Search Results
Overview
| Uniprot ID | P38919 |
|---|---|
| Protein Name | Eukaryotic initiation factor 4A-III |
| Gene Name | EIF4A3 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 152 | NVGEDIRKLDYGQHV |
| 19 | SARKRLLKEEDMTKV |
| 289 | IFCNTKRKVDWLTEK |
Function
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)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0071013 | catalytic step 2 spliceosome |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0030425 | dendrite |
| Cellular Component | GO:0035145 | exon-exon junction complex |
| Cellular Component | GO:0098978 | glutamatergic synapse |
| Cellular Component | GO:0016020 | membrane |
| Cellular Component | GO:0043025 | neuronal cell body |
| Cellular Component | GO:0016607 | nuclear speck |
| Cellular Component | GO:0005730 | nucleolus |
| Cellular Component | GO:0005654 | nucleoplasm |
| Cellular Component | GO:0005634 | nucleus |
| Cellular Component | GO:0098794 | postsynapse |
| Cellular Component | GO:0071006 | U2-type catalytic step 1 spliceosome |
| Molecular Function | GO:0005524 | ATP binding |
| Molecular Function | GO:0016887 | ATP hydrolysis activity |
| Molecular Function | GO:0003729 | mRNA binding |
| Molecular Function | GO:0008143 | poly(A) binding |
| Molecular Function | GO:0043021 | ribonucleoprotein complex binding |
| Molecular Function | GO:0003723 | RNA binding |
| Molecular Function | GO:0003724 | RNA helicase activity |
| Molecular Function | GO:0035613 | RNA stem-loop binding |
| Molecular Function | GO:0035368 | selenocysteine insertion sequence binding |
| Biological Process | GO:0008306 | associative learning |
| Biological Process | GO:1990416 | cellular response to brain-derived neurotrophic factor stimulus |
| Biological Process | GO:0072715 | cellular response to selenite ion |
| Biological Process | GO:0048701 | embryonic cranial skeleton morphogenesis |
| Biological Process | GO:0035640 | exploration behavior |
| Biological Process | GO:0006406 | mRNA export from nucleus |
| Biological Process | GO:0016071 | mRNA metabolic process |
| Biological Process | GO:0000398 | mRNA splicing, via spliceosome |
| Biological Process | GO:0090394 | negative regulation of excitatory postsynaptic potential |
| Biological Process | GO:1904570 | negative regulation of selenocysteine incorporation |
| Biological Process | GO:0017148 | negative regulation of translation |
| Biological Process | GO:0000184 | nuclear-transcribed mRNA catabolic process, nonsense-mediated decay |
| Biological Process | GO:0045727 | positive regulation of translation |
| Biological Process | GO:2000622 | regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay |
| Biological Process | GO:0099578 | regulation of translation at postsynapse, modulating synaptic transmission |
| Biological Process | GO:0006364 | rRNA processing |
Reference
[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.
[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[3] Lin Y, Chen M, Wang D, Yu Y, Chen R et al.. Multi-Proteomic Analysis Reveals the Effect of Protein Lactylation on Matrix and Cholesterol Metabolism in Tendinopathy.. J Proteome Res 22(6):1712-1722. 2023 Jun 2. PMID: 37159428.
[4] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.
[5] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.
[6] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.
[7] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.
[8] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.