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Protein

Eukaryotic initiation factor 4A-III

Gene

Eif4a3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

ATP-dependent RNA helicase. Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). 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. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms; the function is different from the established EJC assembly (By similarity). Involved in craniofacial development (By similarity).By similarity

Catalytic activityi

ATP + H2O = ADP + phosphate.

Enzyme regulationi

The ATPase activity is increased some 4-fold in the presence of RNA.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei60ATP; via carbonyl oxygenBy similarity1
Binding sitei65ATPBy similarity1
Binding sitei342ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi85 – 90ATPPROSITE-ProRule annotation6
Nucleotide bindingi367 – 371ATPPROSITE-ProRule annotation5

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • ATP-dependent RNA helicase activity Source: GO_Central
  • poly(A) binding Source: Ensembl
  • ribonucleoprotein complex binding Source: RGD
  • RNA stem-loop binding Source: RGD
  • selenocysteine insertion sequence binding Source: RGD

GO - Biological processi

  • associative learning Source: RGD
  • cellular response to brain-derived neurotrophic factor stimulus Source: RGD
  • cellular response to selenite ion Source: RGD
  • embryonic cranial skeleton morphogenesis Source: UniProtKB
  • exploration behavior Source: RGD
  • mRNA processing Source: UniProtKB-KW
  • mRNA transport Source: UniProtKB-KW
  • negative regulation of excitatory postsynaptic potential Source: RGD
  • negative regulation of gene expression Source: RGD
  • negative regulation of selenocysteine incorporation Source: RGD
  • negative regulation of selenocysteine insertion sequence binding Source: RGD
  • nuclear-transcribed mRNA catabolic process, nonsense-mediated decay Source: UniProtKB-KW
  • positive regulation of mRNA splicing, via spliceosome Source: Ensembl
  • positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • positive regulation of translation Source: Ensembl
  • regulation of alternative mRNA splicing, via spliceosome Source: UniProtKB
  • regulation of mRNA binding Source: RGD
  • response to organic cyclic compound Source: RGD
  • RNA secondary structure unwinding Source: GO_Central
  • RNA splicing Source: GO_Central
  • rRNA processing Source: UniProtKB-KW

Keywordsi

Molecular functionHelicase, Hydrolase, RNA-binding
Biological processmRNA processing, mRNA splicing, mRNA transport, Nonsense-mediated mRNA decay, rRNA processing, Translation regulation, Transport
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-RNO-109688. Cleavage of Growing Transcript in the Termination Region.
R-RNO-1169408. ISG15 antiviral mechanism.
R-RNO-159236. Transport of Mature mRNA derived from an Intron-Containing Transcript.
R-RNO-429947. Deadenylation of mRNA.
R-RNO-72163. mRNA Splicing - Major Pathway.
R-RNO-72187. mRNA 3'-end processing.
R-RNO-975957. Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).

Names & Taxonomyi

Protein namesi
Recommended name:
Eukaryotic initiation factor 4A-III (EC:3.6.4.13)
Short name:
eIF-4A-III
Short name:
eIF4A-III
Alternative name(s):
ATP-dependent RNA helicase DDX48
ATP-dependent RNA helicase eIF4A-3
DEAD box protein 48
Eukaryotic translation initiation factor 4A isoform 3
Cleaved into the following chain:
Gene namesi
Name:Eif4a3
Synonyms:Ddx48
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 10

Organism-specific databases

RGDi1591139. Eif4a3.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus, Spliceosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00004232711 – 411Eukaryotic initiation factor 4A-IIIAdd BLAST411
Initiator methionineiRemoved; alternateBy similarity
ChainiPRO_00003785552 – 411Eukaryotic initiation factor 4A-III, N-terminally processedAdd BLAST410

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei2N-acetylalanine; in Eukaryotic initiation factor 4A-III, N-terminally processedBy similarity1
Modified residuei10PhosphoserineBy similarity1
Modified residuei12PhosphoserineBy similarity1
Cross-linki19Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei124N6-acetyllysineBy similarity1
Cross-linki152Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei163PhosphothreonineBy similarity1
Modified residuei198N6-acetyllysineBy similarity1
Modified residuei296N6-acetyllysineBy similarity1
Cross-linki314Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei321N6-acetyllysineBy similarity1
Cross-linki374Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Cross-linki382Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ3B8Q2.
PRIDEiQ3B8Q2.

PTM databases

iPTMnetiQ3B8Q2.
PhosphoSitePlusiQ3B8Q2.

Expressioni

Tissue specificityi

Expressed in the CA1 field and dentate gyrus of the hippocampus (at protein level).

Gene expression databases

BgeeiENSRNOG00000045791.
GenevisibleiQ3B8Q2. RN.

Interactioni

Subunit structurei

Part of the mRNA splicing-dependent exon junction complex (EJC) complex; the core complex contains CASC3, EIF4A3, MAGOH and RBM8A. Interacts with CASC3, MAGOH, NXF1, RBM8A and ALYREF/THOC4. Identified in the spliceosome C complex. May interact with NOM1. Interacts with POLDIP3. Interacts with CWC22 and PRPF19 in an RNA-independent manner. Direct interaction with CWC22 is mediated by the helicase C-terminal domain. Full interaction with CWC22 occurs only when EIF4A3 is not part of the EJC and prevents EIF4A3 binding to RNA. Interacts with NCBP3 (By similarity).By similarity

Protein-protein interaction databases

IntActiQ3B8Q2. 1 interactor.
STRINGi10116.ENSRNOP00000066302.

Structurei

3D structure databases

ProteinModelPortaliQ3B8Q2.
SMRiQ3B8Q2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini69 – 239Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST171
Domaini250 – 411Helicase C-terminalPROSITE-ProRule annotationAdd BLAST162

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi38 – 66Q motifAdd BLAST29
Motifi187 – 190DEAD box4

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0327. Eukaryota.
COG0513. LUCA.
GeneTreeiENSGT00530000062880.
InParanoidiQ3B8Q2.
KOiK13025.
OMAiDEMPVNA.
OrthoDBiEOG091G07OI.
PhylomeDBiQ3B8Q2.

Family and domain databases

CDDicd00079. HELICc. 1 hit.
InterProiView protein in InterPro
IPR011545. DEAD/DEAH_box_helicase_dom.
IPR014001. Helicase_ATP-bd.
IPR001650. Helicase_C.
IPR027417. P-loop_NTPase.
IPR000629. RNA-helicase_DEAD-box_CS.
IPR014014. RNA_helicase_DEAD_Q_motif.
PfamiView protein in Pfam
PF00270. DEAD. 1 hit.
PF00271. Helicase_C. 1 hit.
SMARTiView protein in SMART
SM00487. DEXDc. 1 hit.
SM00490. HELICc. 1 hit.
SUPFAMiSSF52540. SSF52540. 1 hit.
PROSITEiView protein in PROSITE
PS00039. DEAD_ATP_HELICASE. 1 hit.
PS51192. HELICASE_ATP_BIND_1. 1 hit.
PS51194. HELICASE_CTER. 1 hit.
PS51195. Q_MOTIF. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q3B8Q2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAATATMATS GSARKRLLKE EDMTKVEFET SEEVDVTPTF DTMGLREDLL
60 70 80 90 100
RGIYAYGFEK PSAIQQRAIK QIIKGRDVIA QSQSGTGKTA TFSISVLQCL
110 120 130 140 150
DIQVRETQAL ILAPTRELAV QIQKGLLALG DYMNVQCHAC IGGTNVGEDI
160 170 180 190 200
RKLDYGQHVV AGTPGRVFDM IRRRSLRTRA IKMLVLDEAD EMLNKGFKEQ
210 220 230 240 250
IYDVYRYLPP ATQVVLISAT LPHEILEMTN KFMTDPIRIL VKRDELTLEG
260 270 280 290 300
IKQFFVAVER EEWKFDTLCD LYDTLTITQA VIFCNTKRKV DWLTEKMREA
310 320 330 340 350
NFTVSSMHGD MPQKERESIM KEFRSGASRV LISTDVWARG LDVPQVSLII
360 370 380 390 400
NYDLPNNREL YIHRIGRSGR YGRKGVAINF VKNDDIRILR DIEQYYSTQI
410
DEMPMNVADL I
Length:411
Mass (Da):46,841
Last modified:November 22, 2005 - v1
Checksum:i987DAF10824DEC4D
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC105875 mRNA. Translation: AAI05876.1.
CH473948 Genomic DNA. Translation: EDM06783.1.
RefSeqiNP_001093628.1. NM_001100158.2.
UniGeneiRn.202617.

Genome annotation databases

EnsembliENSRNOT00000073140; ENSRNOP00000066302; ENSRNOG00000045791.
GeneIDi688288.
KEGGirno:688288.

Similar proteinsi

Entry informationi

Entry nameiIF4A3_RAT
AccessioniPrimary (citable) accession number: Q3B8Q2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 7, 2009
Last sequence update: November 22, 2005
Last modified: October 25, 2017
This is version 93 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Translation initiation factors
    List of translation initiation factor entries
  2. SIMILARITY comments
    Index of protein domains and families