Core component of the 3M and Cul7-RING(FBXW8) complexes, which mediates the ubiquitination of target proteins. Core component of the 3M complex, a complex required to regulate microtubule dynamics and genome integrity. It is unclear how the 3M complex regulates microtubules, it could act by controlling the level of a microtubule stabilizer . Interaction with CUL9 is required to inhibit CUL9 activity and ubiquitination of BIRC5 . Core component of a Cul7-RING ubiquitin-protein ligase with FBXW8, which mediates ubiquitination and consequent degradation of target proteins such as GORASP1, IRS1 and MAP4K1/HPK1 (, ). Ubiquitination of GORASP1 regulates Golgi morphogenesis and dendrite patterning in brain . Mediates ubiquitination and degradation of IRS1 in a mTOR-dependent manner: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2) . The Cul7-RING(FBXW8) complex also mediates ubiquitination of MAP4K1/HPK1: recognizes and binds autophosphorylated MAP4K1/HPK1, leading to its degradation, thereby affecting cell proliferation and differentiation . Acts as a regulator in trophoblast cell epithelial-mesenchymal transition and placental development . Does not promote polyubiquitination and proteasomal degradation of p53/TP53 (, ). While the Cul7-RING(FBXW8) and the 3M complexes are associated and involved in common processes, CUL7 and the Cul7-RING(FBXW8) complex may be have additional functions.
Subcellular locations: Cytoplasm, Cytoplasm, Cytoskeleton, Microtubule organizing center, Centrosome, Cytoplasm, Perinuclear region, Golgi apparatus
Colocalizes with FBXW8 at the Golgi apparatus in neurons; localization to Golgi is mediated by OBSL1. During mitosis, localizes to the mitotic apparatus . CCDC8 is required for centrosomal location .
Highly expressed in fetal kidney and adult skeletal muscle. Also abundant in fetal brain, as well as in adult pancreas, kidney, placenta and heart. Detected in trophoblasts, lymphoblasts, osteoblasts, chondrocytes and skin fibroblasts.