| Written | 1999-09 | Olivier Rosnet |
| Centre d'Immunologie INSERM-CNRS de Marseille-Luminy Case 906, 13288 Marseille Cedex 9, France |
| Identity |
| Alias_names | CBL2 |
| Cas-Br-M (murine) ecotropic retroviral transforming sequence | |
| Cbl proto-oncogene, E3 ubiquitin protein ligase | |
| Alias_symbol (synonym) | RNF55 |
| c-Cbl | |
| Other alias | |
| HGNC (Hugo) | CBL |
| LocusID (NCBI) | 867 |
| Atlas_Id | 171 |
| Location | 11q23.3 [Link to chromosome band 11q23] |
| Location_base_pair | Starts at 119206276 and ends at 119308149 bp from pter ( according to hg19-Feb_2009) [Mapping CBL.png] |
 | |
| CBL (11q23) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. | |
| Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
| CBL (11q23.3) / CBL (11q23.3) | CBL (11q23.3) / CXCR5 (11q23.3) | CBL (11q23.3) / KANK1 (9p24.3) | |
| CBL (11q23.3) / KMT2A (11q23.3) | CBL (11q23.3) / PHLDB1 (11q23.3) | CBL (11q23.3) / SLC25A1 (22q11.21) | |
| CBL (11q23.3) / VWA5A (11q24.2) | KMT2A (11q23.3) / CBL (11q23.3) |
| DNA/RNA |
| Transcription | 10.5 kb; 2718 bp open reading frame |
| Protein |
 | |
| 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 |
| Note | |
| Entity | gastrointestinal tumors (see above) |
| Bibliography |
| The 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, Shapiro M, Morse HC 3rd, Langdon WY |
| Oncogene. 1991 ; 6 (4) : 653-657. |
| PMID 2030914 |
| The coding region of the Bloom syndrome BLM gene and of the CBL proto-oncogene is mutated in genetically unstable sporadic gastrointestinal tumors. |
| Calin G, Herlea V, Barbanti-Brodano G, Negrini M |
| Cancer research. 1998 ; 58 (17) : 3777-3781. |
| PMID 9731483 |
| Association of a chromosome deletion syndrome with a fragile site within the proto-oncogene CBL2. |
| Jones C, Penny L, Mattina T, Yu S, Baker E, Voullaire L, Langdon WY, Sutherland GR, Richards RI, Tunnacliffe A |
| Nature. 1995 ; 376 (6536) : 145-149. |
| PMID 7603564 |
| v-cbl, an oncogene from a dual-recombinant murine retrovirus that induces early B-lineage lymphomas. |
| Langdon WY, Hartley JW, Klinken SP, Ruscetti SK, Morse HC 3rd |
| Proceedings of the National Academy of Sciences of the United States of America. 1989 ; 86 (4) : 1168-1172. |
| PMID 2784003 |
| Cbl: complex formation and functional implications. |
| Liu YC, Altman A |
| Cellular signalling. 1998 ; 10 (6) : 377-385. |
| PMID 9720760 |
| Citation |
| This paper should be referenced as such : |
| Rosnet, O |
| CBL (Cas-Br-M (murine) ecotropic retroviral transforming sequence) |
| Atlas Genet Cytogenet Oncol Haematol. 1999;3(3):130-131. |
| Free journal version : [ pdf ] [ DOI ] |
| On line version : http://AtlasGeneticsOncology.org/Genes/CBLID171.html |
| Other Leukemias implicated (Data extracted from papers in the Atlas) [ 3 ] |
|
del(11)(q23q23) KMT2A/CBL::t(11;11)(q23;q23) KMT2A/CBL
Juvenile myelomonocytic leukemia (JMML) t(9;11)(p24;q23) CBL/KANK1 |
| Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 3 ] |
|
CBL/CXCR5 (11q23)
CBL/PHLDB1 (11q23) t(11;11)(q23;q24) CBL/VWA5A |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed Nov 13 21:07:22 CET 2019 |
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