Cbl-b
E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBL, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA. Expressed in placenta, heart, lung, kidney, spleen, ovary and testis, as well as fetal brain and liver and hematopoietic cell lines, but not in adult brain, liver, pancreas, salivary gland, or skeletal muscle. Present in lymphocytes (at protein level). 3 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Molecular Function: calcium ion binding; phosphotyrosine residue binding; protein kinase binding; receptor tyrosine kinase binding; SH3 domain binding; ubiquitin protein ligase activity; ubiquitin-protein transferase activity
Biological Process: CD4-positive, alpha-beta T cell proliferation; cell surface receptor signaling pathway; cellular response to hydrogen peroxide; immune response; intracellular signal transduction; negative regulation of apoptotic process; negative regulation of CD4-positive, alpha-beta T cell proliferation; negative regulation of epidermal growth factor-activated receptor activity; negative regulation of T cell receptor signaling pathway; peptidyl-amino acid modification; positive regulation of protein catabolic process; positive regulation of protein ubiquitination; positive regulation of T cell anergy; protein catabolic process; protein ubiquitination; regulation of cell adhesion; regulation of GTPase activity; regulation of platelet-derived growth factor receptor-alpha signaling pathway; regulation of protein binding; regulation of signaling; response to gravity; response to hormone; signal transduction; T cell activation; T cell anergy; T cell receptor signaling pathway
