InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Grb10

Summary

InnateDB Protein

IDBP-261929.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Grb10

Protein Name

growth factor receptor bound protein 10

Synonyms

5730571D09Rik; AI325020; Meg1; mKIAA0207;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000105281

InnateDB Gene

IDBG-150690 (Grb10)

Protein Structure

UniProt Annotation

Function

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. A similar role in the mediation of ubiquitination has also been suggested with INSR. 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. {ECO:0000269PubMed:12697834, ECO:0000269PubMed:12829789, ECO:0000269PubMed:15664450, ECO:0000269PubMed:17376403, ECO:0000269PubMed:18286479}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:18286479}. Note=When complexed with NEDD4 and IGF1R, follows IGF1R internalization, remaining associated with early endosomes. Uncouples from IGF1R before the sorting of the receptor to the lysosomal compartment.

Disease Associations

Tissue Specificity

Widely expressed. {ECO:0000269PubMed:7731717, ECO:0000269PubMed:9062339}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 21 experimentally validated interaction(s) in this database.
They are also associated with 32 interaction(s) predicted by orthology.

Experimentally validated
Total	21 [view]
Protein-Protein	21 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	32 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001784	phosphotyrosine binding
GO:0005070	SH3/SH2 adaptor activity
GO:0005158	insulin receptor binding
GO:0005515	protein binding

Biological Process

GO:0007165	signal transduction
GO:0008286	insulin receptor signaling pathway
GO:0030178	negative regulation of Wnt signaling pathway
GO:0030949	positive regulation of vascular endothelial growth factor receptor signaling pathway
GO:0042326	negative regulation of phosphorylation
GO:0042327	positive regulation of phosphorylation
GO:0045719	negative regulation of glycogen biosynthetic process
GO:0046325	negative regulation of glucose import
GO:0046627	negative regulation of insulin receptor signaling pathway
GO:0048009	insulin-like growth factor receptor signaling pathway

Cellular Component

GO:0005829

cytosol

Protein Structure and Domains

PDB ID

MGI:103232

InterPro

IPR000159 Ras-association
IPR000980 SH2 domain
IPR001849 Pleckstrin homology domain
IPR015042 BPS (Between PH and SH2) domain
IPR029071 Ubiquitin-related domain

PFAM

PF00788
PF00017
PF14633
PF00169
PF08947

PRINTS

PR00401

PIRSF

SMART

SM00314
SM00252
SM00233

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt