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GRB2 Gene

protein-coding   GIFtS: 73
GCID: GC17M073313

Growth Factor Receptor-Bound Protein 2

  See GRB2-related disease
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Growth Factor Receptor-Bound Protein 21 2     MST0842
Protein Ash2 3     MSTP0842
ASH2 3     NCKAP22
SH2/SH3 Adapter GRB22 3     Abundant SRC Homology2
EGFRBP-GRB22     Epidermal Growth Factor Receptor-Binding Protein GRB22
Grb3-32     Growth Factor Receptor-Bound Protein 32
HT0272     Adapter Protein GRB23

External Ids:    HGNC: 45661   Entrez Gene: 28852   Ensembl: ENSG000001778857   OMIM: 1083555   UniProtKB: P629933   

Export aliases for GRB2 gene to outside databases

Previous GC identifers: GC17M076374 GC17M073779 GC17M073911 GC17M070825 GC17M068724


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for GRB2 Gene:
The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two
SH3 domains. Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its
SH2 domain binds tyrosine phosphorylated sequences. This gene is similar to the Sem5 gene of C.elegans, which is
involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different
isoforms have been found for this gene. (provided by RefSeq, Jul 2008)

GeneCards Summary for GRB2 Gene:
GRB2 (growth factor receptor-bound protein 2) is a protein-coding gene. Diseases associated with GRB2 include hydrocele. GO annotations related to this gene include SH3 domain binding and identical protein binding. An important paralog of this gene is GRAP.

UniProtKB/Swiss-Prot: GRB2_HUMAN, P62993
Function: Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras
signaling pathway
Function: Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits
EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2
and by suppressing proliferative signals, may trigger active programmed cell death

Gene Wiki entry for GRB2 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000017.10  NC_018928.2  NT_010783.16  
Regulatory elements:
   Regulatory transcription factor binding sites in the GRB2 gene promoter:
         p53   Sp1   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmidGRB2 promoter sequence
   Search Chromatin IP Primers for GRB2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat GRB2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 17q24-q25   Ensembl cytogenetic band:  17q25.1   HGNC cytogenetic band: 17q24-q25

GRB2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
GRB2 gene location

GeneLoc information about chromosome 17         GeneLoc Exon Structure

GeneLoc location for GC17M073313:  view genomic region     (about GC identifiers)

Start:
73,314,157 bp from pter      End:
73,401,790 bp from pter
Size:
87,634 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., and/or eBioscience,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., and/or eBioscience, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, and/or others.)
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UniProtKB/Swiss-Prot: GRB2_HUMAN, P62993 (See protein sequence)
Recommended Name: Growth factor receptor-bound protein 2  
Size: 217 amino acids; 25206 Da
Subunit: Associates with activated Tyr-phosphorylated EGF receptor/EGFR and PDGF receptors via its SH2 domain.
Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, IRS4, SHC and LNK; probably via
the concerted action of both its SH2 and SH3 domains. It also seems to interact with RAS in the signaling pathway
leading to DNA synthesis. Binds to and translocates the guanine nucleotide exchange factors SOS. Interacts with
phosphorylated TOM1L1 and MET. Interacts with the phosphorylated C-terminus of SH2B2. Interacts with
phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation. Interacts with NISCH, PTPNS1,
REPS2 and the syntrophin SNTA1. Interacts with REPS1 and PIK3C2B via its SH3 domains (By similarity). Interacts
with HCV NS5A via its SH3 domains. Interacts with CBL and CBLB. Interacts with AJUBA and CLNK (By similarity).
Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity). Interacts with SHB,
INPP5D/SHIP1, SKAP1 and SKAP2. Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with
SOS1 and the SH2 domain with phosphorylated MUC1. Interacts with PTPN11. Interacts with PRNP and THEMIS (By
similarity). Interacts with FLT1 (tyrosine phosphorylated) and KDR. Interacts with PDGFRA (tyrosine
phosphorylated); the interaction may be indirect (By similarity). Interacts with RALGPS1 and with HCST. Interacts
(via SH3 domain) with HEV ORF3 protein. Interacts with GAPT and PTPRE. Interacts (via SH2 domain) with KIF26A.
Interacts (via SH3 2) with GAB2. Interacts with ADAM15. Interacts with THEMIS2. Interacts (via SH2 domain) with
AXL and KIT (phosphorylated). Interacts with PTPRJ and BCR. Interacts with FLT4 (tyrosine phosphorylated).
Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration. Interacts with PTPN23.
Part of a complex including TNK2, GRB2 and one receptor tyrosine kinase (RTK) such as AXL, in which GRB2 promotes
RTK recruitment by TNK2. Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with ERBB4.
Interacts with NTRK1 (phosphorylated upon ligand-binding). Interacts with PTK2/FAK1 (tyrosine phosphorylated).
Interacts with PTK2B/PYK2 (tyrosine phosphorylated). Isoform 1 interacts with SCIMP. Interacts with PLCG1, LAT
and THEMIS upon TCR activation in thymocytes (By similarity). Interacts with TESPA1 and DAB2. Interacts (via SH3
domains) with GAREM isoform 1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon
EGF stimulation. Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where
it can activate RHOA. Interacts with ASAP3 (phosphorylated form)
Selected PDB 3D structures from and Proteopedia for GRB2 (see all 43):
1AZE (3D)        1BM2 (3D)        1BMB (3D)        1CJ1 (3D)        1FHS (3D)        1FYR (3D)    
Secondary accessions: P29354 Q14450 Q63057 Q63059
Alternative splicing: 2 isoforms:  P62993-1, P29354-1   P62993-2, P29354-2   

Explore the universe of human proteins at neXtProt for GRB2: NX_P62993

Explore proteomics data for GRB2 at MOPED

Post-translational modifications: 

  • Ubiquitination2 at Lys44, Lys56, Lys109
  • Modification sites at PhosphoSitePlus

  • See GRB2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_002077.1  NP_987102.1  

    ENSEMBL proteins: 
     ENSP00000463525   ENSP00000376346   ENSP00000376347   ENSP00000376345   ENSP00000339007  
     ENSP00000464279   ENSP00000462785   ENSP00000317360  
    Reactome Protein details: P62993

    GRB2 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant GRB2 Protein
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    OriGene Purified Proteins for GRB2
    OriGene Protein Over-expression Lysate for GRB2
    OriGene MassSpec for GRB2
    OriGene Custom Protein Services for GRB2
    GenScript Custom Purified and Recombinant Proteins Services for GRB2
    Novus Biologicals GRB2 Proteins
    Novus Biologicals GRB2 Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for GRB2
    Browse Proteins at Cloud-Clone Corp.

     
    Search eBioscience for Proteins for GRB2 

    GRB2 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of GRB2
    R&D Systems Antibodies for GRB2
    Cell Signaling Technology (CST) Antibodies for GRB2 
    OriGene Antibodies for GRB2
    OriGene Custom Antibody Services for GRB2
    Novus Biologicals GRB2 Antibodies
    Abcam antibodies for GRB2
    Browse Antibodies at Cloud-Clone Corp.
    ThermoFisher Antibody for GRB2
    LSBio Antibodies in human, mouse, rat for GRB2

    GRB2 Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for GRB2
    Browse R&D Systems for biochemical assays
    GenScript Custom Assay Services for GRB2
    Browse Enzo Life Sciences for kits & assays
    Browse ELISAs at Cloud-Clone Corp.
    Browse CLIAs at Cloud-Clone Corp.
    Search eBioscience for ELISAs for GRB2 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    SH2D: SH2 domain containing

    2 InterPro protein domains:
     IPR001452 SH3_domain
     IPR000980 SH2

    Graphical View of Domain Structure for InterPro Entry P62993

    ProtoNet protein and cluster: P62993

    UniProtKB/Swiss-Prot: GRB2_HUMAN, P62993
    Domain: The SH3 domains mediate interaction with RALGPS1 and SHB
    Similarity: Belongs to the GRB2/sem-5/DRK family
    Similarity: Contains 1 SH2 domain
    Similarity: Contains 2 SH3 domains


    Find genes that share domains with GRB2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: GRB2_HUMAN, P62993
    Function: Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras
    signaling pathway
    Function: Isoform 2 does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits
    EGF-induced transactivation of a RAS-responsive element. Isoform 2 acts as a dominant negative protein over GRB2
    and by suppressing proliferative signals, may trigger active programmed cell death

         Genatlas biochemistry entry for GRB2:
    growth factor receptor bound protein 2,major CBL associated protein,homolog to Caenorhabditis elegans Sem5 gene
    and Drosophila Drk,STAR playing a key role in insulin signal transduction through connecting with IRS1 and
    IGFR5,and in mitogenic RAS signalic through interaction with SHC1

         Gene Ontology (GO): Selected molecular function terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001784phosphotyrosine binding IEA--
    GO:0005070SH3/SH2 adaptor activity TAS8253073
    GO:0005154epidermal growth factor receptor binding IPI12577067
    GO:0005168neurotrophin TRKA receptor binding IPI15488758
    GO:0005515protein binding IPI10026169
         
    Find genes that share ontologies with GRB2           About GenesLikeMe


    Phenotypes:
         3 GenomeRNAi human phenotypes for GRB2:
     Decreased focal adhesion (FA)   Increased cell death HMECs cel  Upregulation of Wnt/beta-caten 

         Selected MGI mutant phenotypes (inferred from 6 alleles(MGI details for Grb2) (see all 17):
     behavior/neurological  cardiovascular system  cellular  craniofacial  digestive/alimentary 
     embryogenesis  growth/size/body  hearing/vestibular/ear  hematopoietic system  homeostasis/metabolism 
     immune system  mortality/aging  nervous system  normal  renal/urinary system 

    Find genes that share phenotypes with GRB2           About GenesLikeMe

    Animal Models:
         MGI mouse knock-out Grb2tm1Paw for GRB2

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for GRB2
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for GRB2

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for GRB2
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for GRB2

    miRNA
    Products:
        
    miRTarBase miRNAs that target GRB2:
    hsa-mir-7-5p (MIRT025709), hsa-mir-378a-3p (MIRT007278), hsa-mir-92b-3p (MIRT040690), hsa-mir-124-3p (MIRT022221), hsa-mir-433-3p (MIRT001201), hsa-mir-100-5p (MIRT048495), hsa-mir-34a-5p (MIRT025255), hsa-mir-16-5p (MIRT031431), hsa-mir-93-5p (MIRT027965)

    Block miRNA regulation of human, mouse, rat GRB2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate GRB2 (see all 61):
    hsa-miR-4291 hsa-miR-1224-3p hsa-miR-513a-5p hsa-miR-128 hsa-miR-200a hsa-miR-1260b hsa-miR-507 hsa-miR-105
    SwitchGear 3'UTR luciferase reporter plasmidGRB2 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for GRB2
    Predesigned siRNA for gene silencing in human, mouse, rat GRB2

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for GRB2

    Clone
    Products:
         
    OriGene clones in human, mouse for GRB2 (see all 11)
    OriGene ORF clones in mouse, rat for GRB2
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): GRB2 (NM_002086)
    Sino Biological Human cDNA Clone for GRB2
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for GRB2
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat GRB2
    Addgene plasmids for GRB2 

    Cell Line
    Products:
         
    GenScript Custom overexpressing Cell Line Services for GRB2
    Browse ESI BIO Cell Lines and PureStem Progenitors for GRB2 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for GRB2

    Flow Cytometry
    Products:
       

     
    eBioscience FlowRNA Probe Sets ( VA1-12274) for GRB2 


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    GRB2_HUMAN, P62993: Nucleus. Cytoplasm. Endosome. Golgi apparatus (By similarity)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    endosome5
    nucleus5
    cytosol4
    plasma membrane4
    cytoskeleton2
    endoplasmic reticulum2
    extracellular2
    golgi apparatus2

    Gene Ontology (GO): Selected cellular component terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005634nucleus IDA--
    GO:0005737cytoplasm IDA--
    GO:0005768endosome IDA--
    GO:0005794Golgi apparatus IEA--
    GO:0005829cytosol TAS14722116

    Find genes that share ontologies with GRB2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for GRB2 About   (see all 160)  
    See pathways by source

    SuperPathSelected contained pathways About (see all per SuperPath)
    1Immune response Fc epsilon RI pathway
    Immune response Fc epsilon RI pathway0.43
    VEGF - VEGF R2 Signaling Pathways0.35
    Immune response BCR pathway0.43
    Fc-epsilon receptor I signaling in mast cells0.34
    Fc epsilon RI signaling pathway0.41
    2IL-9 Signaling Pathways
    IL-9 Signaling Pathways0.90
    IL-4 Signaling Pathways0.84
    IL-7 Signaling Pathways0.90
    IL-9 Signaling Pathway0.42
    IL-21 Signaling Pathways0.90
    Immune response IL 9 signaling pathway0.42
    Common Cytokine Receptor Gamma-Chain Family Signaling Pathways0.90
    IL-7 Signaling Pathway0.40
    3Translation Insulin regulation of translation
    Translation Insulin regulation of translation0.59
    Cell adhesion PLAU signaling0.35
    Regulation of lipid metabolism Insulin signaling generic cascades0.59
    Transcription PPAR Pathway0.34
    Transcription Receptor mediated HIF regulation0.51
    Development Growth hormone signaling via PI3K AKT and MAPK cascades0.34
    Translation Regulation activity of EIF20.47
    Insulin signaling pathway0.32
    4Development HGF signaling pathway
    Development HGF signaling pathway0.45
    Development EGFR signaling via PIP30.40
    Development Neurotrophin family signaling0.45
    Apoptosis and survival NGF signaling pathway0.36
    Development EGFR signaling via small GTPases0.44
    Neurotrophin signaling pathway0.36
    Development PDGF signaling via MAPK cascades0.41
    Signaling of Hepatocyte Growth Factor Receptor0.35
    5B cell receptor signaling pathway (KEGG)
    B cell receptor signaling pathway0.42
    T cell receptor signaling pathway0.38
    BCR signaling pathway0.42
    TCR Signaling Pathway0.36


    Find genes that share SuperPaths with GRB2           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected R&D Systems Pathways for GRB2 (see all 11)
        IL-21 Signaling Pathways
    IL-2 Signaling Pathways
    IL-4 Signaling Pathways
    Adipocytokines & Insulin Signaling
    Akt Signaling Pathway

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for GRB2 (see all 83)
        Molecular Mechanisms of Cancer
    eIF2 Pathway
    JNK Pathway
    ITK and TCR Signaling
    ErbB Family Pathway

    1 Cell Signaling Technology (CST) Pathway for GRB2
        Tyrosine Kinases / Adaptors

    Selected GeneGo (Thomson Reuters) Pathways for GRB2 (see all 82)
        G-protein signaling H-RAS regulation pathway
    Development CNTF receptor signaling
    Development EGFR signaling pathway
    Immune response IL-9 signaling pathway
    Transcription PPAR Pathway

    Selected BioSystems Pathways for GRB2 (see all 68)
        MAPK signaling pathway
    Focal Adhesion
    Integrin-mediated cell adhesion
    EGFR1 Signaling Pathway
    Insulin Signaling

    2 Sino Biological Pathways for GRB2
        EGFR Signaling Pathway
    VEGF Signaling

    Selected Reactome Pathways for GRB2 (see all 42)
        CD28 dependent Vav1 pathway
    FCERI mediated MAPK activation
    Costimulation by the CD28 family
    EGFR Transactivation by Gastrin
    Downstream signal transduction

    1 PharmGKB Pathway for GRB2
        EGFR Inhibitor Pathway, Pharmacodynamics

    Selected Kegg Pathways  (Kegg details for GRB2) (see all 34):
        MAPK signaling pathway
    ErbB signaling pathway
    Ras signaling pathway
    Chemokine signaling pathway
    FoxO signaling pathway

        Pathway & Disease-focused RT2 Profiler PCR Arrays including GRB2 (see all 16): 
              Insulin Signaling Pathway in human mouse rat
              Multiple Sclerosis in human mouse rat
              Leukemia in human mouse rat
              VEGF Signaling in human mouse rat
              JAK / STAT Signaling Pathway in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for GRB2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for GRB2 (P629931, 2, 3 ENSP000003390074) via UniProtKB, MINT, STRING, and/or I2D (see all 1345)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    LATO435611, 2, 3, ENSP000003541194EBI-401755,EBI-1222766 MINT-3382392 MINT-3382320 MINT-8032277 MINT-3382363 MINT-3382436 MINT-8032322 MINT-8034048 MINT-8032337 MINT-8033992 MINT-3382412 MINT-8034033 I2D: score=7 STRING: ENSP00000354119
    GAB2Q9UQC21, 2, 3EBI-401755,EBI-975200 MINT-7219506 MINT-7219550 MINT-7220613 MINT-7219528 MINT-7221243 MINT-7300447 MINT-7219679 MINT-58401 MINT-7219571 MINT-7219602 MINT-7219698 I2D: score=9 
    ENSG00000225748P486342, 3, ENSP000003874774MINT-62636 MINT-62734 MINT-62810 I2D: score=5 STRING: ENSP00000387477
    HIST1H3AP684312, 3MINT-61561 I2D: score=2 
    HIST1H3CP684312, 3MINT-61561 I2D: score=2 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 30):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0007173epidermal growth factor receptor signaling pathway TAS1322798
    GO:0007265Ras protein signal transduction TAS8253073
    GO:0007267cell-cell signaling TAS8253073
    GO:0007411axon guidance TAS--
    GO:0007568aging IEA--

    Find genes that share ontologies with GRB2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
      Browse compounds at ApexBio 

    Browse Tocris compounds for GRB2

    3 HMDB Compounds for GRB2    About this table
    CompoundSynonyms CAS #PubMed Ids
    Guanosine diphosphate5'-GDP (see all 10)146-91-8--
    Guanosine monophosphate5'-GMP (see all 14)85-32-5--
    Guanosine triphosphate5'-GTP (see all 10)86-01-1--

    2 DrugBank Compounds for GRB2    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    4-[(10s,14s,18s)-18-(2-Amino-2-Oxoethyl)-14-(1-Naphthylmethyl)-8,17,20-Trioxo-7,16,19-Triazaspiro[5.14]Icos-11-En-10-Yl]Benzylphosphonic Acid-- --target--17139284 17016423 10592235
    Pegademase bovineAdenosine aminohydrolase (see all 2)9026-93-1targetbinder9299436

    Selected Novoseek inferred chemical compound relationships for GRB2 gene (see all 52)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    tyrosine 89.5 626 8910422 (5), 8388384 (5), 8491186 (4), 11726515 (4) (see all 99)
    phosphotyrosine 84.4 50 10356320 (2), 8391166 (1), 9183666 (1), 11689444 (1) (see all 34)
    phosphatidylinositol 80.1 91 7961682 (3), 7791764 (3), 7692230 (2), 9565634 (2) (see all 72)
    pp36 79.1 5 9541596 (2), 9529333 (2), 7544353 (1)
    ag 1478 55.7 1 9722539 (1)
    phosphoinositide 49 17 10330169 (1), 12220227 (1), 19438505 (1), 15579470 (1) (see all 13)
    letrozole 45.7 8 15958587 (2), 15967659 (1), 17113978 (1), 19250202 (1) (see all 6)
    wortmannin 45.6 1 16267404 (1)
    phosphatidylinositol-3,4,5-trisphosphate 45.4 2 17923698 (1)
    phenylalanine 44.9 9 11002419 (1), 16407827 (1), 7559570 (1), 8959326 (1) (see all 9)



    Find genes that share compounds with GRB2           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for GRB2 gene (2 alternative transcripts): 
    NM_002086.4  NM_203506.2  

    Unigene Cluster for GRB2:

    Growth factor receptor-bound protein 2
    Hs.444356  [show with all ESTs]
    Unigene Representative Sequence: NM_002086
    11 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000581959 ENST00000392563 ENST00000392564 ENST00000392562 ENST00000316804(uc002jnx.4)
    ENST00000578961 ENST00000462266 ENST00000582582 ENST00000583912 ENST00000577711
    ENST00000316615(uc002jny.4)
    miRNA
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    Selected qRT-PCR Assays for microRNAs that regulate GRB2 (see all 61):
    hsa-miR-4291 hsa-miR-1224-3p hsa-miR-513a-5p hsa-miR-128 hsa-miR-200a hsa-miR-1260b hsa-miR-507 hsa-miR-105
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    Addgene plasmids for GRB2 
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    eBioscience FlowRNA Probe Sets ( VA1-12274) for GRB2 

    Additional mRNA sequence: 

    AF171699.1 AF246238.1 AF302079.1 AF498925.1 AK024539.1 AK091010.1 AK315565.1 BC000631.2 
    BC019082.2 BC033644.1 BC039827.1 BC043007.1 BC127778.1 CR450363.1 CR541942.1 L29511.1 
    M96995.1 X62852.1 

    Selected DOTS entries (see all 26):

    DT.91786336  DT.101985106  DT.455862  DT.100833847  DT.95197797  DT.100827631  DT.97788620  DT.91768193 
    DT.100827630  DT.121008073  DT.121008099  DT.97776617  DT.100039623  DT.121008170  DT.92454820  DT.95197812 
    DT.100827635  DT.121008094  DT.100827636  DT.121008122  DT.65285546  DT.100827634  DT.121008141  DT.91710775 

    Selected AceView cDNA sequences (see all 631):

    BX283751 BU859713 BU678646 BM708461 BF446179 BI765406 AI073688 AI084012 
    BU633055 BM981028 BU632576 BU687777 F10820 CR541942 BM991522 BQ065151 
    BU733359 CB117837 AA373713 AI815684 T57692 BC009417 AI686965 BC000631 

    GeneLoc Exon Structure

    Selected Alternative Splicing Database (ASD) splice patterns (SP) for GRB2 (see all 7)    About this scheme

    ExUns: 1 ^ 2 ^ 3a · 3b · 3c · 3d · 3e ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8a · 8b · 8c · 8d
    SP1:        -     -     -                 -     -                                                   
    SP2:                                      -     -                                                   
    SP3:                                      -     -                       -                           
    SP4:                                      -     -                 -                                 
    SP5:        -     -     -                 -                                                         


    ECgene alternative splicing isoforms for GRB2

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    GRB2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: AAGCCTTGCT
    GRB2 Expression
    About this image


    GRB2 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 10) fully expand
     
     Hypoblast (Extraembryonic Tissues)
             Hypoblast Cells Hypoblast
     
     Bone (Muscoskeletal System)
             Bone Marrow
     
     Brain (Nervous System)
             Cerebral Cortex
     
     Colon (Gastrointestinal Tract)
     
     Lung (Respiratory System)
    GRB2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    GRB2 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.444356
        Pathway & Disease-focused RT2 Profiler PCR Arrays including GRB2 (see all 16): 
              Insulin Signaling Pathway in human mouse rat
              Multiple Sclerosis in human mouse rat
              Leukemia in human mouse rat
              VEGF Signaling in human mouse rat
              JAK / STAT Signaling Pathway in human mouse rat

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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for GRB2

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for GRB2 gene from Selected species (see all 18)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Grb21 , 5 growth factor receptor bound protein 21, 5 92.17(n)1
    99.54(a)1
      11 (80.91 cM)5
    147841  NM_008163.31  NP_032189.11 
     1156440455 
    chicken
    (Gallus gallus)
    Aves GRB21 growth factor receptor-bound protein 2 87.86(n)
    96.31(a)
      386572  NM_204411.1  NP_989742.1 
    lizard
    (Anolis carolinensis)
    Reptilia GRB26
    growth factor receptor-bound protein 2
    97(a)
    1 ↔ 1
    2(114557797-114613731)
    African clawed frog
    (Xenopus laevis)
    Amphibia U89775.12   -- 84.11(n)    U89775.1 
    zebrafish
    (Danio rerio)
    Actinopterygii wufb18e122 Danio rerio cDNA clone MGC73077 IMAGE4146196, complete more 81.67(n)    BC059450.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta drk1 , 3 RAS protein signal transduction SH3/SH2
    adaptor more3
    downstream of receptor kinase1
    65(a)3
    61.54(n)1
    66.83(a)1
      2 50A133
    364971  NM_165998.11  NP_725306.11 
    worm
    (Caenorhabditis elegans)
    Secernentea sem-51 , 3 C. elegans sem-53
    sem-51
    58(a)3
    60.88(n)1
    59.15(a)1
      X(7995288-7996908)3
    1810551  NM_076941.51  NP_509342.11 


    ENSEMBL Gene Tree for GRB2 (if available)
    TreeFam Gene Tree for GRB2 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for GRB2 gene
    GRAP2  GRAPL2  NCK12  NCK22  GRAP22  
    Selected SIMAP similar genes for GRB2 using alignment to 6 protein entries:     GRB2_HUMAN (see all proteins) (see all similar genes):
    ITSN2    GRAPL    GRAP    ARHGEF7    NCK1    SORBS3
    SH3GL2    PTPN11    SH3GL1    ABL2    YES1    FYN
    ABL1    BCR-ABL1 e19a2    FGR    PTK6    BCR-ABL1    BCR/ABL fusion

    Find genes that share paralogs with GRB2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for GRB2 (see all 2054)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 17 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs764217551,2
    C--68765404(+) AAAAAC/AAAAAA 2 -- int12Minor allele frequency- A:0.25WA CSA 4
    rs107147201,2
    C,F--68767670(+) GAACAG/-GGCTG 2 -- int14Minor allele frequency- -:0.50NA CSA 8
    rs346813631,2
    C--68774543(+) TACTC-/TTTAGAT 2 -- int10--------
    rs351580111,2
    C--68774891(+) TTTTTT/-GAGAC 2 -- int11Minor allele frequency- -:0.00NA 2
    rs347273771,2
    C--68776534(+) GTCTC-/AAAAAAA 2 -- int10--------
    rs1997966251,2
    --68804071(+) AAAAG-/CAAA  
            
    CAAAC
    2 -- int10--------
    rs1444716551,2
    C--68804092(+) ACAAA-/CAAA  
     A
    /CAAAC
    AAAAC
    2 -- int10--------
    rs358638581,2
    C--68823982(+) TTTTTT/-AAGTG 2 -- int11Minor allele frequency- -:0.00NA 2
    rs112902881,2
    C,F--73315276(+) CCTGC-/TTTGTC 2 -- ut314Minor allele frequency- T:0.11NS NA CSA 96
    rs717976691,2
    C--73315398(+) AAATT-/AAAAAAA 4 -- ut310--------

    HapMap Linkage Disequilibrium report for GRB2 (73314157 - 73401790 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 5 variations for GRB2:    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2716238CNV Deletion23290073
    nsv908761CNV Loss21882294
    nsv111943CNV Loss16902084
    nsv833541CNV Loss17160897
    nsv510727CNV Loss20534489

    Site Specific Mutation Identification with PCR Assays
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    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 108355    OMIM disorders: --

    1 disease for GRB2:    
    About MalaCards
    hydrocele

    3 diseases from the University of Copenhagen DISEASES database for GRB2:
    Hydrocele     Leukemia     Hypertrophic cardiomyopathy

    Find genes that share disorders with GRB2           About GenesLikeMe

    Selected Novoseek inferred disease relationships for GRB2 gene (see all 31)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    myeloid leukemia chronic 37.9 1 15143164 (1)
    wiskott-aldrich syndrome 37.3 3 9307968 (2), 15579908 (1)
    breast cancer 36.4 33 11175341 (5), 10022814 (5), 8058337 (3), 9390033 (2) (see all 16)
    neoplastic transformation 32.3 2 8084588 (1), 8662827 (1)
    leukemia 21.4 9 9096689 (1), 15143164 (1), 15050920 (1), 10887132 (1) (see all 8)
    leukemogenesis 20.2 2 15143164 (2)
    tumors 17.9 35 11606575 (2), 16309242 (2), 15958587 (2), 12850474 (1) (see all 27)
    cancer 16.7 20 18620523 (2), 9009162 (1), 18216394 (1), 12878216 (1) (see all 14)
    myeloproliferative disorders 6.3 1 10887132 (1)
    melanoma 5.33 1 10091608 (1)

    Genetic Association Database (GAD): GRB2
    Human Genome Epidemiology (HuGE) Navigator: GRB2 (14 documents)
    Tumor Gene Database (TGDB): GRB2

    Export disorders for GRB2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for GRB2 gene, integrated from 10 sources (see all 1236):
    (articles sorted by number of sources associating them with GRB2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine- phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. (PubMed id 8491186)1, 2, 9 Skolnik E.Y....Schlessinger J. (EMBO J. 1993)
    2. Insulin stimulates association of insulin receptor substrate-1 with the protein abundant Src homology/growth factor receptor-bound protein 2. (PubMed id 8388384)1, 2, 9 Tobe K.... Kadowaki T. (J. Biol. Chem. 1993)
    3. Multiple forms of an inositol polyphosphate 5-phosphatase form signaling complexes with Shc and Grb2. (PubMed id 8723348)1, 2, 9 Kavanaugh W.M....Williams L.T. (Curr. Biol. 1996)
    4. Crystal structures of the SH2 domain of Grb2: highlight on the binding of a new high-affinity inhibitor. (PubMed id 11827484)1, 2, 9 Nioche P.... Ducruix A. (J. Mol. Biol. 2002)
    5. Recruitment of the class II phosphoinositide 3-kinase C2beta to the epidermal growth factor receptor: role of Grb2. (PubMed id 11533253)1, 2, 9 Wheeler M. and Domin J. (Mol. Cell. Biol. 2001)
    6. Ligand activation of ELK receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells. (PubMed id 8798570)1, 2, 9 Stein E.... Daniel T.O. (J. Biol. Chem. 1996)
    7. Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2. (PubMed id 7881903)1, 2, 9 Kohda D.... Inagaki F. (Structure 1994)
    8. Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site. (PubMed id 9178760)1, 2, 9 Braunger J.... Janssen J.W. (Oncogene 1997)
    9. Distinct binding modes of two epitopes in Gab2 that interact with the SH3C domain of Grb2. (PubMed id 19523899)1, 2, 9 Harkiolaki M.... Feller S.M. (Structure 2009)
    10. Distinct functions of natural ADAM-15 cytoplasmic domain variants in human mammary carcinoma. (PubMed id 18296648)1, 2, 9 Zhong J.L....Edwards D.R. (Mol. Cancer Res. 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 2885 HGNC: 4566 AceView: GRB2 Ensembl:ENSG00000177885 euGenes: HUgn2885
    ECgene: GRB2 Kegg: 2885 H-InvDB: GRB2

    (According to HUGE)
    About This Section

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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for GRB2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for GRB2 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for GRB2 gene:
    Search GeneIP for patents involving GRB2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, eBioscience, and/or others, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Addgene, Cell lines from GenScript, and ESI BIO, Flow cytometery from eBioscience, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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