Regulatory component of cullin-RING-based SCF (SKP1-Cullin-F-box protein) E3 ubiquitin-protein ligase complexes. Inhibits E3 ubiquitin ligase activity by binding to the RING domain of RBX1 and inhibiting its interaction with the E2 ubiquitin-conjugating enzyme CDC34. Inhibits RBX1-mediated neddylation of CUL1 (By similarity). Required for normal stability and normal cellular levels of key components of SCF ubiquitin ligase complexes, including FBXW7, RBX1, CUL1, CUL2, CUL3, CUL4A, and thereby contributes to the regulation of CCNE1 and MYC levels (PubMed:22405651). Essential for normal development of the vasculature (PubMed:22405651). Contributes to the regulation of RPS6KB1 phosphorylation (By similarity). Interacts with FKBP4 and FKBP1A. Interacts with RBX1 (via RING domain). Identified in complexes that contain RBX1 plus one of the cullins CUL1, CUL2, CUL3, and CUL4A. Identified in a SCF complex composed of CUL1, RBX1, SKP1, FBXW7 and GLMN. Component of a SCF-like complex consisting of CUL7, RBX1, SKP1, FBXW8 and GLMN. Interacts with unphosphorylated MET and is released upon MET phosphorylation. Ubiquitous. Detected in embryonic vasculature and embryonic perichondrium, and in adult eye, brain, heart, testis, kidney, smooth muscle and skeletal muscle. The C-terminal half of the protein is important for interaction with RBX1. Phosphorylated on tyrosine residues. Complete embryonic lethality. Embryos are present at the expected Mendelian rate at 10.5 dpc, but all are dead by 12.5 dpc. Mutant embryos display decreased growth, delayed neural tube closure, incomplete axial turning, pericardial effusion and a failure to form an organized, functional vascular network. Mutant embryos have reduced protein levels of FBXW7, RBX1, CUL1, CUL2, CUL3 and CUL4A, due to increased proteasome-mediated degradation, and increased levels of CCNE1 and MYC.