Gene Ontology annotation through association of InterPro records with GO terms
F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.
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FBXL18 targets FBXL7 for polyubiquitylation and proteasomal degradation, conjugating ubiquitin onto FBXL7 Lys109 and recognizing an FQ motif in FBXL7; this limits FBXL7-induced apoptosis (FBXL18 depletion accentuates, overexpression attenuates, FBXL7-driven apoptosis).
The FBXL family of F-box proteins: variations on a theme.
Falcon deep research report for human FBXL18
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FBXL18 is an SCF substrate receptor that deploys two modes - degradative K48 polyubiquitination and non-degradative K63 ubiquitination.
"FBXL18 (Q96ME1) is best annotated as an **SCF-family E3 ubiquitin ligase substrate receptor** that regulates cellular phenotypes by deploying **two mechanistic modes of ubiquitination**"
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FBXL18 recognizes an N-terminal FQ motif in FBXL7 and uses Lys109 as the ubiquitin acceptor, degrading short-lived FBXL7 to restrain its pro-apoptotic activity.
"Substrate recognition depends on an N-terminal **FQ docking motif** in FBXL7; mutation of that motif disrupts binding. **Lys109** in FBXL7 was identified as an essential ubiquitin acceptor for FBXL18-mediated ubiquitin conjugation."
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SCF^FBXL18 mediates K48-linked degradation of the TFIIH subunit XPB/ERCC3 in a drug-triggered, CDK7- and XPB-Ser90-dependent manner, impairing NER.
"Ueda et al. (Genes to Cells, 2019) established that spironolactone triggers proteasomal degradation of XPB (ERCC3) via **SCF^FBXL18**."
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FBXL18 promotes non-degradative K63-linked ubiquitination of AKT, enhancing AKT-FOXO3a phosphorylation and suppressing apoptosis via Bim in glioma.
"FBXL18 physically interacts with AKT and promotes **K63-linked ubiquitination** of AKT (with minimal effect on K48-linked ubiquitination), including reduced EGF-induced K63 ubiquitination upon FBXL18 knockdown."
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FBXL18 promotes K63-linked ubiquitination of PTEN (non-proteolytic), inhibiting PTEN and activating PI3K/AKT signaling in NSCLC.
"FBXL18 binds PTEN (mapping interaction to PTEN's **C-terminal region/C-tail and PDZ-binding domain**) and promotes **K63-linked ubiquitination** of PTEN in HEK293T and NSCLC models."
SCF-FBXL18 ubiquitinates FBXL7
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