Genome location: Pf3D7_06_v3:1,158,605..1,169,668(+)
Genome classification: Core
Product Description: eukaryotic translation initiation factor 2-alpha kinase
SignalP Peptide: N/A
# Transmembrane Domains: 1
EC Numbers: 2.7.11.1 (Non-specific serine/threonine protein kinase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:1903561 | extracellular vesicle |
| Component | GO:0005634 | nucleus |
| Function | GO:0004686 | elongation factor-2 kinase activity |
| Function | GO:0004672 | protein kinase activity |
| Function | GO:0004713 | protein tyrosine kinase activity |
| Process | GO:0007093 | mitotic cell cycle checkpoint signaling |
| Process | GO:0006468 | protein phosphorylation |
| Process | GO:0009410 | response to xenobiotic stimulus |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | possibly expressed | N/A | N/A |
| Ring | expressed | 1.92 | 0.28 |
| Trophozoite | expressed | 2.07 | 0.18 |
| Schizont | expressed | 1.65 | 0.31 |
| Gametocyte | expressed | 1.43 | 0.35 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0628200
Resistome Missense Mutations: G811D
Resistome Compounds with Missense Mutations: BI-2536
Resistome # Samples with Disruptive Mutations: 2 (2 missense, 2 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.14 | MFS: -2.881 | #Insertions: 0
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1126900)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1126900)
Modification: Disrupted | RMgm-3076
More info: PhenoPlasm Link
AlphaFill Uniprot ID: N/A
"Best" AlphaFill ligand hit: No AlphaFill hits
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.7.11.1 | non-specific serine/threonine protein kinase | ATPKClDTTP53DRBEDTATBCAKN-93K252aCKI-7LAALSTAACS... |
No evidence of orthology to BindingDB entries
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 18 | 87 | 68 | 135 |
| disruptive | 122 | 289 | 151 | 433 |
| missense | 59 | 200 | 132 | 340 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 34 | 196 | 81 | 189 |
| disruptive | 213 | 583 | 324 | 715 |
| missense | 93 | 413 | 266 | 476 |
PlasmoDB Total SNPs: 463
Non-coding: 108 | Synonymous: 197 | Nonsynonymous: 158 | Stop Codon: 0
Protein Length: 3072 | Molecular Weight (kDa): 364.331
PDB ID(s): None
Isoelectric Point: 9.37
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 |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 9371731 | Molecular cloning, characterization and localization of PfPK4, an eIF-2alphakinase-related enzyme from the malarial parasite Plasmodium falciparum. | Mohrle JJ, Zhao Y, ..., Kappes B | 10.1042/bj3280677 |
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 22355110 | PK4, a eukaryotic initiation factor 2alpha(eIF2alpha) kinase, is essential for thedevelopment of the erythrocytic cycle of Plasmodium. | Zhang M, Mishra S, ..., Nussenzweig V | 10.1073/pnas.1121567109 |
| 29241041 | Inhibiting the Plasmodium eIF2alpha Kinase PK4 Prevents Artemisinin-Induced Latency. | Zhang M, Gallego-Delgado J, ..., Sullivan WJ Jr | 10.1016/j.chom.2017.11.005 |
| 30773881 | The Adaptive Proline Response in P. falciparum Is Independent of PfeIK1 and eIF2alphaSignaling. | Fagbami L, Deik AA, ..., Mazitschek R | 10.1021/acsinfecdis.8b00363 |
| 33608523 | 20S proteasomes secreted by the malaria parasite promote its growth. | Dekel E, Yaffe D, ..., Regev-Rudzki N | 10.1038/s41467-021-21344-8 |
| 31087747 | The endoplasmic reticulum chaperone PfGRP170 is essential for asexual developmentand is linked to stress response in malaria parasites | Kudyba HM, Cobb DW, ..., Muralidharan V | 10.1111/cmi.13042 |
| 29241036 | Plasmodium Peekaboo: PK4 Mediates Parasite Latency | Rea E, Holder AA, Tewari R | 10.1016/j.chom.2017.11.011 |