FBXO2: F-Box Protein 2 – Substrate Recognition Component of SCF Ubiquitin Ligase
A key player in ubiquitin-mediated protein degradation, linked to neurodegenerative and cancer pathways.
Gene Information Card
| Symbol | FBXO2 |
|---|---|
| Full Name | F-box protein 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.22 |
| NCBI Gene ID | 26232 ncbi.nlm.nih.gov/gene/26232 |
| Ensembl ID | ENSG00000116661 |
| UniProt ID | Q9UK22 |
| OMIM ID | 607112 |
| HGNC ID | 13581 |
| Aliases | FBX2, F-box only protein 2, NFB42 |
Description
FBXO2 encodes a member of the F-box protein family, which functions as the substrate-recognition component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex. FBXO2 specifically recognizes N-glycosylated proteins, targeting them for ubiquitination and proteasomal degradation. It plays a critical role in the endoplasmic reticulum-associated degradation (ERAD) pathway, quality control of glycoproteins, and regulation of neuronal and cancer-related proteins.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer disease | FBXO2 mediates ubiquitination of β-secretase (BACE1) and presenilin 1, affecting amyloid-β production. | PMID: 23066020; ClinVar |
| Spinocerebellar ataxia type 1 (SCA1) | FBXO2 ubiquitinates ataxin-1; loss of FBXO2 function leads to ataxin-1 accumulation and neurodegeneration. | PMID: 21795692; OMIM 607112 |
| Hepatocellular carcinoma | FBXO2 downregulation correlates with poor prognosis; regulates β-catenin degradation. | PMID: 29367642; COSMIC |
| Colorectal cancer | FBXO2 mutations and altered expression linked to Wnt/β-catenin pathway dysregulation. | PMID: 31073040; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Liver | 6.1 | Low |
| Kidney | 5.4 | Low |
| Heart | 4.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression; used in neurodegeneration studies |
| HepG2 (hepatocellular carcinoma) | 9.8 | Moderate; relevant to liver cancer |
| HEK293 (embryonic kidney) | 7.5 | Moderate; common model for ubiquitination assays |
| HeLa (cervical cancer) | 6.3 | Low; baseline expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.487C>T (p.Arg163Trp) | Missense | 0.001% (gnomAD) | Alters substrate binding; associated with SCA1 modifier effect |
| c.101_102del (p.Leu34fs) | Frameshift | <0.001% | Loss of function; predicted to impair F-box domain |
| c.722G>A (p.Arg241Gln) | Missense | 0.002% | Unknown significance; reported in COSMIC for colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations (e.g., p.Leu34fs) disrupt the F-box domain, preventing SCF complex assembly and substrate ubiquitination.
Gain of Function (GOF)
Not clearly documented; missense variants may alter substrate specificity but no confirmed gain-of-function reported.
Dominant Negative (DN)
Truncating mutations that retain substrate binding but lack F-box domain could act as dominant negatives, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • ER-associated ubiquitin-dependent protein catabolic process (GO:0030433) | • ubiquitin protein ligase binding (GO:0031625) |
| • cytoplasm (GO:0005737) | • SCF ubiquitin ligase complex (GO:0019005) |
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• ERAD pathway (Reactome: R-HSA-9013423)
• SCF complex assembly (Reactome: R-HSA-8951664)
Protein Summary
FBXO2 is a 296-amino acid F-box protein containing an N-terminal F-box domain (required for SKP1 binding) and a C-terminal substrate-binding domain that recognizes high-mannose N-glycans. It localizes to the cytoplasm and endoplasmic reticulum, where it targets misfolded glycoproteins for degradation. The protein is highly expressed in brain and testis, and its dysregulation contributes to neurodegeneration and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FBXO21 Knockout HEK293 Cell Line | EDJ-KQ2318 | Human | 23014 | Details Get a Quote |
| FBXO22 Knockout HEK293 Cell Line | EDJ-KQ2733 | Human | 26263 | Details Get a Quote |
| FBXO28 Knockout HEK293 Cell Line | EDJ-KQ7892 | Human | 23219 | Details Get a Quote |
| FBXO2 Knockout HEK293 Cell Line | EDJ-KQ8474 | Human | 26232 | Details Get a Quote |
| FBXO24 Knockout HEK293 Cell Line | EDJ-KQ8490 | Human | 26261 | Details Get a Quote |
| FBXO27 Knockout HEK293 Cell Line | EDJ-KQ8918 | Human | 126433 | Details Get a Quote |
| FBXO21 Knockout A-549 Cell Line | EDJ-KQ24077 | Human | 23014 | Details Get a Quote |
| FBXO21 Knockout HCT 116 Cell Line | EDJ-KQ24078 | Human | 23014 | Details Get a Quote |
| FBXO21 Knockout HeLa Cell Line | EDJ-KQ24079 | Human | 23014 | Details Get a Quote |
| FBXO27 Knockout A-549 Cell Line | EDJ-KQ34029 | Human | 126433 | Details Get a Quote |
| FBXO22 Knockout A-549 Cell Line | EDJ-KQ23598 | Human | 26263 | Details Get a Quote |
| FBXO22 Knockout HCT 116 Cell Line | EDJ-KQ23599 | Human | 26263 | Details Get a Quote |
| FBXO22 Knockout HeLa Cell Line | EDJ-KQ23600 | Human | 26263 | Details Get a Quote |
| FBXO28 Knockout A-549 Cell Line | EDJ-KQ33488 | Human | 23219 | Details Get a Quote |
| FBXO28 Knockout HCT 116 Cell Line | EDJ-KQ33489 | Human | 23219 | Details Get a Quote |
