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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 (By similarity). This is the case for the cyclins CCND2 and CCND3 which polyubiquitination and subsequent degradation are inhibited by calmodulin (By similarity). Through CCND2 and CCND3 degradation induces cell-cycle arrest in G(0) (By similarity). SCF(FBXL2) also mediates PIK3R2 ubiquitination and proteasomal degradation thereby regulating phosphatidylinositol 3-kinase signaling and autophagy (By similarity). PCYT1A monoubiquitination by SCF(FBXL2) and subsequent degradation regulates synthesis of phosphatidylcholine, which is utilized for formation of membranes and of pulmonary surfactant (PubMed:21343341). The SCF(FBXL2) complex acts as a regulator of inflammation by mediating ubiquitination and degradation of TRAF proteins (TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 and TRAF6) (PubMed:23542741). The SCF(FBXL2) complex acts as a negative regulator of the NLRP3 inflammasome by mediating ubiquitination and degradation of NLRP3 (By similarity). The GGTase-3 complex, composed of PTAR1 and RABGGTB, geranylgeranylates and targets FBXL2 to the cellular membranes, where FBXL2 forms part of the SCF(FBXL2) complex that mediates the degradation of membrane-anchored proteins (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23542741"}],"value":"Protein modification; protein ubiquitination"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q9UKC9"}],"value":"Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL2) composed of CUL1, SKP1, RBX1 and FBXL2 (By similarity). Interacts with calmodulin; may antagonize substrate ubiquitination by SCF(FBXL2) (By similarity). May interact with PIK3R1 (By similarity). 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