CBL (Cas-Br-M (murine) ecotropic retroviral transforming sequence)

1999-09-01   Olivier Rosnet 

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

Identity

HGNC
LOCATION
11q23.3
IMAGE
Atlas Image
LEGEND
CBL (11q23) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
ALIAS
C-CBL,CBL2,FRA11B,NSLL,RNF55
FUSION GENES

DNA/RNA

Transcription

10.5 kb; 2718 bp open reading frame

Proteins

Atlas Image

Description

906 amino acids; 115 kDa; the evolutionarily conserved amino-terminal 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 a carboxy-terminal region with multiple proline-rich sequences, a putative leucine zipper and several potential tyrosine phosphorylation sites

Expression

ubiquitous but predominant in hematopoietic cells

Localisation

cytoplasmic; cellular activation induces translocation of CBL to the plasma membrane or cytoskeleton

Function

CBL has been shown to have a negative regulatory activity in protein tyrosine kinase-mediated signaling pathways; CBL overexpresion inhibits cell growth resulting from activation of the EGF and PDGF receptors (EGFR, PDGFRa, PDFFRb) and enhances ubiquitination and degradation of these receptors; CBL also negatively regulates the tyrosine phosphorylation of ZAP70 substrates in T cells

Mutations

Germinal

the fragile site FRA11B has been localized to a stretch of CCG trinucleotides found in the 5 part of the CBL gene and has been involved in the pathogenesis of a proportion of inherited Jacobsen syndroms (OMIM 147791) which have a del(11)(q23qter) telomeric of an expansion of the stretch of CCG tripletsSOMATIC in 9% of the genetically unstable sporadic gastrointestinal tumors, an extension of an ATG trinucleotide repeat with no translation shift was detected in the coding region of CBL; this alteration was not present in cancers without the mutator phenotype

Implicated in

Entity name
gastrointestinal tumors (see above)

Bibliography

Pubmed IDLast YearTitleAuthors
20309141991The sequences of the human and mouse c-cbl proto-oncogenes show v-cbl was generated by a large truncation encompassing a proline-rich domain and a leucine zipper-like motif.Blake TJ et al
97314831998The coding region of the Bloom syndrome BLM gene and of the CBL proto-oncogene is mutated in genetically unstable sporadic gastrointestinal tumors.Calin G et al
76035641995Association of a chromosome deletion syndrome with a fragile site within the proto-oncogene CBL2.Jones C et al
27840031989v-cbl, an oncogene from a dual-recombinant murine retrovirus that induces early B-lineage lymphomas.Langdon WY et al
97207601998Cbl: complex formation and functional implications.Liu YC et al

Other Information

Locus ID:

NCBI: 867
MIM: 165360
HGNC: 1541
Ensembl: ENSG00000110395

Variants:

dbSNP: 867
ClinVar: 867
TCGA: ENSG00000110395
COSMIC: CBL

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000110395ENST00000264033P22681
ENSG00000110395ENST00000634301A0A0U1RRJ5
ENSG00000110395ENST00000634586A0A0U1RQX8
ENSG00000110395ENST00000634840A0A0U1RR39
ENSG00000110395ENST00000637974A0A1B0GW38

Expression (GTEx)

0
5
10
15
20
25
30

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
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
Signaling by EGFR in CancerREACTOMER-HSA-1643713
Signaling by Ligand-Responsive EGFR Variants in CancerREACTOMER-HSA-5637815
Constitutive Signaling by Ligand-Responsive EGFR Cancer VariantsREACTOMER-HSA-1236382
Signaling by EGFRvIII in CancerREACTOMER-HSA-5637812
Constitutive Signaling by EGFRvIIIREACTOMER-HSA-5637810
Infectious diseaseREACTOMER-HSA-5663205
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
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-3, 5 and GM-CSF signalingREACTOMER-HSA-512988
Regulation of signaling by CBLREACTOMER-HSA-912631
Interleukin-6 signalingREACTOMER-HSA-1059683
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
EGFR downregulationREACTOMER-HSA-182971
Signaling by FGFRREACTOMER-HSA-190236
Signaling by FGFR1REACTOMER-HSA-5654736
Negative regulation of FGFR1 signalingREACTOMER-HSA-5654726
Spry regulation of FGF signalingREACTOMER-HSA-1295596
Signaling by FGFR2REACTOMER-HSA-5654738
Negative regulation of FGFR2 signalingREACTOMER-HSA-5654727
Signaling by FGFR3REACTOMER-HSA-5654741
Negative regulation of FGFR3 signalingREACTOMER-HSA-5654732
Signaling by FGFR4REACTOMER-HSA-5654743
Negative regulation of FGFR4 signalingREACTOMER-HSA-5654733
Signaling by SCF-KITREACTOMER-HSA-1433557
Regulation of KIT signalingREACTOMER-HSA-1433559
Signaling by TGF-beta Receptor ComplexREACTOMER-HSA-170834
TGF-beta receptor signaling activates SMADsREACTOMER-HSA-2173789
Vesicle-mediated transportREACTOMER-HSA-5653656
Membrane TraffickingREACTOMER-HSA-199991
Interleukin-6 family signalingREACTOMER-HSA-6783589
Signaling by PTK6REACTOMER-HSA-8848021
PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1REACTOMER-HSA-8849469
Clathrin-mediated endocytosisREACTOMER-HSA-8856828
Cargo recognition for clathrin-mediated endocytosisREACTOMER-HSA-8856825
Signaling by METREACTOMER-HSA-6806834
Negative regulation of MET activityREACTOMER-HSA-6807004
Listeria monocytogenes entry into host cellsREACTOMER-HSA-8876384
InlB-mediated entry of Listeria monocytogenes into host cellREACTOMER-HSA-8875360

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
118940952002Cbl-CIN85-endophilin complex mediates ligand-induced downregulation of EGF receptors.170
196209602009Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms.141
193870082009Frequent CBL mutations associated with 11q acquired uniparental disomy in myeloproliferative neoplasms.124
118940962002The endophilin-CIN85-Cbl complex mediates ligand-dependent downregulation of c-Met.110
190749042008250K single nucleotide polymorphism array karyotyping identifies acquired uniparental disomy and homozygous mutations, including novel missense substitutions of c-Cbl, in myeloid malignancies.99
206940122010Germline CBL mutations cause developmental abnormalities and predispose to juvenile myelomonocytic leukemia.87
195713182009Mutations in CBL occur frequently in juvenile myelomonocytic leukemia.79
222668212012Structural basis for autoinhibition and phosphorylation-dependent activation of c-Cbl.75
263539302015H19 non coding RNA-derived miR-675 enhances tumorigenesis and metastasis of breast cancer cells by downregulating c-Cbl and Cbl-b.68
208801162010ASXL1 mutation is associated with poor prognosis and acute transformation in chronic myelomonocytic leukaemia.65

Citation

Olivier Rosnet

CBL (Cas-Br-M (murine) ecotropic retroviral transforming sequence)

Atlas Genet Cytogenet Oncol Haematol. 1999-09-01

Online version: http://atlasgeneticsoncology.org/gene/171/cbl