Genome location: Pf3D7_14_v3:1,862,507..1,866,212(-)
Genome classification: Core
Product Description: protein serine/threonine 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:0005634 | nucleus |
| Function | GO:0004712 | protein serine/threonine/tyrosine kinase activity |
| Process | GO:0006468 | protein phosphorylation |
| Process | GO:0045595 | regulation of cell differentiation |
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 | 1.75 | 0.31 |
| Trophozoite | expressed | 0.90 | 0.55 |
| Schizont | expressed | 0.70 | 0.64 |
| Gametocyte | expressed | 1.28 | 0.37 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1445400
Resistome Missense Mutations: M621I
Resistome Compounds with Missense Mutations: AN13762
Resistome # Samples with Disruptive Mutations: 1 (1 missense, 1 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.223 | MFS: -2.602 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1309200)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IL19
"Best" AlphaFill ligand hit: D15 (n-(5-{[(2s)-4-amino-2-(3-chlorophenyl)butanoyl]amino}-1h-indazol-3-yl)benzamide, Local RMSD=0.05) with 2VX3 (Global RMSD=3.48)
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 |
|---|---|---|---|---|
| Q9HAZ1 | Dual specificity protein kinase CLK4 | Homo sapiens | OrthoDB | CHEMBL3297832CHEMBL3775393CHEMBL3774448CHEMBL3815054... |
| P49759 | Dual specificity protein kinase CLK1 | Homo sapiens | OrthoDB | US8546404, 6NR93A55E4... |
| P49760 | Dual specificity protein kinase CLK2 | Homo sapiens | OrthoDB | US9040694, 2US9040694, 3pyrazolo[1,5-a]pyrimidine 4bDorsomorphin... |
| O35492 | Dual specificity protein kinase CLK3 | Mus musculus | OrthoDB | CHEMBL1803078CHEMBL1803082CHEMBL1803083CHEMBL1803085... |
| O35491 | Dual specificity protein kinase CLK2 | Mus musculus | OrthoDB | CHEMBL3589660CHEMBL3589661CHEMBL3589662CHEMBL3589664... |
| O35493 | Dual specificity protein kinase CLK4 | Mus musculus | OrthoDB | CHEMBL3589660CHEMBL3589661CHEMBL3589662CHEMBL3589664... |
| P22518 | Dual specificity protein kinase CLK1 | Mus musculus | OrthoDB | MLS000518915CHEMBL2029615CHEMBL2029618CHEMBL4784564... |
| P49761 | Dual specificity protein kinase CLK3 | OrthoDB | 3A5CHEMBL3297832CHEMBL3774448CHEMBL3885335... |
Ortholog Group (OrthoMCL): OG6_100708
Most Similar Human Ortholog: H3BRE4
TM-align score: 0.95 | RMSD: 1.55
Seq Identity: 0.41 | Length: 190 / 881
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000013441 | CDC like kinase 1 |
| ENSG00000113240 | CDC like kinase 4 |
| ENSG00000176444 | CDC like kinase 2 |
| ENSG00000179335 | CDC like kinase 3 |
| ENSG00000261893 | CDC like kinase 2 |
Protein Length: 881 | Molecular Weight (kDa): 106.754
PDB ID(s): 3LLT
Isoelectric Point: 9.9
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 |
| 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 | 10 | 48 | 31 | 67 |
| disruptive | 34 | 105 | 66 | 138 |
| missense | 21 | 79 | 53 | 118 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 22 | 100 | 32 | 63 |
| disruptive | 69 | 207 | 104 | 220 |
| missense | 35 | 163 | 84 | 151 |
PlasmoDB Total SNPs: 145
Non-coding: 72 | Synonymous: 40 | Nonsynonymous: 33 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 11306117 | Primary structure and sexual stage-specific expression of a LAMMER protein kinaseof Plasmodium falciparum. | Li JL, Targett GA, Baker DA | 10.1016/s0020-7519(01)00126-6 |
| 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 |
| 21312235 | Two nucleus-localized CDK-like kinases with crucial roles for malaria parasiteerythrocytic replication are involved in phosphorylation of splicing factor. | Agarwal S, Kern S, ..., Pradel G | 10.1002/jcb.23034 |