Cbl Cbl proto-oncogene [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Cblprovided by RGD
Official Full Name: Cbl proto-oncogeneprovided by RGD
Primary source: RGD:1561386
See related: EnsemblRapid:ENSRNOG00000008444 AllianceGenome:RGD:1561386
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: c-Cbl; RGD1561386
Summary: Enables several functions, including SH3 domain binding activity; phosphatidylinositol 3-kinase regulatory subunit binding activity; and protein tyrosine kinase binding activity. Involved in several processes, including cellular response to platelet-derived growth factor stimulus; mast cell degranulation; and protein ubiquitination. Located in focal adhesion; growth cone; and perinuclear region of cytoplasm. Used to study transient cerebral ischemia. Biomarker of congenital diaphragmatic hernia; hyperglycemia; and type 1 diabetes mellitus. Human ortholog(s) of this gene implicated in acute myeloid leukemia; congestive heart failure; juvenile myelomonocytic leukemia; lung non-small cell carcinoma; and myeloid neoplasm. Orthologous to human CBL (Cbl proto-oncogene). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in Thymus (RPKM 481.4), Spleen (RPKM 240.5) and 9 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 8q22

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	8	NC_086026.1 (53384656..53468067, complement)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	8	NC_051343.1 (44487824..44571620, complement)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	8	NC_005107.4 (48481256..48564775, complement)

Chromosome 8 - NC_086026.1 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

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

FTO represses NLRP3-mediated pyroptosis and alleviates myocardial ischemia-reperfusion injury via inhibiting CBL-mediated ubiquitination and degradation of beta-catenin.
Title: FTO represses NLRP3-mediated pyroptosis and alleviates myocardial ischemia-reperfusion injury via inhibiting CBL-mediated ubiquitination and degradation of β-catenin.
results suggest that ubiquitin and the E3 ubiquitin ligases c-Cbl and Cbl-b function as neuroimmune modulators in the subacute phase of neuropathic pain after nerve injury.
Title: Increased expression of the Cbl family of E3 ubiquitin ligases decreases Interleukin-2 production in a rat model of peripheral neuropathy.
c-Cbl negatively regulates alphaPix-mediated cell migration and invasion; the lack of c-Cbl in C6 and A172 glioma cells is responsible for their malignant behavior
Title: c-Cbl regulates αPix-mediated cell migration and invasion.
Casitas b-lineage lymphoma (c-Cbl) is involved in focal adhesion and myofibrillar protein stability and turnover in myocytes
Title: c-Cbl ubiquitin ligase regulates focal adhesion protein turnover and myofibril degeneration induced by neutrophil protease cathepsin G.
There is a novel role of c-Cbl in vascular remodeling after injury and modulation of c-Cbl tyrosine phosphorylation may be a therapeutic approach to treat vascular neointimal hyperplasia such as restenosis after angioplasty.
Title: Suppression of c-Cbl tyrosine phosphorylation inhibits neointimal formation in balloon-injured rat arteries.
Cbl has a role in regulating androgen-dependent apoptosis in male germ cells
Title: Androgen-dependent apoptosis in male germ cells is regulated through the proto-oncoprotein Cbl.
results demonstrate that the impairment in insulin-stimulated glucose transport observed in adipocytes after chronic ethanol feeding to rats is associated with a disruption of insulin-mediated Cbl protein/TC10 GTPase signaling
Title: Decreased insulin-dependent glucose transport by chronic ethanol feeding is associated with dysregulation of the Cbl/TC10 pathway in rat adipocytes.

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH142755 (e-PCR)
- UniSTS:232002

D8Got62 (e-PCR)
- UniSTS:115842

Cbl (e-PCR), detects polymorphism
- UniSTS:506781

RH139032 (e-PCR)
- UniSTS:221118

D8Got63 (e-PCR)
- UniSTS:114905

Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables SH3 domain binding	IDA Inferred from Direct Assay more info	PubMed
enables SH3 domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables SH3 domain binding	ISO Inferred from Sequence Orthology more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables ephrin receptor binding	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol 3-kinase regulatory subunit binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphotyrosine residue binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables receptor tyrosine kinase binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase activity	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase activity	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in DNA damage response	IEP Inferred from Expression Pattern more info	PubMed
involved_in cell surface receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to nerve growth factor stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to platelet-derived growth factor stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in male gonad development	IEP Inferred from Expression Pattern more info	PubMed
involved_in mast cell degranulation	IEP Inferred from Expression Pattern more info	PubMed
involved_in negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of apoptotic process	ISO Inferred from Sequence Orthology more info
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	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of receptor-mediated endocytosis	ISO Inferred from Sequence Orthology more info
involved_in protein autoubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein monoubiquitination	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein polyubiquitination	IDA Inferred from Direct Assay more info	PubMed
involved_in protein ubiquitination	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of Rap protein signal transduction	ISO Inferred from Sequence Orthology more info
involved_in regulation of platelet-derived growth factor receptor-alpha signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in response to activity	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to ethanol	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to gamma radiation	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to starvation	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to testosterone	IEP Inferred from Expression Pattern more info	PubMed
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in ubiquitin-dependent endocytosis	ISO Inferred from Sequence Orthology more info
involved_in ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in axon	IDA Inferred from Direct Assay more info	PubMed
located_in cilium	ISO Inferred from Sequence Orthology more info
located_in cytosol	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in cytosol	TAS Traceable Author Statement more info
part_of flotillin complex	ISO Inferred from Sequence Orthology more info
located_in focal adhesion	IDA Inferred from Direct Assay more info	PubMed
located_in growth cone	IDA Inferred from Direct Assay more info	PubMed
is_active_in membrane raft	IBA Inferred from Biological aspect of Ancestor more info
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: E3 ubiquitin-protein ligase CBL

Names: Cas-Br-M (murine) ecotropic retroviral transforming sequence; Casitas B-lineage lymphoma; Cbl proto-oncogene, E3 ubiquitin protein ligase

NP_001406884.1

EC 6.3.2.-

XP_006243027.1

EC 6.3.2.-

XP_038938260.1

EC 6.3.2.-

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001419955.1 → NP_001406884.1 E3 ubiquitin-protein ligase CBL

Status: VALIDATED

Source sequence(s)

JAXUCZ010000008

UniProtKB/TrEMBL

A0A0U1ZFN5, A0A8I6G3R2

Related

ENSRNOP00000079790.1, ENSRNOT00000101607.2

RefSeqs of Annotated Genomes: GCF_036323735.1-RS_2024_02

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

Reference GRCr8

Genomic

NC_086026.1 Reference GRCr8

Range

53384656..53468067 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006242965.5 → XP_006243027.1 E3 ubiquitin-protein ligase CBL isoform X1

See identical proteins and their annotated locations for XP_006243027.1

UniProtKB/TrEMBL

A0A0U1ZFN5, A0A8I6G861

Related

ENSRNOP00000082958.1, ENSRNOT00000113781.2

Conserved Domains (5) summary

cd09920
Location:255 → 351

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

cd00162
Location:380 → 422

RING; RING-finger (Really Interesting New Gene) domain, a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc; defined by the 'cross-brace' motif C-X2-C-X(9-39)-C-X(1-3)- H-X(2-3)-(N/C/H)-X2-C-X(4-48)C-X2-C; probably involved in ...

cd14393
Location:821 → 860

UBA_c-Cbl; UBA domain found in E3 ubiquitin-protein ligase Cbl and similar proteins

pfam02262
Location:53 → 174

Cbl_N; CBL proto-oncogene N-terminal domain 1

pfam02761
Location:178 → 261

Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain
XM_039082332.2 → XP_038938260.1 E3 ubiquitin-protein ligase CBL isoform X2

UniProtKB/TrEMBL

A6J3W2

Conserved Domains (6) summary

cd09920
Location:151 → 247

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

PHA03247
Location:375 → 730

PHA03247; large tegument protein UL36; Provisional

cd14393
Location:761 → 800

UBA_c-Cbl; UBA domain found in E3 ubiquitin-protein ligase Cbl and similar proteins

cd16709
Location:257 → 322

RING-HC_Cbl-b; RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-b and similar proteins

pfam02262
Location:1 → 67

Cbl_N; CBL proto-oncogene N-terminal domain 1

pfam02761
Location:74 → 157

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