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 . Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter brings them to the SCF complex for ubiquitination . Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, RICTOR, and probably PSEN1 . Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation . Involved in bone homeostasis and negative regulation of osteoclast differentiation . Regulates the amplitude of the cyclic expression of hepatic core clock genes and genes involved in lipid and glucose metabolism via ubiquitination and proteasomal degradation of their transcriptional repressor NR1D1; CDK1-dependent phosphorylation of NR1D1 is necessary for SCF(FBXW7)-mediated ubiquitination . Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage . The SCF(FBXW7) complex facilitates double-strand break repair following phosphorylation by ATM: phosphorylation promotes localization to sites of double-strand breaks and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4, enhancing DNA non-homologous end joining .
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Cellular Localization:
[Isoform 1]: Nucleus, nucleoplasm . Chromosome . Localizes to site of double-strand breaks following phosphorylation by ATM. .; [Isoform 2]: Cytoplasm .; [Isoform 3]: Nucleus, nucleolus .
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Tissue Expression:
[Isoform 1]: Widely expressed. ; [Isoform 3]: Expressed in brain.