PMID:34445249

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

SCF complexes modify protein substrates with poly-ubiquitin chains to target them for proteasomal degradation; the variable F-box protein determines substrate specificity, but the function of most individual SCF complexes (including F-box-only proteins like FBXO36) remains largely unknown.

file:human/FBXO36/FBXO36-uniprot.txt

UniProtKB entry Q8NEA4 (FBX36_HUMAN), F-box only protein 36

FBXO36 is the substrate-recognition component of an SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex and directly interacts with SKP1 and CUL1; it carries a single F-box domain (residues 91-137).

file:human/FBXO36/FBXO36-deep-research-falcon.md

Falcon deep research report for human FBXO36

FBXO36 is inferred to be an F-box substrate-recognition adaptor of an SCF/CRL1 complex, but no endogenous FBXO36 substrate has been directly validated in the literature.

"although **no endogenous FBXO36 substrate has been directly validated** in the retrieved literature"
The strongest direct functional evidence is from a TNF/NF-kappa-B RNAi screen in which FBXO36 depletion increased TNF-induced nuclear NF-kappa-B accumulation and altered I-kappa-B/JNK phosphorylation, consistent with FBXO36 modulating SCF-dependent ubiquitin signaling.

"**FBXO36 is likely an F-box adaptor protein that can modulate SCF-dependent ubiquitin signaling, with experimental evidence that FBXO36 depletion alters TNF pathway signaling outputs (NF-κB nuclear accumulation kinetics, I-κB and JNK phosphorylation dynamics, and TNF+CHX apoptosis sensitivity) in human cell lines.**"
FBXO36 depletion increased steady-state beta-catenin, interpreted as a possible modifier of the SCF-betaTrCP axis, but this does not establish beta-catenin as a direct FBXO36 substrate.

"depletion of FBXO36 increased steady-state **β-catenin** levels. They interpreted this as supportive of a possible role as a modifier of the **SCF–βTrCP** axis"