E3 ubiquitin-protein ligase CBL (P22682)

Uniprot ID	P22682
Protein Name	E3 ubiquitin-protein ligase CBL
Gene Name	Cbl
Species	Mus musculus (Mouse)

Signal peptide^(a)	N	Secretome P^(b)	0.51
Function	Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The 'Tyr-737' phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. .
GO - Molecular function	cadherin binding : ISO:MGI calcium ion binding : IEA:InterPro ephrin receptor binding : IPI:UniProtKB epidermal growth factor receptor binding : ISO:MGI phosphatidylinositol 3-kinase regulatory subunit binding : ISO:MGI phosphotyrosine residue binding : IEA:InterPro protein kinase binding : ISO:MGI protein tyrosine kinase binding : ISO:MGI receptor tyrosine kinase binding : IBA:GO_Central SH3 domain binding : IPI:BHF-UCL ubiquitin protein ligase activity : ISO:MGI
GO - Biological process	bone resorption : ISS:UniProtKB cellular response to DNA damage stimulus : IEA:Ensembl cellular response to epidermal growth factor stimulus : ISO:MGI cellular response to nerve growth factor stimulus : IEA:Ensembl cellular response to oxygen-glucose deprivation : IEA:Ensembl cellular response to platelet-derived growth factor stimulus : IEA:Ensembl epidermal growth factor receptor signaling pathway : IBA:GO_Central male gonad development : IEA:Ensembl mast cell degranulation : IEA:Ensembl negative regulation of apoptotic process : ISO:MGI negative regulation of epidermal growth factor receptor signaling pathway : ISS:UniProtKB negative regulation of epidermal growth factor-activated receptor activity : IBA:GO_Central negative regulation of neuron death : ISO:MGI neuron death : IEA:Ensembl positive regulation of phosphatidylinositol 3-kinase signaling : ISO:MGI positive regulation of receptor-mediated endocytosis : ISS:UniProtKB protein monoubiquitination : ISO:MGI protein phosphorylation : ISS:UniProtKB protein polyubiquitination : ISO:MGI proteolysis : IBA:GO_Central response to activity : IEA:Ensembl response to antibiotic : ISO:MGI response to ethanol : IEA:Ensembl response to gamma radiation : IEA:Ensembl response to starvation : IEA:Ensembl response to testosterone : IEA:Ensembl ubiquitin-dependent protein catabolic process : ISS:UniProtKB

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^{(a) The Signal peptide D-score cutoff for "YES"(having signal peptide) is 0.45.}
^{(b) Non-classically secreted proteins should obtain an NN-score(Neural Networks score) exceeding the normal threshold of 0.5, but not at the same time be predicted to contain a signal peptide.}