Cbl Cbl proto-oncogene [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: Cblprovided by FlyBase
Official Full Name: Cbl proto-oncogeneprovided by FlyBase
Primary source: FLYBASE:FBgn0020224
Locus tag: Dmel_CG7037
See related: AllianceGenome:FB:FBgn0020224
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Drosophila melanogaster
Lineage: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
Also known as: anon-WO0118547.68; cbl; CBL; CG7037; CG7043; d-cbl; D-cbl; D-Cbl; D-Cbl L; D-cblL; D-CblL; D-cblS; dCbl; Dcbl; DCbl; Dmel\CG7037; Dv-cbl; Dv-Cbl; F165; v-Cbl
Summary: Enables receptor tyrosine kinase binding activity and ubiquitin protein ligase activity. Involved in several processes, including germ cell development; negative regulation of signal transduction; and positive regulation of border follicle cell migration. Located in cell cortex. Is expressed in several structures, including Malpighian tubule; embryonic/larval hindgut; germarium; nurse cell; and ovary. Human ortholog(s) of this gene implicated in carcinoma (multiple); congestive heart failure; hematologic cancer (multiple); and type 1 diabetes mellitus. Orthologous to several human genes including CBL (Cbl proto-oncogene) and CBLB (Cbl proto-oncogene B). [provided by Alliance of Genome Resources, Dec 2024]
Orthologs: all
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Genomic context

Location:: 66C12-66C12; 3-24 cM

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	3L	NT_037436.4 (8424954..8432246)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	3L	NT_037436.3 (8418054..8425346)

Chromosome 3L - NT_037436.4 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Aubergine and piRNAs promote germline stem cell self-renewal by repressing the proto-oncogene Cbl.
Title: Aubergine and piRNAs promote germline stem cell self-renewal by repressing the proto-oncogene Cbl.
Overexpression of Akap200 not only suppresses the phenotype caused by Dv-cbl expression, but also the severe disruption to eye development caused by the combined expression of Dv-cbl and activated Ras
Title: Akap200 suppresses the effects of Dv-cbl expression in the Drosophila eye.
dCbl regulates life span, stress responses, and metabolism by suppressing dILP production and the EGFR-ERK pathway mediates the dCbl action
Title: Neuronal Cbl controls biosynthesis of insulin-like peptides in Drosophila melanogaster.
Drk plays a negative role in EGFR signaling by enhancing receptor endocytosis through cooperating with the RING domain of D-Cbl.
Title: D-Cbl binding to Drk leads to dose-dependent down-regulation of EGFR signaling and increases receptor-ligand endocytosis.
Distinct isoforms of Cbl regulate EGFR and Notch signaling during Drosophila development.
Title: Regulation of EGFR and Notch signaling by distinct isoforms of D-cbl during Drosophila development.
Here we report that FMRP controls the levels of cbl mRNA in the ovary and that reducing cbl gene dosage by half rescues the dFmr1 oogenesis phenotypes
Title: Drosophila Fragile X protein controls cellular proliferation by regulating cbl levels in the ovary.
Results show that Gurken travels towards the lateral/posterior of the egg chamber in the absence of Cbl, suggesting that Cbl actively regulates Gurken distribution through promoting endocytosis and subsequent degradation.
Title: The gradient of Gurken, a long-range morphogen, is directly regulated by Cbl-mediated endocytosis.
D-cbl mutants show overgrowth, inhibition of apoptosis, differentiation defects and increased ommatidial spacing using genetic interaction and molecular markers, we show that most of these phenotypes are caused by increased activity of the Drosophila EGFR
Title: Drosophila cbl is essential for control of cell death and cell differentiation during eye development.
D-CblS and D-CblL may downregulate Egfr through distinct mechanisms
Title: Differential effects of Cbl isoforms on Egfr signaling in Drosophila.

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables phosphotyrosine residue binding	IEA Inferred from Electronic Annotation more info
enables phosphotyrosine residue binding	ISM Inferred from Sequence Model more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor tyrosine kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables receptor tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables ubiquitin protein ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables ubiquitin-protein transferase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin-protein transferase activity	ISS Inferred from Sequence or Structural Similarity more info
enables zinc ion binding	ISM Inferred from Sequence Model more info	PubMed

Process	Evidence Code	Pubs
involved_in R7 cell fate commitment	IDA Inferred from Direct Assay more info	PubMed
involved_in cell surface receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in dorsal/ventral axis specification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dorsal/ventral axis specification, ovarian follicular epithelium	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dorsal/ventral pattern formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in eye photoreceptor cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in germ-line cyst formation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in imaginal disc-derived wing morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of ERK1 and ERK2 cascade	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of Notch signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of Notch signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of Notch signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of epidermal growth factor receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of epidermal growth factor receptor signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of epidermal growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of hormone biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of positive regulation of apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of border follicle cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of receptor-mediated endocytosis	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of receptor-mediated endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein monoubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of carbohydrate metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cell population proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of signaling	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in ubiquitin-dependent protein catabolic process	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cell cortex	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in membrane raft	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: Cbl proto-oncogene

Names: CG7037-PA; CG7037-PB; Cbl proto-oncogene ortholog; Cbl-PA; Cbl-PB; D-cblLONG; D-cblSHORT; cable

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NT_037436.4 Reference assembly

Range

8424954..8432246

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_139967.2 → NP_648224.1 Cbl proto-oncogene, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_648224.1

Status: REVIEWED

UniProtKB/TrEMBL

Q9GV78, Q9VSK2

Related

FBpp0076342

Conserved Domains (5) summary

cd09920
Location:244 → 340

SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain

cd14318
Location:834 → 873

UBA_Cbl_like; UBA domain found in casitas B-lineage lymphoma (Cbl) proteins

pfam02262
Location:42 → 163

Cbl_N; CBL proto-oncogene N-terminal domain 1

pfam02761
Location:167 → 250

Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain

pfam13920
Location:367 → 415

zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)
NM_168276.2 → NP_729382.1 Cbl proto-oncogene, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_729382.1

Status: REVIEWED

UniProtKB/TrEMBL

O46034, P91683

Related

FBpp0076341

Conserved Domains (4) summary

cd09920
Location:244 → 340

SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain

pfam02262
Location:42 → 163

Cbl_N; CBL proto-oncogene N-terminal domain 1

pfam02761
Location:167 → 250

Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain

pfam13920
Location:367 → 415

zf-C3HC4_3; Zinc finger, C3HC4 type (RING finger)