| Claim / Functional annotation | Evidence type | Key experimental details (cell type / assay / mutants) | Main quantitative / statistical outputs if stated | Source (paper, year, DOI URL) |
|---|---|---|---|---|
| FBXL15 is the substrate-recognition subunit of a functional SCF E3 ubiquitin ligase complex | Biochemical, cell-based | Human FBXL15/FBXO37 identified as an F-box/LRR protein; co-immunoprecipitation showed association with Skp1, Cullin1, and Roc1; FBXL15 deletion mutants lacking an intact F-box failed to support activity; HEK293T-based ubiquitination/degradation assays | Domain architecture reported as F-box aa 22-64 and six LRRs aa 113-269; knockdown of Cullin1, Roc1, or FBXL15 stabilized endogenous Smurf1 and increased its half-life in CHX chase assays (pqac-00000002, pqac-00000004, pqac-00000013) | Cui et al., 2011, EMBO Journal, https://doi.org/10.1038/emboj.2011.155 (pqac-00000002, pqac-00000004, pqac-00000013) |
| Smurf1 is a direct FBXL15 substrate targeted for ubiquitination and proteasomal degradation | Biochemical, cell-based | Yeast two-hybrid and GST pull-down supported direct interaction; HEK293T co-expression of Myc-FBXL15 increased Smurf1 ubiquitination; denaturing IP ubiquitination assays; MG132-sensitive degradation; in vitro reconstituted SCF-GST-FBXL15 ubiquitination assay | FBXL15 promoted Smurf1 ubiquitination in vivo and in vitro; siRNA against Cullin1, Roc1, or FBXL15 reduced Smurf1 ubiquitination; UbcH5c used as E2 in vitro (UbcH7 also tested) (pqac-00000001, pqac-00000002, pqac-00000013) | Cui et al., 2011, EMBO Journal, https://doi.org/10.1038/emboj.2011.155 (pqac-00000001, pqac-00000002, pqac-00000013) |
| FBXL15-mediated ubiquitination of Smurf1 maps primarily to lysines in the WW-HECT linker | Biochemical, mutational mapping | Smurf1 lysine-to-arginine mutants tested in ubiquitination/degradation assays and CHX chase; mapping focused on linker between WW domains and HECT domain | K357 identified as the primary residue and K355 as a secondary residue for FBXL15-mediated degradation; K355+K357R attenuated ubiquitination and stabilized Smurf1; triple K-to-R mutation blocked degradation (pqac-00000001, pqac-00000004) | Cui et al., 2011, EMBO Journal, https://doi.org/10.1038/emboj.2011.155 (pqac-00000001, pqac-00000004) |
| FBXL15 also associates with and can ubiquitinate Smurf2, extending activity to multiple Nedd4-family ligases | Biochemical, cell-based | Interaction studies and ubiquitination assays reported association with multiple Nedd4 family members; Smurf2 specifically tested as an additional substrate candidate | Evidence snippet states FBXL15 associates with multiple Nedd4 family members and can ubiquitinate Smurf2; no effect size stated in snippet (pqac-00000003, pqac-00000005) | Cui et al., 2011, EMBO Journal, https://doi.org/10.1038/emboj.2011.155; summarized in Randle & Laman, 2016, https://doi.org/10.1016/j.semcancer.2015.09.013 (pqac-00000003, pqac-00000005) |
| FBXL15 positively regulates BMP signaling by counteracting Smurf1-mediated inhibition | Cell-based reporter assay | HEK293T/HepG2 BMP pathway assays; BMP-responsive BRE-luciferase reporter tested with Smurf1 and FBXL15 WT versus FBXL15 mutants (ΔF or F-box-only constructs) | Smurf1 inhibited BRE-luc activity, while WT FBXL15 antagonized this inhibition; ΔF and F-box-only mutants did not rescue reporter output (qualitative effect described in figure summary) (pqac-00000003, pqac-00000013) | Cui et al., 2011, EMBO Journal, https://doi.org/10.1038/emboj.2011.155 (pqac-00000003, pqac-00000013) |
| FBXL15 is required for full induction of BMP/Smad target genes after BMP-2 stimulation | Cell-based, gene expression | siRNA depletion of FBXL15 (and of Cullin1/Roc1 in related assays) followed by BMP-2 stimulation; qRT-PCR readout of canonical targets | Knockdown of FBXL15 reduced BMP-2-stimulated BRE reporter activity and diminished induction of ID1 and SMAD6 transcripts; no numeric fold changes stated in snippet (pqac-00000003) | Cui et al., 2011, EMBO Journal, https://doi.org/10.1038/emboj.2011.155 (pqac-00000003) |
| FBXL15 shows broad induced-proximity destabilizer activity in 2024 degrader screens, suggesting utility for targeted protein degradation platforms | Screen, functional genomics | Proteome-scale and focused induced-proximity screens tethered effectors to model substrates via anti-GFP nanobody or ABI1/PYL1 system; follow-up tested 10 model substrates with different subcellular localizations | Approximately half of ~300 tested human ligases significantly decreased the eGFP/BFP ratio; FBXL15 was among a small set (with FBXL12, FBXL14, KBTBD7, PRAME) that destabilized most tested substrates across localizations (pqac-00000008, pqac-00000011) | Hermanns & Hofmann, 2024, Signal Transduction and Targeted Therapy, https://doi.org/10.1038/s41392-024-01884-3; discussing Poirson et al., 2024, Nature, https://doi.org/10.1038/s41586-024-07224-3 (pqac-00000008, pqac-00000011, pqac-00000010) |
| FBXL15 itself appears proteasome-regulated, and its C-terminus can influence apparent stability in tagging assays | Omics/methods, cell-based stability assay | DEGRONOPEDIA report used HiBiT/LgBiT luminescence with N- versus C-terminal HiBiT-tagged FBXL15; CHX chase and MG132 treatment used to monitor turnover | C-terminal HiBiT tagging caused a notable increase in FBXL15 stability after a 4-hour CHX chase versus N-terminal tagging; MG132 increased accumulation of both variants, especially the C-terminally tagged form (pqac-00000009) | Szulc et al., 2024, Nucleic Acids Research, https://doi.org/10.1093/nar/gkae238 (pqac-00000009) |
| Current disease links for FBXL15 are limited and low-confidence in target-disease databases rather than mechanistically established | Database | Open Targets search for FBXL15 target-disease associations | Reported associations included deafness, autosomal recessive nonsyndromic hearing loss 9, MODY, MODY type 3, and MODY type 10; each listed with evidence count = 5 and low association scores (~0.04-0.057); no supporting literature identifiers were provided in the retrieved evidence rows (pqac-00000000) | Open Targets Platform search result for FBXL15, accessed via tool output (pqac-00000000) |


*Table: This table compiles the strongest available evidence for the identity, molecular function, pathway role, and emerging translational relevance of human FBXL15/FBXO37. It separates direct mechanistic findings from newer screening-based and database-based observations so the final report can distinguish established function from inference and low-confidence associations.*