About Gene List

PF3D7_1349300 (TKL3)

Genome location: Pf3D7_13_v3:1,976,376..1,982,692(+)

Genome classification: Core

Function and Localization

Product Description: tyrosine kinase-like protein

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.7.10.2 (Non-specific protein-tyrosine kinase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005737 cytoplasm
Component GO:0015630 microtubule cytoskeleton
Function GO:0004672 protein kinase activity
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 not expressed N/A N/A
Ring not expressed 0.25 0.88
Trophozoite possibly expressed 0.53 0.71
Schizont expressed 0.94 0.51
Gametocyte expressed 0.86 0.54

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1349300

Resistome Missense Mutations: I600S, Y601D, N602D, N609S

Resistome Compounds with Missense Mutations: AN13762

Resistome # Samples with Disruptive Mutations: 1 (1 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Mutable in CDS

MIS: 0.927 | MFS: -2.909 | #Insertions: 1

PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1362100)

  • Relative Growth Rate: 0.97 ± 0.02
  • Confidence: 8.93

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1362100)

Modification: Disrupted | RMgm-3707

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IDK6

"Best" AlphaFill ligand hit: ADN (adenosine, Local RMSD=0.39) with 6FEK (Global RMSD=3.29)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.7.10.2 non-specific protein-tyrosine kinase ADPPP1PP2T47ChkCskPIP2CMP6RNAiWASPmorinAG490...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_100006

Most Similar Human Ortholog: E7ERW9

TM-align score: 0.63 | RMSD: 3.16

Seq Identity: 0.13 | Length: 64 / 1807

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000078061 A-Raf proto-oncogene, serine/threonine kinase
ENSG00000104312 receptor interacting serine/threonine kinase 2
ENSG00000132155 Raf-1 proto-oncogene, serine/threonine kinase
ENSG00000135341 mitogen-activated protein kinase kinase kinase 7
ENSG00000157764 B-Raf proto-oncogene, serine/threonine kinase

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 15 107 65 111
disruptive 112 223 127 292
missense 61 160 115 235

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 28 201 73 127
disruptive 157 416 234 380
missense 80 317 196 278

PlasmoDB Total SNPs: 292

Non-coding: 73 | Synonymous: 118 | Nonsynonymous: 101 | Stop Codon: 0

Protein Information

Protein Length: 1807 | Molecular Weight (kDa): 212.531

UniProt ID(s): Q8IDK6, Q8WSL1

PDB ID(s): None

Isoelectric Point: 6.75

Protein Domain Annotations:

Source Family ID Description
InterPro IPR000719 Protein kinase domain
InterPro IPR001245 Serine-threonine/tyrosine-protein kinase, catalytic domain
InterPro IPR001660 Sterile alpha motif domain
InterPro IPR008271 Serine/threonine-protein kinase, active site
InterPro IPR011009 Protein kinase-like domain superfamily
InterPro IPR013761 Sterile alpha motif/pointed domain superfamily
InterPro IPR017441 Protein kinase, ATP binding site
PFam PF07647 Sterile alpha motif domain
PFam PF07714 Serine-threonine/tyrosine-protein kinase, catalytic domain
Superfamily SSF47769 Sterile alpha motif/pointed domain superfamily
Superfamily SSF56112 Protein kinase-like domain superfamily

Associated Publications

PMID Title Authors DOI/Link
16267556 A protein interaction network of the malaria parasite Plasmodium falciparum. LaCount DJ, Vignali M, ..., Hughes RE 10.1038/nature04104
20582613 SAM domain-dependent activity of PfTKL3, an essential tyrosine kinase-like kinaseof the human malaria parasite Plasmodium falciparum. Abdi A, Eschenlauer S, Reininger L, Doerig C 10.1007/s00018-010-0434-3
25732065 A genome-scale vector resource enables high-throughput reverse genetic screeningin a malaria parasite Gomes AR, Bushell E, ..., Billker O 10.1016/j.chom.2015.01.014