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

Written1999-09Olivier Rosnet
Centre d'Immunologie INSERM-CNRS de Marseille-Luminy Case 906, 13288 Marseille Cedex 9, France

(Note : for Links provided by Atlas : click)

Identity

Alias_namesCBL2
Cas-Br-M (murine) ecotropic retroviral transforming sequence
Cbl proto-oncogene, E3 ubiquitin protein ligase
Alias_symbol (synonym)RNF55
c-Cbl
HGNC (Hugo) CBL
LocusID (NCBI) 867
Atlas_Id 171
Location 11q23.3  [Link to chromosome band 11q23]
Location_base_pair Starts at 119076986 and ends at 119178859 bp from pter ( according to hg19-Feb_2009)  [Mapping CBL.png]
 
  CBL (11q23) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Fusion genes
(updated 2016)
CBL (11q23.3) / CBL (11q23.3)CBL (11q23.3) / CXCR5 (11q23.3)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 ]
  Classification of myelodysplastic syndromes 2015
Chronic Myelomonocytic Leukemia (CMML)
del(11)(q23q23) KMT2A/CBL::t(11;11)(q23;q23) KMT2A/CBL


External links

Nomenclature
HGNC (Hugo)CBL   1541
LRG (Locus Reference Genomic)LRG_608
Cards
AtlasCBLID171
Entrez_Gene (NCBI)CBL  867  Cbl proto-oncogene, E3 ubiquitin protein ligase
AliasesC-CBL; CBL2; FRA11B; NSLL; 
RNF55
GeneCards (Weizmann)CBL
Ensembl hg19 (Hinxton)ENSG00000110395 [Gene_View]  chr11:119076986-119178859 [Contig_View]  CBL [Vega]
Ensembl hg38 (Hinxton)ENSG00000110395 [Gene_View]  chr11:119076986-119178859 [Contig_View]  CBL [Vega]
ICGC DataPortalENSG00000110395
TCGA cBioPortalCBL
AceView (NCBI)CBL
Genatlas (Paris)CBL
WikiGenes867
SOURCE (Princeton)CBL
Genetics Home Reference (NIH)CBL
Genomic and cartography
GoldenPath hg19 (UCSC)CBL  -     chr11:119076986-119178859 +  11q23.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)CBL  -     11q23.3   [Description]    (hg38-Dec_2013)
EnsemblCBL - 11q23.3 [CytoView hg19]  CBL - 11q23.3 [CytoView hg38]
Mapping of homologs : NCBICBL [Mapview hg19]  CBL [Mapview hg38]
OMIM165360   613563   
Gene and transcription
Genbank (Entrez)AA806454 AK092300 AL832396 BC132733 BC136463
RefSeq transcript (Entrez)NM_005188
RefSeq genomic (Entrez)NC_000011 NC_018922 NG_016808 NT_033899 NW_004929381
Consensus coding sequences : CCDS (NCBI)CBL
Cluster EST : UnigeneHs.504096 [ NCBI ]
CGAP (NCI)Hs.504096
Alternative Splicing GalleryENSG00000110395
Gene ExpressionCBL [ NCBI-GEO ]   CBL [ EBI - ARRAY_EXPRESS ]   CBL [ SEEK ]   CBL [ MEM ]
Gene Expression Viewer (FireBrowse)CBL [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)867
GTEX Portal (Tissue expression)CBL
Protein : pattern, domain, 3D structure
UniProt/SwissProtP22681   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP22681  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP22681
Splice isoforms : SwissVarP22681
Catalytic activity : Enzyme6.3.2.- [ Enzyme-Expasy ]   6.3.2.-6.3.2.- [ IntEnz-EBI ]   6.3.2.- [ BRENDA ]   6.3.2.- [ KEGG ]   
PhosPhoSitePlusP22681
Domaine pattern : Prosite (Expaxy)CBL_PTB (PS51506)    UBA (PS50030)    ZF_RING_1 (PS00518)    ZF_RING_2 (PS50089)   
Domains : Interpro (EBI)Adaptor_Cbl    Adaptor_Cbl_EF_hand-like    Adaptor_Cbl_N_hlx    Adaptor_Cbl_SH2-like    Cbl_PTB    EF-hand-dom_pair    SH2    UBA    UBA-like    Znf_RING    Znf_RING/FYVE/PHD    Znf_RING_CS   
Domain families : Pfam (Sanger)Cbl_N (PF02262)    Cbl_N2 (PF02761)    Cbl_N3 (PF02762)    UBA (PF00627)   
Domain families : Pfam (NCBI)pfam02262    pfam02761    pfam02762    pfam00627   
Domain families : Smart (EMBL)RING (SM00184)  UBA (SM00165)  
Conserved Domain (NCBI)CBL
DMDM Disease mutations867
Blocks (Seattle)CBL
PDB (SRS)1B47    1FBV    1YVH    2CBL    2JUJ    2K4D    2OO9    2Y1M    2Y1N    3BUM    3BUN    3BUO    3BUW    3BUX    3OB1    3OB2    3PLF    4A49    4A4B    4A4C    4GPL   
PDB (PDBSum)1B47    1FBV    1YVH    2CBL    2JUJ    2K4D    2OO9    2Y1M    2Y1N    3BUM    3BUN    3BUO    3BUW    3BUX    3OB1    3OB2    3PLF    4A49    4A4B    4A4C    4GPL   
PDB (IMB)1B47    1FBV    1YVH    2CBL    2JUJ    2K4D    2OO9    2Y1M    2Y1N    3BUM    3BUN    3BUO    3BUW    3BUX    3OB1    3OB2    3PLF    4A49    4A4B    4A4C    4GPL   
PDB (RSDB)1B47    1FBV    1YVH    2CBL    2JUJ    2K4D    2OO9    2Y1M    2Y1N    3BUM    3BUN    3BUO    3BUW    3BUX    3OB1    3OB2    3PLF    4A49    4A4B    4A4C    4GPL   
Structural Biology KnowledgeBase1B47    1FBV    1YVH    2CBL    2JUJ    2K4D    2OO9    2Y1M    2Y1N    3BUM    3BUN    3BUO    3BUW    3BUX    3OB1    3OB2    3PLF    4A49    4A4B    4A4C    4GPL   
SCOP (Structural Classification of Proteins)1B47    1FBV    1YVH    2CBL    2JUJ    2K4D    2OO9    2Y1M    2Y1N    3BUM    3BUN    3BUO    3BUW    3BUX    3OB1    3OB2    3PLF    4A49    4A4B    4A4C    4GPL   
CATH (Classification of proteins structures)1B47    1FBV    1YVH    2CBL    2JUJ    2K4D    2OO9    2Y1M    2Y1N    3BUM    3BUN    3BUO    3BUW    3BUX    3OB1    3OB2    3PLF    4A49    4A4B    4A4C    4GPL   
SuperfamilyP22681
Human Protein AtlasENSG00000110395
Peptide AtlasP22681
HPRD01320
IPIIPI00027269   
Protein Interaction databases
DIP (DOE-UCLA)P22681
IntAct (EBI)P22681
FunCoupENSG00000110395
BioGRIDCBL
STRING (EMBL)CBL
ZODIACCBL
Ontologies - Pathways
QuickGOP22681
Ontology : AmiGOphosphotyrosine binding  transcription factor activity, sequence-specific DNA binding  ubiquitin-protein transferase activity  signal transducer activity  calcium ion binding  protein binding  nucleus  cytoplasm  cytosol  plasma membrane  plasma membrane  regulation of transcription, DNA-templated  cell surface receptor signaling pathway  epidermal growth factor receptor signaling pathway  transforming growth factor beta receptor signaling pathway  zinc ion binding  fibroblast growth factor receptor signaling pathway  positive regulation of phosphatidylinositol 3-kinase signaling  protein ubiquitination  flotillin complex  ligase activity  SH3 domain binding  protein kinase binding  negative regulation of epidermal growth factor receptor signaling pathway  negative regulation of epidermal growth factor receptor signaling pathway  protein ubiquitination involved in ubiquitin-dependent protein catabolic process  negative regulation of apoptotic process  positive regulation of epidermal growth factor receptor signaling pathway  ephrin receptor binding  positive regulation of receptor-mediated endocytosis  positive regulation of receptor-mediated endocytosis  ubiquitin protein ligase activity  
Ontology : EGO-EBIphosphotyrosine binding  transcription factor activity, sequence-specific DNA binding  ubiquitin-protein transferase activity  signal transducer activity  calcium ion binding  protein binding  nucleus  cytoplasm  cytosol  plasma membrane  plasma membrane  regulation of transcription, DNA-templated  cell surface receptor signaling pathway  epidermal growth factor receptor signaling pathway  transforming growth factor beta receptor signaling pathway  zinc ion binding  fibroblast growth factor receptor signaling pathway  positive regulation of phosphatidylinositol 3-kinase signaling  protein ubiquitination  flotillin complex  ligase activity  SH3 domain binding  protein kinase binding  negative regulation of epidermal growth factor receptor signaling pathway  negative regulation of epidermal growth factor receptor signaling pathway  protein ubiquitination involved in ubiquitin-dependent protein catabolic process  negative regulation of apoptotic process  positive regulation of epidermal growth factor receptor signaling pathway  ephrin receptor binding  positive regulation of receptor-mediated endocytosis  positive regulation of receptor-mediated endocytosis  ubiquitin protein ligase activity  
Pathways : BIOCARTACBL mediated ligand-induced downregulation of EGF receptors [Genes]    Sprouty regulation of tyrosine kinase signals [Genes]    IL-2 Receptor Beta Chain in T cell Activation [Genes]   
Pathways : KEGGErbB signaling pathway    Ubiquitin mediated proteolysis    Endocytosis    Jak-STAT signaling pathway    T cell receptor signaling pathway    Insulin signaling pathway    Bacterial invasion of epithelial cells    Pathways in cancer    Proteoglycans in cancer    Chronic myeloid leukemia   
REACTOMEP22681 [protein]
REACTOME PathwaysR-HSA-5654726 Negative regulation of FGFR1 signaling [pathway]
REACTOME PathwaysR-HSA-182971 EGFR downregulation [pathway]
REACTOME PathwaysR-HSA-1295596 Spry regulation of FGF signaling [pathway]
REACTOME PathwaysR-HSA-5654727 Negative regulation of FGFR2 signaling [pathway]
REACTOME PathwaysR-HSA-1059683 Interleukin-6 signaling [pathway]
REACTOME PathwaysR-HSA-2173789 TGF-beta receptor signaling activates SMADs [pathway]
REACTOME PathwaysR-HSA-1295596 Spry regulation of FGF signaling [pathway]
REACTOME PathwaysR-HSA-1433559 Regulation of KIT signaling [pathway]
REACTOME PathwaysR-HSA-5654733 Negative regulation of FGFR4 signaling [pathway]
REACTOME PathwaysR-HSA-1236382 Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants [pathway]
REACTOME PathwaysR-HSA-912631 Regulation of signaling by CBL [pathway]
REACTOME PathwaysR-HSA-5654732 Negative regulation of FGFR3 signaling [pathway]
REACTOME PathwaysR-HSA-5637810 Constitutive Signaling by EGFRvIII [pathway]
REACTOME PathwaysR-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers [pathway]
REACTOME PathwaysR-HSA-1295596 Spry regulation of FGF signaling [pathway]
REACTOME PathwaysR-HSA-1295596 Spry regulation of FGF signaling [pathway]
NDEx NetworkCBL
Atlas of Cancer Signalling NetworkCBL
Wikipedia pathwaysCBL
Orthology - Evolution
OrthoDB867
GeneTree (enSembl)ENSG00000110395
Phylogenetic Trees/Animal Genes : TreeFamCBL
HOVERGENP22681
HOGENOMP22681
Homologs : HomoloGeneCBL
Homology/Alignments : Family Browser (UCSC)CBL
Gene fusions - Rearrangements
Fusion : MitelmanCBL/CXCR5 [11q23.3/11q23.3]  
Fusion : MitelmanCBL/PHLDB1 [11q23.3/11q23.3]  [t(11;11)(q23;q23)]  
Fusion : MitelmanCBL/VWA5A [11q23.3/11q24.2]  [t(11;11)(q23;q24)]  
Fusion : COSMICKMT2A [11q23.3]  -  CBL [11q23.3]  [fusion_1970]  [fusion_1971]  
Fusion: TCGACBL 11q23.3 CXCR5 11q23.3 PRAD
Fusion: TCGACBL 11q23.3 PHLDB1 11q23.3 BRCA
Fusion: TCGACBL 11q23.3 VWA5A 11q24.2 LUAD
Fusion : TICdbKMT2A [11q23.3]  -  CBL [11q23.3]
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCBL [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CBL
dbVarCBL
ClinVarCBL
1000_GenomesCBL 
Exome Variant ServerCBL
ExAC (Exome Aggregation Consortium)CBL (select the gene name)
Genetic variants : HAPMAP867
Genomic Variants (DGV)CBL [DGVbeta]
DECIPHER (Syndromes)11:119076986-119178859  ENSG00000110395
CONAN: Copy Number AnalysisCBL 
Mutations
ICGC Data PortalCBL 
TCGA Data PortalCBL 
Broad Tumor PortalCBL
OASIS PortalCBL [ Somatic mutations - Copy number]
Cancer Gene: CensusCBL 
Somatic Mutations in Cancer : COSMICCBL  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCBL
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Mendelian genes
BioMutasearch CBL
DgiDB (Drug Gene Interaction Database)CBL
DoCM (Curated mutations)CBL (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CBL (select a term)
intoGenCBL
NCG5 (London)CBL
Cancer3DCBL(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM165360    613563   
Orphanet22353    11747   
MedgenCBL
Genetic Testing Registry CBL
NextProtP22681 [Medical]
TSGene867
GENETestsCBL
Huge Navigator CBL [HugePedia]
snp3D : Map Gene to Disease867
BioCentury BCIQCBL
ClinGenCBL (curated)
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD867
Chemical/Pharm GKB GenePA26115
Clinical trialCBL
Miscellaneous
canSAR (ICR)CBL (select the gene name)
Probes
Litterature
PubMed499 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCBL
EVEXCBL
GoPubMedCBL
iHOPCBL
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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