Annotation inferences using phylogenetic trees

Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.

Large-scale yeast two-hybrid interactome of neurodegenerative-disease-related proteins; source of the FBXO15-JPH3 (junctophilin-3) binary interaction recorded in IntAct.

PMID:34445249

The SCF Complex Is Essential to Maintain Genome and Chromosome Stability.

Review of the 69 human SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase complexes, in which variable F-box proteins determine substrate specificity and direct substrates to proteasomal degradation.

Reactome:R-HSA-8952618

AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex

Reactome:R-HSA-8952620

NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex

Reactome:R-HSA-8955241

CAND1 binds cytosolic CRL E3 ubiquitin ligases

Reactome:R-HSA-8955289

COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes

Reactome:R-HSA-8956040

COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes

Reactome:R-HSA-8956200

MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex

Reactome:R-HSA-983140

Transfer of Ub from E2 to substrate and release of E2

Reactome:R-HSA-983147

Release of E3 from polyubiquitinated substrate

Reactome:R-HSA-983156

Polyubiquitination of substrate

Reactome:R-HSA-983157

Interaction of E3 with substrate and E2-Ub complex

file:human/FBXO15/FBXO15-deep-research-falcon.md

Falcon deep research report for human FBXO15

FBXO15 is the substrate-recruiting F-box subunit of an SCF (SKP1-CUL1-FBXO15) E3 ligase whose primary biochemical role is protein-protein-interaction-mediated substrate recruitment for polyubiquitination and proteasomal degradation, not small-molecule catalysis.

"its primary biochemical role is **protein–protein interaction–mediated substrate recruitment** to an SCF-type E3 ligase, enabling **target protein polyubiquitination** and **proteasomal degradation**."
FBXO15 uniquely associates with and degrades cardiolipin synthase 1 (CLS1) in a PINK1-linked pathway, recognizing CLS1 via Thr219 and directing ubiquitination at Lys174, an ER/cytosol-associated activity affecting mitochondrial cardiolipin.

"In an unbiased screen of >27 F-box proteins, **FBXO15 uniquely associated with endogenous CLS1**, and **only FBXO15 expression decreased CLS1 levels**"
FBXO15 physically associates with and promotes ubiquitination of P-glycoprotein (ABCB1/MDR1) with the E2 CDC34/UBE2R1, so that FBXO15 knockdown increases P-gp and multidrug resistance.

"FBXO15 is described as part of a **Skp1–Cullin1–FBXO15** E3 complex and physically associates with **P-gp** by co-immunoprecipitation"
In breast cancer FBXO15 promotes ubiquitin-dependent degradation of SOX2 and STAT3, dampening EGFR/ERK/STAT3 signaling and behaving as a tumor suppressor.

"FBXO15 overexpression decreases **SOX2 protein stability** (CHX chase) and increases **SOX2 ubiquitination**"