GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

PMID:10945468

cDNA cloning and expression analysis of new members of the mammalian F-box protein family.

FBS/FBXO8 is one of a family of mammalian F-box proteins; F-box proteins are components of the SCF ubiquitin-protein ligase complex and function in substrate recognition for ubiquitination and proteasomal degradation. FBS uniquely contains a Sec7 domain.

PMID:31024008

FBX8 degrades GSTP1 through ubiquitination to suppress colorectal cancer progression.

FBX8/FBXO8 is a critical component of the SCF (SKP1-CUL1-F-box) E3 ubiquitin ligase and directly targets GSTP1 for ubiquitin-mediated proteasomal degradation; loss of FBX8 accelerates colon tumorigenesis and correlates with increased GSTP1 stability.

PMID:34445249

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

The SCF complex comprises ~69 SKP1-CUL1-F-box E3 ubiquitin ligase complexes distinguished by variable F-box proteins (substrate specificity), which poly-ubiquitinate substrates for proteasomal degradation.

file:human/FBXO8/FBXO8-deep-research-falcon.md

Falcon deep research report for human FBXO8

FBXO8 is an F-box/SCF substrate receptor functionally tied to ARF6-associated membrane trafficking and invasion, reported to bind ARF6 via its Sec7 domain, localize to the plasma membrane, and mediate ARF6 ubiquitination.

"the SCF substrate receptor FBXO8 binds ARF6 via its Sec7 domain, localizes to the plasma membrane via its Sec7 and F-box domains, and mediates ARF6 ubiquitination; places FBXO8 at the interface of membrane trafficking and ubiquitin signaling."
The available evidence supports a Sec7-like ARF6-binding/localization module rather than demonstrated Sec7 GEF catalysis for FBXO8; loss of FBXO8 confers resistance to the vesicular-transport inhibitor brefeldin A.

"loss of FBXO8 renders cells resistant to the vesicular transport inhibitor brefeldin A, a phenotype noted as consistent with FBXO8 containing a Sec7-like domain. This is functional-genetic, not direct biochemical proof of GEF activity."
FBXO8 acts as a tumor suppressor in hepatocellular carcinoma, where it is downregulated, predicts worse survival, and suppresses proliferation, migration, invasion and lung metastasis on re-expression.

"FBXO8 acts as a suppressor of HCC proliferation, migration, invasion, tumor growth, and lung metastasis. FBXO8 was downregulated in HCC tissues/cell lines and was an independent prognostic factor for survival."