Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniPathway vocabulary mapping
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Electronic Gene Ontology annotations created by ARBA machine learning models
SEL-10 interacts with presenilin 1, facilitates its ubiquitination, and alters A-beta peptide production.
Parkin is a component of an SCF-like ubiquitin ligase complex and protects postmitotic neurons from kainate excitotoxicity.
M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP.
Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7.
The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation.
Cornelia de Lange Syndrome and the link between chromosomal function, DNA repair and developmental gene regulation.
SNIP1 is a candidate modifier of the transcriptional activity of c-Myc on E box-dependent target genes.
Large-scale identification of c-MYC-associated proteins using a combined TAP/MudPIT approach.
Structure of a Fbw7-Skp1-cyclin E complex: multisite-phosphorylated substrate recognition by SCF ubiquitin ligases.
The ubiquitin-specific protease USP28 is required for MYC stability.
Fbw7 and Usp28 regulate myc protein stability in response to DNA damage.
Kaposi's sarcoma herpesvirus-encoded latency-associated nuclear antigen stabilizes intracellular activated Notch by targeting the Sel10 protein.
Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma.
F-box protein FBXO31 mediates cyclin D1 degradation to induce G1 arrest after DNA damage.
SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation.
Notch signaling contributes to proliferation and tumor formation of human T-cell leukemia virus type 1-associated adult T-cell leukemia.
Fbxw7 regulates lipid metabolism and cell fate decisions in the mouse liver.
Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics.
PI3K-dependent phosphorylation of Fbw7 modulates substrate degradation and activity.
ERK1 and ERK2 regulate embryonic stem cell self-renewal through phosphorylation of Klf4.
Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition.
NOTCH1 nuclear interactome reveals key regulators of its transcriptional activity and oncogenic function.
FBXW7-mediated degradation of CCDC6 is impaired by ATM during DNA damage response in lung cancer cells.
The ubiquitin ligase FBXW7 modulates leukemia-initiating cell activity by regulating MYC stability.
An SREBP-responsive microRNA operon contributes to a regulatory loop for intracellular lipid homeostasis.
Parkin-dependent degradation of the F-box protein Fbw7beta promotes neuronal survival in response to oxidative stress by stabilizing Mcl-1.
UBE2QL1 is disrupted by a constitutional translocation associated with renal tumor predisposition and is a novel candidate renal tumor suppressor gene.
FAM83D promotes cell proliferation and motility by downregulating tumor suppressor gene FBXW7.
Charting the molecular links between driver and susceptibility genes in colorectal cancer.
Genome-wide RNAi screen identifies the Parkinson disease GWAS risk locus SREBF1 as a regulator of mitophagy.
Cyclin C is a haploinsufficient tumour suppressor.
Rictor Undergoes Glycogen Synthase Kinase 3 (GSK3)-dependent, FBXW7-mediated Ubiquitination and Proteasomal Degradation.
FBXW7 Facilitates Nonhomologous End-Joining via K63-Linked Polyubiquitylation of XRCC4.
Systematic interactome mapping of acute lymphoblastic leukemia cancer gene products reveals EXT-1 tumor suppressor as a Notch1 and FBWX7 common interactor.
Circadian Amplitude Regulation via FBXW7-Targeted REV-ERBalpha Degradation.
Synaptonuclear messenger PRR7 inhibits c-Jun ubiquitination and regulates NMDA-mediated excitotoxicity.
Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors.
Phenotypic and Interaction Profiling of the Human Phosphatases Identifies Diverse Mitotic Regulators.
The pseudophosphatase STYX targets the F-box of FBXW7 and inhibits SCFFBXW7 function.
Architecture of the human interactome defines protein communities and disease networks.
NOTCH2 Hajdu-Cheney Mutations Escape SCF(FBW7)-Dependent Proteolysis to Promote Osteoporosis.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
The SCF Complex Is Essential to Maintain Genome and Chromosome Stability.
A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.
CDK1/FBXW7 facilitates degradation and ubiquitination of MLST8 to inhibit progression of renal cell carcinoma.
Human transcription factor protein interaction networks.
Germline variants in tumor suppressor FBXW7 lead to impaired ubiquitination and a neurodevelopmental syndrome.
Systematic discovery of mutation-directed neo-protein-protein interactions in cancer.
The SCF-FBXW7 E3 ubiquitin ligase triggers degradation of histone 3 lysine 4 methyltransferase complex component WDR5 to prevent mitotic slippage.
Multimodal cell maps as a foundation for structural and functional genomics.
TTC36 promotes proliferation and drug resistance in hepatocellular carcinoma cells by inhibiting c-Myc degradation.
p-NICD1 PEST domain mutants do not bind FBXW7
FBXW7 WD mutants do not bind NICD1
AcM-UBE2M transfers NEDD8 to CRL1 E3 ubiquitin ligase complex
NEDD8:AcM-UBE2M binds CRL1 E3 ubiquitin ligase complex
CAND1 binds cytosolic CRL E3 ubiquitin ligases
COMMDs displace CAND1 from cytosolic CRL E3 ubiquitin ligase complexes
COP9 signalosome deneddylates cytosolic CRL E3 ubiquitin ligase complexes
MyrG-DCUN1D3 binds CRL1 E3 ubiquitin ligase complex
Transfer of Ub from E2 to substrate and release of E2
Release of E3 from polyubiquitinated substrate
Polyubiquitination of substrate
Interaction of E3 with substrate and E2-Ub complex
FBXW7 binds phosphorylated NICD1
FBXW7 mediates ubiquitination of phosphorylated NICD1
FBXW7 promotes ubiquitination of mouse p-NICD4
Falcon deep research report for human FBXW7
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FBXW7 is the substrate-recognition subunit of an SCF (SKP1-CUL1-RBX1) Cullin-RING E3 ubiquitin ligase that recognizes phosphorylated Cdc4 phosphodegrons (CPD) via its WD40 beta-propeller, a high-affinity consensus being pThr-Pro-Pro-X-pSer; WD40 hotspot arginines R465/R479/R505 are required for phosphodegron recognition and are recurrently mutated in cancer.
"FBXW7 recognizes phosphorylated Cdc4 phosphodegrons (CPDs) using its WD40 domain; a high-affinity consensus described in recent review is pThr-Pro-Pro-X-pSer, though lower-affinity/noncanonical CPDs also exist. Substrate phosphorylation is often created or reinforced by GSK3, and can involve kinase cascades including CDK1/2 and ERK/MAPK; hotspot arginines such as R465/R479/R505 are critical for phosphodegron recognition and are recurrently mutated in cancer"
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EGFR is a direct FBXW7 substrate; CPD-like motifs in the EGFR cytoplasmic tail are recognized, and FBXW7 hotspot mutation stabilizes EGFR and dramatically reduces EGF dependency, implying that FBXW7 normally restrains (rather than activates) EGFR signaling by promoting EGFR turnover.
"A 2024 primary study identified **EGFR** as a **direct FBXW7 substrate** in human colon organoids, mapping **CPD-like motifs** in the EGFR cytoplasmic tail. Introducing FBXW7 hotspot mutations increased EGFR stability and caused an approximately **10,000-fold reduction in EGF dependency** for organoid growth, functionally linking FBXW7-mediated EGFR turnover to growth-factor addiction."
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The Wnt effectors LEF1 and TCF7L2 are FBXW7-interacting substrates whose binding depends on the WD40 substrate-binding surface, linking FBXW7 loss to altered Wnt transcriptional output.
"A 2023 mechanistic endometrial cancer study validated **LEF1** and **TCF7L2** as novel FBXW7-interacting substrates. Co-immunoprecipitation showed interaction that was disrupted by an FBXW7 WD40 "hotspot" substrate-binding mutant"
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The cytoplasmic isoform FBW7beta binds endogenous PINK1 in the cytosol and promotes its K48-linked polyubiquitination and proteasomal degradation in an SCF/cullin-1-dependent manner, linking FBXW7 to mitochondrial quality control.
"A 2024 JBC study reports that the cytoplasmic isoform **FBW7β** binds endogenous **PINK1** (interaction detected by co-IP and proximity ligation), primarily in the **cytosol**, and promotes **K48-linked polyubiquitination** and **proteasome-dependent degradation** of PINK1."
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FBXW7 substrate selection is not governed solely by perfect CPD matches; low-affinity and noncanonical degrons can be biologically decisive, and hotspot WD40 mutations differentially disrupt subsets of substrates, helping explain variant-specific cancer phenotypes.
"substrate selection is not governed solely by "perfect" CPD matches; **low-affinity substrates and alternative binding modes** can be decisive, and **hotspot WD40 mutations** may differentially disrupt subsets of substrates—helping explain cancer-specific phenotypes and inconsistent clinical associations."