FBXW11

FBXW11, also known as beta-transducin repeat-containing protein 2 (β-TrCP2), is a human gene encoding an F-box/WD40 repeat-containing protein. It functions as a substrate recognition component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex, selecting phosphorylated substrates for ubiquitination and subsequent proteasomal degradation. The protein has an N-terminal F-box motif that binds SKP1 and a C-terminal WD40-repeat propeller domain that recognizes phosphorylated degron motifs in substrates, enabling assembly of the SCFβ-TrCP2 complex with CUL1, RBX1, and other components.

FBXW11 participates in key cellular pathways by targeting multiple regulators for degradation. It promotes degradation of IκBα to regulate NF-κB signaling, and it targets β-catenin to modulate Wnt signaling. Additional substrates include Emi1, REST, and Snail, among others, linking FBXW11 to control of inflammation, development, and cell cycle progression. In humans there are two β-TrCP paralogs, FBXW11 (β-TrCP2) and FBXW1 (β-TrCP1); they share substantial overlap in substrate recognition but can display context-dependent specificity.

Alterations in FBXW11 expression or function have been associated with disease, including cancer, where dysregulation of β-TrCP–mediated degradation can perturb NF-κB or Wnt signaling. The gene is broadly expressed across tissues and is evolutionarily conserved in vertebrates as part of the β-TrCP family of F-box proteins.