Grb2
entrez
81504
canonical
uniprot
P62994
canonical
ensembl
ENSRNOG00000003990
resolver
ensembl
ENSRNOG00055032965
resolver
ensembl
ENSRNOG00060019266
resolver
ensembl
ENSRNOG00065020618
resolver
ensp
ENSRNOP00000005347
resolver
genesymbol
Grb2
resolver
genesymbol_syn
Ash
resolver
uniprot
P29354
resolver
uniprot
Q14450
resolver
uniprot
Q5BKA7
resolver
uniprot
Q63057
resolver
uniprot
Q63059
resolver
uniprot_entry
GRB2_RAT
resolver
uniprot_sec
P29354
resolver
uniprot_sec
Q14450
resolver
uniprot_sec
Q5BKA7
resolver
uniprot_sec
Q63057
resolver
uniprot_sec
Q63059
resolver
amino_acid_sequence
MEAIAKYDFKATADDELSFKRGDILKVLNEECDQNWYKAELNGKDGFIPKNYIEMKPHPWFFGKIPRAKAEEMLSKQRHDGAFLIRESESAPGDFSLSVKFGNDVQHFKVLRDGAGKYFLWVVKFNSLNELVDYHRSTSVSRNQQIFLRDIEQVPQQPTYVQALFDFDPQEDGELGFRRGDFIHVMDNSDPNWWKGACHGQTGMFPRNYVTPVNRNV
uniprot
proteins
function
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:7775428). 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. Also plays 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. {ECO:0000250|UniProtKB:P62993, ECO:0000269|PubMed:7775428}.
uniprot
proteins
mass_dalton
25206
uniprot
proteins
post_translational_modification
PTM: Phosphorylation of Tyr-209 in the C-terminal SH3 domain reduces its binding to SOS1. {ECO:0000250|UniProtKB:P62993}.; PTM: Ubiquitinated by RNF173, leading to proteasomal degradation and inhibition of the RAF/MEK/ERK pathway. In the nucleus, polyubiquitinated by RBBP6 at Lys-109 at DNA damage sites. {ECO:0000250|UniProtKB:P62993}.
uniprot
proteins
protein_family
GRB2/sem-5/DRK family
uniprot
proteins
pubmed
1384039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
7775428
uniprot
proteins
pubmed
8262059
uniprot
proteins
pubmed
8388384
uniprot
proteins
sequence_length
217
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P62993}. Cytoplasm {ECO:0000250|UniProtKB:P62993}. Endosome {ECO:0000250|UniProtKB:P62993}. Golgi apparatus {ECO:0000250|UniProtKB:Q60631}.
uniprot
proteins