lmmol · Proteins

Growth factor receptor-bound protein 2

UniProt P62993 Organism Homo sapiens Gene ASH, GRB2

Also known as: ASH, GRB2

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. Thus, participates in many biological processes including regulation of innate and adaptive immunity, autophagy, DNA repair or necroptosis. Controls signaling complexes at the T-cell antigen receptor to facilitate the activation, differentiation, and function of T-cells. Mechanistically, engagement of the TCR leads to phosphorylation of the adapter protein LAT, which serves as docking site for GRB2. 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. 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). 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. Regulates miRNA biogenesis by forming a functional ternary complex with AGO2 and DICER1. 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. Additionally, directly recruits and later releases MRE11 at DNA damage sites during the homology-directed repair (HDR) process.

Classification

Family (Pfam)
PF00017 SH2, PF00018 SH3_1
InterPro
Grb2-like, GRB2_C_SH3, GRB2_N_SH3, SH2, SH2_dom_sf, SH3-like_dom_sf, SH3_domain
Functional cluster
Small GTPases (Ras/Rab) & related

Experimental structures · PDB · 55

A predicted model is available from AlphaFold.

Gene Ontology · 44

Neighborhood · nearest proteins

ASHAshGrb2GRB2PRR1411KKiaa1236
Nearest neighbours of Growth factor receptor-bound protein 2: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 101 cited papers

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