FBXW7

Gene Information

Official Symbol: FBXW7
Official Name: F-box and WD repeat domain containing 7
Aliases and Previous Symbols: N/A
Entrez ID: 55294
UniProt: Q969H0
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: 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 Summary: 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:17434132). Identified substrates include cyclin-E (CCNE1 or CCNE2), JUN, MYC, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1 (PubMed:11565034, PubMed:12354302, PubMed:11585921, PubMed:15103331, PubMed:14739463, PubMed:17558397, PubMed:17873522, PubMed:22608923). 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). {ECO:0000250|UniProtKB:Q8VBV4, ECO:0000269|PubMed:11565034, ECO:0000269|PubMed:11585921, ECO:0000269|PubMed:14739463, ECO:0000269|PubMed:15103331, ECO:0000269|PubMed:17434132, ECO:0000269|PubMed:17558397, ECO:0000269|PubMed:17873522, ECO:0000269|PubMed:22608923, ECO:0000305|PubMed:12354302}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
Ixabepilone 0.004 to 0.005μM on day4 R04 exp184	-2.75
UM0125461 0.74μM R02 exp84	-2.72
Ribavirin 10 to 15μM on day4 R04 exp160	-2.58
Rifampicin 30μM R08 exp430	-2.57
Combretastatin A4 0.002 to 0.003μM day4 R04 exp179	-2.45
L-BMAA 500 to 750μM on day4 R04 exp185	-2.4
Pterostilbene 16μM R02 exp78	-2.4
Ibrutinib 10μM R08 exp442	-2.35
TGF-beta1 44ng/ml R08 exp528	-2.3
Aphidicolin 0.4μM R08 exp440	-2.24
Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307	-2.24
Daidzin 10μM R06 exp280	-2.18
Genistein 15μM R07 exp360	-2.16
Cyclosporin-A 0.8μM R07 exp347	-2.14
Quercetin 20μM R08 exp517	-2.08
GSK2606414 1μM R05 exp236	-2.04
BH1 1μM R04 exp169	-2.02
GSK343 3μM R03 exp124	-2.02
Tubacin 1.6μM R07 exp416	-1.99
Bortezomib 0.05μM R00 exp7	-1.98
Sucrose 20000μM R06 exp298	-1.97
Lead acetate 2000μM R08 exp498 no dilution day6	-1.93
FK-506 30μM R07 exp359	-1.91
3-Bromopyruvate 7μM R04 exp175	-1.89
GSK626616 14μM R08 exp485	-1.89
2-Methoxyestradiol 0.55μM R07 exp310	-1.85
VE-822 0.04μM R06 exp300	-1.85
LLY-284 2.6μM R06 exp291	-1.83
Pyronaridine 1μM R06 exp295	-1.83
Celastrol 0.12μM R05 exp225	-1.81
Sulforaphane 9μM R08 exp525	-1.79
THZ531 0.11μM R07 exp409	-1.79
UMK57 1μM R01 exp59	-1.78
Docetaxel 0.001 to 0.002μM on day4 R04 exp159	-1.77
Dynasore 7μM R08 exp436	-1.77
BI-D1870 3.15μM R02 exp66	-1.76
Palbociclib 1μM R07 exp382	-1.76
CoCl2 18μM R07 exp346	-1.73
HMS-I1 1μM R01 exp46	-1.73
Mdivi-1 15μM R05 exp217	-1.72
MK-1775 0.32μM R02 exp75	-1.72
Pomalidomide 20μM R07 exp391	-1.72
Dynasore 10μM R04 exp180	-1.7
Fas-L 44ng/ml R08 exp482	-1.7
Bleomycin 5μM R08 exp459	1.72
LY2090314 0.003μM R08 exp500 no dilution day6	1.95
Cytochalasin-B 5μM R07 exp349	1.99
LY2090314 0.003μM R08 exp499	2.67

Global Fraction of Cell Lines Where Essential: 1/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	1/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 709
Expression level (log2 read counts): 5.42

Expression Distribution

Gene	Correlation
RPP21	0.442
C14orf80	0.431
KMT2D	0.42
RTCB	0.408
OSGEP	0.403

WD40
F-box
F-box-like

negative regulation of SREBP signaling pathway
positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
negative regulation of triglyceride biosynthetic process
phosphothreonine residue binding
regulation of SREBP signaling pathway
Parkin-FBXW7-Cul1 ubiquitin ligase complex
negative regulation of hepatocyte proliferation
positive regulation of oxidative stress-induced neuron death
negative regulation of osteoclast development
positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
negative regulation of DNA endoreduplication
negative regulation of RNA polymerase II regulatory region sequence-specific DNA binding
ubiquitin-protein transferase activator activity
ubiquitin recycling
regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
negative regulation of triglyceride metabolic process
regulation of DNA endoreduplication
positive regulation of epidermal growth factor-activated receptor activity
negative regulation of bone development
regulation of osteoclast development
regulation of RNA polymerase II regulatory region sequence-specific DNA binding
regulation of hepatocyte proliferation
positive regulation of oxidative stress-induced cell death
regulation of triglyceride biosynthetic process
positive regulation of cellular response to oxidative stress
positive regulation of response to oxidative stress
negative regulation of transcription regulatory region DNA binding
regulation of bone development
negative regulation of DNA-dependent DNA replication
regulation of oxidative stress-induced neuron death
regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
negative regulation of osteoclast differentiation
regulation of epidermal growth factor-activated receptor activity
cyclin binding
positive regulation of epidermal growth factor receptor signaling pathway
positive regulation of protein targeting to mitochondrion
positive regulation of ubiquitin-protein transferase activity
positive regulation of ERBB signaling pathway
positive regulation of signaling receptor activity
negative regulation of animal organ morphogenesis