Genome location: Pf3D7_14_v3:1,833,308..1,839,775(-)
Genome classification: Core
Product Description: eukaryotic translation initiation factor 2-alpha kinase 1
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.7.11.1 (Non-specific serine/threonine protein kinase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0022626 | cytosolic ribosome |
| Component | GO:1903561 | extracellular vesicle |
| Function | GO:0005524 | ATP binding |
| Function | GO:0003824 | catalytic activity |
| Function | GO:0004694 | eukaryotic translation initiation factor 2alpha kinase activity |
| Function | GO:0004672 | protein kinase activity |
| Process | GO:0140469 | GCN2-mediated signaling |
| Process | GO:0010608 | posttranscriptional regulation of gene expression |
| Process | GO:0006468 | protein phosphorylation |
| Process | GO:0042594 | response to starvation |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | not expressed | N/A | N/A |
| Ring | expressed | 1.24 | 0.48 |
| Trophozoite | possibly expressed | 0.66 | 0.64 |
| Schizont | possibly expressed | 0.42 | 0.77 |
| Gametocyte | not expressed | 0.72 | 0.61 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1444500
Resistome Missense Mutations: E950K
Resistome Compounds with Missense Mutations: MMV665794
Resistome # Samples with Disruptive Mutations: 2 (2 missense, 0 "interesting" missense)
Zhang Phenotype: Mutable in CDS
MIS: 1 | MFS: -1.267 | #Insertions: 9
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PbANKA_1308400)
Modification: Disrupted | RMgm-4404
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IL26
"Best" AlphaFill ligand hit: MIX (mitoxantrone, Local RMSD=0.67) with 2FUM (Global RMSD=3.99)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.7.11.1 | non-specific serine/threonine protein kinase | ATPKClDTTP53DRBEDTATBCAKN-93K252aCKI-7LAALSTAACS... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P19525 | Interferon-induced, double-stranded RNA-activated protein kinase | Homo sapiens | OrthoMCL BLAST | US9650366, 1US9650366, 2US9650366, 3US9650366, 4... |
Ortholog Group (OrthoMCL): OG6_103908
Most Similar Human Ortholog: Q9BQI3
TM-align score: 0.47 | RMSD: 4.63
Seq Identity: 0.29 | Length: 342 / 1558
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000086232 | eukaryotic translation initiation factor 2 alpha kinase 1 |
Protein Length: 1558 | Molecular Weight (kDa): 184.251
UniProt ID(s): Q8IL26
PDB ID(s): None
Isoelectric Point: 7.96
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000719 | Protein kinase domain |
| InterPro | IPR008271 | Serine/threonine-protein kinase, active site |
| InterPro | IPR011009 | Protein kinase-like domain superfamily |
| InterPro | IPR017441 | Protein kinase, ATP binding site |
| PFam | PF00069 | Protein kinase domain |
| Superfamily | SSF56112 | Protein kinase-like domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 20 | 71 | 46 | 107 |
| disruptive | 54 | 204 | 121 | 238 |
| missense | 32 | 177 | 107 | 202 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 33 | 143 | 72 | 103 |
| disruptive | 105 | 414 | 212 | 358 |
| missense | 63 | 340 | 169 | 272 |
PlasmoDB Total SNPs: 261
Non-coding: 118 | Synonymous: 99 | Nonsynonymous: 44 | 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 |
| 19435497 | PfeIK1, a eukaryotic initiation factor 2alpha kinase of the human malariaparasite Plasmodium falciparum, regulates stress-response to amino-acidstarvation. | Fennell C, Babbitt S, ..., Doerig C | 10.1186/1475-2875-8-99 |
| 33608523 | 20S proteasomes secreted by the malaria parasite promote its growth. | Dekel E, Yaffe D, ..., Regev-Rudzki N | 10.1038/s41467-021-21344-8 |
| 32702775 | The Plasmodium falciparum eIK1 kinase (PfeIK1) is central for melatoninsynchronization in the human malaria parasite. Melatotosil blocks melatoninaction on parasite cell cycle | Dias BKM, Nakabashi M, ..., Garcia CRS | 10.1111/jpi.12685 |
| 36810637 | A non-canonical sensing pathway mediates Plasmodium adaptation to amino aciddeficiency | Marreiros IM, Marques S, ..., Mota MM | 10.1038/s42003-023-04566-y |