Tchem CBLB E3 ubiquitin-protein ligase CBL-B

Protein Summary

Description

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). 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]

Uniprot Accession IDs

• Q13191
• A8K9S7
• B7WNM4
• Q13192
• Q13193
• Q3LIC0
• Q63Z43
• Q8IVC5

Gene Name

• CBLB

Ensembl ID

• ENST00000264122
• ENSP00000264122
• ENSG00000114423
• ENST00000394030
• ENSP00000377598
• ENST00000403724
• ENSP00000384816
• ENST00000405772
• ENSP00000384938

Symbol

• RNF56
• Cbl-b
• RNF56
• Nbla00127

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
protein domain	1
transcription factor perturbation	0.99
hub protein	0.98
biological process	0.89
transcription factor binding site profile	0.71

Protein Classes

PANTHER Classes

Protein / Ligase / E3 Ubiquitin-protein Ligase Cbl-b

DTO Classes

Protein / Enzyme / Ligase / E3 Ubiquitin-protein Ligase Cbl-b

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 18.63   (req: < 5)

Gene RIFs: 68   (req: <= 3)

Antibodies: 232   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 18.63   (req: >= 5)

Gene RIFs: 68   (req: > 3)

Antibodies: 232   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 11

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 1

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0