Linked Life Data

Q60760

Source:http://identifiers.org/uniprot/Q60760

Statements in which the resource exists.
SubjectPredicateObjectContext
http://identifiers.org/unip...rdf:typebiopax3:ProteinReferencelld:biopax3
http://identifiers.org/unip...biopax3:commentSEQUENCE 621 AA; 70585 MW; 6FC737E8F35468BB CRC64;lld:biopax3
http://identifiers.org/unip...biopax3:commentFUNCTION: 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. ENZYME REGULATION: Phosphorylation by mTORC1 stabilizes and activates GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-dependent signaling (By similarity). SUBUNIT: Interacts with ligand-activated tyrosine kinase receptors, including FGFR1, INSR, IGF1R, MET and PDGFRB in a phosphotyrosine-dependent manner through the SH2 domain. Poorly binds to the EGFR. Directly interacts with MAP3K14/NIK and is recruited to the EGFR-ERBB2 complex (By similarity). Interacts with GIGYF1/PERQ1 and GIGYF2/TNRC15. 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. Binds to activated NRAS (By similarity). SUBCELLULAR LOCATION: Cytoplasm. 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. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=3; Name=1; Synonyms=Alpha; IsoId=Q60760-1; Sequence=Displayed; Name=2; Synonyms=Delta; IsoId=Q60760-2; Sequence=VSP_001844; Note=Predominant isoform in most tissues; Name=3; IsoId=Q60760-3; Sequence=VSP_012379; TISSUE SPECIFICITY: Widely expressed. DEVELOPMENTAL STAGE: At 13.5 dpc, expressed in most embryonic tissues and in placenta. At 14.5 dpc, expressed at high levels in a variety of muscle tissues, including that of the face and trunk, the intercostal muscles, the diaphragm and cardiac muscle, the tongue and limbs (at protein level). In the brain, most abundant expression in the subependymal layers, in the meninges and in the choroid plexus (both epithelium and mesenchyme) (at protein level). High levels in the liver, bronchioles and the cartilage of the atlas, ribs and long bones (at protein level). In the kidney, expression limited to the developing tubules and mesenchyme (at protein level). Also detected in the adrenal gland and pancreatic bud (at protein level). At 12.5 dpc, paternal allele expression detected in the cartilage of the limbs, ribs and face and in the meninges. At 14.5 dpc, paternal allele expressed in the cartilage of the axis, ribs, head, and long bones, in the heart, lungs, gut, umbilicus and tongue, as well as in the meninges of the fourth ventricle. Not detected in the skeletal muscle. In most tissues, paternal expression is lower than maternal. DOMAIN: The 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 (By similarity). PTM: Phosphorylated on serine residues upon EGF, FGF and PDGF stimulation. DISRUPTION PHENOTYPE: Disruption of the maternal allele results in overgrowth of both the embryo and placenta such that mutant mice are at birth about 30% larger than normal. This effect occurs during embryogenesis and results in addition in disproportionate overgrowth of the liver with relative sparing of the brain. The major part of the growth phenotype seems to be IGF2-independent. MISCELLANEOUS: The GRB10 locus is imprinted. The maternal allele is expressed in most tissues, except the brain where it is expressed from the paternal allele. Expression from the maternal allele in fetal and adult brain was however described in PubMed:10861285. SIMILARITY: Belongs to the GRB7/10/14 family. SIMILARITY: Contains 1 PH domain. SIMILARITY: Contains 1 Ras-associating domain. SIMILARITY: Contains 1 SH2 domain. SEQUENCE CAUTION: Sequence=AAH53842.1; Type=Erroneous initiation; Sequence=BAE37514.1; Type=Erroneous initiation; GENE SYNONYMS:Grb10 Meg1. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License.lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:UnificationXref:...lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:RelationshipXref...lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:UnificationXref:...lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:UnificationXref:...lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:UnificationXref:...lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:RelationshipXref...lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:RelationshipXref...lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:UnificationXref:...lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:RelationshipXref...lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:UnificationXref:...lld:biopax3
http://identifiers.org/unip...biopax3:xrefurn:biopax:UnificationXref:...lld:biopax3
http://identifiers.org/unip...biopax3:displayNameGRB10_MOUSElld:biopax3
http://identifiers.org/unip...biopax3:nameGrb10lld:biopax3
http://identifiers.org/unip...biopax3:nameGRB10 adapter proteinlld:biopax3
http://identifiers.org/unip...biopax3:nameMaternally expressed gene 1 proteinlld:biopax3
http://identifiers.org/unip...biopax3:entityFeatureurn:biopax:ModificationFeat...lld:biopax3
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http://identifiers.org/unip...biopax3:entityFeatureurn:biopax:ModificationFeat...lld:biopax3
http://identifiers.org/unip...biopax3:entityFeatureurn:biopax:ModificationFeat...lld:biopax3
http://identifiers.org/unip...biopax3:organismhttp://identifiers.org/taxo...lld:biopax3
http://identifiers.org/unip...biopax3:sequenceMNNDINSSVESLNSACNMQSDTDTAPLLEDGQHASNQGAASSSRGQPQASPRQKMQRSQPVHILRRLQEEDQQLRTASLPAIPNPFPELTGAAPGSPPSVAPSSLPPPPSQPPAKHCGRCEKWIPGENTRGNGKRKIWRWQFPPGFQLSKLTRPGLWTKTTARFSKKQPKNQCPTDTVNPVARMPTSQMEKLRLRKDVKVFSEDGTSKVVEILTDMTARDLCQLLVYKSHCVDDNSWTLVEHHPQLGLERCLEDHEIVVQVESTMPSESKFLFRKNYAKYEFFKNPVNFFPDQMVNWCQQSNGGQAQLLQNFLNTSSCPEIQGFLQVKEVGRKSWKKLYVCLRRSGLYYSTKGTSKEPRHLQLLADLEESSIFYLIAGKKQYNAPNEHGMCIKPNKAKTEMKELRLLCAEDEQIRTCWMTAFRLLKYGMLLYQNYRIPQRKGLPPPFNAPMRSVSENSLVAMDFSGQIGRVIDNPAEAQSAALEEGHAWRKRSTRMNILSSQSPLHPSTLNAVIHRTQHWFHGRISREESHRIIKQQGLVDGLFLLRDSQSNPKAFVLTLCHHQKIKNFQILPCEDDGQTFFTLDDGNTKFSDLIQLVDFYQLNKGVLPCKLKHHCIRVALlld:biopax3
http://identifiers.org/unip...biopax3:standardNameGrowth factor receptor-bound protein 10lld:biopax3
http://www.phosphosite.org/...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://www.phosphosite.org/...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://www.phosphosite.org/...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://www.reactome.org/bio...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://www.phosphosite.org/...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://www.phosphosite.org/...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3
http://www.phosphosite.org/...biopax3:entityReferencehttp://identifiers.org/unip...lld:biopax3