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Aliases for CBL Gene

Aliases for CBL Gene

  • Cbl Proto-Oncogene, E3 Ubiquitin Protein Ligase 2 3
  • CBL2 3 4 6
  • Cas-Br-M (Murine) Ecotropic Retroviral Transforming Sequence 2 3
  • Casitas B-Lineage Lymphoma Proto-Oncogene 3 4
  • Signal Transduction Protein CBL 3 4
  • RING Finger Protein 55 3 4
  • Proto-Oncogene C-Cbl 3 4
  • Oncogene CBL2 2 3
  • RNF55 3 4
  • NSLL 3 6
  • Fragile Site, Folic Acid Type, Rare, Fra(11)(Q23.3) 3
  • E3 Ubiquitin-Protein Ligase CBL 3
  • EC 6.3.2.- 4
  • EC 6.3.2 63
  • FRA11B 3
  • C-CBL 3

External Ids for CBL Gene

Previous HGNC Symbols for CBL Gene

  • CBL2

Previous GeneCards Identifiers for CBL Gene

  • GC11M121124
  • GC11P120588
  • GC11P119110
  • GC11P118614
  • GC11P118582
  • GC11P115017

Summaries for CBL Gene

Entrez Gene Summary for CBL Gene

  • This gene is a proto-oncogene that encodes a RING finger E3 ubiquitin ligase. The encoded protein is one of the enzymes required for targeting substrates for degradation by the proteasome. This protein mediates the transfer of ubiquitin from ubiquitin conjugating enzymes (E2) to specific substrates. This protein also contains an N-terminal phosphotyrosine binding domain that allows it to interact with numerous tyrosine-phosphorylated substrates and target them for proteasome degradation. As such it functions as a negative regulator of many signal transduction pathways. This gene has been found to be mutated or translocated in many cancers including acute myeloid leukaemia. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Mar 2012]

GeneCards Summary for CBL Gene

CBL (Cbl Proto-Oncogene, E3 Ubiquitin Protein Ligase) is a Protein Coding gene. Diseases associated with CBL include noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia and noonan syndrome-like disorder with juvenile myelomonocytic leukemia. Among its related pathways are PI-3K cascade and Signaling by FGFR. GO annotations related to this gene include sequence-specific DNA binding transcription factor activity and ubiquitin-protein transferase activity. An important paralog of this gene is CBLB.

UniProtKB/Swiss-Prot for CBL Gene

  • Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The Tyr-731 phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3.

Gene Wiki entry for CBL Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for CBL Gene

Genomics for CBL Gene

Regulatory Elements for CBL Gene

Epigenetics Products

  • DNA Methylation CpG Assay Predesigned for Pyrosequencing in human,mouse,rat

Genomic Location for CBL Gene

Start:
119,206,042 bp from pter
End:
119,308,149 bp from pter
Size:
102,108 bases
Orientation:
Plus strand

Genomic View for CBL Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for CBL Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CBL Gene

Proteins for CBL Gene

  • Protein details for CBL Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P22681-CBL_HUMAN
    Recommended name:
    E3 ubiquitin-protein ligase CBL
    Protein Accession:
    P22681
    Secondary Accessions:
    • A3KMP8

    Protein attributes for CBL Gene

    Size:
    906 amino acids
    Molecular mass:
    99633 Da
    Quaternary structure:
    • Interacts (phosphorylated at Tyr-731) with PIK3R1. Associates with NCK via its SH3 domain. The phosphorylated C-terminus interacts with CD2AP via its second SH3 domain. Binds to UBE2L3. Interacts with adapters SLA, SLA2 and with the phosphorylated C-terminus of SH2B2. Interacts with EGFR, SYK and ZAP70 via the highly conserved Cbl-N region. Also interacts with SORBS1 and INPPL1/SHIP2. Interacts with phosphorylated LAT2. May interact with CBLB (By similarity). Interacts with ALK, AXL, BLK, FGR and FGFR2. Interacts with CSF1R, EPHB1, FLT1, KDR, PDGFRA and PDGFRB; regulates receptor degradation through ubiquitination. Interacts with HCK and LYN. Interacts with TEK/TIE2 (tyrosine phosphorylated).
    Miscellaneous:
    • This protein has one functional calcium-binding site

    Three dimensional structures from OCA and Proteopedia for CBL Gene

neXtProt entry for CBL Gene

Proteomics data for CBL Gene at MOPED

Post-translational modifications for CBL Gene

  • Phosphorylated on tyrosine residues by ALK, EGFR, SYK, FYN and ZAP70 (By similarity). Phosphorylated on tyrosine residues in response to FLT1 and KIT signaling. Phosphorylated on tyrosine residues by INSR and FGR. Phosphorylated on several tyrosine residues by constitutively activated FGFR3. Not phosphorylated at Tyr-731 by FGFR3. Phosphorylated on tyrosine residues by activated CSF1R, PDGFRA and PDGFRB. Phosphorylated on tyrosine residues by HCK.
  • Ubiquitinated, leading to its degradation via the proteasome.
  • Ubiquitination at Lys7, Lys74, Lys105, Lys424, Lys471, and Lys521
  • Modification sites at PhosphoSitePlus

Other Protein References for CBL Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for CBL (Cbl)

Domains for CBL Gene

Gene Families for CBL Gene

HGNC:
  • RNF :RING-type (C3HC4) zinc fingers

Suggested Antigen Peptide Sequences for CBL Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P22681

UniProtKB/Swiss-Prot:

CBL_HUMAN :
  • P22681
Domain:
  • The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme
  • The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain
  • Contains 1 Cbl-PTB (Cbl-type phosphotyrosine-binding) domain.
  • Contains 1 UBA domain.
Similarity:
  • Contains 1 RING-type zinc finger.
genes like me logo Genes that share domains with CBL: view

Function for CBL Gene

Molecular function for CBL Gene

GENATLAS Biochemistry:
Cas-Br-M (murine) ecotropic retroviral transforming sequence,including a CGG trinucleotide repeat,abundantly expressed in thymus,acting as a RING-type E2-dependent ubiquitin protein ligase,binding and stimulating the ubiquitination of PDGFRs,EGFR,CSF1R,also interacting with signal transduction molecules,key mediator of HCK (hematopoietic cell kinase) induced signaling in hematopoietic cells
UniProtKB/Swiss-Prot Function:
Adapter protein that functions as a negative regulator of many signaling pathways that are triggered by activation of cell surface receptors. Acts as an E3 ubiquitin-protein ligase, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and then transfers it to substrates promoting their degradation by the proteasome. Recognizes activated receptor tyrosine kinases, including KIT, FLT1, FGFR1, FGFR2, PDGFRA, PDGFRB, EGFR, CSF1R, EPHA8 and KDR and terminates signaling. Recognizes membrane-bound HCK, SRC and other kinases of the SRC family and mediates their ubiquitination and degradation. Participates in signal transduction in hematopoietic cells. Plays an important role in the regulation of osteoblast differentiation and apoptosis. Essential for osteoclastic bone resorption. The Tyr-731 phosphorylated form induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3.

Enzyme Numbers (IUBMB) for CBL Gene

Gene Ontology (GO) - Molecular Function for CBL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001784 phosphotyrosine binding IEA --
GO:0003700 sequence-specific DNA binding transcription factor activity TAS 2030914
GO:0004842 ubiquitin-protein transferase activity TAS 15465819
GO:0004871 signal transducer activity IEA --
GO:0005509 calcium ion binding IEA --
genes like me logo Genes that share ontologies with CBL: view
genes like me logo Genes that share phenotypes with CBL: view

Animal Models for CBL Gene

MGI Knock Outs for CBL:

Animal Model Products

miRNA for CBL Gene

miRTarBase miRNAs that target CBL

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for CBL

In Situ Assay Products

Flow Cytometry Products

No data available for Transcription Factor Targeting and HOMER Transcription for CBL Gene

Localization for CBL Gene

Subcellular locations from UniProtKB/Swiss-Prot for CBL Gene

Cytoplasm. Cell membrane. Note=Colocalizes with FGFR2 in lipid rafts at the cell membrane.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for CBL Gene COMPARTMENTS Subcellular localization image for CBL gene
Compartment Confidence
plasma membrane 5
cytosol 4
nucleus 3
cytoskeleton 2
endosome 2
lysosome 2
vacuole 2
extracellular 1

Gene Ontology (GO) - Cellular Components for CBL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA --
GO:0005737 cytoplasm IDA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane TAS --
GO:0016600 colocalizes_with flotillin complex ISS --
genes like me logo Genes that share ontologies with CBL: view

Pathways for CBL Gene

genes like me logo Genes that share pathways with CBL: view

PCR Array Products

UniProtKB/Swiss-Prot P22681-CBL_HUMAN

  • Pathway: Protein modification; protein ubiquitination

Interacting Proteins for CBL Gene

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)
http://string-db.org/version_10/api/image/networkList?limit=0&targetmode=proteins&caller_identity=gene_cards&network_flavor=evidence&identifiers=9606.ENSP00000264033%0d%0a9606.ENSP00000350941%0d%0a9606.ENSP00000274335%0d%0a9606.ENSP00000346671%0d%0a9606.ENSP00000344818%0d%0a9606.ENSP00000381717%0d%0a
Selected Interacting proteins: P22681-CBL_HUMAN ENSP00000264033 for CBL Gene via MINT STRING UniProtKB I2D

Symbol External ID(s) Details
SH3KBP1
SPRY2
EGFR
MET
YWHAQ

Gene Ontology (GO) - Biological Process for CBL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006355 regulation of transcription, DNA-templated TAS 2030914
GO:0007166 cell surface receptor signaling pathway TAS 15465819
GO:0007173 epidermal growth factor receptor signaling pathway TAS 15465819
GO:0007179 transforming growth factor beta receptor signaling pathway TAS --
GO:0008543 fibroblast growth factor receptor signaling pathway TAS --
genes like me logo Genes that share ontologies with CBL: view

Compounds for CBL Gene

(5) HMDB Compounds for CBL Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine monophosphate
  • 5'-AMP
61-19-8
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
Calcium
  • Ca
7440-70-2
Phosphoric acid
  • acide phosphorique (FRENCH)
7664-38-2
Pyrophosphate
  • (4-)Diphosphoric acid ion
14000-31-8

(38) Novoseek inferred chemical compound relationships for CBL Gene

Compound -log(P) Hits PubMed IDs
tyrosine 85 261
phosphatidylinositol 66.9 50
phosphotyrosine 65.3 14
piceatannol 61.3 1
thiosemicarbazide 49.9 3
genes like me logo Genes that share compounds with CBL: view

Transcripts for CBL Gene

mRNA/cDNA for CBL Gene

(18) Selected AceView cDNA sequences:
(7) Additional mRNA sequences :
(2) REFSEQ mRNAs :
(1) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for CBL Gene

Cbl proto-oncogene, E3 ubiquitin protein ligase:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for CBL

Primer Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for CBL Gene

No ASD Table

Relevant External Links for CBL Gene

GeneLoc Exon Structure for
CBL
ECgene alternative splicing isoforms for
CBL

Expression for CBL Gene

mRNA expression in normal human tissues for CBL Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CBL Gene

This gene is overexpressed in Whole Blood (5.6).

Protein differential expression in normal tissues for CBL Gene

This gene is overexpressed in Peripheral blood mononuclear cells (14.6), Lymph node (6.3), Fetal ovary (6.3), and CD8 Tcells (6.1).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for CBL Gene

SOURCE GeneReport for Unigene cluster for CBL Gene Hs.504096

genes like me logo Genes that share expressions with CBL: view

Expression partners for CBL Gene

In Situ Assay Products

No data available for mRNA Expression by UniProt/SwissProt for CBL Gene

Orthologs for CBL Gene

This gene was present in the common ancestor of animals.

Orthologs for CBL Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia CBL 35
  • 91.82 (n)
  • 94.29 (a)
CBL 36
  • 92 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CBL 35
  • 91.54 (n)
  • 95.2 (a)
CBL 36
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Cbl 35
  • 88.08 (n)
  • 93.02 (a)
Cbl 16
Cbl 36
  • 91 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia CBL 35
  • 99.78 (n)
  • 100 (a)
CBL 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Cbl 35
  • 87.98 (n)
  • 92.48 (a)
oppossum
(Monodelphis domestica)
Mammalia CBL 36
  • 89 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 100 (a)
OneToMany
-- 36
  • 77 (a)
OneToMany
chicken
(Gallus gallus)
Aves CBL 35
  • 77.65 (n)
  • 85.63 (a)
CBL 36
  • 82 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CBL 36
  • 80 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia cbl 35
  • 71.27 (n)
  • 77.82 (a)
Str.1437 35
African clawed frog
(Xenopus laevis)
Amphibia Cbl 35
zebrafish
(Danio rerio)
Actinopterygii cbl 35
  • 68.48 (n)
  • 73.78 (a)
cbl 36
  • 70 (a)
OneToOne
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.9276 35
fruit fly
(Drosophila melanogaster)
Insecta Cbl 37
  • 71 (a)
Cbl 36
  • 42 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea sli-1 37
  • 54 (a)
sli-1 36
  • 42 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 69 (a)
OneToMany
Species with no ortholog for CBL:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CBL Gene

ENSEMBL:
Gene Tree for CBL (if available)
TreeFam:
Gene Tree for CBL (if available)

Paralogs for CBL Gene

Paralogs for CBL Gene

Selected SIMAP similar genes for CBL Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with CBL: view

Variants for CBL Gene

Sequence variations from dbSNP and Humsavar for CBL Gene

SNP ID Clin Chr 11 pos Sequence Context AA Info Type MAF
rs1918 -- 119,301,696(-) TAGAG(A/G)AGACA utr-variant-3-prime
rs11243 -- 119,307,930(+) ACAGA(A/G)GGTAA utr-variant-3-prime
rs535162 -- 119,293,009(-) TACAA(G/T)GGTGC intron-variant
rs536212 -- 119,292,864(-) TTGAG(A/G)AGCAA intron-variant
rs566766 -- 119,289,562(-) attAC(A/C)AAAAA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for CBL Gene

Variant ID Type Subtype PubMed ID
esv2665710 CNV Deletion 23128226
esv2519793 CNV Insertion 19546169
esv1143209 CNV Insertion 17803354
nsv898417 CNV Loss 21882294
nsv898418 CNV Loss 21882294
nsv525043 CNV Loss 19592680
nsv528636 CNV Gain 19592680

Relevant External Links for CBL Gene

HapMap Linkage Disequilibrium report
CBL
Human Gene Mutation Database (HGMD)
CBL

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CBL Gene

Disorders for CBL Gene

(1) OMIM Diseases for CBL Gene (165360)

UniProtKB/Swiss-Prot

CBL_HUMAN
  • Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL) [MIM:613563]: A syndrome characterized by a phenotype reminiscent of Noonan syndrome. Clinical features are highly variable, including facial dysmorphism, short neck, developmental delay, hyperextensible joints and thorax abnormalities with widely spaced nipples. The facial features consist of triangular face with hypertelorism, large low-set ears, ptosis, and flat nasal bridge. Some patients manifest cardiac defects. Some have an increased risk for certain malignancies, particularly juvenile myelomonocytic leukemia. {ECO:0000269 PubMed:20619386}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(5) University of Copenhagen DISEASES for CBL Gene

(16) Novoseek inferred disease relationships for CBL Gene

Disease -log(P) Hits PubMed IDs
myeloid leukemia 38.7 2
myeloid leukemia chronic 29.5 3
lymphoma 27 8
wiskott-aldrich syndrome 17.9 2
leukemia 17.5 5

Relevant External Links for CBL

Genetic Association Database (GAD)
CBL
Human Genome Epidemiology (HuGE) Navigator
CBL
genes like me logo Genes that share disorders with CBL: view

No data available for Genatlas for CBL Gene

Publications for CBL Gene

  1. 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. (PMID: 2030914) Blake T.J. … Langdon W.Y. (Oncogene 1991) 3 4 23
  2. Coordinated regulation of the tyrosine phosphorylation of Cbl by Fyn and Syk tyrosine kinases. (PMID: 9535867) Deckert M. … Liu Y.C. (J. Biol. Chem. 1998) 3 4 23
  3. Structure of the amino-terminal domain of Cbl complexed to its binding site on ZAP-70 kinase. (PMID: 10078535) Meng W. … Eck M.J. (Nature 1999) 3 4 23
  4. The tyrosine kinase negative regulator c-Cbl as a RING-type, E2- dependent ubiquitin-protein ligase. (PMID: 10514377) Joazeiro C.A. … Liu Y.-C. (Science 1999) 3 4 23
  5. APS facilitates c-Cbl tyrosine phosphorylation and GLUT4 translocation in response to insulin in 3T3-L1 adipocytes. (PMID: 11997497) Liu J. … Saltiel A.R. (Mol. Cell. Biol. 2002) 3 4 23

Products for CBL Gene

Sources for CBL Gene

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