GRB10 - Growth factor receptor-bound protein 10 - human protein (Function)
 
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GRB10 »  Growth factor receptor-bound protein 10
 
Protein also known as:  Insulin receptor-binding protein Grb-IR.
Gene name:  GRB10
Family name: GRB7/10/14
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 63 4
GENE REF ISO

Function

 show evidences
Overview 
Adapter protein which modulates coupling of a number of cell surface receptor kinases with specific signaling pathways. Binds to, and suppress signals from, activated receptors tyrosine kinases, including the insulin (INSR) and insulin-like growth factor (IGF1R) receptors. The inhibitory effect can be achieved by 2 mechanisms: interference with the signaling pathway and increased receptor degradation. Delays and reduces AKT1 phosphorylation in response to insulin stimulation. Blocks association between INSR and IRS1 and IRS2 and prevents insulin-stimulated IRS1 and IRS2 tyrosine phosphorylation. Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased internalization and degradation by both the proteasomal and lysosomal pathways. May play a role in mediating insulin-stimulated ubiquitination of INSR, leading to proteasomal degradation. Negatively regulates Wnt signaling by interacting with LRP6 intracellular portion and interfering with the binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2 signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-2.  
4
  • CuratedUniProtKB
GO molecular function 
Insulin receptor bindingdefinition[GO:0005158]  
1
  • ISSBHF-UCL
  • ISSOrtholog Curator
Protein bindingdefinition[GO:0005515]  
4
  • IPIUniProtKB
  • IPIIntAct
SH3/SH2 adaptor activitydefinition[GO:0005070] silver  
  • IEAOrtholog Compara
GO biological process 
Isoform  Iso 3   Insulin receptor signaling pathwaydefinition[GO:0008286]  
  • ISSOrtholog Curator
Insulin-like growth factor receptor signaling pathwaydefinition[GO:0048009] silver  
  • IEAOrtholog Compara
Negative regulation of glucose importdefinition[GO:0046325]  
1
  • ISSBHF-UCL
Negative regulation of glycogen biosynthetic processdefinition[GO:0045719]  
  • IEAOrtholog Compara
  • ISSOrtholog Curator
Negative regulation of insulin receptor signaling pathwaydefinition[GO:0046627]  
1
  • ISSBHF-UCL
Negative regulation of phosphorylationdefinition[GO:0042326] silver  
  • IEAOrtholog Compara
Negative regulation of Wnt signaling pathwaydefinition[GO:0030178]  
1
  • IDAUniProtKB
Positive regulation of phosphorylationdefinition[GO:0042327]  
  • IEAOrtholog Compara
  • ISSOrtholog Curator
Positive regulation of vascular endothelial growth factor receptor signaling pathwaydefinition[GO:0030949]  
1
  • IDAUniProtKB
Isoform  Iso 3   Response to insulindefinition[GO:0032868]  
  • ISSOrtholog Curator
Enzymatic activity 
It is regulated in the following manner
Phosphorylation by mTORC1 stabilizes and activates GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-dependent signaling.  
1
  • CuratedUniProtKB
Pathways 
According to Reactome, this protein belongs to the following pathways:
Signal attenuation  REACT_508  
Signaling by SCF-KIT  REACT_111040  
Note 
The GRB10 locus is imprinted. During embryonic development, the expression in the brain and spinal cord is from the paternal allele, while in placental villous trophoblasts and skeletal muscle, it is from the maternal one. Expression is biallelic in most other tissues. Paternal expression in the brain is maintained throughout adulthood. Imprinting often is isoform-specific.  
  • CuratedUniProtKB
GRB10 is unlikely to be responsible for Silver-Russell syndrome (SRS).  
  • CuratedUniProtKB
 

Keywords

Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

GeneWiki: GRB10
GenomeRNAi: 2887
PRO: PR:Q13322