Fbw7 is a member of the F box protein family 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 3 classes: Fbws containing WD40 domains, Fbls containing leucine rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. Fbw7 belongs to the Fbws class; in addition to an F box, this protein contains 7 tandem WD40 repeats. It binds directly to cyclin E and probably targets cyclin E for ubiquitin mediated degradation. Mutations of this gene are detected in ovarian and breast cancer cell lines. Alternative splicing of this gene generates 2 transcript variants diverging at the 5' termini.
Function:
Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably recognizes and binds to phosphorylated target proteins. Involved in the degradation of cyclin-E, MYC, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1.
Subunit:
Component of the SCF(FBXW7) complex consisting of CUL1, RBX1, SKP1 and FBXW7. Interacts with PSEN1, cyclin E, NOTCH1 NICD, NOTCH4 NICD and SKP1. Interacts with MYC (when phosphorylated). Isoform 1 interacts with USP28, leading to counteract ubiquitination of MYC. Isoform 4 interacts (via WD repeats) with SV40 large T antigen (via CPD region). Forms a trimeric complex with NOTCH1 and SGK1.
Subcellular Location:
Isoform 1: Nucleus, nucleoplasm. Isoform 2: Cytoplasm. Isoform 4: Nucleus, nucleolus. Nucleus.
Tissue Specificity:
Isoform 1 is widely expressed. Isoform 4 is expressed in brain.
Post-translational modifications:
Phosphorylated upon DNA damage, probably by ATM or ATR.
Similarity:
Contains 1 F-box domain.
Contains 7 WD repeats.
SWISS:
Q969H0
Gene ID:
55294
Database links:
Entrez Gene: 55294 Human
Entrez Gene: 50754 Mouse
Omim: 606278 Human
SwissProt: Q969H0 Human
SwissProt: Q8VBV4 Mouse
Unigene: 561245 Human
Unigene: 196475 Mouse
|
|