CBLB

This gene encodes an E3 ubiquitin-protein ligase which promotes proteosome-mediated protein degradation by transferring ubiquitin from an E2 ubiquitin-conjugating enzyme to a substrate. The encoded protein is involved in the regulation of immune response by limiting T-cell receptor, B-cell receptor, and high affinity immunoglobulin epsilon receptor activation. Studies in mouse suggest that this gene is involved in antifungal host defense and that its inhibition leads to increased fungal killing. Manipulation of this gene may be beneficial in implementing immunotherapies for a variety of conditions, including cancer, autoimmune diseases, allergies, and infections. [provided by RefSeq, Sep 2017]

Cbl Proto-Oncogene 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 (By similarity).

Immune response Source: Ensembl
Intracellular signal transduction Source: Ensembl
Negative regulation of alpha-beta T cell proliferation Source: Ensembl
Negative regulation of epidermal growth factor-activated receptor activity Source: GO_Central
Negative regulation of T cell receptor signaling pathway Source: Ensembl
NLS-bearing protein import into nucleus Source: ProtInc
Peptidyl-amino acid modification Source: Ensembl
Positive regulation of protein catabolic process Source: Ensembl
Positive regulation of protein ubiquitination Source: Ensembl
Positive regulation of T cell anergy Source: Ensembl
Regulation of GTPase activity Source: Ensembl
Regulation of platelet-derived growth factor receptor-alpha signaling pathway Source: UniProtKB
Regulation of protein binding Source: Ensembl
Signal transduction Source: GO_Central
T cell activation Source: Ensembl
T cell receptor signaling pathway Source: Ensembl

Cytoplasm. Upon EGF stimulation, associates with endocytic vesicles.

Phosphorylated on tyrosine and serine residues upon TCR or BCR activation, and upon various types of cell stimulation.
Auto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation.