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.... See more...

Aliases for GRB2 Gene

Aliases for GRB2 Gene

  • Growth Factor Receptor Bound Protein 2 2 3 5
  • Growth Factor Receptor-Bound Protein 2 2 3 4
  • SH2/SH3 Adapter GRB2 3 4
  • Protein Ash 3 4
  • ASH 3 4
  • Epidermal Growth Factor Receptor-Binding Protein GRB2 3
  • Epididymis Secretory Sperm Binding Protein 3
  • Growth Factor Receptor-Bound Protein 3 3
  • Abundant SRC Homology 3
  • Adapter Protein GRB2 4
  • EGFRBP-GRB2 3
  • 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 Hepatitis and Hepatitis E. Among its related pathways are Transcription Androgen Receptor nuclear signaling and Vesicle-mediated transport. Gene Ontology (GO) annotations related to this gene include protein kinase binding. An important paralog of this gene is GRAP.

UniProtKB/Swiss-Prot Summary 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

Additional gene information for GRB2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GRB2 Gene

Genomics for GRB2 Gene

GeneHancer (GH) Regulatory Elements for GRB2 Gene

Promoters and enhancers for GRB2 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GRB2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the GRB2 gene promoter:
  • p53
  • Sp1

Genomic Locations for GRB2 Gene

Genomic Locations for GRB2 Gene
chr17:75,318,076-75,405,709
(GRCh38/hg38)
Size:
87,634 bases
Orientation:
Minus strand
chr17:73,314,157-73,401,790
(GRCh37/hg19)
Size:
87,634 bases
Orientation:
Minus strand

Genomic View for GRB2 Gene

Genes around GRB2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GRB2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
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:
    P62993-GRB2_HUMAN
    Recommended name:
    Growth factor receptor-bound protein 2
    Protein Accession:
    P62993
    Secondary Accessions:
    • P29354
    • Q14450
    • Q63057
    • Q63059

    Protein attributes for GRB2 Gene

    Size:
    217 amino acids
    Molecular mass:
    25206 Da
    Quaternary structure:
    • Associates (via SH2 domain) with activated EGF and PDGF receptors (tyrosine phosphorylated) (PubMed:10026169, PubMed:19836242). Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect (By similarity). 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 (PubMed:8388384, PubMed:8491186, PubMed:9553137, PubMed:11433379). It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Interacts with SOS1 (PubMed:8493579, PubMed:7664271). Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1 (PubMed:7664271). Interacts with phosphorylated MET (PubMed:11063574, PubMed:11827484). Interacts with phosphorylated TOM1L1 (By similarity). Interacts with the phosphorylated C-terminus of SH2B2 (PubMed:9233773). Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation (By similarity) (PubMed:9489702, PubMed:12359715, PubMed:12486104, PubMed:12514734). Interacts with NISCH, PTPNS1 and REPS2 (PubMed:9062191, PubMed:9422736, PubMed:11912194). Interacts with syntrophin SNTA1 (By similarity). Interacts (via SH3 domains) with REPS1 (By similarity). Interacts (via SH3 domains) with PIK3C2B (PubMed:11533253). Interacts with CBL and CBLB (PubMed:10022120, PubMed:10086340). 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 (PubMed:8723348, PubMed:9108392, PubMed:9484780, PubMed:10942756, PubMed:12171928). Interacts with PTPN11 (By similarity). Interacts with PRNP (By similarity). Interacts with RALGPS1 (PubMed:10747847). Interacts with HCST (PubMed:16582911). Interacts with KDR (By similarity). Interacts with FLT1 (tyrosine-phosphorylated) (By similarity). Interacts with GAPT and PTPRE (PubMed:10980613, PubMed:18559951). Interacts (via SH2 domain) with KIF26A (PubMed:19914172). Interacts (via SH3 2) with GAB2 (PubMed:19523899). Interacts with ADAM15 (PubMed:18296648). Interacts with THEMIS2 (By similarity). Interacts (via SH2 domain) with AXL (phosphorylated) (PubMed:9178760, PubMed:19815557). Interacts (via SH2 domain) with KIT (phosphorylated) (PubMed:15526160, PubMed:16129412). Interacts with PTPRJ and BCR (PubMed:12475979, PubMed:15302586). Interacts with PTPN23 (PubMed:21179510). Interacts with FLT4 (tyrosine phosphorylated) (PubMed:15102829). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration (PubMed:8798570, PubMed:12925710). Part of a complex including TNK2, GRB2, LTK and one receptor tyrosine kinase (RTK) such as AXL and PDGFRL, in which GRB2 promotes RTK recruitment by TNK2 (PubMed:9178760, PubMed:19815557). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:8262059). Interacts with ERBB4 (PubMed:10867024). Interacts with NTRK1 (phosphorylated upon ligand-binding) (PubMed:15488758). Interacts with PTK2/FAK1 (tyrosine phosphorylated) (PubMed:9148935). Interacts with PTK2B/PYK2 (tyrosine phosphorylated) (PubMed:20521079). Isoform 1 interacts with SCIMP (PubMed:21930792). Interacts (via SH3 domains) with GAREM1 isoform 1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation (PubMed:19509291). Interacts with DAB2 (By similarity). Interacts with TESPA1 (PubMed:22561606). Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1 (By similarity). Interacts with CD28 (PubMed:24098653). Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA (By similarity). Interacts with ASAP3 (phosphorylated form) (PubMed:22027826). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (By similarity). Interacts with PTPRO (phosphorylated form) (By similarity). Interacts with PTPRB (phosphorylated form) (By similarity). Interacts (via SH3 domain 2) with PRR14 (via proline-rich region) (PubMed:27041574). Interacts with FCRL6 (tyrosine phosphorylated form) (PubMed:20933011). Interacts with RHEX (via tyrosine-phosphorylated form) (PubMed:25092874). Interacts with ST5 (PubMed:29030480).
    • (Microbial infection) Interacts (via SH3 domain) with hepatitis E virus/HEV ORF3 protein.
    • (Microbial infection) Interacts with hepatitis C virus/HCV protein NS5A via its SH3 domains.
    • (Microbial infection) Interacts with herpes simplex virus 1 protein UL46.

    Three dimensional structures from OCA and Proteopedia for GRB2 Gene

    Alternative splice isoforms for GRB2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GRB2 Gene

Post-translational modifications for GRB2 Gene

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

No data available for DME Specific Peptides for GRB2 Gene

Domains & Families for GRB2 Gene

Gene Families for GRB2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Plasma proteins
  • Predicted intracellular proteins

Protein Domains for GRB2 Gene

Suggested Antigen Peptide Sequences for GRB2 Gene

GenScript: Design optimal peptide antigens:
  • cDNA, FLJ96637, Homo sapiens growth factor receptor-bound protein 2 (GRB2), mRNA (B0LPF3_HUMAN)
  • SH2/SH3 adapter GRB2 (GRB2_HUMAN)
  • GRB2 protein (Q6ICN0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P62993

UniProtKB/Swiss-Prot:

GRB2_HUMAN :
  • The SH3 domains mediate interaction with RALGPS1 and SHB.
  • Belongs to the GRB2/sem-5/DRK family.
Domain:
  • The SH3 domains mediate interaction with RALGPS1 and SHB.
Family:
  • 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

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.
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

Phenotypes From GWAS Catalog for GRB2 Gene

Gene Ontology (GO) - Molecular Function for GRB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001784 phosphotyrosine residue binding IPI 20624904
GO:0003723 RNA binding HDA 22658674
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
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:
  • Grb2 Grb2<tm1Paw>
  • Grb2 Grb2<tm1a(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

miRNA for GRB2 Gene

miRTarBase miRNAs that target GRB2

Clone Products

  • Addgene plasmids for GRB2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets 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

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GRB2 gene
Compartment Confidence
plasma membrane 5
nucleus 5
endosome 5
cytosol 5
golgi apparatus 3
extracellular 2
cytoskeleton 2
endoplasmic reticulum 2
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GRB2 Gene

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

Pathways & Interactions for GRB2 Gene

PathCards logo

SuperPathways for GRB2 Gene

SuperPathway Contained pathways
1 RET signaling
2 Downstream signaling of activated FGFR2
3 Regulation of lipid metabolism Insulin signaling-generic cascades
4 Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
5 IL-2 Pathway
.59
.59
.54
.51
.49
.48
.43
.34
genes like me logo Genes that share pathways with GRB2: view

Pathways by source for GRB2 Gene

83 Qiagen pathways for GRB2 Gene
  • 14-3-3 Induced Intracellular Signaling
  • Activation of cAMP-Dependent PKA
  • Angiopoietin-TIE2 Signaling
  • BAD Phosphorylation
  • BDNF Pathway
1 Cell Signaling Technology pathway for GRB2 Gene
1 GeneTex pathway for GRB2 Gene

SIGNOR curated interactions for GRB2 Gene

Activates:
Inactivates:
Is activated by:
Other effect:

Gene Ontology (GO) - Biological Process for GRB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0007173 epidermal growth factor receptor signaling pathway TAS 1322798
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

Drugs & Compounds for GRB2 Gene

(37) Drugs for GRB2 Gene - From: DrugBank, DGIdb, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Pegademase Approved Pharma Target, binder 0
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 Experimental Pharma Target 0
Guanosine diphosphate Experimental Pharma 0
Guanosine monophosphate Experimental Pharma 0
Guanosine triphosphate Experimental Pharma 0

(21) Additional Compounds for GRB2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with GRB2: view

Transcripts for GRB2 Gene

mRNA/cDNA for GRB2 Gene

CRISPR Products

Clone Products

  • Addgene plasmids for GRB2

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
GRB2
ECgene alternative splicing isoforms for
GRB2

Expression for GRB2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE 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 (x5.9).

Protein differential expression in normal tissues from HIPED for GRB2 Gene

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

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GRB2 Gene



Protein tissue co-expression partners for GRB2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of GRB2 Gene:

GRB2

SOURCE GeneReport for Unigene cluster for GRB2 Gene:

Hs.444356

Evidence on tissue expression from TISSUES for GRB2 Gene

  • Nervous system(5)
  • Lung(4.8)
  • Blood(4.6)
  • Skin(4.6)
  • Kidney(2.8)
  • Liver(2.8)
  • Muscle(2.8)
  • Bone marrow(2.7)
  • Heart(2.6)
  • Adrenal gland(2.5)
  • Intestine(2.4)
  • Lymph node(2.4)
  • Pancreas(2.3)
  • Spleen(2.3)
  • Eye(2.2)
  • Stomach(2)
genes like me logo Genes that share expression patterns with GRB2: view

No data available for mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer 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
chimpanzee
(Pan troglodytes)
Mammalia GRB2 33 32
  • 100 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia GRB2 33
  • 98 (a)
OneToOne
dog
(Canis familiaris)
Mammalia GRB2 33 32
  • 94.78 (n)
OneToOne
cow
(Bos Taurus)
Mammalia GRB2 33 32
  • 93.86 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Grb2 17 33 32
  • 92.17 (n)
rat
(Rattus norvegicus)
Mammalia Grb2 32
  • 92.01 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia GRB2 33
  • 83 (a)
OneToOne
chicken
(Gallus gallus)
Aves GRB2 33 32
  • 87.86 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GRB2 33
  • 97 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia grb2 32
  • 80.8 (n)
zebrafish
(Danio rerio)
Actinopterygii grb2a 33
  • 94 (a)
OneToMany
grb2b 33 32
  • 82.33 (n)
OneToMany
wufb18e12 32
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP011768 32
  • 63.3 (n)
fruit fly
(Drosophila melanogaster)
Insecta drk 33 34 32
  • 61.54 (n)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea sem-5 33 34 32
  • 60.88 (n)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PIN3 35
sea squirt
(Ciona savignyi)
Ascidiacea CSA.8309 33
  • 57 (a)
OneToMany
Species where no ortholog for GRB2 was found in the sources mined by GeneCards:
  • 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

ENSEMBL:
Gene Tree for GRB2 (if available)
TreeFam:
Gene Tree for GRB2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GRB2: view image

Paralogs for GRB2 Gene

Paralogs for GRB2 Gene

(26) SIMAP similar genes for GRB2 Gene using alignment to 6 proteins:

  • GRB2_HUMAN
  • B0LPF3_HUMAN
  • J3KT38_HUMAN
  • J3QLF6_HUMAN
  • J3QRL5_HUMAN
  • Q6ICN0_HUMAN