UniProt Accession

 GRB10_MOUSE; Q60760; O35352; Q3TQ71; Q7TSA4; Q8BSH4; Q8BSS5; Q91WC5 

Genbank Protein ID

 U18996; AF022072; AK030727; AK032927; AK163841; AL645803; AL663087; AL645803; AL663087; AL663087; AL645803; AL663087; AL645803; BC016111; BC053842 

Genbank Nucleotide ID

 AAB53687.1; AAB72103.1; BAC27100.1; BAC28088.1; BAE37514.1; CAI23990.1; CAI23990.1; CAI23991.1; CAI23991.1; CAI25685.1; CAI25685.1; CAI25687.1; CAI25687.1; AAH16111.1; AAH53842.1 

Protein Name

 Growth factor receptor-bound protein 10 

Protein Synonyms/Alias

 GRB10 adapter protein; Maternally expressed gene 1 protein 

Gene Name

 Grb10 

Gene Synonyms/Alias

 Meg1 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
191	MPTSQMEKLRLRKDV	ubiquitination	[1]
441	NYRIPQRKGLPPPFN	ubiquitination	[1]
535	EESHRIIKQQGLVDG	ubiquitination	[1]

Reference

 [1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 194 278 Ras-associating.
 DOMAIN 318 427 PH.
 DOMAIN 520 601 SH2.
 MOD_RES 50 50 Phosphoserine (By similarity).
 MOD_RES 96 96 Phosphoserine; by MTOR, MAPK1 and MAPK3
 MOD_RES 455 455 Phosphoserine; by MTOR and PKB/AKT1 (By
 MOD_RES 458 458 Phosphoserine.
 MOD_RES 503 503 Phosphoserine; by MTOR, MAPK1 and MAPK3  

Keyword

 3D-structure; Alternative splicing; Complete proteome; Cytoplasm; Phosphoprotein; Reference proteome; SH2 domain. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 621 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:MGI.
 GO:0005543; F:phospholipid binding; IEA:InterPro.
 GO:0001784; F:phosphotyrosine binding; TAS:BHF-UCL.
 GO:0005070; F:SH3/SH2 adaptor activity; IDA:MGI.
 GO:0008286; P:insulin receptor signaling pathway; IEA:Compara.
 GO:0048009; P:insulin-like growth factor receptor signaling pathway; IPI:MGI.
 GO:0046325; P:negative regulation of glucose import; IMP:BHF-UCL.
 GO:0045719; P:negative regulation of glycogen biosynthetic process; TAS:BHF-UCL.
 GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:BHF-UCL.
 GO:0042326; P:negative regulation of phosphorylation; IDA:BHF-UCL.
 GO:0030178; P:negative regulation of Wnt receptor signaling pathway; IDA:UniProtKB.
 GO:0042327; P:positive regulation of phosphorylation; IEA:Compara.
 GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB. 

Interpro

 IPR015042; BPS-dom.
 IPR011993; PH_like_dom.
 IPR001849; Pleckstrin_homology.
 IPR000159; Ras-assoc.
 IPR000980; SH2. 

Pfam

 PF08947; BPS
 PF00169; PH
 PF00788; RA
 PF00017; SH2 

SMART

 SM00233; PH
 SM00314; RA
 SM00252; SH2 

PROSITE

 PS50003; PH_DOMAIN
 PS50200; RA
 PS50001; SH2 

PRINTS

 PR00401; SH2DOMAIN.