GRB2

Growth factor receptor-bound protein 2, also known as Grb2, is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.[5][6]

GRB2
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesGRB2, ASH, EGFRBP-Grb3-3, MST084, MSTP084, NCKAP2, growth factor receptor bound protein 2
External IDsOMIM: 108355 MGI: 95805 HomoloGene: 1576 GeneCards: GRB2
Orthologs
SpeciesHumanMouse
Entrez

2885

14784

Ensembl

ENSG00000177885

ENSMUSG00000059923

UniProt

P62993

Q60631

RefSeq (mRNA)

NM_203506
NM_002086

NM_008163
NM_001313936
NM_001313937

RefSeq (protein)

NP_002077
NP_987102

NP_001300865
NP_001300866
NP_032189

Location (UCSC)Chr 17: 75.32 – 75.41 MbChr 11: 115.53 – 115.6 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The protein encoded by this gene binds receptors such as 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 sem-5 gene of Caenorhabditis elegans, which is involved in the signal transduction pathway. Two alternatively spliced transcript variants encoding different isoforms have been found for this gene.[7]

Function and expression

Grb2 is widely expressed and is essential for multiple cellular functions. Inhibition of Grb2 function impairs developmental processes in various organisms and blocks transformation and proliferation of various cell types. It is thus not surprising that targeted gene disruption of Grb2 in mice is lethal at an early embryonic stage. Grb2 is best known for its ability to link the epidermal growth factor receptor tyrosine kinase to the activation of Ras and its downstream kinases, ERK1,2. Grb2 is composed of an SH2 domain flanked on each side by an SH3 domain. Grb2 has two closely related proteins with similar domain organizations, Gads and Grap. Gads and Grap are expressed specifically in hematopoietic cells and function in the coordination of tyrosine kinase mediated signal transduction.

Domains

The SH2 domain of Grb2 binds to phosphorylated tyrosine-containing peptides on receptors or scaffold proteins with a preference for pY-X-N-X, where X is generally a hydrophobic residue such as valine (see ).

The N-terminal SH3 domain binds to proline-rich peptides and can bind to the Ras-guanine exchange factor SOS.

The C-terminal SH3 domain binds to peptides conforming to a P-X-I/L/V/-D/N-R-X-X-K-P motif that allows it to specifically bind to proteins such as Gab-1.[8]

Interactions

Grb2 has been shown to interact with:

See also

References
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  2. GRCm38: Ensembl release 89: ENSMUSG00000059923 - Ensembl, May 2017
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  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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