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Aliases for GRB2 Gene

Aliases for GRB2 Gene

  • Growth Factor Receptor-Bound Protein 2 2 3
  • SH2/SH3 Adapter GRB2 3 4
  • Protein Ash 3 4
  • ASH 3 4
  • Epidermal Growth Factor Receptor-Binding Protein GRB2 3
  • Growth Factor Receptor-Bound Protein 3 3
  • Abundant SRC Homology 3
  • Adapter Protein GRB2 4
  • MSTP084 3
  • Grb3-3 3
  • MST084 3
  • NCKAP2 3
  • HT027 3

External Ids for GRB2 Gene

Previous GeneCards Identifiers for GRB2 Gene

  • GC17M073313
  • GC17M076374
  • GC17M073779
  • GC17M073911
  • GC17M070825
  • GC17M068724

Summaries for GRB2 Gene

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. Among its related pathways are PI3K-Akt signaling pathway and PI-3K cascade. GO annotations related to this gene include identical protein binding and SH3 domain binding. An important paralog of this gene is GRAPL.

UniProtKB/Swiss-Prot for GRB2 Gene

  • Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway

  • 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

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for GRB2 Gene

Genomics for GRB2 Gene

Regulatory Elements for GRB2 Gene

Transcription factor binding sites by QIAGEN in the GRB2 gene promoter:

Genomic Location for GRB2 Gene

75,318,076 bp from pter
75,405,709 bp from pter
87,634 bases
Minus strand

Genomic View for GRB2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for GRB2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GRB2 Gene

Proteins for GRB2 Gene

  • Protein details for GRB2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Recommended name:
    Growth factor receptor-bound protein 2
    Protein Accession:
    Secondary Accessions:
    • P29354
    • Q14450
    • Q63057
    • Q63059

    Protein attributes for GRB2 Gene

    217 amino acids
    Molecular mass:
    25206 Da
    Quaternary structure:
    • 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). Interacts with CD28. Interacts with herpes simplex virus 1 UL46.

    Three dimensional structures from OCA and Proteopedia for GRB2 Gene

    Alternative splice isoforms for GRB2 Gene


neXtProt entry for GRB2 Gene

Proteomics data for GRB2 Gene at MOPED

Post-translational modifications for GRB2 Gene

  • Ubiquitination at Lys44, Lys56, and Lys109
  • Modification sites at PhosphoSitePlus

Other Protein References for GRB2 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for GRB2 (Grb2)

No data available for DME Specific Peptides for GRB2 Gene

Domains for GRB2 Gene

Gene Families for GRB2 Gene

  • SH2D :SH2 domain containing

Protein Domains for GRB2 Gene


Graphical View of Domain Structure for InterPro Entry



  • P62993
  • The SH3 domains mediate interaction with RALGPS1 and SHB
  • Contains 1 SH2 domain.
  • Contains 2 SH3 domains.
  • Belongs to the GRB2/sem-5/DRK family.
genes like me logo Genes that share domains with GRB2: view

Function for GRB2 Gene

Molecular function for GRB2 Gene

GENATLAS Biochemistry:
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
UniProtKB/Swiss-Prot Function:
Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway
UniProtKB/Swiss-Prot 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 Ontology (GO) - Molecular Function for GRB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001784 phosphotyrosine binding IEA --
GO:0005070 SH3/SH2 adaptor activity TAS 8253073
GO:0005154 epidermal growth factor receptor binding IPI 12577067
GO:0005168 neurotrophin TRKA receptor binding IPI 15488758
GO:0005515 protein binding IPI 10026169
genes like me logo Genes that share ontologies with GRB2: view
genes like me logo Genes that share phenotypes with GRB2: view

Animal Models for GRB2 Gene

MGI Knock Outs for GRB2:

Animal Model Products

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for GRB2

In Situ Assay Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for GRB2 Gene

Localization for GRB2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GRB2 Gene

Nucleus. Cytoplasm. Endosome. Golgi apparatus.

Subcellular locations from

Jensen Localization Image for GRB2 Gene COMPARTMENTS Subcellular localization image for GRB2 gene
Compartment Confidence
endosome 5
nucleus 5
cytosol 4
plasma membrane 4
cytoskeleton 2
endoplasmic reticulum 2
extracellular 2
golgi apparatus 2

Gene Ontology (GO) - Cellular Components for GRB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IDA --
GO:0005654 nucleoplasm IDA --
GO:0005730 nucleolus IDA --
GO:0005737 cytoplasm IDA 21179510
GO:0005768 endosome IDA 21179510
genes like me logo Genes that share ontologies with GRB2: view

Pathways for GRB2 Gene

SuperPathways for GRB2 Gene

Superpath Contained pathways
1 PI-3K cascade
2 Signaling by FGFR
3 Insulin receptor signalling cascade
4 IL-9 Signaling Pathways
5 Translation Insulin regulation of translation
genes like me logo Genes that share pathways with GRB2: view

PCR Array Products

Interacting Proteins for GRB2 Gene

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)
Selected Interacting proteins: P62993-GRB2_HUMAN ENSP00000339007 for GRB2 Gene via MINT STRING UniProtKB I2D

Symbol External ID(s) Details

Gene Ontology (GO) - Biological Process for GRB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007173 epidermal growth factor receptor signaling pathway TAS 1322798
GO:0007264 small GTPase mediated signal transduction TAS --
GO:0007265 Ras protein signal transduction TAS 8253073
GO:0007267 cell-cell signaling TAS 8253073
GO:0007411 axon guidance TAS --
genes like me logo Genes that share ontologies with GRB2: view

Compounds for GRB2 Gene

(3) HMDB Compounds for GRB2 Gene

Compound Synonyms Cas Number PubMed IDs
Guanosine diphosphate
  • 5'-GDP
Guanosine monophosphate
  • 5'-GMP
Guanosine triphosphate
  • 5'-GTP

(2) Drugbank Compounds for GRB2 Gene

(52) Novoseek inferred chemical compound relationships for GRB2 Gene

Compound -log(P) Hits PubMed IDs
tyrosine 89.5 231
phosphotyrosine 84.4 35
phosphatidylinositol 80.1 84
pp36 79.1 5
ag 1478 55.7 1
genes like me logo Genes that share compounds with GRB2: view

Transcripts for GRB2 Gene

Unigene Clusters for GRB2 Gene

Growth factor receptor-bound protein 2:
Representative Sequences:

miRNA Products

Inhibitory RNA Products

  • Predesigned siRNA for gene silencing in human,mouse,rat for GRB2

Primer Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for GRB2 Gene

ExUns: 1 ^ 2 ^ 3a · 3b · 3c · 3d · 3e ^ 4 ^ 5a · 5b ^ 6 ^ 7 ^ 8a · 8b · 8c · 8d
SP1: - - - - -
SP2: - -
SP3: - - -
SP4: - - -
SP5: - - - -
SP6: - - - -
SP7: - - -

Relevant External Links for GRB2 Gene

GeneLoc Exon Structure for
ECgene alternative splicing isoforms for

Expression for GRB2 Gene

mRNA expression in normal human tissues for GRB2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for GRB2 Gene

This gene is overexpressed in Whole Blood (5.9).

Protein differential expression in normal tissues for GRB2 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (12.6).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for GRB2 Gene

SOURCE GeneReport for Unigene cluster for GRB2 Gene Hs.444356

genes like me logo Genes that share expressions with GRB2: view

Expression partners for GRB2 Gene

In Situ Assay Products

No data available for mRNA Expression by UniProt/SwissProt for GRB2 Gene

Orthologs for GRB2 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for GRB2 Gene

Organism Taxonomy Gene Similarity Type Details
(Bos Taurus)
Mammalia GRB2 35
  • 93.86 (n)
  • 100 (a)
GRB2 36
  • 100 (a)
(Canis familiaris)
Mammalia GRB2 35
  • 94.78 (n)
  • 100 (a)
GRB2 36
  • 100 (a)
(Mus musculus)
Mammalia Grb2 35
  • 92.17 (n)
  • 99.54 (a)
Grb2 16
Grb2 36
  • 100 (a)
(Pan troglodytes)
Mammalia GRB2 35
  • 100 (n)
  • 100 (a)
GRB2 36
  • 100 (a)
(Rattus norvegicus)
Mammalia Grb2 35
  • 92.01 (n)
  • 100 (a)
(Monodelphis domestica)
Mammalia GRB2 36
  • 98 (a)
(Ornithorhynchus anatinus)
Mammalia GRB2 36
  • 83 (a)
(Gallus gallus)
Aves GRB2 35
  • 87.86 (n)
  • 96.31 (a)
GRB2 36
  • 98 (a)
(Anolis carolinensis)
Reptilia GRB2 36
  • 97 (a)
tropical clawed frog
(Silurana tropicalis)
Amphibia grb2 35
  • 80.8 (n)
  • 96.77 (a)
(Danio rerio)
Actinopterygii grb2b 35
  • 82.33 (n)
  • 94.93 (a)
wufb18e12 35
grb2a 36
  • 94 (a)
grb2b 36
  • 95 (a)
fruit fly
(Drosophila melanogaster)
Insecta drk 37
  • 65 (a)
drk 35
  • 61.54 (n)
  • 66.83 (a)
drk 36
  • 65 (a)
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP011768 35
  • 63.3 (n)
  • 65.87 (a)
(Caenorhabditis elegans)
Secernentea sem-5 37
  • 58 (a)
sem-5 35
  • 60.88 (n)
  • 59.15 (a)
sem-5 36
  • 55 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PIN3 38
sea squirt
(Ciona savignyi)
Ascidiacea CSA.8309 36
  • 57 (a)
Species with no ortholog for GRB2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for GRB2 Gene

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

Paralogs for GRB2 Gene

Paralogs for GRB2 Gene

genes like me logo Genes that share paralogs with GRB2: view

Variants for GRB2 Gene

Sequence variations from dbSNP and Humsavar for GRB2 Gene

SNP ID Clin Chr 17 pos Sequence Context AA Info Type MAF
rs7219 -- 75,319,287(-) TAAAG(A/G)CAGTC utr-variant-3-prime
rs755968 -- 75,369,196(-) TTTAT(A/G)TACCA intron-variant
rs892768 -- 75,370,521(-) AGGGA(C/T)GCGTT intron-variant
rs959260 -- 75,373,341(-) TTGAC(A/G)TTCTG intron-variant
rs1043617 -- 75,318,360(-) CTCTT(C/T)TGGGC utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for GRB2 Gene

Variant ID Type Subtype PubMed ID
nsv510727 CNV Loss 20534489
nsv908761 CNV Loss 21882294
nsv833541 CNV Loss 17160897
nsv111943 CNV Loss 16902084
esv2716238 CNV Deletion 23290073

Relevant External Links for GRB2 Gene

HapMap Linkage Disequilibrium report

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GRB2 Gene

Disorders for GRB2 Gene

MalaCards: The human disease database

MalaCards: The human disease database.

Search for GRB2 Gene in MalaCards »

(1) Diseases for GRB2 Gene including...

(3) University of Copenhagen DISEASES for GRB2 Gene

(31) Novoseek inferred disease relationships for GRB2 Gene

Disease -log(P) Hits PubMed IDs
myeloid leukemia chronic 37.9 1
wiskott-aldrich syndrome 37.3 3
breast cancer 36.4 29
neoplastic transformation 32.3 2
leukemia 21.4 8

Relevant External Links for GRB2

Genetic Association Database (GAD)
Human Genome Epidemiology (HuGE) Navigator
Tumor Gene Database (TGDB):
genes like me logo Genes that share disorders with GRB2: view

No data available for OMIM , UniProtKB/Swiss-Prot and Genatlas for GRB2 Gene

Publications for GRB2 Gene

  1. Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein. (PMID: 7664271) Pandey P. … Kufe D. (Cancer Res. 1995) 3 4 23
  2. Solution structure and ligand-binding site of the carboxy-terminal SH3 domain of GRB2. (PMID: 7881903) Kohda D. … Inagaki F. (Structure 1994) 3 4 23
  3. The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine- phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. (PMID: 8491186) Skolnik E.Y. … Schlessinger J. (EMBO J. 1993) 3 4 23
  4. Insulin stimulates association of insulin receptor substrate-1 with the protein abundant Src homology/growth factor receptor-bound protein 2. (PMID: 8388384) Tobe K. … Kadowaki T. (J. Biol. Chem. 1993) 3 4 23
  5. Nuclear magnetic resonance solution structure of the growth factor receptor-bound protein 2 Src homology 2 domain. (PMID: 8794768) Thornton K.H. … Thanabal V. (Biochemistry 1996) 3 4 23

Products for GRB2 Gene

  • Addgene plasmids for GRB2

Sources for GRB2 Gene

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