betaTrCP2

betaTrCP2, also known as beta-transducin repeat-containing protein 2, is a member of the F-box/WD repeat-containing protein family that functions as part of the SCF (SKP1–CUL1–F-box) E3 ubiquitin ligase complex. In humans, it is encoded by the FBXW11 gene. BetaTrCP2 acts as a substrate receptor, recognizing phosphorylated degrons on target proteins and directing their ubiquitination and proteasomal degradation.

Proteins now known to be regulated by betaTrCP2 include inhibitors of NF-κB (IκBα), components of Wnt signaling (β-catenin), and regulators of the cell cycle such as Emi1, among others. Substrate recognition typically depends on a degron motif that becomes accessible after phosphorylation by kinases such as CK1 and GSK3, enabling binding to the WD40 repeats of the betaTrCP2 subunit.

BetaTrCP2 shares functional similarity with its paralog betaTrCP1 (BTRC); both act as substrate adapters in SCF complexes. They can have overlapping as well as distinct substrate pools, and cellular redundancy can influence the outcome of gene knockdowns or mutations.

Dysregulation of betaTrCP2 has been linked to various diseases, most notably cancer and inflammatory conditions, reflecting its broad role in regulating signaling pathways and cell cycle progression. As a result, βTrCP proteins are the subject of ongoing research for understanding their context-dependent roles and therapeutic potential.

BetaTrCP2 is conserved across vertebrates and other eukaryotes, illustrating the evolutionary importance of regulated protein degradation by the SCF ubiquitin ligase system.