FBXW7
FBXW7 (F-box and WD repeat domain containing 7, also known as SEL-10, FBW7, CDC4, AGO and FBX30) is the substrate recognition component of an SCF E3 ubiquitin-protein ligase complex. It targets phosphorylated proteins for ubiquitination and proteasomal degradation. Browse Assay Genie's current range of FBXW7 research reagents below, or read on for the biology behind the target.
FBXW7 acts as the substrate recognition component of an SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. It recognises and binds phosphorylated sites, known as phosphodegrons, within target proteins and brings them to the SCF complex for ubiquitination and subsequent proteasomal degradation. Identified substrates include cyclin E (CCNE1 and CCNE2), DISC1, JUN, MYC, the NOTCH1 intracellular domain, NFE2L1, NOTCH2, MCL1, MLST8 and RICTOR, and probably PSEN1.
Through these substrates the protein takes part in several processes. It is a negative regulator of JNK signalling, binding phosphorylated JUN and promoting its degradation. It is involved in bone homeostasis and the negative regulation of osteoclast differentiation. It also shapes the amplitude of cyclic expression of hepatic core clock genes, and of genes in lipid and glucose metabolism, by degrading their transcriptional repressor NR1D1, a step that requires CDK1-dependent phosphorylation of NR1D1. In response to DNA damage, SCF(FBXW7) can promote 'Lys-63'-linked ubiquitination. After phosphorylation by ATM it localises to double-strand breaks and ubiquitinates phosphorylated XRCC4, enhancing non-homologous end joining.
The FBXW7 gene encodes a member of the F-box protein family, defined by an F-box motif of about 40 amino acids. F-box proteins fall into three classes, and FBXW7 belongs to the Fbws class, containing an F-box plus 7 tandem WD40 repeats. It was previously called FBX30, and its HGNC name records the archipelago homolog from Drosophila. Mutations have been detected in ovarian and breast cancer cell lines, implicating the gene in the pathogenesis of human cancers. Multiple transcript variants encoding different isoforms have been described. UniProt records localisation to the nucleoplasm, nucleolus, chromosome and cytoplasm.
Mutations in FBXW7 are detected in ovarian and breast cancer cell lines, implicating the gene in the pathogenesis of human cancers.
FBXW7 is a model phosphodegron-reading substrate receptor of SCF complexes, linking phosphorylation to proteasomal degradation of targets such as cyclin E and MYC.
After ATM phosphorylation, SCF(FBXW7) localises to double-strand breaks and ubiquitinates XRCC4, enhancing non-homologous end joining.
FBXW7 degrades NR1D1 to regulate the amplitude of hepatic core clock gene expression and genes involved in lipid and glucose metabolism.
FBXW7 is the substrate recognition subunit of an SCF E3 ubiquitin ligase. It binds phosphorylated degrons in target proteins, including cyclin E, MYC, JUN, NOTCH1 and MCL1, and delivers them to the complex for ubiquitination and proteasomal degradation. It also contributes to double-strand break repair.
Aliases include SEL-10, SEL10, FBW7, FBX30, CDC4, AGO, FBXW6 and FLJ11071. Earlier names were F-box and WD-40 domain protein 7 (archipelago homolog, Drosophila) and F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase. Multiple transcript variants encode different isoforms.
Yes. Mouse and rat both have an ortholog named Fbxw7, so the protein can be studied in rodent models. FBXW7 mutations are reported in ovarian and breast cancer cell lines. Check the datasheet of any product for its validated reactivity.
Other SCF complex components, FBXW7 substrates and DNA damage and cell cycle regulators with products at Assay Genie.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q969H0; product specifications from Assay Genie datasheets.