Q13283 (G3BP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Ras GTPase-activating protein-binding protein 1
Short name=G3BP-1
EC=3.6.4.12
EC=3.6.4.13

Alternative name(s):
ATP-dependent DNA helicase VIII
Short name=hDH VIII
GAP SH3 domain-binding protein 1

Gene names

Name:	G3BP1
Synonyms:	G3BP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	466 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be a regulated effector of stress granule assembly. Phosphorylation-dependent sequence-specific endoribonuclease in vitro. Cleaves exclusively between cytosine and adenine and cleaves MYC mRNA preferentially at the 3'-UTR. ATP- and magnesium-dependent helicase. 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. 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. Ref.4 Ref.5
Catalytic activity	ATP + H2O = ADP + phosphate.
Cofactor	Magnesium. Required for helicase activity.
Subunit structure	Binds to the SH3 domain of Ras GTPase-activating protein (RASA1) in proliferating cells. No interaction in quiescent cells Component of a TAU mRNP complex, at least composed of IGF2BP1, ELAVL4 and G3BP1 By similarity. Interacts with USP10, and may regulate it. Forms homodimers and oligomers. Ref.6 Ref.7
Subcellular location	Cytoplasm. Cytoplasm › cytosol. Cell membrane. Nucleus. Note: Cytoplasmic in proliferating cells, can be recruited to the plasma membrane in exponentially growing cells By similarity. Cytosolic and partially nuclear in resting cells. Recruited to stress granules (SGs) upon either arsenite or high temperature treatment. Recruitment to SGs is influenced by HRAS. Ref.7
Tissue specificity	Ubiquitous.
Domain	The NTF2 domain mediates multimerization.
Post-translational modification	Phosphorylated exclusively on serine residues. Hyperphosphorylated in quiescent fibroblasts. Hypophosphorylation leads to a decrease in endoribonuclease activity By similarity. RASA1-dependent phosphorylation of Ser-149 induces a conformational change that prevents self-association. Dephosphorylation after HRAS activation is required for stress granule assembly. Ser-149 phosphorylation induces partial nuclear localization. Ref.3 Ref.5 Ref.7 Arg-435 is dimethylated, probably to asymmetric dimethylarginine. Ref.3
Sequence similarities	Contains 1 NTF2 domain. Contains 1 RRM (RNA recognition motif) domain.

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Ligand	ATP-binding DNA-binding Nucleotide-binding RNA-binding
Molecular function	Endonuclease Helicase Hydrolase Nuclease
PTM	Acetylation Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Traceable author statement Ref.1. Source: ProtInc negative regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara nucleic acid phosphodiester bond hydrolysis Inferred from electronic annotation. Source: GOC transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytoplasm Inferred from direct assay. Source: HPA cytoplasmic stress granule Inferred from electronic annotation. Source: Compara cytosol Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Traceable author statement Ref.4. Source: ProtInc plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent DNA helicase activity Traceable author statement Ref.4. Source: ProtInc ATP-dependent RNA helicase activity Traceable author statement Ref.4. Source: ProtInc DNA binding Inferred from electronic annotation. Source: UniProtKB-KW endonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW mRNA binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.3

Chain

2 – 466

465

Ras GTPase-activating protein-binding protein 1

PRO_0000194798

Regions

Domain

11 – 133

123

NTF2

Domain

340 – 415

76

RRM

Compositional bias

144 – 225

82

Glu-rich

Compositional bias

430 – 461

32

Gly-rich

Sites

Site

2

1

Not acetylated

Amino acid modifications

Modified residue

143

1

Phosphothreonine Ref.16

Modified residue

149

1

Phosphoserine Ref.5 Ref.9 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.21 Ref.23

Modified residue

231

1

Phosphoserine Ref.3

Modified residue

232

1

Phosphoserine Ref.3 Ref.5 Ref.16 Ref.19 Ref.21 Ref.23

Modified residue

268

1

Phosphothreonine By similarity

Modified residue

373

1

Phosphoserine Ref.16 Ref.21

Modified residue

376

1

N6-acetyllysine Ref.20

Modified residue

435

1

Dimethylated arginine; alternate Ref.3

Modified residue

435

1

Omega-N-methylarginine; alternate Ref.3

Modified residue

460

1

Dimethylated arginine; alternate Ref.3

Modified residue

460

1

Omega-N-methylated arginine; alternate Ref.3

Experimental info

Mutagenesis

149

1

S → A: Cytoplasmic; no effect on stress granule assembly. Ref.5 Ref.7

Mutagenesis

149

1

S → E: Cytoplasmic and nuclear; no assembly of stress granules; no homo-oligomerization. Ref.5 Ref.7

Mutagenesis

232

1

S → A: Cytoplasmic. Partially nuclear; when associated with E-149. Ref.5

Mutagenesis

232

1

S → E: Cytoplasmic. Partially nuclear; when associated with E-149. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

466

Helix Strand Turn

Details...

Helix

8 – 25

18

Helix

27 – 33

7

Beta strand

34 – 41

8

Helix

57 – 67

11

Beta strand

74 – 84

11

Helix

86 – 88

3

Beta strand

90 – 99

10

Beta strand

106 – 116

11

Beta strand

118 – 120

3

Beta strand

124 – 133

10

Helix

134 – 136

3

Sequences

	Sequence		Length	Mass (Da)
	Q13283 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 0F9429D78E0C7F59	FASTA	466	52,164
	10 20 30 40 50 60 MVMEKPSPLL VGREFVRQYY TLLNQAPDML HRFYGKNSSY VHGGLDSNGK PADAVYGQKE 70 80 90 100 110 120 IHRKVMSQNF TNCHTKIRHV DAHATLNDGV VVQVMGLLSN NNQALRRFMQ TFVLAPEGSV 130 140 150 160 170 180 ANKFYVHNDI FRYQDEVFGG FVTEPQEESE EEVEEPEERQ QTPEVVPDDS GTFYDQAVVS 190 200 210 220 230 240 NDMEEHLEEP VAEPEPDPEP EPEQEPVSEI QEEKPEPVLE ETAPEDAQKS SSPAPADIAQ 250 260 270 280 290 300 TVQEDLRTFS WASVTSKNLP PSGAVPVTGI PPHVVKVPAS QPRPESKPES QIPPQRPQRD 310 320 330 340 350 360 QRVREQRINI PPQRGPRPIR EAGEQGDIEP RRMVRHPDSH QLFIGNLPHE VDKSELKDFF 370 380 390 400 410 420 QSYGNVVELR INSGGKLPNF GFVVFDDSEP VQKVLSNRPI MFRGEVRLNV EEKKTRAARE 430 440 450 460 GDRRDNRLRG PGGPRGGLGG GMRGPPRGGM VQKPGFGVGR GLAPRQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A Ras-GTPase-activating protein SH3-domain-binding protein." Parker F., Maurier F., Delumeau I., Duchesne M., Faucher D., Debussche L., Dugue A., Schweighoffer F., Tocque B. Mol. Cell. Biol. 16:2561-2569(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Prostate.
[3]	Bienvenut W.V., Heiserich L., Boulahbel H., Gottlieb E., Calvo F., Zebisch A., Lilla S., von Kriegsheim A., Lempens A., Kolch W. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-13; 18-32; 37-59; 65-76; 108-132; 230-276; 308-314; 321-331; 336-370; 377-403; 430-443 AND 448-465, CLEAVAGE OF INITIATOR METHIONINE, LACK OF N-TERMINAL ACETYLATION, METHYLATION AT ARG-435 AND ARG-460, PHOSPHORYLATION AT SER-231 AND SER-232, MASS SPECTROMETRY. Tissue: Cervix carcinoma, Colon carcinoma and Ovarian carcinoma.
[4]	"Human DNA helicase VIII: a DNA and RNA helicase corresponding to the G3BP protein, an element of the ras transduction pathway." Costa M., Ochem A., Staub A., Falaschi A. Nucleic Acids Res. 27:817-821(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 248-257; 336-353; 394-403 AND 444-463, FUNCTION AS A HELICASE.
[5]	"RasGAP-associated endoribonuclease G3Bp: selective RNA degradation and phosphorylation-dependent localization." Tourriere H., Gallouzi I.-E., Chebli K., Capony J.-P., Mouaikel J., van der Geer P., Tazi J. Mol. Cell. Biol. 21:7747-7760(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS AN ENDORIBONUCLEASE, PHOSPHORYLATION AT SER-149 AND SER-232, MUTAGENESIS OF SER-149 AND SER-232.
[6]	"Ras-GAP SH3 domain binding protein (G3BP) is a modulator of USP10, a novel human ubiquitin specific protease." Soncini C., Berdo I., Draetta G. Oncogene 20:3869-3879(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH USP10.
[7]	"The RasGAP-associated endoribonuclease G3BP assembles stress granules." Tourriere H., Chebli K., Zekri L., Courselaud B., Blanchard J.-M., Bertrand E., Tazi J. J. Cell Biol. 160:823-831(2003) [PubMed] [Europe PMC] [Abstract] Cited for: RECRUITMENT TO STRESS GRANULES, DIMERIZATION, SUBCELLULAR LOCATION, PHOSPHORYLATION, MUTAGENESIS OF SER-149.
[8]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[11]	"Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line." Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S. Electrophoresis 28:2027-2034(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Prostate cancer.
[12]	"Quantitative phosphoproteome profiling of Wnt3a-mediated signaling network: indicating the involvement of ribonucleoside-diphosphate reductase M2 subunit phosphorylation at residue serine 20 in canonical Wnt signal transduction." Tang L.-Y., Deng N., Wang L.-S., Dai J., Wang Z.-L., Jiang X.-S., Li S.-J., Li L., Sheng Q.-H., Wu D.-Q., Li L., Zeng R. Mol. Cell. Proteomics 6:1952-1967(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[13]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[14]	"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment." Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J. J. Proteome Res. 7:5167-5176(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: T-cell.
[15]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-143; SER-149; SER-232 AND SER-373, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[17]	"Large-scale phosphoproteome analysis of human liver tissue by enrichment and fractionation of phosphopeptides with strong anion exchange chromatography." Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., Zou H., Gu J. Proteomics 8:1346-1361(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149, MASS SPECTROMETRY. Tissue: Liver.
[18]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[20]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-376, MASS SPECTROMETRY.
[21]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149; SER-232 AND SER-373, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[22]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149 AND SER-232, MASS SPECTROMETRY.
[24]	"Crystal structure of the NTF2 domain of ras GTPase-activating protein-binding protein 1." Structural genomics consortium (SGC) Submitted (FEB-2011) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-139.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U32519 mRNA. Translation: AAB07787.1.
BC006997 mRNA. Translation: AAH06997.1.

IPI

IPI00012442.

RefSeq

NP_005745.1. NM_005754.2.
NP_938405.1. NM_198395.1.

UniGene

Hs.587054.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3Q90	X-ray	1.70	A/B	1-139	[»]

ProteinModelPortal

Q13283.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13283. 43 interactions.

MINT

MINT-5002789.

STRING

9606.ENSP00000348578.

PTM databases

PhosphoSite

Q13283.

Polymorphism databases

DMDM

14916572.

Proteomic databases

PaxDb

Q13283.

PeptideAtlas

Q13283.

PRIDE

Q13283.

Protocols and materials databases

DNASU

10146.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000356245; ENSP00000348578; ENSG00000145907.
ENST00000394123; ENSP00000377681; ENSG00000145907.

GeneID

10146.

KEGG

hsa:10146.

UCSC

uc003lum.3. human.

Organism-specific databases

CTD

10146.

GeneCards

GC05P151151.

HGNC

HGNC:30292. G3BP1.

HPA

HPA004052.

MIM

608431. gene.

neXtProt

NX_Q13283.

PharmGKB

PA162389105.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG324333.

HOGENOM

HOG000220838.

HOVERGEN

HBG007211.

InParanoid

Q13283.

OMA

VVSNDME.

OrthoDB

EOG4XWFZ0.

PhylomeDB

Q13283.

Gene expression databases

ArrayExpress

Q13283.

Bgee

Q13283.

CleanEx

HS_G3BP1.

Genevestigator

Q13283.

GermOnline

ENSG00000145907. Homo sapiens.

Family and domain databases

Gene3D

3.30.70.330. 1 hit.

InterPro

IPR002075. NTF2.
IPR018222. Nuclear_transport_factor_2_euk.
IPR012677. Nucleotide-bd_a/b_plait.
IPR000504. RRM_dom.
[Graphical view]

Pfam

PF02136. NTF2. 1 hit.
PF00076. RRM_1. 1 hit.
[Graphical view]

SMART

SM00360. RRM. 1 hit.
[Graphical view]

PROSITE

PS50177. NTF2_DOMAIN. 1 hit.
PS50102. RRM. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

G3BP1. human.

GenomeRNAi

10146.

NextBio

38391.

SOURCE

Search...

Entry information

Entry name

G3BP1_HUMAN

Accession

Primary (citable) accession number: Q13283

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 11, 2001
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 141 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.