Gene Ontology annotation through association of InterPro records with GO terms
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
Electronic Gene Ontology annotations created by ARBA machine learning models
Identification of a family of human F-box proteins.
FBXL5 interacts with p150Glued and regulates its ubiquitination.
Control of iron homeostasis by an iron-regulated ubiquitin ligase.
An E3 ligase possessing an iron-responsive hemerythrin domain is a regulator of iron homeostasis.
Next-generation sequencing to generate interactome datasets.
Nuclear ubiquitination by FBXL5 modulates Snail1 DNA binding and stability.
A proteome-scale map of the human interactome network.
Architecture of the human interactome defines protein communities and disease networks.
A reference map of the human binary protein interactome.
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.
SKP1:FBXL5:CUL1:NEDD8 ubiquitinylates IREB2
NEDD8 binds CUL1 (in SKP1:CUL1:FXBL5)
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 FBXL5
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FBXL5 is the substrate-recognition (F-box) subunit of an SCF E3 ubiquitin ligase whose three-region architecture (N-terminal hemerythrin-like domain, central F-box, C-terminal LRR) couples metal sensing to IRP2 recognition and SKP1-mediated SCF assembly.
"A structural/functional synthesis of FBXL5 describes three major regions: an **N-terminal hemerythrin-like (Hr) domain**, a **central F-box domain**, and a **C-terminal leucine-rich repeat (LRR) domain** (sicheri2025analysisoffbox pages 4-7). The F-box domain provides a **SKP1-binding interface**, linking FBXL5 to the SCF machinery, while the LRR region mediates key substrate-binding and cofactor-linked regulation (sicheri2025analysisoffbox pages 4-7)."
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FBXL5 stability is governed by both an N-terminal diiron hemerythrin-like center and an oxygen-responsive [2Fe-2S] cluster, making it a combined iron- and oxygen-sensor for IRP2 degradation.
"a review summary likewise states that FBXL5 stability depends on both a **diiron hemerythrin-like domain** and a **[2Fe–2S] cluster** (jain2026ironregulationredox pages 8-10)."
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Under iron-replete conditions FBXL5 is stabilized and recruits IRP2 for proteasomal degradation; under iron deficiency FBXL5 is destabilized and degraded, permitting IRP2 accumulation and the iron-starvation response.
"- **Low iron:** loss of stabilizing metal cofactor occupancy destabilizes FBXL5, leading to FBXL5 degradation and **IRP2 accumulation**, which then drives the IRP/IRE post-transcriptional iron response (chen2026regulationofmitochondrial pages 4-5, jain2026ironregulationredox pages 8-10)."
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FBXL5 acts as a physiological brake on iron accumulation; liver-specific Fbxl5 knockout creates an iron overload-induced hepatic ferroptosis model, demonstrating that loss of FBXL5 sensitizes tissue to ferroptotic injury.
"A translational study used **liver-specific Fbxl5 knockout mice** to create an **iron overload–induced hepatic ferroptosis model** and interrogate injury pathways in ischemia–reperfusion injury (IRI) (matsumoto2025integratedhepaticferroptosis pages 1-5, matsumoto2025integratedhepaticferroptosis pages 8-11)."