CBL 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-731' 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. In association with CBLB, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA. Note: This description may include information from UniProtKB.
Protein type: Adaptor/scaffold; EC 6.3.2.-; EC; Ligase; Motility/polarity/chemotaxis; Oncoprotein; Ubiquitin conjugating system; Ubiquitin ligase
Chromosomal Location of Human Ortholog: 11q23.3
Cellular Component:  cilium; cytosol; focal adhesion; Golgi apparatus; growth cone; mast cell granule; perinuclear region of cytoplasm; plasma membrane
Molecular Function:  calcium ion binding; ephrin receptor binding; epidermal growth factor receptor binding; phosphatidylinositol 3-kinase regulatory subunit binding; phosphotyrosine residue binding; protein binding; SH3 domain binding; ubiquitin protein ligase activity; ubiquitin-protein transferase activity
Biological Process:  cell surface receptor signaling pathway; cellular response to DNA damage stimulus; cellular response to epidermal growth factor stimulus; cellular response to nerve growth factor stimulus; cellular response to oxygen-glucose deprivation; cellular response to platelet-derived growth factor stimulus; cytokine-mediated signaling pathway; entry of bacterium into host cell; epidermal growth factor receptor signaling pathway; fibroblast growth factor receptor signaling pathway; interleukin-6-mediated signaling pathway; male gonad development; mast cell degranulation; membrane organization; negative regulation of apoptotic process; negative regulation of epidermal growth factor receptor signaling pathway; negative regulation of neuron death; neuron death; positive regulation of epidermal growth factor receptor signaling pathway; positive regulation of phosphatidylinositol 3-kinase signaling; positive regulation of receptor-mediated endocytosis; protein monoubiquitination; protein polyubiquitination; protein ubiquitination; regulation of platelet-derived growth factor receptor-alpha signaling pathway; regulation of Rap protein signal transduction; response to activity; response to ethanol; response to gamma radiation; response to starvation; response to testosterone; transforming growth factor beta receptor signaling pathway; ubiquitin-dependent protein catabolic process
Disease: Juvenile Myelomonocytic Leukemia; Noonan Syndrome-like Disorder With Or Without Juvenile Myelomonocytic Leukemia
Reference #:  P22681 (UniProtKB)
Alt. Names/Synonyms: C-CBL; Cas-Br-M (murine) ecotropic retroviral transforming sequence; Casitas B-lineage lymphoma proto-oncogene; CBL; Cbl proto-oncogene; Cbl proto-oncogene, E3 ubiquitin protein ligase; CBL2; E3 ubiquitin-protein ligase CBL; FRA11B; fragile site, folic acid type, rare, fra(11)(q23.3); NSLL; oncogene CBL2; Proto-oncogene c-Cbl; RING finger protein 55; RING-type E3 ubiquitin transferase CBL; RNF55; Signal transduction protein CBL
Gene Symbols: CBL
Molecular weight: 99,633 Da
Basal Isoelectric point: 6.1  Predict pI for various phosphorylation states
CST Pathways:  B Cell Receptor Signaling  |  ErbB/HER Signaling  |  Insulin Receptor Signaling  |  T Cell Receptor Signaling
Protein-Specific Antibodies, siRNAs or Recombinant Proteins from Cell Signaling Technology® Total Proteins
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Protein Structure Not Found.

Cross-references to other databases:  STRING  |  cBioPortal  |  Wikipedia  |  Reactome  |  neXtProt  |  Protein Atlas  |  BioGPS  |  Pfam  |  RCSB PDB  |  ENZYME  |  Phospho3D  |  Phospho.ELM  |  NetworKIN  |  GeneCards  |  UniProtKB  |  Entrez-Gene  |  GenPept  |  Ensembl Gene