Human Gene GRB10 (ENST00000357271.9) Description and Page Index
  Description: Homo sapiens growth factor receptor bound protein 10 (GRB10), transcript variant 2, mRNA. (from RefSeq NM_001001549)
RefSeq Summary (NM_001001549): The product of this gene belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with insulin receptors and insulin-like growth-factor receptors. Overexpression of some isoforms of the encoded protein inhibits tyrosine kinase activity and results in growth suppression. This gene is imprinted in a highly isoform- and tissue-specific manner, with expression observed from the paternal allele in the brain, and from the maternal allele in the placental trophoblasts. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2010].
Gencode Transcript: ENST00000357271.9
Gencode Gene: ENSG00000106070.19
Transcript (Including UTRs)
   Position: hg38 chr7:50,592,580-50,732,353 Size: 139,774 Total Exon Count: 15 Strand: -
Coding Region
   Position: hg38 chr7:50,592,952-50,732,322 Size: 139,371 Coding Exon Count: 15 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated: 2019-09-04

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr7:50,592,580-50,732,353)mRNA (may differ from genome)Protein (548 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsHGNC
HPRDLynxMGIneXtProtOMIMPubMed
ReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: GRB10_HUMAN
DESCRIPTION: RecName: Full=Growth factor receptor-bound protein 10; AltName: Full=GRB10 adapter protein; AltName: Full=Insulin receptor-binding protein Grb-IR;
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.
ENZYME REGULATION: Phosphorylation by mTORC1 stabilizes and activates GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-dependent signaling.
SUBUNIT: Interacts 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.
INTERACTION: P54762:EPHB1; NbExp=2; IntAct=EBI-80275, EBI-80252;
SUBCELLULAR LOCATION: Cytoplasm (By similarity). 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).
TISSUE SPECIFICITY: Widely expressed in fetal and adult tissues, including fetal and postnatal liver, lung, kidney, skeletal muscle, heart, spleen, skin and brain.
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.
PTM: Phosphorylated on serine residues upon EGF, FGF and PDGF stimulation (By similarity). Phosphorylated at Tyr-67 by TEC.
MISCELLANEOUS: The 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.
MISCELLANEOUS: GRB10 is unlikely to be responsible for Silver- Russell syndrome (SRS).
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=BAA13198.2; Type=Erroneous initiation;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/GRB10ID278.html";

-  MalaCards Disease Associations
  MalaCards Gene Search: GRB10
Diseases sorted by gene-association score: silver-russell syndrome (14), silver spastic paraplegia syndrome (8), adult syndrome (5), diabetes mellitus, transient neonatal, 1 (4)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D001564 Benzo(a)pyrene
  • D016572 Cyclosporine
  • D013749 Tetrachlorodibenzodioxin
  • C014175 pyrazolo(3,4-d)pyrimidine
  • C017947 sodium arsenite
  • C479799 (E)-4-((2-N-(4-methoxybenzenesulfonyl)amino)stilbazole)1-oxide
  • C111118 2',3,3',4',5-pentachloro-4-hydroxybiphenyl
  • C063002 2,3-dimethoxy-1,4-naphthoquinone
  • C009505 4,4'-diaminodiphenylmethane
  • C075773 4-phenylbutyric acid
          more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 22.93 RPKM in Pancreas
Total median expression: 482.86 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR 0.00310.000 Picture PostScript Text
3' UTR -110.10372-0.296 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR015042 - BPS-dom
IPR011993 - PH_like_dom
IPR001849 - Pleckstrin_homology
IPR000159 - Ras-assoc
IPR000980 - SH2

Pfam Domains:
PF08947 - BPS (Between PH and SH2)
PF00169 - PH domain
PF00788 - Ras association (RalGDS/AF-6) domain
PF00017 - SH2 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

1NRV
- X-ray MuPIT

3HK0
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q13322
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005070 SH3/SH2 adaptor activity
GO:0005158 insulin receptor binding
GO:0005515 protein binding
GO:0042802 identical protein binding

Biological Process:
GO:0007165 signal transduction
GO:0007411 axon guidance
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: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:0005737 cytoplasm
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0032991 macromolecular complex


-  Descriptions from all associated GenBank mRNAs
  BX649028 - Homo sapiens mRNA; cDNA DKFZp686P1694 (from clone DKFZp686P1694).
D86962 - Homo sapiens mRNA for KIAA0207 gene, partial cds.
U69276 - Human hGrbIRbeta/hGrb10 (GRBIRbeta/GRB10) mRNA, complete cds.
U34355 - Human skeletal muscle insulin receptor binding protein (Grb-IR) mRNA, complete cds.
BC024285 - Homo sapiens growth factor receptor-bound protein 10, mRNA (cDNA clone MGC:39227 IMAGE:4590330), complete cds.
AJ271366 - Homo sapiens mRNA for putative adaptor protein (GRB10 gene).
AF000018 - Homo sapiens adapter protein mRNA, partial cds.
U66065 - Human Grb10- and Grb-IR-related splice variant 1 mRNA, complete cds.
AK289511 - Homo sapiens cDNA FLJ76730 complete cds, highly similar to Homo sapiens growth factor receptor-bound protein 10 (GRB10), transcript variant 3, mRNA.
AF000017 - Homo sapiens adapter protein (hGrb10zeta) mRNA, complete cds.
AF001534 - Homo sapiens insulin receptor binding protein (Grb-IR/hGrb10) mRNA, complete cds.
AB000731 - Homo sapiens mRNA for Grb-10, complete cds.
DQ891700 - Synthetic construct clone IMAGE:100004330; FLH183443.01X; RZPDo839C07142D growth factor receptor-bound protein 10 (GRB10) gene, encodes complete protein.
DQ896846 - Synthetic construct Homo sapiens clone IMAGE:100011306; FLH183439.01L; RZPDo839C07141D growth factor receptor-bound protein 10 (GRB10) gene, encodes complete protein.
AB383799 - Synthetic construct DNA, clone: pF1KSDA0207, Homo sapiens GRB10 gene for growth factor receptor-bound protein 10, complete cds, without stop codon, in Flexi system.
JD452124 - Sequence 433148 from Patent EP1572962.
JD155723 - Sequence 136747 from Patent EP1572962.
JD290690 - Sequence 271714 from Patent EP1572962.
JD177785 - Sequence 158809 from Patent EP1572962.
AK021643 - Homo sapiens cDNA FLJ11581 fis, clone HEMBA1003598.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q13322 (Reactome details) participates in the following event(s):

R-HSA-110011 Binding of Grb10 to the insulin receptor
R-HSA-1433501 Interaction of other adapter proteins with p-KIT
R-HSA-8853753 2x p-5Y-RET:GDNF:GFRA complexes bind GRB7,10
R-HSA-74749 Signal attenuation
R-HSA-1433557 Signaling by SCF-KIT
R-HSA-8853659 RET signaling
R-HSA-74751 Insulin receptor signalling cascade
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-422475 Axon guidance
R-HSA-74752 Signaling by Insulin receptor
R-HSA-162582 Signal Transduction
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: A4D258, A7VJ95, A8K0E6, D3DVM9, GRB10_HUMAN, GRBIR, KIAA0207, NM_001001549, O00427, O00701, O75222, Q13322, Q92606, Q92907, Q92948, uc003tpj.1, uc003tpj.2, uc003tpj.3
UCSC ID: uc003tpj.3
RefSeq Accession: NM_001001549
Protein: Q13322 (aka GRB10_HUMAN)
CCDS: CCDS47586.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.