Genome location: Pf3D7_14_v3:2,824,250..2,826,936(+)
Genome classification: Core
Product Description: eukaryotic initiation factor 4A
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 3.6.4.12 (DNA helicase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Component | GO:0010494 | cytoplasmic stress granule |
| Component | GO:0016281 | eukaryotic translation initiation factor 4F complex |
| Component | GO:1903561 | extracellular vesicle |
| Component | GO:0020020 | food vacuole |
| Component | GO:0005634 | nucleus |
| Function | GO:0033679 | 3'-5' DNA/RNA helicase activity |
| Function | GO:0016887 | ATP hydrolysis activity |
| Function | GO:0003723 | RNA binding |
| Function | GO:0000339 | RNA cap binding |
| Function | GO:0004386 | helicase activity |
| Function | GO:0003729 | mRNA binding |
| Function | GO:0003743 | translation initiation factor activity |
| Process | GO:0002183 | cytoplasmic translational initiation |
| Process | GO:0006446 | regulation of translational initiation |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | expressed | N/A | N/A |
| Ring | expressed | 1.04 | 0.53 |
| Trophozoite | expressed | 1.14 | 0.44 |
| Schizont | expressed | 0.26 | 0.84 |
| Gametocyte | possibly expressed | 0.40 | 0.77 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1468700
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 2 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.12 | MFS: -2.99 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IKF0
"Best" AlphaFill ligand hit: AGS (phosphothiophosphoric acid-adenylate ester, Local RMSD=0.11) with 1OYY (Global RMSD=3.19)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.6.4.12 | DNA helicase | No BRENDA inhibitors |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P60842 | Eukaryotic initiation factor 4A-I | Homo sapiens | HOGENOM, OrthoDB | HippuristanolCHEMBL2058177CHEMBL2058177CHEMBL2170718... |
| P38919 | Eukaryotic initiation factor 4A-III | HOGENOM, OrthoDB | eIF4A3 inhibitor, 1eIF4A3 inhibitor, 2CHEMBL4070102CHEMBL4070102... | |
| Q5E175 | ATP-dependent RNA helicase RhlE | Plasmodium falciparum | OMA | Chem Biol Compound 2Sulfonamide 12bSulfonamide 17Sulfonamide 12aa... |
Ortholog Group (OrthoMCL): OG6_101294
Most Similar Human Ortholog: J3QLN6
TM-align score: 0.98 | RMSD: 0.52
Seq Identity: 0.67 | Length: 162 / 398
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000156976 | eukaryotic translation initiation factor 4A2 |
| ENSG00000161960 | eukaryotic translation initiation factor 4A1 |
Protein Length: 398 | Molecular Weight (kDa): 45.31
UniProt ID(s): O97223, Q2PZH3, Q8IKF0
PDB ID(s): None
Isoelectric Point: 5.38
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000629 | ATP-dependent RNA helicase DEAD-box, conserved site |
| InterPro | IPR001650 | Helicase, C-terminal |
| InterPro | IPR011545 | DEAD/DEAH box helicase domain |
| InterPro | IPR014001 | Helicase superfamily 1/2, ATP-binding domain |
| InterPro | IPR027417 | P-loop containing nucleoside triphosphate hydrolase |
| PFam | PF00270 | DEAD/DEAH box helicase domain |
| PFam | PF00271 | Helicase, C-terminal |
| Superfamily | SSF52540 | P-loop containing nucleoside triphosphate hydrolase |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 7 | 39 | 33 | 24 |
| disruptive | 0 | 1 | 4 | 56 |
| missense | 0 | 1 | 4 | 42 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 15 | 84 | 17 | 13 |
| disruptive | 0 | 17 | 24 | 91 |
| missense | 0 | 11 | 19 | 60 |
PlasmoDB Total SNPs: 116
Non-coding: 99 | Synonymous: 16 | Nonsynonymous: 1 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 19751846 | Isolation and functional characterization of eIF4F components and poly(A)-bindingprotein from Plasmodium falciparum. | Tuteja R, Pradhan A | 10.1016/j.parint.2009.09.001 |
| 21136929 | Food vacuole proteome of the malarial parasite Plasmodium falciparum. | Lamarque M, Tastet C, ..., Dubremetz JF | 10.1002/prca.200700112 |
| 22750398 | Enhanced purification and characterization of the PfeIF4A (PfH45) helicase fromPlasmodium falciparum using a codon-optimised clone. | Evans L, Gowers D, Firman K, Youell J | 10.1016/j.pep.2012.06.010 |
| 28944300 | Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyanclinical isolate defines a core parasite secretome. | Abdi A, Yu L, ..., Rayner J | 10.12688/wellcomeopenres.11910.2 |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |
| 33906926 | Functional Characterization of the m(6)A-Dependent Translational Modulator PfYTH | Sinha A, Baumgarten S, ..., Scherf A | 10.1128/mBio.00661-21 |
| 37808713 | Human eukaryotic initiation factor 4G directly binds the 40S ribosomal subunit topromote efficient translation | Villa N, Fraser CS | 10.1101/2023.09.29.560218 |
| 38018538 | Architecture, domain organization, and functional signatures of trypanosomatidkeIF4A1s and Plasmodium peIF4A1s suggest conserved functions | Dadwal A, DAS S | https://pubmed.ncbi.nlm.nih.gov/38018538/ |
| 38232291 | A second-generation eIF4A RNA helicase inhibitor exploits translational reprogramming as a vulnerability in triple-negative breast cancer | Cencic R, Im YK, ..., Pelletier J | 10.1073/pnas.2318093121 |
| 38287194 | The structure of a human translation initiation complex reveals two independent roles for the helicase eIF4A | Brito Querido J, Sokabe M, ..., Ramakrishnan V | 10.1038/s41594-023-01196-0 |
| 37997253 | Decoding the Heterogeneity and Specialized Function of Translation MachineryThrough Ribosome Profiling in Yeast Mutants of Initiation Factors | Wang J, Zhang G, Qian W, Li K | 10.1002/adbi.202300494 |
| 37865179 | Eukaryotic Initiation Factor 4E (eIF4E) as a Target of Anti-Psoriatic Treatment | Golob-Schwarzl N, Pilic J, ..., Wolf P | 10.1016/j.jid.2022.12.028 |