G3BP
entrez
10146
canonical
uniprot
Q13283
canonical
ensembl
ENSG00000145907
resolver
ensp
ENSP00000348578
resolver
ensp
ENSP00000377681
resolver
genesymbol
G3BP
resolver
genesymbol
G3BP1
resolver
genesymbol_syn
DKFZp686L1159
resolver
genesymbol_syn
G3BP
resolver
hgnc
HGNC:30292
resolver
uniprot
Q5HYE9
resolver
uniprot
Q5U0Q1
resolver
uniprot
Q6ZP53
resolver
uniprot_entry
G3BP1_HUMAN
resolver
uniprot_entry
Q5U0Q1_HUMAN
resolver
uniprot_entry
Q6ZP53_HUMAN
resolver
uniprot_sec
Q5HYE9
resolver
activity_regulation
ACTIVITY REGULATION: Under physiological conditions, G3BP1 adopts a compact state that is stabilized by intramolecular interactions between the RG-rich and the acidic regions that inhibit phase separation (PubMed:32302570, PubMed:32302571, PubMed:32302572). Upon stress, polysomes disassemble and mRNAs are released in an unfolded protein-free state (PubMed:32302570, PubMed:32302571, PubMed:32302572). Binding of unfolded mRNA to G3BP1 outcompetes the intramolecular interactions and RNA-bound G3BP1 adopts an expanded conformation in which the RG-rich region becomes exposed to engage in protein-protein and protein-RNA interactions, allowing physical cross-linking of RNA molecules to form protein-RNA condensates, leading to liquid-liquid phase separation (LLPS) (PubMed:32302570, PubMed:32302571, PubMed:32302572). {ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:32302571, ECO:0000269|PubMed:32302572}.
uniprot
proteins
amino_acid_sequence
MVMEKPSPLLVGREFVRQYYTLLNQAPDMLHRFYGKNSSYVHGGLDSNGKPADAVYGQKEIHRKVMSQNFTNCHTKIRHVDAHATLNDGVVVQVMGLLSNNNQALRRFMQTFVLAPEGSVANKFYVHNDIFRYQDEVFGGFVTEPQEESEEEVEEPEERQQTPEVVPDDSGTFYDQAVVSNDMEEHLEEPVAEPEPDPEPEPEQEPVSEIQEEKPEPVLEETAPEDAQKSSSPAPADIAQTVQEDLRTFSWASVTSKNLPPSGAVPVTGIPPHVVKVPASQPRPESKPESQIPPQRPQRDQRVREQRINIPPQRGPRPIREAGEQGDIEPRRMVRHPDSHQLFIGNLPHEVDKSELKDFFQSYGNVVELRINSGGKLPNFGFVVFDDSEPVQKVLSNRPIMFRGEVRLNVEEKKTRAAREGDRRDNRLRGPGGPRGGLGGGMRGPPRGGMVQKPGFGVGRGLAPRQ
uniprot
proteins
ec_number
3.6.4.12
uniprot
proteins
ec_number
3.6.4.13
uniprot
proteins
function
FUNCTION: Protein involved in various processes, such as stress granule formation and innate immunity (PubMed:37672657, PubMed:20180778, PubMed:23279204, PubMed:30510222, PubMed:30804210). Plays an essential role in stress granule formation (PubMed:37672657, PubMed:20180778, PubMed:23279204, PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:34739333, PubMed:35977029, PubMed:36183834, PubMed:36279435, PubMed:36692217, PubMed:37379838). Stress granules are membraneless compartments that store mRNAs and proteins, such as stalled translation pre-initiation complexes, in response to stress (PubMed:37672657, PubMed:20180778, PubMed:23279204, PubMed:27022092, PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:36279435, PubMed:37379838). Promotes formation of stress granules phase-separated membraneless compartment by undergoing liquid-liquid phase separation (LLPS) upon unfolded RNA-binding: functions as a molecular switch that triggers RNA-dependent LLPS in response to a rise in intracellular free RNA concentrations (PubMed:32302570, PubMed:32302571, PubMed:32302572, PubMed:34739333, PubMed:36279435, PubMed:36692217). Also acts as an ATP- and magnesium-dependent helicase: unwinds DNA/DNA, RNA/DNA, and RNA/RNA substrates with comparable efficiency (PubMed:9889278). Acts unidirectionally by moving in the 5' to 3' direction along the bound single-stranded DNA (PubMed:9889278). Unwinds preferentially partial DNA and RNA duplexes having a 17 bp annealed portion and either a hanging 3' tail or hanging tails at both 5'- and 3'-ends (PubMed:9889278). Plays an essential role in innate immunity by promoting CGAS and RIGI activity (PubMed:30510222, PubMed:30804210). Participates in the DNA-triggered cGAS/STING pathway by promoting the DNA binding and activation of CGAS (PubMed:30510222). Triggers the condensation of cGAS, a process probably linked to the formation of membrane-less organelles (PubMed:34779554). Also enhances RIGI-induced type I interferon production probably by helping RIGI at sensing pathogenic RNA (PubMed:30804210). May also act as a phosphorylation-dependent sequence-specific endoribonuclease in vitro: Cleaves exclusively between cytosine and adenine and cleaves MYC mRNA preferentially at the 3'-UTR (PubMed:11604510). {ECO:0000269|PubMed:11604510, ECO:0000269|PubMed:20180778, ECO:0000269|PubMed:23279204, ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:30510222, ECO:0000269|PubMed:30804210, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:32302571, ECO:0000269|PubMed:32302572, ECO:0000269|PubMed:34739333, ECO:0000269|PubMed:34779554, ECO:0000269|PubMed:35977029, ECO:0000269|PubMed:36183834, ECO:0000269|PubMed:36279435, ECO:0000269|PubMed:36692217, ECO:0000269|PubMed:37379838, ECO:0000269|PubMed:37672657, ECO:0000269|PubMed:9889278}.
uniprot
proteins
mass_dalton
52164
uniprot
proteins
mutagenesis
MUTAGEN 15; /note="F->W: Decreased interaction with USP10."; /evidence="ECO:0000269|PubMed:36183834"; MUTAGEN 33; /note="F->W: Abolished interaction with CAPRIN1 and ability to undergo liquid-liquid phase separation. Abolished interaction with USP10."; /evidence="ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:32302571, ECO:0000269|PubMed:36279435"; MUTAGEN 36; /note="K->R: In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-50, R-59, R-64, R-76, R-123, R-353, R-357, R-376 and R-393. In 6KR; strongly decreased ubiquitination in response to heat shock, leading to decreased stress granule disassembly; when associated with R-50, R-59, R-64, R-76 and R-123. In 4KR; decreased ubiquitination in response to heat shock, leading to slightly decreased stress granule disassembly; when associated with R-50, R-59 and R-64."; /evidence="ECO:0000269|PubMed:34739333"; MUTAGEN 50; /note="K->R: In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-59, R-64, R-76, R-123, R-353, R-357, R-376 and R-393. In 6KR; strongly decreased ubiquitination in response to heat shock, leading to decreased stress granule disassembly; when associated with R-36, R-59, R-64, R-76 and R-123. In 4KR; decreased ubiquitination in response to heat shock, leading to slightly decreased stress granule disassembly; when associated with R-36, R-59 and R-64."; /evidence="ECO:0000269|PubMed:34739333"; MUTAGEN 59; /note="K->R: In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-64, R-76, R-123, R-353, R-357, R-376 and R-393. In 6KR; strongly decreased ubiquitination in response to heat shock, leading to decreased stress granule disassembly; when associated with R-36, R-50, R-64, R-76 and R-123. In 4KR; decreased ubiquitination in response to heat shock, leading to slightly decreased stress granule disassembly; when associated with R-36, R-50 and R-64."; /evidence="ECO:0000269|PubMed:34739333"; MUTAGEN 64; /note="K->R: In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-59, R-76, R-123, R-353, R-357, R-376 and R-393. In 6KR; strongly decreased ubiquitination in response to heat shock, leading to decreased stress granule disassembly; when associated with R-36, R-50, R-59, R-76 and R-123. In 4KR; decreased ubiquitination in response to heat shock, leading to slightly decreased stress granule disassembly; when associated with R-36, R-50 and R-59."; /evidence="ECO:0000269|PubMed:34739333"; MUTAGEN 76; /note="K->R: In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-59, R-64, R-123, R-353, R-357, R-376 and R-393. In 6KR; strongly decreased ubiquitination in response to heat shock, leading to decreased stress granule disassembly; when associated with R-36, R-50, R-59, R-64 and R-123."; /evidence="ECO:0000269|PubMed:34739333"; MUTAGEN 123; /note="K->R: In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-59, R-64, R-76, R-353, R-357, R-376 and R-393. In 6KR; strongly decreased ubiquitination in response to heat shock, leading to decreased stress granule disassembly; when associated with R-36, R-50, R-59, R-64 and R-76."; /evidence="ECO:0000269|PubMed:34739333"; MUTAGEN 124; /note="F->W: Does not affect interaction with USP10."; /evidence="ECO:0000269|PubMed:36183834"; MUTAGEN 149; /note="S->A: Slightly increased ability to undergo liquid-liquid phase separation. Increased ability to undergo liquid-liquid phase separation; when associated with A-232. Cytoplasmic."; /evidence="ECO:0000269|PubMed:11604510, ECO:0000269|PubMed:32302571, ECO:0000269|PubMed:32302572, ECO:0000269|PubMed:37672657"; MUTAGEN 149; /note="S->E: Mimics phosphorylation; decreased ability to undergo liquid-liquid phase separation. Cytoplasmic and nuclear."; /evidence="ECO:0000269|PubMed:11604510, ECO:0000269|PubMed:32302571"; MUTAGEN 232; /note="S->A: Slightly increased ability to undergo liquid-liquid phase separation; when associated with A-149. Cytoplasmic. Partially nuclear; when associated with E-149."; /evidence="ECO:0000269|PubMed:11604510, ECO:0000269|PubMed:32302572"; MUTAGEN 232; /note="S->E: Cytoplasmic. Partially nuclear; when associated with E-149."; /evidence="ECO:0000269|PubMed:11604510"; MUTAGEN 325; /note="Q->G: Loss of cleavage by human enterovirus 71 protease 3C."; /evidence="ECO:0000269|PubMed:30006004"; MUTAGEN 353; /note="K->R: In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-59, R-64, R-76, R-123,R-357, R-376 and R-393."; /evidence="ECO:0000269|PubMed:34739333"; MUTAGEN 357; /note="K->R: In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-59, R-64, R-76, R-123, R-353, R-376 and R-393."; /evidence="ECO:0000269|PubMed:34739333"; MUTAGEN 376; /note="K->R: In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-59, R-64, R-76, R-123, R-353, R-357 and R-393."; /evidence="ECO:0000269|PubMed:34739333"; MUTAGEN 380..382; /note="FGF->GDG: Abolished mRNA-binding and ability to undergo liquid-liquid phase separation."; /evidence="ECO:0000269|PubMed:32302571"; MUTAGEN 393; /note="K->R: In 10KR; abolished ubiquitination in response to heat shock, leading to decreased stress granule disassembly when associated with R-36, R-50, R-59, R-64, R-76, R-123, R-353, R-357 and R-376."; /evidence="ECO:0000269|PubMed:34739333
uniprot
proteins
post_translational_modification
PTM: Phosphorylation of the acidic disordered region regulates stress granule assembly (PubMed:32302571, PubMed:32302572). Dephosphorylation after HRAS activation is required for stress granule assembly (PubMed:11604510, PubMed:37672657). Ser-149 phosphorylation induces partial nuclear localization (PubMed:11604510). {ECO:0000269|PubMed:11604510, ECO:0000269|PubMed:32302571, ECO:0000269|PubMed:32302572, ECO:0000269|PubMed:37672657}.; PTM: Ubiquitinated by TRIM21 via 'Lys-63'-linked polyubiquitination in the NTF2 domain in response to heat shock, leading to stress granule disassembly: ubiquitination promotes interaction with the FAF2 adapter, followed by interaction with VCP, which extracts G3BP1 from stress granules, leading to stress granule disassembly (PubMed:34739333, PubMed:36692217). In case of prolonged stress, ubiquitination by TRIM21 leads to autophagy-dependent degradation of G3BP1 via recruitment of ubiquitinated G3BP1 by SQSTM1 and/or CALCOCO2 to autophagosomes (PubMed:34739333, PubMed:36692217). {ECO:0000269|PubMed:34739333, ECO:0000269|PubMed:36692217}.; PTM: (Microbial infection) Cleaved by human enterovirus 71; this cleavage induces the disassembly of cytoplasmic stress granules (PubMed:30006004). Cleaved by Foot-and-mouth disease virus; this cleavage suppresses the formation of cytoplasmic stress granules (PubMed:30404792). {ECO:0000269|PubMed:30006004, ECO:0000269|PubMed:30404792}.; PTM: Arg-435 is dimethylated, probably to asymmetric dimethylarginine.; PTM: (Microbial infection) Cleaved by Encephalomyocarditis virus protease 3C; this cleavage suppresses the formation of cytoplasmic stress granules. {ECO:0000269|PubMed:23785203}.
uniprot
proteins
pubmed
11439350
uniprot
proteins
pubmed
11604510
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15144186
uniprot
proteins
pubmed
15372022
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16964243
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17210633
uniprot
proteins
pubmed
17487921
uniprot
proteins
pubmed
17693683
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18318008
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18684830
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19367720
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20180778
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
23087212
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23209657
uniprot
proteins
pubmed
23279204
uniprot
proteins
pubmed
23785203
uniprot
proteins
pubmed
23953116
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24324649
uniprot
proteins
pubmed
24623412
uniprot
proteins
pubmed
25658430
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
27022092
uniprot
proteins
pubmed
27383630
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
28592527
uniprot
proteins
pubmed
28794026
uniprot
proteins
pubmed
30006004
uniprot
proteins
pubmed
30404792
uniprot
proteins
pubmed
30510222
uniprot
proteins
pubmed
30804210
uniprot
proteins
pubmed
31981475
uniprot
proteins
pubmed
32302570
uniprot
proteins
pubmed
32302571
uniprot
proteins
pubmed
32302572
uniprot
proteins
pubmed
34739333
uniprot
proteins
pubmed
34779554
uniprot
proteins
pubmed
35977029
uniprot
proteins
pubmed
36183834
uniprot
proteins
pubmed
36279435
uniprot
proteins
pubmed
36692217
uniprot
proteins
pubmed
37379838
uniprot
proteins
pubmed
37672657
uniprot
proteins
pubmed
39135075
uniprot
proteins
pubmed
8649363
uniprot
proteins
pubmed
9889278
uniprot
proteins
sequence_length
466
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:20180778, ECO:0000269|PubMed:30510222}. Perikaryon {ECO:0000250|UniProtKB:P97855}. Cytoplasm, Stress granule {ECO:0000269|PubMed:17210633, ECO:0000269|PubMed:20180778, ECO:0000269|PubMed:23953116, ECO:0000269|PubMed:27022092, ECO:0000269|PubMed:30404792, ECO:0000269|PubMed:32302570, ECO:0000269|PubMed:32302571, ECO:0000269|PubMed:32302572, ECO:0000269|PubMed:37672657}. Nucleus {ECO:0000269|PubMed:11604510}. Note=Cytoplasmic in proliferating cells (PubMed:11604510). Cytosolic and partially nuclear in resting cells (PubMed:11604510). Recruited to stress granules in response to arsenite treatment (PubMed:37672657, PubMed:20180778). The unphosphorylated form is recruited to stress granules (PubMed:37672657). HRAS signaling contributes to this process by regulating G3BP dephosphorylation (PubMed:37672657). {ECO:0000269|PubMed:11604510, ECO:0000269|PubMed:20180778, ECO:0000269|PubMed:37672657}.
uniprot
proteins