| Post Translational Modifications | Phosphorylation at Thr-205 promotes interaction with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation. Phosphorylated by ATM at Ser-26 in response to DNA damage, promoting recruitment to DNA damage sites and 'Lys-63'-linked ubiquitination of phosphorylated XRCC4. Ubiquitinated: autoubiquitinates following phosphorylation at Thr-205 and subsequent interaction with PIN1. Ubiquitination leads to its proteasomal degradation. |
| 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. 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, MLST8, 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. |
| Protein Name | F-Box/Wd Repeat-Containing Protein 7Archipelago HomologHagoF-Box And Wd-40 Domain-Containing Protein 7F-Box Protein Fbx30Sel-10Hcdc4 |
| Database Links | Reactome: R-HSA-2122947Reactome: R-HSA-2644606Reactome: R-HSA-2644607Reactome: R-HSA-2894862Reactome: R-HSA-390471Reactome: R-HSA-8951664Reactome: R-HSA-9604323Reactome: R-HSA-983168 |
| Cellular Localisation | Isoform 1: NucleusNucleoplasmChromosomeLocalizes To Site Of Double-Strand Breaks Following Phosphorylation By AtmIsoform 2: CytoplasmIsoform 3: NucleusNucleolus |
| Alternative Protein Names | F-Box/Wd Repeat-Containing Protein 7 proteinArchipelago Homolog proteinHago proteinF-Box And Wd-40 Domain-Containing Protein 7 proteinF-Box Protein Fbx30 proteinSel-10 proteinHcdc4 proteinFBXW7 proteinFBW7 proteinFBX30 proteinSEL10 protein |
Information sourced from Uniprot.org
