Gene Ontology annotation through association of InterPro records with GO terms
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP.
WD40 protein FBW5 promotes ubiquitination of tumor suppressor TSC2 by DDB1-CUL4-ROC1 ligase.
Array MAPPIT: high-throughput interactome analysis in mammalian cells.
The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication.
Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair.
A proteome-scale map of the human interactome network.
A High-Density Map for Navigating the Human Polycomb Complexome.
A reference map of the human binary protein interactome.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
SCF(Fbxw5) targets kinesin-13 proteins to facilitate ciliogenesis.
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SCF(FBXW5) polyubiquitinates kinesin-13 microtubule depolymerases MCAK/KIF2C, KIF2A and KIF2B and targets MCAK for proteasomal degradation predominantly in G2; loss of FBXW5 raises MCAK at basal bodies and impairs ciliogenesis in the subsequent G1/G0, rescued by kinesin-13 knockdown.
Structure of the human signal peptidase complex reveals the determinants for signal peptide cleavage.
The SCF Complex Is Essential to Maintain Genome and Chromosome Stability.
Multimodal cell maps as a foundation for structural and functional genomics.
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
Falcon deep research report for human FBXW5
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FBXW5 is a substrate receptor that uses its WD40 repeats for substrate docking and its F-box for SCF assembly; F-box deletion abolishes SKP1 binding but preserves DDB1-CUL4A bridging, demonstrating SCF-independent CRL4 assembly.
"Importantly, deletion of the F-box can abolish SKP1 binding yet retain the ability to bridge substrates to DDB1–CUL4A, demonstrating **SCF-independent CRL4 assembly**."
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SCF(FBXW5) targets kinesin-13 proteins including MCAK/KIF2C for K48-linked polyubiquitylation and proteasomal degradation in G2, and FBXW5 loss raises MCAK at basal bodies impairing ciliogenesis.
"FBXW5 functions in SCF^FBXW5^ to polyubiquitylate kinesin-13 proteins, including **MCAK/KIF2C**, promoting proteasomal degradation predominantly in **G2**."
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FBXW5 ubiquitinates ASK1 with non-degradative Lys63-linked chains, activating JNK/p38 MAPK stress signaling in NASH, in contrast to its degradative K48 modification of other substrates.
"In hepatocytes, FBXW5 in an **SCF complex** directly interacts with and ubiquitinates **ASK1**, promoting **Lys63-linked polyubiquitination** that enhances ASK1 activation and downstream **JNK/p38 MAPK signaling** in diet-induced NASH models."
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In NSCLC, FBXW5 acts as the substrate receptor of CRL4A (CUL4A-DDB1-FBXW5) to polyubiquitinate and degrade the RhoGAP tumor suppressor DLC1; CUL4A or DDB1 depletion (but not CUL4B) stabilizes DLC1.
"In NSCLC, FBXW5 functions as a substrate receptor within **CRL4A (CUL4A–DDB1–FBXW5)** to promote polyubiquitination and proteasomal degradation of the RhoGAP tumor suppressor **DLC1**."
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SCF(FBXW5) degrades AQP3 in hepatocellular carcinoma, and AQP3 accumulation after FBXW5 loss lowers PDPK1/AKT/mTOR signaling and increases autophagic cell death; the AQP3 ubiquitin acceptor site is K282.
"increased AQP3 after FBXW5 knockdown leads to **lysosomal-dependent reduction of PDPK1**, decreased **AKT phosphorylation**, and reduced downstream **mTOR activity**"