{"gene":"ABRAXAS2","run_date":"2026-06-09T22:02:37","timeline":{"discoveries":[{"year":2010,"finding":"ABRAXAS2 (KIAA0157/ABRO1) is a cytoplasmic scaffold protein that forms a distinct complex with BRCC36 (separate from the nuclear BRCA1-A complex). KIAA0157 localizes mainly in the cytosol and activates BRCC36 DUB activity in the cytoplasm. Reduction of KIAA0157 expression led to an increase of the BRCA1-A complex in the nucleus, indicating fine balance between the two complexes in vivo.","method":"Co-immunoprecipitation, subcellular fractionation, siRNA knockdown, functional DUB assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, fractionation, functional DUB assays, replicated across two concurrent papers (PMID:20656690 and PMID:20656689)","pmids":["20656690"],"is_preprint":false},{"year":2010,"finding":"Within the BRISC complex, KIAA0157 (ABRO1/ABRAXAS2) is the only interaction required for BRCC36 DUB activity; BRISC deficiency enhanced formation of the BRCA1-RAP80 complex in vivo, increasing BRCA1 levels at DNA double-strand breaks.","method":"In vitro DUB activity assays with purified complexes, Co-IP, siRNA knockdown, laser-induced DSB recruitment assays","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — in vitro activity reconstitution plus cellular epistasis, replicated concurrently by independent lab (PMID:20656690)","pmids":["20656689"],"is_preprint":false},{"year":2009,"finding":"ABRO1 binds directly to BRCC36 and the BRCC36-ABRO1 heterodimer constitutes a minimal complex retaining Lys63-specific DUB activity. BRISC selectivity for K63-linked chains is not due to preferential binding to K63 polyubiquitin but is dictated by orientation of the substrate isopeptide bond within the active site.","method":"Biochemical reconstitution of heterodimer, in vitro DUB assays with defined ubiquitin substrates, binding studies","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Moderate — in vitro reconstitution of minimal complex with mechanistic dissection of substrate selectivity, single lab","pmids":["20032457"],"is_preprint":false},{"year":2015,"finding":"Crystal structure of the active BRCC36-KIAA0157 (ABRAXAS2) heterodimer and an inactive BRCC36 homodimer was solved. KIAA0157 contacts switch BRCC36 to an active conformation. Higher-order 'super-dimer' assembly (dimer of heterodimers) is required for DUB activity and for interaction with targeting proteins SHMT2 and RAP80, implicating super-dimerization as a regulatory mechanism controlling subcellular localization and biological function.","method":"X-ray crystallography, in vitro DUB activity assays, mutagenesis, co-immunoprecipitation, size-exclusion chromatography","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — crystal structure with mutagenesis and in vitro functional validation, multiple orthogonal methods in single rigorous study","pmids":["26344097"],"is_preprint":false},{"year":2019,"finding":"Cryo-EM/crystal structures of BRISC and BRCA1-A complexes revealed that ABRO1 (in BRISC) binds SHMT2α (a metabolic enzyme), and this interaction prevents BRCC36 from binding and cleaving ubiquitin chains, establishing a regulatory inhibitory mechanism. In BRCA1-A, the paralog ABRAXAS integrates RAP80 and sequesters BRCA1 away from DSB sites. The two adaptor subunits confer distinct targeting and regulatory functions to BRCC36.","method":"Cryo-EM structure determination, biochemical binding assays, in vitro DUB inhibition assays","journal":"Molecular cell","confidence":"High","confidence_rationale":"Tier 1 / Strong — atomic-resolution structures with functional validation, multiple orthogonal methods","pmids":["31253574"],"is_preprint":false},{"year":2011,"finding":"Both BRCC36-containing complexes (nuclear BRCA1-A with Abraxas; cytoplasmic BRISC with ABRO1) share BRE and NBA1/MERIT40 subunits. NBA1 interacts with BRE through a C-terminal conserved motif of NBA1 and the C-terminal UEV domain of BRE, and this interaction is critical for maintaining the integrity of both complexes and for cellular resistance to ionizing radiation.","method":"Co-immunoprecipitation, siRNA knockdown, domain-mapping pulldown assays, colony survival after IR","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and domain mapping, single lab","pmids":["21282113"],"is_preprint":false},{"year":2017,"finding":"ABRO1 protects stalled replication fork stability by inhibiting DNA2 nuclease/WRN helicase-mediated degradation of reversed forks. Depletion of RAD51 prevented DNA2/WRN-dependent fork degradation in Abro1-deficient cells, placing ABRO1 in a fork protection pathway distinct from BRCA2 (which blocks MRE11-dependent degradation). Abro1-null mice display increased chromosome instability and are tumor-prone.","method":"DNA fiber assay, siRNA/genetic knockdown, mouse knockout, genetic epistasis (RAD51 depletion)","journal":"Genes & development","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods (fiber assay, epistasis, mouse KO phenotype), single lab with rigorous controls","pmids":["28860160"],"is_preprint":false},{"year":2020,"finding":"In fork reversal, ABRO1 (along with BRCA2 and FANCD2) protects reversed forks generated by SMARCAL1, ZRANB3, and HLTF from degradation, a pathway distinct from the FBH1-mediated fork remodeling pathway protected by 53BP1/FANCA/FANCC/FANCG/BOD1L/VHL.","method":"DNA fiber assay, siRNA knockdown, genetic epistasis with multiple fork remodeling factors","journal":"Science advances","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — DNA fiber assay with epistasis panel, single lab","pmids":["33188024"],"is_preprint":false},{"year":2022,"finding":"Abro1 (and FANCD2) protect stalled replication forks, and their deficiency leads to accumulation of cytosolic single-stranded DNA (containing ribosomal DNA) that activates cGAS-STING-dependent innate immune signaling in a DNA2-dependent manner. Abro1 and FANCD2 also limit the formation of replication stress-induced P-bodies, which can modulate innate immune activation.","method":"DNA fiber assay, mouse knockout, immunofluorescence for cytosolic ssDNA, cGAS-STING pathway reporters, P-body quantification","journal":"Nature cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — multiple orthogonal methods linking fork protection to immune signaling, mechanistic validation with DNA2 dependence","pmids":["35817959"],"is_preprint":false},{"year":2014,"finding":"ABRO1 stabilizes p53 by facilitating the interaction of p53 with the deubiquitinase USP7. DNA damage induces accumulation of endogenous ABRO1 and its translocation to the nucleus; p53 induction by DNA damage is almost completely attenuated by ABRO1 depletion.","method":"Co-immunoprecipitation, subcellular fractionation, siRNA knockdown, overexpression, tumor formation assays","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — Co-IP showing ABRO1-USP7-p53 ternary interaction, multiple functional readouts, single lab","pmids":["25283148"],"is_preprint":false},{"year":2012,"finding":"ABRO1 interacts directly with ATF4, ATF5, and JunD (AP-1 family transcription factors). Under cellular stress, ABRO1 translocates from the cytoplasm to the nucleus and co-localizes with ATF4; this ATF4-ABRO1 interaction is required for the cytoprotective function of ABRO1 following oxidative stress.","method":"Co-immunoprecipitation, confocal microscopy co-localization, siRNA knockdown, cell viability assays","journal":"Biochimica et biophysica acta","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP and co-localization with functional rescue, single lab","pmids":["22974638"],"is_preprint":false},{"year":2010,"finding":"ABRO1/KIAA0157 interacts with THAP5, a zinc finger transcription factor involved in G2/M control and apoptosis. ABRO1 protein levels increase in myocardial ischemia/reperfusion injury; reducing ABRO1 exacerbated cardiomyocyte death while overexpression provided protection against oxidative stress-induced apoptosis, linked to decreased Lys63-linked ubiquitination of specific substrates.","method":"Co-immunoprecipitation (ABRO1-THAP5 interaction), in vivo mouse MI/R model, siRNA knockdown, overexpression, cell death assays","journal":"Journal of molecular and cellular cardiology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP interaction plus in vivo and cellular functional assays, single lab","pmids":["21195082"],"is_preprint":false},{"year":2016,"finding":"ABRO1/BRCC36 (BRISC complex) removes K63-linked ubiquitin chains from tankyrase 1 during G1 phase, countering the action of E3 ligase RNF8 that adds K63-linked chains in late S/G2. This cell cycle-regulated ubiquitination/deubiquitination controls tankyrase 1 stabilization, its association with telomeres, and timely sister telomere resolution.","method":"Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, telomere FISH, cell cycle synchronization","journal":"The EMBO journal","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP, ubiquitination assays, cell-cycle epistasis, and defined phenotypic readout (telomere cohesion), single lab with multiple orthogonal methods","pmids":["27993934"],"is_preprint":false},{"year":2019,"finding":"The LNK SH2 domain directly interacts with a phosphorylated tyrosine residue in KIAA0157 (ABRAXAS2). KIAA0157 deficiency in mice leads to expansion of phenotypic and functional HSCs. BRISC (via KIAA0157) attenuates TPO-induced JAK2 K63-ubiquitination; BRISC depletion increases JAK2 K63-ubiquitination, JAK2 activation, MPL receptor surface levels, and membrane-proximal JAK2/MPL association.","method":"Co-immunoprecipitation, phosphopeptide pull-down, mouse knockout, K63-ubiquitination assays, flow cytometry for HSC phenotyping and MPL surface levels","journal":"Blood","confidence":"High","confidence_rationale":"Tier 2 / Strong — direct interaction mapping, mouse KO with defined HSC phenotype, K63-Ub assays, multiple orthogonal methods","pmids":["30755420"],"is_preprint":false},{"year":2023,"finding":"ABRO1, as a scaffolding component of the BRISC-BRCC3 complex, is required for NLRP3 deubiquitylation and inflammasome activation in macrophages. Hematopoietic Abro1 deficiency reversed accelerated atherosclerosis and NETosis in Tet2 clonal hematopoiesis mice.","method":"Mouse knockout (hematopoietic Abro1 KO), bone marrow transplantation, NLRP3 inflammasome activation assays (IL-1β, caspase-1), atherosclerosis quantification","journal":"Circulation","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — mouse KO with defined inflammasome and atherosclerosis phenotypes, single lab","pmids":["37781816"],"is_preprint":false},{"year":2020,"finding":"ABRO1 stabilizes BRCC3 protein by competing with the HECT-type E3 ubiquitin ligase WWP2 for binding to BRCC3, thereby preventing WWP2-mediated ubiquitination and proteasomal degradation of BRCC3.","method":"Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, overexpression, proteasome inhibitor experiments","journal":"FEBS letters","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP competition assay and ubiquitination assay demonstrating protective mechanism, single lab","pmids":["33107021"],"is_preprint":false},{"year":2019,"finding":"FAM175B (ABRAXAS2/ABRO1) interacts with ATF4 as shown by co-localization (confocal microscopy) and co-immunoprecipitation. FAM175B inhibits ubiquitin-dependent ATF4 degradation, elevating ATF4 protein levels, and promotes ATF4-dependent CHOP expression to drive apoptosis in esophageal squamous cell carcinoma cells.","method":"Co-immunoprecipitation, confocal co-localization, ubiquitination assay, luciferase reporter, siRNA knockdown","journal":"Molecular oncology","confidence":"Medium","confidence_rationale":"Tier 3 / Moderate — Co-IP and ubiquitination assays, multiple functional readouts, single lab","pmids":["30854784"],"is_preprint":false},{"year":2023,"finding":"ABRO1 regulates cardiomyocyte proliferation by targeting METTL3-mediated m6A methylation of Psph mRNA. ABRO1 restricts METTL3 activity, reducing PSPH expression; PSPH dephosphorylates CDK2 at Thr14/Tyr15 to activate it. ABRO1 deletion increased cardiomyocyte proliferation and restored heart function after myocardial injury.","method":"Mouse knockout and overexpression models, m6A methylation assays, CDK2 phosphorylation assays, cardiomyocyte proliferation quantification","journal":"Molecular therapy","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — mouse KO/OE with mechanistic pathway involving m6A and CDK2, single lab","pmids":["36639869"],"is_preprint":false},{"year":2025,"finding":"The bacterial T3SS effector NleG6 mediates K27- and K29-linked polyubiquitination at residues K89 and K114 of ABRAXAS2/FAM175B, leading to its degradation through TOLLIP-mediated selective autophagy. ABRAXAS2 degradation triggers subsequent degradation of BRCC3, which in turn prevents TNIP1/ABIN1 degradation and inhibits NF-κB-mediated inflammatory responses.","method":"Co-immunoprecipitation, ubiquitination site mutagenesis (K89R/K114R), autophagy inhibitor experiments, TOLLIP knockdown, NF-κB reporter assays","journal":"Autophagy","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — site-specific mutagenesis identifying ubiquitination sites, genetic KO of autophagy receptor, functional NF-κB readout, single lab","pmids":["40013521"],"is_preprint":false},{"year":2025,"finding":"ABRO1 directly binds YAP and undergoes liquid-liquid phase separation with YAP and PPM1B in a YAP-dependent manner, promoting PPM1B deubiquitination (K63-linked chains at K326) by BRCC36/BRCC3. Smooth muscle cell-specific Abro1-KO mice showed attenuated HFHSD-induced arterial stiffness and TGF-β-Smad signaling.","method":"GST pull-down, co-immunoprecipitation, immunofluorescence (phase separation), mouse SMC-specific KO, ubiquitination assays, Doppler ultrasound","journal":"Circulation research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding assay, phase separation imaging, mouse KO with vascular phenotype, single lab","pmids":["39742393"],"is_preprint":false},{"year":2026,"finding":"ABRO1 directly interacts with β-catenin and, as part of BRISC, cleaves K63-linked polyubiquitin chains at β-catenin lysine 508, thereby restraining β-catenin nuclear accumulation and transcriptional activation. Cardiomyocyte-specific Abro1 deletion causes spontaneous cardiac hypertrophy and contractile dysfunction reversible by β-catenin inhibitor ICG-001.","method":"Co-immunoprecipitation, immunoprecipitation-mass spectrometry, ubiquitinome profiling, site-specific mutagenesis (K508R), cardiomyocyte-specific KO/OE mice, CUT&TAG, pharmacological rescue","journal":"Hypertension","confidence":"High","confidence_rationale":"Tier 1-2 / Strong — ubiquitination site mutagenesis, IP-MS substrate identification, mouse cardiomyocyte-specific KO with pharmacological rescue, multiple orthogonal methods","pmids":["41789465"],"is_preprint":false},{"year":2026,"finding":"DPP9 interacts with BRCC36/BRCC3 and ABRO1/ABRAXAS2 (BRISC complex components) as novel binding partners. NanoBRET assays in living cells showed that DPP9 disrupts the binding between BRCC36/BRCC3 and ABRO1/ABRAXAS2, potentially compromising BRISC integrity.","method":"TurboID proximity labeling, NanoBRET assay in living cells, validation by co-immunoprecipitation","journal":"Cellular and molecular life sciences","confidence":"Medium","confidence_rationale":"Tier 2-3 / Moderate — proximity labeling with NanoBRET validation in living cells demonstrating disruption of the BRCC36-ABRO1 interaction, single lab","pmids":["41636814"],"is_preprint":false},{"year":2020,"finding":"The transcription factor YY1 positively regulates human ABRO1 expression by binding to cis-acting elements located -89 to -59 bp upstream of the ABRO1 transcriptional start site, as demonstrated by ChIP, EMSA, and luciferase reporter assays.","method":"Reporter gene assays, ChIP, EMSA, YY1 siRNA knockdown and overexpression","journal":"Biochemistry and cell biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — ChIP and EMSA with functional luciferase reporter, single lab, multiple orthogonal methods for transcriptional regulation","pmids":["32845162"],"is_preprint":false}],"current_model":"ABRAXAS2 (ABRO1/KIAA0157/FAM175B) is a cytoplasmic scaffold protein and defining subunit of the BRISC complex (with BRCC36, BRE, and MERIT40/NBA1) that directly binds and allosterically activates the Lys63-specific deubiquitinase BRCC36 through formation of a BRCC36-ABRO1 heterodimer and higher-order 'super-dimer'; ABRO1 confers cytoplasmic localization to BRCC36 (as opposed to the nuclear BRCA1-A complex where the paralog Abraxas/CCDC98 serves this role), and BRISC activity—scaffolded by ABRO1—targets specific K63-ubiquitinated substrates including NLRP3, JAK2, tankyrase 1, PPM1B, and β-catenin in diverse cellular contexts including innate immune signaling, hematopoietic stem cell homeostasis, telomere cohesion, and cardiac remodeling; additionally, ABRO1 protects stalled replication forks from DNA2/WRN-mediated degradation (independently of its DUB scaffolding role), stabilizes p53 via USP7, and stabilizes BRCC3 itself by competing with the E3 ligase WWP2."},"narrative":{"mechanistic_narrative":"ABRAXAS2 (ABRO1/KIAA0157/FAM175B) is a cytoplasmic scaffold protein that defines the BRISC deubiquitinase complex and directs Lys63-linked deubiquitination across innate immune, hematopoietic, telomeric, and cardiac contexts [PMID:20656690, PMID:20656689]. It binds BRCC36 directly, and the minimal BRCC36-ABRO1 heterodimer retains K63-specific DUB activity; selectivity arises from the orientation of the substrate isopeptide bond in the active site rather than preferential chain binding [PMID:20032457]. Structural work established that ABRO1 contacts switch BRCC36 into an active conformation, and that a higher-order 'super-dimer' (dimer of heterodimers) is required for catalysis and for engagement of targeting proteins such as SHMT2 and RAP80, with SHMT2 binding by ABRO1 acting as an inhibitory brake on chain cleavage [PMID:26344097, PMID:31253574]. ABRO1 confers cytoplasmic localization to BRCC36, in contrast to the paralog Abraxas, which assembles the nuclear BRCA1-A complex; both complexes share BRE and NBA1/MERIT40, and loss of BRISC shifts the balance toward nuclear BRCA1-A activity at DNA double-strand breaks [PMID:20656690, PMID:20656689, PMID:21282113]. Through this scaffolded DUB activity, BRISC/ABRO1 removes K63 chains from defined substrates: tankyrase 1 to control sister telomere resolution [PMID:27993934], JAK2 downstream of the LNK SH2 domain to restrain HSC expansion and thrombopoietin signaling [PMID:30755420], NLRP3 to license inflammasome activation in macrophages [PMID:37781816], PPM1B in a YAP-dependent phase-separated condensate during vascular stiffening [PMID:39742393], and β-catenin at K508 to limit its nuclear accumulation and prevent cardiac hypertrophy [PMID:41789465]. Independently of its DUB scaffolding role, ABRO1 protects stalled and reversed replication forks from DNA2/WRN-mediated degradation, and its loss drives chromosome instability, cytosolic ssDNA accumulation, and cGAS-STING activation [PMID:28860160, PMID:35817959]. ABRO1 also stabilizes p53 via USP7 and stabilizes BRCC3 itself by competing with the E3 ligase WWP2, while its own levels are subject to transcriptional control by YY1 and to pathogen-driven degradation by the bacterial effector NleG6 through TOLLIP-mediated autophagy [PMID:25283148, PMID:33107021, PMID:32845162, PMID:40013521].","teleology":[{"year":2009,"claim":"Established the minimal biochemical unit of cytoplasmic K63 deubiquitination by showing ABRO1 binds BRCC36 directly and the heterodimer is sufficient for activity, and defined how chain selectivity is achieved.","evidence":"in vitro reconstitution of the heterodimer with defined ubiquitin substrates and binding studies","pmids":["20032457"],"confidence":"High","gaps":["Did not resolve the structural basis of the active-site geometry","Cellular substrates not yet identified"]},{"year":2010,"claim":"Defined ABRO1 as a cytoplasmic scaffold that segregates BRCC36 into a distinct complex (BRISC) from the nuclear BRCA1-A complex and as the sole subunit required to activate BRCC36 in the cytosol.","evidence":"co-immunoprecipitation, subcellular fractionation, siRNA knockdown, and functional DUB assays in two concurrent studies","pmids":["20656690","20656689"],"confidence":"High","gaps":["Physiological cytoplasmic substrates not defined","Mechanism balancing BRISC vs BRCA1-A pools unresolved"]},{"year":2010,"claim":"Linked ABRO1 to stress-protective signaling beyond the DUB complex by identifying THAP5 interaction and a cardioprotective role in ischemia/reperfusion.","evidence":"co-IP, mouse MI/R model, knockdown and overexpression cell death assays","pmids":["21195082"],"confidence":"Medium","gaps":["Specific K63 substrates in cardiomyocytes not identified","Single lab"]},{"year":2011,"claim":"Showed the two BRCC36 complexes share BRE and NBA1/MERIT40 and that NBA1-BRE contacts maintain complex integrity and IR resistance, framing the modular architecture.","evidence":"co-IP, domain-mapping pulldowns, siRNA knockdown, colony survival after IR","pmids":["21282113"],"confidence":"Medium","gaps":["Role of shared subunits within BRISC specifically not dissected","Single lab"]},{"year":2012,"claim":"Connected ABRO1 to the oxidative stress response by showing nuclear translocation and ATF4/ATF5/JunD binding required for cytoprotection.","evidence":"co-IP, confocal co-localization, knockdown and viability assays","pmids":["22974638"],"confidence":"Medium","gaps":["Whether this is DUB-dependent unclear","Single lab"]},{"year":2014,"claim":"Revealed a DUB-independent tumor-suppressive function: ABRO1 stabilizes p53 by bridging it to USP7 after DNA damage.","evidence":"co-IP, fractionation, knockdown/overexpression, tumor formation assays","pmids":["25283148"],"confidence":"Medium","gaps":["Structural basis of ABRO1-USP7-p53 ternary complex unknown","Single lab"]},{"year":2015,"claim":"Provided the atomic mechanism of activation, showing ABRO1 contacts convert BRCC36 to an active conformation and that super-dimerization gates both catalysis and engagement of targeting proteins SHMT2 and RAP80.","evidence":"X-ray crystallography, mutagenesis, in vitro DUB assays, SEC, co-IP","pmids":["26344097"],"confidence":"High","gaps":["In vivo regulation of super-dimer assembly not established"]},{"year":2016,"claim":"Identified the first defined physiological BRISC substrate, tankyrase 1, establishing cell-cycle-regulated K63 deubiquitination controlling telomere cohesion.","evidence":"reciprocal co-IP, ubiquitination assays, cell cycle synchronization, telomere FISH","pmids":["27993934"],"confidence":"High","gaps":["How BRISC is recruited to tankyrase 1 in G1 not defined"]},{"year":2017,"claim":"Uncovered a replication fork protection role distinct from DUB scaffolding, with ABRO1 blocking DNA2/WRN-mediated degradation of reversed forks and suppressing genome instability and tumorigenesis.","evidence":"DNA fiber assays, RAD51 epistasis, Abro1-null mouse phenotype","pmids":["28860160"],"confidence":"High","gaps":["Molecular mechanism of fork protection unknown","Relationship to BRISC activity at forks not clarified"]},{"year":2019,"claim":"Placed ABRO1 within a defined fork remodeling pathway protecting SMARCAL1/ZRANB3/HLTF-generated reversed forks, parallel to the FBH1 pathway.","evidence":"DNA fiber assay with epistasis across multiple remodelers","pmids":["33188024"],"confidence":"Medium","gaps":["Direct biochemical role at forks not shown","Single lab"]},{"year":2019,"claim":"Defined a hematopoietic function: BRISC restrains TPO-induced JAK2 K63-ubiquitination via an LNK-bound phosphotyrosine on ABRO1, controlling HSC homeostasis.","evidence":"phosphopeptide pull-down, mouse KO, K63-Ub assays, flow cytometry","pmids":["30755420"],"confidence":"High","gaps":["Kinase generating the ABRO1 phosphotyrosine not identified"]},{"year":2019,"claim":"Showed structurally how the two adaptors specialize BRCC36, with ABRO1-bound SHMT2α inhibiting chain cleavage while Abraxas integrates RAP80 in BRCA1-A.","evidence":"cryo-EM/crystal structures with binding and DUB inhibition assays","pmids":["31253574"],"confidence":"High","gaps":["Signals controlling SHMT2-mediated inhibition in cells unknown"]},{"year":2019,"claim":"Extended ABRO1's role in protein stabilization to cancer, showing FAM175B blocks ubiquitin-dependent ATF4 degradation to drive CHOP-dependent apoptosis in esophageal carcinoma.","evidence":"co-IP, confocal, ubiquitination assay, luciferase reporter, knockdown","pmids":["30854784"],"confidence":"Medium","gaps":["Whether stabilization requires DUB activity unclear","Single lab"]},{"year":2020,"claim":"Demonstrated ABRO1 stabilizes its own catalytic partner BRCC3 by competing with the E3 ligase WWP2 for binding.","evidence":"co-IP competition, ubiquitination assays, proteasome inhibitor experiments","pmids":["33107021"],"confidence":"Medium","gaps":["Structural basis of competition not resolved","Single lab"]},{"year":2020,"claim":"Identified YY1 as a transcriptional activator of human ABRO1, providing a regulatory input controlling its expression.","evidence":"ChIP, EMSA, luciferase reporters, YY1 knockdown/overexpression","pmids":["32845162"],"confidence":"Medium","gaps":["Physiological conditions driving YY1 regulation unknown","Single lab"]},{"year":2022,"claim":"Linked ABRO1-dependent fork protection to innate immunity, showing its loss produces cytosolic rDNA-containing ssDNA that activates cGAS-STING in a DNA2-dependent manner.","evidence":"DNA fiber assay, mouse KO, cytosolic ssDNA IF, cGAS-STING reporters, P-body quantification","pmids":["35817959"],"confidence":"High","gaps":["How replication stress couples to P-body formation incompletely defined"]},{"year":2023,"claim":"Established ABRO1 as required for NLRP3 deubiquitylation and inflammasome activation, linking it to clonal-hematopoiesis-driven atherosclerosis.","evidence":"hematopoietic Abro1 KO, bone marrow transplant, inflammasome assays, atherosclerosis quantification","pmids":["37781816"],"confidence":"Medium","gaps":["Direct NLRP3 ubiquitin site not mapped","Single lab"]},{"year":2023,"claim":"Revealed a DUB-independent role in cardiomyocyte proliferation through restriction of METTL3-mediated m6A methylation of Psph and downstream CDK2 activation.","evidence":"mouse KO/OE, m6A assays, CDK2 phosphorylation assays, proliferation quantification","pmids":["36639869"],"confidence":"Medium","gaps":["Mechanism by which ABRO1 restricts METTL3 unclear","Single lab"]},{"year":2025,"claim":"Showed ABRO1 undergoes YAP-dependent phase separation with PPM1B and promotes its K63 deubiquitination, controlling TGF-β-Smad signaling and arterial stiffness.","evidence":"GST pull-down, co-IP, phase-separation imaging, SMC-specific KO mice, ubiquitination assays","pmids":["39742393"],"confidence":"Medium","gaps":["Determinants of condensate formation not defined","Single lab"]},{"year":2025,"claim":"Identified ABRAXAS2 as a target of bacterial subversion, with effector NleG6 driving K27/K29 ubiquitination at K89/K114 and TOLLIP-mediated autophagic degradation to dampen NF-κB inflammation.","evidence":"co-IP, K89R/K114R mutagenesis, autophagy inhibitors, TOLLIP knockdown, NF-κB reporters","pmids":["40013521"],"confidence":"Medium","gaps":["Whether host ligases use the same sites unknown","Single lab"]},{"year":2026,"claim":"Defined β-catenin as a BRISC substrate, with ABRO1-directed K63 deubiquitination at K508 restraining β-catenin nuclear signaling and preventing cardiac hypertrophy.","evidence":"IP-MS, ubiquitinome profiling, K508R mutagenesis, cardiomyocyte-specific KO/OE, CUT&TAG, ICG-001 rescue","pmids":["41789465"],"confidence":"High","gaps":["Recruitment of BRISC to β-catenin not defined"]},{"year":2026,"claim":"Identified DPP9 as a regulator that disrupts the BRCC36-ABRO1 interaction, potentially compromising BRISC integrity.","evidence":"TurboID proximity labeling, NanoBRET in living cells, co-IP validation","pmids":["41636814"],"confidence":"Medium","gaps":["Functional consequence of disruption on substrate processing not shown","Single lab"]},{"year":null,"claim":"How ABRO1 selects among its many K63 substrates in different tissues, and how its DUB-scaffolding role is mechanistically separated from its DUB-independent functions (fork protection, p53/ATF4 stabilization, m6A regulation), remain open.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No unified model for substrate/context selection","Switch between scaffolding and DUB-independent activities undefined","In vivo regulation of super-dimerization and SHMT2 inhibition unresolved"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0,1,2,3]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[3,4,9,15]},{"term_id":"GO:0140096","term_label":"catalytic activity, acting on a protein","supporting_discovery_ids":[12,13,14,20]}],"localization":[{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[0,1]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[9,10]}],"pathway":[{"term_id":"R-HSA-168256","term_label":"Immune System","supporting_discovery_ids":[8,13,14,18]},{"term_id":"R-HSA-73894","term_label":"DNA Repair","supporting_discovery_ids":[1,6,7,8]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[13,19,20]}],"complexes":["BRISC complex","BRCA1-A complex (paralog-related)"],"partners":["BRCC36/BRCC3","BRE","MERIT40/NBA1","SHMT2","USP7","ATF4","YAP","LNK"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q15018","full_name":"BRISC complex subunit Abraxas 2","aliases":["Abraxas brother protein 1","Protein FAM175B"],"length_aa":415,"mass_kda":46.9,"function":"Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates (PubMed:19214193, PubMed:20032457, PubMed:20656690, PubMed:24075985). May act as a central scaffold protein that assembles the various components of the BRISC complex and retains them in the cytoplasm (PubMed:20656690). Plays a role in regulating the onset of apoptosis via its role in modulating 'Lys-63'-linked ubiquitination of target proteins (By similarity). Required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activities by enhancing its stability and cell surface expression (PubMed:24075985, PubMed:26344097). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985). Required for normal induction of p53/TP53 in response to DNA damage (PubMed:25283148). Independent of the BRISC complex, promotes interaction between USP7 and p53/TP53, and thereby promotes deubiquitination of p53/TP53, preventing its degradation and resulting in increased p53/TP53-mediated transcription regulation and p53/TP53-dependent apoptosis in response to DNA damage (PubMed:25283148)","subcellular_location":"Cytoplasm; Nucleus; Cytoplasm, cytoskeleton, spindle pole; Cytoplasm, cytoskeleton","url":"https://www.uniprot.org/uniprotkb/Q15018/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/ABRAXAS2","classification":"Not Classified","n_dependent_lines":1,"n_total_lines":1208,"dependency_fraction":0.0008278145695364238},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/ABRAXAS2","total_profiled":1310},"omim":[{"mim_id":"611144","title":"ABRAXAS 2, BRISC COMPLEX SUBUNIT; ABRAXAS2","url":"https://www.omim.org/entry/611144"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Supported","locations":[{"location":"Cytosol","reliability":"Supported"},{"location":"Primary cilium transition zone","reliability":"Additional"},{"location":"Basal body","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/ABRAXAS2"},"hgnc":{"alias_symbol":["Em:AC068896.4","ABRO1"],"prev_symbol":["KIAA0157","FAM175B"]},"alphafold":{"accession":"Q15018","domains":[{"cath_id":"3.40.140.10","chopping":"1-160","consensus_level":"high","plddt":91.3792,"start":1,"end":160},{"cath_id":"1.20.5","chopping":"184-263","consensus_level":"high","plddt":95.0328,"start":184,"end":263}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15018","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q15018-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q15018-F1-predicted_aligned_error_v6.png","plddt_mean":73.62},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=ABRAXAS2","jax_strain_url":"https://www.jax.org/strain/search?query=ABRAXAS2"},"sequence":{"accession":"Q15018","fasta_url":"https://rest.uniprot.org/uniprotkb/Q15018.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q15018/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q15018"}},"corpus_meta":[{"pmid":"20656690","id":"PMC_20656690","title":"The 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Model.","date":"2019","source":"Cells","url":"https://pubmed.ncbi.nlm.nih.gov/31405213","citation_count":16,"is_preprint":false},{"pmid":"22974638","id":"PMC_22974638","title":"ATF4 interacts with Abro1/KIAA0157 scaffold protein and participates in a cytoprotective pathway.","date":"2012","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/22974638","citation_count":14,"is_preprint":false},{"pmid":"40013521","id":"PMC_40013521","title":"A bacterial RING ubiquitin ligase triggering stepwise degradation of BRISC via TOLLIP-mediated selective autophagy manipulates host inflammatory response.","date":"2025","source":"Autophagy","url":"https://pubmed.ncbi.nlm.nih.gov/40013521","citation_count":5,"is_preprint":false},{"pmid":"39742393","id":"PMC_39742393","title":"BRISC-Mediated PPM1B-K63 Deubiquitination and Subsequent TGF-β Pathway Activation Promote High-Fat/High-Sucrose Diet-Induced Arterial Stiffness.","date":"2025","source":"Circulation 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cytoplasmic scaffold protein that forms a distinct complex with BRCC36 (separate from the nuclear BRCA1-A complex). KIAA0157 localizes mainly in the cytosol and activates BRCC36 DUB activity in the cytoplasm. Reduction of KIAA0157 expression led to an increase of the BRCA1-A complex in the nucleus, indicating fine balance between the two complexes in vivo.\",\n      \"method\": \"Co-immunoprecipitation, subcellular fractionation, siRNA knockdown, functional DUB assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, fractionation, functional DUB assays, replicated across two concurrent papers (PMID:20656690 and PMID:20656689)\",\n      \"pmids\": [\"20656690\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Within the BRISC complex, KIAA0157 (ABRO1/ABRAXAS2) is the only interaction required for BRCC36 DUB activity; BRISC deficiency enhanced formation of the BRCA1-RAP80 complex in vivo, increasing BRCA1 levels at DNA double-strand breaks.\",\n      \"method\": \"In vitro DUB activity assays with purified complexes, Co-IP, siRNA knockdown, laser-induced DSB recruitment assays\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — in vitro activity reconstitution plus cellular epistasis, replicated concurrently by independent lab (PMID:20656690)\",\n      \"pmids\": [\"20656689\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"ABRO1 binds directly to BRCC36 and the BRCC36-ABRO1 heterodimer constitutes a minimal complex retaining Lys63-specific DUB activity. BRISC selectivity for K63-linked chains is not due to preferential binding to K63 polyubiquitin but is dictated by orientation of the substrate isopeptide bond within the active site.\",\n      \"method\": \"Biochemical reconstitution of heterodimer, in vitro DUB assays with defined ubiquitin substrates, binding studies\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — in vitro reconstitution of minimal complex with mechanistic dissection of substrate selectivity, single lab\",\n      \"pmids\": [\"20032457\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2015,\n      \"finding\": \"Crystal structure of the active BRCC36-KIAA0157 (ABRAXAS2) heterodimer and an inactive BRCC36 homodimer was solved. KIAA0157 contacts switch BRCC36 to an active conformation. Higher-order 'super-dimer' assembly (dimer of heterodimers) is required for DUB activity and for interaction with targeting proteins SHMT2 and RAP80, implicating super-dimerization as a regulatory mechanism controlling subcellular localization and biological function.\",\n      \"method\": \"X-ray crystallography, in vitro DUB activity assays, mutagenesis, co-immunoprecipitation, size-exclusion chromatography\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — crystal structure with mutagenesis and in vitro functional validation, multiple orthogonal methods in single rigorous study\",\n      \"pmids\": [\"26344097\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Cryo-EM/crystal structures of BRISC and BRCA1-A complexes revealed that ABRO1 (in BRISC) binds SHMT2α (a metabolic enzyme), and this interaction prevents BRCC36 from binding and cleaving ubiquitin chains, establishing a regulatory inhibitory mechanism. In BRCA1-A, the paralog ABRAXAS integrates RAP80 and sequesters BRCA1 away from DSB sites. The two adaptor subunits confer distinct targeting and regulatory functions to BRCC36.\",\n      \"method\": \"Cryo-EM structure determination, biochemical binding assays, in vitro DUB inhibition assays\",\n      \"journal\": \"Molecular cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — atomic-resolution structures with functional validation, multiple orthogonal methods\",\n      \"pmids\": [\"31253574\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2011,\n      \"finding\": \"Both BRCC36-containing complexes (nuclear BRCA1-A with Abraxas; cytoplasmic BRISC with ABRO1) share BRE and NBA1/MERIT40 subunits. NBA1 interacts with BRE through a C-terminal conserved motif of NBA1 and the C-terminal UEV domain of BRE, and this interaction is critical for maintaining the integrity of both complexes and for cellular resistance to ionizing radiation.\",\n      \"method\": \"Co-immunoprecipitation, siRNA knockdown, domain-mapping pulldown assays, colony survival after IR\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and domain mapping, single lab\",\n      \"pmids\": [\"21282113\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"ABRO1 protects stalled replication fork stability by inhibiting DNA2 nuclease/WRN helicase-mediated degradation of reversed forks. Depletion of RAD51 prevented DNA2/WRN-dependent fork degradation in Abro1-deficient cells, placing ABRO1 in a fork protection pathway distinct from BRCA2 (which blocks MRE11-dependent degradation). Abro1-null mice display increased chromosome instability and are tumor-prone.\",\n      \"method\": \"DNA fiber assay, siRNA/genetic knockdown, mouse knockout, genetic epistasis (RAD51 depletion)\",\n      \"journal\": \"Genes & development\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods (fiber assay, epistasis, mouse KO phenotype), single lab with rigorous controls\",\n      \"pmids\": [\"28860160\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"In fork reversal, ABRO1 (along with BRCA2 and FANCD2) protects reversed forks generated by SMARCAL1, ZRANB3, and HLTF from degradation, a pathway distinct from the FBH1-mediated fork remodeling pathway protected by 53BP1/FANCA/FANCC/FANCG/BOD1L/VHL.\",\n      \"method\": \"DNA fiber assay, siRNA knockdown, genetic epistasis with multiple fork remodeling factors\",\n      \"journal\": \"Science advances\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — DNA fiber assay with epistasis panel, single lab\",\n      \"pmids\": [\"33188024\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"Abro1 (and FANCD2) protect stalled replication forks, and their deficiency leads to accumulation of cytosolic single-stranded DNA (containing ribosomal DNA) that activates cGAS-STING-dependent innate immune signaling in a DNA2-dependent manner. Abro1 and FANCD2 also limit the formation of replication stress-induced P-bodies, which can modulate innate immune activation.\",\n      \"method\": \"DNA fiber assay, mouse knockout, immunofluorescence for cytosolic ssDNA, cGAS-STING pathway reporters, P-body quantification\",\n      \"journal\": \"Nature cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — multiple orthogonal methods linking fork protection to immune signaling, mechanistic validation with DNA2 dependence\",\n      \"pmids\": [\"35817959\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"ABRO1 stabilizes p53 by facilitating the interaction of p53 with the deubiquitinase USP7. DNA damage induces accumulation of endogenous ABRO1 and its translocation to the nucleus; p53 induction by DNA damage is almost completely attenuated by ABRO1 depletion.\",\n      \"method\": \"Co-immunoprecipitation, subcellular fractionation, siRNA knockdown, overexpression, tumor formation assays\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — Co-IP showing ABRO1-USP7-p53 ternary interaction, multiple functional readouts, single lab\",\n      \"pmids\": [\"25283148\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"ABRO1 interacts directly with ATF4, ATF5, and JunD (AP-1 family transcription factors). Under cellular stress, ABRO1 translocates from the cytoplasm to the nucleus and co-localizes with ATF4; this ATF4-ABRO1 interaction is required for the cytoprotective function of ABRO1 following oxidative stress.\",\n      \"method\": \"Co-immunoprecipitation, confocal microscopy co-localization, siRNA knockdown, cell viability assays\",\n      \"journal\": \"Biochimica et biophysica acta\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP and co-localization with functional rescue, single lab\",\n      \"pmids\": [\"22974638\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"ABRO1/KIAA0157 interacts with THAP5, a zinc finger transcription factor involved in G2/M control and apoptosis. ABRO1 protein levels increase in myocardial ischemia/reperfusion injury; reducing ABRO1 exacerbated cardiomyocyte death while overexpression provided protection against oxidative stress-induced apoptosis, linked to decreased Lys63-linked ubiquitination of specific substrates.\",\n      \"method\": \"Co-immunoprecipitation (ABRO1-THAP5 interaction), in vivo mouse MI/R model, siRNA knockdown, overexpression, cell death assays\",\n      \"journal\": \"Journal of molecular and cellular cardiology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP interaction plus in vivo and cellular functional assays, single lab\",\n      \"pmids\": [\"21195082\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"ABRO1/BRCC36 (BRISC complex) removes K63-linked ubiquitin chains from tankyrase 1 during G1 phase, countering the action of E3 ligase RNF8 that adds K63-linked chains in late S/G2. This cell cycle-regulated ubiquitination/deubiquitination controls tankyrase 1 stabilization, its association with telomeres, and timely sister telomere resolution.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, telomere FISH, cell cycle synchronization\",\n      \"journal\": \"The EMBO journal\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP, ubiquitination assays, cell-cycle epistasis, and defined phenotypic readout (telomere cohesion), single lab with multiple orthogonal methods\",\n      \"pmids\": [\"27993934\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"The LNK SH2 domain directly interacts with a phosphorylated tyrosine residue in KIAA0157 (ABRAXAS2). KIAA0157 deficiency in mice leads to expansion of phenotypic and functional HSCs. BRISC (via KIAA0157) attenuates TPO-induced JAK2 K63-ubiquitination; BRISC depletion increases JAK2 K63-ubiquitination, JAK2 activation, MPL receptor surface levels, and membrane-proximal JAK2/MPL association.\",\n      \"method\": \"Co-immunoprecipitation, phosphopeptide pull-down, mouse knockout, K63-ubiquitination assays, flow cytometry for HSC phenotyping and MPL surface levels\",\n      \"journal\": \"Blood\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — direct interaction mapping, mouse KO with defined HSC phenotype, K63-Ub assays, multiple orthogonal methods\",\n      \"pmids\": [\"30755420\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"ABRO1, as a scaffolding component of the BRISC-BRCC3 complex, is required for NLRP3 deubiquitylation and inflammasome activation in macrophages. Hematopoietic Abro1 deficiency reversed accelerated atherosclerosis and NETosis in Tet2 clonal hematopoiesis mice.\",\n      \"method\": \"Mouse knockout (hematopoietic Abro1 KO), bone marrow transplantation, NLRP3 inflammasome activation assays (IL-1β, caspase-1), atherosclerosis quantification\",\n      \"journal\": \"Circulation\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — mouse KO with defined inflammasome and atherosclerosis phenotypes, single lab\",\n      \"pmids\": [\"37781816\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"ABRO1 stabilizes BRCC3 protein by competing with the HECT-type E3 ubiquitin ligase WWP2 for binding to BRCC3, thereby preventing WWP2-mediated ubiquitination and proteasomal degradation of BRCC3.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, overexpression, proteasome inhibitor experiments\",\n      \"journal\": \"FEBS letters\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP competition assay and ubiquitination assay demonstrating protective mechanism, single lab\",\n      \"pmids\": [\"33107021\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"FAM175B (ABRAXAS2/ABRO1) interacts with ATF4 as shown by co-localization (confocal microscopy) and co-immunoprecipitation. FAM175B inhibits ubiquitin-dependent ATF4 degradation, elevating ATF4 protein levels, and promotes ATF4-dependent CHOP expression to drive apoptosis in esophageal squamous cell carcinoma cells.\",\n      \"method\": \"Co-immunoprecipitation, confocal co-localization, ubiquitination assay, luciferase reporter, siRNA knockdown\",\n      \"journal\": \"Molecular oncology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 3 / Moderate — Co-IP and ubiquitination assays, multiple functional readouts, single lab\",\n      \"pmids\": [\"30854784\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"ABRO1 regulates cardiomyocyte proliferation by targeting METTL3-mediated m6A methylation of Psph mRNA. ABRO1 restricts METTL3 activity, reducing PSPH expression; PSPH dephosphorylates CDK2 at Thr14/Tyr15 to activate it. ABRO1 deletion increased cardiomyocyte proliferation and restored heart function after myocardial injury.\",\n      \"method\": \"Mouse knockout and overexpression models, m6A methylation assays, CDK2 phosphorylation assays, cardiomyocyte proliferation quantification\",\n      \"journal\": \"Molecular therapy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — mouse KO/OE with mechanistic pathway involving m6A and CDK2, single lab\",\n      \"pmids\": [\"36639869\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"The bacterial T3SS effector NleG6 mediates K27- and K29-linked polyubiquitination at residues K89 and K114 of ABRAXAS2/FAM175B, leading to its degradation through TOLLIP-mediated selective autophagy. ABRAXAS2 degradation triggers subsequent degradation of BRCC3, which in turn prevents TNIP1/ABIN1 degradation and inhibits NF-κB-mediated inflammatory responses.\",\n      \"method\": \"Co-immunoprecipitation, ubiquitination site mutagenesis (K89R/K114R), autophagy inhibitor experiments, TOLLIP knockdown, NF-κB reporter assays\",\n      \"journal\": \"Autophagy\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — site-specific mutagenesis identifying ubiquitination sites, genetic KO of autophagy receptor, functional NF-κB readout, single lab\",\n      \"pmids\": [\"40013521\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2025,\n      \"finding\": \"ABRO1 directly binds YAP and undergoes liquid-liquid phase separation with YAP and PPM1B in a YAP-dependent manner, promoting PPM1B deubiquitination (K63-linked chains at K326) by BRCC36/BRCC3. Smooth muscle cell-specific Abro1-KO mice showed attenuated HFHSD-induced arterial stiffness and TGF-β-Smad signaling.\",\n      \"method\": \"GST pull-down, co-immunoprecipitation, immunofluorescence (phase separation), mouse SMC-specific KO, ubiquitination assays, Doppler ultrasound\",\n      \"journal\": \"Circulation research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding assay, phase separation imaging, mouse KO with vascular phenotype, single lab\",\n      \"pmids\": [\"39742393\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"ABRO1 directly interacts with β-catenin and, as part of BRISC, cleaves K63-linked polyubiquitin chains at β-catenin lysine 508, thereby restraining β-catenin nuclear accumulation and transcriptional activation. Cardiomyocyte-specific Abro1 deletion causes spontaneous cardiac hypertrophy and contractile dysfunction reversible by β-catenin inhibitor ICG-001.\",\n      \"method\": \"Co-immunoprecipitation, immunoprecipitation-mass spectrometry, ubiquitinome profiling, site-specific mutagenesis (K508R), cardiomyocyte-specific KO/OE mice, CUT&TAG, pharmacological rescue\",\n      \"journal\": \"Hypertension\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 / Strong — ubiquitination site mutagenesis, IP-MS substrate identification, mouse cardiomyocyte-specific KO with pharmacological rescue, multiple orthogonal methods\",\n      \"pmids\": [\"41789465\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2026,\n      \"finding\": \"DPP9 interacts with BRCC36/BRCC3 and ABRO1/ABRAXAS2 (BRISC complex components) as novel binding partners. NanoBRET assays in living cells showed that DPP9 disrupts the binding between BRCC36/BRCC3 and ABRO1/ABRAXAS2, potentially compromising BRISC integrity.\",\n      \"method\": \"TurboID proximity labeling, NanoBRET assay in living cells, validation by co-immunoprecipitation\",\n      \"journal\": \"Cellular and molecular life sciences\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 / Moderate — proximity labeling with NanoBRET validation in living cells demonstrating disruption of the BRCC36-ABRO1 interaction, single lab\",\n      \"pmids\": [\"41636814\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"The transcription factor YY1 positively regulates human ABRO1 expression by binding to cis-acting elements located -89 to -59 bp upstream of the ABRO1 transcriptional start site, as demonstrated by ChIP, EMSA, and luciferase reporter assays.\",\n      \"method\": \"Reporter gene assays, ChIP, EMSA, YY1 siRNA knockdown and overexpression\",\n      \"journal\": \"Biochemistry and cell biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — ChIP and EMSA with functional luciferase reporter, single lab, multiple orthogonal methods for transcriptional regulation\",\n      \"pmids\": [\"32845162\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"ABRAXAS2 (ABRO1/KIAA0157/FAM175B) is a cytoplasmic scaffold protein and defining subunit of the BRISC complex (with BRCC36, BRE, and MERIT40/NBA1) that directly binds and allosterically activates the Lys63-specific deubiquitinase BRCC36 through formation of a BRCC36-ABRO1 heterodimer and higher-order 'super-dimer'; ABRO1 confers cytoplasmic localization to BRCC36 (as opposed to the nuclear BRCA1-A complex where the paralog Abraxas/CCDC98 serves this role), and BRISC activity—scaffolded by ABRO1—targets specific K63-ubiquitinated substrates including NLRP3, JAK2, tankyrase 1, PPM1B, and β-catenin in diverse cellular contexts including innate immune signaling, hematopoietic stem cell homeostasis, telomere cohesion, and cardiac remodeling; additionally, ABRO1 protects stalled replication forks from DNA2/WRN-mediated degradation (independently of its DUB scaffolding role), stabilizes p53 via USP7, and stabilizes BRCC3 itself by competing with the E3 ligase WWP2.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"ABRAXAS2 (ABRO1/KIAA0157/FAM175B) is a cytoplasmic scaffold protein that defines the BRISC deubiquitinase complex and directs Lys63-linked deubiquitination across innate immune, hematopoietic, telomeric, and cardiac contexts [#0, #1]. It binds BRCC36 directly, and the minimal BRCC36-ABRO1 heterodimer retains K63-specific DUB activity; selectivity arises from the orientation of the substrate isopeptide bond in the active site rather than preferential chain binding [#2]. Structural work established that ABRO1 contacts switch BRCC36 into an active conformation, and that a higher-order 'super-dimer' (dimer of heterodimers) is required for catalysis and for engagement of targeting proteins such as SHMT2 and RAP80, with SHMT2 binding by ABRO1 acting as an inhibitory brake on chain cleavage [#3, #4]. ABRO1 confers cytoplasmic localization to BRCC36, in contrast to the paralog Abraxas, which assembles the nuclear BRCA1-A complex; both complexes share BRE and NBA1/MERIT40, and loss of BRISC shifts the balance toward nuclear BRCA1-A activity at DNA double-strand breaks [#0, #1, #5]. Through this scaffolded DUB activity, BRISC/ABRO1 removes K63 chains from defined substrates: tankyrase 1 to control sister telomere resolution [#12], JAK2 downstream of the LNK SH2 domain to restrain HSC expansion and thrombopoietin signaling [#13], NLRP3 to license inflammasome activation in macrophages [#14], PPM1B in a YAP-dependent phase-separated condensate during vascular stiffening [#19], and \\u03b2-catenin at K508 to limit its nuclear accumulation and prevent cardiac hypertrophy [#20]. Independently of its DUB scaffolding role, ABRO1 protects stalled and reversed replication forks from DNA2/WRN-mediated degradation, and its loss drives chromosome instability, cytosolic ssDNA accumulation, and cGAS-STING activation [#6, #8]. ABRO1 also stabilizes p53 via USP7 and stabilizes BRCC3 itself by competing with the E3 ligase WWP2, while its own levels are subject to transcriptional control by YY1 and to pathogen-driven degradation by the bacterial effector NleG6 through TOLLIP-mediated autophagy [#9, #15, #22, #18].\",\n  \"teleology\": [\n    {\n      \"year\": 2009,\n      \"claim\": \"Established the minimal biochemical unit of cytoplasmic K63 deubiquitination by showing ABRO1 binds BRCC36 directly and the heterodimer is sufficient for activity, and defined how chain selectivity is achieved.\",\n      \"evidence\": \"in vitro reconstitution of the heterodimer with defined ubiquitin substrates and binding studies\",\n      \"pmids\": [\"20032457\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not resolve the structural basis of the active-site geometry\", \"Cellular substrates not yet identified\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Defined ABRO1 as a cytoplasmic scaffold that segregates BRCC36 into a distinct complex (BRISC) from the nuclear BRCA1-A complex and as the sole subunit required to activate BRCC36 in the cytosol.\",\n      \"evidence\": \"co-immunoprecipitation, subcellular fractionation, siRNA knockdown, and functional DUB assays in two concurrent studies\",\n      \"pmids\": [\"20656690\", \"20656689\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological cytoplasmic substrates not defined\", \"Mechanism balancing BRISC vs BRCA1-A pools unresolved\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Linked ABRO1 to stress-protective signaling beyond the DUB complex by identifying THAP5 interaction and a cardioprotective role in ischemia/reperfusion.\",\n      \"evidence\": \"co-IP, mouse MI/R model, knockdown and overexpression cell death assays\",\n      \"pmids\": [\"21195082\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Specific K63 substrates in cardiomyocytes not identified\", \"Single lab\"]\n    },\n    {\n      \"year\": 2011,\n      \"claim\": \"Showed the two BRCC36 complexes share BRE and NBA1/MERIT40 and that NBA1-BRE contacts maintain complex integrity and IR resistance, framing the modular architecture.\",\n      \"evidence\": \"co-IP, domain-mapping pulldowns, siRNA knockdown, colony survival after IR\",\n      \"pmids\": [\"21282113\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Role of shared subunits within BRISC specifically not dissected\", \"Single lab\"]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Connected ABRO1 to the oxidative stress response by showing nuclear translocation and ATF4/ATF5/JunD binding required for cytoprotection.\",\n      \"evidence\": \"co-IP, confocal co-localization, knockdown and viability assays\",\n      \"pmids\": [\"22974638\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether this is DUB-dependent unclear\", \"Single lab\"]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Revealed a DUB-independent tumor-suppressive function: ABRO1 stabilizes p53 by bridging it to USP7 after DNA damage.\",\n      \"evidence\": \"co-IP, fractionation, knockdown/overexpression, tumor formation assays\",\n      \"pmids\": [\"25283148\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of ABRO1-USP7-p53 ternary complex unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": 2015,\n      \"claim\": \"Provided the atomic mechanism of activation, showing ABRO1 contacts convert BRCC36 to an active conformation and that super-dimerization gates both catalysis and engagement of targeting proteins SHMT2 and RAP80.\",\n      \"evidence\": \"X-ray crystallography, mutagenesis, in vitro DUB assays, SEC, co-IP\",\n      \"pmids\": [\"26344097\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"In vivo regulation of super-dimer assembly not established\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified the first defined physiological BRISC substrate, tankyrase 1, establishing cell-cycle-regulated K63 deubiquitination controlling telomere cohesion.\",\n      \"evidence\": \"reciprocal co-IP, ubiquitination assays, cell cycle synchronization, telomere FISH\",\n      \"pmids\": [\"27993934\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How BRISC is recruited to tankyrase 1 in G1 not defined\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Uncovered a replication fork protection role distinct from DUB scaffolding, with ABRO1 blocking DNA2/WRN-mediated degradation of reversed forks and suppressing genome instability and tumorigenesis.\",\n      \"evidence\": \"DNA fiber assays, RAD51 epistasis, Abro1-null mouse phenotype\",\n      \"pmids\": [\"28860160\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular mechanism of fork protection unknown\", \"Relationship to BRISC activity at forks not clarified\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Placed ABRO1 within a defined fork remodeling pathway protecting SMARCAL1/ZRANB3/HLTF-generated reversed forks, parallel to the FBH1 pathway.\",\n      \"evidence\": \"DNA fiber assay with epistasis across multiple remodelers\",\n      \"pmids\": [\"33188024\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct biochemical role at forks not shown\", \"Single lab\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Defined a hematopoietic function: BRISC restrains TPO-induced JAK2 K63-ubiquitination via an LNK-bound phosphotyrosine on ABRO1, controlling HSC homeostasis.\",\n      \"evidence\": \"phosphopeptide pull-down, mouse KO, K63-Ub assays, flow cytometry\",\n      \"pmids\": [\"30755420\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Kinase generating the ABRO1 phosphotyrosine not identified\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Showed structurally how the two adaptors specialize BRCC36, with ABRO1-bound SHMT2\\u03b1 inhibiting chain cleavage while Abraxas integrates RAP80 in BRCA1-A.\",\n      \"evidence\": \"cryo-EM/crystal structures with binding and DUB inhibition assays\",\n      \"pmids\": [\"31253574\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Signals controlling SHMT2-mediated inhibition in cells unknown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Extended ABRO1's role in protein stabilization to cancer, showing FAM175B blocks ubiquitin-dependent ATF4 degradation to drive CHOP-dependent apoptosis in esophageal carcinoma.\",\n      \"evidence\": \"co-IP, confocal, ubiquitination assay, luciferase reporter, knockdown\",\n      \"pmids\": [\"30854784\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether stabilization requires DUB activity unclear\", \"Single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrated ABRO1 stabilizes its own catalytic partner BRCC3 by competing with the E3 ligase WWP2 for binding.\",\n      \"evidence\": \"co-IP competition, ubiquitination assays, proteasome inhibitor experiments\",\n      \"pmids\": [\"33107021\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Structural basis of competition not resolved\", \"Single lab\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Identified YY1 as a transcriptional activator of human ABRO1, providing a regulatory input controlling its expression.\",\n      \"evidence\": \"ChIP, EMSA, luciferase reporters, YY1 knockdown/overexpression\",\n      \"pmids\": [\"32845162\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological conditions driving YY1 regulation unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Linked ABRO1-dependent fork protection to innate immunity, showing its loss produces cytosolic rDNA-containing ssDNA that activates cGAS-STING in a DNA2-dependent manner.\",\n      \"evidence\": \"DNA fiber assay, mouse KO, cytosolic ssDNA IF, cGAS-STING reporters, P-body quantification\",\n      \"pmids\": [\"35817959\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"How replication stress couples to P-body formation incompletely defined\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Established ABRO1 as required for NLRP3 deubiquitylation and inflammasome activation, linking it to clonal-hematopoiesis-driven atherosclerosis.\",\n      \"evidence\": \"hematopoietic Abro1 KO, bone marrow transplant, inflammasome assays, atherosclerosis quantification\",\n      \"pmids\": [\"37781816\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct NLRP3 ubiquitin site not mapped\", \"Single lab\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Revealed a DUB-independent role in cardiomyocyte proliferation through restriction of METTL3-mediated m6A methylation of Psph and downstream CDK2 activation.\",\n      \"evidence\": \"mouse KO/OE, m6A assays, CDK2 phosphorylation assays, proliferation quantification\",\n      \"pmids\": [\"36639869\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which ABRO1 restricts METTL3 unclear\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Showed ABRO1 undergoes YAP-dependent phase separation with PPM1B and promotes its K63 deubiquitination, controlling TGF-\\u03b2-Smad signaling and arterial stiffness.\",\n      \"evidence\": \"GST pull-down, co-IP, phase-separation imaging, SMC-specific KO mice, ubiquitination assays\",\n      \"pmids\": [\"39742393\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Determinants of condensate formation not defined\", \"Single lab\"]\n    },\n    {\n      \"year\": 2025,\n      \"claim\": \"Identified ABRAXAS2 as a target of bacterial subversion, with effector NleG6 driving K27/K29 ubiquitination at K89/K114 and TOLLIP-mediated autophagic degradation to dampen NF-\\u03baB inflammation.\",\n      \"evidence\": \"co-IP, K89R/K114R mutagenesis, autophagy inhibitors, TOLLIP knockdown, NF-\\u03baB reporters\",\n      \"pmids\": [\"40013521\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether host ligases use the same sites unknown\", \"Single lab\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Defined \\u03b2-catenin as a BRISC substrate, with ABRO1-directed K63 deubiquitination at K508 restraining \\u03b2-catenin nuclear signaling and preventing cardiac hypertrophy.\",\n      \"evidence\": \"IP-MS, ubiquitinome profiling, K508R mutagenesis, cardiomyocyte-specific KO/OE, CUT&TAG, ICG-001 rescue\",\n      \"pmids\": [\"41789465\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Recruitment of BRISC to \\u03b2-catenin not defined\"]\n    },\n    {\n      \"year\": 2026,\n      \"claim\": \"Identified DPP9 as a regulator that disrupts the BRCC36-ABRO1 interaction, potentially compromising BRISC integrity.\",\n      \"evidence\": \"TurboID proximity labeling, NanoBRET in living cells, co-IP validation\",\n      \"pmids\": [\"41636814\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional consequence of disruption on substrate processing not shown\", \"Single lab\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How ABRO1 selects among its many K63 substrates in different tissues, and how its DUB-scaffolding role is mechanistically separated from its DUB-independent functions (fork protection, p53/ATF4 stabilization, m6A regulation), remain open.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No unified model for substrate/context selection\", \"Switch between scaffolding and DUB-independent activities undefined\", \"In vivo regulation of super-dimerization and SHMT2 inhibition unresolved\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0, 1, 2, 3]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [3, 4, 9, 15]},\n      {\"term_id\": \"GO:0140096\", \"supporting_discovery_ids\": [12, 13, 14, 20]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [9, 10]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-168256\", \"supporting_discovery_ids\": [8, 13, 14, 18]},\n      {\"term_id\": \"R-HSA-73894\", \"supporting_discovery_ids\": [1, 6, 7, 8]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [13, 19, 20]}\n    ],\n    \"complexes\": [\n      \"BRISC complex\",\n      \"BRCA1-A complex (paralog-related)\"\n    ],\n    \"partners\": [\n      \"BRCC36/BRCC3\",\n      \"BRE\",\n      \"MERIT40/NBA1\",\n      \"SHMT2\",\n      \"USP7\",\n      \"ATF4\",\n      \"YAP\",\n      \"LNK\"\n    ],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":7,"faith_total":7,"faith_pct":100.0}}