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.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Supported nuclear localization. ABRAXAS1 acts in the nuclear DNA damage response and localizes to DNA damage sites within the nucleus. 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. Supporting Evidence: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt Nucleus {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122}. PMID:17525340 RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation |
| GO:0008017 microtubule binding | IBA GO_REF:0000033 | UNDECIDED | Summary: The ABRAXAS2-grounded ancestral spindle/microtubule assertion is unresolved for ABRAXAS1. Reason: PAINT places this assertion at PTN001272083 with ABRAXAS2/Q15018 experimental support. PMID:26195665 directly establishes BRISC/ABRO1 microtubule association and NuMA-dependent spindle regulation. ABRAXAS1 assembles the distinct BRCA1-A complex, which makes functional divergence plausible, but its major nuclear DNA-repair role is not proof of exclusive localization or absence of mitotic activity. The existing OpenScientist report conflates lack of target assays with refutation and relies on donor identity without demonstrating target-specific loss. Retain uncertainty until mitotic localization, binding, or functional comparison resolves inheritance. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001272083 · PTN001272083 UNRESOLVED The metazoan IBD is experimentally seeded by ABRAXAS2. Distinct BRCA1-A versus BRISC partners suggest possible divergence but do not establish loss in ABRAXAS1. Supporting Evidence: PMID:26195665 BRISC distributes along and directly binds to MTs during mitosis file:human/ABRAXAS1/ABRAXAS1-hypotheses/function-hypothesis-go-0008017/openscientist.md The IBA "microtubule binding" annotation on ABRAXAS1 is not supported by any primary experimental evidence for ABRAXAS1 itself. |
| GO:0008608 attachment of spindle microtubules to kinetochore | IBA GO_REF:0000033 | UNDECIDED | Summary: The ABRAXAS2-grounded ancestral spindle/microtubule assertion is unresolved for ABRAXAS1. Reason: PAINT places this assertion at PTN001272083 with ABRAXAS2/Q15018 experimental support. PMID:26195665 directly establishes BRISC/ABRO1 microtubule association and NuMA-dependent spindle regulation. ABRAXAS1 assembles the distinct BRCA1-A complex, which makes functional divergence plausible, but its major nuclear DNA-repair role is not proof of exclusive localization or absence of mitotic activity. The existing OpenScientist report conflates lack of target assays with refutation and relies on donor identity without demonstrating target-specific loss. Retain uncertainty until mitotic localization, binding, or functional comparison resolves inheritance. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001272083 · PTN001272083 UNRESOLVED The metazoan IBD is experimentally seeded by ABRAXAS2. Distinct BRCA1-A versus BRISC partners suggest possible divergence but do not establish loss in ABRAXAS1. Supporting Evidence: PMID:26195665 BRISC distributes along and directly binds to MTs during mitosis file:human/ABRAXAS1/ABRAXAS1-hypotheses/function-hypothesis-go-0008017/openscientist.md The IBA "microtubule binding" annotation on ABRAXAS1 is not supported by any primary experimental evidence for ABRAXAS1 itself. |
| GO:0031593 polyubiquitin modification-dependent protein binding | IBA GO_REF:0000033 | ACCEPT | Summary: Core molecular function. ABRAXAS1 is part of a BRCA1-A/RAP80 complex that recognizes ubiquitinated damage-site chromatin and has polyubiquitin-binding capacity. 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. Supporting Evidence: PMID:19261749 four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability PMID:20656689 RAP80, in turn, is recruited to DSBs through its tandem ubiquitin-interacting motifs (UIMs) ( 6 , 14 – 16 ), which specifically recognize K63-Ub chains |
| GO:0090307 mitotic spindle assembly | IBA GO_REF:0000033 | UNDECIDED | Summary: The ABRAXAS2-grounded ancestral spindle/microtubule assertion is unresolved for ABRAXAS1. Reason: PAINT places this assertion at PTN001272083 with ABRAXAS2/Q15018 experimental support. PMID:26195665 directly establishes BRISC/ABRO1 microtubule association and NuMA-dependent spindle regulation. ABRAXAS1 assembles the distinct BRCA1-A complex, which makes functional divergence plausible, but its major nuclear DNA-repair role is not proof of exclusive localization or absence of mitotic activity. The existing OpenScientist report conflates lack of target assays with refutation and relies on donor identity without demonstrating target-specific loss. Retain uncertainty until mitotic localization, binding, or functional comparison resolves inheritance. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN001272083 · PTN001272083 UNRESOLVED The metazoan IBD is experimentally seeded by ABRAXAS2. Distinct BRCA1-A versus BRISC partners suggest possible divergence but do not establish loss in ABRAXAS1. Supporting Evidence: PMID:26195665 BRISC distributes along and directly binds to MTs during mitosis file:human/ABRAXAS1/ABRAXAS1-hypotheses/function-hypothesis-go-0008017/openscientist.md The IBA "microtubule binding" annotation on ABRAXAS1 is not supported by any primary experimental evidence for ABRAXAS1 itself. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Supported nuclear localization. ABRAXAS1 acts in the nuclear DNA damage response and localizes to DNA damage sites within the nucleus. 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. Supporting Evidence: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt Nucleus {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122}. PMID:17525340 RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation |
| GO:0005515 protein binding | IPI PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | REMOVE | Summary: Generic protein binding is not an informative function for this scaffold. Reason: Specific BRCA1-A assembly and polyubiquitin-dependent recruitment describe the function; generic protein binding is removed under project policy without declaring the interaction false. Supporting Evidence: PMID:17525340 identified a protein, Abraxas, that directly binds the BRCA1 BRCT repeats PMID:20656689 The RAP80 complex is a five-member stoichiometric complex consisting of RAP80, BRCC36, BRCC45, Abraxas, and MERIT40 |
| GO:0005515 protein binding | IPI PMID:17643121 CCDC98 targets BRCA1 to DNA damage sites. | REMOVE | Summary: Generic protein binding is not an informative function for this scaffold. Reason: Specific BRCA1-A assembly and polyubiquitin-dependent recruitment describe the function; generic protein binding is removed under project policy without declaring the interaction false. Supporting Evidence: PMID:17643121 CCDC98 is a BRCA1 binding partner that mediates BRCA1 function in response to DNA damage. PMID:20656689 The RAP80 complex is a five-member stoichiometric complex consisting of RAP80, BRCC36, BRCC45, Abraxas, and MERIT40 |
| GO:0005515 protein binding | IPI PMID:18077395 Ubc13/Rnf8 ubiquitin ligases control foci formation of the R... | REMOVE | Summary: Generic protein binding is not an informative function for this scaffold. Reason: Specific BRCA1-A assembly and polyubiquitin-dependent recruitment describe the function; generic protein binding is removed under project policy without declaring the interaction false. Supporting Evidence: PMID:18077395 Rap80 contains an Abraxas interaction domain PMID:20656689 The RAP80 complex is a five-member stoichiometric complex consisting of RAP80, BRCC36, BRCC45, Abraxas, and MERIT40 |
| GO:0005515 protein binding | IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... | REMOVE | Summary: Generic protein binding is not an informative function for this scaffold. Reason: Specific BRCA1-A assembly and polyubiquitin-dependent recruitment describe the function; generic protein binding is removed under project policy without declaring the interaction false. Supporting Evidence: PMID:19615732 We identified 774 candidate interacting proteins associated with 75 Dubs. |
| GO:0005515 protein binding | IPI PMID:29656893 DNA Repair Network Analysis Reveals Shieldin as a Key Regula... | REMOVE | Summary: Generic protein binding is not an informative function for this scaffold. Reason: Specific BRCA1-A assembly and polyubiquitin-dependent recruitment describe the function; generic protein binding is removed under project policy without declaring the interaction false. Supporting Evidence: PMID:29656893 we generated high-resolution interaction neighborhood maps of the endogenously expressed DNA repair factors 53BP1, BRCA1, and MDC1 |
| GO:0005515 protein binding | IPI PMID:34591612 A protein interaction landscape of breast cancer. | REMOVE | Summary: Generic protein binding is not an informative function for this scaffold. Reason: Specific BRCA1-A assembly and polyubiquitin-dependent recruitment describe the function; generic protein binding is removed under project policy without declaring the interaction false. Supporting Evidence: PMID:34591612 we generated comprehensive interaction maps for 40 frequently altered BC proteins |
| GO:0005515 protein binding | IPI PMID:35156780 CFTR interactome mapping using the mammalian membrane two-hy... | REMOVE | Summary: Generic protein binding is not an informative function for this scaffold. Reason: Specific BRCA1-A assembly and polyubiquitin-dependent recruitment describe the function; generic protein binding is removed under project policy without declaring the interaction false. Supporting Evidence: PMID:35156780 high-throughput screening variant of the Mammalian Membrane Two-Hybrid |
| GO:0005515 protein binding | IPI PMID:36012204 Differential CFTR-Interactome Proximity Labeling Procedures ... | REMOVE | Summary: Generic protein binding is not an informative function for this scaffold. Reason: Specific BRCA1-A assembly and polyubiquitin-dependent recruitment describe the function; generic protein binding is removed under project policy without declaring the interaction false. Supporting Evidence: PMID:36012204 proximity labeling approaches identified both known and additional CFTR protein partners |
| GO:0005515 protein binding | IPI PMID:39009827 Proteome-scale characterisation of motif-based interactome r... | REMOVE | Summary: Generic protein binding is not an informative function for this scaffold. Reason: Specific BRCA1-A assembly and polyubiquitin-dependent recruitment describe the function; generic protein binding is removed under project policy without declaring the interaction false. Supporting Evidence: PMID:39009827 we identified 366 mutation-modulated interactions |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Non-core localization. HPA reports nuclear-body staining, while mechanistic ABRAXAS1 biology centers on DNA damage foci/BRCA1-A complex recruitment. 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. Supporting Evidence: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt Localizes at sites of DNA damage at double-strand breaks (DSBs). |
| GO:0005634 nucleus | NAS PMID:20656689 Differential regulation of JAMM domain deubiquitinating enzy... | ACCEPT | Summary: Supported nuclear localization. ABRAXAS1 acts in the nuclear DNA damage response and localizes to DNA damage sites within the nucleus. 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. Supporting Evidence: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt Nucleus {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122}. PMID:17525340 RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation |
| GO:0006282 regulation of DNA repair | NAS PMID:20656689 Differential regulation of JAMM domain deubiquitinating enzy... | MODIFY | Summary: The broad regulation-of-DNA-repair annotation is directionally correct but less precise than positive regulation of DNA repair for ABRAXAS1. 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 replacements: positive regulation of DNA repair Supporting Evidence: PMID:17525340 Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. PMID:19261748 a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization |
| GO:0044818 mitotic G2/M transition checkpoint | NAS PMID:22369660 BRCA1 tumor suppressor network: focusing on its tail. | MODIFY | Summary: The ComplexPortal/NAS checkpoint annotation is real but should be represented using the more specific DNA-damage checkpoint signaling term. Reason: ABRAXAS1 evidence concerns BRCA1-dependent G2/M checkpoint activation in response to DNA damage, not the generic mitotic G2/M transition checkpoint. Proposed replacements: mitotic G2 DNA damage checkpoint signaling Supporting Evidence: PMID:17643121 CCDC98 controls both DNA damage-induced formation of BRCA1 foci and BRCA1-dependent G2/M checkpoint activation PMID:22369660 Studies on A, B and C complexes of BRCA1 indicate that these complexes carry out functions of BRCA1 in cell cycle checkpoint control. |
| GO:0070531 BRCA1-A complex | NAS PMID:20656689 Differential regulation of JAMM domain deubiquitinating enzy... | ACCEPT | Summary: Core complex membership. ABRAXAS1 is a BRCA1-A complex subunit that organizes BRCA1, UIMC1/RAP80, BRCC3/BRCC36, BABAM proteins, and related DDR functions. 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. Supporting Evidence: PMID:19261749 Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IMP PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | ACCEPT | Summary: Core checkpoint process. ABRAXAS1/CCDC98 is required for BRCA1-dependent G2/M checkpoint signaling after DNA damage. 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. Supporting Evidence: PMID:17643121 CCDC98 controls both DNA damage-induced formation of BRCA1 foci and BRCA1-dependent G2/M checkpoint activation PMID:22369660 Studies on A, B and C complexes of BRCA1 indicate that these complexes carry out functions of BRCA1 in cell cycle checkpoint control. |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IMP PMID:17643121 CCDC98 targets BRCA1 to DNA damage sites. | ACCEPT | Summary: Core checkpoint process. ABRAXAS1/CCDC98 is required for BRCA1-dependent G2/M checkpoint signaling after DNA damage. 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. Supporting Evidence: PMID:17643121 CCDC98 controls both DNA damage-induced formation of BRCA1 foci and BRCA1-dependent G2/M checkpoint activation PMID:22369660 Studies on A, B and C complexes of BRCA1 indicate that these complexes carry out functions of BRCA1 in cell cycle checkpoint control. |
| GO:0007095 mitotic G2 DNA damage checkpoint signaling | IMP PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: Core checkpoint process. ABRAXAS1/CCDC98 is required for BRCA1-dependent G2/M checkpoint signaling after DNA damage. 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. Supporting Evidence: PMID:17643121 CCDC98 controls both DNA damage-induced formation of BRCA1 foci and BRCA1-dependent G2/M checkpoint activation PMID:22369660 Studies on A, B and C complexes of BRCA1 indicate that these complexes carry out functions of BRCA1 in cell cycle checkpoint control. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683384 | ACCEPT | Summary: Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. 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. Supporting Evidence: Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683385 | ACCEPT | Summary: Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. 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. Supporting Evidence: Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683735 | ACCEPT | Summary: Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. 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. Supporting Evidence: Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5683801 | ACCEPT | Summary: Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. 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. Supporting Evidence: Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684052 | ACCEPT | Summary: Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. 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. Supporting Evidence: Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5684071 | ACCEPT | Summary: Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. 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. Supporting Evidence: Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5686685 | ACCEPT | Summary: Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. 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. Supporting Evidence: Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5691411 | ACCEPT | Summary: Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. 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. Supporting Evidence: Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-5693551 | ACCEPT | Summary: Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. 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. Supporting Evidence: Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-69891 | ACCEPT | Summary: Supported Reactome-derived nuclear compartment annotation. The BRCA1-A complex events involving FAM175A/ABRAXAS1 are modeled at nuclear DNA double-strand breaks. 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. Supporting Evidence: Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0005515 protein binding | IPI PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | REMOVE | Summary: Generic protein binding is not an informative function for this scaffold. Reason: Specific BRCA1-A assembly and polyubiquitin-dependent recruitment describe the function; generic protein binding is removed under project policy without declaring the interaction false. Supporting Evidence: PMID:19261748 CCDC98 binds to RAP80 via a large N-terminal region PMID:20656689 The RAP80 complex is a five-member stoichiometric complex consisting of RAP80, BRCC36, BRCC45, Abraxas, and MERIT40 |
| GO:0005515 protein binding | IPI PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | REMOVE | Summary: Generic protein binding is not an informative function for this scaffold. Reason: Specific BRCA1-A assembly and polyubiquitin-dependent recruitment describe the function; generic protein binding is removed under project policy without declaring the interaction false. Supporting Evidence: PMID:19261749 four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability PMID:20656689 The RAP80 complex is a five-member stoichiometric complex consisting of RAP80, BRCC36, BRCC45, Abraxas, and MERIT40 |
| GO:0005634 nucleus | IDA PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | ACCEPT | Summary: Supported nuclear localization. ABRAXAS1 acts in the nuclear DNA damage response and localizes to DNA damage sites within the nucleus. 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. Supporting Evidence: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt Nucleus {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122}. PMID:17525340 RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation |
| GO:0005634 nucleus | IDA PMID:17643121 CCDC98 targets BRCA1 to DNA damage sites. | ACCEPT | Summary: Supported nuclear localization. ABRAXAS1 acts in the nuclear DNA damage response and localizes to DNA damage sites within the nucleus. 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. Supporting Evidence: file:human/ABRAXAS1/ABRAXAS1-uniprot.txt Nucleus {ECO:0000269|PubMed:17525340, ECO:0000269|PubMed:17643121, ECO:0000269|PubMed:17643122}. PMID:17525340 RAP80 was required for optimal accumulation of BRCA1 on damaged DNA (foci) in response to ionizing radiation |
| GO:0006302 double-strand break repair | IMP PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | ACCEPT | Summary: Core biological process. ABRAXAS1 is required for efficient DNA double-strand break repair through BRCA1-A recruitment and ubiquitin-dependent damage-site signaling. 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. Supporting Evidence: PMID:17525340 Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. PMID:19261748 a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization |
| GO:0006302 double-strand break repair | IMP PMID:17643121 CCDC98 targets BRCA1 to DNA damage sites. | ACCEPT | Summary: Core biological process. ABRAXAS1 is required for efficient DNA double-strand break repair through BRCA1-A recruitment and ubiquitin-dependent damage-site signaling. 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. Supporting Evidence: PMID:17525340 Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. PMID:19261748 a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization |
| GO:0006302 double-strand break repair | IMP PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: Core biological process. ABRAXAS1 is required for efficient DNA double-strand break repair through BRCA1-A recruitment and ubiquitin-dependent damage-site signaling. 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. Supporting Evidence: PMID:17525340 Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. PMID:19261748 a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization |
| GO:0010212 response to ionizing radiation | IMP PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | KEEP AS NON CORE | Summary: Supported but non-core phenotype/context annotation. Ionizing radiation is the experimental damage stimulus used to reveal ABRAXAS1 DNA damage-response function. 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. Supporting Evidence: PMID:18077395 the entire Brca1 A complex to DNA-damage foci PMID:19261749 required for resistance to ionizing radiation |
| GO:0010212 response to ionizing radiation | IMP PMID:17643121 CCDC98 targets BRCA1 to DNA damage sites. | KEEP AS NON CORE | Summary: Supported but non-core phenotype/context annotation. Ionizing radiation is the experimental damage stimulus used to reveal ABRAXAS1 DNA damage-response function. 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. Supporting Evidence: PMID:18077395 the entire Brca1 A complex to DNA-damage foci PMID:19261749 required for resistance to ionizing radiation |
| GO:0010212 response to ionizing radiation | IMP PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | KEEP AS NON CORE | Summary: Supported but non-core phenotype/context annotation. Ionizing radiation is the experimental damage stimulus used to reveal ABRAXAS1 DNA damage-response function. 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. Supporting Evidence: PMID:18077395 the entire Brca1 A complex to DNA-damage foci PMID:19261749 required for resistance to ionizing radiation |
| GO:0031593 polyubiquitin modification-dependent protein binding | IDA PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | ACCEPT | Summary: Core molecular function. ABRAXAS1 is part of a BRCA1-A/RAP80 complex that recognizes ubiquitinated damage-site chromatin and has polyubiquitin-binding capacity. 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. Supporting Evidence: PMID:19261749 four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability PMID:20656689 RAP80, in turn, is recruited to DSBs through its tandem ubiquitin-interacting motifs (UIMs) ( 6 , 14 – 16 ), which specifically recognize K63-Ub chains |
| GO:0045739 positive regulation of DNA repair | IMP PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | ACCEPT | Summary: Core regulatory process. ABRAXAS1 positively supports DNA repair by assembling/stabilizing the RAP80-BRCA1-A complex at DNA damage sites. 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. Supporting Evidence: PMID:17525340 Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. PMID:19261748 a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization PMID:20656689 Abraxas and BRCC45 were essential for BRCC36 DUB activity within the RAP80 complex |
| GO:0045739 positive regulation of DNA repair | IMP PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: Core regulatory process. ABRAXAS1 positively supports DNA repair by assembling/stabilizing the RAP80-BRCA1-A complex at DNA damage sites. 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. Supporting Evidence: PMID:17525340 Both Abraxas and RAP80 were required for DNA damage resistance, G(2)-M checkpoint control, and DNA repair. PMID:19261748 a stable complex containing MERIT40 acts early in DNA damage response and regulates damage-dependent BRCA1 localization PMID:20656689 Abraxas and BRCC45 were essential for BRCC36 DUB activity within the RAP80 complex |
| GO:0070531 BRCA1-A complex | IDA PMID:17525340 Abraxas and RAP80 form a BRCA1 protein complex required for ... | ACCEPT | Summary: Core complex membership. ABRAXAS1 is a BRCA1-A complex subunit that organizes BRCA1, UIMC1/RAP80, BRCC3/BRCC36, BABAM proteins, and related DDR functions. 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. Supporting Evidence: PMID:19261749 Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0070531 BRCA1-A complex | IDA PMID:19261746 MERIT40 controls BRCA1-Rap80 complex integrity and recruitme... | ACCEPT | Summary: Core complex membership. ABRAXAS1 is a BRCA1-A complex subunit that organizes BRCA1, UIMC1/RAP80, BRCC3/BRCC36, BABAM proteins, and related DDR functions. 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. Supporting Evidence: PMID:19261749 Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0070531 BRCA1-A complex | IDA PMID:19261748 MERIT40 facilitates BRCA1 localization and DNA damage repair... | ACCEPT | Summary: Core complex membership. ABRAXAS1 is a BRCA1-A complex subunit that organizes BRCA1, UIMC1/RAP80, BRCC3/BRCC36, BABAM proteins, and related DDR functions. 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. Supporting Evidence: PMID:19261749 Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
| GO:0070531 BRCA1-A complex | IDA PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | ACCEPT | Summary: Core complex membership. ABRAXAS1 is a BRCA1-A complex subunit that organizes BRCA1, UIMC1/RAP80, BRCC3/BRCC36, BABAM proteins, and related DDR functions. 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. Supporting Evidence: PMID:19261749 Proteomic analysis revealed that NBA1 is a component of the BRCA1 A complex, which also contains Brca1/Bard1, Abra1, RAP80, BRCC36, and BRE. Reactome:R-HSA-5683385 Together, BRCA1, BARD1, UIMC1, FAM175A, BRCC36, BRE and BABAM1 form the so-called BRCA1-A complex at DNA DSBs |
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Download this section (compressed HTML)Q: 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?
Suggested experts: Wang B, Greenberg RA, Elledge SJ
Q: 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?
Suggested experts: Wiesmuller L, Pylkas K
Q: 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?
Suggested experts: Diederichs S
Experiment: 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.
Hypothesis: The PANTHER-derived spindle and microtubule annotations are ABRAXAS2/paralog-specific and do not apply to ABRAXAS1.
Type: comparative cell biology
Experiment: 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.
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.
Type: DSB-repair pathway reporter assay
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