Genome location: Pf3D7_13_v3:1,527,826..1,531,730(-)
Genome classification: Core
Product Description: calcium-dependent protein kinase 5
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.7.1.1 (Hexokinase);2.7.11.1 (Non-specific serine/threonine protein kinase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0045177 | apical part of cell |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0020009 | microneme |
| Function | GO:0004683 | calmodulin-dependent protein kinase activity |
| Function | GO:0004674 | protein serine/threonine kinase activity |
| Process | GO:0035891 | exit from host cell |
| 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 | expressed | N/A | N/A |
| Ring | expressed | 0.99 | 0.66 |
| Trophozoite | not expressed | 0.18 | 0.89 |
| Schizont | expressed | 0.31 | 0.83 |
| Gametocyte | not expressed | 0.09 | 0.95 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1337800
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: 0.125 | MFS: -3.188 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1351500)
RMgmDB ABS Phenotype: Not tested (Pb ortholog: PBANKA_1351500)
Modification: Mutated | RMgm-4869
More info: PhenoPlasm Link
AlphaFill Uniprot ID: A0A5K1K8H0
"Best" AlphaFill ligand hit: PGO (s-1,2-propanediol, Local RMSD=0.28) with 3BQR (Global RMSD=7.29)
BRENDA EC Inhibitors:
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q6S4W0 | Calcium-dependent protein kinase 1 | OMA, OrthoMCL BLAST | CHEMBL2069957CHEMBL2069954CHEMBL1784959CHEMBL1784960... | |
| Q5CTY5 | Calcium/calmodulin dependent protein kinase with a kinas domain and 4 calmodulin-like EF hands | OrthoDB | CHEMBL2069954CHEMBL1784959CHEMBL1784960CHEMBL1784961... | |
| A0A7S7LIM2 | Uncharacterized protein | OrthoMCL BLAST | CHEMBL3108912CHEMBL2069957CHEMBL3108913CHEMBL2070049... | |
| P62343 | Calcium-dependent protein kinase 1 | Plasmodium falciparum | OrthoMCL BLAST | Purfalcamine, 1CID24762167CID24762168CID24762169... |
| A3FQ16 | Calmodulin-domain protein kinase 1, putative | OrthoMCL BLAST | CHEMBL2069954CHEMBL1784959CHEMBL1784960CHEMBL1784961... |
Ortholog Group (OrthoMCL): OG6_100153
Most Similar Human Ortholog: C9JEC5
TM-align score: 0.89 | RMSD: 1.57
Seq Identity: 0.31 | Length: 85 / 568
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000130822 | pregnancy up-regulated nonubiquitous CaM kinase |
| ENSG00000134072 | calcium/calmodulin dependent protein kinase I |
| ENSG00000152495 | calcium/calmodulin dependent protein kinase IV |
| ENSG00000183049 | calcium/calmodulin dependent protein kinase ID |
Protein Length: 568 | Molecular Weight (kDa): 66.248
UniProt ID(s): A0A5K1K8H0
PDB ID(s): None
Isoelectric Point: 6.43
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 | 3 | 36 | 18 | 39 |
| disruptive | 3 | 21 | 8 | 28 |
| missense | 3 | 21 | 8 | 22 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 9 | 69 | 27 | 34 |
| disruptive | 7 | 47 | 27 | 87 |
| missense | 7 | 37 | 25 | 59 |
PlasmoDB Total SNPs: 167
Non-coding: 141 | Synonymous: 21 | Nonsynonymous: 5 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 19507895 | Identification and characterization of novel small molecules as potent inhibitorsof the plasmodial calcium-dependent protein kinase 1. | Lemercier G, Fernandez-Montalvan A, ..., Leroy D | 10.1021/bi9005122 |
| 20466936 | A plant-like kinase in Plasmodium falciparum regulates parasite egress fromerythrocytes. | Dvorin JD, Martyn DC, ..., Duraisingh MT | 10.1126/science.1188191 |
| 25422853 | Pyrazoleamide compounds are potent antimalarials that target Na+ homeostasis inintraerythrocytic Plasmodium falciparum. | Vaidya AB, Morrisey JM, ..., Bergman LW | 10.1038/ncomms6521 |
| 29487234 | Calcium-Dependent Protein Kinase 5 Is Required for Release of Egress-Specific Organelles in Plasmodium falciparum | Absalon S, Blomqvist K, ..., Dvorin JD | 10.1128/mBio.00130-18 |
| 31915223 | Influence of Plasmodium falciparum Calcium-Dependent Protein Kinase 5 (Pf CDPK5)on the Late Schizont Stage Phosphoproteome | Blomqvist K, Helmel M, ..., Dvorin JD | 10.1128/mSphere.00921-19 |
| 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 |
| 30409756 | In silico analysis of plasmodium falciparum CDPK5 protein through molecularmodeling, docking and dynamics | Rout S, Mahapatra RK | 10.1016/j.jtbi.2018.10.045 |
| 32121557 | Genotypic Variation in Resistance Gene-Mediated Calcium Signaling and HormonalSignaling Involved in Effector-Triggered Immunity or Disease Susceptibility inthe Xanthomonas campestris pv. Campestris-Brassica napus Pathosystem | Mamun MA, Islam MT, ..., Kim TH | 10.3390/plants9030303 |
| 30782859 | Cryptosporidium parvum Subtilisin-Like Serine Protease (SUB1) Is Crucial for Parasite Egress from Host Cells | Nava S, White AC Jr, Castellanos-Gonzalez A | 10.1128/IAI.00784-18 |
| 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 |
| 24789795 | Evaluation of immune responses in mice after DNA immunization with putativeToxoplasma gondii calcium-dependent protein kinase 5 | Zhang NZ, Huang SY, ..., Zhu XQ | 10.1128/CVI.00059-14 |
| 27923926 | Reduced Activity of Mutant Calcium-Dependent Protein Kinase 1 Is Compensated inPlasmodium falciparum through the Action of Protein Kinase G | Bansal A, Ojo KK, ..., Miller LH | 10.1128/mBio.02011-16 |