CBLB

Gene Information

Official Symbol: CBLB
Official Name: Cbl proto-oncogene B
Aliases and Previous Symbols: N/A
Entrez ID: 868
UniProt: Q13191
Interactions: BioGRID
PubMed articles: Open PubMed
OMIM: Open OMIM

Function Summary

Entrez Summary: 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 Summary: 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. {ECO:0000269|PubMed:10022120, ECO:0000269|PubMed:10086340, ECO:0000269|PubMed:11087752, ECO:0000269|PubMed:11526404, ECO:0000269|PubMed:14661060, ECO:0000269|PubMed:20525694}.

Pfam Domains GO Terms

CRISPR Data

Compound Hit Most Correlated Genes in Chemogenomics Tissues where Essential in the Avana Dataset (DepMap 20Q1)

Screen	Score
MS023 2μM R03 exp134	1.72
CCT251545 0.2μM R06 exp271	1.79
Sucrose 20000μM R06 exp298	2.07
SB203580 25μM R03 exp149	2.29
Geldanamycin 0.015 to 0.05μM on day4 R07 exp317	3

Global Fraction of Cell Lines Where Essential: 0/739

Tissue	Fraction Of Cell Lines Where Essential
1290807.0	0/1
909776.0	0/1
bile duct	0/28
blood	0/28
bone	0/26
breast	0/33
central nervous system	0/56
cervix	0/4
colorectal	0/17
esophagus	0/13
fibroblast	0/1
gastric	0/16
kidney	0/21
liver	0/20
lung	0/75
lymphocyte	0/16
ovary	0/26
pancreas	0/24
peripheral nervous system	0/16
plasma cell	0/15
prostate	0/1
skin	0/24
soft tissue	0/9
thyroid	0/2
upper aerodigestive	0/22
urinary tract	0/29
uterus	0/5

Essentiality in NALM6

Essentiality Rank: 5745
Expression level (log2 read counts): 3.43

Expression Distribution

Cbl N
zf-C3HC4
Cbl N3
Cbl N2

regulation of platelet-derived growth factor receptor-alpha signaling pathway
negative regulation of epidermal growth factor-activated receptor activity
NLS-bearing protein import into nucleus
regulation of platelet-derived growth factor receptor signaling pathway
regulation of epidermal growth factor-activated receptor activity
negative regulation of protein tyrosine kinase activity
phosphotyrosine residue binding
negative regulation of epidermal growth factor receptor signaling pathway
negative regulation of peptidyl-tyrosine phosphorylation
negative regulation of ERBB signaling pathway
receptor tyrosine kinase binding
negative regulation of signaling receptor activity
regulation of epidermal growth factor receptor signaling pathway
regulation of protein tyrosine kinase activity
regulation of ERBB signaling pathway
protein import into nucleus
import into nucleus
SH3 domain binding
protein import
protein localization to nucleus
regulation of signaling receptor activity
ubiquitin protein ligase activity
membrane raft
negative regulation of protein kinase activity
negative regulation of kinase activity
regulation of peptidyl-tyrosine phosphorylation
nucleocytoplasmic transport
nuclear transport
negative regulation of transferase activity
negative regulation of protein phosphorylation
establishment of protein localization to organelle
negative regulation of phosphorylation
negative regulation of phosphate metabolic process
negative regulation of phosphorus metabolic process
negative regulation of protein modification process
protein ubiquitination
calcium ion binding
protein localization to organelle
protein modification by small protein conjugation
negative regulation of catalytic activity