GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000041

Gene Ontology annotation based on UniPathway vocabulary mapping

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

PMID:10531035

Identification of a family of human F-box proteins.

FBXO25/FBX25 was identified as one of a family of 26 human F-box proteins; F-box proteins are the substrate-recruiting subunit of SCF (SKP1-CUL1-F-box-RBX1) ubiquitin ligases.

PMID:16278047

Characterization of FBX25, encoding a novel brain-expressed F-box protein.

hFBX25 was established as an F-box protein by verifying its interaction with SKP1 and CUL1; an atypical F-box serine (Ser244) is crucial for SKP1 binding; subcellular localization was determined (nuclear, non-nucleolar, SKP1-colocalized subnuclear domains) and strong brain expression was observed.

PMID:34445249

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

The SCF complex comprises ~69 E3 ubiquitin ligase complexes distinguished by variable F-box proteins that determine substrate specificity and target substrates with poly-ubiquitin chains for proteasomal degradation; functions of most individual SCF complexes remain largely unknown.

file:human/FBXO25/FBXO25-deep-research-falcon.md

Falcon deep research report for human FBXO25

FBXO25 assembles an active SCF1(FBXO25) complex with SKP1, CUL1, and Roc1/RBX1, and its best-validated endogenous substrate is the transcription factor ELK-1, which it ubiquitinates for proteasome-dependent degradation.

"Validated substrate: The transcription factor **ELK-1** is the clearest experimentally validated endogenous substrate. FBXO25 physically associates with ELK-1 and promotes ELK-1 ubiquitination and proteasome-dependent degradation in human cells."
By degrading ELK-1, FBXO25 suppresses mitogen-induced ELK-1 target genes c-fos and egr-1, linking it to regulation of mitogen-responsive transcription.

"FBXO25 overexpression suppresses induction of ELK-1 target genes **c-fos** and **egr-1** following mitogen stimulation (PMA), consistent with reduced ELK-1 activity due to decreased ELK-1 protein levels."
FBXO25 localizes to discrete nuclear puncta (FBXO25-associated nuclear domains, FANDs) that co-localize with the proteasome and ubiquitinated proteins, and whose integrity depends on actin polymerization and RNA polymerase I activity, suggesting a nuclear proteostasis compartment.

"FBXO25 is not merely diffuse in the nucleus; it localizes to discrete nuclear puncta termed **FBXO25-associated nuclear domains (FANDs)**. These FANDs are reported to co-localize with the **proteasome** and **ubiquitinated proteins**, suggesting FBXO25 participates in a nuclear proteostasis/ubiquitin signaling compartment."
In human umbilical-cord MSCs, FBXO25 promotes histone H2B K120 monoubiquitination (with downstream H3K4me3 and OSX/SP7 activation) during osteogenic differentiation, indicating a chromatin-linked role beyond classical substrate degradation.

"In human umbilical cord-derived MSCs (hUC-MSCs), He et al. report that FBXO25 promotes **H2B K120 monoubiquitination (H2BK120ub)**, which is associated with increased **H3K4 trimethylation (H3K4me3)** and transcriptional activation of the osteogenic transcription factor **OSX (osterix/SP7)**."