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

Identity

Other names	CBL2
HGNC	CBL
Location	11q23-q25
	CBL (11q23) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics. Laboratories willing to validate the probes are welcome : contact rocchi@biologia.uniba.it

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)

External links

	Nomenclature
HGNC	CBL   1541
Entrez_Gene	CBL  867  Cas-Br-M (murine) ecotropic retroviral transforming sequence
	Cards
Atlas	CBLID171
GeneCards	CBL
Ensembl	CBL [Search_View]   ENSG00000110395 [Gene_View]
Genatlas	CBL
GeneLynx	CBL
eGenome	CBL
euGene	867
	Genomic and cartography
GoldenPath	CBL  -     chr11:118582200-118684069 +  11q23.3-qter   [Description]    (hg18-Mar_2006)
Ensembl	CBL - 11q23.3-qter [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	CBL
	Gene and transcription
Genbank	AK092300 [ ENTREZ ]
Genbank	AL832396 [ ENTREZ ]
Genbank	BC132733 [ ENTREZ ]
Genbank	BG722940 [ ENTREZ ]
Genbank	BX648139 [ ENTREZ ]
RefSeq	NM_005188 [ SRS ]    NM_005188 [ ENTREZ ]
RefSeq	AC_000054 [ SRS ]    AC_000054 [ ENTREZ ]
RefSeq	AC_000143 [ SRS ]    AC_000143 [ ENTREZ ]
RefSeq	NC_000011 [ SRS ]    NC_000011 [ ENTREZ ]
RefSeq	NT_033899 [ SRS ]    NT_033899 [ ENTREZ ]
RefSeq	NW_001838042 [ SRS ]    NW_001838042 [ ENTREZ ]
RefSeq	NW_925173 [ SRS ]    NW_925173 [ ENTREZ ]
AceView	CBL AceView - NCBI
Unigene	Hs.504096 [ SRS ]    Hs.504096 [ NCBI ]     HS504096 [ spliceNest ]
Fast-db	14496 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P22681 [ SRS]    P22681 [ EXPASY ]     P22681 [ INTERPRO ]     P22681 [ UNIPROT ]
Prosite	PS50001 SH2 [ SRS ]    PS50001 SH2 [ Expasy ]
Prosite	PS50030 UBA [ SRS ]    PS50030 UBA [ Expasy ]
Prosite	PS00518 ZF_RING_1 [ SRS ]    PS00518 ZF_RING_1 [ Expasy ]
Prosite	PS50089 ZF_RING_2 [ SRS ]    PS50089 ZF_RING_2 [ Expasy ]
Interpro	IPR014741 Adaptor_Cbl_EF_Hand-like [ SRS ]    IPR014741 Adaptor_Cbl_EF_Hand-like [ EBI ]
Interpro	IPR003153 Adaptor_Cbl_N [ SRS ]    IPR003153 Adaptor_Cbl_N [ EBI ]
Interpro	IPR014742 Adaptor_Cbl_SH2-like [ SRS ]    IPR014742 Adaptor_Cbl_SH2-like [ EBI ]
Interpro	IPR011992 EF-Hand_type [ SRS ]    IPR011992 EF-Hand_type [ EBI ]
Interpro	IPR000980 SH2 [ SRS ]    IPR000980 SH2 [ EBI ]
Interpro	IPR000449 UBA/transl_elong_EF1B_N [ SRS ]    IPR000449 UBA/transl_elong_EF1B_N [ EBI ]
Interpro	IPR015940 UBA/transl_elong_EF1B_N_euk [ SRS ]    IPR015940 UBA/transl_elong_EF1B_N_euk [ EBI ]
Interpro	IPR001841 Znf_RING [ SRS ]    IPR001841 Znf_RING [ EBI ]
Interpro	IPR013083 Znf_RING/FYVE/PHD [ SRS ]    IPR013083 Znf_RING/FYVE/PHD [ EBI ]
CluSTr	P22681
Pfam	PF02262 Cbl_N [ SRS ]    PF02262 Cbl_N [ Sanger ]    pfam02262 [ NCBI-CDD ]
Pfam	PF02761 Cbl_N2 [ SRS ]    PF02761 Cbl_N2 [ Sanger ]    pfam02761 [ NCBI-CDD ]
Pfam	PF02762 Cbl_N3 [ SRS ]    PF02762 Cbl_N3 [ Sanger ]    pfam02762 [ NCBI-CDD ]
Pfam	PF00627 UBA [ SRS ]    PF00627 UBA [ Sanger ]    pfam00627 [ NCBI-CDD ]
Pfam	PF00097 zf-C3HC4 [ SRS ]    PF00097 zf-C3HC4 [ Sanger ]    pfam00097 [ NCBI-CDD ]
Smart	SM00184 RING [EMBL]
Smart	SM00165 UBA [EMBL]
Blocks	P22681
PDB	1B47 [ SRS ]    1B47 [ PdbSum ],   1B47 [ IMB ]   1B47 [ RSDB ]
PDB	1FBV [ SRS ]    1FBV [ PdbSum ],   1FBV [ IMB ]   1FBV [ RSDB ]
PDB	1YVH [ SRS ]    1YVH [ PdbSum ],   1YVH [ IMB ]   1YVH [ RSDB ]
PDB	2CBL [ SRS ]    2CBL [ PdbSum ],   2CBL [ IMB ]   2CBL [ RSDB ]
PDB	2OO9 [ SRS ]    2OO9 [ PdbSum ],   2OO9 [ IMB ]   2OO9 [ RSDB ]
PDB	3BUM [ SRS ]    3BUM [ PdbSum ],   3BUM [ IMB ]   3BUM [ RSDB ]
PDB	3BUN [ SRS ]    3BUN [ PdbSum ],   3BUN [ IMB ]   3BUN [ RSDB ]
PDB	3BUO [ SRS ]    3BUO [ PdbSum ],   3BUO [ IMB ]   3BUO [ RSDB ]
PDB	3BUW [ SRS ]    3BUW [ PdbSum ],   3BUW [ IMB ]   3BUW [ RSDB ]
PDB	3BUX [ SRS ]    3BUX [ PdbSum ],   3BUX [ IMB ]   3BUX [ RSDB ]
HPRD	01320
	Protein Interaction databases
DIP	P22681
IntAct	P22681
	Polymorphism : SNP, mutations, diseases
OMIM	165360    [ map ]
GENECLINICS	165360
SNP	CBL [dbSNP-NCBI]
SNP	NM_005188 [SNP-NCI]
SNP	CBL [GeneSNPs - Utah]  CBL] [HGBASE - SRS]
HAPMAP	CBL [HAPMAP]
COSMIC	CBL [Somatic mutation (COSMIC-CGP-Sanger)]
TICdb	CBL [Translocation breakpoints In Cancer]
HGMD	CBL
	General knowledge
Family Browser	CBL [UCSC Family Browser]
SOURCE	NM_005188
SMD	Hs.504096
SAGE	Hs.504096
Enzyme	6.3.2.- [ Enzyme-Expasy ]   6.3.2.- [ Enzyme-SRS ]   6.3.2.- [ IntEnz-EBI ]   6.3.2.- [ BRENDA ]   6.3.2.- [ KEGG ]   6.3.2.- [ WIT ]
GO	transcription factor activity [Amigo]  transcription factor activity
GO	ubiquitin-protein ligase activity [Amigo]  ubiquitin-protein ligase activity
GO	ubiquitin-protein ligase activity [Amigo]  ubiquitin-protein ligase activity
GO	signal transducer activity [Amigo]  signal transducer activity
GO	calcium ion binding [Amigo]  calcium ion binding
GO	protein binding [Amigo]  protein binding
GO	nucleus [Amigo]  nucleus
GO	cytoplasm [Amigo]  cytoplasm
GO	cytosol [Amigo]  cytosol
GO	plasma membrane [Amigo]  plasma membrane
GO	plasma membrane [Amigo]  plasma membrane
GO	cell surface receptor linked signal transduction [Amigo]  cell surface receptor linked signal transduction
GO	epidermal growth factor receptor signaling pathway [Amigo]  epidermal growth factor receptor signaling pathway
GO	zinc ion binding [Amigo]  zinc ion binding
GO	protein ubiquitination [Amigo]  protein ubiquitination
GO	ligase activity [Amigo]  ligase activity
GO	positive regulation of receptor-mediated endocytosis [Amigo]  positive regulation of receptor-mediated endocytosis
BIOCARTA	CBL mediated ligand-induced downregulation of EGF receptors    [Genes]
BIOCARTA	IL-2 Receptor Beta Chain in T cell Activation    [Genes]
BIOCARTA	Sprouty regulation of tyrosine kinase signals    [Genes]
KEGG	Jak-STAT signaling pathway
KEGG	T cell receptor signaling pathway
KEGG	Insulin signaling pathway
PubGene	CBL
TreeFam	CBL
CTD	867 [Comparative ToxicoGenomics Database]
	Other databases
	Probes
Probe	Cancer Cytogenetics (Bari)
Probe	CBL Related clones (RZPD - Berlin)
	PubMed
PubMed	164 Pubmed reference(s) in LocusLink

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 articles	automatic search in PubMed
Last year publications	automatic search in PubMed

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Contributor(s)

Written	09-1999	Olivier 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. September 1999 . URL : http://AtlasGeneticsOncology.org/Genes/CBLID171.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Aug 11 21:12:45 2008