Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
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
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
SCFFBXL¹⁵ regulates BMP signalling by directing the degradation of HECT-type ubiquitin ligase Smurf1.
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SCF(FBXL15) targets the HECT E3 ligase SMURF1 (also SMURF2/WWP2) for ubiquitination and proteasomal degradation, recognizing the N-lobe of the SMURF1 HECT domain; by lowering SMURF1 it positively regulates BMP signaling, affecting dorsoventral patterning (zebrafish) and bone mass (rat).
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 FBXL15
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FBXL15 is the substrate-recognition adaptor of an SCF (SKP1-CUL1-RBX1/Roc1) E3 ligase that confers target specificity for K48-like degradative ubiquitination and proteasomal turnover, rather than catalyzing ubiquitin transfer itself.
"Its primary molecular function is as a **substrate-recognition adaptor** that confers target specificity to an **SCF-type RING E3 ligase**, thereby promoting **K48-like degradative ubiquitination** and **proteasomal turnover** of the recruited substrate(s)."
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SCF(FBXL15)-mediated SMURF1 degradation maps primarily to SMURF1 WW-HECT linker lysine K357, with K355 secondary.
"K357 identified as the primary residue and K355 as a secondary residue for FBXL15-mediated degradation; a K355/K357 double mutant attenuates ubiquitination and stabilizes SMURF1"
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By counteracting the BMP-inhibitor SMURF1, FBXL15 is required for full BMP/SMAD transcriptional output, including BMP-2-stimulated induction of the target genes ID1 and SMAD6.
"FBXL15 knockdown reduces BMP-2-stimulated signaling outputs, including reduced BRE reporter activity and decreased induction of BMP/Smad target genes ID1 and SMAD6 by qRT-PCR"