Product Description: cyclin-dependent-like kinase CLK3
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:0005737 | cytoplasm |
| Component | GO:0005634 | nucleus |
| Function | GO:0004674 | protein serine/threonine kinase activity |
| Process | GO:0018105 | peptidyl-serine phosphorylation |
| Process | GO:0018107 | peptidyl-threonine phosphorylation |
| Process | GO:0006468 | protein phosphorylation |
| Process | GO:0006355 | regulation of transcription, DNA-templated |
| 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 | expressed | N/A | N/A |
| Ring | expressed | 0.45 | 0.78 |
| Trophozoite | expressed | 0.67 | 0.62 |
| Schizont | expressed | 0.57 | 0.66 |
| Gametocyte | expressed | 0.68 | 0.64 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1114700
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.449 | MFS: -2.375 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0933000)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IIL5
"Best" AlphaFill ligand hit: D15 (n-(5-{[(2s)-4-amino-2-(3-chlorophenyl)butanoyl]amino}-1h-indazol-3-yl)benzamide, Local RMSD=0.02) with 2VX3 (Global RMSD=1.88)
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 |
|---|---|---|---|---|
| Q9UQ88 | Cyclin-dependent kinase 11A | Homo sapiens | OMA | CHEMBL1989043CHEMBL5206282CHEMBL5169674CHEMBL5185655... |
| Q13523 | Serine/threonine-protein kinase PRP4 homolog | OrthoDB, OrthoMCL BLAST | 4-ylmethyl)-carbamoyl]-thiophen-2-yl}-benzo[b]thiophene-2-carboxylic acid amine (Compound A)CHEMBL5186861 |
Ortholog Group (OrthoMCL): OG6_102293
Most Similar Human Ortholog: H0YDJ3
TM-align score: 0.63 | RMSD: 3.22
Seq Identity: 0.47 | Length: 397 / 699
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000112739 | pre-mRNA processing factor 4B |
Protein Length: 699 | Molecular Weight (kDa): 81.092
UniProt ID(s): Q8IIL5
PDB ID(s): None
Isoelectric Point: 7.95
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 | 8 | 42 | 23 | 57 |
| disruptive | 7 | 52 | 33 | 73 |
| missense | 7 | 51 | 32 | 71 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 15 | 75 | 27 | 63 |
| disruptive | 18 | 123 | 65 | 154 |
| missense | 13 | 110 | 61 | 104 |
PlasmoDB Total SNPs: 267
Non-coding: 240 | Synonymous: 22 | Nonsynonymous: 5 | 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 |
| 25188378 | Inhibition of the SR protein-phosphorylating CLK kinases of Plasmodium falciparumimpairs blood stage replication and malaria transmission. | Kern S, Agarwal S, ..., Pradel G | 10.1371/journal.pone.0105732 |
| 31467193 | Validation of the protein kinase Pf CLK3 as a multistage cross-species malarialdrug target | Alam MM, Sanchez-Azqueta A, ..., Tobin AB | 10.1126/science.aau1682 |
| 32946682 | Temperature does matter-an additional dimension in kinase inhibitor development. | Strauch M, Heyd F | 10.1111/febs.15564 |
| 35921477 | Altiratinib blocks Toxoplasma gondii and Plasmodium falciparum development byselectively targeting a spliceosome kinase. | Swale C, Bellini V, ..., Hakimi MA | 10.1126/scitranslmed.abn3231 |
| 32453420 | Targeting CLK3 inhibits the progression of cholangiocarcinoma by reprogramming nucleotide metabolism | Zhou Q, Lin M, ..., Zhang Z | 10.1084/jem.20191779 |
| 33612795 | Plasmodium falciparum protein kinase as a potential therapeutic target for antimalarial drugs development | Mahmud F, Lee PC, ..., Lai NS | 10.47665/tb.37.3.822 |