CUL7

CUL7 (Cullin 7) is a Protein Coding gene. Diseases associated with CUL7 include Three M Syndrome 1 and Dubowitz Syndrome. Among its related pathways are Innate Immune System and Class I MHC mediated antigen processing and presentation. Gene Ontology (GO) annotations related to this gene include binding and ubiquitin protein ligase binding. An important paralog of this gene is CUL9.

Full Name

cullin 7

Function

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 (PubMed:24793695).

Interaction with CUL9 is required to inhibit CUL9 activity and ubiquitination of BIRC5 (PubMed:24793696).

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 (PubMed:21572988, PubMed:24362026).

Ubiquitination of GORASP1 regulates Golgi morphogenesis and dendrite patterning in brain (PubMed:21572988).

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) (PubMed:18498745).

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 (PubMed:24362026).

Acts as a regulator in trophoblast cell epithelial-mesenchymal transition and placental development (PubMed:20139075).

Does not promote polyubiquitination and proteasomal degradation of p53/TP53 (PubMed:16547496, PubMed:17332328).

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.

Biological Process

Epithelial to mesenchymal transition Source: UniProtKB
Golgi organization Source: UniProtKB
IRE1-mediated unfolded protein response Source: Reactome
Microtubule cytoskeleton organization Source: UniProtKB
Mitotic cytokinesis Source: UniProtKB
Placenta development Source: UniProtKB
Positive regulation of dendrite morphogenesis Source: UniProtKB
Post-translational protein modification Source: Reactome
Protein ubiquitination Source: UniProtKB
Proteolysis Source: UniProtKB
Regulation of mitotic nuclear division Source: UniProtKB
Ubiquitin-dependent protein catabolic process Source: InterPro
Vasculogenesis Source: UniProtKB
Viral process Source: UniProtKB-KW

Cellular Location

Centrosome; Cytoplasm; Golgi apparatus; Perinuclear region. Colocalizes with FBXW8 at the Golgi apparatus in neurons; localization to Golgi is mediated by OBSL1. During mitosis, localizes to the mitotic apparatus (PubMed:24793695). CCDC8 is required for centrosomal location (PubMed:24793695).

Involvement in disease

3M syndrome 1 (3M1):
An autosomal recessive disorder characterized by severe pre- and postnatal growth retardation, facial dysmorphism, large head circumference, and normal intelligence and endocrine function. Skeletal changes include long slender tubular bones and tall vertebral bodies.

PTM

According to a report, may not be neddylated despite the conserved consensus site for neddylation at Lys-1576.