About Gene List

PF3D7_0615500 (CRK5)

Genome location: Pf3D7_06_v3:642,699..646,241(+)

Genome classification: Core

Function and Localization

Product Description: cdc2-related protein kinase 5

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:0005737 cytoplasm
Component GO:1903561 extracellular vesicle
Component GO:0016592 mediator complex
Component GO:0016020 membrane
Component GO:0005634 nucleus
Component GO:0048471 perinuclear region of cytoplasm
Function GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity
Function GO:0004693 cyclin-dependent protein serine/threonine kinase activity
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 expressed N/A N/A
Ring not expressed 0.06 0.97
Trophozoite expressed 0.37 0.78
Schizont expressed 0.33 0.81
Gametocyte expressed 0.54 0.71

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0615500

Resistome Missense Mutations: N330D

Resistome Compounds with Missense Mutations: AN13762, DSM1, Halofuginone

Resistome # Samples with Disruptive Mutations: 28 (28 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.133 | MFS: -2.786 | #Insertions: 0

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: Not tested (Pb ortholog: PBANKA_1230200)

Modification: Tagged | RMgm-4848

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: C6KSZ6

"Best" AlphaFill ligand hit: HVK (pyridin-2-amine, Local RMSD=0.07) with 6QA1 (Global RMSD=5.01)

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_160728

No human ortholog(s)

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 3 30 14 60
disruptive 39 46 24 75
missense 11 20 15 52

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 10 85 34 50
disruptive 60 129 63 172
missense 17 64 49 101

PlasmoDB Total SNPs: 208

Non-coding: 162 | Synonymous: 27 | Nonsynonymous: 19 | Stop Codon: 0

Protein Information

Protein Length: 705 | Molecular Weight (kDa): 82.948

UniProt ID(s): C6KSZ6

PDB ID(s): None

Isoelectric Point: 8.82

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
12368867 Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. Hall N, Pain A, ..., Barrell BG 10.1038/nature01095
33608523 20S proteasomes secreted by the malaria parasite promote its growth. Dekel E, Yaffe D, ..., Regev-Rudzki N 10.1038/s41467-021-21344-8
14756307 Sensitization of defense responses and activation of programmed cell death by apathogen-induced receptor-like protein kinase in Arabidopsis Chen K, Du L, Chen Z 10.1023/B:PLAN.0000009265.72567.58
28830940 The Toxoplasma Centrocone Houses Cell Cycle Regulatory Factors Naumov A, Kratzer S, ..., White MW 10.1128/mBio.00579-17
29141230 Sub-minute Phosphoregulation of Cell Cycle Systems during Plasmodium GameteFormation Invergo BM, Brochet M, ..., Billker O 10.1016/j.celrep.2017.10.071
32568069 A divergent cyclin/cyclin-dependent kinase complex controls the atypicalreplication of a malaria parasite during gametogony and transmission Balestra AC, Zeeshan M, ..., Brochet M 10.7554/eLife.56474
36154191 Plasmodium falciparum CRK5 Is Critical for Male Gametogenesis and Infection ofthe Mosquito Kumar S, Gargaro OR, Kappe SHI 10.1128/mbio.02227-22
31817249 CRK5 Protein Kinase Contributes to the Progression of Embryogenesis ofArabidopsis thaliana Baba AI, Valkai I, ..., Cseplo A 10.3390/ijms20246120
22047078 Structural and evolutionary divergence of eukaryotic protein kinases inApicomplexa Talevich E, Mirza A, Kannan N 10.1186/1471-2148-11-321
27406784 Overexpression of an Arabidopsis cysteine-rich receptor-like protein kinase,CRK5, enhances abscisic acid sensitivity and confers drought tolerance Lu K, Liang S, ..., Zhang DP 10.1093/jxb/erw266