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
F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box protein that regulates sarcomeric protein turnover and is essential for maintenance of contractile function in vivo.
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FBXL22 is a cardiac-enriched, Z-disc-localized F-box protein that interacts with SKP1 and CUL1 and promotes the proteasome-dependent degradation of the sarcomeric proteins alpha-actinin (ACTN2) and filamin C (FLNC); FBXL22 knockdown causes alpha-actinin accumulation, impaired contractile function and cardiomyopathy in vivo.
A reference map of the human binary protein interactome.
The FBXL family of F-box proteins: variations on a theme.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Falcon deep research report for human FBXL22
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FBXL22 is a striated-muscle-enriched SCF (Cullin-1) substrate adaptor at the Z-disc that polyubiquitinates ACTN2 and FLNC for proteasome-mediated clearance.
"Fbxl22 **binds ACTN2 and FLNC** and that Fbxl22-containing CRLs **poly-ubiquitylate** these proteins, promoting **proteasome-mediated clearance**"
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FBXL22 is a substrate-selection adaptor, not a small-molecule enzyme; it selects substrates for ubiquitylation by the SCF machinery.
"FBXL22 is **not an enzyme that catalyzes a small-molecule reaction**; rather, its primary biochemical role is to **select specific protein substrates** for **ubiquitylation** (typically poly-ubiquitylation) by the SCF E3 ligase machinery, which can route substrates toward **proteasomal degradation** and/or alter their cellular behavior"
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Loss of fbxl22 in zebrafish causes ACTN2 accumulation and progressive reduction of cardiac contractility, consistent with impaired sarcomeric protein turnover.
"Fbxl22 loss-of-function in zebrafish leads to **ACTN2 accumulation** and **progressive reduction of cardiac contractility**, consistent with impaired sarcomeric protein turnover"
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In skeletal muscle FBXL22 is an atrogene-like factor strongly and transiently induced after denervation (~15-fold at day 3, returning to baseline by day 7).
"strong, stimulus-timed induction of Fbxl22 in neurogenic atrophy: **~15-fold mRNA increase at day 3 after denervation** in mouse gastrocnemius complex, returning to baseline by day 7"
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In zebrafish heart regeneration fbxl22 expression is regulated by AP-1-dependent chromatin accessibility and it regulates sarcomere disassembly.
"AP-1 blockade decreases chromatin accessibility at the **fbxl22 locus**, and the study explicitly describes fbxl22 as regulating **sarcomere disassembly**, a key step for cardiomyocyte regenerative behavior"
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