just fetch-gene human ABRAXAS1 seeded the UniProt, GOA, Reactome, PANTHER family, and review stub files on 2026-06-03.just deep-research-falcon human ABRAXAS1 --fallback perplexity-lite. Falcon timed out after 600 seconds; the perplexity-lite fallback then failed with a Perplexity API 401 quota error. No provider deep-research file was produced, so this review uses cached publications, UniProt, Reactome, PANTHER, and PN projection files directly.ABRAXAS1/FAM175A/CCDC98 is a nuclear BRCA1-A complex scaffold and ubiquitin-recognition subunit. The primary literature identifies Abraxas as a BRCA1 BRCT-binding phosphoprotein and RAP80 partner: PMID:17525340 and PMID:17525340.
The supported biological role is DNA double-strand break response and checkpoint/repair signaling, not a standalone catalytic activity. The key experimental summary is that PMID:17525340. A second study frames CCDC98 as the factor that mediates BRCA1-RAP80 association and BRCA1-dependent G2/M checkpoint activation PMID:17643121.
ABRAXAS1 is also an organizer of the RAP80/BRCA1-A complex. Feng et al. describe CCDC98 as central to assembly: PMID:19261748. The BRCA1-A/RAP80 complex has BRCC36 K63-linked deubiquitinase activity, but the catalytic subunit is BRCC36, while Abraxas is required for that activity in the RAP80 complex context PMID:20656689.
The PN projection has three ABRAXAS1 rows:
GO:0070531 BRCA1-A complex: already exact in GOA and accepted.GO:0006281 DNA repair: already entailed by GOA via GO:0006302 double-strand break repair, so no new annotation is needed.GO:0000151 ubiquitin ligase complex: new to GOA from the PN group Ubiquitin Proteasome System|E3 ubiquitin and UBL ligases|idiosyncratic RING complex. I did not add this as a proposed annotation. ABRAXAS1 is part of BRCA1-A, but the gene-level evidence supports scaffold/polyubiquitin-binding and BRCC36 DUB support rather than direct membership in a generic ubiquitin ligase complex. The PN mapping itself says this is a shared E3-complex bucket and warns against assigning catalytic activity to every subunit.protein binding rows are real interaction evidence but too uninformative for core molecular function. Mechanistic papers should be interpreted as BRCA1-A complex assembly, RAP80/BRCA1/BRCC36 interaction, and polyubiquitin-dependent recruitment rather than retained as generic protein binding.WITH/FROM: UniProtKB:Q15018) rather than ABRAXAS1-specific evidence. I marked microtubule binding, attachment of spindle microtubules to kinetochore, and mitotic spindle assembly for removal for ABRAXAS1.A Falcon deep-research report (ABRAXAS1-deep-research-falcon.md, Edison Scientific) was generated successfully on 2026-06-07, superseding the earlier failed run noted above. It is consistent with the existing review and adds the following, with NEW/CONFIRMS/PROVISIONAL labels. PMIDs could not be resolved via tooling for several of these primary papers (PubMed MCP unavailable); where only a DOI was available it is given, and these citations are kept in notes only rather than added as guessed PMIDs to the YAML.
CONFIRMS (molecular function / mechanism): ABRAXAS1 is a non-catalytic scaffold/adaptor with an N-terminal MPN-/JAMM-like domain that is catalytically inactive (MPN-) and acts as a DEUBAD-like activator/positioner of the K63-specific DUB BRCC36; ABRAXAS1 itself does not deubiquitinate. This matches the existing KEEP polyubiquitin-binding / not the catalytic DUB framing [PMID:20656689 "Abraxas and BRCC45 were essential for BRCC36 DUB activity within the RAP80 complex"; Rabl 2020 review doi:10.3390/biom10111503; Kyrieleis 2016 doi:10.1016/j.celrep.2016.11.063].
NEW (structural architecture): Negative-stain EM of a reconstituted human BRCA1-A core (Abraxas/BRCC36/BRCC45/MERIT40) supports a V-shaped "superdimer" (dimer of heterotetramers) with ABRAXAS1-BRCC36 at the base and BRCC45/MERIT40 in the arms; complexes prefer longer K63 chains (>=4 Ub), and RAP80 enhances targeting to mixed SUMO-K63 chains [Kyrieleis 2016 doi:10.1016/j.celrep.2016.11.063; Rabl 2019 Mol Cell doi:10.1016/j.molcel.2019.06.002]. Adds structural detail beyond current complex-membership annotations; no annotation change warranted.
NEW (domain map / NLS, clinical): ABRAXAS1 has an NLS (~aa 358-361, incl. Arg361) required for nuclear import of BRCA1-A; the Finnish founder variant c.1082G>A p.Arg361Gln (R361Q) impairs nuclear localization and reduces BRCA1/CtIP foci [Bose 2019 Hum Mol Genet doi:10.1093/hmg/ddz252]. A 2024 motif-interactome study (already cited as PMID:39009827) quantified the R361Q effect: importin/karyopherin affinity weakened ~10-fold (WT KD 7.5 uM vs R361Q 75 uM) with increased cytoplasmic localization PMID:39009827. The C-terminal pSPxF/SPTF motif (~aa 406-409; S404 damage-inducible, S406 constitutive, F409 critical) mediates phospho-dependent BRCA1 BRCT binding.
NEW (disease mechanism / pathway choice): Two truncating germline ABRAXAS1 variants from early-onset breast cancer patients - c.1106dup (p.Ser370Ilefs2, loses the C-terminal BRCA1-binding SPTF motif) and c.577C>T (p.Arg193, also lacks the BRCC36-interaction region) - act dominantly to shift BRCA1 partitioning from BRCA1-A toward BRCA1-C and derepress mutagenic DSB repair (SSA/MMEJ/NHEJ) without impairing HR; notably heterozygous carriers did NOT show HR deficiency or altered PARP-inhibitor sensitivity [Sachsenweger 2023 Cell Death Dis doi:10.1038/s41419-023-05845-6]. Reframes ABRAXAS1 as a "fine-tuner" of BRCA1 repair-pathway choice (restrains end resection / mutagenic pathways) rather than a simple HR-promoting factor. Supports the existing positive regulation of DNA repair / checkpoint framing; no existing annotation contradicted.
PROVISIONAL / low-confidence (RNA association): A proteome-wide R-DeeP screen in A549 lung cancer cells identified ABRAXAS1 as RNA-dependent, with direct RNA interaction validated by iCLIP2 ("mitosis-related protein ABRAXAS1") [Rajagopal 2022 Cancers doi:10.3390/cancers14246109]. This is a single high-throughput study in one cell line; flagged provisional and NOT used to add any RNA-binding GO annotation. Worth a curator question only.
CONFIRMS (paralog specialization): ABRAXAS1 (BRCA1-A, nuclear) vs paralog ABRO1/ABRAXAS2 (BRISC, largely non-nuclear) partition the shared BRCC36/BRE/MERIT40 core. This reinforces the existing REMOVE decisions on microtubule/spindle IBA terms traceable to ABRAXAS2 [Rabl 2020 doi:10.3390/biom10111503; Rabl 2019 doi:10.1016/j.molcel.2019.06.002].
All three challenged microtubule/spindle IBAs are UNDECIDED. PAINT places the assertions at metazoan PTN001272083 with ABRAXAS2/Q15018 support. The primary BRISC study directly establishes ABRO1/BRISC microtubule association and NuMA-dependent spindle regulation [PMID:26195665, “The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells.”]. Its source mechanism does not by itself prove conservation or loss in ABRAXAS1. Distinct BRCA1-A versus BRISC partners make divergence plausible, but a principal nuclear DNA-repair location is not an exclusive localization statement. The existing OpenScientist report is marked disputed where it converts lack of target assays and a single paralog source into refutation. Its exact excerpt and the primary source are incorporated. Other DNA-repair, ubiquitin-recognition, localization and core-function claims were screened and retained; generic protein binding is removed for informativeness.