Browse FBXW7

Summary
SymbolFBXW7
NameF-box and WD repeat domain containing 7, E3 ubiquitin protein ligase
Aliases AGO; FLJ11071; SEL-10; SEL10; FBW7; CDC4; archipelago homolog (Drosophila); F-box and WD-40 domain protein 7 ......
Chromosomal Location4q31.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Isoform 1: Nucleus, nucleoplasm ; SUBCELLULAR LOCATION: Isoform 2: Cytoplasm ; SUBCELLULAR LOCATION: Isoform 3: Nucleus, nucleolus
Domain PF12937 F-box-like
PF00400 WD domain
Function

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), NOTCH2, and probably PSEN1 (PubMed:11565034, PubMed:12354302, PubMed:11585921, PubMed:15103331, PubMed:14739463, PubMed:17558397, PubMed:17873522, PubMed:22608923, PubMed:29149593, PubMed:25775507). 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).

> Gene Ontology
 
Biological Process GO:0000209 protein polyubiquitination
GO:0000422 mitophagy
GO:0000819 sister chromatid segregation
GO:0001889 liver development
GO:0006260 DNA replication
GO:0006261 DNA-dependent DNA replication
GO:0006275 regulation of DNA replication
GO:0006626 protein targeting to mitochondrion
GO:0006638 neutral lipid metabolic process
GO:0006639 acylglycerol metabolic process
GO:0006641 triglyceride metabolic process
GO:0006839 mitochondrial transport
GO:0006914 autophagy
GO:0006979 response to oxidative stress
GO:0006984 ER-nucleus signaling pathway
GO:0006991 response to sterol depletion
GO:0007059 chromosome segregation
GO:0007062 sister chromatid cohesion
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0007176 regulation of epidermal growth factor-activated receptor activity
GO:0007219 Notch signaling pathway
GO:0008156 negative regulation of DNA replication
GO:0008593 regulation of Notch signaling pathway
GO:0008631 intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0009894 regulation of catabolic process
GO:0009896 positive regulation of catabolic process
GO:0010469 regulation of receptor activity
GO:0010498 proteasomal protein catabolic process
GO:0010506 regulation of autophagy
GO:0010821 regulation of mitochondrion organization
GO:0010822 positive regulation of mitochondrion organization
GO:0010866 regulation of triglyceride biosynthetic process
GO:0010868 negative regulation of triglyceride biosynthetic process
GO:0010876 lipid localization
GO:0010883 regulation of lipid storage
GO:0010948 negative regulation of cell cycle process
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0018212 peptidyl-tyrosine modification
GO:0019216 regulation of lipid metabolic process
GO:0019432 triglyceride biosynthetic process
GO:0019915 lipid storage
GO:0022612 gland morphogenesis
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
GO:0031329 regulation of cellular catabolic process
GO:0031331 positive regulation of cellular catabolic process
GO:0031396 regulation of protein ubiquitination
GO:0031398 positive regulation of protein ubiquitination
GO:0031647 regulation of protein stability
GO:0032386 regulation of intracellular transport
GO:0032388 positive regulation of intracellular transport
GO:0032875 regulation of DNA endoreduplication
GO:0032876 negative regulation of DNA endoreduplication
GO:0032933 SREBP signaling pathway
GO:0033157 regulation of intracellular protein transport
GO:0033674 positive regulation of kinase activity
GO:0034599 cellular response to oxidative stress
GO:0036473 cell death in response to oxidative stress
GO:0036475 neuron death in response to oxidative stress
GO:0036480 neuron intrinsic apoptotic signaling pathway in response to oxidative stress
GO:0038127 ERBB signaling pathway
GO:0042023 DNA endoreduplication
GO:0042058 regulation of epidermal growth factor receptor signaling pathway
GO:0042176 regulation of protein catabolic process
GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
GO:0043410 positive regulation of MAPK cascade
GO:0043523 regulation of neuron apoptotic process
GO:0043525 positive regulation of neuron apoptotic process
GO:0044770 cell cycle phase transition
GO:0044786 cell cycle DNA replication
GO:0044843 cell cycle G1/S phase transition
GO:0045017 glycerolipid biosynthetic process
GO:0045732 positive regulation of protein catabolic process
GO:0045741 positive regulation of epidermal growth factor-activated receptor activity
GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway
GO:0045746 negative regulation of Notch signaling pathway
GO:0045786 negative regulation of cell cycle
GO:0045833 negative regulation of lipid metabolic process
GO:0045860 positive regulation of protein kinase activity
GO:0045862 positive regulation of proteolysis
GO:0046460 neutral lipid biosynthetic process
GO:0046463 acylglycerol biosynthetic process
GO:0046486 glycerolipid metabolic process
GO:0046890 regulation of lipid biosynthetic process
GO:0048732 gland development
GO:0050673 epithelial cell proliferation
GO:0050678 regulation of epithelial cell proliferation
GO:0050680 negative regulation of epithelial cell proliferation
GO:0050730 regulation of peptidyl-tyrosine phosphorylation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0050821 protein stabilization
GO:0051052 regulation of DNA metabolic process
GO:0051053 negative regulation of DNA metabolic process
GO:0051055 negative regulation of lipid biosynthetic process
GO:0051222 positive regulation of protein transport
GO:0051235 maintenance of location
GO:0051402 neuron apoptotic process
GO:0051438 regulation of ubiquitin-protein transferase activity
GO:0051443 positive regulation of ubiquitin-protein transferase activity
GO:0055088 lipid homeostasis
GO:0061008 hepaticobiliary system development
GO:0061097 regulation of protein tyrosine kinase activity
GO:0061098 positive regulation of protein tyrosine kinase activity
GO:0061136 regulation of proteasomal protein catabolic process
GO:0061726 mitochondrion disassembly
GO:0070371 ERK1 and ERK2 cascade
GO:0070372 regulation of ERK1 and ERK2 cascade
GO:0070374 positive regulation of ERK1 and ERK2 cascade
GO:0070585 protein localization to mitochondrion
GO:0070997 neuron death
GO:0071501 cellular response to sterol depletion
GO:0072574 hepatocyte proliferation
GO:0072575 epithelial cell proliferation involved in liver morphogenesis
GO:0072576 liver morphogenesis
GO:0072655 establishment of protein localization to mitochondrion
GO:0090207 regulation of triglyceride metabolic process
GO:0090209 negative regulation of triglyceride metabolic process
GO:0090316 positive regulation of intracellular protein transport
GO:0090329 regulation of DNA-dependent DNA replication
GO:0097193 intrinsic apoptotic signaling pathway
GO:0098813 nuclear chromosome segregation
GO:1900407 regulation of cellular response to oxidative stress
GO:1900409 positive regulation of cellular response to oxidative stress
GO:1901184 regulation of ERBB signaling pathway
GO:1901186 positive regulation of ERBB signaling pathway
GO:1901214 regulation of neuron death
GO:1901216 positive regulation of neuron death
GO:1901800 positive regulation of proteasomal protein catabolic process
GO:1901987 regulation of cell cycle phase transition
GO:1902175 regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO:1902177 positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
GO:1902806 regulation of cell cycle G1/S phase transition
GO:1902882 regulation of response to oxidative stress
GO:1902884 positive regulation of response to oxidative stress
GO:1903008 organelle disassembly
GO:1903050 regulation of proteolysis involved in cellular protein catabolic process
GO:1903052 positive regulation of proteolysis involved in cellular protein catabolic process
GO:1903146 regulation of mitophagy
GO:1903201 regulation of oxidative stress-induced cell death
GO:1903203 regulation of oxidative stress-induced neuron death
GO:1903209 positive regulation of oxidative stress-induced cell death
GO:1903214 regulation of protein targeting to mitochondrion
GO:1903223 positive regulation of oxidative stress-induced neuron death
GO:1903320 regulation of protein modification by small protein conjugation or removal
GO:1903322 positive regulation of protein modification by small protein conjugation or removal
GO:1903362 regulation of cellular protein catabolic process
GO:1903364 positive regulation of cellular protein catabolic process
GO:1903376 regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
GO:1903378 positive regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway
GO:1903533 regulation of protein targeting
GO:1903747 regulation of establishment of protein localization to mitochondrion
GO:1903749 positive regulation of establishment of protein localization to mitochondrion
GO:1903829 positive regulation of cellular protein localization
GO:1903955 positive regulation of protein targeting to mitochondrion
GO:1904951 positive regulation of establishment of protein localization
GO:2000027 regulation of organ morphogenesis
GO:2000058 regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2000060 positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
GO:2000104 negative regulation of DNA-dependent DNA replication
GO:2000273 positive regulation of receptor activity
GO:2000345 regulation of hepatocyte proliferation
GO:2000346 negative regulation of hepatocyte proliferation
GO:2000638 regulation of SREBP signaling pathway
GO:2000639 negative regulation of SREBP signaling pathway
GO:2001233 regulation of apoptotic signaling pathway
GO:2001235 positive regulation of apoptotic signaling pathway
GO:2001242 regulation of intrinsic apoptotic signaling pathway
GO:2001244 positive regulation of intrinsic apoptotic signaling pathway
Molecular Function GO:0004842 ubiquitin-protein transferase activity
GO:0019787 ubiquitin-like protein transferase activity
GO:0030332 cyclin binding
GO:0030674 protein binding, bridging
GO:0031625 ubiquitin protein ligase binding
GO:0044389 ubiquitin-like protein ligase binding
GO:0045309 protein phosphorylated amino acid binding
GO:0050816 phosphothreonine binding
GO:0051219 phosphoprotein binding
GO:0055103 ligase regulator activity
GO:0055106 ubiquitin-protein transferase regulator activity
GO:0060090 binding, bridging
GO:0097027 ubiquitin-protein transferase activator activity
Cellular Component GO:0000151 ubiquitin ligase complex
GO:0019005 SCF ubiquitin ligase complex
GO:0031461 cullin-RING ubiquitin ligase complex
GO:1990452 Parkin-FBXW7-Cul1 ubiquitin ligase complex
> KEGG and Reactome Pathway
 
KEGG hsa04120 Ubiquitin mediated proteolysis
Reactome R-HSA-1280218: Adaptive Immune System
R-HSA-983168: Antigen processing
R-HSA-390471: Association of TriC/CCT with target proteins during biosynthesis
R-HSA-390466: Chaperonin-mediated protein folding
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-2894862: Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-2644606: Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-2644605: FBXW7 Mutants and NOTCH1 in Cancer
R-HSA-168256: Immune System
R-HSA-2644607: Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling
R-HSA-392499: Metabolism of proteins
R-HSA-2122947: NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-391251: Protein folding
R-HSA-162582: Signal Transduction
R-HSA-157118: Signaling by NOTCH
R-HSA-1980143: Signaling by NOTCH1
R-HSA-2894858: Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-2644602: Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2644603: Signaling by NOTCH1 in Cancer
Summary
SymbolFBXW7
NameF-box and WD repeat domain containing 7, E3 ubiquitin protein ligase
Aliases AGO; FLJ11071; SEL-10; SEL10; FBW7; CDC4; archipelago homolog (Drosophila); F-box and WD-40 domain protein 7 ......
Chromosomal Location4q31.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between FBXW7 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between FBXW7 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
26523864Ovarian CarcinomaInhibit immunity (T cell function)EZH2 activated the Notch pathway by suppressing Notch repressors Numb and Fbxw7 via trimethylation of histone H3 at Lys27 and, consequently, stimulated T cell polyfunctional cytokine expression and promoted their survival via Bcl-2 signaling.
Summary
SymbolFBXW7
NameF-box and WD repeat domain containing 7, E3 ubiquitin protein ligase
Aliases AGO; FLJ11071; SEL-10; SEL10; FBW7; CDC4; archipelago homolog (Drosophila); F-box and WD-40 domain protein 7 ......
Chromosomal Location4q31.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of FBXW7 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NSNA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NSNA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 NA/NSNA/NS
28723893CRISPR-Cas9 melanomaB16GVAX NA/NSNA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NSNA/NS
24476824shRNAmelanomaB16Primary screen NA/NSNA/NS
24476824shRNAmelanomaB16Secondary screen NA/NSNA/NS
Summary
SymbolFBXW7
NameF-box and WD repeat domain containing 7, E3 ubiquitin protein ligase
Aliases AGO; FLJ11071; SEL-10; SEL10; FBW7; CDC4; archipelago homolog (Drosophila); F-box and WD-40 domain protein 7 ......
Chromosomal Location4q31.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of FBXW7 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)14120.1110.638
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.1890.883
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)870.0590.947
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 916-0.1010.73
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590.1380.947
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47-0.4050.876
729033130MelanomaallAnti-PD-1 (nivolumab) 2623-0.0160.956
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 15110.0540.967
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 1112-0.0990.945
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.0220.98
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.6670.573
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.0360.576
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of FBXW7 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14170001
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 4140001
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277314.85.59.30.206
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275914.86.880.252
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21170001
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)860001
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 38272.602.61
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 16146.206.21
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolFBXW7
NameF-box and WD repeat domain containing 7, E3 ubiquitin protein ligase
Aliases AGO; FLJ11071; SEL-10; SEL10; FBW7; CDC4; archipelago homolog (Drosophila); F-box and WD-40 domain protein 7 ......
Chromosomal Location4q31.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of FBXW7. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolFBXW7
NameF-box and WD repeat domain containing 7, E3 ubiquitin protein ligase
Aliases AGO; FLJ11071; SEL-10; SEL10; FBW7; CDC4; archipelago homolog (Drosophila); F-box and WD-40 domain protein 7 ......
Chromosomal Location4q31.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of FBXW7. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by FBXW7.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolFBXW7
NameF-box and WD repeat domain containing 7, E3 ubiquitin protein ligase
Aliases AGO; FLJ11071; SEL-10; SEL10; FBW7; CDC4; archipelago homolog (Drosophila); F-box and WD-40 domain protein 7 ......
Chromosomal Location4q31.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of FBXW7. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolFBXW7
NameF-box and WD repeat domain containing 7, E3 ubiquitin protein ligase
Aliases AGO; FLJ11071; SEL-10; SEL10; FBW7; CDC4; archipelago homolog (Drosophila); F-box and WD-40 domain protein 7 ......
Chromosomal Location4q31.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of FBXW7 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolFBXW7
NameF-box and WD repeat domain containing 7, E3 ubiquitin protein ligase
Aliases AGO; FLJ11071; SEL-10; SEL10; FBW7; CDC4; archipelago homolog (Drosophila); F-box and WD-40 domain protein 7 ......
Chromosomal Location4q31.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between FBXW7 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolFBXW7
NameF-box and WD repeat domain containing 7, E3 ubiquitin protein ligase
Aliases AGO; FLJ11071; SEL-10; SEL10; FBW7; CDC4; archipelago homolog (Drosophila); F-box and WD-40 domain protein 7 ......
Chromosomal Location4q31.23
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting FBXW7 collected from DrugBank database.
> Drugs from DrugBank database
 

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