UniProt Accession

 IF4A3_HUMAN; P38919; Q15033; Q6IBQ2; Q96A18 

Genbank Protein ID

 X79538; D21853; AK290608; CR456750; AC087741; CH471099; BC003662; BC004386; BC011151 

Genbank Nucleotide ID

 CAA56074.1; BAA04879.2; BAF83297.1; CAG33031.1; EAW89584.1; AAH03662.1; AAH04386.1; AAH11151.1 

Protein Name

 Eukaryotic initiation factor 4A-III 

Protein Synonyms/Alias

 eIF-4A-III; eIF4A-III; ATP-dependent RNA helicase DDX48; ATP-dependent RNA helicase eIF4A-3; DEAD box protein 48; Eukaryotic initiation factor 4A-like NUK-34; Eukaryotic translation initiation factor 4A isoform 3; Nuclear matrix protein 265; NMP 265; hNMP 265; Eukaryotic initiation factor 4A-III, N-terminally processed 

Gene Name

 EIF4A3 

Gene Synonyms/Alias

 DDX48; KIAA0111 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
60	IYAYGFEKPSAIQQR	acetylation	[1]
60	IYAYGFEKPSAIQQR	ubiquitination	[2, 3, 4, 5, 6]
70	AIQQRAIKQIIKGRD	methylation	[7]
70	AIQQRAIKQIIKGRD	ubiquitination	[6]
152	NVGEDIRKLDYGQHV	ubiquitination	[4, 6, 8]
182	SLRTRAIKMLVLDEA	ubiquitination	[4, 6]
195	EADEMLNKGFKEQIY	ubiquitination	[4]
198	EMLNKGFKEQIYDVY	ubiquitination	[3, 6]
264	AVEREEWKFDTLCDL	ubiquitination	[9]
287	AVIFCNTKRKVDWLT	ubiquitination	[9]
289	IFCNTKRKVDWLTEK	ubiquitination	[4, 6, 10]
296	KVDWLTEKMREANFT	acetylation	[1]
296	KVDWLTEKMREANFT	ubiquitination	[4, 6, 9]
314	MHGDMPQKERESIMK	ubiquitination	[3, 6]
321	KERESIMKEFRSGAS	acetylation	[1]
321	KERESIMKEFRSGAS	ubiquitination	[3, 6, 8, 9]
374	RSGRYGRKGVAINFV	methylation	[7]
374	RSGRYGRKGVAINFV	ubiquitination	[4, 6]
382	GVAINFVKNDDIRIL	acetylation	[8]
382	GVAINFVKNDDIRIL	ubiquitination	[3, 4, 8]

Reference

 [1] 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 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] Mass spectrometric analysis of lysine ubiquitylation reveals promiscuity at site level.
 Danielsen JM, Sylvestersen KB, Bekker-Jensen S, Szklarczyk D, Poulsen JW, Horn H, Jensen LJ, Mailand N, Nielsen ML.
 Mol Cell Proteomics. 2011 Mar;10(3):M110.003590. [PMID: 21139048]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [5] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [6] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [7] Mass spectrometry-based identification and characterisation of lysine and arginine methylation in the human proteome.
 Bremang M, Cuomo A, Agresta AM, Stugiewicz M, Spadotto V, Bonaldi T.
 Mol Biosyst. 2013 Jul 30;9(9):2231-47. [PMID: 23748837]
 [8] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [9] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [10] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 69 239 Helicase ATP-binding.
 DOMAIN 250 411 Helicase C-terminal.
 NP_BIND 85 90 ATP.
 NP_BIND 367 371 ATP.
 MOTIF 38 66 Q motif.
 MOTIF 187 190 DEAD box.
 BINDING 60 60 ATP; via carbonyl oxygen.
 BINDING 65 65 ATP.
 BINDING 342 342 ATP.
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 2 2 N-acetylalanine; in Eukaryotic initiation
 MOD_RES 12 12 Phosphoserine.
 MOD_RES 163 163 Phosphothreonine.
 MOD_RES 296 296 N6-acetyllysine.
 MOD_RES 321 321 N6-acetyllysine.  

Keyword

 3D-structure; Acetylation; ATP-binding; Complete proteome; Cytoplasm; Direct protein sequencing; Helicase; Hydrolase; mRNA processing; mRNA splicing; mRNA transport; Nonsense-mediated mRNA decay; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; RNA-binding; rRNA processing; Spliceosome; Translation regulation; Transport. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 411 AA 

Protein Sequence

Gene Ontology

 GO:0071013; C:catalytic step 2 spliceosome; IDA:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0035145; C:exon-exon junction complex; IDA:UniProtKB.
 GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IDA:HGNC.
 GO:0004004; F:ATP-dependent RNA helicase activity; IDA:HGNC.
 GO:0008143; F:poly(A) RNA binding; IDA:HGNC.
 GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome.
 GO:0000398; P:mRNA splicing, via spliceosome; IC:UniProtKB.
 GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
 GO:0017148; P:negative regulation of translation; IDA:HGNC.
 GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IMP:UniProtKB.
 GO:0000289; P:nuclear-transcribed mRNA poly(A) tail shortening; TAS:Reactome.
 GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
 GO:0006364; P:rRNA processing; IEA:UniProtKB-KW. 

Interpro

 IPR011545; DNA/RNA_helicase_DEAD/DEAH_N.
 IPR014001; Helicase_ATP-bd.
 IPR001650; Helicase_C.
 IPR027417; P-loop_NTPase.
 IPR000629; RNA-helicase_DEAD-box_CS.
 IPR014014; RNA_helicase_DEAD_Q_motif. 

Pfam

 PF00270; DEAD
 PF00271; Helicase_C 

SMART

 SM00487; DEXDc
 SM00490; HELICc 

PROSITE

 PS00039; DEAD_ATP_HELICASE
 PS51192; HELICASE_ATP_BIND_1
 PS51194; HELICASE_CTER
 PS51195; Q_MOTIF 

PRINTS