| Aspect | ABRAXAS2-specific summary | Evidence type | Key quantitative data | Year | DOI / URL |
|---|---|---|---|---|---|
| Verified protein identity | Human **ABRAXAS2** encodes **BRISC complex subunit Abraxas 2**; common synonyms include **ABRO1**, **FAM175B**, and **KIAA0157**. It is the **ABRAXAS paralog that defines BRISC**, not BRCA1-A. Literature distinguishes ABRO1/ABRAXAS2 from **ABRAXAS/FAM175A**, the BRCA1-A scaffold subunit (pqac-00000001, pqac-00000003, pqac-00000005, pqac-00000008). | Structural, review synthesis | Protein length reported in review: **415 aa** (pqac-00000003) | 2019, 2020 | https://doi.org/10.1016/j.molcel.2019.06.002 ; https://doi.org/10.3390/biom10111503 |
| Complex membership | **ABRAXAS2/ABRO1 is a core scaffold subunit of BRISC** together with **BRCC36/BRCC3, BRE, and MERIT40**; BRISC can assemble with **SHMT2α**. By contrast, **BRCA1-A** contains **ABRAXAS (FAM175A)** plus **RAP80** and binds BRCA1, whereas BRISC contains **ABRO1** and does not recruit BRCA1 in the same way (pqac-00000001, pqac-00000004, pqac-00000005, pqac-00000007, pqac-00000008). | Structural, biochemical | BRISC structure reported with **two copies each of BRCC36, ABRO1, BRE, MERIT40, and SHMT2α** (pqac-00000004) | 2019, 2020 | https://doi.org/10.1016/j.molcel.2019.06.002 ; https://doi.org/10.3390/biom10111503 |
| Core interactors | Key ABRAXAS2-associated proteins are **BRCC36/BRCC3** (catalytic JAMM DUB), **BRE**, **MERIT40**, **SHMT2α**, and **LNK**; ABRO1 confers **specific high-affinity SHMT2α binding** to BRISC, while its C-terminal **pY377** recruits **LNK SH2** in JAK2 signaling contexts (pqac-00000001, pqac-00000002, pqac-00000003, pqac-00000006). | Structural, biochemical | SHMT2α binding described as **low-nanomolar affinity** (pqac-00000001, pqac-00000014) | 2019, 2020 | https://doi.org/10.1016/j.molcel.2019.06.002 ; https://doi.org/10.3390/biom10111503 |
| Molecular function | ABRAXAS2 is a **noncatalytic MPN− scaffold/activator** that enables assembly-dependent activation of the **BRCC36** deubiquitinase. ABRO1 contributes **Asn164** to position the BRCC36 catalytic machinery/E-loop, allowing BRCC36 activity within BRISC. BRCC36 is the catalytic enzyme; ABRAXAS2 functions as its structural activator/specifier (pqac-00000001, pqac-00000003, pqac-00000004, pqac-00000014). | Structural, biochemical | Assembly-dependent activation involves **ABRO1 N164**; BRCC36 is inactive alone and active in assembled complex (pqac-00000001, pqac-00000004) | 2019, 2020 | https://doi.org/10.1016/j.molcel.2019.06.002 ; https://doi.org/10.3390/biom10111503 |
| Ubiquitin-chain specificity | Through BRCC36, BRISC is **strictly K63-linkage specific**. ABRAXAS2 therefore functions in a complex that edits **K63-linked polyubiquitin** rather than catalyzing chemistry directly itself (pqac-00000001, pqac-00000005, pqac-00000008, pqac-00000014). | Biochemical, structural | BRCC36/BRISC described as **strictly specific for K63-linked ubiquitin chains** (pqac-00000001, pqac-00000014) | 2019, 2020 | https://doi.org/10.1016/j.molcel.2019.06.002 ; https://doi.org/10.3390/biom10111503 |
| Chain-length preference | Assembled BRISC shows **preferential cleavage of longer K63 polyubiquitin chains**, especially **tetraubiquitin and above**, consistent with avidity created by the arc-shaped multiprotein scaffold (pqac-00000001, pqac-00000004). | Biochemical, structural | Preferential cleavage of **(Ub)4** and longer chains reported (pqac-00000004) | 2019, 2020 | https://doi.org/10.1016/j.molcel.2019.06.002 ; https://doi.org/10.3390/biom10111503 |
| Regulation by SHMT2 and PLP | **ABRO1 mediates SHMT2α docking to BRISC**, and bound **apo-SHMT2α** sterically blocks the BRCC36 active site, functioning as a **protein inhibitor** of BRISC. **PLP** promotes SHMT2 tetramerization, weakens BRISC association, and can release active BRISC (pqac-00000001, pqac-00000002, pqac-00000014). | Structural, biochemical | SHMT2α acts as a **high-affinity/low-nanomolar** BRISC inhibitor; **PLP** shifts SHMT2 equilibrium and regulates BRISC DUB activity (pqac-00000001, pqac-00000014) | 2019, 2020 | https://doi.org/10.1038/s41586-019-1232-1 ; https://doi.org/10.1016/j.molcel.2019.06.002 ; https://doi.org/10.3390/biom10111503 |
| Subcellular localization | BRISC containing ABRAXAS2 is reported in **both nucleus and cytoplasm**, unlike BRCA1-A which is predominantly nuclear. Quantitative imaging also examined **mitochondrial association/colocalization** of endogenous **ABRO1 and SHMT2**, supporting distribution across **nucleus, cytosol, and mitochondria-associated pools** (pqac-00000004, pqac-00000006, pqac-00000015). | Structural, imaging | Figure evidence indicates localization in **nucleus, cytosol, and mitochondria** (pqac-00000015) | 2019 | https://doi.org/10.1016/j.molcel.2019.06.002 |
| Distinction from BRCA1-A | ABRAXAS2 should not be confused with **ABRAXAS/FAM175A**. BRCA1-A uses ABRAXAS, recruits **RAP80**, and binds BRCA1 BRCT repeats; ABRAXAS2 instead functionalizes BRISC, especially via SHMT2 and immune/endosomal signaling. This distinction is central for correct annotation (pqac-00000002, pqac-00000005, pqac-00000007). | Structural, biochemical | In BRCA1-A, assembled complex binds BRCA1 BRCT with **Kd ~80 nM** via ABRAXAS phospho-tail, illustrating a paralog-specific property not attributed to ABRAXAS2 (pqac-00000007) | 2019, 2020 | https://doi.org/10.1016/j.molcel.2019.06.002 ; https://doi.org/10.3390/biom10111503 |
| IFN signaling / receptor trafficking | ABRAXAS2-containing BRISC promotes **deubiquitination of IFNAR1**, limiting receptor internalization/endocytosis and stabilizing type I interferon receptor signaling outputs. This is one of the clearest physiological substrate contexts for BRISC (pqac-00000001, pqac-00000013, pqac-00000014). | Biochemical, cellular, genetic | Qualitative mechanism: BRISC deubiquitinates **IFNAR1 K63-Ub**, limiting endocytosis (pqac-00000001, pqac-00000014) | 2020, 2023 | https://doi.org/10.3390/biom10111503 ; https://doi.org/10.1038/s41419-023-06268-z |
| Inflammasome / NLRP3 biology | ABRAXAS2 has been implicated in recruiting BRISC to **NLRP3**, enabling **deubiquitination of NLRP3** and promoting inflammasome activation. This places ABRAXAS2 in innate immune signaling beyond IFNAR1 regulation (pqac-00000009, pqac-00000013). | Genetic, cellular, pathway analysis | Reported qualitatively as promoting **NLRP3-dependent IL-1β and IL-18** responses; no exact numeric effect size captured in available excerpts (pqac-00000013) | 2023 | https://doi.org/10.1038/s41419-023-06268-z |
| NF-κB in Kupffer cells / acute liver injury | 2023 work shows ABRO1/ABRAXAS2 is required for **optimal canonical NF-κB activation** in **LPS-stimulated Kupffer cells**. Loss of ABRO1 impairs **IκBα phosphorylation/degradation**, **p65 phosphorylation**, **p65 nuclear translocation**, NF-κB reporter activity, and cytokine production, while MAPKs are largely unaffected (pqac-00000009, pqac-00000010, pqac-00000011, pqac-00000012, pqac-00000013). | Genetic, cellular, in vivo mouse model | **Serum TNF-α reduced by 48.5%** and **hepatic TNF-α by 45.5% at 1 h** post D-GalN/LPS in **Abro1−/−** mice; lethal challenge caused **100% WT mortality within 8 h** versus **>70% survival** in **Abro1−/−** and **Brcc3−/−** mice (pqac-00000012, pqac-00000013) | 2023 | https://doi.org/10.1038/s41419-023-06268-z |
| Cytokine/chemokine outputs | In ABRO1-deficient settings, **TNF-α, IL-6, IL-1β, MCP-1, MIP-1α, and MIP-1β** are reduced in serum, liver, or isolated Kupffer cells after inflammatory challenge, indicating ABRAXAS2 promotes early inflammatory cytokine amplification in liver macrophages (pqac-00000010, pqac-00000011, pqac-00000012). | Genetic, flow cytometry, ELISA/CBA, RT-PCR | LPS-induced cytokine reductions seen across **0.1 ng/mL to 1 μg/mL** LPS in KCs; early cytokine defects evident **1 h** after challenge (pqac-00000011, pqac-00000012) | 2023 | https://doi.org/10.1038/s41419-023-06268-z |
| Mitosis and other roles | Reviews summarize ABRAXAS2/BRISC functions in **mitosis** (including **NuMA ubiquitination**), **telomere-associated tankyrase regulation**, **hematopoiesis**, and **JAK2** signaling through **LNK**, extending its annotation beyond innate immunity (pqac-00000001, pqac-00000008, pqac-00000014). | Review synthesis from primary studies | Quantitative values not captured in available excerpts; roles supported by curated review of primary literature (pqac-00000001, pqac-00000008) | 2020 | https://doi.org/10.3390/biom10111503 |
| Therapeutic relevance | Pharmacologic **BRISC inhibition** is proposed as therapeutically useful in inflammatory disease. In the 2023 liver study, **thiolutin (THL)** markedly alleviated D-GalN/LPS-induced injury, and NF-κB activators rescued cytokine production in ABRO1-deficient Kupffer cells, functionally tying BRISC to this pathway (pqac-00000010, pqac-00000011). | Pharmacologic, genetic | THL increased survival, reduced **ALT/AST**, serum **TNF-α/MCP-1**, necrosis, and ex vivo KC cytokine release; exogenous **TNF-α 15 μg/kg** abolished THL protection (pqac-00000011) | 2023 | https://doi.org/10.1038/s41419-023-06268-z |


*Table: This table summarizes verified identity, complex membership, molecular mechanism, localization, signaling roles, and therapeutic relevance of human ABRAXAS2/ABRO1/FAM175B. It is useful for distinguishing ABRAXAS2 from the related BRCA1-A scaffold ABRAXAS and for tracing the strongest structural, biochemical, and genetic evidence.*