FBXW8

This gene encodes a member of the F-box protein family, members of which are characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into three classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene contains a WD-40 domain, in addition to an F-box motif, so it belongs to the Fbw class. Alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene.

Full Name

F-Box And WD Repeat Domain Containing 8

Research Area

Substrate-recognition component of a Cul7-RING ubiquitin-protein ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. The Cul7-RING(FBXW8) complex mediates ubiquitination and consequent degradation of GORASP1, acting as a component of the ubiquitin ligase pathway that 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).

Associated component of the 3M complex, suggesting that it mediates some of 3M complex functions (PubMed:24793695).

Biological Process

Cell population proliferation Source: UniProtKB
Golgi organization Source: UniProtKB
Labyrinthine layer blood vessel development Source: Ensembl
Positive regulation of dendrite morphogenesis Source: UniProtKB
Positive regulation of transcription factor catabolic process Source: Ensembl
Protein ubiquitination Source: UniProtKB
Spongiotrophoblast layer development Source: Ensembl

Cellular Location

Golgi apparatus; Perinuclear region. Colocalizes with CUL7 at the Golgi apparatus in neurons.