ABRAXAS2 encodes Abraxas 2/ABRO1, a noncatalytic MPN-domain scaffold subunit of the BRISC K63-linked deubiquitinating complex. Together with BRCC3/BRCC36, BABAM1/MERIT40, and BABAM2/BRE, ABRAXAS2 helps assemble and localize BRISC in the cytoplasm and nucleus, where the complex removes K63-linked ubiquitin chains from substrates involved in immune receptor signaling and mitotic spindle organization. ABRAXAS2 also provides the BRISC-specific interface for SHMT2-dependent regulation and targeting, and it can translocate to the nucleus during cellular stress to influence p53-dependent DNA-damage signaling. Unlike ABRAXAS1, ABRAXAS2 lacks the BRCA1-interacting C-terminal phospho-motif and is not a canonical BRCA1-A DNA-repair adaptor.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nuclear localization is supported as a minor/stress-induced pool. Reason: Although ABRAXAS2 is mainly cytoplasmic, several studies report nuclear localization or nuclear translocation during DNA damage/oxidative stress, so nucleus annotations are acceptable when not interpreted as BRCA1-A complex membership [PMID:22974638; PMID:25283148]. Supporting Evidence: PMID:25283148 DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus PMID:22974638 during cellular stress it enters the nucleus and co-localizes with ATF4 PMID:24075985 presence of the BRISC-SHMT complex in both the cytoplasm and nucleus |
| GO:0008017 microtubule binding | IBA GO_REF:0000033 | ACCEPT | Summary: microtubule binding is supported by ABRAXAS2/BRISC localization to mitotic microtubule structures and functional spindle defects after BRISC depletion. Reason: PMID:26195665 directly shows ABRAXAS2/BRISC binds microtubules, localizes to K-fiber minus ends and spindle poles, and promotes bipolar spindle assembly through NUMA1 deubiquitination. This is an experimentally supported ABRAXAS2 cellular role rather than a generic cell-cycle phenotype. Supporting Evidence: PMID:26195665 BRISC is a microtubule (MT)-associated protein complex that predominantly localizes to the minus ends of K-fibers and spindle poles and directly binds to MTs PMID:26195665 promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). |
| GO:0008608 attachment of spindle microtubules to kinetochore | IBA GO_REF:0000033 | ACCEPT | Summary: attachment of spindle microtubules to kinetochore is supported by ABRAXAS2/BRISC localization to mitotic microtubule structures and functional spindle defects after BRISC depletion. Reason: PMID:26195665 directly shows ABRAXAS2/BRISC binds microtubules, localizes to K-fiber minus ends and spindle poles, and promotes bipolar spindle assembly through NUMA1 deubiquitination. This is an experimentally supported ABRAXAS2 cellular role rather than a generic cell-cycle phenotype. Supporting Evidence: PMID:26195665 BRISC is a microtubule (MT)-associated protein complex that predominantly localizes to the minus ends of K-fibers and spindle poles and directly binds to MTs PMID:26195665 promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). |
| GO:0031593 polyubiquitin modification-dependent protein binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: ABRAXAS2 participates in a K63-ubiquitin-directed BRISC complex, but direct polyubiquitin-dependent binding should not be treated as an independently enabled ABRAXAS2 molecular function. Reason: The term is related to the K63-ubiquitin substrate-recognition biology of BRISC, but ABRAXAS2 is best interpreted as a noncatalytic scaffold/adaptor within the complex. The over-annotation concern is specifically that this annotation says ABRAXAS2 individually enables polyubiquitin-dependent binding, whereas the stronger evidence is that the BRISC complex processes K63-linked ubiquitin chains. The core annotation should emphasize BRISC complex membership and participation in K63-linked deubiquitination contexts rather than direct enabling of polyubiquitin-dependent binding by ABRAXAS2 itself. Supporting Evidence: PMID:19214193 the activity was intrinsic to PA700 and the Brcc36 isopeptidase complex (BRISC) PMID:20656690 KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm. PMID:31253574 Both BRCC36-containing complexes are specific for lysine-63-linked ubiquitin (K63-Ub) chains |
| GO:0090307 mitotic spindle assembly | IBA GO_REF:0000033 | ACCEPT | Summary: mitotic spindle assembly is supported by ABRAXAS2/BRISC localization to mitotic microtubule structures and functional spindle defects after BRISC depletion. Reason: PMID:26195665 directly shows ABRAXAS2/BRISC binds microtubules, localizes to K-fiber minus ends and spindle poles, and promotes bipolar spindle assembly through NUMA1 deubiquitination. This is an experimentally supported ABRAXAS2 cellular role rather than a generic cell-cycle phenotype. Supporting Evidence: PMID:26195665 BRISC is a microtubule (MT)-associated protein complex that predominantly localizes to the minus ends of K-fibers and spindle poles and directly binds to MTs PMID:26195665 promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). |
| GO:0000922 spindle pole | IEA GO_REF:0000044 | ACCEPT | Summary: Spindle-pole localization is supported by mitotic imaging. Reason: ABRAXAS2/BRISC localizes to centrosomes and spindle poles during mitosis [PMID:26195665]. Supporting Evidence: PMID:26195665 ABRO1 was shown to be located at the centrosomes in interphase PMID:26195665 BRISC localizes at centrosomes, spindle poles, and midbody during mitosis. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nuclear localization is supported as a minor/stress-induced pool. Reason: Although ABRAXAS2 is mainly cytoplasmic, several studies report nuclear localization or nuclear translocation during DNA damage/oxidative stress, so nucleus annotations are acceptable when not interpreted as BRCA1-A complex membership [PMID:22974638; PMID:25283148]. Supporting Evidence: PMID:25283148 DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus PMID:22974638 during cellular stress it enters the nucleus and co-localizes with ATF4 PMID:24075985 presence of the BRISC-SHMT complex in both the cytoplasm and nucleus |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic localization is well supported. Reason: ABRAXAS2/ABRO1 is predominantly cytoplasmic and acts as the scaffold for cytoplasmic BRISC, with additional stress- and mitosis-specific localizations [PMID:20656690; PMID:21282113; PMID:24075985; PMID:26195665]. Supporting Evidence: PMID:20656690 KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm. PMID:21282113 ABRO1 is mainly localized in the cytoplasm. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | MODIFY | Summary: Cytoskeleton is directionally correct but too broad for the available evidence. Reason: ABRAXAS2/BRISC is specifically associated with microtubule structures, especially spindle poles and K-fiber minus ends. The broader cytoskeleton term should be replaced with microtubule/spindle-related components. Proposed replacements: microtubule spindle pole Supporting Evidence: PMID:26195665 ABRO1 was shown to be located at the centrosomes in interphase PMID:26195665 BRISC localizes at centrosomes, spindle poles, and midbody during mitosis. |
| GO:0005515 protein binding | IPI PMID:19615732 Defining the human deubiquitinating enzyme interaction lands... | REMOVE | Summary: Generic protein-binding annotation from interaction-screen data. Reason: GO:0005515 does not describe ABRAXAS2 function. These interaction datasets may be useful as evidence for physical partners, but ABRAXAS2 should instead be represented by specific BRISC complex, K63-linked deubiquitination, microtubule, or pathway annotations when supported. Supporting Evidence: PMID:19615732 We identified 774 candidate interacting proteins associated with 75 Dubs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Generic protein-binding annotation from interaction-screen data. Reason: GO:0005515 does not describe ABRAXAS2 function. These interaction datasets may be useful as evidence for physical partners, but ABRAXAS2 should instead be represented by specific BRISC complex, K63-linked deubiquitination, microtubule, or pathway annotations when supported. Supporting Evidence: PMID:32296183 A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Generic protein-binding annotation from interaction-screen data. Reason: GO:0005515 does not describe ABRAXAS2 function. These interaction datasets may be useful as evidence for physical partners, but ABRAXAS2 should instead be represented by specific BRISC complex, K63-linked deubiquitination, microtubule, or pathway annotations when supported. Supporting Evidence: PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | REMOVE | Summary: Generic protein-binding annotation from interaction-screen data. Reason: GO:0005515 does not describe ABRAXAS2 function. These interaction datasets may be useful as evidence for physical partners, but ABRAXAS2 should instead be represented by specific BRISC complex, K63-linked deubiquitination, microtubule, or pathway annotations when supported. Supporting Evidence: PMID:36115835 Quantitative fragmentomics allow affinity mapping of interactomes. |
| GO:0005515 protein binding | IPI PMID:37398436 AI-guided pipeline for protein-protein interaction drug disc... | REMOVE | Summary: Generic protein-binding annotation from interaction-screen data. Reason: GO:0005515 does not describe ABRAXAS2 function. These interaction datasets may be useful as evidence for physical partners, but ABRAXAS2 should instead be represented by specific BRISC complex, K63-linked deubiquitination, microtubule, or pathway annotations when supported. Supporting Evidence: PMID:37398436 AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosol localization is consistent with ABRAXAS2 as a major cytosolic BRISC scaffold. Reason: Multiple studies describe ABRAXAS2/ABRO1/KIAA0157 as mainly cytoplasmic/cytosolic, while also allowing stress-induced nuclear pools. Supporting Evidence: PMID:20656690 KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm. PMID:21282113 ABRO1 is mainly localized in the cytoplasm. |
| GO:0005634 nucleus | EXP PMID:21282113 NBA1/MERIT40 and BRE interaction is required for the integri... | ACCEPT | Summary: Nuclear localization is supported as a minor/stress-induced pool. Reason: Although ABRAXAS2 is mainly cytoplasmic, several studies report nuclear localization or nuclear translocation during DNA damage/oxidative stress, so nucleus annotations are acceptable when not interpreted as BRCA1-A complex membership [PMID:22974638; PMID:25283148]. Supporting Evidence: PMID:25283148 DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus PMID:22974638 during cellular stress it enters the nucleus and co-localizes with ATF4 PMID:24075985 presence of the BRISC-SHMT complex in both the cytoplasm and nucleus |
| GO:0005634 nucleus | EXP PMID:22974638 ATF4 interacts with Abro1/KIAA0157 scaffold protein and part... | ACCEPT | Summary: Nuclear localization is supported as a minor/stress-induced pool. Reason: Although ABRAXAS2 is mainly cytoplasmic, several studies report nuclear localization or nuclear translocation during DNA damage/oxidative stress, so nucleus annotations are acceptable when not interpreted as BRCA1-A complex membership [PMID:22974638; PMID:25283148]. Supporting Evidence: PMID:25283148 DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus PMID:22974638 during cellular stress it enters the nucleus and co-localizes with ATF4 PMID:24075985 presence of the BRISC-SHMT complex in both the cytoplasm and nucleus |
| GO:0005634 nucleus | EXP PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in... | ACCEPT | Summary: Nuclear localization is supported as a minor/stress-induced pool. Reason: Although ABRAXAS2 is mainly cytoplasmic, several studies report nuclear localization or nuclear translocation during DNA damage/oxidative stress, so nucleus annotations are acceptable when not interpreted as BRCA1-A complex membership [PMID:22974638; PMID:25283148]. Supporting Evidence: PMID:25283148 DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus PMID:22974638 during cellular stress it enters the nucleus and co-localizes with ATF4 PMID:24075985 presence of the BRISC-SHMT complex in both the cytoplasm and nucleus |
| GO:0005634 nucleus | EXP PMID:25283148 ABRO1 suppresses tumourigenesis and regulates the DNA damage... | ACCEPT | Summary: Nuclear localization is supported as a minor/stress-induced pool. Reason: Although ABRAXAS2 is mainly cytoplasmic, several studies report nuclear localization or nuclear translocation during DNA damage/oxidative stress, so nucleus annotations are acceptable when not interpreted as BRCA1-A complex membership [PMID:22974638; PMID:25283148]. Supporting Evidence: PMID:25283148 DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus PMID:22974638 during cellular stress it enters the nucleus and co-localizes with ATF4 PMID:24075985 presence of the BRISC-SHMT complex in both the cytoplasm and nucleus |
| GO:0005737 cytoplasm | EXP PMID:20656690 The Lys63-specific deubiquitinating enzyme BRCC36 is regulat... | ACCEPT | Summary: Cytoplasmic localization is well supported. Reason: ABRAXAS2/ABRO1 is predominantly cytoplasmic and acts as the scaffold for cytoplasmic BRISC, with additional stress- and mitosis-specific localizations [PMID:20656690; PMID:21282113; PMID:24075985; PMID:26195665]. Supporting Evidence: PMID:20656690 KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm. PMID:21282113 ABRO1 is mainly localized in the cytoplasm. |
| GO:0005737 cytoplasm | EXP PMID:21282113 NBA1/MERIT40 and BRE interaction is required for the integri... | ACCEPT | Summary: Cytoplasmic localization is well supported. Reason: ABRAXAS2/ABRO1 is predominantly cytoplasmic and acts as the scaffold for cytoplasmic BRISC, with additional stress- and mitosis-specific localizations [PMID:20656690; PMID:21282113; PMID:24075985; PMID:26195665]. Supporting Evidence: PMID:20656690 KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm. PMID:21282113 ABRO1 is mainly localized in the cytoplasm. |
| GO:0005737 cytoplasm | EXP PMID:22974638 ATF4 interacts with Abro1/KIAA0157 scaffold protein and part... | ACCEPT | Summary: Cytoplasmic localization is well supported. Reason: ABRAXAS2/ABRO1 is predominantly cytoplasmic and acts as the scaffold for cytoplasmic BRISC, with additional stress- and mitosis-specific localizations [PMID:20656690; PMID:21282113; PMID:24075985; PMID:26195665]. Supporting Evidence: PMID:20656690 KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm. PMID:21282113 ABRO1 is mainly localized in the cytoplasm. |
| GO:0005737 cytoplasm | EXP PMID:25283148 ABRO1 suppresses tumourigenesis and regulates the DNA damage... | ACCEPT | Summary: Cytoplasmic localization is well supported. Reason: ABRAXAS2/ABRO1 is predominantly cytoplasmic and acts as the scaffold for cytoplasmic BRISC, with additional stress- and mitosis-specific localizations [PMID:20656690; PMID:21282113; PMID:24075985; PMID:26195665]. Supporting Evidence: PMID:20656690 KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm. PMID:21282113 ABRO1 is mainly localized in the cytoplasm. |
| GO:0005737 cytoplasm | IPI PMID:31253574 Structural Basis of BRCC36 Function in DNA Repair and Immune... | ACCEPT | Summary: Cytoplasmic localization is well supported. Reason: ABRAXAS2/ABRO1 is predominantly cytoplasmic and acts as the scaffold for cytoplasmic BRISC, with additional stress- and mitosis-specific localizations [PMID:20656690; PMID:21282113; PMID:24075985; PMID:26195665]. Supporting Evidence: PMID:20656690 KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm. PMID:21282113 ABRO1 is mainly localized in the cytoplasm. |
| GO:0005737 cytoplasm | NAS PMID:31253574 Structural Basis of BRCC36 Function in DNA Repair and Immune... | ACCEPT | Summary: Cytoplasmic localization is well supported. Reason: ABRAXAS2/ABRO1 is predominantly cytoplasmic and acts as the scaffold for cytoplasmic BRISC, with additional stress- and mitosis-specific localizations [PMID:20656690; PMID:21282113; PMID:24075985; PMID:26195665]. Supporting Evidence: PMID:20656690 KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm. PMID:21282113 ABRO1 is mainly localized in the cytoplasm. |
| GO:0034516 response to vitamin B6 | NAS PMID:31142841 Metabolic control of BRISC-SHMT2 assembly regulates immune s... | MODIFY | Summary: Vitamin B6/PLP regulates SHMT2 oligomer state and thus BRISC-SHMT2 assembly, but ABRAXAS2 is not best described as executing a vitamin B6 response. Reason: The supported ABRAXAS2 process in this study is BRISC-SHMT2-dependent positive regulation of type I interferon signaling. PLP is the metabolite that shifts SHMT2 dimer/tetramer state and thereby modulates BRISC-SHMT2 interaction; annotating ABRAXAS2 itself to response to vitamin B6 overstates the causal process. The same ComplexPortal NAS annotation may merit reassessment for the other BRISC subunits annotated from this study. Proposed replacements: positive regulation of type I interferon-mediated signaling pathway Supporting Evidence: PMID:31142841 Intracellular levels of PLP regulate the interaction between BRISC and SHMT2, as well as inflammatory cytokine responses. PMID:31142841 Mutations in BRISC that disrupt SHMT2 binding impair type I interferon signalling in response to inflammatory stimuli. |
| GO:0070552 BRISC complex | IPI PMID:31253574 Structural Basis of BRCC36 Function in DNA Repair and Immune... | ACCEPT | Summary: ABRAXAS2 is a bona fide BRISC complex subunit. Reason: Multiple biochemical, structural, UniProt, and ComplexPortal sources identify ABRAXAS2/ABRO1 as the BRISC-specific scaffold paired with BRCC36/BRCC3, BABAM1/MERIT40, and BABAM2/BRE. This is the safest PN-projected annotation and is already in GOA. Supporting Evidence: PMID:21282113 ABRO1 complex does not interact with BRCA1 PMID:31253574 in BRCA1-A, BRCC36 is supported by ABRAXAS (Wang et al., 2007), whereas in BRISC, it is paired with ABRO1 file:human/ABRAXAS2/ABRAXAS2-deep-research-falcon.md **ABRAXAS2/ABRO1 is a core scaffold subunit of BRISC** |
| GO:0070552 BRISC complex | NAS PMID:31253574 Structural Basis of BRCC36 Function in DNA Repair and Immune... | ACCEPT | Summary: ABRAXAS2 is a bona fide BRISC complex subunit. Reason: Multiple biochemical, structural, UniProt, and ComplexPortal sources identify ABRAXAS2/ABRO1 as the BRISC-specific scaffold paired with BRCC36/BRCC3, BABAM1/MERIT40, and BABAM2/BRE. This is the safest PN-projected annotation and is already in GOA. Supporting Evidence: PMID:21282113 ABRO1 complex does not interact with BRCA1 PMID:31253574 in BRCA1-A, BRCC36 is supported by ABRAXAS (Wang et al., 2007), whereas in BRISC, it is paired with ABRO1 |
| GO:0005515 protein binding | IPI PMID:26195665 The deubiquitinating enzyme complex BRISC is required for pr... | REMOVE | Summary: Generic protein-binding annotation for the ABRAXAS2/NUMA1 interaction. Reason: The interaction is biologically important, but GO:0005515 is uninformative. The same paper supports the more specific ABRAXAS2/BRISC roles in microtubule binding, mitotic spindle assembly, and K63-linked deubiquitination of NUMA1 [PMID:26195665]. Supporting Evidence: PMID:26195665 BRISC is a microtubule (MT)-associated protein complex that predominantly localizes to the minus ends of K-fibers and spindle poles and directly binds to MTs PMID:26195665 promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). |
| GO:0005829 cytosol | TAS Reactome:R-HSA-5691439 | ACCEPT | Summary: Cytosol localization is consistent with ABRAXAS2 as a major cytosolic BRISC scaffold. Reason: Multiple studies describe ABRAXAS2/ABRO1/KIAA0157 as mainly cytoplasmic/cytosolic, while also allowing stress-induced nuclear pools. Supporting Evidence: Reactome:R-HSA-5691439 FAM175B (ABRO1), another BRISC subunit, binds directly to NLRP3 leading to FAM175B-dependent recruitment of the BRISC complex |
| GO:0000278 mitotic cell cycle | IMP PMID:26195665 The deubiquitinating enzyme complex BRISC is required for pr... | MODIFY | Summary: Mitotic cell cycle is supported but too broad relative to the specific spindle defects. Reason: ABRAXAS2/BRISC depletion affects mitosis through spindle assembly, kinetochore-microtubule attachment, and chromosome segregation. More specific existing terms capture this biology better than the broad mitotic cell cycle term. Proposed replacements: mitotic spindle assembly attachment of spindle microtubules to kinetochore chromosome segregation Supporting Evidence: PMID:26195665 BRISC is a microtubule (MT)-associated protein complex that predominantly localizes to the minus ends of K-fibers and spindle poles and directly binds to MTs PMID:26195665 promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). |
| GO:0005737 cytoplasm | IDA PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in... | ACCEPT | Summary: Cytoplasmic localization is well supported. Reason: ABRAXAS2/ABRO1 is predominantly cytoplasmic and acts as the scaffold for cytoplasmic BRISC, with additional stress- and mitosis-specific localizations [PMID:20656690; PMID:21282113; PMID:24075985; PMID:26195665]. Supporting Evidence: PMID:20656690 KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm. PMID:21282113 ABRO1 is mainly localized in the cytoplasm. |
| GO:0005813 centrosome | IDA PMID:26195665 The deubiquitinating enzyme complex BRISC is required for pr... | ACCEPT | Summary: Centrosome colocalization is experimentally supported in mitotic-cell imaging. Reason: ABRAXAS2/BRISC localizes to centrosomes and spindle poles during the cell cycle [PMID:26195665]. Supporting Evidence: PMID:26195665 ABRO1 was shown to be located at the centrosomes in interphase PMID:26195665 BRISC localizes at centrosomes, spindle poles, and midbody during mitosis. |
| GO:0007059 chromosome segregation | IMP PMID:26195665 The deubiquitinating enzyme complex BRISC is required for pr... | ACCEPT | Summary: Chromosome-segregation defects follow ABRAXAS2/BRISC depletion. Reason: ABRAXAS2 depletion produces lagging chromosomes and spindle defects, supporting involvement in chromosome segregation through its spindle assembly role [PMID:26195665]. Supporting Evidence: PMID:26195665 BRISC is a microtubule (MT)-associated protein complex that predominantly localizes to the minus ends of K-fibers and spindle poles and directly binds to MTs PMID:26195665 promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). |
| GO:0008017 microtubule binding | IDA PMID:26195665 The deubiquitinating enzyme complex BRISC is required for pr... | ACCEPT | Summary: microtubule binding is supported by ABRAXAS2/BRISC localization to mitotic microtubule structures and functional spindle defects after BRISC depletion. Reason: PMID:26195665 directly shows ABRAXAS2/BRISC binds microtubules, localizes to K-fiber minus ends and spindle poles, and promotes bipolar spindle assembly through NUMA1 deubiquitination. This is an experimentally supported ABRAXAS2 cellular role rather than a generic cell-cycle phenotype. Supporting Evidence: PMID:26195665 BRISC is a microtubule (MT)-associated protein complex that predominantly localizes to the minus ends of K-fibers and spindle poles and directly binds to MTs PMID:26195665 promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). |
| GO:0008608 attachment of spindle microtubules to kinetochore | IMP PMID:26195665 The deubiquitinating enzyme complex BRISC is required for pr... | ACCEPT | Summary: attachment of spindle microtubules to kinetochore is supported by ABRAXAS2/BRISC localization to mitotic microtubule structures and functional spindle defects after BRISC depletion. Reason: PMID:26195665 directly shows ABRAXAS2/BRISC binds microtubules, localizes to K-fiber minus ends and spindle poles, and promotes bipolar spindle assembly through NUMA1 deubiquitination. This is an experimentally supported ABRAXAS2 cellular role rather than a generic cell-cycle phenotype. Supporting Evidence: PMID:26195665 BRISC is a microtubule (MT)-associated protein complex that predominantly localizes to the minus ends of K-fibers and spindle poles and directly binds to MTs PMID:26195665 promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). |
| GO:0030496 midbody | IDA PMID:26195665 The deubiquitinating enzyme complex BRISC is required for pr... | ACCEPT | Summary: midbody localization is supported by mitotic imaging. Reason: ABRAXAS2/BRISC was observed at centrosomes, spindle poles, K-fiber minus ends, and midbody during mitosis [PMID:26195665]. Supporting Evidence: PMID:26195665 ABRO1 was shown to be located at the centrosomes in interphase PMID:26195665 BRISC localizes at centrosomes, spindle poles, and midbody during mitosis. |
| GO:0031616 spindle pole centrosome | IDA PMID:26195665 The deubiquitinating enzyme complex BRISC is required for pr... | ACCEPT | Summary: spindle pole centrosome localization is supported by mitotic imaging. Reason: ABRAXAS2/BRISC was observed at centrosomes, spindle poles, K-fiber minus ends, and midbody during mitosis [PMID:26195665]. Supporting Evidence: PMID:26195665 ABRO1 was shown to be located at the centrosomes in interphase PMID:26195665 BRISC localizes at centrosomes, spindle poles, and midbody during mitosis. |
| GO:0036449 microtubule minus-end | IDA PMID:26195665 The deubiquitinating enzyme complex BRISC is required for pr... | ACCEPT | Summary: microtubule minus-end localization is supported by mitotic imaging. Reason: ABRAXAS2/BRISC was observed at centrosomes, spindle poles, K-fiber minus ends, and midbody during mitosis [PMID:26195665]. Supporting Evidence: PMID:26195665 ABRO1 was shown to be located at the centrosomes in interphase PMID:26195665 BRISC localizes at centrosomes, spindle poles, and midbody during mitosis. |
| GO:0070536 protein K63-linked deubiquitination | IMP PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in... | ACCEPT | Summary: Protein K63-linked deubiquitination is the central BRISC pathway function involving ABRAXAS2. Reason: ABRAXAS2 is not the catalytic subunit, but it is a required scaffold/adaptor of BRISC, the BRCC36/BRCC3 K63-linked DUB complex. The cited studies support substrate-specific K63 deubiquitination of IFNAR1 or NUMA1 by ABRAXAS2-containing BRISC. Supporting Evidence: PMID:24075985 SHMT directs BRISC activity at K63-Ub chains conjugated to the type 1 interferon (IFN) receptor chain 1 (IFNAR1). PMID:31142841 Direct interaction with SHMT2 enhances BRISC delivery to ubiquitylated type I interferon (IFN) receptors (IFNAR1/2) |
| GO:0070536 protein K63-linked deubiquitination | IMP PMID:26195665 The deubiquitinating enzyme complex BRISC is required for pr... | ACCEPT | Summary: Protein K63-linked deubiquitination is the central BRISC pathway function involving ABRAXAS2. Reason: ABRAXAS2 is not the catalytic subunit, but it is a required scaffold/adaptor of BRISC, the BRCC36/BRCC3 K63-linked DUB complex. The cited studies support substrate-specific K63 deubiquitination of IFNAR1 or NUMA1 by ABRAXAS2-containing BRISC. Supporting Evidence: PMID:26195665 BRISC is a microtubule (MT)-associated protein complex that predominantly localizes to the minus ends of K-fibers and spindle poles and directly binds to MTs PMID:26195665 promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). |
| GO:0070552 BRISC complex | IDA PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in... | ACCEPT | Summary: ABRAXAS2 is a bona fide BRISC complex subunit. Reason: Multiple biochemical, structural, UniProt, and ComplexPortal sources identify ABRAXAS2/ABRO1 as the BRISC-specific scaffold paired with BRCC36/BRCC3, BABAM1/MERIT40, and BABAM2/BRE. This is the safest PN-projected annotation and is already in GOA. Supporting Evidence: PMID:21282113 ABRO1 complex does not interact with BRCA1 PMID:31253574 in BRCA1-A, BRCC36 is supported by ABRAXAS (Wang et al., 2007), whereas in BRISC, it is paired with ABRO1 |
| GO:0090307 mitotic spindle assembly | IMP PMID:26195665 The deubiquitinating enzyme complex BRISC is required for pr... | ACCEPT | Summary: mitotic spindle assembly is supported by ABRAXAS2/BRISC localization to mitotic microtubule structures and functional spindle defects after BRISC depletion. Reason: PMID:26195665 directly shows ABRAXAS2/BRISC binds microtubules, localizes to K-fiber minus ends and spindle poles, and promotes bipolar spindle assembly through NUMA1 deubiquitination. This is an experimentally supported ABRAXAS2 cellular role rather than a generic cell-cycle phenotype. Supporting Evidence: PMID:26195665 BRISC is a microtubule (MT)-associated protein complex that predominantly localizes to the minus ends of K-fibers and spindle poles and directly binds to MTs PMID:26195665 promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). |
| GO:0002931 response to ischemia | IMP PMID:21195082 Regulation of Abro1/KIAA0157 during myocardial infarction an... | KEEP AS NON CORE | Summary: Response to ischemia is supported in a cardiac injury model but is context-specific. Reason: ABRO1 protein increases after myocardial ischemia/reperfusion and knockdown exacerbates cardiomyocyte damage, supporting the annotation. This is a tissue/stress phenotype rather than the core molecular function of ABRAXAS2. Supporting Evidence: PMID:21195082 Reducing the Abro1 protein level exacerbated cellular damage and cell death of cardiomyocytes due to MI/R injury. |
| GO:0005737 cytoplasm | IDA PMID:21195082 Regulation of Abro1/KIAA0157 during myocardial infarction an... | ACCEPT | Summary: Cytoplasmic localization is well supported. Reason: ABRAXAS2/ABRO1 is predominantly cytoplasmic and acts as the scaffold for cytoplasmic BRISC, with additional stress- and mitosis-specific localizations [PMID:20656690; PMID:21282113; PMID:24075985; PMID:26195665]. Supporting Evidence: PMID:20656690 KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm. PMID:21282113 ABRO1 is mainly localized in the cytoplasm. |
| GO:0070552 BRISC complex | IDA PMID:19214193 K63-specific deubiquitination by two JAMM/MPN+ complexes: BR... | ACCEPT | Summary: ABRAXAS2 is a bona fide BRISC complex subunit. Reason: Multiple biochemical, structural, UniProt, and ComplexPortal sources identify ABRAXAS2/ABRO1 as the BRISC-specific scaffold paired with BRCC36/BRCC3, BABAM1/MERIT40, and BABAM2/BRE. This is the safest PN-projected annotation and is already in GOA. Supporting Evidence: PMID:21282113 ABRO1 complex does not interact with BRCA1 PMID:31253574 in BRCA1-A, BRCC36 is supported by ABRAXAS (Wang et al., 2007), whereas in BRISC, it is paired with ABRO1 |
| GO:0031593 polyubiquitin modification-dependent protein binding | IDA PMID:19261749 NBA1, a new player in the Brca1 A complex, is required for D... | MARK AS OVER ANNOTATED | Summary: Polyubiquitin-dependent binding is plausible for the BRCC36 complex family, but this PMID directly concerns BRCA1-A rather than ABRAXAS2-containing BRISC. Reason: ABRAXAS2-containing BRISC is a K63-ubiquitin-directed DUB complex, but the cited paper supports polyubiquitin-chain binding in the BRCA1-A complex, not direct ABRAXAS2 binding. Later structural and functional studies support BRISC ubiquitin-chain processing and substrate targeting, so the biological context is related, but this IDA annotation overstates direct evidence for ABRAXAS2 as the enabling binder [PMID:19261749; PMID:31253574]. Supporting Evidence: PMID:19261749 four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability |
| GO:0060340 positive regulation of type I interferon-mediated signaling pathway | IMP PMID:24075985 A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates in... | NEW | Summary: NEW annotation: ABRAXAS2-containing BRISC promotes type I interferon signaling by deubiquitinating/stabilizing IFNAR1. Reason: BRISC-SHMT targets K63-ubiquitinated IFNAR1, limits receptor internalization/degradation, and is required for full interferon responses. The GO term is more specific and better supported than a broad vitamin B6-response annotation. Supporting Evidence: PMID:24075985 SHMT directs BRISC activity at K63-Ub chains conjugated to the type 1 interferon (IFN) receptor chain 1 (IFNAR1). PMID:31142841 Direct interaction with SHMT2 enhances BRISC delivery to ubiquitylated type I interferon (IFN) receptors (IFNAR1/2) |
| GO:0043517 positive regulation of DNA damage response, signal transduction by p53 class mediator | IMP PMID:25283148 ABRO1 suppresses tumourigenesis and regulates the DNA damage... | NEW | Summary: NEW annotation: ABRAXAS2/ABRO1 positively regulates p53-mediated DNA-damage signaling. Reason: The supported DNA-damage role is p53 stabilization and p53-dependent DNA-damage response, not direct DNA repair. This is why the PN-projected broad GO:0006281 DNA repair term is not proposed as a direct ABRAXAS2 annotation here. Supporting Evidence: PMID:25283148 ABRO1 stabilizes p53 by facilitating the interaction of p53 with USP7. PMID:25283148 the induction of p53 by DNA damage is almost completely attenuated by ABRO1 depletion |
Loading supporting content…
Download this section (compressed HTML)Q: Does ABRAXAS2-containing BRISC directly participate in DNA repair, or is its DNA-damage role limited to p53 stabilization and stress-response signaling outside the BRCA1-A repair complex?
Q: Which ABRAXAS2/BRISC substrates besides IFNAR1, NLRP3, and NUMA1 are physiologically dominant in primary human tissues?
Q: Should BRISC-SHMT2 metabolite-sensitive regulation be represented in GO as interferon-signaling regulation rather than broad vitamin B6 response for each BRISC component?
Experiment: Test ABRAXAS2 knockout and rescue with BRISC-assembly-defective and SHMT2-binding-defective ABRAXAS2 mutants in IFN-stimulated primary cells, measuring IFNAR1 K63 ubiquitination, receptor surface abundance, and STAT1 phosphorylation.
Experiment: Compare ABRAXAS2 and ABRAXAS1 recruitment after DNA double-strand breaks using live-cell imaging and chromatin fractionation, with BRCA1, RAP80, and p53/USP7 readouts, to separate direct DNA-repair targeting from p53-mediated DNA-damage signaling.
Experiment: Reconstitute purified human BRISC variants with NUMA1 fragments and K63-linked ubiquitin chains to test whether ABRAXAS2 microtubule-binding and scaffold regions control substrate selection during spindle assembly.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)