Calcium-activated substrate recognition component of the SCF (SKP1-cullin-F-box protein) E3 ubiquitin-protein ligase complex, SCF(FBXL2), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Unlike many F-box proteins, FBXL2 does not seem to target phosphodegron within its substrates but rather calmodulin-binding motifs and is thereby antagonized by calmodulin. This is the case for the cyclins CCND2 and CCND3 which polyubiquitination and subsequent degradation are inhibited by calmodulin. Through CCND2 and CCND3 degradation may induce cell-cycle arrest in G(0). SCF(FBXL2) may also mediate PIK3R2 ubiquitination and proteasomal degradation thereby regulating phosphatidylinositol 3-kinase signaling and indirectly autophagy (PubMed:22323446, PubMed:22020328, PubMed:23604317). PCYT1A monoubiquitination by SCF(FBXL2) and subsequent degradation may regulate synthesis of phosphatidylcholine, which is utilized for formation of membranes and of pulmonary surfactant (By similarity).
