| Feature | Molecular detail (residues/motif where available) | Functional consequence | Key sources (citation IDs) | URL (if available) |
|---|---|---|---|---|
| Verified identity | Human ABRAXAS1 / ABRA1 / CCDC98 / FAM175A; UniProt Q6UWZ7; ~409 aa scaffold/adaptor | Confirms the target is the BRCA1-A complex subunit Abraxas 1, not the paralog ABRO1/Abraxas2 | (pqac-00000001, pqac-00000006) | https://doi.org/10.3390/biom10111503; https://doi.org/10.1093/hmg/ddz252 |
| N-terminal MPN-like domain | JAMM/MPN− domain; aa ~11–121; catalytically inactive due to loss of Zn-binding catalytic configuration | Binds and activates the catalytic MPN+ DUB BRCC36; scaffold role rather than protease activity | (pqac-00000002, pqac-00000024, pqac-00000030) | https://doi.org/10.3390/biom10111503; https://doi.org/10.1016/j.celrep.2016.11.063 |
| Coiled-coil region | aa ~206–260 | Supports higher-order assembly/dimerization and contributes to interactions within BRCA1-A; loss with deeper truncation derepresses mutagenic DSBR pathways | (pqac-00000002, pqac-00000008, pqac-00000010) | https://doi.org/10.3390/biom10111503; https://doi.org/10.1038/s41419-023-05845-6 |
| Nuclear localization signal (NLS) | aa ~358–361; includes Arg361 | Required for nuclear import of ABRAXAS1/BRCA1-A; R361Q impairs nuclear localization and BRCA1 focus formation | (pqac-00000002, pqac-00000006, pqac-00000022) | https://doi.org/10.3390/biom10111503; https://doi.org/10.1093/hmg/ddz252; https://doi.org/10.1038/s44320-024-00055-4 |
| C-terminal BRCA1-binding motif | pSPxF / SPTF motif at aa ~406–409; S404 damage-inducible, S406 constitutive, terminal F409 critical | Phospho-dependent binding to BRCA1 BRCT domains; drives BRCA1 recruitment/sequestration in BRCA1-A | (pqac-00000005, pqac-00000006, pqac-00000007) | https://doi.org/10.3390/biom10111503; https://doi.org/10.1093/hmg/ddz252; https://doi.org/10.1038/s41419-023-05845-6 |
| BRCC36 interaction | N-terminal scaffold interaction via MPN dimer with BRCC36 | Activates the K63-specific BRCC36 deubiquitinase and organizes the DUB core | (pqac-00000024, pqac-00000026, pqac-00000031) | https://doi.org/10.3390/biom10111503; https://doi.org/10.1016/j.celrep.2016.11.063 |
| RAP80 integration | ABRAXAS1 C-terminal/unstructured region binds on top of RAP80; RAP80 is constitutive BRCA1-A subunit | Couples BRCA1-A to K63-Ub and SUMO-ubiquitin damage marks at DSB-flanking chromatin | (pqac-00000002, pqac-00000003, pqac-00000028) | https://doi.org/10.3390/biom10111503; https://doi.org/10.1016/j.molcel.2019.06.002 |
| BRCA1-A complex membership | Core complex: ABRAXAS1, BRCC36, BRE/BRCC45, MERIT40, RAP80; BRCA1 binds via ABRAXAS1 phospho-tail | Recruits/positions BRCA1-A at DNA damage foci, edits K63-Ub chromatin signals, limits end resection and suppresses excessive HR/SSA | (pqac-00000001, pqac-00000003, pqac-00000008) | https://doi.org/10.3390/biom10111503; https://doi.org/10.1016/j.molcel.2019.06.002; https://doi.org/10.1038/s41419-023-05845-6 |
| BRISC distinction | ABRAXAS1 is not the BRISC-specific adaptor; ABRO1/Abraxas2 replaces ABRAXAS1 in BRISC | Explains why ABRAXAS1 is primarily linked to nuclear DNA-damage signaling, whereas BRISC has mostly non-nuclear/immune roles | (pqac-00000001, pqac-00000004) | https://doi.org/10.3390/biom10111503; https://doi.org/10.1016/j.molcel.2019.06.002 |
| Cellular localization | Predominantly nuclear; nuclear import depends on ABRAXAS1 NLS; BRCA1-A accumulates at DNA repair foci | Ensures BRCA1-A function at chromatin near DSBs; defective localization perturbs DDR and checkpoint control | (pqac-00000002, pqac-00000004, pqac-00000006) | https://doi.org/10.3390/biom10111503; https://doi.org/10.1016/j.molcel.2019.06.002; https://doi.org/10.1093/hmg/ddz252 |
| Structural architecture | BRCA1-A core forms a V-shaped superdimer/dimer-of-heterotetramers with ABRAXAS1-BRCC36 at the base and BRCC45/MERIT40 in the arms | Supports stable assembly, substrate engagement, and efficient K63-linked ubiquitin-chain processing | (pqac-00000029, pqac-00000031) | https://doi.org/10.1016/j.celrep.2016.11.063 |
| DUB pathway function | BRCC36 active site is K63-linkage specific; ABRAXAS1 acts as DEUBAD-like adaptor and targeting subunit | Places K63-specific deubiquitination on chromatin at DNA breaks; helps delimit ubiquitin signaling domains around lesions | (pqac-00000024, pqac-00000026, pqac-00000027) | https://doi.org/10.3390/biom10111503 |
| Patient-relevant truncation variants | c.1106dup (p.Ser370Ilefs*2) loses C-terminal BRCA1-binding motif; c.577C>T (p.Arg193*) also lacks BRCC36-interaction region | Shift BRCA1 partitioning from BRCA1-A toward BRCA1-C, increase SSA/MMEJ/NHEJ-associated phenotypes, and destabilize genome maintenance | (pqac-00000009, pqac-00000010, pqac-00000015) | https://doi.org/10.1038/s41419-023-05845-6 |
| RNA-dependent / RNA-binding evidence | Identified as RNA-dependent protein in A549 cells; direct RNA interaction validated by iCLIP2 | Suggests an additional context-dependent RNA-associated behavior beyond canonical BRCA1-A scaffolding | (pqac-00000019, pqac-00000018) | https://doi.org/10.3390/cancers14246109 |


*Table: This table compacts the key domain architecture, binding partners, complex membership, and localization features of human ABRAXAS1 (Q6UWZ7). It is useful as a quick-reference map linking specific motifs and residues to experimentally supported functions and recent disease-relevant findings.*