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FBXW7

Engineered Antibody
This gene encodes a member of the F-box protein family which is characterized by an approximately 40 amino acid motif, the F-box. The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which function in phosphorylation-dependent ubiquitination. The F-box proteins are divided into 3 classes: Fbws containing WD-40 domains, Fbls containing leucine-rich repeats, and Fbxs containing either different protein-protein interaction modules or no recognizable motifs. The protein encoded by this gene was previously referred to as FBX30, and belongs to the Fbws class; in addition to an F-box, this protein contains 7 tandem WD40 repeats. This protein binds directly to cyclin E and probably targets cyclin E for ubiquitin-mediated degradation. Mutations in this gene are detected in ovarian and breast cancer cell lines, implicating the gene's potential role in the pathogenesis of human cancers. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2012]
FBXW7
Protein class

Cancer-related genes

Predicted location

Intracellular

Single cell type specificity

Cell type enhanced (Excitatory neurons, Basal keratinocytes)

Immune cell specificity

Immune cell enhanced (basophil)

Cell line specificity

Cell line enhanced (U-266/70)

Interaction

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, counteracting 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, disrupting 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, counteracting ubiquitination of MYC (PubMed:25775507). Interacts with NR1D1 (PubMed:27238018). Interacts with RICTOR; mediates RICTOR ubiquitination and degradation (PubMed:25897075). (Microbial infection) Interacts (via WD repeats) with SV40 large T antigen (via CPD region).

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