InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: GRB10

Summary

InnateDB Protein

IDBP-16690.7

Last Modified

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

Gene Symbol

GRB10

Protein Name

growth factor receptor-bound protein 10

Synonyms

Grb-10; GRB-IR; IRBP; MEG1; RSS;

Species

Homo sapiens

Ensembl Protein

ENSP00000338543

InnateDB Gene

IDBG-16688 (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. 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. {ECO:0000269PubMed:12493740, ECO:0000269PubMed:15060076, ECO:0000269PubMed:16434550, ECO:0000269PubMed:17376403}.

Subcellular Localization

Cytoplasm {ECO:0000250}. Note=When complexed with NEDD4 and IGF1R, follows IGF1R internalization, remaining associated with early endosomes. Uncouples from IGF1R-containing endosomes before the sorting of the receptor to the lysosomal compartment (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Widely expressed in fetal and adult tissues, including fetal and postnatal liver, lung, kidney, skeletal muscle, heart, spleen, skin and brain. {ECO:0000269PubMed:11527390}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 55 experimentally validated interaction(s) in this database.
They are also associated with 9 interaction(s) predicted by orthology.

Experimentally validated
Total	55 [view]
Protein-Protein	55 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	9 [view]

Gene Ontology

Molecular Function

Accession	GO Term
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:0032868	response to insulin
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

Cellular Component

GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0005886	plasma membrane

Protein Structure and Domains

PDB ID

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