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MGP001310

UniProt Annotations

Entry Information
Gene Namegrowth factor receptor-bound protein 10
Protein EntryGRB10_HUMAN
UniProt IDQ13322
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Comment=Additional isoforms seem to exist, many of which involve splicing of 5' non-coding exons.; Name=3; Synonyms=Zeta; IsoId=Q13322-1; Sequence=Displayed; Name=1; Synonyms=Beta; IsoId=Q13322-2; Sequence=VSP_001843; Name=2; Synonyms=Gamma, Beta, SV-1; IsoId=Q13322-3; Sequence=VSP_001842; Name=4; Synonyms=Epsilon; IsoId=Q13322-4; Sequence=VSP_038784; Note=No experimental confirmation available.;
DomainThe PH domain binds relatively non-specifically to several phosphoinositides, including PI(5)P, PI(4,5)P2, PI(3,4)P2 and PI(3,4,5)P3, with modest affinities.
Enzyme RegulationPhosphorylation by mTORC1 stabilizes and activates GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-dependent signaling. {ECO:0000269|PubMed:21659604}.
FunctionAdapter 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:0000269|PubMed:12493740, ECO:0000269|PubMed:15060076, ECO:0000269|PubMed:16434550, ECO:0000269|PubMed:17376403}.
InteractionP54762:EPHB1; NbExp=2; IntAct=EBI-80275, EBI-80252; P06213:INSR; NbExp=3; IntAct=EBI-80275, EBI-475899;
MiscellaneousGRB10 is unlikely to be responsible for Silver- Russell syndrome (SRS).
MiscellaneousThe 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.
PtmPhosphorylated on serine residues upon EGF, FGF and PDGF stimulation (By similarity). Phosphorylated at Tyr-67 by TEC. {ECO:0000250, ECO:0000269|PubMed:15722337, ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:18220336, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:21659604, ECO:0000269|PubMed:9753425}.
Sequence CautionSequence=BAA13198.2; Type=Erroneous initiation; Evidence={ECO:0000305};
SimilarityBelongs to the GRB7/10/14 family. {ECO:0000305}.
SimilarityContains 1 PH domain. {ECO:0000255|PROSITE- ProRule:PRU00145}.
SimilarityContains 1 Ras-associating domain. {ECO:0000255|PROSITE-ProRule:PRU00166}.
SimilarityContains 1 SH2 domain. {ECO:0000255|PROSITE- ProRule:PRU00191}.
Subcellular LocationCytoplasm {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}.
SubunitInteracts with ligand-activated tyrosine kinase receptors, including FGFR1, INSR, IGF1R, MET and PDGFRB in a phosphotyrosine-dependent manner through the SH2 domain (By similarity). Poorly binds to the EGFR (By similarity). Directly interacts with MAP3K14/NIK and is recruited to the EGFR-ERBB2 complex. Interacts with GIGYF1/PERQ1 and GIGYF2/TNRC15 (By similarity). When unphosphorylated, interacts with AKT1 and when phosphorylated with YWHAE/14-3-3 epsilon. Interacts with NEDD4. Interacts with LRP6, thus interfering with the binding of AXIN1 to LRP6 (By similarity). Binds to activated NRAS. {ECO:0000250, ECO:0000269|PubMed:12493740, ECO:0000269|PubMed:12853971, ECO:0000269|PubMed:15060076, ECO:0000269|PubMed:15722337, ECO:0000269|PubMed:19648926}.
Tissue SpecificityWidely expressed in fetal and adult tissues, including fetal and postnatal liver, lung, kidney, skeletal muscle, heart, spleen, skin and brain. {ECO:0000269|PubMed:11527390}.
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/GRB10ID278.html";
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