Cancer Protein Description
This report provides a detailed description of a selected cancer protein with information collected from various sources, including UniProt, the Wellcome Trust Sanger Institute’s Catalogue of Somatic Mutations in Cancer (COSMIC), and the Atlas of Genetics and Cytogenetics in Oncology and Haematology.
| Protein Name: | Cbl |
| Gene Name: | CBL |
| Protein Full Name: | E3 ubiquitin-protein ligase CBL |
| Alias: | Cas-Br-M (murine) ecotropic retroviral transforming; Cas-Br-M (murine) ecotropic retroviral transforming sequence; CBL E3 ubiquitin protein ligase; CBL2; Oncogene CBL2; Proto-oncogene c-CBL; RNF55; Signal transduction protein CBL |
| Mass (Da): | 99633 |
| Number AA: | 906 |
| UniProt ID: | P22681 |
| Locus ID: | 867 |
| COSMIC ID: | CBL |
| Gene location on chromosome: | 11q23-q25 |
| Cancer protein type: | TSP |
| Effect of cancer mutation on protein: | LOSS |
| Effect of active protein on cancer: | INHIBITS |
| Number of cancer specimens: | 28105 |
| Percent of cancer specimens with mutations: | 1.85 |
| General distribution of mutations: | Multi-site |
| Location of most mutations: | While point mutations are spread out over the protein length, there is a strong cluster from AA 366-420. This region. This region also includes insertions and deletions. It seems feasible that disruption of this region might relieve an inhibition. |
| Commonly recorded point mutations: | G13R (319); G12V (252); Q61R (207); Q61L (155); Q61K (87); G12S (80); G12D (68); |
| Mutations observed as inherited: | Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) (heterozygous mutation sometimes inherited from an unaffected carrier father) |
| Deregulated in translocations: | 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, which have a del(11)(q23qter) telomeric of an expa |
| Transduced into viral genome: | Cas NS-1 virus - Mouse |
| Normal role description: | CBL functions as an adaptor protein for RTK's by positive regulation of RTK ubiquitination in an SH-2 and RING finger domain dependent manner. Ubiquitination of receptor RTK's terminates signalling by marking active receptors for degradation. CBL also negatively regulates the tyrosine phosphorylation of ZAP70 substrates in T cells. Defects in CBL are the cause of Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL). |
| Commentary on involvement of protein in cancer: | * Note: not all 131 haematopoietic/lymphoid samples are from CML. A portion of samples are from myelofibrosis/juvenile myelomonocytic leukemia/acute myeloid leukemia/myelodysplastic syndrome tumour tissue. The gene is also mutated in 2% of lung- and ovary samples, and in 1% of breast cancer samples. 27/159 juvenile myelomonocytic leukemia samples in one study (10/49 samples in another study) were mutated with mutations mainly located throughout the linker and RING finger domains, with the most common affected residue being tyr371 (Cited in OMIM) |