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Recombinant Human GRB2 protein (Tagged) is a Human Full Length protein, in the 2 to 217 aa range, expressed in Escherichia coli, with >90% purity and suitable for SDS-PAGE.

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Key facts

Purity
>90% SDS-PAGE
Expression system
Escherichia coli
Tags
Tag free
Applications
SDS-PAGE
Biologically active
No

Amino acid sequence

M A S M T G G Q Q M G R G H H H H H H E N L Y F Q G G S E A I A K Y D F K A T A D D E L S F K R G D I L K V L N E E C D Q N W Y K A E L N G K D G F I P K N Y I E M K P H P W F F G K I P R A K A E E M L S K Q R H D G A F L I R E S E S A P G D F S L S V K F G N D V Q H F K V L R D G A G K Y F L W V V K F N S L N E L V D Y H R S T S V S R N Q Q I F L R D I E Q V P Q Q P T Y V Q A L F D F D P Q E D G E L G F R R G D F I H V M D N S D P N W W K G A C H G Q T G M F P R N Y V T P V N R N V

Reactivity data

Application
SDS-PAGE
Reactivity
Reacts
Dilution info
-
Notes

-

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Target data

Function

Non-enzymatic adapter protein that plays a pivotal role in precisely regulated signaling cascades from cell surface receptors to cellular responses, including signaling transduction and gene expression (PubMed:11726515, PubMed:37626338). Thus, participates in many biological processes including regulation of innate and adaptive immunity, autophagy, DNA repair or necroptosis (PubMed:35831301, PubMed:37626338, PubMed:38182563). Controls signaling complexes at the T-cell antigen receptor to facilitate the activation, differentiation, and function of T-cells (PubMed:36864087, PubMed:9489702). Mechanistically, engagement of the TCR leads to phosphorylation of the adapter protein LAT, which serves as docking site for GRB2 (PubMed:9489702). In turn, GRB2 establishes a a connection with SOS1 that acts as a guanine nucleotide exchange factor and serves as a critical regulator of KRAS/RAF1 leading to MAPKs translocation to the nucleus and activation (PubMed:12171928, PubMed:25870599). Functions also a role in B-cell activation by amplifying Ca(2+) mobilization and activation of the ERK MAP kinase pathway upon recruitment to the phosphorylated B-cell antigen receptor (BCR) (PubMed:25413232, PubMed:29523808). Plays a role in switching between autophagy and programmed necrosis upstream of EGFR by interacting with components of necrosomes including RIPK1 and with autophagy regulators SQSTM1 and BECN1 (PubMed:35831301, PubMed:38182563). Regulates miRNA biogenesis by forming a functional ternary complex with AGO2 and DICER1 (PubMed:37328606). Functions in the replication stress response by protecting DNA at stalled replication forks from MRE11-mediated degradation. Mechanistically, inhibits RAD51 ATPase activity to stabilize RAD51 on stalled replication forks (PubMed:38459011). Additionally, directly recruits and later releases MRE11 at DNA damage sites during the homology-directed repair (HDR) process (PubMed:34348893). Isoform 2. Does not bind to phosphorylated epidermal growth factor receptor (EGFR) but inhibits EGF-induced transactivation of a RAS-responsive element. Acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active programmed cell death. Mechanistically, inhibits RAS-ERK signaling and downstream cell proliferation by competing with GRB2 for SOS1 binding and thus by regulating SOS1 membrane recruitment (PubMed:36171279).

Alternative names

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Recombinant Human GRB2 protein (Tagged) is a Human Full Length protein, in the 2 to 217 aa range, expressed in Escherichia coli, with >90% purity and suitable for SDS-PAGE.

Key facts

Purity
>90% SDS-PAGE
Expression system
Escherichia coli
Applications
SDS-PAGE
Accession
P62993-1
Animal free
No
Species
Human
Concentration
Loading...
Storage buffer

pH: 8
Constituents: 0.32% Tris HCl

Sequence info

Amino acid sequence

M A S M T G G Q Q M G R G H H H H H H E N L Y F Q G G S E A I A K Y D F K A T A D D E L S F K R G D I L K V L N E E C D Q N W Y K A E L N G K D G F I P K N Y I E M K P H P W F F G K I P R A K A E E M L S K Q R H D G A F L I R E S E S A P G D F S L S V K F G N D V Q H F K V L R D G A G K Y F L W V V K F N S L N E L V D Y H R S T S V S R N Q Q I F L R D I E Q V P Q Q P T Y V Q A L F D F D P Q E D G E L G F R R G D F I H V M D N S D P N W W K G A C H G Q T G M F P R N Y V T P V N R N V
Accession
P62993
Protein length
Full Length
Predicted molecular weight
28.18 kDa
Amino acids
2 to 217
Nature
Recombinant

Specifications

Form
Liquid

General info

Function

Non-enzymatic adapter protein that plays a pivotal role in precisely regulated signaling cascades from cell surface receptors to cellular responses, including signaling transduction and gene expression (PubMed:11726515, PubMed:37626338). Thus, participates in many biological processes including regulation of innate and adaptive immunity, autophagy, DNA repair or necroptosis (PubMed:35831301, PubMed:37626338, PubMed:38182563). Controls signaling complexes at the T-cell antigen receptor to facilitate the activation, differentiation, and function of T-cells (PubMed:36864087, PubMed:9489702). Mechanistically, engagement of the TCR leads to phosphorylation of the adapter protein LAT, which serves as docking site for GRB2 (PubMed:9489702). In turn, GRB2 establishes a a connection with SOS1 that acts as a guanine nucleotide exchange factor and serves as a critical regulator of KRAS/RAF1 leading to MAPKs translocation to the nucleus and activation (PubMed:12171928, PubMed:25870599). Functions also a role in B-cell activation by amplifying Ca(2+) mobilization and activation of the ERK MAP kinase pathway upon recruitment to the phosphorylated B-cell antigen receptor (BCR) (PubMed:25413232, PubMed:29523808). Plays a role in switching between autophagy and programmed necrosis upstream of EGFR by interacting with components of necrosomes including RIPK1 and with autophagy regulators SQSTM1 and BECN1 (PubMed:35831301, PubMed:38182563). Regulates miRNA biogenesis by forming a functional ternary complex with AGO2 and DICER1 (PubMed:37328606). Functions in the replication stress response by protecting DNA at stalled replication forks from MRE11-mediated degradation. Mechanistically, inhibits RAD51 ATPase activity to stabilize RAD51 on stalled replication forks (PubMed:38459011). Additionally, directly recruits and later releases MRE11 at DNA damage sites during the homology-directed repair (HDR) process (PubMed:34348893).

Sequence similarities

Belongs to the GRB2/sem-5/DRK family.

Post-translational modifications

Phosphorylation of Tyr-209 in the C-terminal SH3 domain reduces its binding to SOS1.

Subcellular localisation
Nucleus, Endosome

Storage

Shipped at conditions
Blue Ice
Appropriate short-term storage duration
1-2 weeks
Appropriate short-term storage conditions
+4°C
Appropriate long-term storage conditions
-80°C
Storage information
Avoid freeze / thaw cycle

Supplementary info

This supplementary information is collated from multiple sources and compiled automatically.
Activity summary

The GRB2 protein also known as growth factor receptor-bound protein 2 is instrumental in signal transduction. GRB2 has a molecular weight of about 25 kDa. It comprises one SH2 domain and two SH3 domains which facilitate its role in linking receptor tyrosine kinases to downstream signaling molecules. GRB2 is ubiquitously expressed in various tissues signifying its importance in diverse cellular functions.

Biological function summary

GRB2 functions as an adaptor protein that connects activated receptor tyrosine kinases to intracellular pathways. It often forms complexes with other proteins such as the SOS protein which further propagates signaling cascades critical for cell proliferation and differentiation. GRB2’s ability to mediate these interactions contributes to cellular responses to external stimuli including growth factors and hormones.

Pathways

GRB2 plays an important role in the Ras-MAPK signaling pathway. It interacts with proteins like SOS and Ras enabling signal transduction from the cell surface to the nucleus which is vital for processes such as cell growth and survival. GRB2 is also implicated in the PI3K-Akt pathway connecting it to another set of signaling proteins that regulate metabolism growth and survival.

Associated diseases and disorders

GRB2 has significant associations with cancer and immune disorders. Aberrant activation of pathways involving GRB2 can lead to uncontrolled cell proliferation contributing to oncogenesis in different cancers. Additionally GRB2’s interactions with proteins like BCR-ABL in chronic myeloid leukemia highlight its potential role as a therapeutic target. GRB2 inhibitors could therefore offer promising avenues for treating such conditions by disrupting its pathological signaling interactions.

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