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Aliases for CBL Gene

Aliases for CBL Gene

  • Cbl Proto-Oncogene 2 3
  • Cbl Proto-Oncogene, E3 Ubiquitin Protein Ligase 2 3 5
  • 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
  • CBL2 3 4
  • Fragile Site, Folic Acid Type, Rare, Fra(11)(Q23.3) 3
  • EC 6.3.2.- 4
  • EC 6.3.2 63
  • FRA11B 3
  • C-CBL 3
  • NSLL 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) 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 Signaling by GPCR and Immune System. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and ligase 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

Promoters for CBL Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around CBL on UCSC Golden Path with GeneCards custom track

Genomic Location for CBL Gene

Chromosome:
11
Start:
119,206,276 bp from pter
End:
119,308,149 bp from pter
Size:
101,874 bases
Orientation:
Plus strand

Genomic View for CBL Gene

Genes around CBL on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CBL Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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). Interacts with SH3KBP1 and this interaction is inhibited in the presence of SHKBP1 (By similarity).
    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 Lys 7, Lys 74, Lys 105, Lys 424, Lys 471, and Lys 521
  • Modification sites at PhosphoSitePlus

Other Protein References for CBL Gene

Antibody Products

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

Domains & Families for CBL Gene

Gene Families for CBL Gene

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 :
  • The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.
  • Contains 1 RING-type zinc finger.
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:0005509 calcium ion binding IEA --
GO:0005515 protein binding IEA,IPI 5668240
GO:0016874 ligase activity IEA --
genes like me logo Genes that share ontologies with CBL: view
genes like me logo Genes that share phenotypes with CBL: view

Human Phenotype Ontology for CBL Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CBL Gene

MGI Knock Outs for CBL:

Animal Model Products

No data available for Transcription Factor Targets 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
cytosol 5
plasma membrane 5
nucleus 4
lysosome 3
cytoskeleton 2
endosome 2
vacuole 2
extracellular 1
mitochondrion 1

No data available for Gene Ontology (GO) - Cellular Components for CBL Gene

Pathways & Interactions for CBL Gene

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

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.ENSP00000244007%0d%0a9606.ENSP00000264972%0d%0a9606.ENSP00000288986%0d%0a9606.ENSP00000300574%0d%0a9606.ENSP00000317272%0d%0a
Selected Interacting proteins: P22681-CBL_HUMAN ENSP00000264033 for CBL Gene via MINT I2D UniProtKB STRING

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

SIGNOR curated interactions for CBL Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for CBL Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007173 epidermal growth factor receptor signaling pathway TAS 15465819
GO:0016567 protein ubiquitination TAS 15465819
GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process IMP 25178484
GO:0043066 negative regulation of apoptotic process IMP 18070883
genes like me logo Genes that share ontologies with CBL: view

Drugs & Compounds for CBL Gene

(25) Drugs for CBL Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine monophosphate Approved Nutra 0
Adenosine triphosphate Approved Nutra 0
Diphosphate Experimental Pharma 0
calcium Nutra 0

(17) Additional Compounds for CBL Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
phosphoric acid
  • Acide phosphorique (FRENCH)
  • Acido fosforico [Italian]
  • Acidum phosphoricum
  • Diphosphate tetrasodium
  • Fosforzuuroplossingen [Dutch]
7664-38-2
genes like me logo Genes that share compounds with CBL: view

Transcripts for CBL Gene

mRNA/cDNA for CBL Gene

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

Unigene Clusters for CBL Gene

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

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 (x5.6).

Protein differential expression in normal tissues from HIPED 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 in normal tissues and cell lines 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 expression patterns with CBL: view

Protein tissue co-expression partners for CBL Gene

Primer Products

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
chimpanzee
(Pan troglodytes)
Mammalia CBL 36
  • 100 (a)
OneToOne
CBL 35
  • 99.78 (n)
  • 100 (a)
cow
(Bos Taurus)
Mammalia CBL 36
  • 92 (a)
OneToOne
CBL 35
  • 91.82 (n)
  • 94.29 (a)
dog
(Canis familiaris)
Mammalia CBL 35
  • 91.54 (n)
  • 95.2 (a)
CBL 36
  • 92 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Cbl 36
  • 91 (a)
OneToOne
Cbl 16
Cbl 35
  • 88.08 (n)
  • 93.02 (a)
oppossum
(Monodelphis domestica)
Mammalia CBL 36
  • 89 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 36
  • 100 (a)
OneToMany
-- 36
  • 77 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Cbl 35
  • 87.98 (n)
  • 92.48 (a)
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
African clawed frog
(Xenopus laevis)
Amphibia Cbl 35
tropical clawed frog
(Silurana tropicalis)
Amphibia cbl 35
  • 71.27 (n)
  • 77.82 (a)
Str.1437 35
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.9276 35
zebrafish
(Danio rerio)
Actinopterygii cbl 36
  • 70 (a)
OneToOne
cbl 35
  • 68.48 (n)
  • 73.78 (a)
fruit fly
(Drosophila melanogaster)
Insecta Cbl 37
  • 71 (a)
Cbl 36
  • 42 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea sli-1 36
  • 42 (a)
OneToMany
sli-1 37
  • 54 (a)
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

(3) 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
rs2227988 - 119,285,483(+) ACTCA(C/T)TTCCA reference, missense
rs2229073 - 119,298,451(+) TGTGC(C/T)GGCCG reference, missense
rs17122769 - 119,299,770(+) CCCAT(A/G)TAGCT reference, missense
VAR_064332 Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL)
VAR_064333 Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL)

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

Variation tolerance for CBL Gene

Residual Variation Intolerance Score: 13.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.23; 52.48% of all genes are more intolerant (likely to be disease-causing)

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

MalaCards: The human disease database

(23) MalaCards diseases for CBL Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia
  • noonan-like syndrome disorder with or without juvenile myelomonocytic leukemia
noonan syndrome-like disorder with juvenile myelomonocytic leukemia
  • cbl syndrome
noonan syndrome 8
  • ns8
leukemia, acute myelomonocytic, somatic, somatic
  • leukemia, juvenile myelomonocytic, somatic
hematologic cancer
  • blood cancer
- elite association - COSMIC cancer census association via MalaCards
Search CBL in MalaCards View complete list of genes associated with diseases

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.

Relevant External Links for CBL

Genetic Association Database (GAD)
CBL
Human Genome Epidemiology (HuGE) Navigator
CBL
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
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. 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 67
  2. [Expression of c-Cbl, Cbl-b, and epidermal growth factor receptor in gastric carcinoma and their clinical significance]. (PMID: 20038312) Dong Q. … Li L.L. (Chin J Cancer 2010) 3 23
  3. Termination of tyrphostin AG1478 application results in different recovery of EGF receptor tyrosine residues 1045 and 1173 phosphorylation in A431 cells. (PMID: 19947936) Kondratov K.A. … Kornilova E.S. (Cell Biol. Int. 2010) 3 23
  4. Differential subcellular localization regulates c-Cbl E3 ligase activity upon Notch3 protein in T-cell leukemia. (PMID: 19966856) Checquolo S. … Screpanti I. (Oncogene 2010) 3 23
  5. Cbl negatively regulates JNK activation and cell death. (PMID: 19546888) Sproul A.A. … Greene L.A. (Cell Res. 2009) 3 23

Products for CBL Gene

Sources for CBL Gene

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