FEATURES

DESCRIPTION

Also known as CBL_HUMAN, CBL, CBL2, RNF55. 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 (PubMed:17094949). Ubiquitinates SPRY2 (PubMed:17094949, PubMed:17974561). Ubiquitinates EGFR (PubMed:17974561). Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, 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 (By similarity). Forms homodimers; IFT20 promotes the formation of stable homodimers (PubMed:29237719). Interacts (phosphorylated at Tyr-731) with PIK3R1. Associates with NCK via its SH3 domain. The phosphorylated C-terminus interacts with CD2AP via its second SH3 domain. Binds to UBE2L3. Interacts with adapters SLA, SLA2 and with the phosphorylated C-terminus of SH2B2. Interacts with EGFR, SYK and ZAP70 via the highly conserved Cbl-N region. Also interacts with SORBS1 and INPPL1/SHIP2. Interacts with phosphorylated LAT2 (By similarity). Interacts with CBLB (PubMed:29237719). Interacts with ALK, AXL, BLK, FGR and FGFR2. Interacts with CSF1R, EPHB1, FLT1, KDR, PDGFRA and PDGFRB; regulates receptor degradation through ubiquitination. Interacts with HCK and LYN. Interacts with ATX2 (By similarity). Interacts with TEK/TIE2 (tyrosine phosphorylated). Interacts with SH3KBP1 and this interaction is inhibited in the presence of SHKBP1 (By similarity). Interacts with SIGLEC10 (By similarity). Interacts with IFT20 (PubMed:29237719). Interacts with SPRY2; the interaction inhibits CBL-mediated ubiquitination of EGFR (PubMed:17974561).

EXTERNAL LINKS

CBL

Mutations

Mutation(s) distribution

Mutations table