Annotation inferences using phylogenetic trees
A novel human gene encoding an F-box/WD40 containing protein maps in the SHFM3 critical region on 10q24.
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Cloning of human Dactylin/FBXW4, an F-box/WD40 protein at 10q24.3 within the SHFM3 critical region; expressed in brain, kidney, lung and liver; proposed as a candidate gene for split hand/foot malformation acting via ubiquitination of signaling-pathway proteins in limb development.
A novel member of the F-box/WD40 gene family, encoding dactylin, is disrupted in the mouse dactylaplasia mutant.
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Positional cloning of the mouse dactylaplasia (Dac) gene identifies dactylin (Fbxw4 ortholog); Dac disrupts maintenance of the apical ectodermal ridge and truncates the autopod, resembling human SHFM, demonstrating the importance of the F-box/WD40 family in vertebrate limb development.
cDNA cloning and expression analysis of new members of the mammalian F-box protein family.
Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair.
A High-Density Map for Navigating the Human Polycomb Complexome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
The SCF Complex Is Essential to Maintain Genome and Chromosome Stability.
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 FBXW4
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FBXW4 assembles with the canonical SCF core (SKP1, CUL1, RBX1) and with COP9 signalosome subunits in an F-box-dependent manner, providing direct biochemical evidence (beyond family inference) that it is an SCF substrate-recognition subunit rather than an enzyme or transporter.
"FBXW4 co-purifies/interacts with **SKP1, CUL1, RBX1** and multiple **COP9 signalosome (COPS)** subunits, and these interactions are **F-box dependent**"
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FBXW4 associates with ubiquitinated cellular proteins, and this association increases upon proteasome inhibition in an F-box-dependent way, consistent with substrate engagement in ubiquitin-dependent turnover.
"FBXW4 interacts with **ubiquitinated cellular proteins**, and the interaction increases with **proteasome inhibition (MG132)** in an **F-box-dependent** manner, consistent with substrate engagement in ubiquitin-dependent turnover pathways"
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The endogenous substrate(s) of SCF(FBXW4) remain undefined; the primary biochemical study frames substrate identification as a future direction.
"The specific endogenous **substrate(s)** targeted by SCF^FBXW4 remain insufficiently defined in the retrieved evidence; the 2013 study frames substrate identification as a future direction"
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FBXW4 is recurrently mutated, lost, and under-expressed across human cancers, consistent with a possible tumor-suppressor role, though causal substrates/pathways are unclear.
"FBXW4 is mutated, lost, and under-expressed in human cancers, and argue this pattern is consistent with a potential **tumor suppressor** role, though definitive causal substrates/pathways remain unclear"
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SHFM3 at 10q24 is best explained as a cis-regulatory / multi-gene misexpression disorder; recurrent duplications include FBXW4 with neighboring genes, and enhancer perturbation in mouse alters Fbxw4 expression rather than acting through an FBXW4 coding mutation.
"SVs likely perturb **cis-regulatory elements**, **3D chromatin architecture**, and/or coordinated expression of multiple genes in the region"