{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P38919","secondaryAccessions":["Q15033","Q6IBQ2","Q96A18"],"uniProtkbId":"IF4A3_HUMAN","entryAudit":{"firstPublicDate":"1995-02-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-01-23","entryVersion":260,"sequenceVersion":4},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Eukaryotic initiation factor 4A-III"},"shortNames":[{"value":"eIF-4A-III"},{"value":"eIF4A-III"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16170325"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17375189"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22961380"}],"value":"3.6.4.13"}]},"alternativeNames":[{"fullName":{"value":"ATP-dependent RNA helicase DDX48"}},{"fullName":{"value":"ATP-dependent RNA helicase eIF4A-3"}},{"fullName":{"value":"DEAD box protein 48"}},{"fullName":{"value":"Eukaryotic initiation factor 4A-like NUK-34"}},{"fullName":{"value":"Eukaryotic translation initiation factor 4A isoform 3"}},{"fullName":{"value":"Nuclear matrix protein 265"},"shortNames":[{"value":"NMP 265"},{"value":"hNMP 265"}]}],"contains":[{"recommendedName":{"fullName":{"value":"Eukaryotic initiation factor 4A-III, N-terminally processed"}}}]},"genes":[{"geneName":{"value":"EIF4A3"},"synonyms":[{"value":"DDX48"},{"value":"KIAA0111"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11991638"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15034551"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16170325"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16209946"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16314458"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16923391"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16931718"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17375189"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19033377"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19409878"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20479275"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22203037"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22961380"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24360810"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28076346"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28502770"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29301961"}],"value":"ATP-dependent RNA helicase (PubMed:16170325). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:22961380, PubMed:28076346, PubMed:28502770, PubMed:29301961). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs (PubMed:16170325, PubMed:16209946, PubMed:16314458, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275). 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 (PubMed:22203037). Involved in craniofacial development (PubMed:24360810)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"ATP + H2O = ADP + phosphate + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:13065"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"3.6.4.13","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16170325"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17375189"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22961380"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22961380"}],"value":"The ATPase activity is increased some 4-fold in the presence of RNA"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11991638"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14730019"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15034551"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16170325"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16314458"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16495234"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16923391"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16931718"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18423201"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19033377"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20479275"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22959432"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22961380"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23236153"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23917022"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24218557"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25220460"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26382858"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28076346"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28502770"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29301961"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30538148"}],"value":"Identified in the spliceosome C complex (PubMed:11991638, PubMed:22961380, PubMed:28076346, PubMed:28502770, PubMed:29301961). Core component of the mRNA splicing-dependent exon junction complex (EJC); the core complex contains CASC3, EIF4A3, MAGOH or MAGOHB, and RBM8A (PubMed:14730019, PubMed:15034551, PubMed:16170325, PubMed:16314458, PubMed:16923391, PubMed:16931718, PubMed:19033377, PubMed:20479275, PubMed:23917022). Interacts with CASC3, MAGOH, NXF1, RBM8A and ALYREF/THOC4 (PubMed:14730019, PubMed:16170325, PubMed:16495234, PubMed:22961380). 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 (PubMed:14730019, PubMed:16314458, PubMed:37020021). May interact with NOM1. Interacts with POLDIP3 (PubMed:18423201). Interacts with CWC22 and PRPF19 in an RNA-independent manner (PubMed:22959432, PubMed:22961380, PubMed:23236153, PubMed:24218557). Direct interaction with CWC22 is mediated by the helicase C-terminal domain (PubMed:22959432, PubMed:24218557). 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) (PubMed:20479275). Interacts with NCBP3 (PubMed:26382858). Interacts with NRDE2 (PubMed:30538148). Interacts with DHX34; the interaction is RNA-independent (PubMed:25220460)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q9H257-2","geneName":"CARD9","intActId":"EBI-11530605"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"O15234","geneName":"CASC3","intActId":"EBI-299118"},"numberOfExperiments":39,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q6PII3","geneName":"CCDC174","intActId":"EBI-747830"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q96GN5","geneName":"CDCA7L","intActId":"EBI-5278764"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q6P9H4","geneName":"CNKSR3","intActId":"EBI-10253274"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q9HCG8","geneName":"CWC22","intActId":"EBI-373289"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q96D03","geneName":"DDIT4L","intActId":"EBI-742054"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q9NY93","geneName":"DDX56","intActId":"EBI-372376"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q9NRI5-2","geneName":"DISC1","intActId":"EBI-11988027"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"P55039","geneName":"DRG2","intActId":"EBI-750565"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q96KQ7","geneName":"EHMT2","intActId":"EBI-744366"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q8TBB1","geneName":"LNX1","intActId":"EBI-739832"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"P61326","geneName":"MAGOH","intActId":"EBI-299134"},"numberOfExperiments":30,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"P50221","geneName":"MEOX1","intActId":"EBI-2864512"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q6FHY5","geneName":"MEOX2","intActId":"EBI-16439278"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q9GZT8","geneName":"NIF3L1","intActId":"EBI-740897"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q5C9Z4","geneName":"NOM1","intActId":"EBI-2685618"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q3KNR5","geneName":"PAX4","intActId":"EBI-10240813"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q53EL6","geneName":"PDCD4","intActId":"EBI-935824"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"Q9NRD5","geneName":"PICK1","intActId":"EBI-79165"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"P62487","geneName":"POLR2G","intActId":"EBI-347928"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"O14744","geneName":"PRMT5","intActId":"EBI-351098"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P38919","intActId":"EBI-299104"},"interactantTwo":{"uniProtKBAccession":"P25786","geneName":"PSMA1","intActId":"EBI-359352"},"numberOfExper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LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q3B8Q2"}],"value":"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)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10623621"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11991638"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22961380"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28076346"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28502770"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29301961"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10623621"}],"value":"Nucleus speckle","id":"SL-0186"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q3B8Q2"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10623621"}],"value":"Ubiquitously expressed"}],"commentType":"TISSUE SPECIFICITY"},{"commentType":"DISEASE","disease":{"diseaseId":"Richieri-Costa-Pereira syndrome","diseaseAccession":"DI-04063","acronym":"RCPS","description":"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.","diseaseCrossReference":{"database":"MIM","id":"268305"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24360810"}]},"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24360810"}],"value":"The disease is caused by variants 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)"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the DEAD box helicase family. eIF4A subfamily"}],"commentType":"SIMILARITY"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"BAA04879.2","note":"Extended N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":411,"modifier":"EXACT"}},"description":"Eukaryotic initiation factor 4A-III","featureId":"PRO_0000423267"},{"type":"Initiator methionine","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":1,"modifier":"EXACT"}},"description":"Removed; 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