FEATURES

DESCRIPTION

Also known as FBXW7_HUMAN, FBXW7, FBW7, FBX30, SEL10. 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:22748924, PubMed:17434132, PubMed:26976582, PubMed:28727686). Recognizes and binds phosphorylated sites/phosphodegrons within target proteins and thereafter bring them to the SCF complex for ubiquitination (PubMed:22748924, PubMed:26774286, PubMed:17434132, PubMed:26976582, PubMed:28727686). Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), NFE2L1, NOTCH2, MCL1, and probably PSEN1 (PubMed:11565034, PubMed:12354302, PubMed:11585921, PubMed:15103331, PubMed:14739463, PubMed:17558397, PubMed:17873522, PubMed:22608923, PubMed:22748924, PubMed:29149593, PubMed:25775507, PubMed:28007894, PubMed:26976582, PubMed:28727686). Acts as a negative regulator of JNK signaling by binding to phosphorylated JUN and promoting its ubiquitination and subsequent degradation (PubMed:14739463). 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 (PubMed:26774286). 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 (PubMed:26774286). Homodimer; homodimerization plays a role in substrate binding and/or ubiquitination and degradation (PubMed:22608923, PubMed:17434132, PubMed:28007894). Component of the SCF(FBXW7) complex consisting of CUL1, RBX1, SKP1 and FBXW7 (PubMed:11565034, PubMed:15103331, PubMed:22748924, PubMed:26774286, PubMed:28007894, PubMed:26976582, PubMed:28727686). Interacts (via F-box domain) with SKP1 (PubMed:11585921, PubMed:17434132, PubMed:28007894, PubMed:26976582, PubMed:28727686). Interacts (via F-box domain) with pseudophosphatase STYX; the interaction is direct and prevents FBXW7 interaction with SKP1 (PubMed:28007894). Interacts with cyclin-E (CCNE1 or CCNE2) (PubMed:11565034, PubMed:17434132). Interacts with PSEN1 (PubMed:12354302). Forms a trimeric complex with NOTCH1 and SGK1 (PubMed:21147854). Interacts with NOTCH1 intracellular domain/NICD and NOTCH4 intracellular domain/NICD (PubMed:11585921). Interacts with NOTCH2 intracellular domain (N2ICD) (PubMed:29149593). Interacts with MYC (when phosphorylated) (PubMed:17873522, PubMed:25775507, PubMed:28007894). Interacts with USP28, leading to counteract ubiquitination of MYC (PubMed:17873522). Interacts with JUN (PubMed:14739463, PubMed:22608923). Found in a complex with JUN and PRR7 (PubMed:27458189). Interacts with JUN and PRR7; the interaction inhibits ubiquitination-mediated JUN degradation promoting its phosphorylation and transcriptional activity (PubMed:27458189). Interacts (when phosphorylated at Thr-205) with PIN1, leading to disrupt FBXW7 dimerization and promoting FBXW7 autoubiquitination and degradation (PubMed:22608923). Interacts with UBE2QL1 (PubMed:24000165). Interacts with FAM83D; promotes FBXW7 degradation (PubMed:24344117). Interacts with MYCN; FBXW7 competes with AURKA for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (PubMed:27837025). Interacts with STOML1 (PubMed:23082202). Interacts with NFE2L1 (By similarity). Interacts with USP36, leading to counteract ubiquitination of MYC (PubMed:25775507). Interacts with NR1D1 (PubMed:27238018).

EXTERNAL LINKS

FBXW7

F-box/WD repeat-containing protein 7

FBXW7

Molecular Synopsis