Ras GTPase-activating protein-binding protein 1 (G3BP1)

The protein contains 466 amino acids for an estimated molecular weight of 52164 Da.

 

ATP- and magnesium-dependent helicase that plays an essential role in innate immunity (PubMed:30510222). Participates in the DNA-triggered cGAS/STING pathway by promoting the DNA binding and activation of CGAS. Enhances also DDX58-induced type I interferon production probably by helping DDX58 at sensing pathogenic RNA (PubMed:30804210). In addition, plays an essential role in stress granule formation (PubMed:12642610, PubMed:20180778, PubMed:23279204). 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). 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). Phosphorylation-dependent sequence-specific endoribonuclease in vitro (PubMed:11604510). Cleaves exclusively between cytosine and adenine and cleaves MYC mRNA preferentially at the 3'-UTR (PubMed:11604510). (updated: May 8, 2019)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.


Interpro domains
Total structural coverage: 31%
Model score: 0
MODL_I-TASSER-3.0

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The reference OMIM entry for this protein is 608431

Gtpase-activating protein sh3 domain-binding protein 1; g3bp1
Ras-gtpase-activating protein sh3 domain-binding protein
Gap sh3 domain-binding protein; g3bp
Human dna helicase viii
Hdh-viii

CLONING

Parker et al. (1996) identified G3bp through its binding to the SH3 domain of GAP (RASA1; 139150) in lysates of exponentially growing Chinese hamster lung fibroblasts engineered to overexpress human epidermal growth factor receptor (131550). By PCR using primers designed from the peptide sequence, followed by screening a placenta cDNA library screening, they cloned human G3BP. The deduced 466-amino acid protein has a calculated molecular mass of 52 kD. G3BP contains an acid-rich amino acid domain between amino acids 144 and 221, followed by 2 consensus RNA-binding motifs and several C-terminal arg/gly-rich boxes, which are also implicated in RNA binding. Northern blot analysis detected a 3.3-kb G3BP transcript in all fetal and adult tissues examined, with prominent expression in adult skeletal muscle. Immunofluorescence analysis of several mammalian cell lines localized G3BP within the cytoplasm. The staining intensity varied between cells, but the intensity and localization were unaltered under various experimental conditions. G3bp purified from Chinese hamster lung fibroblasts and recombinant G3BP expressed in insect cells both showed apparent molecular masses of 68 kD.

GENE FUNCTION

Parker et al. (1996) confirmed that recombinant G3BP expressed in insect cells bound to the SH3 domain of GAP. G3BP coimmunoprecipitated with GAP only when cells were proliferating. Parker et al. (1996) concluded that recruitment of the GAP-G3BP complex occurs only when Ras (190020) is in its activated conformation. Costa et al. (1999) purified human G3BP, which they called HDH-VIII, in a systematic study of DNA-unwinding enzymes present in HeLa cells. They found that G3BP could unwind DNA and RNA partial duplexes in an ATP- and Mg(2+)-dependent manner, even though it lacks the canonical helicase domain. G3BP preferentially unwound partial duplex substrates having a 17-bp annealed portion and either a hanging 3-prime tail or hanging tails at both the 3-prime and 5-prime ends. It unwound DNA/DNA, RNA/DNA, and RNA/RNA substrates with comparable efficiency. G3BP failed to unwind a substrate with a 40-bp annealed section. It appeared to unwind unidirectionally by moving in the 5-prime-to-3-prime direction along the bound single-stranded DNA. Tourriere et al. (2003) found that endogenous G3bp localized in large cytoplasmic structures resembling stress granules (SGs) in COS cells following exposure to either arsenite or high temperature. They found that the N-terminal NTF2 (605813)-like domain and the RNA-binding domains of G3BP mediated its recruitment to SGs. Overexpression of G3BP induced SG assembly, whereas overexpression of only the central RasGAP-binding domain inhibited SG assembly. Within the RasGAP-binding domain, dephosphorylation of a critical serine (ser149) was induced by arsenite treatments. A phosphomimetic mutant at this position failed to oligomerize and to assemble SGs, whereas a nonphosphorylatable G3BP mutant did both. Tourriere et al. (2003) concluded that G3BP is an effector of SG assembly and that Ras signaling contributes to this process by regulating G3BP dephosphorylation.

MAPPING

The International Radiation Hybrid Mapping Consortium mapped the G3BP gene to chromosome 5 (TMAP SHGC-133085). ... More on the omim web site

Subscribe to this protein entry history

May 12, 2019: Protein entry updated
Automatic update: model status changed

May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Nov. 17, 2018: Protein entry updated
Automatic update: model status changed

July 2, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Oct. 27, 2017: Protein entry updated
Automatic update: model status changed

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 608431 was added.

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed