkpoint signaling. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685341 | ACCEPT | Summary: Reactome - BCDX2 complex stabilizes RAD51 filament. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5685838 | ACCEPT | Summary: Reactome - CX3 complex binds D-loop. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686410 | ACCEPT | Summary: Reactome - BLM mediates dissolution of double Holliday junction. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686440 | ACCEPT | Summary: Reactome - MUS81:EME1,EME2 cleaves D-loop. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686469 | ACCEPT | Summary: Reactome - Resolution of D-loops. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686483 | ACCEPT | Summary: Reactome - Resolution of Holliday junctions. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693539 | ACCEPT | Summary: Reactome - Ligation of DNA and Holliday structure formation. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693561 | ACCEPT | Summary: Reactome - RAD51 binds BRCA2 at resected DSBs. Reason: Core nucleoplasm localization for HR. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693584 | ACCEPT | Summary: Reactome - Cleavage of Holliday junctions. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693589 | ACCEPT | Summary: Reactome - D-loop dissociation and strand annealing. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693593 | ACCEPT | Summary: Reactome - D-loop extension by DNA polymerases. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693620 | ACCEPT | Summary: Reactome - D-loop formation mediated by PALB2, BRCA2 and RAD51. Reason: Core nucleoplasm localization for HR function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9701199 | ACCEPT | Summary: Reactome - Defective D-loop formation due to BRCA1 loss. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704330 | ACCEPT | Summary: Reactome - Defective D-loop formation due to PALB2 loss. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9704408 | ACCEPT | Summary: Reactome - Defective D-loop formation. Reason: Nucleoplasm localization. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9853389 | ACCEPT | Summary: Reactome - FIGNL1 binds RAD51. Reason: Nucleoplasm localization. |
| GO:0005813 centrosome | IDA PMID:21276791 Homologous recombination proteins are associated with centro... | KEEP AS NON CORE | Summary: HR proteins including BRCA2 associate with centrosomes. Reason: Centrosome localization is secondary to nuclear DNA repair function. Supporting Evidence: PMID:21276791 Epub 2011 Jan 27. Homologous recombination proteins are associated with centrosomes and are required for mitotic stability. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9709273 | ACCEPT | Summary: Reactome - BRCA2 translocates to nucleus. Reason: Nucleoplasm localization. |
| GO:0051298 centrosome duplication | IMP PMID:17286961 Interference with BRCA2, which localizes to the centrosome d... | KEEP AS NON CORE | Summary: BRCA2 interference leads to abnormal centrosome duplication. Reason: BRCA2 affects centrosome function but this is secondary to HR. Supporting Evidence: PMID:17286961 Interference with BRCA2, which localizes to the centrosome during S and early M phase, leads to abnormal nuclear division. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:9126734 Transcriptional activation functions in BRCA2. | KEEP AS NON CORE | Summary: BRCA2 contains transcriptional activation functions in its N-terminus. Reason: BRCA2 has transcriptional activation activity but this is not its primary function. Supporting Evidence: PMID:9126734 Transcriptional activation functions in BRCA2. |
| GO:0033593 BRCA2-MAGE-D1 complex | IDA PMID:15930293 BRCA2 suppresses cell proliferation via stabilizing MAGE-D1. | KEEP AS NON CORE | Summary: BRCA2 forms complex with MAGE-D1 to suppress cell proliferation. Reason: This complex has anti-proliferative function but is not central to BRCA2's HR role. Supporting Evidence: PMID:15930293 BRCA2 suppresses cell proliferation via stabilizing MAGE-D1. |
| GO:0033600 negative regulation of mammary gland epithelial cell proliferation | IDA PMID:15930293 BRCA2 suppresses cell proliferation via stabilizing MAGE-D1. | KEEP AS NON CORE | Summary: BRCA2-MAGE-D1 complex suppresses mammary epithelial proliferation. Reason: Anti-proliferative function is tissue-specific and secondary. Supporting Evidence: PMID:15930293 BRCA2 suppresses cell proliferation via stabilizing MAGE-D1. |
| GO:0005634 nucleus | IDA PMID:17286961 Interference with BRCA2, which localizes to the centrosome d... | ACCEPT | Summary: Nuclear localization during S and early M phase. Reason: Core nuclear localization. Supporting Evidence: PMID:17286961 Interference with BRCA2, which localizes to the centrosome during S and early M phase, leads to abnormal nuclear division. |
| GO:0005634 nucleus | IDA PMID:9560268 The BRC repeats in BRCA2 are critical for RAD51 binding and ... | ACCEPT | Summary: Nuclear localization for RAD51 binding. Reason: Core nuclear localization. Supporting Evidence: PMID:9560268 The BRC repeats in BRCA2 are critical for RAD51 binding and resistance to methyl methanesulfonate treatment. |
| GO:0005634 nucleus | IDA PMID:9774970 Stable interaction between the products of the BRCA1 and BRC... | ACCEPT | Summary: Nuclear localization in mitotic and meiotic cells. Reason: Core nuclear localization. Supporting Evidence: PMID:9774970 Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells. |
| GO:0005813 centrosome | IDA PMID:17286961 Interference with BRCA2, which localizes to the centrosome d... | KEEP AS NON CORE | Summary: Centrosome localization during S and early M phase. Reason: Secondary localization. Supporting Evidence: PMID:17286961 Interference with BRCA2, which localizes to the centrosome during S and early M phase, leads to abnormal nuclear division. |
| GO:0006289 nucleotide-excision repair | IMP PMID:16845393 The role of BRCA2 in replication-coupled DNA interstrand cro... | KEEP AS NON CORE | Summary: BRCA2 role in replication-coupled DNA interstrand cross-link repair. Reason: BRCA2's primary role is HR, but it participates in ICL repair which involves NER components. Supporting Evidence: PMID:16845393 Jul 16. The role of BRCA2 in replication-coupled DNA interstrand cross-link repair in vitro. |
| GO:0006302 double-strand break repair | IMP PMID:16845393 The role of BRCA2 in replication-coupled DNA interstrand cro... | ACCEPT | Summary: BRCA2 required for DSB repair in ICL repair context. Reason: DSB repair is a core BRCA2 function. Supporting Evidence: PMID:16845393 Jul 16. The role of BRCA2 in replication-coupled DNA interstrand cross-link repair in vitro. |
| GO:0030141 secretory granule | IDA PMID:8589722 BRCA1 is secreted and exhibits properties of a granin. | UNDECIDED | Summary: Old study claiming BRCA1 secretion and granin properties. Reference seems to be about BRCA1 not BRCA2. Reason: This reference (PMID:8589722) appears to be about BRCA1, not BRCA2. Possible annotation error. Needs verification. Supporting Evidence: PMID:8589722 BRCA1 is secreted and exhibits properties of a granin. |
| GO:0000730 DNA recombinase assembly | IEA | NEW | Summary: BRCA2 facilitates RAD51 recombinase assembly on single-stranded DNA by targeting RAD51 to ssDNA over dsDNA, enabling RAD51 to displace RPA and stabilizing RAD51-ssDNA nucleoprotein filaments. Reason: BRCA2 promotes assembly of RAD51 onto single-stranded DNA. This is a core function essential for homologous recombination repair. Well-supported by biochemical studies. Supporting Evidence: file:human/BRCA2/BRCA2-deep-research-falcon.md BRCA2 mediates homologous recombination (HR) by loading and stabilizing the recombinase RAD51 on resected single-stranded DNA (ssDNA) to form the presynaptic filament required for homology search and strand exchange PMID:36976771 BRCA2 regulates recombination by initiating RAD51 filament formation |
| GO:0042148 DNA strand invasion | IEA | NEW | Summary: BRCA2 facilitates strand invasion during homologous recombination by promoting RAD51 nucleoprotein filament formation. BRCA2 may also play a role in the extension step after strand invasion at replication-dependent DSBs. Reason: BRCA2 promotes RAD51 filament formation which is essential for strand invasion during HR. Working with PALB2, BRCA2 is involved in POLH localization at collapsed forks and DNA polymerization. Supporting Evidence: file:human/BRCA2/BRCA2-deep-research-falcon.md D-loop formation mediated by PALB2, BRCA2 and RAD51 |
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