CBL - E3 ubiquitin-protein ligase CBL - human protein (Function)
 
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CBL »  E3 ubiquitin-protein ligase CBL
 
Gene name:  CBL
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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.  
9
  • CuratedUniProtKB
GO molecular function 
Calcium ion bindingdefinition[GO:0005509] silver  
  • IEAInterPro 2 GO
Ephrin receptor bindingdefinition[GO:0046875]  
1
  • IPIUniProtKB
Ligase activitydefinition[GO:0016874]  
  • IEAUniProtKB KW
Phosphotyrosine bindingdefinition[GO:0001784] silver  
  • IEAInterPro 2 GO
Protein bindingdefinition[GO:0005515]  
44
  • IPIIntAct
  • IPIUniProtKB
  • IPIBHF-UCL
Sequence-specific DNA binding transcription factor activitydefinition[GO:0003700]  
1
  • TASPINC
SH3 domain bindingdefinition[GO:0017124]  
1
  • IPIBHF-UCL
Signal transducer activitydefinition[GO:0004871] silver  
  • IEAInterPro 2 GO
Ubiquitin-protein transferase activitydefinition[GO:0004842]  
1
  • TASHGNC
Zinc ion bindingdefinition[GO:0008270] silver  
  • IEAInterPro 2 GO
GO biological process 
Cell surface receptor signaling pathwaydefinition[GO:0007166]  
1
  • TASHGNC
Epidermal growth factor receptor signaling pathwaydefinition[GO:0007173]  
1
  • TASHGNC
Negative regulation of apoptotic processdefinition[GO:0043066]  
1
  • IMPUniProtKB
Positive regulation of phosphatidylinositol 3-kinase signalingdefinition[GO:0014068]  
1
  • IMPBHF-UCL
Positive regulation of receptor-mediated endocytosisdefinition[GO:0048260]  
1
  • TASHGNC
Protein ubiquitinationdefinition[GO:0016567]  
1
  • TASHGNC
  • IEAUniPathway
Regulation of transcription, DNA-templateddefinition[GO:0006355]  
1
  • TASGOC
Pathways 
This protein is involved in the following pathway
According to KEGG, this protein belongs to the following pathways:
Bacterial invasion of epithelial cells  hsa05100+867  
Chronic myeloid leukemia  hsa05220+867  
Endocytosis  hsa04144+867  
ErbB signaling pathway  hsa04012+867  
Insulin signaling pathway  hsa04910+867  
Jak-STAT signaling pathway  hsa04630+867  
Pathways in cancer  hsa05200+867  
T cell receptor signaling pathway  hsa04660+867  
Ubiquitin mediated proteolysis  hsa04120+867  
According to Reactome, this protein belongs to the following pathways:
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers  REACT_118700  
EGFR downregulation  REACT_12484  
Interleukin-6 signaling  REACT_27307  
Negative regulation of FGFR signaling  REACT_111184  
Regulation of KIT signaling  REACT_111225  
Regulation of signaling by CBL  REACT_23787  
Signaling by constitutively active EGFR  REACT_115852  
Spry regulation of FGF signaling  REACT_111080  
TGF-beta receptor signaling activates SMADs  REACT_120850  
Note 
This protein has one functional calcium-binding site.  
  • CuratedUniProtKB
 

Keywords

Biological process 
Ubl conjugation pathway  definition   [KW-0833]
Molecular function 
Ligase  definition   [KW-0436]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: CBL_(gene)
GenomeRNAi: 867
PRO: PR:P22681