Product Description: calcium-dependent protein kinase 4
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:0042555 | MCM complex |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005634 | nucleus |
| Function | GO:0005509 | calcium ion binding |
| Function | GO:0009931 | calcium-dependent protein serine/threonine kinase activity |
| Function | GO:0004723 | calcium-dependent protein serine/threonine phosphatase activity |
| Function | GO:0005516 | calmodulin binding |
| Function | GO:0003824 | catalytic activity |
| Process | GO:0006260 | DNA replication |
| Process | GO:0035556 | intracellular signal transduction |
| Process | GO:0090307 | mitotic spindle assembly |
| Process | GO:0018105 | peptidyl-serine phosphorylation |
| Process | GO:0036388 | pre-replicative complex assembly |
| Process | GO:0046777 | protein autophosphorylation |
| Process | GO:0006468 | protein phosphorylation |
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 | 0.20 | 0.90 |
| Trophozoite | expressed | 0.45 | 0.74 |
| Schizont | expressed | 1.66 | 0.25 |
| Gametocyte | expressed | 0.68 | 0.66 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0717500
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Mutable in CDS
MIS: 0.999 | MFS: -2.794 | #Insertions: 2
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_0615200)
RMgmDB ABS Phenotype: Not tested (Pb ortholog: PBANKA_0615200)
Modification: Mutated | RMgm-4868
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IBS5
"Best" AlphaFill ligand hit: PGO (s-1,2-propanediol, Local RMSD=0.03) with 2VZ6 (Global RMSD=1.79)
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 |
|---|---|---|---|---|
| Q8IBS5 | Calcium-dependent protein kinase 4 | Plasmodium falciparum (isolate 3D7) | HOGENOM, OMA, OrthoDB, OrthoMCL, OrthoMCL BLAST | CHEMBL2069957CHEMBL2070050CHEMBL2070050CHEMBL2070081 |
| A3FQ16 | Calmodulin-domain protein kinase 1, putative | OMA, OrthoDB, OrthoMCL, OrthoMCL BLAST | CHEMBL2069954CHEMBL1784959CHEMBL1784960CHEMBL1784961... | |
| A0A7S7LIM2 | Uncharacterized protein | OMA, OrthoMCL BLAST | CHEMBL3108912CHEMBL2069957CHEMBL3108913CHEMBL2070049... | |
| Q5CTY5 | Calcium/calmodulin dependent protein kinase with a kinas domain and 4 calmodulin-like EF hands | OrthoMCL BLAST | CHEMBL2069954CHEMBL1784959CHEMBL1784960CHEMBL1784961... | |
| P62343 | Calcium-dependent protein kinase 1 | Plasmodium falciparum | OrthoMCL BLAST | Purfalcamine, 1CID24762167CID24762168CID24762169... |
| A0A0F7UUA6 | CAM kinase, CDPK family TgCDPK1 | OrthoMCL BLAST | US10632122, Example 1US10632122, Example 2US10632122, Example 3US10632122, Example 4... | |
| Q9BJF5 | Calmodulin-domain protein kinase 1 | OrthoMCL BLAST | CHEMBL3108912CHEMBL2069957CHEMBL3108913CHEMBL2070049... |
Ortholog Group (OrthoMCL): OG6_100515
Most Similar Human Ortholog: E9PBE8
TM-align score: 0.80 | RMSD: 2.15
Seq Identity: 0.38 | Length: 150 / 528
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000058404 | calcium/calmodulin dependent protein kinase II beta |
| ENSG00000070808 | calcium/calmodulin dependent protein kinase II alpha |
| ENSG00000145349 | calcium/calmodulin dependent protein kinase II delta |
| ENSG00000148660 | calcium/calmodulin dependent protein kinase II gamma |
Protein Length: 528 | Molecular Weight (kDa): 60.78
UniProt ID(s): Q8IBS5
Isoelectric Point: 6.93
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000719 | Protein kinase domain |
| InterPro | IPR002048 | EF-hand domain |
| InterPro | IPR008271 | Serine/threonine-protein kinase, active site |
| InterPro | IPR011009 | Protein kinase-like domain superfamily |
| InterPro | IPR011992 | EF-hand domain pair |
| InterPro | IPR017441 | Protein kinase, ATP binding site |
| InterPro | IPR018247 | EF-Hand 1, calcium-binding site |
| PFam | PF00069 | Protein kinase domain |
| PFam | PF13499 | EF-hand domain |
| Superfamily | SSF47473 | EF-hand domain pair |
| 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 | 2 | 17 | 9 | 33 |
| disruptive | 1 | 6 | 6 | 14 |
| missense | 1 | 6 | 6 | 9 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 56 | 28 | 35 |
| disruptive | 5 | 21 | 16 | 60 |
| missense | 1 | 14 | 9 | 43 |
PlasmoDB Total SNPs: 217
Non-coding: 187 | Synonymous: 27 | Nonsynonymous: 3 | 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 |
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 12368870 | Analysis of the Plasmodium falciparum proteome by high-accuracy massspectrometry. | Lasonder E, Ishihama Y, ..., Mann M | 10.1038/nature01111 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 16313614 | An atypical mitogen-activated protein kinase controls cytokinesis and flagellarmotility during male gamete formation in a malaria parasite. | Tewari R, Dorin D, ..., Billker O | 10.1111/j.1365-2958.2005.04793.x |
| 18768477 | The motor complex of Plasmodium falciparum: phosphorylation by acalcium-dependent protein kinase. | Green JL, Rees-Channer RR, ..., Holder AA | 10.1074/jbc.M803129200 |
| 19307175 | Dissection of mechanisms involved in the regulation of Plasmodium falciparumcalcium-dependent protein kinase 4. | Ranjan R, Ahmed A, Gourinath S, Sharma P | 10.1074/jbc.M900656200 |
| 19666141 | Characterization of Plasmodium falciparum calcium-dependent protein kinase 4. | Kato K, Sudo A, ..., Akashi H | 10.1016/j.parint.2009.08.001 |
| 28481199 | Multiple short windows of calcium-dependent protein kinase 4 activity coordinatedistinct cell cycle events during Plasmodium gametogenesis | Fang H, Klages N, ..., Brochet M | 10.7554/eLife.26524 |
| 33612795 | Plasmodium falciparum protein kinase as a potential therapeutic target forantimalarial drugs development | Mahmud F, Lee PC, ..., Lai NS | 10.47665/tb.37.3.822 |
| 26499803 | Evaluation of the basic functions of six calcium-dependent protein kinases inToxoplasma gondii using CRISPR-Cas9 system | Wang JL, Huang SY, ..., Zhu XQ | 10.1007/s00436-015-4791-6 |
| 33549149 | Bioinformatics analysis of calcium-dependent protein kinase 4 (CDPK4) asToxoplasma gondii vaccine target | Foroutan M, Ghaffari AD, ..., Sabaghan M | 10.1186/s13104-021-05467-1 |
| 31824917 | Integrative Multi-Kinase Approach for the Identification of Potent AntiplasmodialHits | Lima MNN, Cassiano GC, ..., Andrade CH | 10.3389/fchem.2019.00773 |
| 30409996 | Inducing controlled cell cycle arrest and re-entry during asexual proliferationof Plasmodium falciparum malaria parasites | van Biljon R, Niemand J, ..., Birkholtz LM | 10.1038/s41598-018-34964-w |
| 24123773 | A specific inhibitor of PfCDPK4 blocks malaria transmission: chemical-geneticvalidation | Ojo KK, Eastman RT, ..., Van Voorhis WC | 10.1093/infdis/jit522 |
| 29141230 | Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium GameteFormation | Invergo BM, Brochet M, ..., Billker O | 10.1016/j.celrep.2017.10.071 |
| 26934697 | Biochemical Screening of Five Protein Kinases from Plasmodium falciparum against14,000 Cell-Active Compounds | Crowther GJ, Hillesland HK, ..., Ojo KK | 10.1371/journal.pone.0149996 |
| 27425827 | Invasion of hepatocytes by Plasmodium sporozoites requires cGMP-dependent proteinkinase and calcium dependent protein kinase 4 | Govindasamy K, Jebiwott S, ..., Bhanot P | 10.1111/mmi.13466 |
| 32866196 | Overlapping and distinct roles of CDPK family members in the pre-erythrocyticstages of the rodent malaria parasite, Plasmodium berghei | Govindasamy K, Bhanot P | 10.1371/journal.ppat.1008131 |
| 30315162 | Epistasis studies reveal redundancy among calcium-dependent protein kinases inmotility and invasion of malaria parasites | Fang H, Gomes AR, ..., Brochet M | 10.1038/s41467-018-06733-w |
| 26222913 | Global expression profiling reveals shared and distinct transcript signatures inarrested act2(-) and CDPK4(-) Plasmodium berghei gametocytes | Andreadaki M, Mollenkopf HJ, ..., Siden-Kiamos I | 10.1016/j.molbiopara.2015.07.001 |
| 34724830 | Plasmodium falciparum Calcium-Dependent Protein Kinase 4 is Critical for MaleGametogenesis and Transmission to the Mosquito Vector | Kumar S, Haile MT, ..., Swearingen KE | 10.1128/mBio.02575-21 |
| 37535401 | Plasmodium microtubule-binding protein EB1 is critical for partitioning of nucleiin male gametogenesis | Mauer S, Camargo N, ..., Kumar S | 10.1128/mbio.00822-23 |
| 38127294 | Structure-based virtual screening against multiple Plasmodium falciparum kinasesreveals antimalarial compounds | Godara P, Reddy KS, ..., Prusty D | 10.1007/s11030-023-10770-z |