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GRB10 (growth factor receptor-bound protein 10)

Written2002-08Sébastien Degot
I.G.B.M.C, 1, rue Laurent FRIES, BP 163 67404 ILLKIRH, France

(Note : for Links provided by Atlas : click)


Alias_namesgrowth factor receptor-bound protein 10
Other aliasRSS
HGNC (Hugo) GRB10
LocusID (NCBI) 2887
Atlas_Id 278
Location 7p12.1  [Link to chromosome band 7p12]
Location_base_pair Starts at 50590068 and ends at 50782896 bp from pter ( according to hg19-Feb_2009)  [Mapping GRB10.png]
Local_order between two potential genes LOC221982 (in telomeric position) and LOC222987 (in centromeric position).
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
GRB10 (7p12.1) / CSTF3 (11p13)GRB10 (7p12.1) / MAD1L1 (7p22.3)GRB10 (7p12.1) / R3HDM1 (2q21.3)
GRB10 (7p12.1) / SDK1 (7p22.2)GRB10 (7p12.1) / SLC2A13 (12q12)GRB10 (7p12.1) / STEAP1B (7p15.3)
VOPP1 (7p11.2) / GRB10 (7p12.1)


Description at least 16 exons spanning approximately 50 kb
Transcription Four splicing variants are known for human Grb10 gene :
hGrb10 beta alias Grb-IR (accession number U34355)
hGrb10 gamma alias Grb10/IR-SV1 or hGrb-IRbeta/hGrb10
hGrb10 epsilon alias KIAA0207 (accession number D86962)
hGrb10 zeta alias hGrb10 gamma
This nomenclature is a new nomenclature for Grb10 splice variants that was agreed by several researchers
Grb10 gene has a broad expression profile with different size of transcripts depending on the isoforms. Moreover, Grb10 is imprinted in a highly isoform- and tissue-specific manner.


Description isoform beta: 548 aa, 62 kDa (aa: amino acids)
isoform gamma: 536 aa, 61 kDa
isoform epsilon: 588 aa, 66 kDa
isoform zeta: 594 aa, 67 kDa
The different splice variants share a similar structure with :
  • a small proline-rich sequence (11 aa) close to the amino-terminus that can interact with SH3 domain of c-Abl in vitro (domain named Pro on the figure above).
  • a Ras-associated-like domain (84 aa) homologous to the C. elegans MIG-10 protein raising the possibility that Grb10 could directly interact with Ras-like GTP-binding protein (domain named RA on the figure above).
  • a central Pleckstrin homology domain of 124 aa except for the isoform alpha which contains only 85 aa (domain named PH on the figure above).This domain was proposed to play an important role in targeting Grb10 to the mitochondria.
  • the BPS (Between PH and SH2) domain is composed of 48 aa and binds to the activated insulin and/or IGF-1 receptors.
  • an SH2 domain (104 aa) which interacts with phosphotyrosine of several proteins.
  • PH domain, BPS domain and SH2 domain compose a region of 300 aa termed GM (Grb/Mig). Grb10 is able to dimerize/oligomerize through interaction between the N-terminal domain of one molecule and the GM region of another one
  • Expression Grb10 protein has been detected in most human cell lines using a highly specific antibody.
    Localisation Most of the endogenous Grb10 is peripherally associated with the mitochondria where it interacts with pools of Raf-1. Treatment with serum or IGF-I is able to induce the relocalization of a small proportion of the endogenous Grb10 to the plasma membrane.
    Function Grb10 is able to interact with a lot of proteins (Insulin receptor, IGF-1 receptor, ELK receptor, PDGFRB, GHR, EGFR, RET, HGFR, FGFR, RAF-1, MEK1, JAK2, BCR-Abl TEC kinase, NEDD4, cABL, AKT, c-KIT).
    Several studies suggest a role for Grb10 in cell proliferation. However, despite the clear involvement of Grb10 in pathways activated by IR and IGF-R, there is still some controversy about whether its effect is inhibitory or stimulatory. One report showed that stable overexpression of mGRB10 alpha inhibits IGF-1 mediated cell proliferation, whereas another report demonstrated that overexpression of the same mGrb10 alpha increased DNA synthesis upon growth factor stimulation (PDGFBB, IG-1, or insulin). These contradictions might be explained by the use of different cell lines or experimental procedures.
    Grb10 seems to have also a role in apoptosis regulation. Grb10 SH2 domain is able to interact with Raf1 and MEK1. Transfection of SH2 domain Grb10 mutants induces apoptosis in HTC-IR and COS-7 cells suggesting that Grb10 may influence the equilibrium between ERK and JNK pathways and determine the choice between proliferation and programmed cell death. As Grb10 is located at the mitochondrial membrane it may be involved in communication between plasma membrane receptors and apoptosis regulators located on the mitochondrial outer membrane.
    Grb10 interacts with Akt and is proposed to be a positive regulator of the Akt pathway downstream of PI3-K. By acting as an adaptator involved in the relocalization of Akt to the cell membrane, Grb10 may contribute to Akt activation and regulation of different biological processes such as proliferation, apoptosis and growth.
    Homology Grb10 is a member of the Grb7 family of adapter molecules which contains three member Grb7, Grb10 and Grb14. Grb10 counterparts are found in mouse, rat, fly and worm.

    Implicated in

    Disease The mapping of Grb10 gene to 7p made it a candidate gene for Russel-Silver Syndrome (RSS). But recent data suggest that Grb10 is unlikely to be the gene responsible for RSS.


    Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10gamma.
    Dong LQ, Du H, Porter SG, Kolakowski LF Jr, Lee AV, Mandarino LJ, Fan J, Yee D, Liu F
    The Journal of biological chemistry. 1997 ; 272 (46) : 29104-29112.
    PMID 9360986
    Inhibition of hGrb10 binding to the insulin receptor by functional domain-mediated oligomerization.
    Dong LQ, Porter S, Hu D, Liu F
    The Journal of biological chemistry. 1998 ; 273 (28) : 17720-17725.
    PMID 9651371
    Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains.
    Frantz JD, Giorgetti-Peraldi S, Ottinger EA, Shoelson SE
    The Journal of biological chemistry. 1997 ; 272 (5) : 2659-2667.
    PMID 9006901
    The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions.
    Han DC, Shen TL, Guan JL
    Oncogene. 2001 ; 20 (44) : 6315-6321.
    PMID 11607834
    Role for the adaptor protein Grb10 in the activation of Akt.
    Jahn T, Seipel P, Urschel S, Peschel C, Duyster J
    Molecular and cellular biology. 2002 ; 22 (4) : 979-991.
    PMID 11809791
    Assignment of growth factor receptor-bound protein 10 (GRB10) to human chromosome 7p11.2-p12.
    Jerome CA, Scherer SW, Tsui LC, Gietz RD, Triggs-Raine B
    Genomics. 1997 ; 40 (1) : 215-216.
    PMID 9070953
    Grb-IR: a SH2-domain-containing protein that binds to the insulin receptor and inhibits its function.
    Liu F, Roth RA
    Proceedings of the National Academy of Sciences of the United States of America. 1995 ; 92 (22) : 10287-10291.
    PMID 7479769
    Evidence against GRB10 as the gene responsible for Silver-Russell syndrome.
    McCann JA, Zheng H, Islam A, Goodyer CG, Polychronakos C
    Biochemical and biophysical research communications. 2001 ; 286 (5) : 943-948.
    PMID 11527390
    The role of mGrb10alpha in insulin-like growth factor I-mediated growth.
    Morrione A, Valentinis B, Resnicoff M, Xu S, Baserga R
    The Journal of biological chemistry. 1997 ; 272 (42) : 26382-26387.
    PMID 9334212
    Localization of endogenous Grb10 to the mitochondria and its interaction with the mitochondrial-associated Raf-1 pool.
    Nantel A, Huber M, Thomas DY
    The Journal of biological chemistry. 1999 ; 274 (50) : 35719-35724.
    PMID 10585452
    Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases.
    Nantel A, Mohammad-Ali K, Sherk J, Posner BI, Thomas DY
    The Journal of biological chemistry. 1998 ; 273 (17) : 10475-10484.
    PMID 9553107
    Interaction of a GRB-IR splice variant (a human GRB10 homolog) with the insulin and insulin-like growth factor I receptors. Evidence for a role in mitogenic signaling.
    O'Neill TJ, Rose DW, Pillay TS, Hotta K, Olefsky JM, Gustafson TA
    The Journal of biological chemistry. 1996 ; 271 (37) : 22506-22513.
    PMID 8798417
    Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis.
    Wang J, Dai H, Yousaf N, Moussaif M, Deng Y, Boufelliga A, Swamy OR, Leone ME, Riedel H
    Molecular and cellular biology. 1999 ; 19 (9) : 6217-6228.
    PMID 10454568
    Sequence analysis identifies a ras-associating (RA)-like domain in the N-termini of band 4.1/JEF domains and in the Grb7/10/14 adapter family.
    Wojcik J, Girault JA, Labesse G, Chomilier J, Mornon JP, Callebaut I
    Biochemical and biophysical research communications. 1999 ; 259 (1) : 113-120.
    PMID 10334925
    Imprinting of human GRB10 and its mutations in two patients with Russell-Silver syndrome.
    Yoshihashi H, Maeyama K, Kosaki R, Ogata T, Tsukahara M, Goto Y, Hata J, Matsuo N, Smith RJ, Kosaki K
    American journal of human genetics. 2000 ; 67 (2) : 476-482.
    PMID 10856193


    This paper should be referenced as such :
    Degot, S
    GRB10 (growth factor receptor-bound protein 10)
    Atlas Genet Cytogenet Oncol Haematol. 2003;7(1):1-3.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
      t(7;7)(p12;p22) GRB10/SDK1

    Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 6 ]
      Lung: Translocations in Squamous Cell Carcinoma
    t(7;7)(p11;p12) VOPP1/GRB10
    t(7;7)(p12;p15) GRB10/STEAP1B
    t(7;7)(p12;p22) GRB10/MAD1L1
    t(7;11)(p12;p13) GRB10/CSTF3
    t(7;12)(p12;q12) GRB10/SLC2A13

    External links

    HGNC (Hugo)GRB10   4564
    LRG (Locus Reference Genomic)LRG_1032
    Entrez_Gene (NCBI)GRB10  2887  growth factor receptor bound protein 10
    AliasesGRB-IR; Grb-10; IRBP; MEG1; 
    GeneCards (Weizmann)GRB10
    Ensembl hg19 (Hinxton)ENSG00000106070 [Gene_View]
    Ensembl hg38 (Hinxton)ENSG00000106070 [Gene_View]  ENSG00000106070 [Sequence]  chr7:50590068-50782896 [Contig_View]  GRB10 [Vega]
    ICGC DataPortalENSG00000106070
    TCGA cBioPortalGRB10
    AceView (NCBI)GRB10
    Genatlas (Paris)GRB10
    SOURCE (Princeton)GRB10
    Genetics Home Reference (NIH)GRB10
    Genomic and cartography
    GoldenPath hg38 (UCSC)GRB10  -     chr7:50590068-50782896 -  7p12.1   [Description]    (hg38-Dec_2013)
    GoldenPath hg19 (UCSC)GRB10  -     7p12.1   [Description]    (hg19-Feb_2009)
    GoldenPathGRB10 - 7p12.1 [CytoView hg19]  GRB10 - 7p12.1 [CytoView hg38]
    Genome Data Viewer NCBIGRB10 [Mapview hg19]  
    Gene and transcription
    Genbank (Entrez)AB000731 AF000017 AF000018 AF001534 AI360831
    RefSeq transcript (Entrez)NM_001001549 NM_001001550 NM_001001555 NM_001350814 NM_001350815 NM_001350816 NM_001371008 NM_001371009 NM_005311
    RefSeq genomic (Entrez)
    Consensus coding sequences : CCDS (NCBI)GRB10
    Alternative Splicing GalleryENSG00000106070
    Gene ExpressionGRB10 [ NCBI-GEO ]   GRB10 [ EBI - ARRAY_EXPRESS ]   GRB10 [ SEEK ]   GRB10 [ MEM ]
    Gene Expression Viewer (FireBrowse)GRB10 [ Firebrowse - Broad ]
    GenevisibleExpression of GRB10 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
    BioGPS (Tissue expression)2887
    GTEX Portal (Tissue expression)GRB10
    Human Protein AtlasENSG00000106070-GRB10 [pathology]   [cell]   [tissue]
    Protein : pattern, domain, 3D structure
    UniProt/SwissProtQ13322   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
    NextProtQ13322  [Sequence]  [Exons]  [Medical]  [Publications]
    With graphics : InterProQ13322
    Splice isoforms : SwissVarQ13322
    Domaine pattern : Prosite (Expaxy)PH_DOMAIN (PS50003)    RA (PS50200)    SH2 (PS50001)   
    Domains : Interpro (EBI)BPS-dom    GRB/APBB1IP    Grb10    Grb10_SH2    PH-like_dom_sf    PH_APBB1IP    PH_domain    RA_dom    SH2    SH2_dom_sf    Ubiquitin-like_domsf   
    Domain families : Pfam (Sanger)BPS (PF08947)    PH (PF00169)    RA (PF00788)    SH2 (PF00017)   
    Domain families : Pfam (NCBI)pfam08947    pfam00169    pfam00788    pfam00017   
    Domain families : Smart (EMBL)PH (SM00233)  RA (SM00314)  SH2 (SM00252)  
    Conserved Domain (NCBI)GRB10
    DMDM Disease mutations2887
    PDB (RSDB)1NRV    3HK0   
    PDB Europe1NRV    3HK0   
    PDB (PDBSum)1NRV    3HK0   
    PDB (IMB)1NRV    3HK0   
    Structural Biology KnowledgeBase1NRV    3HK0   
    SCOP (Structural Classification of Proteins)1NRV    3HK0   
    CATH (Classification of proteins structures)1NRV    3HK0   
    Human Protein Atlas [tissue]ENSG00000106070-GRB10 [tissue]
    Peptide AtlasQ13322
    IPIIPI00012752   IPI00218909   IPI00218910   IPI00790216   IPI00871859   IPI00384887   IPI00879698   IPI00789632   
    Protein Interaction databases
    DIP (DOE-UCLA)Q13322
    IntAct (EBI)Q13322
    Ontologies - Pathways
    Ontology : AmiGOinsulin receptor binding  insulin receptor binding  protein binding  cytoplasm  cytosol  plasma membrane  axon guidance  insulin receptor signaling pathway  negative regulation of Wnt signaling pathway  negative regulation of Wnt signaling pathway  positive regulation of vascular endothelial growth factor receptor signaling pathway  protein-containing complex  negative regulation of glucose import  negative regulation of insulin receptor signaling pathway  negative regulation of insulin receptor signaling pathway  positive regulation of cold-induced thermogenesis  
    Ontology : EGO-EBIinsulin receptor binding  insulin receptor binding  protein binding  cytoplasm  cytosol  plasma membrane  axon guidance  insulin receptor signaling pathway  negative regulation of Wnt signaling pathway  negative regulation of Wnt signaling pathway  positive regulation of vascular endothelial growth factor receptor signaling pathway  protein-containing complex  negative regulation of glucose import  negative regulation of insulin receptor signaling pathway  negative regulation of insulin receptor signaling pathway  positive regulation of cold-induced thermogenesis  
    REACTOMEQ13322 [protein]
    REACTOME PathwaysR-HSA-8853659 [pathway]   
    NDEx NetworkGRB10
    Atlas of Cancer Signalling NetworkGRB10
    Wikipedia pathwaysGRB10
    Orthology - Evolution
    GeneTree (enSembl)ENSG00000106070
    Phylogenetic Trees/Animal Genes : TreeFamGRB10
    Homologs : HomoloGeneGRB10
    Homology/Alignments : Family Browser (UCSC)GRB10
    Gene fusions - Rearrangements
    Fusion : MitelmanGRB10/CSTF3 [7p12.1/11p13]  
    Fusion : MitelmanGRB10/MAD1L1 [7p12.1/7p22.3]  
    Fusion : MitelmanGRB10/SDK1 [7p12.1/7p22.2]  
    Fusion : MitelmanGRB10/SLC2A13 [7p12.1/12q12]  
    Fusion : MitelmanGRB10/STEAP1B [7p12.1/7p15.3]  
    Fusion : MitelmanVOPP1/GRB10 [7p11.2/7p12.1]  
    Fusion PortalGRB10 7p12.1 CSTF3 11p13 OV
    Fusion PortalGRB10 7p12.1 MAD1L1 7p22.3 LUAD
    Fusion PortalGRB10 7p12.1 SLC2A13 12q12 BRCA
    Fusion PortalGRB10 7p12.1 STEAP1B 7p15.3 BLCA
    Fusion : Fusion_HubAVL9--GRB10    CPA1--GRB10    CREB5--GRB10    EGFR--GRB10    EIF3A--GRB10    ELMO1--GRB10    FCGR3B--GRB10    GAS7--GRB10    GLI3--GRB10    GNA12--GRB10    GRB10--AHCYL2    GRB10--APOL2    GRB10--C15ORF27    GRB10--COL1A2    GRB10--CSTF3   
    GRB10--DDC    GRB10--EEPD1    GRB10--FLT1    GRB10--GAS7    GRB10--GCA    GRB10--GIMAP8    GRB10--GNAS    GRB10--GTPBP10    GRB10--HIBADH    GRB10--HPCAL1    GRB10--MAD1L1    GRB10--PIP4K2C    GRB10--PSMG2    GRB10--R3HDM1    GRB10--RBM17   
    GRB10--SCMH1    GRB10--SHROOM4    GRB10--SLC2A13    GRB10--STEAP1B    GRB10--STK17A    GRB10--TRIB3    GRB10--TRRAP    GRB10--TUBGCP3    GRB10--UBE2QL1    GRB10--VOPP1    GRB10--XAB2    GRB10--ZNF706    GRB10--ZPBP    HLCS--GRB10    KIRREL--GRB10   
    MRPS6--GRB10    NLK--GRB10    NRIP1--GRB10    SKAP2--GRB10    TNS3--GRB10   
    Fusion : QuiverGRB10
    Polymorphisms : SNP and Copy number variants
    NCBI Variation ViewerGRB10 [hg38]
    dbSNP Single Nucleotide Polymorphism (NCBI)GRB10
    Exome Variant ServerGRB10
    GNOMAD BrowserENSG00000106070
    Varsome BrowserGRB10
    Genetic variants : HAPMAP2887
    Genomic Variants (DGV)GRB10 [DGVbeta]
    DECIPHERGRB10 [patients]   [syndromes]   [variants]   [genes]  
    CONAN: Copy Number AnalysisGRB10 
    ICGC Data PortalGRB10 
    TCGA Data PortalGRB10 
    Broad Tumor PortalGRB10
    OASIS PortalGRB10 [ Somatic mutations - Copy number]
    Somatic Mutations in Cancer : COSMICGRB10  [overview]  [genome browser]  [tissue]  [distribution]  
    Somatic Mutations in Cancer : COSMIC3DGRB10
    Mutations and Diseases : HGMDGRB10
    LOVD (Leiden Open Variation Database)Whole genome datasets
    LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
    LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
    BioMutaselect GRB10
    DgiDB (Drug Gene Interaction Database)GRB10
    DoCM (Curated mutations)GRB10 (select the gene name)
    CIViC (Clinical Interpretations of Variants in Cancer)GRB10 (select a term)
    NCG6 (London) select GRB10
    Cancer3DGRB10 (select the gene name)
    Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
    Genetic Testing Registry GRB10
    NextProtQ13322 [Medical]
    Open Targets GeneticsENSG00000106070  [validation]
    snp3D : Map Gene to Disease2887
    BioCentury BCIQGRB10
    ClinGenGRB10 (curated)
    Clinical trials, drugs, therapy
    Protein Interactions : CTD2887
    Pharm GKB GenePA28960
    Clinical trialGRB10
    canSAR (ICR)GRB10 (select the gene name)
    DataMed IndexGRB10
    Other databaseThe Grb7, Grb10 and Grb14 protein family
    PubMed110 Pubmed reference(s) in Entrez
    GeneRIFsGene References Into Functions (Entrez)
    REVIEW articlesautomatic search in PubMed
    Last year publicationsautomatic search in PubMed

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    indexed on : Sat Jul 11 20:27:16 CEST 2020

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