Grb2
entrez
14784
canonical
uniprot
Q60631
canonical
ensembl
ENSMUSG00000059923
resolver
ensp
ENSMUSP00000021090
resolver
ensp
ENSMUSP00000102106
resolver
ensp
ENSMUSP00000314648
resolver
genesymbol
Grb2
resolver
uniprot
Q3U1Q4
resolver
uniprot
Q3U5I5
resolver
uniprot
Q61240
resolver
uniprot_entry
GRB2_MOUSE
resolver
uniprot_entry
Q3U1Q4_MOUSE
resolver
uniprot_entry
Q3U5I5_MOUSE
resolver
uniprot_sec
Q61240
resolver
amino_acid_sequence
MEAIAKYDFKATADDELSFKRGDILKVLNEECDQNWYKAELNGKDGFIPKNYIEMKPHPWFFGKIPRAKAEEMLSKQRHDGAFLIRESESAPGDFSLSVKFGNDVQHFKVLRDGAGKYFLWVVKFNSLNELVDYHRSTSVSRNQQIFLRDIEQMPQQPTYVQALFDFDPQEDGELGFRRGDFIHVMDNSDPNWWKGACHGQTGMFPRNYVTPVNRNV
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:28964849). 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 functions 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:34697226). 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:28964849, ECO:0000269|PubMed:34697226}.; FUNCTION: [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. {ECO:0000250|UniProtKB:P62993}.
uniprot
proteins
mass_dalton
25238
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
10068651
uniprot
proteins
pubmed
10330178
uniprot
proteins
pubmed
10377264
uniprot
proteins
pubmed
10521483
uniprot
proteins
pubmed
11113178
uniprot
proteins
pubmed
11463797
uniprot
proteins
pubmed
11551227
uniprot
proteins
pubmed
11571277
uniprot
proteins
pubmed
11711534
uniprot
proteins
pubmed
12925710
uniprot
proteins
pubmed
14610044
uniprot
proteins
pubmed
15477348
uniprot
proteins
pubmed
15477350
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16249387
uniprot
proteins
pubmed
16475793
uniprot
proteins
pubmed
16582911
uniprot
proteins
pubmed
16966330
uniprot
proteins
pubmed
19597497
uniprot
proteins
pubmed
19597498
uniprot
proteins
pubmed
19805304
uniprot
proteins
pubmed
20398064
uniprot
proteins
pubmed
20644716
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21543326
uniprot
proteins
pubmed
21930792
uniprot
proteins
pubmed
22561606
uniprot
proteins
pubmed
26552706
uniprot
proteins
pubmed
28098138
uniprot
proteins
pubmed
28290451
uniprot
proteins
pubmed
28964849
uniprot
proteins
pubmed
32930093
uniprot
proteins
pubmed
34697226
uniprot
proteins
pubmed
7689150
uniprot
proteins
pubmed
7997267
uniprot
proteins
pubmed
8943348
uniprot
proteins
pubmed
9135122
uniprot
proteins
pubmed
9312046
uniprot
proteins
pubmed
9395447
uniprot
proteins
pubmed
9569023
uniprot
proteins
pubmed
9722576
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:0000269|PubMed:11571277}.
uniprot
proteins