About Gene List

PF3D7_0317200 (CRK4)

Genome location: Pf3D7_03_v3:689,618..696,787(-)

Genome classification: Core

Function and Localization

Product Description: cdc2-related protein kinase 4

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.7.11.22 (Cyclin-dependent kinase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005829 cytosol
Component GO:0005634 nucleus
Component GO:0005956 protein kinase CK2 complex
Function GO:0004672 protein kinase activity
Function GO:0004674 protein serine/threonine kinase activity
Process GO:0006260 DNA replication
Process GO:0000278 mitotic cell cycle
Process GO:0018105 peptidyl-serine phosphorylation
Process GO:0018107 peptidyl-threonine phosphorylation
Process GO:0006468 protein phosphorylation
Process GO:0051726 regulation of cell cycle

Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):

Stage LR class MCA mean MCA prop. zeros
Sporozoite not expressed N/A N/A
Ring possibly expressed 0.14 0.93
Trophozoite expressed 0.93 0.54
Schizont expressed 1.54 0.36
Gametocyte expressed 0.40 0.77

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0317200

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: Non - Mutable in CDS

MIS: 0.325 | MFS: -2.565 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0808000)

  • Relative Growth Rate: 0.05 ± 0.06
  • Confidence: 7.17

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: O77385

"Best" AlphaFill ligand hit: 42J (2-(3,4-dichlorophenyl)ethanamine, Local RMSD=0.11) with 5CLP (Global RMSD=13.71)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.7.11.22 cyclin-dependent kinase AMPDRBp16p18p21p27NMDATHZ1ICK1ICK2ICK3ICK4...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_146112

No human ortholog(s)

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 17 63 37 95
disruptive 97 193 120 222
missense 35 126 95 178

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 25 129 63 109
disruptive 143 378 189 312
missense 61 244 148 226

PlasmoDB Total SNPs: 283

Non-coding: 150 | Synonymous: 61 | Nonsynonymous: 72 | Stop Codon: 0

Protein Information

Protein Length: 1553 | Molecular Weight (kDa): 182.219

UniProt ID(s): O77385, Q25018

PDB ID(s): None

Isoelectric Point: 8.26

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
PFam PF00069 Protein kinase domain
Superfamily SSF56112 Protein kinase-like domain superfamily

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
16267556 A protein interaction network of the malaria parasite Plasmodium falciparum. LaCount DJ, Vignali M, ..., Hughes RE 10.1038/nature04104
28211852 Plasmodium falciparum CRK4 directs continuous rounds of DNA replication duringschizogony. Ganter M, Goldberg JM, ..., Duraisingh MT 10.1038/nmicrobiol.2017.17
37345936 Plasmodium falciparum CRK4 links early mitotic events to the onset of S-phaseduring schizogony Machado M, Klaus S, ..., Ganter M 10.1128/mbio.00779-23
15821135 Pairwise knockdowns of cdc2-related kinases (CRKs) in Trypanosoma bruceiidentified the CRKs for G1/S and G2/M transitions and demonstrated distinctivecytokinetic regulations between two developmental stages of the organism Tu X, Wang CC 10.1128/EC.4.4.755-764.2005
28263306 Erratum: Plasmodium falciparum CRK4 directs continuous rounds of DNA replicationduring schizogony Ganter M, Goldberg JM, ..., Duraisingh MT 10.1038/nmicrobiol.2017.38