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

Identity

Other namesCBL2
HGNC (Hugo) CBL
LocusID (NCBI) 867
Location 11q23.3
Location_base_pair Starts at 119076986 and ends at 119178859 bp from pter ( according to hg19-Feb_2009)  [Mapping]
 
  CBL (11q23) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.

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

Entity gastrointestinal tumors (see above)
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias 11q23ChildAMLID1615

External links

Nomenclature
HGNC (Hugo)CBL   1541
Cards
AtlasCBLID171
Entrez_Gene (NCBI)CBL  867  Cbl proto-oncogene, E3 ubiquitin protein ligase
GeneCards (Weizmann)CBL
Ensembl (Hinxton)ENSG00000110395 [Gene_View]  chr11:119076986-119178859 [Contig_View]  CBL [Vega]
ICGC DataPortalENSG00000110395
cBioPortalCBL
AceView (NCBI)CBL
Genatlas (Paris)CBL
WikiGenes867
SOURCE (Princeton)NM_005188
Genomic and cartography
GoldenPath (UCSC)CBL  -  11q23.3   chr11:119076986-119178859 +  11q23.3-qter   [Description]    (hg19-Feb_2009)
EnsemblCBL - 11q23.3-qter [CytoView]
Mapping of homologs : NCBICBL [Mapview]
OMIM165360   600651   613563   
Gene and transcription
Genbank (Entrez)AA806454 AK092300 AL832396 BC132733 BC136463
RefSeq transcript (Entrez)NM_005188
RefSeq genomic (Entrez)AC_000143 NC_000011 NC_018922 NG_016808 NT_033899 NW_001838042 NW_004929381
Consensus coding sequences : CCDS (NCBI)CBL
Cluster EST : UnigeneHs.504096 [ NCBI ]
CGAP (NCI)Hs.504096
Alternative Splicing : Fast-db (Paris)GSHG0005316
Alternative Splicing GalleryENSG00000110395
Gene ExpressionCBL [ NCBI-GEO ]     CBL [ SEEK ]   CBL [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP22681 (Uniprot)
NextProtP22681  [Medical]
With graphics : InterProP22681
Splice isoforms : SwissVarP22681 (Swissvar)
Catalytic activity : Enzyme6.3.2.- [ Enzyme-Expasy ]   6.3.2.-6.3.2.- [ IntEnz-EBI ]   6.3.2.- [ BRENDA ]   6.3.2.- [ KEGG ]   
Domaine pattern : Prosite (Expaxy)CBL_PTB (PS51506)    UBA (PS50030)    ZF_RING_1 (PS00518)    ZF_RING_2 (PS50089)   
Domains : Interpro (EBI)Adaptor_Cbl [organisation]   Adaptor_Cbl_EF_hand-like [organisation]   Adaptor_Cbl_N_hlx [organisation]   Adaptor_Cbl_SH2-like [organisation]   Cbl_PTB [organisation]   EF-hand-dom_pair [organisation]   SH2 [organisation]   UBA-like [organisation]   UBA/transl_elong_EF1B_N_euk [organisation]   UBA/Ts_N [organisation]   Znf_C3HC4_RING-type [organisation]   Znf_RING [organisation]   Znf_RING/FYVE/PHD [organisation]   Znf_RING_CS [organisation]  
Related proteins : CluSTrP22681
Domain families : Pfam (Sanger)Cbl_N (PF02262)    Cbl_N2 (PF02761)    Cbl_N3 (PF02762)    UBA (PF00627)    zf-C3HC4 (PF00097)   
Domain families : Pfam (NCBI)pfam02262    pfam02761    pfam02762    pfam00627    pfam00097   
Domain families : Smart (EMBL)RING (SM00184)  UBA (SM00165)  
DMDM Disease mutations867
Blocks (Seattle)P22681
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   
Human Protein AtlasENSG00000110395 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasP22681
HPRD01320
IPIIPI00027269   
Protein Interaction databases
DIP (DOE-UCLA)P22681
IntAct (EBI)P22681
FunCoupENSG00000110395
BioGRIDCBL
InParanoidP22681
Interologous Interaction database P22681
IntegromeDBCBL
STRING (EMBL)CBL
Ontologies - Pathways
Ontology : AmiGOphosphotyrosine binding  sequence-specific DNA binding transcription factor activity  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  protein ubiquitination  flotillin complex  ligase activity  SH3 domain binding  negative regulation of epidermal growth factor receptor signaling pathway  negative regulation of apoptotic process  ephrin receptor binding  positive regulation of receptor-mediated endocytosis  
Ontology : EGO-EBIphosphotyrosine binding  sequence-specific DNA binding transcription factor activity  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  protein ubiquitination  flotillin complex  ligase activity  SH3 domain binding  negative regulation of epidermal growth factor receptor signaling pathway  negative regulation of apoptotic process  ephrin receptor binding  positive regulation of receptor-mediated endocytosis  
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   
Protein Interaction DatabaseCBL
Wikipedia pathwaysCBL
Gene fusion - rearrangments
Rearrangement : TICdbKMT2A [11q23.3]  -  CBL [1q21.3]
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)CBL
snp3D : Map Gene to Disease867
SNP (GeneSNP Utah)CBL
SNP : HGBaseCBL
Genetic variants : HAPMAPCBL
Exome VariantCBL
1000_GenomesCBL 
ICGC programENSG00000110395 
Cancer Gene: CensusCBL 
Somatic Mutations in Cancer : COSMICCBL 
CONAN: Copy Number AnalysisCBL 
Mutations and Diseases : HGMDCBL
Mutations and Diseases : intOGenCBL
Genomic VariantsCBL  CBL [DGVbeta]
dbVarCBL
ClinVarCBL
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM165360    600651    613563   
MedgenCBL
GENETestsCBL
Disease Genetic AssociationCBL
Huge Navigator CBL [HugePedia]  CBL [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneCBL
Homology/Alignments : Family Browser (UCSC)CBL
Phylogenetic Trees/Animal Genes : TreeFamCBL
Chemical/Protein Interactions : CTD867
Chemical/Pharm GKB GenePA26115
Clinical trialCBL
Cancer Resource (Charite)ENSG00000110395
Other databases
Probes
ProbeCancer Cytogenetics (Bari)
Litterature
PubMed499 Pubmed reference(s) in Entrez
CoreMineCBL
iHOPCBL
OncoSearchCBL

Bibliography

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
 
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
 
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
 
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
 
Cbl: complex formation and functional implications.
Liu YC, Altman A
Cellular signalling. 1998 ; 10 (6) : 377-385.
PMID 9720760
 
Cbl: complex formation and functional implications.
Liu YC, Altman A
Cellular signalling. 1998 ; 10 (6) : 377-385.
PMID 9720760
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written09-1999Olivier Rosnet

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 online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/CBLID171.html

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indexed on : Tue Aug 26 15:26:52 CEST 2014

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