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 (PubMed:21953459, PubMed:22748924). Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter brings them to the SCF complex for ubiquitination (PubMed:22748924). Mediates ubiquitination and subsequent degradation of CCNE1 and MYC (PubMed:22748924). Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NOTCH2, MCL1, RICTOR and probably PSEN1 (By similarity). Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation (By similarity). SCF(FBXW7) complex mediates the ubiquitination and subsequent degradation of NFE2L1 (PubMed:21953459). Involved in bone homeostasis and negative regulation of osteoclast differentiation (PubMed:29149593). 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 (PubMed:27238018). Also able to promote 'Lys-63'-linked ubiquitination in response to DNA damage (By similarity). 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 (By similarity). Homodimer; homodimerization plays a role in substrate binding and/or ubiquitination and degradation (By similarity). Component of the SCF(FBXW7) complex consisting of CUL1, RBX1, SKP1 and FBXW7 (PubMed:11735228). Interacts (via F-box domain) with SKP1 (PubMed:11735228). Interacts (via F-box domain) with pseudophosphatase STYX; the interaction is direct and prevents FBXW7 interaction with SKP1 (By similarity). Interacts with cyclin-E (CCNE1 or CCNE2) (By similarity). Interacts with PSEN1 (By similarity). Forms a trimeric complex with NOTCH1 and SGK1 (By similarity). Interacts with NOTCH1 intracellular domain/NICD and NOTCH4 intracellular domain/NICD (PubMed:11425854, PubMed:11461910). Interacts with NOTCH2 intracellular domain (N2ICD) (By similarity). Interacts with MYC (when phosphorylated) (By similarity). Interacts with USP28, counteracting ubiquitination of MYC (By similarity). Interacts (when phosphorylated at Thr-208) with PIN1, disrupting FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (By similarity). Interacts with UBE2QL1 (By similarity). Interacts with FAM83D; promotes FBXW7 degradation (By similarity). Interacts with MYCN; FBXW7 competes with AURKA for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (By similarity). Interacts with JUN (By similarity). Found in a complex with JUN and PRR7 (By similarity). Interacts with JUN and PRR7; the interaction inhibits ubiquitination-mediated JUN degradation, promoting its phosphorylation and transcriptional activity (By similarity). Interacts with NFE2L1 (PubMed:21953459). Interacts with NR1D1 (By similarity). Interacts with RICTOR; mediates RICTOR ubiquitination and degradation (By similarity). Localizes to site of double-strand breaks following phosphorylation by ATM. Widely expressed with highest levels in brain, heart and testis. The WD repeats mediate interaction with substrates of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. The F-box domain mediates interaction with SKP1. Phosphorylation at Thr-208 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-208 and subsequent interaction with PIN1 (By similarity). Ubiquitination leads to its proteasomal degradation (PubMed:22748924). Whole body FBW7 knockout is embryonic lethal. Conditional knockout mice in which FBW7 expression is specifically abolished in osteoclasts display severe bone resorption, bone fragility and low bone mass (PubMed:29149593). Conditional knockout in liver reduces the amplitude of the diurnal expression of many core clock genes and the altered expression of a large number of genes controlling liver metabolic pathways (PubMed:27238018).