Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Combined Automated Annotation using Multiple IEA Methods
Identification of a family of human F-box proteins.
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FBXO22 (FBX22) was identified among a family of 26 human F-box proteins; F-box proteins are the substrate-recognition subunits of SCF ubiquitin protein ligases (together with Skp1, a cullin, and Roc1/Rbx1).
A family of mammalian F-box proteins.
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F-box proteins contain a C-terminal substrate-binding domain and an F-box motif that binds Skp1, linking the F-box protein to a core ubiquitin ligase composed of Cul1, Rbx1 and an E2; the catalytic core is the cullin-RING module, not the F-box protein.
Dynamics of cullin-RING ubiquitin ligase network revealed by systematic quantitative proteomics.
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
A High-Density Map for Navigating the Human Polycomb Complexome.
A reference map of the human binary protein interactome.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
The SCF Complex Is Essential to Maintain Genome and Chromosome Stability.
The tRNA-GCN2-FBXO22-axis-mediated mTOR ubiquitination senses amino acid insufficiency.
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Upon amino-acid depletion, uncharged tRNAs stimulate GCN2 to phosphorylate FBXO22, which accumulates in the cytoplasm and ubiquitinates mTOR at Lys2066 in a K27-linked manner, inhibiting mTORC1 by preventing substrate recruitment.
E3 ubiquitin ligase FBXO22 inhibits SARS-CoV-2 replication via promoting proteasome-dependent degradation of NSP5.
Multimodal cell maps as a foundation for structural and functional genomics.
Falcon deep research report for human FBXO22
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FBXO22 is the substrate-recognition subunit of an SCF (SKP1-CUL1-RBX1/CRL1) E3 ligase; its N-terminal F-box binds SKP1 and its C-terminal FIST-C region binds substrates such as KDM4A.
"FBXO22 contains an N-terminal **F-box domain** mediating SCF assembly via SKP1, and a C-terminal **FIST/FIST-C** substrate-binding region (e.g., KDM4A binding mapped to the FBXO22 FIST-C domain)."
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In ER-positive breast cancer, SCF(FBXO22) ubiquitylates and degrades KDM4B when KDM4B is complexed with tamoxifen-bound estrogen receptor, releasing steroid receptor coactivator and shaping SERM pharmacology.
"In ER-positive breast cancer models, **SCF^FBXO22^ ubiquitylates and degrades KDM4B** when KDM4B is **complexed with tamoxifen-bound ER**, which in turn **releases steroid receptor coactivator (SRC)** from ER and shapes SERM pharmacology."
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FBXO22 ubiquitinates nuclear, but not cytoplasmic, PTEN at Lys221 for proteasomal degradation.
"FBXO22 **ubiquitylates nuclear (but not cytoplasmic) PTEN** at **lysine 221**, leading to proteasome-mediated degradation and nuclear PTEN depletion."
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FBXO22 recognizes a phosphodegron motif XXPpSPXPXX and degrades BAG3 in an ERK-S377-phosphorylation-dependent manner, defining an ERK-FBXO22-BAG3 axis.
"A 2022 systems/biochemical study defined a **FBXO22-recognized phosphodegron motif** **XXPpSPXPXX** and validated **BAG3** as a bona fide FBXO22 substrate. BAG3 degradation requires **ERK-dependent phosphorylation at S377**, establishing an ERK→FBXO22→BAG3 axis linked to tumorigenesis phenotypes."
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FBXO22 is a recruitable E3 ligase for targeted protein degradation; an aldehyde metabolite of alkylamine-tethered degraders covalently adducts Cys326 in its C-terminal domain to drive ternary-complex formation and degradation.
"Alkylamine-tethered degraders can be metabolized to an **active aldehyde** that **covalently adduces Cys326** in the FBXO22 C-terminal domain."
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