Substrate-recognition component of the SCF(FBXL3) E3 ubiquitin ligase complex involved in circadian rhythm function. Plays a key role in the maintenance of both the speed and the robustness of the circadian clock oscillation. The SCF(FBXL3) complex mainly acts in the nucleus and mediates ubiquitination and subsequent degradation of CRY1 and CRY2. Activity of the SCF(FBXL3) complex is counteracted by the SCF(FBXL21) complex. Protein modification; protein ubiquitination. Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL3) composed of CUL1, SKP1, RBX1 and FBXL3. Interacts with HDAC3 (PubMed:26776516). Interacts with CRY1 and CRY2 (phosphorylated) (PubMed:23452856, PubMed:30500822). Interacts with KDM8 (PubMed:30500822). Predominantly nuclear. Ubiquitously expressed but enriched in brain. Diffusely expressed in the suprachiasmatic nucleus, SCN. Undergoes autophagy-mediated degradation in the liver in a time-dependent manner. Mice show defects in behavioral rhythms with an extremely long-period activity phenotype. The onset of active phase is abnormally delayed from the light-to-dark transition: in constant darkness (DD), mice show significantly longer rhythmic activities. Mice lacking both Fbxl3 and Fbxl21 show an attenuated phenotype in behavioral rhythm compared to Fbxl3-deficient mice; however, they exhibit unstable behavioral rhythms, sometimes eliciting arrhythmicity. Extended N-terminus. Extended N-terminus. Extended N-terminus.