FBXL2 Gene - F-Box and Leucine Rich Repeat Protein 2

FBXL2 encodes a member of the F-box protein family, characterized by an F-box domain and leucine-rich repeats (LRRs). As a substrate recognition component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, FBXL2 targets specific proteins for ubiquitination and proteasomal degradation. It plays a critical role in cell cycle progression, apoptosis, and tumor suppression by regulating the stability of key proteins such as cyclin D2, cyclin D3, and CDK6. FBXL2 is located on chromosome 3p22.3, a region frequently deleted in various cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Ubiquitin mediated proteolysis (KEGG: hsa04120)

• Cell cycle (KEGG: hsa04110)

• SCF complex assembly (Reactome: R-HSA-8951664)

FBXL2 is a 433-amino acid protein containing an N-terminal F-box domain (residues 33-78) and C-terminal leucine-rich repeats (LRRs, residues 120-420). The F-box domain mediates interaction with SKP1, while LRRs are responsible for substrate recognition. FBXL2 targets cyclin D2, cyclin D3, and CDK6 for ubiquitination and degradation, thereby negatively regulating cell cycle progression. Loss of FBXL2 expression or function contributes to tumorigenesis in multiple cancer types.