About Gene List

PF3D7_0310100 (CDPK3)

Genome location: Pf3D7_03_v3:422,379..424,680(+)

Genome classification: Core

Function and Localization

Product Description: calcium-dependent protein kinase 3

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.7.11.17 (Calcium/calmodulin-dependent protein kinase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005737 cytoplasm
Component GO:0005634 nucleus
Function GO:0009931 calcium-dependent protein serine/threonine kinase activity
Function GO:0005516 calmodulin binding
Function GO:0004683 calmodulin-dependent protein kinase activity
Process GO:0035556 intracellular signal transduction
Process GO:0018105 peptidyl-serine phosphorylation
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 0.15 0.92
Trophozoite possibly expressed 0.04 0.98
Schizont possibly expressed 0.02 0.98
Gametocyte expressed 0.10 0.94

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0310100

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Mutable in CDS

MIS: 1 | MFS: -3.018 | #Insertions: 2

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1351500)

  • Relative Growth Rate: 0.24 ± 0.22
  • Confidence: 4.39

RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_0408200)

Modification: Disrupted | RMgm-4547

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q9NJU9

"Best" AlphaFill ligand hit: PGO (s-1,2-propanediol, Local RMSD=0.09) with 2VZ6 (Global RMSD=2.06)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.7.11.17 Ca2+/calmodulin-dependent protein kinase NOADPGTPW13AIPEDTAEGTADTNBKN93KN62KN-93KN-62...

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
Q8IBS5 Calcium-dependent protein kinase 4 Plasmodium falciparum (isolate 3D7) HOGENOM CHEMBL2069957CHEMBL2070050CHEMBL2070050CHEMBL2070081
Q5CTY5 Calcium/calmodulin dependent protein kinase with a kinas domain and 4 calmodulin-like EF hands OrthoDB CHEMBL2069954CHEMBL1784959CHEMBL1784960CHEMBL1784961...
Q6S4W0 Calcium-dependent protein kinase 1 OrthoMCL BLAST CHEMBL2069957CHEMBL2069954CHEMBL1784959CHEMBL1784960...

Orthology Information

Ortholog Group (OrthoMCL): OG6_100153

Most Similar Human Ortholog: C9JEC5

TM-align score: 0.89 | RMSD: 1.17

Seq Identity: 0.25 | Length: 84 / 562

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 Information

Protein Length: 562 | Molecular Weight (kDa): 65.288

UniProt ID(s): Q9NJU9

PDB ID(s): 3K21

Isoelectric Point: 9.84

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

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 8 43 22 49
disruptive 4 13 14 53
missense 4 13 14 42

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 16 82 30 36
disruptive 10 56 44 142
missense 5 40 33 89

PlasmoDB Total SNPs: 140

Non-coding: 121 | Synonymous: 17 | Nonsynonymous: 2 | Stop Codon: 0

Associated Publications

PMID Title Authors DOI/Link
10448855 The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. Bowman S, Lawson D, ..., Barrell BG 10.1038/22964
12368867 Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. Hall N, Pain A, ..., Barrell BG 10.1038/nature01095
28746405 Biophysical characterization of the calmodulin-like domain of Plasmodiumfalciparum calcium dependent protein kinase 3. Andresen C, Niklasson M, ..., Lundstrom P 10.1371/journal.pone.0181721
32864371 In-depth computational analysis of calcium-dependent protein kinase 3 ofToxoplasma gondii provides promising targets for vaccination Majidiani H, Soltani S, ..., Foroutan M 10.7774/cevr.2020.9.2.146
24945436 The calcium-dependent protein kinase 3 of toxoplasma influences basal calciumlevels and functions beyond egress as revealed by quantitative phosphoproteomeanalysis Treeck M, Sanders JL, ..., Boothroyd JC 10.1371/journal.ppat.1004197
24514873 Two calcium-dependent protein kinases from Chlamydomonas reinhardtii are transcriptionally regulated by nutrient starvation Motiwalla MJ, Sequeira MP, D'Souza JS 10.4161/psb.27969
36818849 Calcium-dependent protein kinase CDPK16 phosphorylates serine-856 of glutamatereceptor-like GLR3.6 protein leading to salt-responsive root growth inArabidopsis() Silamparasan D, Chang IF, Jinn TL 10.3389/fpls.2023.1093472
24974733 Rapid construction and screening of artificial microRNA systems in Chlamydomonasreinhardtii Hu J, Deng X, ..., Huang K 10.1111/tpj.12606
36265000 A positive feedback loop mediates crosstalk between calcium, cyclic nucleotideand lipid signalling in calcium-induced Toxoplasma gondii egress Nofal SD, Dominicus C, ..., Treeck M 10.1371/journal.ppat.1010901
31425673 Vaccination with recombinant Toxoplasma gondii CDPK3 induces protective immunityagainst experimental toxoplasmosis Wu M, An R, ..., Du J 10.1016/j.actatropica.2019.105148
30673152 Calcium negatively regulates secretion from dense granules in Toxoplasma gondii Katris NJ, Ke H, ..., Waller RF 10.1111/cmi.13011
35757711 Toxoplasma gondii CDPK3 Controls the Intracellular Proliferation of Parasites inMacrophages Wu M, An R, ..., Du J 10.3389/fimmu.2022.905142
16796674 Plasmodium berghei calcium-dependent protein kinase 3 is required for ookinetegliding motility and mosquito midgut invasion Siden-Kiamos I, Ecker A, ..., Billker O 10.1111/j.1365-2958.2006.05189.x
24176018 Protective immunity against Toxoplasma gondii induced by DNA immunization withthe gene encoding a novel vaccine candidate: calcium-dependent protein kinase 3 Zhang NZ, Huang SY, ..., Zhu XQ 10.1186/1471-2334-13-512
35986017 Live-attenuated ME49Deltacdpk3 strain of Toxoplasma gondii protects against acute andchronic toxoplasmosis Wu M, Liu S, ..., Du J 10.1038/s41541-022-00518-5
35142606 Anti-Toxoplasma gondii effect of lupane-type triterpenes from the bark of blackalder (Alnus glutinosa) and identification of a potential target by reversedocking Darme P, Escotte-Binet S, ..., Aubert D 10.1051/parasite/2022008
35003067 Protective Effect Against Toxoplasmosis in BALB/c Mice Vaccinated WithRecombinant Toxoplasma gondii MIF, CDPK3, and 14-3-3 Protein Cocktail Vaccine Liu F, Wu M, ..., Du J 10.3389/fimmu.2021.755792
38310017 Protective effect against toxoplasmosis in BALB/C mice vaccinated withrecombinant Toxoplasma gondii CDPK3, GRA35, and ROP46 protein cocktail vaccine Li D, Han M, ..., An R 10.1016/j.vaccine.2024.01.050
30402958 Characterisation of the Toxoplasma gondii tyrosine transporter and itsphosphorylation by the calcium-dependent protein kinase 3 Wallbank BA, Dominicus CS, ..., Treeck M 10.1111/mmi.14156
28258212 A forward genetic screen identifies a negative regulator of rapidCa(2+)-dependent cell egress (MS1) in the intracellular parasite Toxoplasmagondii McCoy JM, Stewart RJ, ..., Tonkin CJ 10.1074/jbc.M117.775114
37272703 Identification of Toxoplasma calcium-dependent protein kinase 3 as astress-activated elongation factor 2 kinase Lis A, Baptista CG, ..., Blader IJ 10.1128/msphere.00156-23