Grb2 Family

Aliases: growth factor receptor-bound protein 2, SH2/SH3 adapter GRB2, Protein Ash, HT027, Adapter protein GRB2, abundant SRC homology, growth factor receptor-bound protein 3, epidermal growth factor receptor-binding protein GRB2, GRB2, MSTP084, NCKAP2, ASH, MST084, Grb3-3, EGFRBP-GRB2

Pfam Domain Structure

From GRB2 (human)

Members of the Grb2 Family
1: GRB2 » Human Mouse Rat Chicken Fly Worm
CMKB GRB2 Grb2 Grb2 GRB2 drk sem-5
Entrez Gene 2885 14784 81504 386572 36497 181055
Uniprot GRB2_HUMAN GRB2_MOUSE GRB2_RAT GRB2_CHICK DRK_DROME SEM5_CAEEL
OMIM 108355 - - - - -
Reagents - 2 available - - - -
Results 5 available - - - 3 available -
Family Summary

Grb2 is an adaptor protein with N- and C-terminal src homology 3 (SH3) domains and a central src homology 2 (SH2) domain. The SH2 domain can bind to phosphoTyr residues of receptors or other adaptor proteins, such as SHC. The SH3 domains bind the Ras exchange factor SOS, but can also bind to other adaptor proteins such as GAB1 and GAB2. Thus, Grb-2 is involved in activation of Ras but can also play a role in other signaling pathways in mammalian cells.

References
  1. Dharmawardana PG, Peruzzi B, Giubellino A, Burke TR, Bottaro DP. Molecular targeting of growth factor receptor-bound 2 (Grb2) as an anti-cancer strategy. Anticancer Drugs 2006; 17:13-20 (PubMed)
  2. Feller SM, Lewitzky M. Potential disease targets for drugs that disrupt protein-- protein interactions of Grb2 and Crk family adaptors. Curr. Pharm. Des. 2006; 12:529-48 (PubMed)
  3. Johannessen LE, Pedersen NM, Pedersen KW, Madshus IH, Stang E. Activation of the epidermal growth factor (EGF) receptor induces formation of EGF receptor- and Grb2-containing clathrin-coated pits. Mol. Cell. Biol. 2006; 26:389-401 (Full Text)
  4. Natarajan K, Berk BC. Crosstalk coregulation mechanisms of G protein-coupled receptors and receptor tyrosine kinases. Methods Mol. Biol. 2006; 332:51-77 (PubMed)
  5. Sármay G, Angyal A, Kertész A, Maus M, Medgyesi D. The multiple function of Grb2 associated binder (Gab) adaptor/scaffolding protein in immune cell signaling. Immunol. Lett. 2006; 104:76-82 (PubMed)
  6. Zarich N, Oliva JL, Martínez N, Jorge R, Ballester A, Gutiérrez-Eisman S, García-Vargas S, Rojas JM. Grb2 is a negative modulator of the intrinsic Ras-GEF activity of hSos1. Mol. Biol. Cell 2006; 17:3591-7 (Full Text)
Consortium Results & Data
Discovery» siRNA migration screen using a wound healing approach
Gene Description     MCF-10A phenotype     Secondary screen Wound Image Morphology Time-lapse
GRB2
Aliases: ASH, Grb3-3, MST084, MSTP084, EGFRBP-GRB2
Entrez Gene: 2885
siRNA catalog
growth factor receptor-bound protein 2
mRNA: NM_002086
Library: MAR
Classification: adaptor
Focal Adhesion Related: Yes
Final bin: Low Alamar - MC
SMARTpool bin: Low Alamar
Avg area: 4.05
Avg Alamar: 0.51
Knockdown %: not done
ERBB2: No Change
BCL2: Low Alamar
GRB2
Link
GRB2
Link
 
Discovery» siRNA Focal Adhesion Phenotypes
Gene Description High-Res Montage
GRB2
Aliases: ASH, Grb3-3, MST084, MSTP084, EGFRBP-GRB2
Entrez Gene: 2885
siRNA catalog
growth factor receptor-bound protein 2
mRNA: NM_002086
Library: MAR
GRB2
Link
GRB2
Link
Proteomics» Table 1. Identification and Quantitation of Proteins from Cell Body (CB) and Pseudopodium (PD) fractions
IPI Locus Description CB Spectra CB peptide PD Spectra PD peptide ratio
IPI00021327 GRB2 GROWTH FACTOR RECEPTOR-BOUND PROTEIN 2. 3 2 3 2 1.00
Proteomics» Table 2. Proteins in major organelles and subcellular compartments
IPI Locus Description CB Spectra PD Spectra ratio Location
IPI00021327 GRB2 GROWTH FACTOR RECEPTOR-BOUND PROTEIN 2. 3 3 1 cytosol
Discovery» Genes that increase migratory behavior in MCF-10A cells
Protein Protein Class BC-1000
cDNA
mcf7/
mcf10a
mcf7/
mcf10a-csf1r
mcf7/
mcf-10a-csf1r_csf
mcf7/
mcf10a-erbb2
GRB2
Entrez GeneID: 2885
CMKB Orthologs
Signal transduction
+++
Discovery» Drosophila Migration Genes
Gene Name Function Cell
Type
Phenotypes Reagents/
Alleles
Reference
drk
Entrez: CG6033
Flybase: FBgn0004638
Downstream of receptor kinase signal transduction, adaptor embryonic hemocyte Loss of function: no zygotic phenotype not clear what kind of allele: drkDP2 Cho 2002
Discovery» wt-migratory_cells vs wt-non-migratory_cells
Symbol Description Median Values Fold Change Probe ID
drk
Flybase
Entrez
CMCKB
downstream of receptor kinase Mig: 83.8
Non-Mig: 51.1
1.63990 153747_at
Discovery» Drosophila Morphology Genes
Gene Name Cell Count/
Normalization
Stellate11
NumCorners
Stellate22
Binsum6
Non-Spreading3
CG6033
Entrez Gene: 36497
downstream of receptor kinase
Aliases: Enhancer of sevenless-2B; downstream receptor kinase
5.688
1.129
1.173 1.026 Actin: 0.849
Area: 1.129
Ratio: 0.752
Consortium Related Products*
Mice » activity page
Ortholog Species Name Method Phenotype Status Jax Availability Source Publications
GRB2 mouse Grb2 - hypomorph
-
Perinatal death due to cleft palate. completed
-
-
Saxton et al.
GRB2 mouse Grb2
-
Embryonic lethality at E4. Failure in endoderm differentiation. Chimeric embryos show that Grb2-null cells do not contribute to the epiblast. completed
-
-
Saxton et al., Cheng et al.

* The resources presented here are largely those generated by the Consortium. The sidebar provides public databases that complement Consortium activities. For mice and biosensors, a public database is not available and therefore we have attempted to generate a migration related list for your convenience.

The primary classification of CMKB families is the homeomorphic family, whose members are both homologous (evolved from a common ancestor) and homeomorphic (sharing full-length sequence similarity and a common domain architecture).