| Category | Protein class/domain | Complex | Validated substrates | Recognition/degron determinants | Subcellular localization/site of action | Biological processes | Disease/clinical links | Key quantitative/statistical findings | Key references with year/DOI |
|---|---|---|---|---|---|---|---|---|---|
| CLS1/PINK1 pneumonia axis | FBXO15 is an FBXO-family F-box substrate receptor in the ubiquitin-proteasome system (pqac-00000011, pqac-00000017) | SCF^FBXO15; literature explicitly refers to an SCF^Fbxo15 complex targeting CLS1 (pqac-00000011, pqac-00000012) | Cardiolipin synthase 1 (CLS1) (pqac-00000002, pqac-00000011) | CLS1 aa ~200–250 docking region; Thr219 required for FBXO15 binding and acts as a PINK1-related phospho-recognition site; Lys174 is a ubiquitin acceptor, with K174R partially resistant to polyubiquitination and degradation (pqac-00000011, pqac-00000012) | FBXO15 was not detected in mitochondria; authors propose ubiquitination/degradation of CLS1 occurs in ER/cytosol after biosynthesis, limiting mitochondrial delivery of CLS1 (pqac-00000023) | Cardiolipin homeostasis, mitochondrial membrane potential, ATP production, lung injury responses in pneumonia (pqac-00000002, pqac-00000011, pqac-00000039) | Experimental pneumonia; human pneumonia lung tissue also examined for FBXO15/PINK1/CLS1 changes (pqac-00000038) | PINK1 overexpression decreased CLS1/cardiolipin/ATP; PINK1 knockdown increased CLS1/cardiolipin (*p<0.05 for cardiolipin, *p<0.01 for ATP); S. aureus pneumonia models used n=4 or n=6/group depending experiment; infection doses reported as 10^7 cfu/mouse at early time points and 10^5 cfu/mouse at 24 h; multiple physiologic endpoints significant at *p<0.05 (pqac-00000011, pqac-00000038, pqac-00000039) | Chen et al., 2014, Cell Reports, doi:10.1016/j.celrep.2014.02.048 (pqac-00000002, pqac-00000011) |
| ABCB1/P-gp drug resistance | FBXO15 functions as an F-box substrate receptor controlling membrane transporter abundance post-translationally (pqac-00000003, pqac-00000004) | Skp1-Cullin1-FBXO15 / SCF^Fbx15 with E2 Ube2r1/Cdc34 (pqac-00000004, pqac-00000015) | P-glycoprotein / ABCB1 / MDR1 (pqac-00000003, pqac-00000025) | No degron residue mapped in the retrieved evidence; FBXO15 binds P-gp and promotes ubiquitination in cooperation with Ube2r1 (pqac-00000003, pqac-00000025) | No compartment resolved in extracted text; ubiquitination demonstrated in cell lysates with MG132, consistent with proteasomal turnover of P-gp (pqac-00000025) | Drug efflux regulation and multidrug resistance via control of P-gp protein stability, not MDR1 mRNA (pqac-00000003, pqac-00000013) | Cancer chemoresistance / vincristine sensitivity (pqac-00000013, pqac-00000037) | Preliminary vincristine IC50 values: ~100 nM (HCT-15, HT1080/3HisMDR), 10 nM (SW620-14), 2 nM (HT1080); FBXO15 knockdown increased resistance to vincristine and reduced rhodamine-123 accumulation; VCR assay n=6, *P<0.002 (pqac-00000034, pqac-00000037) | Katayama et al., 2013, Cancer Science, doi:10.1111/cas.12145 (pqac-00000003, pqac-00000013) |
| SOX2/STAT3/EGFR breast cancer axis | FBXO15 acts as a tumor-suppressive F-box protein in breast cancer (pqac-00000018, pqac-00000030) | SCF-type role inferred from F-box identity; direct assays show FBXO15 interaction with SOX2 and STAT3 and promotion of their ubiquitination/degradation (pqac-00000018, pqac-00000019) | SOX2 and STAT3 are directly supported; EGFR is regulated downstream through SOX2 stabilization and signaling effects (pqac-00000018, pqac-00000019) | CHX pulse-chase, ubiquitination assays, co-IP and in situ assays support degradation of SOX2 and STAT3; no specific degron residue reported in extracted text (pqac-00000018, pqac-00000019) | Compartment not explicitly resolved in extracted text; IHC and in situ assays support tumor-cell expression and interactions (pqac-00000024) | Suppression of EMT and cancer stem-cell programs; inhibition of EGFR/ERK/STAT3 signaling; reduced growth, invasion, migration, sphere formation, anchorage-independent growth, xenograft burden and lung metastasis (pqac-00000018, pqac-00000028) | Breast cancer prognosis/biomarker potential; FBXO15 higher in normal tissue than IDC and higher in luminal than basal tumors; high expression associated with improved survival and independent disease-free survival association (pqac-00000018, pqac-00000019, pqac-00000028) | Orthotopic xenografts used n=5/group; qualitative survival benefit by Kaplan–Meier; no hazard ratio extracted from available text (pqac-00000019); mechanistic figure panels available for expression/survival/model (pqac-00000020, pqac-00000021, pqac-00000022) | Zhao et al., 2021, Signal Transduction and Targeted Therapy, doi:10.1038/s41392-021-00605-4 (pqac-00000018, pqac-00000019) |
| Stem cell mitochondrial biogenesis acetyl-degron | FBXO15 is a stem-cell-preferential F-box substrate adaptor; review/commentary explicitly places it in SCF complexes (pqac-00000005, pqac-00000031) | SCF^FBXO15 in mouse ESCs (pqac-00000005, pqac-00000006) | KBP/KIF1BP in mESCs (mouse evidence; useful for mechanistic inference, not direct human validation) (pqac-00000005, pqac-00000006) | Acetylation-dependent degron: GCN5L1 and TDH-driven mitochondrial acetyl-CoA promote KBP Lys501 acetylation, enabling recognition by Fbxo15; K→R mutation blocks degradation (pqac-00000006) | Fractionation evidence indicates compartmental regulation linked to mitochondrial biogenesis; retrieved review/commentary emphasizes mitochondrial metabolic coupling, though exact human localization is not established (pqac-00000006, pqac-00000026) | Limits mitochondrial biogenesis in self-renewing ESCs; links metabolism, acetylation, ubiquitination, respiration, ROS, proliferation, and differentiation competence (pqac-00000006, pqac-00000031) | Stem-cell state marker and pluripotency-associated pathway; mainly developmental/stem-cell biology rather than direct human disease evidence in retrieved texts (pqac-00000031) | FBXO15 is preferentially expressed in undifferentiated cells and silenced at differentiation onset; stabilization of KBP increases mitochondrial mass, respiration and ROS, while ectopic FBXO15 impairs differentiation (pqac-00000006, pqac-00000031) | Donato et al., 2017, Nature Cell Biology, doi:10.1038/ncb3491; Werner & Rape, 2017, Cell Death Differ., doi:10.1038/cdd.2017.142 (pqac-00000005, pqac-00000006) |
| Expression in breast cancer datasets | FBXO15 is part of an SCF/F-box transcriptional signature in breast cancer datasets (pqac-00000010, pqac-00000033) | Not a mechanistic complex study; expression profiling context (pqac-00000010, pqac-00000033) | Not applicable | Not applicable | Tissue/tumor expression by RNA-seq, TCGA and IHC (pqac-00000010, pqac-00000032, pqac-00000033) | Tumor-associated expression program; possible biomarker/signature component (pqac-00000010, pqac-00000036) | Breast carcinoma profiling/signature studies (pqac-00000010, pqac-00000036) | FBXO15 mRNA increased up to 7.7-fold in paired breast carcinoma vs normal tissue; protein elevated ~3.6–5.2-fold across BRCA stages 0–IV vs normal (***p<0.001); mRNA increased in MCF7 and MDA-MB231 vs MCF10A (***p<0.001); ~89% knockdown had no detectable effect on viability/proliferation in that assay context (pqac-00000010, pqac-00000032, pqac-00000035, pqac-00000036) | Chang et al., 2021, Cancers, doi:10.3390/cancers13122873 (pqac-00000010, pqac-00000032) |
| General SCF/F-box definition | F-box proteins are substrate receptors; SCF contains SKP1 adaptor, CUL1 scaffold, RBX1/2 RING protein, plus variable F-box protein; FBXO subfamily are “F-box only” proteins lacking LRR/WD40 repeat classes (pqac-00000017) | Canonical SCF (SKP1-CUL1-RBX1/2-F-box) (pqac-00000017) | Not applicable | Many SCF substrates require post-translationally generated degrons; FBXO15-specific examples include phospho- and acetyldegron recognition from other rows (pqac-00000011, pqac-00000005, pqac-00000017) | Ubiquitin-proteasome system; compartment varies by substrate (pqac-00000017) | Protein homeostasis, signaling, cell cycle, differentiation, stress responses, cancer biology (pqac-00000017) | Framework for interpreting FBXO15 as a substrate-recognition module in disease pathways (pqac-00000017) | Review notes ~37 human FBXO-family members (pqac-00000017) | Tekcham et al., 2020, Theranostics, doi:10.7150/thno.42735 (pqac-00000017) |
| OpenTargets GWAS credible sets | Human FBXO15 is recognized as an approved target/gene entity in Open Targets (ENSG00000141665) (pqac-00000008) | Not a mechanistic protein complex entry | Not applicable | Not applicable | Genetics/association layer rather than localization data (pqac-00000008) | Suggests possible roles in complex traits/disease susceptibility but not mechanism (pqac-00000008) | Reported associations include bacterial disease, body weight gain, smoking initiation, Abruptio Placentae, and glomerulonephritis (pqac-00000008) | Open Targets scores: bacterial disease 0.3129; Abruptio Placentae 0.3000; body weight gain 0.2461; glomerulonephritis 0.1654; smoking initiation 0.1477. Evidence count=4, from GWAS credible sets; cited PMIDs include 40770095, 40069456, 39024449, but effect sizes were not available in retrieved context (pqac-00000008) | Open Targets Platform query (context evidence generated from current platform output; article cited by platform: Buniello et al., 2025, Nucleic Acids Res.) (pqac-00000008) |


*Table: This table summarizes experimentally supported functions, substrates, mechanisms, localization, and disease relevance of human FBXO15, with emphasis on primary mechanistic studies and recent genetic-association context. It is designed as a compact evidence map for interpreting FBXO15 as an SCF-type F-box substrate receptor.*