id: Q15018
gene_symbol: ABRAXAS2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Nuclear localization is supported as a minor/stress-induced pool.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:25283148
      supporting_text: DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus
    - reference_id: PMID:22974638
      supporting_text: during cellular stress it enters the nucleus and co-localizes with ATF4
    - reference_id: PMID:24075985
      supporting_text: presence of the BRISC-SHMT complex in both the cytoplasm and nucleus
- term:
    id: GO:0008017
    label: microtubule binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: microtubule binding is supported by ABRAXAS2/BRISC localization to mitotic microtubule structures and functional spindle defects after BRISC depletion.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: 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
    - reference_id: PMID:26195665
      supporting_text: promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA).
- 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: attachment of spindle microtubules to kinetochore is supported by ABRAXAS2/BRISC localization to mitotic microtubule structures and functional spindle defects after BRISC depletion.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: 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
    - reference_id: PMID:26195665
      supporting_text: promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA).
- term:
    id: GO:0031593
    label: polyubiquitin modification-dependent protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    additional_reference_ids:
    - PMID:31253574
    supported_by:
    - reference_id: PMID:19214193
      supporting_text: the activity was intrinsic to PA700 and the Brcc36 isopeptidase complex (BRISC)
    - reference_id: PMID:20656690
      supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
    - reference_id: PMID:31253574
      supporting_text: Both BRCC36-containing complexes are specific for lysine-63-linked ubiquitin (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: mitotic spindle assembly is supported by ABRAXAS2/BRISC localization to mitotic microtubule structures and functional spindle defects after BRISC depletion.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: 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
    - reference_id: PMID:26195665
      supporting_text: promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA).
- term:
    id: GO:0000922
    label: spindle pole
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Spindle-pole localization is supported by mitotic imaging.
    action: ACCEPT
    reason: ABRAXAS2/BRISC localizes to centrosomes and spindle poles during mitosis [PMID:26195665].
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: ABRO1 was shown to be located at the centrosomes in interphase
    - reference_id: PMID:26195665
      supporting_text: BRISC localizes at centrosomes, spindle poles, and midbody during mitosis.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Nuclear localization is supported as a minor/stress-induced pool.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:25283148
      supporting_text: DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus
    - reference_id: PMID:22974638
      supporting_text: during cellular stress it enters the nucleus and co-localizes with ATF4
    - reference_id: PMID:24075985
      supporting_text: presence of the BRISC-SHMT complex in both the cytoplasm and nucleus
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Cytoplasmic localization is well supported.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:20656690
      supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
    - reference_id: PMID:21282113
      supporting_text: ABRO1 is mainly localized in the cytoplasm.
- term:
    id: GO:0005856
    label: cytoskeleton
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Cytoskeleton is directionally correct but too broad for the available evidence.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0005874
      label: microtubule
    - id: GO:0000922
      label: spindle pole
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: ABRO1 was shown to be located at the centrosomes in interphase
    - reference_id: PMID:26195665
      supporting_text: BRISC localizes at centrosomes, spindle poles, and midbody during mitosis.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:19615732
  qualifier: enables
  review:
    summary: Generic protein-binding annotation from interaction-screen data.
    action: REMOVE
    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.
    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:32296183
  qualifier: enables
  review:
    summary: Generic protein-binding annotation from interaction-screen data.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:32296183
      supporting_text: A reference map of the human binary protein interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: Generic protein-binding annotation from interaction-screen data.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:33961781
      supporting_text: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:36115835
  qualifier: enables
  review:
    summary: Generic protein-binding annotation from interaction-screen data.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:36115835
      supporting_text: Quantitative fragmentomics allow affinity mapping of interactomes.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37398436
  qualifier: enables
  review:
    summary: Generic protein-binding annotation from interaction-screen data.
    action: REMOVE
    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.
    supported_by:
    - reference_id: PMID:37398436
      supporting_text: AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Cytosol localization is consistent with ABRAXAS2 as a major cytosolic BRISC scaffold.
    action: ACCEPT
    reason: Multiple studies describe ABRAXAS2/ABRO1/KIAA0157 as mainly cytoplasmic/cytosolic, while also allowing stress-induced nuclear pools.
    supported_by:
    - reference_id: PMID:20656690
      supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
    - reference_id: PMID:21282113
      supporting_text: ABRO1 is mainly localized in the cytoplasm.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:21282113
  qualifier: located_in
  review:
    summary: Nuclear localization is supported as a minor/stress-induced pool.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:25283148
      supporting_text: DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus
    - reference_id: PMID:22974638
      supporting_text: during cellular stress it enters the nucleus and co-localizes with ATF4
    - reference_id: PMID:24075985
      supporting_text: presence of the BRISC-SHMT complex in both the cytoplasm and nucleus
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:22974638
  qualifier: located_in
  review:
    summary: Nuclear localization is supported as a minor/stress-induced pool.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:25283148
      supporting_text: DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus
    - reference_id: PMID:22974638
      supporting_text: during cellular stress it enters the nucleus and co-localizes with ATF4
    - reference_id: PMID:24075985
      supporting_text: presence of the BRISC-SHMT complex in both the cytoplasm and nucleus
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:24075985
  qualifier: located_in
  review:
    summary: Nuclear localization is supported as a minor/stress-induced pool.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:25283148
      supporting_text: DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus
    - reference_id: PMID:22974638
      supporting_text: during cellular stress it enters the nucleus and co-localizes with ATF4
    - reference_id: PMID:24075985
      supporting_text: presence of the BRISC-SHMT complex in both the cytoplasm and nucleus
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: EXP
  original_reference_id: PMID:25283148
  qualifier: located_in
  review:
    summary: Nuclear localization is supported as a minor/stress-induced pool.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:25283148
      supporting_text: DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus
    - reference_id: PMID:22974638
      supporting_text: during cellular stress it enters the nucleus and co-localizes with ATF4
    - reference_id: PMID:24075985
      supporting_text: presence of the BRISC-SHMT complex in both the cytoplasm and nucleus
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:20656690
  qualifier: located_in
  review:
    summary: Cytoplasmic localization is well supported.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:20656690
      supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
    - reference_id: PMID:21282113
      supporting_text: ABRO1 is mainly localized in the cytoplasm.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:21282113
  qualifier: located_in
  review:
    summary: Cytoplasmic localization is well supported.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:20656690
      supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
    - reference_id: PMID:21282113
      supporting_text: ABRO1 is mainly localized in the cytoplasm.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:22974638
  qualifier: located_in
  review:
    summary: Cytoplasmic localization is well supported.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:20656690
      supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
    - reference_id: PMID:21282113
      supporting_text: ABRO1 is mainly localized in the cytoplasm.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:25283148
  qualifier: located_in
  review:
    summary: Cytoplasmic localization is well supported.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:20656690
      supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
    - reference_id: PMID:21282113
      supporting_text: ABRO1 is mainly localized in the cytoplasm.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IPI
  original_reference_id: PMID:31253574
  qualifier: located_in
  review:
    summary: Cytoplasmic localization is well supported.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:20656690
      supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
    - reference_id: PMID:21282113
      supporting_text: ABRO1 is mainly localized in the cytoplasm.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: NAS
  original_reference_id: PMID:31253574
  qualifier: located_in
  review:
    summary: Cytoplasmic localization is well supported.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:20656690
      supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
    - reference_id: PMID:21282113
      supporting_text: ABRO1 is mainly localized in the cytoplasm.
- term:
    id: GO:0034516
    label: response to vitamin B6
  evidence_type: NAS
  original_reference_id: PMID:31142841
  qualifier: involved_in
  review:
    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.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0060340
      label: positive regulation of type I interferon-mediated signaling pathway
    supported_by:
    - reference_id: PMID:31142841
      supporting_text: Intracellular levels of PLP regulate the interaction between BRISC and SHMT2, as well as inflammatory cytokine responses.
    - reference_id: PMID:31142841
      supporting_text: Mutations in BRISC that disrupt SHMT2 binding impair type I interferon signalling in response to inflammatory stimuli.
- term:
    id: GO:0070552
    label: BRISC complex
  evidence_type: IPI
  original_reference_id: PMID:31253574
  qualifier: part_of
  review:
    summary: ABRAXAS2 is a bona fide BRISC complex subunit.
    action: ACCEPT
    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.
    additional_reference_ids:
    - file:human/ABRAXAS2/ABRAXAS2-deep-research-falcon.md
    supported_by:
    - reference_id: PMID:21282113
      supporting_text: ABRO1 complex does not interact with BRCA1
    - reference_id: PMID:31253574
      supporting_text: in BRCA1-A, BRCC36 is supported by ABRAXAS (Wang et al., 2007), whereas in BRISC, it is paired with ABRO1
    - reference_id: file:human/ABRAXAS2/ABRAXAS2-deep-research-falcon.md
      supporting_text: '**ABRAXAS2/ABRO1 is a core scaffold subunit of BRISC**'
- term:
    id: GO:0070552
    label: BRISC complex
  evidence_type: NAS
  original_reference_id: PMID:31253574
  qualifier: part_of
  review:
    summary: ABRAXAS2 is a bona fide BRISC complex subunit.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:21282113
      supporting_text: ABRO1 complex does not interact with BRCA1
    - reference_id: PMID:31253574
      supporting_text: in BRCA1-A, BRCC36 is supported by ABRAXAS (Wang et al., 2007), whereas in BRISC, it is paired with ABRO1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:26195665
  qualifier: enables
  review:
    summary: Generic protein-binding annotation for the ABRAXAS2/NUMA1 interaction.
    action: REMOVE
    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].
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: 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
    - reference_id: PMID:26195665
      supporting_text: promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA).
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-5691439
  qualifier: located_in
  review:
    summary: Cytosol localization is consistent with ABRAXAS2 as a major cytosolic BRISC scaffold.
    action: ACCEPT
    reason: Multiple studies describe ABRAXAS2/ABRO1/KIAA0157 as mainly cytoplasmic/cytosolic, while also allowing stress-induced nuclear pools.
    supported_by:
    - reference_id: Reactome:R-HSA-5691439
      supporting_text: FAM175B (ABRO1), another BRISC subunit, binds directly to NLRP3 leading to FAM175B-dependent recruitment of the BRISC complex
- term:
    id: GO:0000278
    label: mitotic cell cycle
  evidence_type: IMP
  original_reference_id: PMID:26195665
  qualifier: involved_in
  review:
    summary: Mitotic cell cycle is supported but too broad relative to the specific spindle defects.
    action: MODIFY
    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_replacement_terms:
    - id: GO:0090307
      label: mitotic spindle assembly
    - id: GO:0008608
      label: attachment of spindle microtubules to kinetochore
    - id: GO:0007059
      label: chromosome segregation
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: 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
    - reference_id: PMID:26195665
      supporting_text: promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA).
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:24075985
  qualifier: located_in
  review:
    summary: Cytoplasmic localization is well supported.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:20656690
      supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
    - reference_id: PMID:21282113
      supporting_text: ABRO1 is mainly localized in the cytoplasm.
- term:
    id: GO:0005813
    label: centrosome
  evidence_type: IDA
  original_reference_id: PMID:26195665
  qualifier: colocalizes_with
  review:
    summary: Centrosome colocalization is experimentally supported in mitotic-cell imaging.
    action: ACCEPT
    reason: ABRAXAS2/BRISC localizes to centrosomes and spindle poles during the cell cycle [PMID:26195665].
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: ABRO1 was shown to be located at the centrosomes in interphase
    - reference_id: PMID:26195665
      supporting_text: BRISC localizes at centrosomes, spindle poles, and midbody during mitosis.
- term:
    id: GO:0007059
    label: chromosome segregation
  evidence_type: IMP
  original_reference_id: PMID:26195665
  qualifier: involved_in
  review:
    summary: Chromosome-segregation defects follow ABRAXAS2/BRISC depletion.
    action: ACCEPT
    reason: ABRAXAS2 depletion produces lagging chromosomes and spindle defects, supporting involvement in chromosome segregation through its spindle assembly role [PMID:26195665].
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: 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
    - reference_id: PMID:26195665
      supporting_text: promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA).
- term:
    id: GO:0008017
    label: microtubule binding
  evidence_type: IDA
  original_reference_id: PMID:26195665
  qualifier: enables
  review:
    summary: microtubule binding is supported by ABRAXAS2/BRISC localization to mitotic microtubule structures and functional spindle defects after BRISC depletion.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: 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
    - reference_id: PMID:26195665
      supporting_text: promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA).
- term:
    id: GO:0008608
    label: attachment of spindle microtubules to kinetochore
  evidence_type: IMP
  original_reference_id: PMID:26195665
  qualifier: involved_in
  review:
    summary: attachment of spindle microtubules to kinetochore is supported by ABRAXAS2/BRISC localization to mitotic microtubule structures and functional spindle defects after BRISC depletion.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: 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
    - reference_id: PMID:26195665
      supporting_text: promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA).
- term:
    id: GO:0030496
    label: midbody
  evidence_type: IDA
  original_reference_id: PMID:26195665
  qualifier: colocalizes_with
  review:
    summary: midbody localization is supported by mitotic imaging.
    action: ACCEPT
    reason: ABRAXAS2/BRISC was observed at centrosomes, spindle poles, K-fiber minus ends, and midbody during mitosis [PMID:26195665].
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: ABRO1 was shown to be located at the centrosomes in interphase
    - reference_id: PMID:26195665
      supporting_text: BRISC localizes at centrosomes, spindle poles, and midbody during mitosis.
- term:
    id: GO:0031616
    label: spindle pole centrosome
  evidence_type: IDA
  original_reference_id: PMID:26195665
  qualifier: colocalizes_with
  review:
    summary: spindle pole centrosome localization is supported by mitotic imaging.
    action: ACCEPT
    reason: ABRAXAS2/BRISC was observed at centrosomes, spindle poles, K-fiber minus ends, and midbody during mitosis [PMID:26195665].
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: ABRO1 was shown to be located at the centrosomes in interphase
    - reference_id: PMID:26195665
      supporting_text: BRISC localizes at centrosomes, spindle poles, and midbody during mitosis.
- term:
    id: GO:0036449
    label: microtubule minus-end
  evidence_type: IDA
  original_reference_id: PMID:26195665
  qualifier: colocalizes_with
  review:
    summary: microtubule minus-end localization is supported by mitotic imaging.
    action: ACCEPT
    reason: ABRAXAS2/BRISC was observed at centrosomes, spindle poles, K-fiber minus ends, and midbody during mitosis [PMID:26195665].
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: ABRO1 was shown to be located at the centrosomes in interphase
    - reference_id: PMID:26195665
      supporting_text: BRISC localizes at centrosomes, spindle poles, and midbody during mitosis.
- term:
    id: GO:0070536
    label: protein K63-linked deubiquitination
  evidence_type: IMP
  original_reference_id: PMID:24075985
  qualifier: involved_in
  review:
    summary: Protein K63-linked deubiquitination is the central BRISC pathway function involving ABRAXAS2.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:24075985
      supporting_text: SHMT directs BRISC activity at K63-Ub chains conjugated to the type 1 interferon (IFN) receptor chain 1 (IFNAR1).
    - reference_id: PMID:31142841
      supporting_text: Direct interaction with SHMT2 enhances BRISC delivery to ubiquitylated type I interferon (IFN) receptors (IFNAR1/2)
- term:
    id: GO:0070536
    label: protein K63-linked deubiquitination
  evidence_type: IMP
  original_reference_id: PMID:26195665
  qualifier: involved_in
  review:
    summary: Protein K63-linked deubiquitination is the central BRISC pathway function involving ABRAXAS2.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: 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
    - reference_id: PMID:26195665
      supporting_text: promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA).
- term:
    id: GO:0070552
    label: BRISC complex
  evidence_type: IDA
  original_reference_id: PMID:24075985
  qualifier: part_of
  review:
    summary: ABRAXAS2 is a bona fide BRISC complex subunit.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:21282113
      supporting_text: ABRO1 complex does not interact with BRCA1
    - reference_id: PMID:31253574
      supporting_text: in BRCA1-A, BRCC36 is supported by ABRAXAS (Wang et al., 2007), whereas in BRISC, it is paired with ABRO1
- term:
    id: GO:0090307
    label: mitotic spindle assembly
  evidence_type: IMP
  original_reference_id: PMID:26195665
  qualifier: involved_in
  review:
    summary: mitotic spindle assembly is supported by ABRAXAS2/BRISC localization to mitotic microtubule structures and functional spindle defects after BRISC depletion.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:26195665
      supporting_text: 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
    - reference_id: PMID:26195665
      supporting_text: promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA).
- term:
    id: GO:0002931
    label: response to ischemia
  evidence_type: IMP
  original_reference_id: PMID:21195082
  qualifier: involved_in
  review:
    summary: Response to ischemia is supported in a cardiac injury model but is context-specific.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:21195082
      supporting_text: Reducing the Abro1 protein level exacerbated cellular damage and cell death of cardiomyocytes due to MI/R injury.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:21195082
  qualifier: located_in
  review:
    summary: Cytoplasmic localization is well supported.
    action: ACCEPT
    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].
    supported_by:
    - reference_id: PMID:20656690
      supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
    - reference_id: PMID:21282113
      supporting_text: ABRO1 is mainly localized in the cytoplasm.
- term:
    id: GO:0070552
    label: BRISC complex
  evidence_type: IDA
  original_reference_id: PMID:19214193
  qualifier: part_of
  review:
    summary: ABRAXAS2 is a bona fide BRISC complex subunit.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:21282113
      supporting_text: ABRO1 complex does not interact with BRCA1
    - reference_id: PMID:31253574
      supporting_text: in BRCA1-A, BRCC36 is supported by ABRAXAS (Wang et al., 2007), whereas in BRISC, it is paired with ABRO1
- term:
    id: GO:0031593
    label: polyubiquitin modification-dependent protein binding
  evidence_type: IDA
  original_reference_id: PMID:19261749
  qualifier: enables
  review:
    summary: Polyubiquitin-dependent binding is plausible for the BRCC36 complex family, but this PMID directly concerns BRCA1-A rather than ABRAXAS2-containing BRISC.
    action: MARK_AS_OVER_ANNOTATED
    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].
    additional_reference_ids:
    - PMID:31253574
    supported_by:
    - reference_id: PMID:19261749
      supporting_text: four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability
- term:
    id: GO:0060340
    label: positive regulation of type I interferon-mediated signaling pathway
  evidence_type: IMP
  original_reference_id: PMID:24075985
  qualifier: involved_in
  review:
    summary: 'NEW annotation: ABRAXAS2-containing BRISC promotes type I interferon signaling by deubiquitinating/stabilizing IFNAR1.'
    action: NEW
    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.
    additional_reference_ids:
    - PMID:31142841
    supported_by:
    - reference_id: PMID:24075985
      supporting_text: SHMT directs BRISC activity at K63-Ub chains conjugated to the type 1 interferon (IFN) receptor chain 1 (IFNAR1).
    - reference_id: PMID:31142841
      supporting_text: Direct interaction with SHMT2 enhances BRISC delivery to ubiquitylated type I interferon (IFN) receptors (IFNAR1/2)
- term:
    id: GO:0043517
    label: positive regulation of DNA damage response, signal transduction by p53 class mediator
  evidence_type: IMP
  original_reference_id: PMID:25283148
  qualifier: involved_in
  review:
    summary: 'NEW annotation: ABRAXAS2/ABRO1 positively regulates p53-mediated DNA-damage signaling.'
    action: NEW
    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.
    supported_by:
    - reference_id: PMID:25283148
      supporting_text: ABRO1 stabilizes p53 by facilitating the interaction of p53 with USP7.
    - reference_id: PMID:25283148
      supporting_text: the induction of p53 by DNA damage is almost completely attenuated by ABRO1 depletion
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings:
  - statement: PANTHER phylogenetic annotations propagate conserved ABRAXAS2/ABRO1 family localization, microtubule, ubiquitin-chain binding, and mitotic spindle terms.
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings:
  - statement: UniProt subcellular-location keyword mapping supports broad nucleus, cytoplasm, cytoskeleton, and spindle-pole cellular component annotations.
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings:
  - statement: Human Protein Atlas immunofluorescence curation supports ABRAXAS2 cytosol localization.
- id: PMID:19214193
  title: 'K63-specific deubiquitination by two JAMM/MPN+ complexes: BRISC-associated Brcc36 and proteasomal Poh1.'
  findings:
  - statement: Biochemical fractionation identifies BRISC as a Brcc36-containing K63-specific deubiquitinating complex.
    supporting_text: the activity was intrinsic to PA700 and the Brcc36 isopeptidase complex (BRISC)
    reference_section_type: ABSTRACT
- id: PMID:19261749
  title: NBA1, a new player in the Brca1 A complex, is required for DNA damage resistance and checkpoint control.
  findings:
  - statement: The BRCA1-A complex study supports polyubiquitin-chain binding by related complex components, but its direct evidence is for BRCA1-A/ABRAXAS1 rather than ABRAXAS2/BRISC.
    supporting_text: four members of the BRCA1-A complex possess a polyubiquitin chain-binding capability
    reference_section_type: ABSTRACT
- id: PMID:19615732
  title: Defining the human deubiquitinating enzyme interaction landscape.
  findings:
  - statement: Proteomic interactome mapping places ABRAXAS2 among DUB-associated interaction data but does not by itself define an informative GO molecular function beyond generic protein binding.
    supporting_text: We identified 774 candidate interacting proteins associated with 75 Dubs.
    reference_section_type: ABSTRACT
- id: PMID:20656690
  title: The Lys63-specific deubiquitinating enzyme BRCC36 is regulated by two scaffold proteins localizing in different subcellular compartments.
  findings:
  - statement: KIAA0157/ABRAXAS2 is a cytosolic scaffold that activates BRCC36 in the BRISC complex and distinguishes BRISC from nuclear BRCA1-A.
    supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
    reference_section_type: ABSTRACT
- id: PMID:21195082
  title: Regulation of Abro1/KIAA0157 during myocardial infarction and cell death reveals a novel cardioprotective mechanism for Lys63-specific deubiquitination.
  findings:
  - statement: ABRO1 is induced in myocardial ischemia/reperfusion and contributes to cardioprotection through K63-linked deubiquitination.
    supporting_text: Reducing the Abro1 protein level exacerbated cellular damage and cell death of cardiomyocytes due to MI/R injury.
    reference_section_type: ABSTRACT
- id: PMID:21282113
  title: NBA1/MERIT40 and BRE interaction is required for the integrity of two distinct deubiquitinating enzyme BRCC36-containing complexes.
  findings:
  - statement: ABRO1-containing BRISC is mainly cytoplasmic, lacks the BRCA1-interacting motif, and does not interact with BRCA1.
    supporting_text: Because it lacks the BRCA1-interacting motif, the ABRO1 complex does not interact with BRCA1.
    reference_section_type: ABSTRACT
- id: PMID:22974638
  title: ATF4 interacts with Abro1/KIAA0157 scaffold protein and participates in a cytoprotective pathway.
  findings:
  - statement: ABRO1 can enter the nucleus during cellular stress and interact with ATF4 in a cytoprotective pathway.
    supporting_text: Abro1 is predominantly cytoplasmic, but during cellular stress it enters the nucleus and co-localizes with ATF4.
    reference_section_type: ABSTRACT
- id: PMID:24075985
  title: A BRISC-SHMT complex deubiquitinates IFNAR1 and regulates interferon responses.
  findings:
  - statement: SHMT2 targets BRISC to K63-ubiquitinated IFNAR1, promoting receptor deubiquitination and type I interferon responses.
    supporting_text: SHMT directs BRISC activity at K63-Ub chains conjugated to the type 1 interferon (IFN) receptor chain 1 (IFNAR1).
    reference_section_type: ABSTRACT
- id: PMID:25283148
  title: ABRO1 suppresses tumourigenesis and regulates the DNA damage response by stabilizing p53.
  findings:
  - statement: ABRO1 promotes p53 stability by facilitating USP7-p53 interaction and is induced/translocated after DNA damage.
    supporting_text: ABRO1 stabilizes p53 by facilitating the interaction of p53 with USP7.
    reference_section_type: ABSTRACT
- id: PMID:26195665
  title: The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells.
  findings:
  - statement: BRISC localizes to microtubule minus ends and spindle poles, binds microtubules, and promotes spindle assembly by deubiquitinating NUMA.
    supporting_text: 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
    reference_section_type: ABSTRACT
- id: PMID:31142841
  title: Metabolic control of BRISC-SHMT2 assembly regulates immune signalling.
  findings:
  - statement: PLP-dependent SHMT2 oligomerization regulates BRISC-SHMT2 assembly and type I interferon signaling.
    supporting_text: Mutations in BRISC that disrupt SHMT2 binding impair type I interferon signalling in response to inflammatory stimuli.
    reference_section_type: ABSTRACT
- id: PMID:31253574
  title: Structural Basis of BRCC36 Function in DNA Repair and Immune Regulation.
  findings:
  - statement: Structures distinguish ABRAXAS/BRCA1-A DNA-repair targeting from ABRO1/BRISC immune-stress signaling and SHMT2 regulation.
    supporting_text: The BRCA1-A and BRISC complexes serve in DNA double-strand break repair and immune signaling
    reference_section_type: ABSTRACT
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings:
  - statement: Large-scale binary interactome data support generic interaction evidence but not a specific ABRAXAS2 molecular function.
    supporting_text: A reference map of the human binary protein interactome.
    reference_section_type: RESULTS
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings:
  - statement: Proteome-scale AP-MS interaction data support generic interaction evidence but not a specific ABRAXAS2 molecular function.
    supporting_text: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
    reference_section_type: RESULTS
- id: PMID:36115835
  title: Quantitative fragmentomics allow affinity mapping of interactomes.
  findings:
  - statement: Fragment-level interactome data support generic interaction evidence but not a specific ABRAXAS2 molecular function.
    supporting_text: Quantitative fragmentomics allow affinity mapping of interactomes.
    reference_section_type: ABSTRACT
- id: PMID:37398436
  title: AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor.
  findings:
  - statement: A preprint interactome/drug-discovery pipeline reports generic interaction evidence that is not an informative ABRAXAS2 GO function.
    supporting_text: AI-guided pipeline for protein-protein interaction drug discovery identifies a SARS-CoV-2 inhibitor.
    reference_section_type: ABSTRACT
- id: Reactome:R-HSA-5691439
  title: BRISC complex deubiquitinates NLRP3
  findings:
  - statement: Reactome places ABRO1/FAM175B in cytosolic BRISC-mediated K63 deubiquitination of NLRP3.
    supporting_text: FAM175B (ABRO1), another BRISC subunit, binds directly to NLRP3 leading to FAM175B-dependent recruitment of the BRISC complex
    reference_section_type: RESULTS
- id: file:human/ABRAXAS2/ABRAXAS2-notes.md
  title: ABRAXAS2 review notes
  findings:
  - statement: Local notes summarize the Proteostasis Network projected context and the conservative decision not to propagate broad DNA repair from PN context alone.
- id: file:human/ABRAXAS2/ABRAXAS2-deep-research-falcon.md
  title: ABRAXAS2 Falcon deep research report
  findings:
  - statement: Falcon deep research produced a secondary synthesis for ABRAXAS2; it was used only as orientation because the primary curation decisions were checked against cached primary literature and project files.
aliases:
- ABRO1
- FAM175B
- KIAA0157
core_functions:
- description: ABRAXAS2 is the BRISC-specific MPN-domain scaffold/adaptor paired with BRCC3/BRCC36 in a K63-linked deubiquitinating complex. Its core role is not catalysis; instead, ABRAXAS2 organizes the BRISC assembly, helps determine cytoplasmic/nuclear targeting, and provides an interaction surface that distinguishes BRISC from ABRAXAS1-containing BRCA1-A. Through this complex, ABRAXAS2 supports K63-linked deubiquitination of substrates such as IFNAR1 and NUMA1, with NLRP3 inflammasome recruitment supported as an additional BRISC substrate-targeting context.
  directly_involved_in:
  - id: GO:0070536
    label: protein K63-linked deubiquitination
  - id: GO:0060340
    label: positive regulation of type I interferon-mediated signaling pathway
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005634
    label: nucleus
  in_complex:
    id: GO:0070552
    label: BRISC complex
  supported_by:
  - reference_id: PMID:19214193
    supporting_text: the activity was intrinsic to PA700 and the Brcc36 isopeptidase complex (BRISC)
  - reference_id: PMID:20656690
    supporting_text: KIAA0157 mainly localizes in cytosol and activates BRCC36 in the cytoplasm.
  - reference_id: PMID:24075985
    supporting_text: SHMT directs BRISC activity at K63-Ub chains conjugated to the type 1 interferon (IFN) receptor chain 1 (IFNAR1).
  - reference_id: PMID:31142841
    supporting_text: Direct interaction with SHMT2 enhances BRISC delivery to ubiquitylated type I interferon (IFN) receptors (IFNAR1/2)
  - reference_id: PMID:21282113
    supporting_text: ABRO1 complex does not interact with BRCA1
  - reference_id: PMID:31253574
    supporting_text: in BRCA1-A, BRCC36 is supported by ABRAXAS (Wang et al., 2007), whereas in BRISC, it is paired with ABRO1
  - reference_id: Reactome:R-HSA-5691439
    supporting_text: FAM175B (ABRO1), another BRISC subunit, binds directly to NLRP3 leading to FAM175B-dependent recruitment of the BRISC complex
- molecular_function:
    id: GO:0008017
    label: microtubule binding
  description: ABRAXAS2-containing BRISC binds mitotic microtubule structures, accumulates at K-fiber minus ends, spindle poles, centrosomes, and midbody, and promotes functional bipolar spindle assembly. Mechanistically, BRISC deubiquitinates K63-linked ubiquitin chains on NUMA1, influencing NUMA1 interactions needed for spindle-pole organization and kinetochore-microtubule attachment.
  directly_involved_in:
  - id: GO:0090307
    label: mitotic spindle assembly
  - id: GO:0008608
    label: attachment of spindle microtubules to kinetochore
  - id: GO:0007059
    label: chromosome segregation
  - id: GO:0070536
    label: protein K63-linked deubiquitination
  locations:
  - id: GO:0000922
    label: spindle pole
  - id: GO:0031616
    label: spindle pole centrosome
  - id: GO:0036449
    label: microtubule minus-end
  - id: GO:0030496
    label: midbody
  supported_by:
  - reference_id: PMID:26195665
    supporting_text: 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
  - reference_id: PMID:26195665
    supporting_text: promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA).
  - reference_id: PMID:26195665
    supporting_text: ABRO1 was shown to be located at the centrosomes in interphase
  - reference_id: PMID:26195665
    supporting_text: BRISC localizes at centrosomes, spindle poles, and midbody during mitosis.
- description: A secondary, stress-responsive ABRAXAS2 activity is p53 pathway regulation. ABRO1/ABRAXAS2 can accumulate and translocate to the nucleus after DNA damage, promotes USP7-p53 interaction, and stabilizes p53, thereby supporting p53-mediated DNA-damage signaling. This supports a specific p53-pathway process annotation but does not justify broad direct DNA repair annotation.
  directly_involved_in:
  - id: GO:0043517
    label: positive regulation of DNA damage response, signal transduction by p53 class mediator
  locations:
  - id: GO:0005634
    label: nucleus
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:25283148
    supporting_text: ABRO1 stabilizes p53 by facilitating the interaction of p53 with USP7.
  - reference_id: PMID:25283148
    supporting_text: the induction of p53 by DNA damage is almost completely attenuated by ABRO1 depletion
  - reference_id: PMID:25283148
    supporting_text: DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus
  - reference_id: PMID:22974638
    supporting_text: during cellular stress it enters the nucleus and co-localizes with ATF4
proposed_new_terms: []
suggested_questions:
- question: 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?
- question: Which ABRAXAS2/BRISC substrates besides IFNAR1, NLRP3, and NUMA1 are physiologically dominant in primary human tissues?
- question: Should BRISC-SHMT2 metabolite-sensitive regulation be represented in GO as interferon-signaling regulation rather than broad vitamin B6 response for each BRISC component?
suggested_experiments:
- description: 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.
- description: 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.
- description: 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.