Ras GTPase-activating protein-binding protein 1

Function

Protein involved in various processes, such as stress granule formation and innate immunity. Plays an essential role in stress granule formation. Stress granules are membraneless compartments that store mRNAs and proteins, such as stalled translation pre-initiation complexes, in response to stress. 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. Also acts as an ATP- and magnesium-dependent helicase: unwinds DNA/DNA, RNA/DNA, and RNA/RNA substrates with comparable efficiency. Acts unidirectionally by moving in the 5' to 3' direction along the bound single-stranded DNA. 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. Plays an essential role in innate immunity by promoting CGAS and RIGI activity. Participates in the DNA-triggered cGAS/STING pathway by promoting the DNA binding and activation of CGAS. Triggers the condensation of cGAS, a process probably linked to the formation of membrane-less organelles. Also enhances RIGI-induced type I interferon production probably by helping RIGI at sensing pathogenic RNA. 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.

Classification

Family (Pfam)

PF02136 NTF2, PF00076 RRM_1

InterPro

G3BP1_RRM, NTF2-like_dom_sf, NTF2_dom, Nuclear_transport_factor_2_euk, Nucleotide-bd_a/b_plait_sf, Ras_GTPase_bind_prot, RBD_domain_sf, RRM_dom

Functional cluster

Translation Initiation/Elongation GTPases

Experimental structures · PDB · 20

• 3Q90 X-ray 1.70A
• 4FCJ X-ray 1.62A
• 4FCM X-ray 2.69A
• 4IIA X-ray 3.30A
• 5FW5 X-ray 1.92A
• 6TA7 X-ray 1.93A
• 7S17 X-ray 2.36A
• 7SUO X-ray 2.35A
• 7XHF X-ray 2.68A
• 7XHG X-ray 2.46A
• 8TH1 X-ray 1.80A
• 8TH5 X-ray 2.62A
• … and 8 more

A predicted model is available from AlphaFold.

Gene Ontology · 22

• GO:0005737 cytoplasm
• GO:0010494 cytoplasmic stress granule
• GO:0005829 cytosol
• GO:0005925 focal adhesion
• GO:0005634 nucleus
• GO:0043204 perikaryon
• GO:0005524 ATP binding
• GO:0016887 ATP hydrolysis activity
• GO:0003677 DNA binding
• GO:0003678 DNA helicase activity
• GO:0033677 DNA/RNA helicase activity
• GO:0004519 endonuclease activity
• GO:0140693 molecular condensate scaffold activity
• GO:0003729 mRNA binding
• GO:0043024 ribosomal small subunit binding
• GO:0003723 RNA binding
• GO:0003724 RNA helicase activity
• GO:0051607 defense response to virus
• GO:0045087 innate immune response
• GO:0032481 positive regulation of type I interferon production
• GO:0007265 Ras protein signal transduction
• GO:0034063 stress granule assembly

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Ras GTPase-activating protein-binding protein 1 1.00
• Ras GTPase-activating protein-binding protein 1 0.99
• Ras GTPase-activating protein-binding protein 2 0.97
• Ras GTPase-activating protein-binding protein 2 0.97
• Ras GTPase-activating protein-binding protein 2 0.97
• Nuclear transport factor 2 0.75
• Putative G3BP-like protein 0.65
• Eukaryotic translation initiation factor 4B 0.62
• RGG repeats nuclear RNA binding protein A 0.61
• SERPINE1 mRNA-binding protein 1 0.61
• SERPINE1 mRNA-binding protein 1 0.61
• Ras GTPase-activating protein-binding protein gtbp-1 0.61

Co-cited proteins · studied together in the literature

• Ras GTPase-activating protein-binding protein 1 3 shared papers
• Ras GTPase-activating protein-binding protein 2 9 shared papers
• Caprin-1 10 shared papers
• Polyprotein P1234 4 shared papers
• Ubiquitin carboxyl-terminal hydrolase 10 8 shared papers
• Serine/threonine/tyrosine-interacting-like protein 1 1 shared papers
• Genome polyprotein 1 shared papers
• Genome polyprotein 1 shared papers
• Polyprotein P1234 2 shared papers
• Caprin-1 1 shared papers
• Genome polyprotein 1 shared papers
• E3 ubiquitin-protein ligase TRIM21 1 shared papers

Literature · 62 cited papers

• SARS-CoV-2 nucleocapsid protein promotes self-deacetylation by inducing HDAC6 to facilitate viral replication. Virol. J. · 2024
• The RasGAP-associated endoribonuclease G3BP mediates stress granule assembly. J. Cell Biol. · 2023
• QKI shuttles internal m7G-modified transcripts into stress granules and modulates mRNA metabolism. Cell · 2023
• Stress granule homeostasis is modulated by TRIM21-mediated ubiquitination of G3BP1 and autophagy-dependent elimination of stress granules. Autophagy · 2023
• Yin and yang regulation of stress granules by Caprin-1. Proc. Natl. Acad. Sci. U.S.A. · 2022
• Tryptophan mutations in G3BP1 tune the stability of a cellular signaling hub by weakening transient interactions with Caprin1 and USP10. J. Biol. Chem. · 2022
• De novo variants in genes regulating stress granule assembly associate with neurodevelopmental disorders. Sci. Adv. · 2022
• The stress granule protein G3BP1 promotes pre-condensation of cGAS to allow rapid responses to DNA. EMBO Rep. · 2022
• Ubiquitination of G3BP1 mediates stress granule disassembly in a context-specific manner. Science · 2021
• RNA-Induced conformational switching and clustering of G3BP drive stress granule assembly by condensation. Cell · 2020
• G3BP1 is a tunable switch that triggers phase separation to assemble stress granules. Cell · 2020
• Competing protein-RNA interaction networks control multiphase intracellular organization. Cell · 2020
• … and 50 more in the literature graph