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Aliases for GRB2 Gene

Aliases for GRB2 Gene

  • Growth Factor Receptor Bound Protein 2 2 3 5
  • 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 2 2
  • 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 wiskott-aldrich syndrome and silver-russell syndrome. Among its related pathways are Platelet activation, signaling and aggregation and Signaling by GPCR. GO annotations related to this gene include poly(A) RNA binding and protein kinase 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

Promoters for GRB2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around GRB2 on UCSC Golden Path with GeneCards custom track

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

Genomic Location for GRB2 Gene

Chromosome:
17
Start:
75,318,076 bp from pter
End:
75,405,709 bp from pter
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 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 GAREM1 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

    UniProtKB/Swiss-Prot:

neXtProt entry for GRB2 Gene

Proteomics data for GRB2 Gene at MOPED

Post-translational modifications for GRB2 Gene

  • Ubiquitination at Lys 44, Lys 56, and Lys 109
  • Modification sites at PhosphoSitePlus

Antibody Products

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

No data available for DME Specific Peptides for GRB2 Gene

Domains & Families for GRB2 Gene

Gene Families for GRB2 Gene

Protein Domains for GRB2 Gene

InterPro:
ProtoNet:

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.
  • Contains 1 SH2 domain.
  • Contains 2 SH3 domains.
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

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:0016303 1-phosphatidylinositol-3-kinase activity TAS --
GO:0019904 protein domain specific binding IEA --
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 for GRB2 Gene

miRTarBase miRNAs that target GRB2

Inhibitory RNA Products

In Situ Assay Products

Flow Cytometry Products

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
Jensen Localization Image for GRB2 Gene COMPARTMENTS Subcellular localization image for GRB2 gene
Compartment Confidence
cytosol 5
endosome 5
extracellular 5
nucleus 5
plasma membrane 5
golgi apparatus 3
cytoskeleton 2
endoplasmic reticulum 2
lysosome 1
vacuole 1

Gene Ontology (GO) - Cellular Components for GRB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0070062 extracellular exosome IDA 19056867
genes like me logo Genes that share ontologies with GRB2: view

Pathways & Interactions for GRB2 Gene

SuperPathways for GRB2 Gene

Superpath Contained pathways
1 Interleukin-3, 5 and GM-CSF signaling
2 PI3K events in ERBB4 signaling
3 IL-7 Signaling Pathways
4 Translation Insulin regulation of translation
5 Signaling by ERBB2
genes like me logo Genes that share pathways with GRB2: view

Interacting Proteins for GRB2 Gene

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)
http://string-db.org/version_10/api/image/networkList?limit=0&targetmode=proteins&caller_identity=gene_cards&network_flavor=evidence&identifiers=9606.ENSP00000339007%0d%0a9606.ENSP00000046794%0d%0a9606.ENSP00000262995%0d%0a9606.ENSP00000264033%0d%0a9606.ENSP00000274335%0d%0a9606.ENSP00000275493%0d%0a
Selected Interacting proteins: P62993-GRB2_HUMAN ENSP00000339007 for GRB2 Gene via MINT I2D UniProtKB STRING

Symbol External ID(s) Details
EGFR
SHC1
SOS1
GAB2
LAT

SIGNOR curated interactions for GRB2 Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for GRB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0000186 activation of MAPKK activity TAS --
GO:0007411 axon guidance TAS --
GO:0008543 fibroblast growth factor receptor signaling pathway TAS --
GO:0030154 cell differentiation IEA --
genes like me logo Genes that share ontologies with GRB2: view

Drugs & Compounds for GRB2 Gene

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Pegademase bovine 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

(22) 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

Unigene Clusters for GRB2 Gene

Growth factor receptor-bound protein 2:
Representative Sequences:

Inhibitory RNA 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
GRB2
ECgene alternative splicing isoforms for
GRB2

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 (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, PaxDb, MOPED, and MaxQB for GRB2 Gene



SOURCE GeneReport for Unigene cluster for GRB2 Gene Hs.444356

genes like me logo Genes that share expression patterns with GRB2: view

Protein tissue co-expression partners for GRB2 Gene

- Elite partner

Primer Products

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
chimpanzee
(Pan troglodytes)
Mammalia GRB2 35
  • 100 (n)
  • 100 (a)
GRB2 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia GRB2 36
  • 100 (a)
OneToOne
GRB2 35
  • 93.86 (n)
  • 100 (a)
dog
(Canis familiaris)
Mammalia GRB2 35
  • 94.78 (n)
  • 100 (a)
GRB2 36
  • 100 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Grb2 16
Grb2 36
  • 100 (a)
OneToOne
Grb2 35
  • 92.17 (n)
  • 99.54 (a)
oppossum
(Monodelphis domestica)
Mammalia GRB2 36
  • 98 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia GRB2 36
  • 83 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Grb2 35
  • 92.01 (n)
  • 100 (a)
chicken
(Gallus gallus)
Aves GRB2 36
  • 98 (a)
OneToOne
GRB2 35
  • 87.86 (n)
  • 96.31 (a)
lizard
(Anolis carolinensis)
Reptilia GRB2 36
  • 97 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia grb2 35
  • 80.8 (n)
  • 96.77 (a)
zebrafish
(Danio rerio)
Actinopterygii grb2a 36
  • 94 (a)
OneToMany
grb2b 36
  • 95 (a)
OneToMany
grb2b 35
  • 82.33 (n)
  • 94.93 (a)
wufb18e12 35
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP011768 35
  • 63.3 (n)
  • 65.87 (a)
fruit fly
(Drosophila melanogaster)
Insecta drk 35
  • 61.54 (n)
  • 66.83 (a)
drk 37
  • 65 (a)
drk 36
  • 65 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea sem-5 35
  • 60.88 (n)
  • 59.15 (a)
sem-5 36
  • 55 (a)
OneToMany
sem-5 37
  • 58 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes PIN3 38
sea squirt
(Ciona savignyi)
Ascidiacea CSA.8309 36
  • 57 (a)
OneToMany
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

ENSEMBL:
Gene Tree for GRB2 (if available)
TreeFam:
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
rs7219 -- 75,319,287(-) TAAAG(A/G)CAGTC utr-variant-3-prime
rs1076094 -- 75,348,630(+) GGAAA(C/T)TGCTG intron-variant
rs892768 -- 75,370,521(-) AGGGA(C/T)GCGTT intron-variant
rs959260 -- 75,373,341(-) TTGAC(A/G)TTCTG intron-variant
rs1529844 -- 75,332,692(-) AAGTT(A/C/G)AGCTC intron-variant

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

Variation tolerance for GRB2 Gene

Residual Variation Intolerance Score: 36.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.04; 0.94% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for GRB2 Gene

HapMap Linkage Disequilibrium report
GRB2

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

Disorders for GRB2 Gene

MalaCards: The human disease database

(7) MalaCards diseases for GRB2 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
wiskott-aldrich syndrome
  • wiskott syndrome
silver-russell syndrome
  • silver russell dwarfism
leukemia, chronic myeloid, somatic
  • chronic myeloid leukemia
pilocytic astrocytoma
  • grade i astrocytic tumor
breast cancer
  • breast cancer, invasive ductal
- elite association - COSMIC cancer census association via MalaCards
Search GRB2 in MalaCards View complete list of genes associated with diseases

Relevant External Links for GRB2

Genetic Association Database (GAD)
GRB2
Human Genome Epidemiology (HuGE) Navigator
GRB2
Tumor Gene Database (TGDB):
GRB2
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
GRB2
genes like me logo Genes that share disorders with GRB2: view

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

Publications for GRB2 Gene

  1. The gene structure of the human growth factor bound protein GRB2. (PMID: 10051406) Bochmann H. … Jaross W. (Genomics 1999) 2 3 4 67
  2. Tyrosine phosphorylation of Grb2: role in prolactin/epidermal growth factor cross talk in mammary epithelial cell growth and differentiation. (PMID: 19273609) Haines E. … Ali S. (Mol. Cell. Biol. 2009) 3 23
  3. Overexpression of Grb2/HER2 signaling in Chinese gastric cancer: their relationship with clinicopathological parameters and prognostic significance. (PMID: 19337752) Yu G.Z. … Wang J.J. (J. Cancer Res. Clin. Oncol. 2009) 3 23
  4. Expression of Grb2 distinguishes classical Hodgkin lymphomas from primary mediastinal B-cell lymphomas and other diffuse large B-cell lymphomas. (PMID: 19716163) Miles R.R. … Lim M.S. (Hum. Pathol. 2009) 3 23
  5. Integration of the beta-catenin-dependent Wnt pathway with integrin signaling through the adaptor molecule Grb2. (PMID: 19924227) Crampton S.P. … Hughes C.C. (PLoS ONE 2009) 3 23

Products for GRB2 Gene

Sources for GRB2 Gene

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