Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Identification of a family of human F-box proteins.
F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7.
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FBXL7 is a proapoptotic SCF subunit that induces mitotic arrest; its abundance is controlled by FBXL18, which ubiquitinates FBXL7 (at Lys109, via an FQ recognition motif) for proteasomal degradation, thereby limiting FBXL7-driven apoptosis.
The Proapoptotic F-box Protein Fbxl7 Regulates Mitochondrial Function by Mediating the Ubiquitylation and Proteasomal Degradation of Survivin.
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FBXL7, a component of the SCF (SKP1-CUL1-F-box) E3 ligase that regulates mitotic progression, mediates polyubiquitylation (at survivin Lys90/Lys91, via FBXL7 contact with survivin Glu126) and proteasomal degradation of survivin/BIRC5, regulating mitochondrial function.
Aurora kinase A regulates Survivin stability through targeting FBXL7 in gastric cancer drug resistance and prognosis.
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In gastric cancer, AURKA upregulates the anti-apoptotic protein survivin; FBXL7 interacts with and polyubiquitinates survivin/BIRC5 for proteasomal degradation, linking the AURKA-FBXL7-survivin axis to drug resistance and prognosis.
A reference map of the human binary protein interactome.
The FBXL family of F-box proteins: variations on a theme.
SCF-FBXL7 ubiquitinates AURKA
Proteasome degrades AURKA ubiquitinated by SCF-FBXL7
SCF-FBXL18 ubiquitinates FBXL7
Formation of the SCF-FBXL7 complex
Proteasome-mediated degradation of PolyUb-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
Falcon deep research report for human FBXL7
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FBXL7 is a 491-residue FBXL-family protein with an N-terminal F-box motif (for SKP1/SCF assembly) and roughly eleven C-terminal leucine-rich repeats (the substrate-binding interface); it is the substrate-recognition subunit of an SCF (SKP1-CUL1-RBX1-F-box) E3 ligase.
"A 2022 expert review explicitly describes **human FBXL7** as a **491-aa** protein on chromosome **5p15.1** containing an **N-terminal F-box motif** (for SCF complex binding) and **~11 C-terminal leucine-rich repeats (LRRs)** (substrate binding), matching the UniProt domain expectations (F-box + LRRs) and the FBXL family classification."
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FBXL7 colocalizes with Aurora A and targets it for centrosomal polyubiquitylation and degradation during mitosis, linking FBXL7 to spindle defects, polyploidy, and G2/M / mitotic arrest.
"Multiple authoritative sources cite **Aurora A kinase (AURKA)** as an early/central FBXL7 substrate, with FBXL7 promoting AURKA polyubiquitylation and degradation during mitosis and associating this with mitotic spindle/cell-cycle phenotypes."
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SCF-FBXL7 targets the anti-apoptotic protein survivin/BIRC5 for proteasomal degradation (recognition via survivin E126, ubiquitin acceptor sites K90/K91), making FBXL7 proapoptotic and regulating mitochondrial function.
"Mapping of FBXL7–survivin interaction determinants and ubiquitylation acceptor sites: **E126** is important for recognition, and **K90/K91** serve as ubiquitin acceptors (mutants resist FBXL7-mediated effects)."
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FBXL7 acts as a metastasis suppressor by ubiquitinating and degrading additional substrates - active c-SRC (after Ser104 phosphorylation) and the EMT transcription factor SNAI1/Snail1 - and is itself silenced in cancer by promoter hypermethylation and by hypoxia-induced EZH2 (which stabilizes the FBXL7 substrate PFKFB4 to drive glycolysis).
"A high-impact cancer epigenetics study established FBXL7 as a **metastasis-suppressor axis component** through control of **active c-SRC**: FBXL7 mediates **ubiquitylation and proteasomal degradation of active c-SRC after phosphorylation at Ser104**, and loss of FBXL7 promotes EMT and metastasis."