InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: EIF4A3

Summary

InnateDB Protein

IDBP-71464.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

EIF4A3

Protein Name

eukaryotic translation initiation factor 4A3

Synonyms

DDX48; eIF4AIII; MUK34; NMP265; NUK34; RCPS;

Species

Homo sapiens

Ensembl Protein

ENSP00000269349

InnateDB Gene

IDBG-71462 (EIF4A3)

Protein Structure

UniProt Annotation

Function

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 such as Bcl-X(S); the function is different from the established EJC assembly. Involved in craniofacial development. {ECO:0000269PubMed:15034551, ECO:0000269PubMed:16170325, ECO:0000269PubMed:16209946, ECO:0000269PubMed:17375189, ECO:0000269PubMed:19409878, ECO:0000269PubMed:22203037, ECO:0000269PubMed:24360810}.

Subcellular Localization

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). {ECO:0000250}.

Disease Associations

Richieri-Costa-Pereira syndrome (RCPS) [MIM:268305]: A syndrome characterized by a unique pattern of anomalies consisting of microstomia, micrognathia, abnormal fusion of mandible, cleft palate/Robin sequence, absence of central lower incisors, minor ears anomalies, hypoplastic first ray, abnormal tibiae, hypoplastic halluces, and clubfeet. Learning disability is also a common finding. {ECO:0000269PubMed:24360810}. Note=The disease is caused by mutations affecting the gene represented in this entry. EIF4A3 mutations resulting in Richieri-Costa-Pereira syndrome include a repeat expansion of 18 or 20 nucleotides in the 5' untranslated region. Affected individuals have 14 to 16 repeats, while healthy individuals have 3 to 12 repeats (PubMed:24360810). {ECO:0000269PubMed:24360810}.

Tissue Specificity

Ubiquitously expressed. {ECO:0000269PubMed:10623621}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 272 experimentally validated interaction(s) in this database.

Experimentally validated
Total	272 [view]
Protein-Protein	272 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003676	nucleic acid binding
GO:0003729	mRNA binding
GO:0004004	ATP-dependent RNA helicase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008143	poly(A) binding
GO:0044822	poly(A) RNA binding

Biological Process

GO:0000184	nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
GO:0000288	nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
GO:0000289	nuclear-transcribed mRNA poly(A) tail shortening
GO:0000398	mRNA splicing, via spliceosome
GO:0006200	ATP catabolic process
GO:0006364	rRNA processing
GO:0010467	gene expression
GO:0016070	RNA metabolic process
GO:0016071	mRNA metabolic process
GO:0017148	negative regulation of translation
GO:0019221	cytokine-mediated signaling pathway
GO:0045727	positive regulation of translation
GO:0048701	embryonic cranial skeleton morphogenesis
GO:0051028	mRNA transport

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005829	cytosol
GO:0016020	membrane
GO:0016607	nuclear speck
GO:0035145	exon-exon junction complex
GO:0071013	catalytic step 2 spliceosome

Protein Structure and Domains

PDB ID

InterPro

IPR001650 Helicase, C-terminal
IPR011545 DEAD/DEAH box helicase domain
IPR014001 Helicase, superfamily 1/2, ATP-binding domain
IPR014014 RNA helicase, DEAD-box type, Q motif
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM

PF00271
PF00270

PRINTS

PIRSF

SMART

SM00490
SM00487

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P38919