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General Information
Symbol
Dmel\Cbl
Species
D. melanogaster
Name
Cbl proto-oncogene
Annotation Symbol
CG7037
Feature Type
FlyBase ID
FBgn0020224
Gene Model Status
Stock Availability
Gene Snapshot
Cbl proto-oncogene (Cbl) encodes an E3 protein-ubiquitin ligase for protein post-translational modification in RTK signaling (EGFR, VEGFR, FGF, and RET families) and non-RTK signaling (Src family). After the ubiquitination mediated by the product of Cbl, the substrates will be targeted to protein degradation for controlling cell growth, survival, migration and inflammation. [Date last reviewed: 2019-03-07]
Also Known As
D-cbl, dCbl, D-cblL, D-cblS, cable
Key Links
Genomic Location
Cytogenetic map
Sequence location
3L:8,424,954..8,432,246 [+]
Recombination map
3-24
Sequence
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
GO Summary Ribbons
Protein Family (UniProt)
-
Summaries
Gene Group (FlyBase)
OTHER RING DOMAIN UBIQUITIN LIGASES -
The RING (Really Interesting New Gene) finger domain co-ordinates two Zn2+ ions via conserved Cys and His residues. Most proteins which contain a RING finger are assumed to be ubiquitin (E3) ligases. The RING finger binds ubiquitin-conjugating enzymes (E2) and promotes direct transfer of ubiquitin to the target protein. (Adapted from FBrf0215242 and PMID:19489725).
Pathway (FlyBase)
Negative Regulators of Epidermal Growth Factor Receptor Signaling Pathway -
Negative regulators of Epidermal Growth Factor Receptor signaling down-regulate the pathway, suppressing the activation of ERK kinase (rl) or acting on downstream effectors.
Negative Regulators of Notch Signaling Pathway -
The Notch receptor signaling pathway is activated by the binding of the transmembrane receptor Notch (N) to transmembrane ligands, Dl or Ser, presented on adjacent cells. This results in the proteolytic cleavage of N, releasing the intracellular domain (NICD). NICD translocates into the nucleus, interacting with Su(H) and mam to form a transcription complex, which up-regulates transcription of Notch-responsive genes. Negative regulators of the pathway down-regulate the signal from the sending cell or the response in the receiving cell. (Adapted from FBrf0225731 and FBrf0192604).
Summary (Interactive Fly)
Gene Model and Products
Number of Transcripts
2
Number of Unique Polypeptides
2

Please see the GBrowse view of Dmel\Cbl or the JBrowse view of Dmel\Cbl for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Comments on Gene Model
Gene model reviewed during 5.46
Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0076614
2948
448
FBtr0076615
4902
878
Additional Transcript Data and Comments
Reported size (kB)
2.5, 1.5 (northern blot)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
RefSeq ID
GenBank
FBpp0076341
51.5
448
7.80
FBpp0076342
94.8
878
7.35
Polypeptides with Identical Sequences

None of the polypeptides share 100% sequence identity.

Additional Polypeptide Data and Comments
Reported size (kDa)
448 (aa); 52 (kD observed)
Comments
Cbl protein lacks proline-rich sequences at the carboxy-terminus that are found in related proteins which allow binding to SH3-domain containing adaptor proteins. An in vitro protein interaction assay was used to show that Cbl protein does not interact with drk protein. It does, however associate with activated Egfr protein in vivo.
External Data
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Cbl using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
Linkouts
Gene Ontology (32 terms)
Molecular Function (8 terms)
Terms Based on Experimental Evidence (3 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (7 terms)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR014741
(assigned by InterPro )
inferred from electronic annotation with InterPro:IPR024159
(assigned by InterPro )
inferred from sequence model
inferred from biological aspect of ancestor with PANTHER:PTN000544009
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN001124099
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN001124099
(assigned by GO_Central )
inferred from sequence or structural similarity with HGNC:15961
inferred from sequence model
Biological Process (20 terms)
Terms Based on Experimental Evidence (17 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from genetic interaction with FLYBASE:N; FB:FBgn0004647
inferred from direct assay
inferred from mutant phenotype
inferred from direct assay
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000544009
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN001124099
(assigned by GO_Central )
inferred from sequence or structural similarity with HGNC:15961
Cellular Component (4 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN001124099
(assigned by GO_Central )
inferred from biological aspect of ancestor with PANTHER:PTN001124099
(assigned by GO_Central )
Expression Data
Expression Summary Ribbons
Colored tiles in ribbon indicate that expression data has been curated by FlyBase for that anatomical location. Colorless tiles indicate that there is no curated data for that location.
For complete stage-specific expression data, view the modENCODE Development RNA-Seq section under High-Throughput Expression below.
Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
organism

Comment: 0-8 hr AEL, peak at 0-2 hr AEL; short isoform

organism

Comment: long isoform; very faint in males

Additional Descriptive Data
Both Cbl transcript isoforms are expressed during oogenesis. The long isoform can be detected in the germarium, while the short isoform becomes detectable in nurse and follicle cells at stage 5 of oogenesis; neither isoform is expressed in oocytes.
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
western blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Both Cbl protein isoforms, as assayed by Western blot analysis, are expressed at all embryonic stages, all larval instars, and in ovaries. The short isoform is predominant at all stages.
Cbl protein was observed only in early embryos on Western blots. It is detected most strongly in blastoderm embryos by immunolocalization. At later stages, it is observed in pharyngeal muscle, hindgut and Malpighian tubules.
Marker for
 
Subcellular Localization
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

GBrowse - Visual display of RNA-Seq signals

View Dmel\Cbl in GBrowse 2
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
FLIGHT - Cell culture data for RNAi and other high-throughput technologies
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Flygut - An atlas of the Drosophila adult midgut
Images
Alleles, Insertions, and Transgenic Constructs
Classical and Insertion Alleles ( 13 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 26 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Cbl
Transgenic constructs containing regulatory region of Cbl
Deletions and Duplications ( 3 )
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
Orthologs
Human Orthologs (via DIOPT v7.1)
Homo sapiens (Human) (3)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
12 of 15
Yes
Yes
 
12 of 15
Yes
Yes
5 of 15
No
Yes
Model Organism Orthologs (via DIOPT v7.1)
Mus musculus (laboratory mouse) (3)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
12 of 15
Yes
Yes
11 of 15
No
Yes
5 of 15
No
Yes
Rattus norvegicus (Norway rat) (3)
9 of 13
Yes
Yes
8 of 13
No
Yes
4 of 13
No
Yes
Xenopus tropicalis (Western clawed frog) (3)
7 of 12
Yes
Yes
4 of 12
No
Yes
1 of 12
No
Yes
Danio rerio (Zebrafish) (4)
11 of 15
Yes
Yes
8 of 15
No
Yes
8 of 15
No
Yes
1 of 15
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (1)
12 of 15
Yes
Yes
Arabidopsis thaliana (thale-cress) (0)
No records found.
Saccharomyces cerevisiae (Brewer's yeast) (0)
No records found.
Schizosaccharomyces pombe (Fission yeast) (0)
No records found.
Orthologs in Drosophila Species (via OrthoDB v9.1) ( EOG091903RI )
Organism
Common Name
Gene
AAA Syntenic Ortholog
Multiple Dmel Genes in this Orthologous Group
Drosophila melanogaster
fruit fly
Drosophila suzukii
Spotted wing Drosophila
Drosophila simulans
Drosophila erecta
Drosophila yakuba
Drosophila ananassae
Drosophila pseudoobscura pseudoobscura
Drosophila persimilis
Drosophila willistoni
Drosophila virilis
Drosophila mojavensis
Drosophila grimshawi
Orthologs in non-Drosophila Dipterans (via OrthoDB v9.1) ( EOG091509LT )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Musca domestica
House fly
Glossina morsitans
Tsetse fly
Lucilia cuprina
Australian sheep blowfly
Mayetiola destructor
Hessian fly
Aedes aegypti
Yellow fever mosquito
Anopheles gambiae
Malaria mosquito
Culex quinquefasciatus
Southern house mosquito
Culex quinquefasciatus
Southern house mosquito
Orthologs in non-Dipteran Insects (via OrthoDB v9.1) ( EOG090W0AOA )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Bombyx mori
Silkmoth
Danaus plexippus
Monarch butterfly
Heliconius melpomene
Postman butterfly
Apis florea
Little honeybee
Apis mellifera
Western honey bee
Bombus impatiens
Common eastern bumble bee
Bombus terrestris
Buff-tailed bumblebee
Linepithema humile
Argentine ant
Megachile rotundata
Alfalfa leafcutting bee
Nasonia vitripennis
Parasitic wasp
Dendroctonus ponderosae
Mountain pine beetle
Tribolium castaneum
Red flour beetle
Pediculus humanus
Human body louse
Rhodnius prolixus
Kissing bug
Cimex lectularius
Bed bug
Acyrthosiphon pisum
Pea aphid
Zootermopsis nevadensis
Nevada dampwood termite
Orthologs in non-Insect Arthropods (via OrthoDB v9.1) ( EOG090X0AL7 )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strigamia maritima
European centipede
Ixodes scapularis
Black-legged tick
Stegodyphus mimosarum
African social velvet spider
Stegodyphus mimosarum
African social velvet spider
Stegodyphus mimosarum
African social velvet spider
Tetranychus urticae
Two-spotted spider mite
Orthologs in non-Arthropod Metazoa (via OrthoDB v9.1) ( EOG091G0GPE )
Organism
Common Name
Gene
Multiple Dmel Genes in this Orthologous Group
Strongylocentrotus purpuratus
Purple sea urchin
Strongylocentrotus purpuratus
Purple sea urchin
Ciona intestinalis
Vase tunicate
Ciona intestinalis
Vase tunicate
Gallus gallus
Domestic chicken
Gallus gallus
Domestic chicken
Paralogs
Paralogs (via DIOPT v7.1)
Drosophila melanogaster (Fruit fly) (0)
No records found.
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Model Summary Ribbon
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 1 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Comments on Models/Modifiers Based on Experimental Evidence ( 0 )
     
    Disease Associations of Human Orthologs (via DIOPT v7.1 and OMIM)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Functional Complementation Data
    Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
    Interactions
    Summary of Physical Interactions
    Summary of Genetic Interactions
    esyN Network Diagram
    esyN Network Key:
    Suppression
    Enhancement

    Please look at the allele data for full details of the genetic interactions
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DroID - A comprehensive database of gene and protein interactions.
    InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
    MIST (genetic) - An integrated Molecular Interaction Database
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Gene Group - Pathway Membership (FlyBase)
    Negative Regulators of Epidermal Growth Factor Receptor Signaling Pathway -
    Negative regulators of Epidermal Growth Factor Receptor signaling down-regulate the pathway, suppressing the activation of ERK kinase (rl) or acting on downstream effectors.
    Negative Regulators of Notch Signaling Pathway -
    The Notch receptor signaling pathway is activated by the binding of the transmembrane receptor Notch (N) to transmembrane ligands, Dl or Ser, presented on adjacent cells. This results in the proteolytic cleavage of N, releasing the intracellular domain (NICD). NICD translocates into the nucleus, interacting with Su(H) and mam to form a transcription complex, which up-regulates transcription of Notch-responsive genes. Negative regulators of the pathway down-regulate the signal from the sending cell or the response in the receiving cell. (Adapted from FBrf0225731 and FBrf0192604).
    External Data
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    3L
    Recombination map
    3-24
    Cytogenetic map
    Sequence location
    3L:8,424,954..8,432,246 [+]
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    66C12-66C12
    Limits computationally determined from genome sequence between P{lacW}l(3)L0139L0139 and P{PZ}Gug03928&P{EP}CG6745EP595b
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    66C-66C
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Location
    Notes
    Stocks and Reagents
    Stocks (11)
    Genomic Clones (12)
     

    Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

    cDNA Clones (132)
     

    Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.

    cDNA clones, fully sequences
    BDGP DGC clones
    Other clones
    Drosophila Genomics Resource Center cDNA clones

    For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

    cDNA Clones, End Sequenced (ESTs)
    RNAi and Array Information
    Linkouts
    DRSC - Results frm RNAi screens
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    Antibody Information
    Laboratory Generated Antibodies
    Commercially Available Antibodies
     
    Developmental Studies Hybridoma Bank - Monoclonal antibodies for use in research
    Other Information
    Relationship to Other Genes
    Source for database identify of
    Source for database merge of
    Source for merge of: Cbl F165
    Source for merge of: Cbl anon-WO0118547.68
    Source for merge of: Cbl CG7043
    Additional comments
    Annotations CG7037 and CG7043 merged as CG7037 in release 3 of the genome annotation.
    Source for merge of Cbl anon-WO0118547.68 was sequence comparison ( date:051113 ).
    Other Comments
    Area matching Drosophila Cbl gene, Acc. No. U87925. This association is confirmed by overlap with Drosophila EST AA441040.
    Cbl gene activity is required in the ventral follicle cells, and negatively regulates the Egfr pathway.
    Mutations in Cbl produce dorsalised egg shells and embryos, and also cause an extra vein phenotype in the wing.
    Cbl is a negative regulator of the Egfr pathway and is required for dorsoventral patterning in oogenesis.
    Mutation in Cbl result in hyperactivation of the Egfr pathway.
    The predicted protein lacks the proline rich domain and the putative leucine zipper of c-cbl.
    Cbl has been cloned from a D.melanogaster embryonic cDNA library, using a human c-Cbl cDNA as a probe.
    Cbl protein is unable to bind drk protein, although it associates with activated Egfr protein in vivo.
    Cbl protein lacks the entire C-terminal proline-rich domain of mammalian Cbl. Cbl acts as a negative regulator of one or more receptor tyrosine kinase pathways that are essential for photoreceptor differentiation.
    Origin and Etymology
    Discoverer
    Etymology
    Named 'Cbl' after the human ortholog.
    Identification
    External Crossreferences and Linkouts ( 89 )
    Sequence Crossreferences
    NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
    GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
    GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
    RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
    UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
    Other crossreferences
    BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
    Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
    Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
    Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
    Flygut - An atlas of the Drosophila adult midgut
    GenomeRNAi - A database for cell-based and in vivo RNAi phenotypes and reagents
    iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
    KEGG Genes - Molecular building blocks of life in the genomic space.
    KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
    modMine - A data warehouse for the modENCODE project
    SignaLink - A signaling pathway resource with multi-layered regulatory networks.
    Linkouts
    ApoDroso - Functional genomic database for photoreceptor development, survival and function
    BioGRID - A database of protein and genetic interactions.
    DPiM - Drosophila Protein interaction map
    DroID - A comprehensive database of gene and protein interactions.
    DRSC - Results frm RNAi screens
    Developmental Studies Hybridoma Bank - Monoclonal antibodies for use in research
    FLIGHT - Cell culture data for RNAi and other high-throughput technologies
    FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
    FlyMine - An integrated database for Drosophila genomics
    Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
    InterologFinder - Protein-protein interactions (PPI) from both known and predicted PPI data sets.
    KEGG Pathways - Wiring diagrams of molecular interactions, reactions and relations.
    MIST (genetic) - An integrated Molecular Interaction Database
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Synonyms and Secondary IDs (25)
    Reported As
    Symbol Synonym
    CG7043
    F165
    anon-WO0118547.68
    Name Synonyms
    Cbl proto-oncogene
    Cbl proto-oncogene ortholog
    Secondary FlyBase IDs
    • FBgn0035894
    • FBgn0041253
    • FBgn0061761
    Datasets (0)
    Study focus (0)
    Experimental Role
    Project
    Project Type
    Title
    References (141)