Gene Ontology annotation based on UniPathway vocabulary mapping
Electronic Gene Ontology annotations created by ARBA machine learning models
The Human IL-22 Receptor Is Regulated through the Action of the Novel E3 Ligase Subunit FBXW12, Which Functions as an Epithelial Growth Suppressor.
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FBXW12 destabilizes human IL-22R (IL22RA1) in lung epithelia, binds SKP1, and facilitates IL22RA1 ubiquitination in a defined cell-free SCF system; FBXW12 knockdown increases IL22RA1 abundance and IL-22-induced STAT3 phosphorylation, and FBXW12 acts as an epithelial cell-growth suppressor (knockdown increases proliferation, cell-cycle progression and JNK/ERK activation).
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 FBXW12
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FBXW12 is an SCF-family E3 ligase subunit that physically associates with SKP1 and CUL1 and with IL-22R (IL22RA1), and reconstitutes IL-22R ubiquitination in a cell-free system, confirming it as a substrate-recognition adaptor rather than an enzyme.
"FBXW12 associates with SCF components including **SKP1** and **CUL1**, consistent with being an SCF substrate receptor"
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Ectopic FBXW12 accelerates IL-22R turnover (half-life ~6 h to ~2 h), and FBXW12 knockdown increases IL-22R abundance and IL-22-induced STAT3, ERK and JNK signaling, defining FBXW12 as a negative post-translational regulator of IL-22 signaling and an epithelial growth suppressor.
"IL-22R half-life is reported to be ~**6 hours** at baseline and is accelerated to ~**2 hours** with FBXW12 overexpression"
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Beyond IL-22R no additional validated FBXW12 substrate, ubiquitin linkage type, or definitive subcellular localization has been established, so substrate scope remains open.
"additional validated FBXW12 protein substrates, ubiquitin linkage types, and definitive subcellular localization were not identified in the retrieved materials"
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A circular RNA (circ-FBXW12) from the FBXW12 locus is discussed in diabetic nephropathy, but this circRNA biology is distinct from and must not be conflated with the linear FBXW12 protein's E3-adaptor function.
"This evidence concerns **circRNA biology**, and should not be conflated with the **linear FBXW12 protein**'s E3-ligase substrate receptor activity"