The function of FBXO3 (F-box protein 3, ENSG00000110429) is as follows. Substrate recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex, SCF(FBXO3), which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:18809579, PubMed:26037928). Mediates the ubiquitination of HIPK2 and probably that of EP300, leading to rapid degradation by the proteasome (PubMed:18809579). In the presence of PML, HIPK2 ubiquitination still occurs, but degradation is prevented (PubMed:18809579). PML, HIPK2 and FBXO3 may act synergically to activate p53/TP53-dependent transactivation (PubMed:18809579). The SCF(FBXO3) also acts as a regulator of inflammation by mediating ubiquitination and degradation of FBXL2 in response to lipopolysaccharide (LPS) (PubMed:26037928, PubMed:27010866). The SCF(FBXO3) complex specifically recognizes FBXL2 phosphorylated at 'Thr-404' and promotes its ubiquitination (PubMed:27010866). {ECO:0000250|UniProtKB:Q9DC63, ECO:0000269|PubMed:18809579, ECO:0000269|PubMed:26037928, ECO:0000269|PubMed:27010866}. (Microbial infection) Associates with the Rift valley fever virus NSs to form a remodeled E3 ligase that triggers efficient proteasomal degradation of targeted proteins. The filamentous E3 ligase targets the TFIIH complex leading to robust inhibition of antiviral immunity and enhances viral pathogenesis. .