| FBXO2/Fbs1 role | Key substrate(s) / process | Main evidence type | Recent source(s) (2023–2024) | Foundational source(s) | Year(s) | DOI / URL | Citation |
|---|---|---|---|---|---|---|---|
| SCF-type F-box substrate receptor for glycoprotein quality control; binds innermost **Man3GlcNAc2** N-glycan core via substrate-binding domain after SKP1 association through the F-box domain | Recognition of misfolded/high-mannose glycoproteins in ERAD; broad lectin-like glycan sensing rather than classical enzyme catalysis | Structural biology, SCF complex modeling, glycan-binding biochemistry, review synthesis | — | Yoshida et al., *Front Physiol* (2019); Suzuki & Fujihira, *Comprehensive Glycoscience* (2021) | 2019, 2021 | https://doi.org/10.3389/fphys.2019.00104 ; https://doi.org/10.1016/B978-0-12-409547-2.14947-9 | (pqac-00000001, pqac-00000002, pqac-00000017) |
| Glycan-directed ER-associated degradation adaptor in the cytosol/nucleocytoplasm | ERAD substrates cited for Fbs1/Fbs2 pathway include **CFTRΔF508, TCRα, integrin β1, asialoglycoprotein receptor H2a** | Review of primary ERAD studies; substrate lists from prior cell-based and biochemical work | HGSOC biomarker study links FBXO2 to ER protein processing and chemoresistance-related ER pathways | Yoshida et al., *Front Physiol* (2019); Yoshida & Tanaka, *BioEssays* (2018) | 2018, 2019, 2024 | https://doi.org/10.3389/fphys.2019.00104 ; https://doi.org/10.1002/bies.201700215 ; https://doi.org/10.1016/j.heliyon.2024.e28490 | (pqac-00000003, pqac-00000006, pqac-00000011) |
| Neuron-enriched SCF adaptor regulating APP pathway glycoproteins | **APP** is a reported FBXO2 substrate; FBXO2 also reduces **BACE1** levels, lowering amyloidogenic processing | In vitro/in vivo substrate studies, knockout mouse/neuron experiments, disease-focused reviews | 2024 preprint: FBXO2 downregulation in human iPSC-derived neurons induces Aβ aggregation and tau hyperphosphorylation | Atkin et al., *J Biol Chem* (2014); Suzuki & Fujihira (2021); Yoshida et al. (2019) | 2014, 2019, 2021, 2024 | https://doi.org/10.1074/jbc.M113.515056 ; https://doi.org/10.3389/fphys.2019.00104 ; https://doi.org/10.1016/B978-0-12-409547-2.14947-9 ; https://doi.org/10.1101/2024.09.01.610673 | (pqac-00000002, pqac-00000003, pqac-00000004) |
| Metabolic regulator when induced in liver; still acting through ubiquitin-ligase substrate recognition rather than catalysis | **Insulin receptor** ubiquitination reported in obese liver context, disrupting glucose homeostasis | Review synthesis of prior mechanistic studies | — | Yoshida & Tanaka, *BioEssays* (2018) | 2018 | https://doi.org/10.1002/bies.201700215 | (pqac-00000006) |
| CNS lysosomal quality-control factor; glycan-binding F-box protein in an SCF complex | **Damaged lysosome clearance / lysophagy** in CNS; loss delays damaged lysosome clearance and reduces viability after lysosomal injury | Mouse primary cortical culture assays, NPC human fibroblast sensitivity assays, knockout disease model | — | Liu et al., *JCI Insight* (2020) | 2020 | https://doi.org/10.1172/jci.insight.136676 | (pqac-00000005) |
| Recurrent glioblastoma-associated FBXO2 program, likely via tumor–microenvironment interactions | Increased FBXO2 abundance in recurrent glioblastoma; enriched in tumor infiltration zone; associated with synaptic signaling processes | SWATH-MS proteomics, immunohistochemistry, CRISPR/KO, orthotopic xenografts, organotypic brain slices | Buehler et al., *Neuro-Oncology* (2023) | — | 2023 | https://doi.org/10.1093/neuonc/noac169 | (pqac-00000016) |
| Oncogenic FBXO2 in papillary thyroid carcinoma acting through ubiquitin-mediated substrate turnover | **p53** direct binding, ubiquitination, and degradation; FBXO2 overexpression correlates with tumor size, lymph-node metastasis, and invasion; mainly cytoplasmic localization in PTC cells | Co-IP, GST pulldown, in vivo ubiquitination assay, IF/IHC, xenografts, proliferation/apoptosis assays | Guo et al., *Scientific Reports* (2024) | — | 2024 | https://doi.org/10.1038/s41598-024-73455-z | (pqac-00000012, pqac-00000013, pqac-00000014) |
| Tumor-suppressive FBXO2 in hepatocellular carcinoma through degradation of a pro-fibrotic chaperone | **Hsp47/SERPINH1** ubiquitination and proteasomal degradation; FBXO2 protein low in **149/258** HCCs; low FBXO2 associated with advanced stage and worse median survival | Human tumor IHC, ubiquitination and half-life studies, phospho-regulation analysis, hepatocyte-specific knockout mice, metastasis assays | Xue et al., bioRxiv (2024) | — | 2024 | https://doi.org/10.1101/2024.03.28.586926 | (pqac-00000009, pqac-00000010, pqac-00000015) |
| Candidate biomarker/therapeutic target in ovarian chemoresistance with ER-processing links | High FBXO2 associated with worse OS/DFS; FBXO2 knockdown lowers cisplatin IC50 in A2780 and SKOV3 cells | scRNA-seq + bulk RNA-seq integration, survival analysis, cisplatin-response assays, knockdown | Lai et al., *Heliyon* (2024) | — | 2024 | https://doi.org/10.1016/j.heliyon.2024.e28490 | (pqac-00000011) |


*Table: This table summarizes the best-supported molecular roles, substrates/processes, and evidence types for human FBXO2/Fbs1, contrasting recent 2023–2024 disease studies with foundational mechanistic literature on SCF assembly and glycan recognition.*