ID:IF4A3_HUMAN DESCRIPTION: RecName: Full=Eukaryotic initiation factor 4A-III; Short=eIF-4A-III; Short=eIF4A-III; EC=3.6.4.13; AltName: Full=ATP-dependent RNA helicase DDX48; AltName: Full=ATP-dependent RNA helicase eIF4A-3; AltName: Full=DEAD box protein 48; AltName: Full=Eukaryotic initiation factor 4A-like NUK-34; AltName: Full=Eukaryotic translation initiation factor 4A isoform 3; AltName: Full=Nuclear matrix protein 265; Short=NMP 265; Short=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 + H(2)O = ADP + phosphate. SUBUNIT: 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. INTERACTION: O15234:CASC3; NbExp=6; IntAct=EBI-299104, EBI-299118; P61326:MAGOH; NbExp=9; IntAct=EBI-299104, EBI-299134; Q9Y5S9:RBM8A; NbExp=8; IntAct=EBI-299104, EBI-447231; Q9BZI7:UPF3B; NbExp=4; IntAct=EBI-299104, EBI-372780; 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 (By similarity). TISSUE SPECIFICITY: Ubiquitously expressed. SIMILARITY: Belongs to the DEAD box helicase family. eIF4A subfamily. SIMILARITY: Contains 1 helicase ATP-binding domain. SIMILARITY: Contains 1 helicase C-terminal domain. SEQUENCE CAUTION: Sequence=BAA04879.2; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P38919
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Protein P38919 (Reactome details) participates in the following event(s):
R-HSA-72130 Formation of an intermediate Spliceosomal C (Bact) complex R-HSA-429955 CCR4-NOT complex deadenylates mRNA R-HSA-429992 PARN deadenylates mRNA R-HSA-72143 Lariat Formation and 5'-Splice Site Cleavage R-HSA-72139 Formation of the active Spliceosomal C (B*) complex R-HSA-156661 Formation of Exon Junction Complex R-HSA-430021 PAN2-PAN3 complex partially deadenylates mRNA R-HSA-8941312 ZCCHC6, ZCCHC11 are mRNA uridyltransferases R-HSA-1678842 Competitive inhibition of translation initiation by ISGylated 4EHP R-HSA-927832 UPF1 binds an mRNP with a termination codon preceding an Exon Junction Complex R-HSA-75098 mRNP complex dissociates from cytosolic face of NPC R-HSA-8849157 TREX complex binds spliced, capped mRNA:CBC:EJC cotranscriptionally R-HSA-72185 mRNA polyadenylation R-HSA-72180 Cleavage of mRNA at the 3'-end R-HSA-75096 Docking of the TAP:EJC Complex with the NPC R-HSA-159101 NXF1:NXT1 (TAP:p15) binds capped mRNA:CBC:EJC:TREX (minus DDX39B) R-HSA-927889 SMG1 phosphorylates UPF1 (enhanced by Exon Junction Complex) R-HSA-72163 mRNA Splicing - Major Pathway R-HSA-429947 Deadenylation of mRNA R-HSA-72172 mRNA Splicing R-HSA-9010553 Regulation of expression of SLITs and ROBOs R-HSA-1169408 ISG15 antiviral mechanism R-HSA-429914 Deadenylation-dependent mRNA decay R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) R-HSA-376176 Signaling by ROBO receptors R-HSA-159236 Transport of Mature mRNA derived from an Intron-Containing Transcript R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes R-HSA-8953854 Metabolism of RNA R-HSA-72187 mRNA 3'-end processing R-HSA-109688 Cleavage of Growing Transcript in the Termination Region R-HSA-927802 Nonsense-Mediated Decay (NMD) R-HSA-422475 Axon guidance R-HSA-72202 Transport of Mature Transcript to Cytoplasm R-HSA-913531 Interferon Signaling R-HSA-73856 RNA Polymerase II Transcription Termination R-HSA-1266738 Developmental Biology R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-73857 RNA Polymerase II Transcription R-HSA-168256 Immune System R-HSA-74160 Gene expression (Transcription)