Tbio FBXW7 F-box/WD repeat-containing protein 7

Protein Summary

Description

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 bring them to the SCF complex for ubiquitination (PubMed:22748924, PubMed:17434132, PubMed:26976582, PubMed:28727686). Identified substrates include cyclin-E (CCNE1 or CCNE2), DISC1, JUN, MYC, NOTCH1 released notch intracellular domain (NICD), 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). SCF(FBXW7) complex mediates the ubiquitination and subsequent degradation of NFE2L1 (By similarity). Involved in bone homeostasis and negative regulation of osteoclast differentiation (PubMed:29149593). 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]

Uniprot Accession IDs

• Q969H0
• B7ZLP9
• Q68DR0
• Q96A16
• Q96LE0
• Q96RI2
• Q9NUX6

Gene Name

• FBXW7

Ensembl ID

• ENST00000263981
• ENSP00000263981
• ENSG00000109670
• ENST00000281708
• ENSP00000281708
• ENST00000296555
• ENSP00000296555
• ENST00000393956
• ENSP00000377528
• ENST00000603548
• ENSP00000474725
• ENST00000603841
• ENSP00000474971

Symbol

• FBW7
• FBX30
• SEL10
• AGO
• CDC4
• FBW6
• FBW7
• hAgo
• FBX30
• FBXW6
• SEL10
• hCdc4
• FBXO30
• SEL-10

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	0.94
kinase perturbation	0.91
transcription factor perturbation	0.88
kinase	0.87

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / F-box/wd Repeat-containing Protein 7

DTO Classes

Protein / Enzyme Modulator / F-box/wd Repeat-containing Protein 7

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 752.99   (req: < 5)

Gene RIFs: 371   (req: <= 3)

Antibodies: 595   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 752.99   (req: >= 5)

Gene RIFs: 371   (req: > 3)

Antibodies: 595   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 46

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0