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Eukaryotic initiation factor 4A-III

 
Known also as: ATP-dependent RNA helicase DDX48, ATP-dependent RNA helicase eIF4A-3, DEAD box protein 48, Eukaryotic initiation factor 4A-like NUK-34, Nuclear matrix protein 265

Known abbreviations: EIF4A3,DDX48, KIAA0111, eIF-4A-III, eIF4A-III, NMP 265, hNMP 265

 

FUNCTION:
 
ATP-dependent RNA helicase. Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Core components of the EJC, that remains bound to spliced mRNAs throughout all stages of mRNA metabolism, functions to mark the position of the exon-exon junction in the mature mRNA and thereby influences downstream processes of gene expression including mRNA splicing, nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Constitutes at least part of the platform anchoring other EJC proteins to spliced mRNAs. Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH/RBM8A heterodimer, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH/RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Shows higher affinity for single-stranded RNA in an ATP-bound core EJC complex than after the ATP is hydrolyzed. 
 
CATALYTIC ACTIVITY:
 
ATP + H2O = ADP + phosphate.
 
SUBUNIT STRUCTURE:
 
Part of the EJC core complex that contains CASC3, EIF4A3, MAGOH and RBM8A. Found in a mRNA splicing-dependent exon junction complex (EJC), at least composed of ACIN1, CASC3, EIF4A3, MAGOH, PNN, RBM8A, RNPS1, SAP18 and ALYREF/THOC4. Interacts with CASC3, MAGOH, NXF1, RBM8A and ALYREF/THOC4. Identified in the spliceosome C complex. May interact with NOM1. Interacts with POLDIP3. 
 
CELLULAR LOCALIZATION:
 
Nucleus. Nucleus speckle. Cytoplasm. Note: Nucleocytoplasmic shuttling protein. Travels to the cytoplasm as part of the exon junction complex (EJC) bound to mRNA. Detected in dendritic layer as well as the nuclear and cytoplasmic (somatic) compartments of neurons. Colocalizes with STAU1 and FMR1 in dendrites (By similarity). 
 
TISSUE SPECIFICITY:
 
Ubiquitously expressed



This protein can be a part of a given complexes:
NCBI GI number(s): 7661920
288915541
Species: Homo sapiens

Links to other databases:

Database ID Link
Uniprot P38919 P38919
BRENDA - -
KEGG hsa:9775 hsa:9775
PFAM: PF00270
PF00271
PF00270
PF00271
InterPro: IPR011545
IPR014001
IPR001650
IPR000629
IPR014014
IPR011545
IPR014001
IPR001650
IPR000629
IPR014014
CATH: - -
SCOP: - -
Solved crystal structures: 2XB2
3EX7
2J0U
2J0S
2J0Q
2HYI
2HXY
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]
[PDB] [details]


Protein sequence:
MATTATMATSGSARKRLLKEEDMTKVEFETSEEVDVTPTFDTMGLREDLL
RGIYAYGFEKPSAIQQRAIKQIIKGRDVIAQSQSGTGKTATFSISVLQCL
DIQVRETQALILAPTRELAVQIQKGLLALGDYMNVQCHACIGGTNVGEDI
RKLDYGQHVVAGTPGRVFDMIRRRSLRTRAIKMLVLDEADEMLNKGFKEQ
IYDVYRYLPPATQVVLISATLPHEILEMTNKFMTDPIRILVKRDELTLEG
IKQFFVAVEREEWKFDTLCDLYDTLTITQAVIFCNTKRKVDWLTEKMREA
NFTVSSMHGDMPQKERESIMKEFRSGASRVLISTDVWARGLDVPQVSLII
NYDLPNNRELYIHRIGRSGRYGRKGVAINFVKNDDIRILRDIEQYYSTQI
DEMPMNVADLI

Eukaryotic initiation factor 4A-III (Homo sapiens) is product of expression of EIF4A3 gene.

References:

Title Authors Journal Publication date (Issue) PubMed ID
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, K Genome Res 2004-10-01 (14) 15489334
Complete sequencing and characterization of 21,243 full-length human cDNAs. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K Nat Genet 2004-02-01 (36) 14702039
Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis. Jurica MS, Licklider LJ, Gygi SR, Grigorieff N, Moore MJ RNA 2002-04-01 (8) 11991638
Exon-junction complex components specify distinct routes of nonsense-mediated mRNA decay with differential cofactor requirements. Gehring NH, Kunz JB, Neu-Yilik G, Breit S, Viegas MH, Hentze MW, Kulozik AE Mol Cell 2005-10-07 (20) 16209946
Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S Anal Chem 2009-06-01 (81) 19413330
Initial characterization of the human central proteome. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J BMC Syst Biol 2011-01-01 (5) 21269460
DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK Nature 2006-04-20 (440) 16625196
Lysine acetylation targets protein complexes and co-regulates major cellular functions. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M Science 2009-08-14 (325) 19608861
A quantitative atlas of mitotic phosphorylation. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP Proc Natl Acad Sci U S A 2008-08-05 (105) 18669648
Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M Mol Cell 2008-08-08 (31) 18691976
Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd J Proteome Res 2008-03-01 (7) 18220336
SKAR links pre-mRNA splicing to mTOR/S6K1-mediated enhanced translation efficiency of spliced mRNAs. Ma XM, Yoon SO, Richardson CJ, Julich K, Blenis J Cell 2008-04-18 (133) 18423201
Biochemical analysis of the EJC reveals two new factors and a stable tetrameric protein core. Tange TO, Shibuya T, Jurica MS, Moore MJ RNA 2005-12-01 (11) 16314458
eIF4A3 is a novel component of the exon junction complex. Chan CC, Dostie J, Diem MD, Feng W, Mann M, Rappsilber J, Dreyfuss G RNA 2004-01-01 (10) 14730019
Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Wang B, Malik R, Nigg EA, Korner R Anal Chem 2008-12-15 (80) 19007248
Prediction of the coding sequences of unidentified human genes. III. The coding sequences of 40 new genes (KIAA0081-KIAA0120) deduced by analysis of cDNA clones from human cell line KG-1. Nagase T, Miyajima N, Tanaka A, Sazuka T, Seki N, Sato S, Tabata S, Ishikawa K, Kawarabayasi Y, Kotani H, et al. DNA Res 1995-01-01 (2) 7788527
A human common nuclear matrix protein homologous to eukaryotic translation initiation factor 4A. Holzmann K, Gerner C, Poltl A, Schafer R, Obrist P, Ensinger C, Grimm R, Sauermann G Biochem Biophys Res Commun 2000-02-07 (267) 10623621
eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decay. Shibuya T, Tange TO, Sonenberg N, Moore MJ Nat Struct Mol Biol 2004-04-01 (11) 15034551
Identification of NOM1, a nucleolar, eIF4A binding protein encoded within the chromosome 7q36 breakpoint region targeted in cases of pediatric acute myeloid leukemia. Simmons HM, Ruis BL, Kapoor M, Hudacek AW, Conklin KF Gene 2005-01-28 (347) 15715967
The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity. Ballut L, Marchadier B, Baguet A, Tomasetto C, Seraphin B, Le Hir H Nat Struct Mol Biol 2005-10-01 (12) 16170325
Mutational analysis of human eIF4AIII identifies regions necessary for exon junction complex formation and nonsense-mediated mRNA decay. Shibuya T, Tange TO, Stroupe ME, Moore MJ RNA 2006-03-01 (12) 16495234
MLN51 stimulates the RNA-helicase activity of eIF4AIII. Noble CG, Song H PLoS One 2007-01-01 (2) 17375189
Exon junction complex enhances translation of spliced mRNAs at multiple steps. Lee HC, Choe J, Chi SG, Kim YK Biochem Biophys Res Commun 2009-07-03 (384) 19409878
Large-scale proteomics analysis of the human kinome. Oppermann FS, Gnad F, Olsen JV, Hornberger R, Greff Z, Keri G, Mann M, Daub H Mol Cell Proteomics 2009-07-01 (8) 19369195
The crystal structure of the exon junction complex reveals how it maintains a stable grip on mRNA. Bono F, Ebert J, Lorentzen E, Conti E Cell 2006-08-25 (126) 16923391
Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA. Andersen CB, Ballut L, Johansen JS, Chamieh H, Nielsen KH, Oliveira CL, Pedersen JS, Seraphin B, Le Hir H, Andersen GR Science 2006-09-01 (313) 16931718
Mechanism of ATP turnover inhibition in the EJC. Nielsen KH, Chamieh H, Andersen CB, Fredslund F, Hamborg K, Le Hir H, Andersen GR RNA 2009-02-01 (15) 19033377



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Last modification of this entry: Sept. 25, 2012.

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