Q91VC3 · IF4A3_MOUSE

  • Protein
    Eukaryotic initiation factor 4A-III
  • Gene
    Eif4a3
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

ATP-dependent RNA helicase. Involved in pre-mRNA splicing as component of the spliceosome. 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. Involved in craniofacial development.

Catalytic activity

Activity regulation

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

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site60ATP (UniProtKB | ChEBI)
Binding site65ATP (UniProtKB | ChEBI)
Binding site85-90ATP (UniProtKB | ChEBI)
Binding site342ATP (UniProtKB | ChEBI)
Binding site367-371ATP (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentcatalytic step 2 spliceosome
Cellular Componentcytoplasm
Cellular Componentdendrite
Cellular Componentexon-exon junction complex
Cellular Componentglutamatergic synapse
Cellular Componentneuronal cell body
Cellular Componentnuclear speck
Cellular Componentnucleolus
Cellular Componentnucleus
Cellular Componentpostsynapse
Cellular Componentribonucleoprotein complex
Cellular ComponentU2-type catalytic step 1 spliceosome
Molecular FunctionATP binding
Molecular FunctionATP hydrolysis activity
Molecular FunctionmRNA binding
Molecular Functionribonucleoprotein complex binding
Molecular FunctionRNA helicase activity
Molecular FunctionRNA stem-loop binding
Molecular Functionselenocysteine insertion sequence binding
Biological Processembryonic cranial skeleton morphogenesis
Biological ProcessmRNA export from nucleus
Biological ProcessmRNA splicing, via spliceosome
Biological Processnegative regulation of excitatory postsynaptic potential
Biological Processnegative regulation of gene expression
Biological Processnegative regulation of selenocysteine incorporation
Biological Processnuclear-transcribed mRNA catabolic process, nonsense-mediated decay
Biological Processpositive regulation of mRNA splicing, via spliceosome
Biological Processpositive regulation of transcription by RNA polymerase II
Biological Processregulation of alternative mRNA splicing, via spliceosome
Biological Processregulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
Biological Processregulation of translation at postsynapse, modulating synaptic transmission
Biological ProcessrRNA processing

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

Gene names

    • Name
      Eif4a3
    • Synonyms
      Ddx48

Organism names

  • Taxonomic identifier
  • Strains
    • BALB/cJ
    • C57BL/6J
    • DBA/2J
    • NOD
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q91VC3
  • Secondary accessions
    • B2RY38
    • Q3TEZ8
    • Q3UD29
    • Q8BVY3

Proteomes

Organism-specific databases

Subcellular Location

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.

Keywords

Phenotypes & Variants

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 21 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain, cross-link.

TypeIDPosition(s)Description
Initiator methionine1Removed; alternate
Modified residue1N-acetylmethionine
ChainPRO_00004232691-411Eukaryotic initiation factor 4A-III
Modified residue2N-acetylalanine; in Eukaryotic initiation factor 4A-III, N-terminally processed
ChainPRO_00000549442-411Eukaryotic initiation factor 4A-III, N-terminally processed
Modified residue10Phosphoserine
Modified residue12Phosphoserine
Cross-link19Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Modified residue124N6-acetyllysine
Cross-link152Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Modified residue163Phosphothreonine
Modified residue198N6-acetyllysine
Modified residue296N6-acetyllysine
Cross-link314Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Modified residue321N6-acetyllysine
Cross-link374Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)
Cross-link382Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)

Keywords

Proteomic databases

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Identified in the spliceosome C complex. Core component of the mRNA splicing-dependent exon junction complex (EJC); the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A. Interacts with CASC3, MAGOH, NXF1, RBM8A and ALYREF/THOC4. Component of the ALYREF/THOC4-EJC-RNA complex; in the complex interacts with MAGOH, RBM8A and THOC4 (via the WXHD motif); these interactions are likely specific to RNA-bound EJC (By similarity).
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. Identified in a complex composed of the EJC core, UPF3B and UPF2. The EJC core can also interact with UPF3A (in vitro). Interacts with NCBP3 (By similarity).
Interacts with NRDE2 (By similarity).
Interacts with DHX34; the interaction is RNA-independent (By similarity).
View interactors in UniProtKB
View CPX-635 in Complex Portal

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for motif, domain.

TypeIDPosition(s)Description
Motif38-66Q motif
Domain69-239Helicase ATP-binding
Motif187-190DEAD box
Domain250-411Helicase C-terminal

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    411
  • Mass (Da)
    46,840
  • Last updated
    2007-01-23 v3
  • Checksum
    2639EA64F5332A54
MAANATMATSGSARKRLLKEEDMTKVEFETSEEVDVTPTFDTMGLREDLLRGIYAYGFEKPSAIQQRAIKQIIKGRDVIAQSQSGTGKTATFSVSVLQCLDIQVRETQALILAPTRELAVQIQKGLLALGDYMNVQCHACIGGTNVGEDIRKLDYGQHVVAGTPGRVFDMIRRRSLRTRAIKMLVLDEADEMLNKGFKEQIYDVYRYLPPATQVVLISATLPHEILEMTNKFMTDPIRILVKRDELTLEGIKQFFVAVEREEWKFDTLCDLYDTLTITQAVIFCNTKRKVDWLTEKMREANFTVSSMHGDMPQKERESIMKEFRSGASRVLISTDVWARGLDVPQVSLIINYDLPNNRELYIHRIGRSGRYGRKGVAINFVKNDDIRILRDIEQYYSTQIDEMPMNVADLI

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A2AFK7A2AFK7_MOUSEEif4a3299

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict3-4in Ref. 4; AAI58084
Sequence conflict6in Ref. 4; AAI58084
Sequence conflict11in Ref. 4; AAI58084
Sequence conflict22in Ref. 4; AAI58084
Sequence conflict36in Ref. 4; AAI58084
Sequence conflict38in Ref. 4; AAI58084
Sequence conflict47in Ref. 1; BAC36054
Sequence conflict94in Ref. 4; AAI58084
Sequence conflict177in Ref. 4; AAI58084
Sequence conflict200in Ref. 1; BAE41100
Sequence conflict235in Ref. 4; AAI58084
Sequence conflict285in Ref. 4; AAI58084
Sequence conflict407in Ref. 4; AAI58084

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AK075920
EMBL· GenBank· DDBJ
BAC36054.1
EMBL· GenBank· DDBJ
mRNA
AK146385
EMBL· GenBank· DDBJ
BAE27130.1
EMBL· GenBank· DDBJ
mRNA
AK150277
EMBL· GenBank· DDBJ
BAE29433.1
EMBL· GenBank· DDBJ
mRNA
AK152824
EMBL· GenBank· DDBJ
BAE31525.1
EMBL· GenBank· DDBJ
mRNA
AK153359
EMBL· GenBank· DDBJ
BAE31931.1
EMBL· GenBank· DDBJ
mRNA
AK157855
EMBL· GenBank· DDBJ
BAE34233.1
EMBL· GenBank· DDBJ
mRNA
AK167107
EMBL· GenBank· DDBJ
BAE39256.1
EMBL· GenBank· DDBJ
mRNA
AK168319
EMBL· GenBank· DDBJ
BAE40258.1
EMBL· GenBank· DDBJ
mRNA
AK169350
EMBL· GenBank· DDBJ
BAE41100.1
EMBL· GenBank· DDBJ
mRNA
AK169815
EMBL· GenBank· DDBJ
BAE41387.1
EMBL· GenBank· DDBJ
mRNA
AL645911
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL672140
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
CH466558
EMBL· GenBank· DDBJ
EDL34693.1
EMBL· GenBank· DDBJ
Genomic DNA
BC008132
EMBL· GenBank· DDBJ
AAH08132.1
EMBL· GenBank· DDBJ
mRNA
BC012862
EMBL· GenBank· DDBJ
AAH12862.1
EMBL· GenBank· DDBJ
mRNA
BC158083
EMBL· GenBank· DDBJ
AAI58084.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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