| Category | Key finding | Evidence type | Key citation (author-year) | Publication date | URL/DOI |
|---|---|---|---|---|---|
| Identity/domains | Human FBXO25 corresponds to UniProt Q8TCJ0, “F-box only protein 25,” an F-box substrate-recognition protein in an SCF/CRL1 E3 ligase. Primary literature consistently treats it as a human nuclear F-box protein rather than a different FBXO family member (pqac-00000003, pqac-00000011). | Primary study, database summary | Teixeira 2013; Teixeira 2010 | 2013-09; 2010-08 | https://doi.org/10.1074/jbc.M113.504308; https://doi.org/10.1002/pmic.200900419 |
| SCF complex | FBXO25 assembles an active SCF1(FBXO25) complex with SKP1, CUL1, and Roc1/RBX1 in HEK293T cells, supporting its core molecular role as the substrate adaptor for ubiquitination. Complex purification used tagged HA-SKP1, CUL1-FLAG, Myc-Roc1, and GST-HA-FBXO25-FLAG (pqac-00000003, pqac-00000008, pqac-00000013). | Primary study | Teixeira 2013 | 2013-09 | https://doi.org/10.1074/jbc.M113.504308 |
| Localization | FBXO25 localizes to distinct nuclear puncta termed FBXO25-associated nuclear domains (FANDs), which co-localize with proteasomes and ubiquitinated proteins. FAND integrity is disrupted by actin depolymerization and by RNA polymerase I inhibition, supporting a regulated nuclear-compartment function (pqac-00000011, pqac-00000012). | Primary study | Teixeira 2010 | 2010-08 | https://doi.org/10.1002/pmic.200900419 |
| Validated substrates | ELK-1 is the best-supported endogenous FBXO25 substrate. FBXO25 binds ELK-1, promotes its ubiquitination, accelerates ELK-1 turnover in methionine-chase assays, and the degradation is blocked by epoxomicin, demonstrating proteasome dependence; FBXO25 overexpression also suppresses ELK-1 target genes c-fos and egr-1 (pqac-00000001, pqac-00000002, pqac-00000003, pqac-00000006, pqac-00000014). | Primary study | Teixeira 2013 | 2013-09 | https://doi.org/10.1074/jbc.M113.504308 |
| Other reported targets/candidates | A protoarray ubiquitination screen identified 75 putative SCF1(FBXO25) substrates from ~8,000 human proteins; named candidates include GTF2B, ODF2, SAMHD1, RPS10, ADRBK1, CDK9, EGFR, and RABEP2. These are candidates rather than comparably validated substrates, so confidence is lower than for ELK-1 (pqac-00000006, pqac-00000010, pqac-00000013). | Primary study | Teixeira 2013 | 2013-09 | https://doi.org/10.1074/jbc.M113.504308 |
| Regulatory interactions | An integrated proteomics approach identified 132 novel potential FBXO25-interacting partners; β-actin was a validated interactor that binds the N-terminus of FBXO25 and is enriched in FANDs. Proteomics also recovered major SCF-related components, consistent with FBXO25 acting in a broader nuclear interaction network (pqac-00000011, pqac-00000012, pqac-00000015). | Primary study | Teixeira 2010 | 2010-08 | https://doi.org/10.1002/pmic.200900419 |
| Regulatory interactions | In hUC-MSCs, lncRNA ODIR1 binds FBXO25 and promotes its proteasome-dependent degradation by recruiting CUL3; FBXO25 in turn promotes H2BK120 monoubiquitination and downstream H3K4me3, increasing transcription of the osteogenic factor OSX. This places FBXO25 in a chromatin-linked regulatory axis rather than only a classic protein-degradation role (pqac-00000009, pqac-00000017). | Primary study | He 2019 | 2019-12 | https://doi.org/10.1038/s41419-019-2148-2 |
| Phenotypes/disease links | In neonatal rat cardiomyocytes, Fbxo25 depletion increased cell size by ~37% and 3H-isoleucine incorporation by ~41%, and upregulated Anp/Bnp; in vivo, Fbxo25 protein increased ~4.5-fold after transverse aortic constriction. These data support a conserved antihypertrophic role, but they are from rodent models rather than direct human functional experiments (pqac-00000016). | Primary study, model-organism | Fischer 2023 | 2023-03 | https://doi.org/10.3389/fphys.2023.1134339 |
| Phenotypes/disease links | Human genetic and fly-model evidence links FBXO25 to ADHD-related phenotypes. In a large ADHD GWAS meta-analysis (n=55,374), gene-based analysis implicated FBXO25 (reported p=0.010756), and Drosophila pan-neuronal overexpression increased nocturnal locomotor activity and reduced sleep; sample sizes were n=64 and n=56 for two overexpression lines versus n=63 controls, with p-values 0.0013 to <0.0001 depending on assay (pqac-00000022, pqac-00000023, pqac-00000024, pqac-00000026, pqac-00000028). | Primary study, database summary, model-organism | Harich 2020; OpenTargets | 2020-12; OpenTargets accessed in current query | https://doi.org/10.1111/jcpp.13161; https://platform.opentargets.org/target/ENSG00000147364 |
| Phenotypes/disease links | A single-patient case report described a novel FBXO25–SEPT14 fusion in chronic myeloid leukemia, joining FBXO25 exon 4 to SEPT14 exon 10, in a patient with persistent suboptimal molecular response to TKIs. The authors suggest a possible association with TKI resistance, but evidence is limited to one observational case without functional validation (pqac-00000018, pqac-00000019, pqac-00000020). | Primary study, single-case report | Liao 2023 | 2023-09 | https://doi.org/10.1515/oncologie-2023-0217 |
| Key quantitative data | Quantitative highlights across studies: 132 potential interactors and β-actin with 63 yeast-two-hybrid hits; 75 putative ubiquitination substrates; cardiac phenotypes of ~37% larger cardiomyocyte area, ~41% higher protein synthesis, and ~4.5-fold TAC-induced protein increase; ADHD GWAS meta-analysis n=55,374 with FBXO25 p=0.010756; Drosophila overexpression ~450% or ~650% expression versus control with behavioral sample sizes n=64, n=56, n=63 and significant night-activity/sleep effects; one reported FBXO25–SEPT14 CML case (pqac-00000015, pqac-00000016, pqac-00000022, pqac-00000024, pqac-00000026, pqac-00000020). | Primary study, database summary | Teixeira 2010; Fischer 2023; Harich 2020; OpenTargets; Liao 2023 | 2010-08; 2023-03; 2020-12; OpenTargets accessed in current query; 2023-09 | https://doi.org/10.1002/pmic.200900419; https://doi.org/10.3389/fphys.2023.1134339; https://doi.org/10.1111/jcpp.13161; https://platform.opentargets.org/target/ENSG00000147364; https://doi.org/10.1515/oncologie-2023-0217 |


*Table: This table summarizes the best-supported validated and proposed functions of human FBXO25, emphasizing molecular function, localization, substrates, regulatory interactions, and disease links. It also flags where evidence comes from model systems, candidate screens, or a single-case clinical report.*