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CBL Cbl proto-oncogene [ Homo sapiens (human) ]

Gene ID: 867, updated on 1-Aug-2020

Summary

Official Symbol
CBLprovided by HGNC
Official Full Name
Cbl proto-oncogeneprovided by HGNC
Primary source
HGNC:HGNC:1541
See related
Ensembl:ENSG00000110395 MIM:165360
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CBL2; NSLL; C-CBL; RNF55; FRA11B
Summary
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, and expansion of CGG repeats in the 5' UTR has been associated with Jacobsen syndrome. Mutations in this gene are also the cause of Noonan syndrome-like disorder. [provided by RefSeq, Jul 2016]
Expression
Broad expression in testis (RPKM 12.3), lymph node (RPKM 6.0) and 23 other tissues See more
Orthologs

Genomic context

See CBL in Genome Data Viewer
Location:
11q23.3
Exon count:
16
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 11 NC_000011.10 (119206339..119308149)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (119076986..119178859)

Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene Sharpr-MPRA regulatory region 11099 Neighboring gene coiled-coil domain containing 153 Neighboring gene fragile site, folic acid type, rare, fra(11)(q23.3) Neighboring gene RNA, U6 small nuclear 262, pseudogene Neighboring gene melanoma cell adhesion molecule Neighboring gene microRNA 6756 Neighboring gene ring finger protein 26

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Juvenile myelomonocytic leukemia
MedGen: C0349639 OMIM: 607785 GeneReviews: Not available
Compare labs
Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia
MedGen: C3150803 OMIM: 613563 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Haploinsufficency

No evidence available (Last evaluated (2019-04-24)

ClinGen Genome Curation Page
Triplosensitivity

No evidence available (Last evaluated (2019-04-24)

ClinGen Genome Curation Page

NHGRI GWAS Catalog

Description
New gene functions in megakaryopoiesis and platelet formation.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Nef nef In the presence of Nef, lipid raft Cdc42 is activated and forms a ternary complex between the c-Cbl-interacting protein p85Cool-1/betaPix and c-Cbl, displacing UbcH7 from rafts PubMed
nef HIV-1 Nef enhances the phosphorylation of c-Cbl in CD4+ T cells, an effect that requires the Src tyrosine kinase Lck PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
SH3 domain binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
SH3 domain binding IPI
Inferred from Physical Interaction
more info
PubMed 
cadherin binding HDA PubMed 
calcium ion binding IEA
Inferred from Electronic Annotation
more info
 
ephrin receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
epidermal growth factor receptor binding IEA
Inferred from Electronic Annotation
more info
 
phosphatidylinositol 3-kinase regulatory subunit binding IEA
Inferred from Electronic Annotation
more info
 
phosphotyrosine residue binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
receptor tyrosine kinase binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin protein ligase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
ubiquitin protein ligase activity TAS
Traceable Author Statement
more info
 
ubiquitin-protein transferase activity TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
cell surface receptor signaling pathway TAS
Traceable Author Statement
more info
PubMed 
cellular response to DNA damage stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to epidermal growth factor stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to nerve growth factor stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to oxygen-glucose deprivation IEA
Inferred from Electronic Annotation
more info
 
cellular response to platelet-derived growth factor stimulus IEA
Inferred from Electronic Annotation
more info
 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
 
entry of bacterium into host cell TAS
Traceable Author Statement
more info
 
epidermal growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
PubMed 
fibroblast growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
interleukin-6-mediated signaling pathway TAS
Traceable Author Statement
more info
 
male gonad development IEA
Inferred from Electronic Annotation
more info
 
mast cell degranulation IEA
Inferred from Electronic Annotation
more info
 
membrane organization TAS
Traceable Author Statement
more info
 
negative regulation of apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of epidermal growth factor receptor signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of epidermal growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
negative regulation of epidermal growth factor-activated receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of neuron death IEA
Inferred from Electronic Annotation
more info
 
neuron death IEA
Inferred from Electronic Annotation
more info
 
positive regulation of epidermal growth factor receptor signaling pathway TAS
Traceable Author Statement
more info
 
positive regulation of phosphatidylinositol 3-kinase signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of receptor-mediated endocytosis IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of receptor-mediated endocytosis TAS
Traceable Author Statement
more info
PubMed 
protein monoubiquitination IEA
Inferred from Electronic Annotation
more info
 
protein polyubiquitination IEA
Inferred from Electronic Annotation
more info
 
protein ubiquitination TAS
Traceable Author Statement
more info
PubMed 
regulation of Rap protein signal transduction IEA
Inferred from Electronic Annotation
more info
 
regulation of platelet-derived growth factor receptor-alpha signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
response to activity IEA
Inferred from Electronic Annotation
more info
 
response to antibiotic IEA
Inferred from Electronic Annotation
more info
 
response to ethanol IEA
Inferred from Electronic Annotation
more info
 
response to gamma radiation IEA
Inferred from Electronic Annotation
more info
 
response to starvation IEA
Inferred from Electronic Annotation
more info
 
response to testosterone IEA
Inferred from Electronic Annotation
more info
 
signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transforming growth factor beta receptor signaling pathway TAS
Traceable Author Statement
more info
 
ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
Golgi apparatus IDA
Inferred from Direct Assay
more info
PubMed 
cilium IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
 
cytosol TAS
Traceable Author Statement
more info
 
colocalizes_with flotillin complex ISS
Inferred from Sequence or Structural Similarity
more info
 
focal adhesion IEA
Inferred from Electronic Annotation
more info
 
growth cone IEA
Inferred from Electronic Annotation
more info
 
mast cell granule IEA
Inferred from Electronic Annotation
more info
 
membrane raft IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
perinuclear region of cytoplasm IEA
Inferred from Electronic Annotation
more info
 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
plasma membrane TAS
Traceable Author Statement
more info
 

General protein information

Preferred Names
E3 ubiquitin-protein ligase CBL
Names
Cas-Br-M (murine) ecotropic retroviral transforming sequence
Cbl proto-oncogene, E3 ubiquitin protein ligase
RING finger protein 55
RING-type E3 ubiquitin transferase CBL
casitas B-lineage lymphoma proto-oncogene
fragile site, folic acid type, rare, fra(11)(q23.3)
oncogene CBL2
proto-oncogene c-Cbl
signal transduction protein CBL
NP_005179.2

NCBI Reference Sequences (RefSeq)

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.

Genomic

  1. NG_016808.1 RefSeqGene

    Range
    4997..106870
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_608

mRNA and Protein(s)

  1. NM_005188.4NP_005179.2  E3 ubiquitin-protein ligase CBL

    See identical proteins and their annotated locations for NP_005179.2

    Status: REVIEWED

    Source sequence(s)
    AA806454, AP002956, BC132733, DB457271
    Consensus CDS
    CCDS8418.1
    UniProtKB/Swiss-Prot
    P22681
    Related
    ENSP00000264033.3, ENST00000264033.6
    Conserved Domains (6) summary
    cd09920
    Location:256352
    SH2_Cbl-b_TKB; Src homology 2 (SH2) domain found in the Cbl-b TKB domain
    cd14393
    Location:857896
    UBA_c-Cbl; UBA domain found in E3 ubiquitin-protein ligase Cbl and similar proteins
    pfam02262
    Location:54175
    Cbl_N; CBL proto-oncogene N-terminal domain 1
    pfam02761
    Location:179262
    Cbl_N2; CBL proto-oncogene N-terminus, EF hand-like domain
    cd16709
    Location:362427
    RING-HC_Cbl-b; RING finger, HC subclass, found in E3 ubiquitin-protein ligase Cbl-b and similar proteins
    cl26464
    Location:480810
    Atrophin-1; Atrophin-1 family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109.20200522

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000011.10 Reference GRCh38.p13 Primary Assembly

    Range
    119206339..119308149
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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