id: Q6UWZ7 gene_symbol: ABRAXAS1 product_type: PROTEIN status: DRAFT taxon: id: NCBITaxon:9606 label: Homo sapiens description: >- ABRAXAS1 encodes a nuclear BRCA1-A complex subunit that acts as a scaffold linking BRCA1, UIMC1/RAP80, BRCC3/BRCC36, BABAM proteins, and ubiquitin-dependent DNA damage-site signaling. The protein contains an MPN-like domain, binds polyubiquitin as part of the BRCA1-A/RAP80 complex, and supports BRCA1 recruitment, DNA double-strand break repair, K63-ubiquitin signal editing by BRCC36, and G2/M DNA damage checkpoint responses. alternative_products: - name: '1' id: Q6UWZ7-1 - name: '2' id: Q6UWZ7-2 sequence_note: VSP_058196 existing_annotations: - term: id: GO:0005634 label: nucleus evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in review: summary: >- Supported nuclear localization. ABRAXAS1 acts in the nuclear DNA damage response and localizes to DNA damage sites within the nucleus. action: ACCEPT reason: >- The UniProt record and the original BRCA1-A studies place ABRAXAS1 in the nucleus, where it recruits/organizes BRCA1-A complex activity at DNA double-strand breaks. supported_by: - reference_id: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122}. - reference_id: PMID:17525340 supporting_text: RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation - term: id: GO:0008017 label: microtubule binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: >- Likely paralog/family over-propagation. The IBA trace for this microtubule-binding term cites ABRAXAS2 rather than ABRAXAS1-specific evidence. action: REMOVE reason: >- ABRAXAS1 literature, UniProt, Reactome, and PN context support a nuclear BRCA1-A DNA damage-response scaffold, not microtubule binding. No ABRAXAS1-specific microtubule-binding evidence was found in the cached evidence set. additional_reference_ids: - file:interpro/panther/PTHR31728/PTHR31728-entries.csv supported_by: - reference_id: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt supporting_text: Involved in DNA damage response and double-strand break (DSB) repair. - reference_id: file:human/ABRAXAS1/ABRAXAS1-notes.md supporting_text: The IBA microtubule/spindle annotations are projected through a PANTHER node supported by ABRAXAS2 - term: id: GO:0008608 label: attachment of spindle microtubules to kinetochore evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: >- Likely paralog/family over-propagation. The kinetochore-microtubule attachment IBA is not supported by ABRAXAS1-specific DNA damage literature. action: REMOVE reason: >- The with/from metadata points to ABRAXAS2 for the spindle branch, while ABRAXAS1 evidence supports BRCA1-A complex-mediated DNA damage signaling. This process would overstate ABRAXAS1 biology. additional_reference_ids: - file:interpro/panther/PTHR31728/PTHR31728-entries.csv supported_by: - reference_id: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt supporting_text: Involved in DNA damage response and double-strand break (DSB) repair. - reference_id: file:human/ABRAXAS1/ABRAXAS1-notes.md supporting_text: I marked `microtubule binding`, `attachment of spindle microtubules to kinetochore`, and `mitotic spindle assembly` for removal for ABRAXAS1. - term: id: GO:0031593 label: polyubiquitin modification-dependent protein binding evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables review: summary: >- Core molecular function. ABRAXAS1 is part of a BRCA1-A/RAP80 complex that recognizes ubiquitinated damage-site chromatin and has polyubiquitin-binding capacity. action: ACCEPT reason: >- The term captures the ubiquitin-recognition side of ABRAXAS1 biology better than generic protein binding. It should be retained for both direct IDA and IBA evidence. supported_by: - reference_id: PMID:19261749 supporting_text: four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability - reference_id: PMID:20656689 supporting_text: RAP80, in turn, is recruited to DSBs through its tandem ubiquitin-interacting motifs (UIMs) ( 6 , 14 – 16 ), which specifically recognize K63-Ub chains - term: id: GO:0090307 label: mitotic spindle assembly evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in review: summary: >- Likely paralog/family over-propagation. The mitotic-spindle-assembly IBA is not supported for ABRAXAS1 by the reviewed evidence. action: REMOVE reason: >- ABRAXAS1 participates in nuclear DNA damage repair/checkpoint signaling. The PANTHER IBA spindle call is traceable to ABRAXAS2 and should not be propagated to ABRAXAS1 without gene-specific evidence. additional_reference_ids: - file:interpro/panther/PTHR31728/PTHR31728-entries.csv supported_by: - reference_id: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt supporting_text: Involved in DNA damage response and double-strand break (DSB) repair. - reference_id: file:human/ABRAXAS1/ABRAXAS1-notes.md supporting_text: I marked `microtubule binding`, `attachment of spindle microtubules to kinetochore`, and `mitotic spindle assembly` for removal for ABRAXAS1. - term: id: GO:0005634 label: nucleus evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in review: summary: >- Supported nuclear localization. ABRAXAS1 acts in the nuclear DNA damage response and localizes to DNA damage sites within the nucleus. action: ACCEPT reason: >- The UniProt record and the original BRCA1-A studies place ABRAXAS1 in the nucleus, where it recruits/organizes BRCA1-A complex activity at DNA double-strand breaks. supported_by: - reference_id: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122}. - reference_id: PMID:17525340 supporting_text: RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17525340 qualifier: enables review: summary: >- Interaction evidence is real, but the GO term protein binding is too generic to describe ABRAXAS1 function. action: MARK_AS_OVER_ANNOTATED reason: >- These IPI rows should not be treated as core molecular-function annotations. The informative biology is BRCA1-A complex assembly, RAP80/BRCA1/BRCC36 interactions, and polyubiquitin-dependent recruitment; broad interactome rows are even less suitable as function claims. supported_by: - reference_id: PMID:17525340 supporting_text: identified a protein, Abraxas, that directly binds the BRCA1 BRCT repeats - reference_id: PMID:20656689 supporting_text: The RAP80 complex is a five-member stoichiometric complex consisting of RAP80, BRCC36, BRCC45, Abraxas, and MERIT40 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:17643121 qualifier: enables review: summary: >- Interaction evidence is real, but the GO term protein binding is too generic to describe ABRAXAS1 function. action: MARK_AS_OVER_ANNOTATED reason: >- These IPI rows should not be treated as core molecular-function annotations. The informative biology is BRCA1-A complex assembly, RAP80/BRCA1/BRCC36 interactions, and polyubiquitin-dependent recruitment; broad interactome rows are even less suitable as function claims. supported_by: - reference_id: PMID:17643121 supporting_text: CCDC98 is a BRCA1 binding partner that mediates BRCA1 function in response to DNA damage. - reference_id: PMID:20656689 supporting_text: The RAP80 complex is a five-member stoichiometric complex consisting of RAP80, BRCC36, BRCC45, Abraxas, and MERIT40 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:18077395 qualifier: enables review: summary: >- Interaction evidence is real, but the GO term protein binding is too generic to describe ABRAXAS1 function. action: MARK_AS_OVER_ANNOTATED reason: >- These IPI rows should not be treated as core molecular-function annotations. The informative biology is BRCA1-A complex assembly, RAP80/BRCA1/BRCC36 interactions, and polyubiquitin-dependent recruitment; broad interactome rows are even less suitable as function claims. supported_by: - reference_id: PMID:18077395 supporting_text: Rap80 contains an Abraxas interaction domain - reference_id: PMID:20656689 supporting_text: The RAP80 complex is a five-member stoichiometric complex consisting of RAP80, BRCC36, BRCC45, Abraxas, and MERIT40 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19615732 qualifier: enables review: summary: >- Interaction evidence is real, but the GO term protein binding is too generic to describe ABRAXAS1 function. action: MARK_AS_OVER_ANNOTATED reason: >- These IPI rows should not be treated as core molecular-function annotations. The informative biology is BRCA1-A complex assembly, RAP80/BRCA1/BRCC36 interactions, and polyubiquitin-dependent recruitment; broad interactome rows are even less suitable as function claims. supported_by: - reference_id: PMID:19615732 supporting_text: We identified 774 candidate interacting proteins associated with 75 Dubs. - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:29656893 qualifier: enables review: summary: >- Interaction evidence is real, but the GO term protein binding is too generic to describe ABRAXAS1 function. action: MARK_AS_OVER_ANNOTATED reason: >- These IPI rows should not be treated as core molecular-function annotations. The informative biology is BRCA1-A complex assembly, RAP80/BRCA1/BRCC36 interactions, and polyubiquitin-dependent recruitment; broad interactome rows are even less suitable as function claims. supported_by: - reference_id: PMID:29656893 supporting_text: we generated high-resolution interaction neighborhood maps of the endogenously expressed DNA repair factors 53BP1, BRCA1, and MDC1 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:34591612 qualifier: enables review: summary: >- Interaction evidence is real, but the GO term protein binding is too generic to describe ABRAXAS1 function. action: MARK_AS_OVER_ANNOTATED reason: >- These IPI rows should not be treated as core molecular-function annotations. The informative biology is BRCA1-A complex assembly, RAP80/BRCA1/BRCC36 interactions, and polyubiquitin-dependent recruitment; broad interactome rows are even less suitable as function claims. supported_by: - reference_id: PMID:34591612 supporting_text: we generated comprehensive interaction maps for 40 frequently altered BC proteins - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:35156780 qualifier: enables review: summary: >- Interaction evidence is real, but the GO term protein binding is too generic to describe ABRAXAS1 function. action: MARK_AS_OVER_ANNOTATED reason: >- These IPI rows should not be treated as core molecular-function annotations. The informative biology is BRCA1-A complex assembly, RAP80/BRCA1/BRCC36 interactions, and polyubiquitin-dependent recruitment; broad interactome rows are even less suitable as function claims. supported_by: - reference_id: PMID:35156780 supporting_text: high-throughput screening variant of the Mammalian Membrane Two-Hybrid - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:36012204 qualifier: enables review: summary: >- Interaction evidence is real, but the GO term protein binding is too generic to describe ABRAXAS1 function. action: MARK_AS_OVER_ANNOTATED reason: >- These IPI rows should not be treated as core molecular-function annotations. The informative biology is BRCA1-A complex assembly, RAP80/BRCA1/BRCC36 interactions, and polyubiquitin-dependent recruitment; broad interactome rows are even less suitable as function claims. supported_by: - reference_id: PMID:36012204 supporting_text: proximity labeling approaches identified both known and additional CFTR protein partners - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:39009827 qualifier: enables review: summary: >- Interaction evidence is real, but the GO term protein binding is too generic to describe ABRAXAS1 function. action: MARK_AS_OVER_ANNOTATED reason: >- These IPI rows should not be treated as core molecular-function annotations. The informative biology is BRCA1-A complex assembly, RAP80/BRCA1/BRCC36 interactions, and polyubiquitin-dependent recruitment; broad interactome rows are even less suitable as function claims. supported_by: - reference_id: PMID:39009827 supporting_text: we identified 366 mutation-modulated interactions - term: id: GO:0016604 label: nuclear body evidence_type: IDA original_reference_id: GO_REF:0000052 qualifier: located_in review: summary: >- Non-core localization. HPA reports nuclear-body staining, while mechanistic ABRAXAS1 biology centers on DNA damage foci/BRCA1-A complex recruitment. action: KEEP_AS_NON_CORE reason: >- This cellular component is plausible as a localization observation, but it is less informative than nucleus/nucleoplasm and BRCA1-A complex membership for the gene product function. supported_by: - reference_id: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt supporting_text: Localizes at sites of DNA damage at double-strand breaks (DSBs). - term: id: GO:0005634 label: nucleus evidence_type: NAS original_reference_id: PMID:20656689 qualifier: located_in review: summary: >- Supported nuclear localization. ABRAXAS1 acts in the nuclear DNA damage response and localizes to DNA damage sites within the nucleus. action: ACCEPT reason: >- The UniProt record and the original BRCA1-A studies place ABRAXAS1 in the nucleus, where it recruits/organizes BRCA1-A complex activity at DNA double-strand breaks. supported_by: - reference_id: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122}. - reference_id: PMID:17525340 supporting_text: RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation - term: id: GO:0006282 label: regulation of DNA repair evidence_type: NAS original_reference_id: PMID:20656689 qualifier: involved_in review: summary: >- The broad regulation-of-DNA-repair annotation is directionally correct but less precise than positive regulation of DNA repair for ABRAXAS1. action: MODIFY reason: >- ABRAXAS1 promotes BRCA1-A complex recruitment/stability and DNA repair after damage; the reviewed IMP annotations already use the more informative positive-regulation term. proposed_replacement_terms: - id: GO:0045739 label: positive regulation of DNA repair supported_by: - reference_id: PMID:17525340 supporting_text: Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. - reference_id: PMID:19261748 supporting_text: a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization - term: id: GO:0044818 label: mitotic G2/M transition checkpoint evidence_type: NAS original_reference_id: PMID:22369660 qualifier: involved_in review: summary: >- The ComplexPortal/NAS checkpoint annotation is real but should be represented using the more specific DNA-damage checkpoint signaling term. action: MODIFY reason: >- ABRAXAS1 evidence concerns BRCA1-dependent G2/M checkpoint activation in response to DNA damage, not the generic mitotic G2/M transition checkpoint. proposed_replacement_terms: - id: GO:0007095 label: mitotic G2 DNA damage checkpoint signaling supported_by: - reference_id: PMID:17643121 supporting_text: CCDC98 controls both DNA damage-induced formation of BRCA1 foci and BRCA1-dependent G2/M checkpoint activation - reference_id: PMID:22369660 supporting_text: Studies on A, B and C complexes of BRCA1 indicate that these complexes carry out functions of BRCA1 in cell cycle checkpoint control. - term: id: GO:0070531 label: BRCA1-A complex evidence_type: NAS original_reference_id: PMID:20656689 qualifier: part_of review: summary: >- Core complex membership. ABRAXAS1 is a BRCA1-A complex subunit that organizes BRCA1, UIMC1/RAP80, BRCC3/BRCC36, BABAM proteins, and related DDR functions. action: ACCEPT reason: >- Multiple primary studies and Reactome support ABRAXAS1/FAM175A as a BRCA1-A complex component. This is more precise than the PN-projected generic ubiquitin-ligase-complex bucket. additional_reference_ids: - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv - file:projects/PROTEOSTASIS/mappings/ubiquitin_proteasome_system.yaml supported_by: - reference_id: PMID:19261749 supporting_text: Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0007095 label: mitotic G2 DNA damage checkpoint signaling evidence_type: IMP original_reference_id: PMID:17525340 qualifier: involved_in review: summary: >- Core checkpoint process. ABRAXAS1/CCDC98 is required for BRCA1-dependent G2/M checkpoint signaling after DNA damage. action: ACCEPT reason: >- The original ABRAXAS1/CCDC98 work and later BRCA1-A review evidence support a G2 DNA damage checkpoint role. This is part of the DNA damage response function rather than a general mitotic-spindle role. supported_by: - reference_id: PMID:17643121 supporting_text: CCDC98 controls both DNA damage-induced formation of BRCA1 foci and BRCA1-dependent G2/M checkpoint activation - reference_id: PMID:22369660 supporting_text: Studies on A, B and C complexes of BRCA1 indicate that these complexes carry out functions of BRCA1 in cell cycle checkpoint control. - term: id: GO:0007095 label: mitotic G2 DNA damage checkpoint signaling evidence_type: IMP original_reference_id: PMID:17643121 qualifier: involved_in review: summary: >- Core checkpoint process. ABRAXAS1/CCDC98 is required for BRCA1-dependent G2/M checkpoint signaling after DNA damage. action: ACCEPT reason: >- The original ABRAXAS1/CCDC98 work and later BRCA1-A review evidence support a G2 DNA damage checkpoint role. This is part of the DNA damage response function rather than a general mitotic-spindle role. supported_by: - reference_id: PMID:17643121 supporting_text: CCDC98 controls both DNA damage-induced formation of BRCA1 foci and BRCA1-dependent G2/M checkpoint activation - reference_id: PMID:22369660 supporting_text: Studies on A, B and C complexes of BRCA1 indicate that these complexes carry out functions of BRCA1 in cell cycle checkpoint control. - term: id: GO:0007095 label: mitotic G2 DNA damage checkpoint signaling evidence_type: IMP original_reference_id: PMID:19261748 qualifier: involved_in review: summary: >- Core checkpoint process. ABRAXAS1/CCDC98 is required for BRCA1-dependent G2/M checkpoint signaling after DNA damage. action: ACCEPT reason: >- The original ABRAXAS1/CCDC98 work and later BRCA1-A review evidence support a G2 DNA damage checkpoint role. This is part of the DNA damage response function rather than a general mitotic-spindle role. supported_by: - reference_id: PMID:17643121 supporting_text: CCDC98 controls both DNA damage-induced formation of BRCA1 foci and BRCA1-dependent G2/M checkpoint activation - reference_id: PMID:22369660 supporting_text: Studies on A, B and C complexes of BRCA1 indicate that these complexes carry out functions of BRCA1 in cell cycle checkpoint control. - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5683384 qualifier: located_in review: summary: >- Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. action: ACCEPT reason: >- The nucleoplasm location is consistent with ABRAXAS1 nuclear localization and Reactome DNA double-strand break events. These duplicate TAS rows reflect pathway-event participation rather than distinct localizations. supported_by: - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5683385 qualifier: located_in review: summary: >- Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. action: ACCEPT reason: >- The nucleoplasm location is consistent with ABRAXAS1 nuclear localization and Reactome DNA double-strand break events. These duplicate TAS rows reflect pathway-event participation rather than distinct localizations. supported_by: - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5683735 qualifier: located_in review: summary: >- Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. action: ACCEPT reason: >- The nucleoplasm location is consistent with ABRAXAS1 nuclear localization and Reactome DNA double-strand break events. These duplicate TAS rows reflect pathway-event participation rather than distinct localizations. supported_by: - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5683801 qualifier: located_in review: summary: >- Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. action: ACCEPT reason: >- The nucleoplasm location is consistent with ABRAXAS1 nuclear localization and Reactome DNA double-strand break events. These duplicate TAS rows reflect pathway-event participation rather than distinct localizations. supported_by: - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5684052 qualifier: located_in review: summary: >- Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. action: ACCEPT reason: >- The nucleoplasm location is consistent with ABRAXAS1 nuclear localization and Reactome DNA double-strand break events. These duplicate TAS rows reflect pathway-event participation rather than distinct localizations. supported_by: - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5684071 qualifier: located_in review: summary: >- Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. action: ACCEPT reason: >- The nucleoplasm location is consistent with ABRAXAS1 nuclear localization and Reactome DNA double-strand break events. These duplicate TAS rows reflect pathway-event participation rather than distinct localizations. supported_by: - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5686685 qualifier: located_in review: summary: >- Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. action: ACCEPT reason: >- The nucleoplasm location is consistent with ABRAXAS1 nuclear localization and Reactome DNA double-strand break events. These duplicate TAS rows reflect pathway-event participation rather than distinct localizations. supported_by: - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5691411 qualifier: located_in review: summary: >- Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. action: ACCEPT reason: >- The nucleoplasm location is consistent with ABRAXAS1 nuclear localization and Reactome DNA double-strand break events. These duplicate TAS rows reflect pathway-event participation rather than distinct localizations. supported_by: - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-5693551 qualifier: located_in review: summary: >- Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. action: ACCEPT reason: >- The nucleoplasm location is consistent with ABRAXAS1 nuclear localization and Reactome DNA double-strand break events. These duplicate TAS rows reflect pathway-event participation rather than distinct localizations. supported_by: - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0005654 label: nucleoplasm evidence_type: TAS original_reference_id: Reactome:R-HSA-69891 qualifier: located_in review: summary: >- Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. action: ACCEPT reason: >- The nucleoplasm location is consistent with ABRAXAS1 nuclear localization and Reactome DNA double-strand break events. These duplicate TAS rows reflect pathway-event participation rather than distinct localizations. supported_by: - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19261748 qualifier: enables review: summary: >- Interaction evidence is real, but the GO term protein binding is too generic to describe ABRAXAS1 function. action: MARK_AS_OVER_ANNOTATED reason: >- These IPI rows should not be treated as core molecular-function annotations. The informative biology is BRCA1-A complex assembly, RAP80/BRCA1/BRCC36 interactions, and polyubiquitin-dependent recruitment; broad interactome rows are even less suitable as function claims. supported_by: - reference_id: PMID:19261748 supporting_text: CCDC98 binds to RAP80 via a large N-terminal region - reference_id: PMID:20656689 supporting_text: The RAP80 complex is a five-member stoichiometric complex consisting of RAP80, BRCC36, BRCC45, Abraxas, and MERIT40 - term: id: GO:0005515 label: protein binding evidence_type: IPI original_reference_id: PMID:19261749 qualifier: enables review: summary: >- Interaction evidence is real, but the GO term protein binding is too generic to describe ABRAXAS1 function. action: MARK_AS_OVER_ANNOTATED reason: >- These IPI rows should not be treated as core molecular-function annotations. The informative biology is BRCA1-A complex assembly, RAP80/BRCA1/BRCC36 interactions, and polyubiquitin-dependent recruitment; broad interactome rows are even less suitable as function claims. supported_by: - reference_id: PMID:19261749 supporting_text: four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability - reference_id: PMID:20656689 supporting_text: The RAP80 complex is a five-member stoichiometric complex consisting of RAP80, BRCC36, BRCC45, Abraxas, and MERIT40 - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:17525340 qualifier: located_in review: summary: >- Supported nuclear localization. ABRAXAS1 acts in the nuclear DNA damage response and localizes to DNA damage sites within the nucleus. action: ACCEPT reason: >- The UniProt record and the original BRCA1-A studies place ABRAXAS1 in the nucleus, where it recruits/organizes BRCA1-A complex activity at DNA double-strand breaks. supported_by: - reference_id: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122}. - reference_id: PMID:17525340 supporting_text: RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation - term: id: GO:0005634 label: nucleus evidence_type: IDA original_reference_id: PMID:17643121 qualifier: located_in review: summary: >- Supported nuclear localization. ABRAXAS1 acts in the nuclear DNA damage response and localizes to DNA damage sites within the nucleus. action: ACCEPT reason: >- The UniProt record and the original BRCA1-A studies place ABRAXAS1 in the nucleus, where it recruits/organizes BRCA1-A complex activity at DNA double-strand breaks. supported_by: - reference_id: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt supporting_text: Nucleus {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122}. - reference_id: PMID:17525340 supporting_text: RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation - term: id: GO:0006302 label: double-strand break repair evidence_type: IMP original_reference_id: PMID:17525340 qualifier: involved_in review: summary: >- Core biological process. ABRAXAS1 is required for efficient DNA double-strand break repair through BRCA1-A recruitment and ubiquitin-dependent damage-site signaling. action: ACCEPT reason: >- Loss/depletion experiments in the original ABRAXAS1/CCDC98 papers support DNA repair and DNA damage resistance. The PN-projected broader DNA repair term is already entailed by this annotation. additional_reference_ids: - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv supported_by: - reference_id: PMID:17525340 supporting_text: Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. - reference_id: PMID:19261748 supporting_text: a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization - term: id: GO:0006302 label: double-strand break repair evidence_type: IMP original_reference_id: PMID:17643121 qualifier: involved_in review: summary: >- Core biological process. ABRAXAS1 is required for efficient DNA double-strand break repair through BRCA1-A recruitment and ubiquitin-dependent damage-site signaling. action: ACCEPT reason: >- Loss/depletion experiments in the original ABRAXAS1/CCDC98 papers support DNA repair and DNA damage resistance. The PN-projected broader DNA repair term is already entailed by this annotation. additional_reference_ids: - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv supported_by: - reference_id: PMID:17525340 supporting_text: Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. - reference_id: PMID:19261748 supporting_text: a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization - term: id: GO:0006302 label: double-strand break repair evidence_type: IMP original_reference_id: PMID:19261748 qualifier: involved_in review: summary: >- Core biological process. ABRAXAS1 is required for efficient DNA double-strand break repair through BRCA1-A recruitment and ubiquitin-dependent damage-site signaling. action: ACCEPT reason: >- Loss/depletion experiments in the original ABRAXAS1/CCDC98 papers support DNA repair and DNA damage resistance. The PN-projected broader DNA repair term is already entailed by this annotation. additional_reference_ids: - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv supported_by: - reference_id: PMID:17525340 supporting_text: Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. - reference_id: PMID:19261748 supporting_text: a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization - term: id: GO:0010212 label: response to ionizing radiation evidence_type: IMP original_reference_id: PMID:17525340 qualifier: involved_in review: summary: >- Supported but non-core phenotype/context annotation. Ionizing radiation is the experimental damage stimulus used to reveal ABRAXAS1 DNA damage-response function. action: KEEP_AS_NON_CORE reason: >- The IR response annotations should be retained as useful experimental context, but the core process is DNA double-strand break repair/checkpoint signaling through BRCA1-A. supported_by: - reference_id: PMID:18077395 supporting_text: the entire Brca1 A complex to DNA-damage foci - reference_id: PMID:19261749 supporting_text: required for resistance to ionizing radiation - term: id: GO:0010212 label: response to ionizing radiation evidence_type: IMP original_reference_id: PMID:17643121 qualifier: involved_in review: summary: >- Supported but non-core phenotype/context annotation. Ionizing radiation is the experimental damage stimulus used to reveal ABRAXAS1 DNA damage-response function. action: KEEP_AS_NON_CORE reason: >- The IR response annotations should be retained as useful experimental context, but the core process is DNA double-strand break repair/checkpoint signaling through BRCA1-A. supported_by: - reference_id: PMID:18077395 supporting_text: the entire Brca1 A complex to DNA-damage foci - reference_id: PMID:19261749 supporting_text: required for resistance to ionizing radiation - term: id: GO:0010212 label: response to ionizing radiation evidence_type: IMP original_reference_id: PMID:19261748 qualifier: involved_in review: summary: >- Supported but non-core phenotype/context annotation. Ionizing radiation is the experimental damage stimulus used to reveal ABRAXAS1 DNA damage-response function. action: KEEP_AS_NON_CORE reason: >- The IR response annotations should be retained as useful experimental context, but the core process is DNA double-strand break repair/checkpoint signaling through BRCA1-A. supported_by: - reference_id: PMID:18077395 supporting_text: the entire Brca1 A complex to DNA-damage foci - reference_id: PMID:19261749 supporting_text: required for resistance to ionizing radiation - term: id: GO:0031593 label: polyubiquitin modification-dependent protein binding evidence_type: IDA original_reference_id: PMID:19261749 qualifier: enables review: summary: >- Core molecular function. ABRAXAS1 is part of a BRCA1-A/RAP80 complex that recognizes ubiquitinated damage-site chromatin and has polyubiquitin-binding capacity. action: ACCEPT reason: >- The term captures the ubiquitin-recognition side of ABRAXAS1 biology better than generic protein binding. It should be retained for both direct IDA and IBA evidence. supported_by: - reference_id: PMID:19261749 supporting_text: four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability - reference_id: PMID:20656689 supporting_text: RAP80, in turn, is recruited to DSBs through its tandem ubiquitin-interacting motifs (UIMs) ( 6 , 14 – 16 ), which specifically recognize K63-Ub chains - term: id: GO:0045739 label: positive regulation of DNA repair evidence_type: IMP original_reference_id: PMID:17525340 qualifier: involved_in review: summary: >- Core regulatory process. ABRAXAS1 positively supports DNA repair by assembling/stabilizing the RAP80-BRCA1-A complex at DNA damage sites. action: ACCEPT reason: >- The evidence supports a positive role in DNA repair through BRCA1 localization, complex integrity, and BRCC36-associated ubiquitin editing rather than direct DNA repair catalysis. supported_by: - reference_id: PMID:17525340 supporting_text: Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. - reference_id: PMID:19261748 supporting_text: a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization - reference_id: PMID:20656689 supporting_text: Abraxas and BRCC45 were essential for BRCC36 DUB activity within the RAP80 complex - term: id: GO:0045739 label: positive regulation of DNA repair evidence_type: IMP original_reference_id: PMID:19261748 qualifier: involved_in review: summary: >- Core regulatory process. ABRAXAS1 positively supports DNA repair by assembling/stabilizing the RAP80-BRCA1-A complex at DNA damage sites. action: ACCEPT reason: >- The evidence supports a positive role in DNA repair through BRCA1 localization, complex integrity, and BRCC36-associated ubiquitin editing rather than direct DNA repair catalysis. supported_by: - reference_id: PMID:17525340 supporting_text: Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. - reference_id: PMID:19261748 supporting_text: a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization - reference_id: PMID:20656689 supporting_text: Abraxas and BRCC45 were essential for BRCC36 DUB activity within the RAP80 complex - term: id: GO:0070531 label: BRCA1-A complex evidence_type: IDA original_reference_id: PMID:17525340 qualifier: part_of review: summary: >- Core complex membership. ABRAXAS1 is a BRCA1-A complex subunit that organizes BRCA1, UIMC1/RAP80, BRCC3/BRCC36, BABAM proteins, and related DDR functions. action: ACCEPT reason: >- Multiple primary studies and Reactome support ABRAXAS1/FAM175A as a BRCA1-A complex component. This is more precise than the PN-projected generic ubiquitin-ligase-complex bucket. additional_reference_ids: - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv - file:projects/PROTEOSTASIS/mappings/ubiquitin_proteasome_system.yaml supported_by: - reference_id: PMID:19261749 supporting_text: Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0070531 label: BRCA1-A complex evidence_type: IDA original_reference_id: PMID:19261746 qualifier: part_of review: summary: >- Core complex membership. ABRAXAS1 is a BRCA1-A complex subunit that organizes BRCA1, UIMC1/RAP80, BRCC3/BRCC36, BABAM proteins, and related DDR functions. action: ACCEPT reason: >- Multiple primary studies and Reactome support ABRAXAS1/FAM175A as a BRCA1-A complex component. This is more precise than the PN-projected generic ubiquitin-ligase-complex bucket. additional_reference_ids: - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv - file:projects/PROTEOSTASIS/mappings/ubiquitin_proteasome_system.yaml supported_by: - reference_id: PMID:19261749 supporting_text: Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0070531 label: BRCA1-A complex evidence_type: IDA original_reference_id: PMID:19261748 qualifier: part_of review: summary: >- Core complex membership. ABRAXAS1 is a BRCA1-A complex subunit that organizes BRCA1, UIMC1/RAP80, BRCC3/BRCC36, BABAM proteins, and related DDR functions. action: ACCEPT reason: >- Multiple primary studies and Reactome support ABRAXAS1/FAM175A as a BRCA1-A complex component. This is more precise than the PN-projected generic ubiquitin-ligase-complex bucket. additional_reference_ids: - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv - file:projects/PROTEOSTASIS/mappings/ubiquitin_proteasome_system.yaml supported_by: - reference_id: PMID:19261749 supporting_text: Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - term: id: GO:0070531 label: BRCA1-A complex evidence_type: IDA original_reference_id: PMID:19261749 qualifier: part_of review: summary: >- Core complex membership. ABRAXAS1 is a BRCA1-A complex subunit that organizes BRCA1, UIMC1/RAP80, BRCC3/BRCC36, BABAM proteins, and related DDR functions. action: ACCEPT reason: >- Multiple primary studies and Reactome support ABRAXAS1/FAM175A as a BRCA1-A complex component. This is more precise than the PN-projected generic ubiquitin-ligase-complex bucket. additional_reference_ids: - file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv - file:projects/PROTEOSTASIS/mappings/ubiquitin_proteasome_system.yaml supported_by: - reference_id: PMID:19261749 supporting_text: Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs references: - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees 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:0000052 title: Gene Ontology annotation based on curation of immunofluorescence data findings: [] - id: PMID:17525340 title: Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response. findings: - statement: ABRAXAS1/Abraxas binds BRCA1 BRCT repeats and RAP80, and is required for DNA damage resistance, G2/M checkpoint control, and DNA repair. supporting_text: Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. reference_section_type: ABSTRACT - id: PMID:17643121 title: CCDC98 targets BRCA1 to DNA damage sites. findings: [] - id: PMID:18077395 title: Ubc13/Rnf8 ubiquitin ligases control foci formation of the Rap80/Abraxas/Brca1/Brcc36 complex in response to DNA damage. findings: [] - id: PMID:19261746 title: MERIT40 controls BRCA1-Rap80 complex integrity and recruitment to DNA double-strand breaks. findings: [] - id: PMID:19261748 title: MERIT40 facilitates BRCA1 localization and DNA damage repair. findings: - statement: CCDC98/ABRAXAS1 is a central component for assembly of the RAP80-containing BRCA1-A complex at DNA damage sites. supporting_text: CCDC98 as the central component that facilitates the assembly of this protein complex reference_section_type: DISCUSSION - id: PMID:19261749 title: NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control. findings: [] - id: PMID:19615732 title: Defining the human deubiquitinating enzyme interaction landscape. findings: [] - id: PMID:20656689 title: Differential regulation of JAMM domain deubiquitinating enzyme activity within the RAP80 complex. findings: - statement: ABRAXAS1 is required for BRCC36 DUB activity in the RAP80/BRCA1-A complex context, but is not itself the catalytic DUB. supporting_text: Abraxas and BRCC45 were essential for BRCC36 DUB activity within the RAP80 complex reference_section_type: ABSTRACT - id: PMID:22369660 title: 'BRCA1 tumor suppressor network: focusing on its tail.' findings: [] - id: PMID:29656893 title: DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. findings: [] - id: PMID:34591612 title: A protein interaction landscape of breast cancer. findings: [] - id: PMID:35156780 title: CFTR interactome mapping using the mammalian membrane two-hybrid high-throughput screening system. findings: [] - id: PMID:36012204 title: Differential CFTR-Interactome Proximity Labeling Procedures Identify Enrichment in Multiple SLC Transporters. findings: [] - id: PMID:39009827 title: Proteome-scale characterisation of motif-based interactome rewiring by disease mutations. full_text_unavailable: true findings: - statement: ABRAXAS1 contains a functional nuclear localization signal around Arg361; the breast-cancer-associated R361Q mutation weakens importin/karyopherin binding approximately tenfold and increases cytoplasmic localization, providing a molecular basis for impaired nuclear import of the BRCA1-A complex. - id: Reactome:R-HSA-5683384 title: UIMC1 and FAM175A bind DNA DSBs findings: [] - id: Reactome:R-HSA-5683385 title: Formation of BRCA1-A complex at DNA DSBs findings: [] - id: Reactome:R-HSA-5683735 title: CHEK2 is recruited to DNA DSBs findings: [] - id: Reactome:R-HSA-5683801 title: CHEK2 phosphorylates BRCA1 findings: [] - id: Reactome:R-HSA-5684052 title: PIAS4 SUMOylates MDC1 findings: [] - id: Reactome:R-HSA-5684071 title: RNF4 ubiquitinates MDC1 findings: [] - id: Reactome:R-HSA-5686685 title: RIF1 and PAX1IP bind TP53BP1 at DNA DSBs findings: [] - id: Reactome:R-HSA-5691411 title: BRCA1-A complex deubiquitinates K63polyUb-histone H2A findings: [] - id: Reactome:R-HSA-5693551 title: Phosphorylation of BRCA1-A complex at multiple sites by ATM findings: [] - id: Reactome:R-HSA-69891 title: Phosphorylation and activation of CHEK2 by ATM findings: [] - id: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt title: ABRAXAS1 UniProtKB record findings: [] - id: file:human/ABRAXAS1/ABRAXAS1-notes.md title: ABRAXAS1 manual review notes and failed deep-research provenance findings: [] - id: file:projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv title: Proteostasis PN projected GO summary for ABRAXAS1 findings: [] - id: file:projects/PROTEOSTASIS/mappings/ubiquitin_proteasome_system.yaml title: Proteostasis ubiquitin proteasome system mapping file findings: [] - id: file:interpro/panther/PTHR31728/PTHR31728-entries.csv title: PANTHER PTHR31728 reviewed protein members findings: [] core_functions: - molecular_function: id: GO:0031593 label: polyubiquitin modification-dependent protein binding description: >- ABRAXAS1 is a scaffold and ubiquitin-recognition subunit of the nuclear BRCA1-A/RAP80 complex. It helps assemble BRCA1, UIMC1/RAP80, BRCC3/BRCC36, BABAM proteins, and related partners at ubiquitinated DNA double-strand break sites, thereby supporting BRCA1 recruitment, BRCC36-dependent K63-ubiquitin signal editing, DNA repair, and G2/M DNA damage checkpoint signaling. directly_involved_in: - id: GO:0006302 label: double-strand break repair - id: GO:0045739 label: positive regulation of DNA repair - id: GO:0007095 label: mitotic G2 DNA damage checkpoint signaling locations: - id: GO:0005634 label: nucleus - id: GO:0005654 label: nucleoplasm in_complex: id: GO:0070531 label: BRCA1-A complex supported_by: - reference_id: PMID:17525340 supporting_text: Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. - reference_id: PMID:19261748 supporting_text: CCDC98 as the central component that facilitates the assembly of this protein complex - reference_id: PMID:19261749 supporting_text: four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability - reference_id: PMID:20656689 supporting_text: Abraxas and BRCC45 were essential for BRCC36 DUB activity within the RAP80 complex - reference_id: Reactome:R-HSA-5683385 supporting_text: Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs - reference_id: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt supporting_text: Involved in DNA damage response and double-strand break (DSB) repair. proposed_new_terms: [] suggested_questions: - question: Should GO curation represent ABRAXAS1 only as part of the BRCA1-A complex, or is there enough evidence to annotate ABRAXAS1 to a broader ubiquitin ligase complex term despite its scaffold/DUB-support role? experts: - Wang B - Greenberg RA - Elledge SJ - question: Given evidence that ABRAXAS1 truncations shift BRCA1 partitioning toward BRCA1-C and derepress mutagenic repair (SSA/MMEJ) without impairing HR, should ABRAXAS1 carry a negative-regulation annotation for low-fidelity double-strand break repair pathways (e.g. single-strand annealing) in addition to its positive role in DNA repair? experts: - Wiesmuller L - Pylkas K - question: Is the reported RNA-dependent / direct RNA-binding behavior of ABRAXAS1 (R-DeeP and iCLIP2 in a single lung-cancer cell line) reproducible and functionally meaningful, or a cell-line-specific high-throughput artifact, before any RNA-binding annotation is considered? experts: - Diederichs S suggested_experiments: - hypothesis: The PANTHER-derived spindle and microtubule annotations are ABRAXAS2/paralog-specific and do not apply to ABRAXAS1. description: Compare ABRAXAS1 and ABRAXAS2 depletion or rescue in synchronized human cells using spindle assembly, kinetochore-microtubule attachment, and DNA damage-response readouts in the same experimental system. experiment_type: comparative cell biology - hypothesis: ABRAXAS1 restrains end resection and mutagenic double-strand break repair (single-strand annealing / microhomology-mediated end joining) by sequestering BRCA1 in the BRCA1-A complex, rather than simply promoting homologous recombination. description: Use chromosomally integrated DSB-repair reporters (HR, NHEJ, MMEJ, SSA) in cells expressing wild-type ABRAXAS1 versus C-terminal SPTF-motif and BRCC36-interaction truncation variants, measuring pathway-frequency shifts and end-resection markers (RPA, pRPA32, MRE11) to test pathway-choice control. experiment_type: DSB-repair pathway reporter assay