CBLB (Cas-Br-M (murine) ecotropic retroviral transforming sequence b)

1999-09-01   Olivier Rosnet 

Centre dImmunologie INSERM-CNRS de Marseille-Luminy Case 906, 13288 Marseille Cedex 9, France

Identity

HGNC
LOCATION
3q13.11
LOCUSID
ALIAS
Cbl-b,Nbla00127,RNF56
FUSION GENES

DNA/RNA

Transcription

major mRNA species of 4-5 kb and a less prominent species of 6-8 kb; 2946 bp open reading frame

Proteins

Description

982 amino acids; 120 kDa; the overall structure of CBLb is very close to the sructure of CBL: the evolutionarily conserved aminoterminal region of CBL is composed of three interacting domains: a four-helix bundle (4H), an EF-hand calcium binding domain, and a divergent SH2 domain; the three domains together form an integrated phosphoprotein -recognition module; this aminoterminal region is followed by a central Ring finger with a Cys3HisCys4 motif and an aminoterminal region with multiple proline-rich sequences, a putative leucine zipper and several potential tyrosine phosphorylation sites; two alternatively spliced mRNA code form CBLb proteins lacking the leucine zipper

Expression

expression of CBLb was seen in several human adult tissues including lung, spleen and testis but not in human brain, liver, pancreas, salivary gland or skeletal muscle; expression was also detected in fetal brain and liver, in hematopoietic cell lines and in normal and malignant mammary epithelial cell lines

Localisation

cytoplasmic

Function

regulation of signal transduction; CBLb has been shown to inhibit c-Jun terminal kinase (JNK) activation mediated by the (VAV oncoprotein and EGF receptor (EGFR) signaling; in contrast, a direct interaction between CBLb and the kinase ZAP-70 induces a positive signal in T cells

Mutations

Note

no genomic alterations described to date

Bibliography

Pubmed IDLast YearTitleAuthors
93996391997Cbl-b, a member of the Sli-1/c-Cbl protein family, inhibits Vav-mediated c-Jun N-terminal kinase activation.Bustelo XR et al
100863401999cbl-b inhibits epidermal growth factor receptor signaling.Ettenberg SA et al
77840851995Cloning and characterization of cbl-b: a SH3 binding protein with homology to the c-cbl proto-oncogene.Keane MM et al
96141021998The CBL-related protein CBLB participates in FLT3 and interleukin-7 receptor signal transduction in pro-B cells.Lavagna-Sévenier C et al
100744321999A direct interaction between the adaptor protein Cbl-b and the kinase zap-70 induces a positive signal in T cells.Zhang Z et al

Other Information

Locus ID:

NCBI: 868
MIM: 604491
HGNC: 1542
Ensembl: ENSG00000114423

Variants:

dbSNP: 868
ClinVar: 868
TCGA: ENSG00000114423
COSMIC: CBLB

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000114423ENST00000394030Q13191
ENSG00000114423ENST00000403724Q13191
ENSG00000114423ENST00000405772Q13191
ENSG00000114423ENST00000438603C9JRB3
ENSG00000114423ENST00000443752C9K048
ENSG00000114423ENST00000447441C9JU85
ENSG00000114423ENST00000642241A0A2R8Y582
ENSG00000114423ENST00000643192C9K048
ENSG00000114423ENST00000643322A0A2R8YFD4
ENSG00000114423ENST00000643403A0A2R8YDW4
ENSG00000114423ENST00000645425A0A2R8Y5E1
ENSG00000114423ENST00000645759A0A2R8Y7I2
ENSG00000114423ENST00000646499A0A2R8Y875
ENSG00000114423ENST00000646825A0A2R8Y8D8

Expression (GTEx)

0
5
10
15
20
25
30
35

Pathways

PathwaySourceExternal ID
ErbB signaling pathwayKEGGko04012
Ubiquitin mediated proteolysisKEGGko04120
T cell receptor signaling pathwayKEGGko04660
Insulin signaling pathwayKEGGko04910
Chronic myeloid leukemiaKEGGko05220
ErbB signaling pathwayKEGGhsa04012
Ubiquitin mediated proteolysisKEGGhsa04120
T cell receptor signaling pathwayKEGGhsa04660
Insulin signaling pathwayKEGGhsa04910
Pathways in cancerKEGGhsa05200
Chronic myeloid leukemiaKEGGhsa05220
EndocytosisKEGGko04144
EndocytosisKEGGhsa04144
Bacterial invasion of epithelial cellsKEGGko05100
Bacterial invasion of epithelial cellsKEGGhsa05100
MeaslesKEGGko05162
MeaslesKEGGhsa05162
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Antigen activates B Cell Receptor (BCR) leading to generation of second messengersREACTOMER-HSA-983695
Class I MHC mediated antigen processing & presentationREACTOMER-HSA-983169
Antigen processing: Ubiquitination & Proteasome degradationREACTOMER-HSA-983168

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
204538402010Variants within the immunoregulatory CBLB gene are associated with multiple sclerosis.72
263539302015H19 non coding RNA-derived miR-675 enhances tumorigenesis and metastasis of breast cancer cells by downregulating c-Cbl and Cbl-b.68
174759122007Novel c-CBL and CBL-b ubiquitin ligase mutations in human acute myeloid leukemia.50
213462572011CBL, CBLB, TET2, ASXL1, and IDH1/2 mutations and additional chromosomal aberrations constitute molecular events in chronic myelogenous leukemia.47
221589022011Autoinhibition and phosphorylation-induced activation mechanisms of human cancer and autoimmune disease-related E3 protein Cbl-b.42
152737202004Cbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b.38
183163982008A tale of two Cbls: interplay of c-Cbl and Cbl-b in epidermal growth factor receptor downregulation.36
248851942014Ubiquitin ligase Cbl-b represses IGF-I-induced epithelial mesenchymal transition via ZEB2 and microRNA-200c regulation in gastric cancer cells.29
202374962010New genetic associations detected in a host response study to hepatitis B vaccine.27
198345032009Replication of CD58 and CLEC16A as genome-wide significant risk genes for multiple sclerosis.26

Citation

Olivier Rosnet

CBLB (Cas-Br-M (murine) ecotropic retroviral transforming sequence b)

Atlas Genet Cytogenet Oncol Haematol. 1999-09-01

Online version: http://atlasgeneticsoncology.org/gene/193/cblb