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The proto-oncogene on chromosome 11q23.3-qter that encodes Cbl proto-oncogene—E3 ubiquitin protein ligase (OMIM: 165360, UniProtKB: P22681), a RING finger E3 ubiquitin ligase, which targets substrates for proteosomal degradation by mediating the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. It acts as an adapter protein that down-regulates many signaling pathways triggered by cell surface receptor kinase activation–e.g., KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. It participates in signal transduction in hematopoiesis, plays a key role in regulating osteoblast differentiation and apoptosis and is essential for osteoclastic bone resorption.
The Tyr-731 phosphorylated form of the ligase activates and recruits phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function.
Molecular pathology This gene is mutated or translocated in many cancers–e.g., acute myeloid leukaemia. Defects cause Noonan syndrome-like disorder with or without juvenile myelomonocytic leukaemia (OMIM:613563).
Synonyms CCBL, CBL2, FRA11B, RNF55, NSLL, Cas-Br-M (murine) ecotropic retroviral transforming sequence, E3 ubiquitin-protein ligaseCBL, casitas B-lineage lymphoma proto-oncogene, fragile site—folic acid type—rare—fra(11)(Q23.3), oncogene CBL2, signal transduction proteinCBL, EC 6.3.2.-, RING finger protein 55