About Gene List

PF3D7_0719200 (NEK4)

Genome location: Pf3D7_07_v3:840,693..843,025(+)

Genome classification: Core

Function and Localization

Product Description: NIMA related kinase 4

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
Function GO:0005524 ATP binding
Function GO:0004674 protein serine/threonine kinase activity
Process GO:0006468 protein phosphorylation
Process GO:0007165 signal transduction

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 not expressed 0.00 1.00
Trophozoite not expressed 0.01 0.99
Schizont not expressed 0.01 0.99
Gametocyte expressed 0.63 0.70

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0719200

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: 0.195 | MFS: -2.384 | #Insertions: 0

PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_0616700)

  • Relative Growth Rate: 0.97 ± 0.04
  • Confidence: 8.06

RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PY17X_0619400)

Modification: Disrupted | RMgm-4817

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: C0H4N8

"Best" AlphaFill ligand hit: OCT (n-octane, Local RMSD=0.08) with 1APM (Global RMSD=4.39)

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
P46734 Dual specificity mitogen-activated protein kinase kinase 3 Homo sapiens HOGENOM US8546404, 6CHEMBL3746157CHEMBL3746484CHEMBL3747095...
P45985 Dual specificity mitogen-activated protein kinase kinase 4 Homo sapiens HOGENOM US11370770, Compound 6aUS11370770, Compound 6bUS11370770, Compound 6cUS11370770, Compound 6d...
Q13188 Serine/threonine-protein kinase 3 Homo sapiens HOGENOM BI-D1870US10710978, Compound I-1US10710978, Compound I-9US10710978, Compound I-12...
Q8TDX7 Serine/threonine-protein kinase Nek7 Homo sapiens HOGENOM, OrthoDB US11713321, Example 1US11713321, Example 6US11713321, Example 7US11713321, Example 8...
P31938 Dual specificity mitogen-activated protein kinase kinase 1 Mus musculus HOGENOM CHEMBL188343CHEMBL1998165US8575391, Q
Q01986 Dual specificity mitogen-activated protein kinase kinase 1/2 HOGENOM CHEMBL3326331
P51955 Serine/threonine-protein kinase Nek2 HOGENOM, OrthoDB US9505766, 10US9505766, 11US9505766, 12US9505766, 13...
O14733 Dual specificity mitogen-activated protein kinase kinase 7 HOGENOM CHEBI:67559CHEMBL507249CHEMBL4095253CHEMBL1801950...
Q9P289 Serine/threonine-protein kinase 26 Homo sapiens HOGENOM US9156845, 4US9156845, 6CHEMBL3393445CHEMBL3393450...
P52564 Dual specificity mitogen-activated protein kinase kinase 6 Homo sapiens HOGENOM Staurosporine, 8L-783277Staurosporine, 8CHEMBL4568087...
P36506 Dual specificity mitogen-activated protein kinase kinase 2 HOGENOM PD-98059CHEMBL3326332CHEMBL3326319CHEMBL3326325...
Q86SG6 Serine/threonine-protein kinase Nek8 OrthoDB Staurosporine, 8Staurosporine, 8
Q6P3R8 Serine/threonine-protein kinase Nek5 Homo sapiens OrthoDB CHEMBL3745885Staurosporine, 8Staurosporine, 8
Q8TD19 Serine/threonine-protein kinase Nek9 Homo sapiens OrthoDB Staurosporine, 8Staurosporine, 8CHEMBL4793380
Q9HC98 Serine/threonine-protein kinase Nek6 Homo sapiens OrthoDB CHEMBL1272140CHEMBL1271644CHEMBL1271870med.21724, Compound 4...
Q8NG66 Serine/threonine-protein kinase Nek11 Homo sapiens OrthoDB Staurosporine, 8Staurosporine, 8
P51957 Serine/threonine-protein kinase Nek4 Homo sapiens OrthoDB CHEMBL2171124Staurosporine, 8CHEMBL4550702CHEMBL4568087...
Q96PY6 Serine/threonine-protein kinase Nek1 OrthoDB US9051313, StaurosporineUS9051313, StaurosporineCHEMBL3745885CHEMBL1276848...

Orthology Information

Ortholog Group (OrthoMCL): OG6_105432

Most Similar Human Ortholog: P51957

TM-align score: 0.87 | RMSD: 2.83

Seq Identity: 0.38 | Length: 299 / 310

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000114904 NIMA related kinase 4

Protein Information

Protein Length: 310 | Molecular Weight (kDa): 36.35

UniProt ID(s): C0H4N8

PDB ID(s): None

Isoelectric Point: 9.69

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
InterPro IPR017441 Protein kinase, ATP binding site
PFam PF00069 Protein kinase domain
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 2 8 6 21
disruptive 0 0 1 8
missense 0 0 1 6

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 3 16 13 22
disruptive 0 9 5 36
missense 0 5 4 21

PlasmoDB Total SNPs: 161

Non-coding: 145 | Synonymous: 12 | Nonsynonymous: 2 | Stop Codon: 2

Associated Publications

PMID Title Authors DOI/Link
15970588 A NIMA-related protein kinase is essential for completion of the sexual cycle ofmalaria parasites. Reininger L, Billker O, ..., Doerig C 10.1074/jbc.M504523200
36810637 A non-canonical sensing pathway mediates Plasmodium adaptation to amino aciddeficiency Marreiros IM, Marques S, ..., Mota MM 10.1038/s42003-023-04566-y