Product Description: calcium-dependent protein 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:0005737 | cytoplasm |
| Component | GO:0016020 | membrane |
| Component | GO:0005634 | nucleus |
| Component | GO:0005886 | plasma membrane |
| Component | GO:0020004 | symbiont-containing vacuolar space |
| Component | GO:0020003 | symbiont-containing vacuole |
| Component | GO:0020005 | symbiont-containing vacuole membrane |
| Function | GO:0071889 | 14-3-3 protein binding |
| Function | GO:0009931 | calcium-dependent protein serine/threonine kinase activity |
| Function | GO:0005516 | calmodulin binding |
| Function | GO:0005515 | protein binding |
| Function | GO:0004674 | protein serine/threonine kinase activity |
| Process | GO:0044409 | entry into host |
| Process | GO:0035891 | exit from host cell |
| Process | GO:0035556 | intracellular signal transduction |
| Process | GO:0018105 | peptidyl-serine phosphorylation |
| Process | GO:0046777 | protein autophosphorylation |
| Process | GO:0006468 | protein phosphorylation |
| Process | GO:0042493 | response to drug |
| 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 | 0.19 | 0.92 |
| Trophozoite | expressed | 0.10 | 0.93 |
| Schizont | expressed | 1.65 | 0.30 |
| Gametocyte | expressed | 0.32 | 0.81 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0217500
Resistome Missense Mutations: Q358E
Resistome Compounds with Missense Mutations: MMV1081413, OSM-S-106
Resistome # Samples with Disruptive Mutations: 7 (7 missense, 7 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.27 | MFS: -2.631 | #Insertions: 0
PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_0314200)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0314200)
Modification: Tagged | RMgm-4553
More info: PhenoPlasm Link
AlphaFill Uniprot ID: P62344
"Best" AlphaFill ligand hit: D1D ((4s,5s)-1,2-dithiane-4,5-diol, Local RMSD=0.25) with 2YA9 (Global RMSD=2.71)
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, OrthoDB, OrthoMCL BLAST | CHEMBL2069957CHEMBL2070050CHEMBL2070050CHEMBL2070081 |
| A3FQ16 | Calmodulin-domain protein kinase 1, putative | OrthoDB, OrthoMCL BLAST | CHEMBL2069954CHEMBL1784959CHEMBL1784960CHEMBL1784961... | |
| Q5CTY5 | Calcium/calmodulin dependent protein kinase with a kinas domain and 4 calmodulin-like EF hands | OrthoMCL BLAST | CHEMBL2069954CHEMBL1784959CHEMBL1784960CHEMBL1784961... | |
| A0A7S7LIM2 | Uncharacterized protein | OrthoMCL BLAST | CHEMBL3108912CHEMBL2069957CHEMBL3108913CHEMBL2070049... | |
| 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... |
Protein Length: 524 | Molecular Weight (kDa): 60.8
UniProt ID(s): A0A143ZWW4, P62344
PDB ID(s): None
Isoelectric Point: 7.57
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 | 35 | 21 | 43 |
| disruptive | 0 | 3 | 6 | 14 |
| missense | 0 | 2 | 6 | 11 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 9 | 68 | 30 | 42 |
| disruptive | 0 | 22 | 21 | 82 |
| missense | 0 | 13 | 16 | 53 |
PlasmoDB Total SNPs: 347
Non-coding: 311 | Synonymous: 32 | Nonsynonymous: 2 | Stop Codon: 2
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 8142371 | Calcium-binding properties of a calcium-dependent protein kinase from Plasmodiumfalciparum and the significance of individual calcium-binding sites for kinaseactivation. | Zhao Y, Pokutta S, ..., Kappes B | 10.1021/bi00178a031 |
| 9804551 | Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Tettelin H, ..., Hoffman SL | 10.1126/science.282.5391.1126 |
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 15491359 | Export of Plasmodium falciparum calcium-dependent protein kinase 1 to theparasitophorous vacuole is dependent on three N-terminal membrane anchor motifs. | Moskes C, Burghaus PA, ..., Kappes B | 10.1111/j.1365-2958.2004.04313.x |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 20485427 | Thousands of chemical starting points for antimalarial lead identification. | Gamo FJ, Sanz LM, ..., Garcia-Bustos JF | 10.1038/nature09107 |
| 22479457 | Subcellular location, phosphorylation and assembly into the motor complex ofGAP45 during Plasmodium falciparum schizont development. | Ridzuan MA, Moon RW, ..., Green JL | 10.1371/journal.pone.0033845 |
| 23204525 | Characterization of Plasmodium falciparum calcium-dependent protein kinase 1(PfCDPK1) and its role in microneme secretion during erythrocyte invasion. | Bansal A, Singh S, ..., Chitnis CE | 10.1074/jbc.M112.411934 |
| 23548171 | Inhibition of Plasmodium falciparum CDPK1 by conditional expression of itsJ-domain demonstrates a key role in schizont development. | Azevedo MF, Sanders PR, ..., Gilson PR | 10.1042/BJ20130124 |
| 25070106 | Biochemical and antiparasitic properties of inhibitors of the Plasmodiumfalciparum calcium-dependent protein kinase PfCDPK1. | Ansell KH, Jones HM, ..., Holder AA | 10.1128/AAC.02959-14 |
| 26149123 | Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hubregulating egress and invasion. | Alam MM, Solyakov L, ..., Tobin AB | 10.1038/ncomms8285 |
| 28680058 | PfCDPK1 mediated signaling in erythrocytic stages of Plasmodium falciparum. | Kumar S, Kumar M, ..., Sharma P | 10.1038/s41467-017-00053-1 |
| 29311293 | PfCDPK1 is critical for malaria parasite gametogenesis and mosquito infection. | Bansal A, Molina-Cruz A, ..., Miller LH | 10.1073/pnas.1715443115 |
| 29716996 | Calcium-dependent phosphorylation of Plasmodium falciparum serine repeat antigen5 triggers merozoite egress. | Iyer GR, Singh S, ..., Malhotra P | 10.1074/jbc.RA117.001540 |
| 32003970 | Protein S-Palmitoylation Is Responsive to External Signals and Plays a RegulatoryRole in Microneme Secretion in Plasmodium falciparum Merozoites. | Siddiqui MA, Singh S, Malhotra P, Chitnis CE | 10.1021/acsinfecdis.9b00321 |
| 32484216 | Molecular dynamics simulations and biochemical characterization of Pf14-3-3 andPfCDPK1 interaction towards its role in growth of human malaria parasite. | Jain R, Dey P, ..., Singh S | 10.1042/BCJ20200145 |
| 32817103 | Phosphorylation-Dependent Assembly of a 14-3-3 Mediated Signaling Complex during Red Blood Cell Invasion by Plasmodium falciparum Merozoites | More KR, Kaur I, ..., Chitnis CE | 10.1128/mBio.01287-20 |
| 33024030 | Phosphorylation of Rhoptry Protein Rhop H3 Is Critical for Host Cell Invasion bythe Malaria Parasite | Ekka R, Gupta A, ..., Sharma P | 10.1128/mBio.00166-20 |
| 36712004 | Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulatesmicroneme exocytosis in Toxoplasma | Chan AW, Broncel M, ..., Lourido S | 10.1101/2023.01.11.523553 |
| 37889572 | An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion andCongenital Infection in Sheep Experimentally Infected With Toxoplasma gondii | Sanchez-Sanchez R, Imhof D, ..., Ortega-Mora LM | 10.1093/infdis/jiad470 |
| 35216497 | Common Molecular Targets of a Quinolone Based Bumped Kinase Inhibitor in Neosporacaninum and Danio rerio | Muller J, Anghel N, ..., Hemphill A | 10.3390/ijms23042381 |
| 34030110 | In vitro activity, safety and in vivo efficacy of the novel bumped kinaseinhibitor BKI-1748 in non-pregnant and pregnant mice experimentally infected withNeospora caninum tachyzoites and Toxoplasma gondii oocysts | Imhof D, Anghel N, ..., Hemphill A | 10.1016/j.ijpddr.2021.05.001 |
| 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 |
| 34108954 | cAMP-Dependent Signaling Pathways as Potential Targets for Inhibition ofPlasmodium falciparum Blood Stages | Lasonder E, More K, ..., Chitnis CE | 10.3389/fmicb.2021.684005 |
| 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 |
| 37933960 | Analysis of CDPK1 targets identifies a trafficking adaptor complex that regulatesmicroneme exocytosis in Toxoplasma | Chan AW, Broncel M, ..., Lourido S | 10.7554/eLife.85654 |
| 36012208 | Mitogen-Activated Protein Kinases Associated Sites of Tobacco Repression of ShootGrowth Regulates Its Localization in Plant Cells | Wang L, Gui Y, ..., Jiang C | 10.3390/ijms23168941 |
| 37610220 | CDPK2A and CDPK1 form a signaling module upstream of Toxoplasma motility | Shortt E, Hackett CG, ..., Lourido S | 10.1128/mbio.01358-23 |
| 35775739 | Inner membrane complex proteomics reveals a palmitoylation regulation criticalfor intraerythrocytic development of malaria parasite | Qian P, Wang X, ..., Yuan J | 10.7554/eLife.77447 |
| 35709874 | Allosteric regulation of the inactive to active state conformational transitionin CDPK1 protein of Plasmodium falciparum | Gupta P, Mohanty D | 10.1016/j.ijbiomac.2022.06.065 |
| 34569223 | Chemogenomic Fingerprints Associated with Stage-Specific Gametocytocidal CompoundAction against Human Malaria Parasites | Niemand J, van Biljon R, ..., Birkholtz LM | 10.1021/acsinfecdis.1c00373 |