======= FBXW7 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: FBXW7
  * **<color #00a2e8>Official Name</color>**: F-box and WD repeat domain containing 7
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=55294|55294]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q969H0|Q969H0]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=FBXW7&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20FBXW7|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/606278|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|WD40|
|F-box|
|F-box-like|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|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|
|regulation of triglyceride metabolic process|
|regulation of cell migration involved in sprouting angiogenesis|
|negative regulation of DNA replication|
|negative regulation of Notch signaling pathway|
|regulation of autophagy of mitochondrion|
|regulation of protein targeting to mitochondrion|
|regulation of lipid storage|
|protein destabilization|
|negative regulation of myeloid leukocyte differentiation|
|negative regulation of lipid biosynthetic process|
|sister chromatid cohesion|
|regulation of ubiquitin-protein transferase activity|
|regulation of transcription regulatory region DNA binding|
|regulation of DNA-dependent DNA replication|
|positive regulation of neuron apoptotic process|
|positive regulation of protein tyrosine kinase activity|
|negative regulation of DNA binding|
|positive regulation of intrinsic apoptotic signaling pathway|
|positive regulation of establishment of protein localization to mitochondrion|
|regulation of oxidative stress-induced cell death|
|SCF ubiquitin ligase complex|
|regulation of osteoclast differentiation|
|vasculogenesis|
|regulation of sprouting angiogenesis|
|regulation of establishment of protein localization to mitochondrion|
|regulation of cellular response to oxidative stress|
|negative regulation of myeloid cell differentiation|
|protein binding, bridging|
|ubiquitin binding|
|regulation of protein targeting|
|negative regulation of lipid metabolic process|
|regulation of epidermal growth factor receptor signaling pathway|
|regulation of response to oxidative stress|
|regulation of protein tyrosine kinase activity|
|regulation of blood vessel endothelial cell migration|
|regulation of ERBB signaling pathway|
|positive regulation of neuron death|
|SCF-dependent proteasomal ubiquitin-dependent protein catabolic process|
|positive regulation of ubiquitin-dependent protein catabolic process|
|negative regulation of leukocyte differentiation|
|regulation of Notch signaling pathway|
|positive regulation of proteasomal protein catabolic process|
|regulation of DNA replication|
|regulation of circadian rhythm|
|positive regulation of protein ubiquitination|
|regulation of myeloid leukocyte differentiation|
|positive regulation of mitochondrion organization|
|positive regulation of proteolysis involved in cellular protein catabolic process|
|negative regulation of epithelial cell proliferation|
|Notch signaling pathway|
|regulation of DNA binding|
|lipid homeostasis|
|positive regulation of protein modification by small protein conjugation or removal|
|negative regulation of hemopoiesis|
|regulation of lipid localization|
|positive regulation of cellular protein catabolic process|
|sister chromatid segregation|
|regulation of ubiquitin-dependent protein catabolic process|
|positive regulation of intracellular protein transport|
|regulation of endothelial cell migration|
|regulation of intrinsic apoptotic signaling pathway|
|regulation of cell cycle G1/S phase transition|
|lung development|
|negative regulation of binding|
|respiratory tube development|
|regulation of signaling receptor activity|
|positive regulation of apoptotic signaling pathway|
|protein stabilization|
|regulation of mitochondrion organization|
|regulation of proteasomal protein catabolic process|
|regulation of lipid biosynthetic process|
|positive regulation of peptidyl-tyrosine phosphorylation|
|respiratory system development|
|regulation of protein ubiquitination|
|regulation of neuron apoptotic process|
|positive regulation of intracellular transport|
|positive regulation of ERK1 and ERK2 cascade|
|positive regulation of protein catabolic process|
|regulation of proteolysis involved in cellular protein catabolic process|
|nuclear chromosome segregation|
|regulation of epithelial cell migration|
|regulation of myeloid cell differentiation|
|regulation of protein modification by small protein conjugation or removal|
|regulation of intracellular protein transport|
|regulation of cellular protein catabolic process|
|regulation of peptidyl-tyrosine phosphorylation|
|regulation of animal organ morphogenesis|
|regulation of leukocyte differentiation|
|chromosome segregation|
|rhythmic process|
|regulation of angiogenesis|
|regulation of protein stability|
|regulation of ERK1 and ERK2 cascade|
|ubiquitin protein ligase binding|
|protein polyubiquitination|
|regulation of neuron death|
|regulation of vasculature development|
|proteasome-mediated ubiquitin-dependent protein catabolic process|
|positive regulation of cellular protein localization|
|negative regulation of cell cycle process|
|regulation of autophagy|
|regulation of epithelial cell proliferation|
|negative regulation of cell development|
|proteasomal protein catabolic process|
|regulation of intracellular transport|
|positive regulation of proteolysis|
|post-translational protein modification|
|positive regulation of cellular catabolic process|
|regulation of binding|
|regulation of protein catabolic process|
|regulation of lipid metabolic process|
|regulation of apoptotic signaling pathway|
|blood vessel morphogenesis|
|positive regulation of protein transport|
|positive regulation of catabolic process|
|negative regulation of immune system process|
|regulation of cell cycle phase transition|
|regulation of hemopoiesis|
|positive regulation of establishment of protein localization|
|blood vessel development|
|vasculature development|
|cardiovascular system development|
|ubiquitin-dependent protein catabolic process|
|modification-dependent protein catabolic process|
|positive regulation of protein kinase activity|
|regulation of cellular protein localization|
|positive regulation of MAPK cascade|
|modification-dependent macromolecule catabolic process|
|negative regulation of cell cycle|
|positive regulation of kinase activity|
|proteolysis involved in cellular protein catabolic process|
|cellular protein catabolic process|
|positive regulation of organelle organization|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|tube morphogenesis|
|positive regulation of transferase activity|
|negative regulation of cell population proliferation|
|protein catabolic process|
|protein ubiquitination|
|perinuclear region of cytoplasm|
|positive regulation of cell death|
|viral process|
|regulation of protein transport|
|negative regulation of cell differentiation|
|regulation of proteolysis|
|regulation of cellular response to stress|
|regulation of peptide transport|
|regulation of establishment of protein localization|
|regulation of MAPK cascade|
|regulation of cell cycle process|
|protein modification by small protein conjugation|
|symbiotic process|
|regulation of protein kinase activity|
|interspecies interaction between organisms|
|regulation of cellular catabolic process|
|tube development|
|regulation of cell migration|
|nucleolus|
|circulatory system development|
|regulation of kinase activity|
|cellular homeostasis|
|cellular macromolecule catabolic process|
|regulation of cell motility|
|regulation of cellular localization|
|regulation of cell development|
|negative regulation of developmental process|
|regulation of transferase activity|
|regulation of locomotion|
|Golgi apparatus|
|protein modification by small protein conjugation or removal|
|positive regulation of transport|
|regulation of catabolic process|
|regulation of cellular component movement|
|cell cycle process|
|endoplasmic reticulum|
|positive regulation of protein phosphorylation|
|positive regulation of intracellular signal transduction|
|regulation of protein localization|
|macromolecule catabolic process|
|positive regulation of phosphorylation|
|regulation of anatomical structure morphogenesis|
|organonitrogen compound catabolic process|
|chromosome organization|
|identical protein binding|
|chemical homeostasis|
|positive regulation of phosphorus metabolic process|
|positive regulation of phosphate metabolic process|
|negative regulation of molecular function|
|regulation of cell cycle|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|positive regulation of protein modification process|
|mitochondrion|
|negative regulation of signal transduction|
|proteolysis|
|regulation of organelle organization|
|cell cycle|
|negative regulation of cell communication|
|negative regulation of signaling|
|negative regulation of cellular macromolecule biosynthetic process|
|positive regulation of catalytic activity|
|regulation of protein phosphorylation|
|negative regulation of macromolecule biosynthetic process|
|regulation of response to stress|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|regulation of programmed cell death|
|regulation of phosphorylation|
|positive regulation of cellular protein metabolic process|
|regulation of cell population proliferation|
|negative regulation of response to stimulus|
|homeostatic process|
|regulation of immune system process|
|positive regulation of signal transduction|
|regulation of cell death|
|positive regulation of protein metabolic process|
|negative regulation of gene expression|
|organic substance catabolic process|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|cellular catabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|regulation of transport|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

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

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:r:rpp21|RPP21]]|0.442|
|[[:human genes:c:c14orf80|C14orf80]]|0.431|
|[[:human genes:k:kmt2d|KMT2D]]|0.42|
|[[:human genes:r:rtcb|RTCB]]|0.408|
|[[:human genes:o:osgep|OSGEP]]|0.403|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
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|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 709
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.42 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='FBXW7 Expression in NALM6 Cells: 5.42'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>