lmmol · Proteins

Eukaryotic initiation factor 4A-III

UniProt P38919 Organism Homo sapiens Gene DDX48, EIF4A3, KIAA0111 EC 3.6.4.13

Also known as: DDX48, EIF4A3, KIAA0111

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 such as Bcl-X(S); the function is different from the established EJC assembly. Involved in craniofacial development.

Classification

Family (Pfam)
PF00270 DEAD, PF00271 Helicase_C
InterPro
DEAD/DEAH_box_helicase_dom, Helicase_ATP-bd, Helicase_C-like, P-loop_NTPase, RNA-helicase_DEAD-box_CS, RNA_helicase_DEAD_Q_motif
Functional cluster
Serine/Threonine Protein Kinases

Experimental structures · PDB · 22

A predicted model is available from AlphaFold.

Gene Ontology · 39

Disease associations

Neighborhood · nearest proteins

DDX48Ddx48DDX48DDX48CWC22ddx48CASC3
Nearest neighbours of Eukaryotic initiation factor 4A-III: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 50 cited papers

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