About Gene List

PF3D7_0211700 (TKL1)

Genome location: Pf3D7_02_v3:469,408..474,167(+)

Genome classification: Core

Function and Localization

Product Description: tyrosine kinase-like protein, putative

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
Component GO:0005737 cytoplasm
Component GO:1903561 extracellular vesicle
Component GO:0005739 mitochondrion
Function GO:0004672 protein 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 0.10 0.95
Trophozoite expressed 0.78 0.58
Schizont possibly expressed 0.43 0.74
Gametocyte possibly expressed 0.45 0.75

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0211700

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: -2.366 | #Insertions: 7

PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_0308500)

  • Relative Growth Rate: 0.99 ± 0.05
  • Confidence: 7.58

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0308500)

Modification: Disrupted | RMgm-1780

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: O96197

"Best" AlphaFill ligand hit: H52 ((s)-2-methyl-1-[(4-methyl-5-isoquinoline)sulfonyl]-homopiperazine, Local RMSD=0.49) with 4F1T (Global RMSD=3.89)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.7.11.1 non-specific serine/threonine protein kinase ATPKClDTTP53DRBEDTATBCAKN-93K252aCKI-7LAALSTAACS...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_105153

Most Similar Human Ortholog: C9IYH2

TM-align score: 0.76 | RMSD: 1.85

Seq Identity: 0.05 | Length: 37 / 1233

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000073803 mitogen-activated protein kinase kinase kinase 13
ENSG00000139625 mitogen-activated protein kinase kinase kinase 12

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 10 41 26 58
disruptive 82 170 80 171
missense 52 105 60 122

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 14 85 28 55
disruptive 148 285 110 240
missense 68 197 90 168

PlasmoDB Total SNPs: 304

Non-coding: 118 | Synonymous: 80 | Nonsynonymous: 106 | Stop Codon: 0

Protein Information

Protein Length: 1233 | Molecular Weight (kDa): 148.227

UniProt ID(s): O96197

PDB ID(s): None

Isoelectric Point: 10.07

Protein Domain Annotations:

Source Family ID Description
InterPro IPR000719 Protein kinase domain
InterPro IPR001245 Serine-threonine/tyrosine-protein kinase, catalytic domain
InterPro IPR003409 MORN motif
InterPro IPR008271 Serine/threonine-protein kinase, active site
InterPro IPR011009 Protein kinase-like domain superfamily
InterPro IPR013761 Sterile alpha motif/pointed domain superfamily
PFam PF00069 Protein kinase domain
Superfamily SSF47769 Sterile alpha motif/pointed domain superfamily
Superfamily SSF56112 Protein kinase-like domain superfamily

Associated Publications

PMID Title Authors DOI/Link
9804551 Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Tettelin H, ..., Hoffman SL 10.1126/science.282.5391.1126
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
33608523 20S proteasomes secreted by the malaria parasite promote its growth. Dekel E, Yaffe D, ..., Regev-Rudzki N 10.1038/s41467-021-21344-8
34494883 A Prioritized and Validated Resource of Mitochondrial Proteins in PlasmodiumIdentifies Unique Biology. van Esveld SL, Meerstein-Kessel L, ..., Huynen MA 10.1128/mSphere.00614-21
32307750 Development of new dominant selectable markers for the nonconventional yeastsOgataea polymorpha and Candida famata Bratiichuk D, Kurylenko O, ..., Sibirny A 10.1002/yea.3467
28352301 Functional overexpression of genes involved in erythritol synthesis in the yeastYarrowia lipolytica Mironczuk AM, Biegalska A, Dobrowolski A 10.1186/s13068-017-0772-6
29729128 A High-throughput workflow for CRISPR/Cas9 mediated combinatorial promoterreplacements and phenotype characterization in yeast Kuivanen J, Holmstrom S, ..., Jantti J 10.1002/biot.201700593
34592433 Crabtree/Warburg-like aerobic xylose fermentation by engineered Saccharomycescerevisiae Lee SB, Tremaine M, ..., Sato TK 10.1016/j.ymben.2021.09.008
30252062 Reassessment of requirements for anaerobic xylose fermentation by engineered,non-evolved Saccharomyces cerevisiae strains Bracher JM, Martinez-Rodriguez OA, ..., Pronk JT 10.1093/femsyr/foy104
30711353 Peroxisomal Fba2p and Tal2p complementally function in the rearrangement pathwayfor xylulose 5-phosphate in the methylotrophic yeast Pichia pastoris Fukuoka H, Kawase T, ..., Nakagawa T 10.1016/j.jbiosc.2019.01.008
30586497 Metabolic Engineering of Saccharomyces cerevisiae for Production of Shinorine, aSunscreen Material, from Xylose Park SH, Lee K, Jang JW, Hahn JS 10.1021/acssynbio.8b00388
31996457 Toxoplasma gondii tkl1 Deletion Mutant Is a Promising Vaccine against Acute,Chronic, and Congenital Toxoplasmosis in Mice Wang JL, Liang QL, ..., Zhu XQ 10.4049/jimmunol.1900410
28181081 Genetic improvement of xylose metabolism by enhancing the expression of pentosephosphate pathway genes in Saccharomyces cerevisiae IR-2 for high-temperatureethanol production Kobayashi Y, Sahara T, ..., Fujimori KE 10.1007/s10295-017-1912-5
30034524 Peroxisomes and peroxisomal transketolase and transaldolase enzymes are essentialfor xylose alcoholic fermentation by the methylotrophic thermotolerant yeast,Ogataea (Hansenula) polymorpha Kurylenko OO, Ruchala J, ..., Sibirny AA 10.1186/s13068-018-1203-z
29621349 Signature pathway expression of xylose utilization in the genetically engineeredindustrial yeast Saccharomyces cerevisiae Feng Q, Liu ZL, Weber SA, Li S 10.1371/journal.pone.0195633
31863218 Comparative transcriptome analysis of genomic region deletion strain withenhanced L-tyrosine production in Saccharomyces cerevisiae Wu Y, Cai M, ..., Qiao M 10.1007/s10529-019-02784-1
30151682 Systematic optimization of gene expression of pentose phosphate pathway enhancesethanol production from a glucose/xylose mixed medium in a recombinantSaccharomyces cerevisiae Kobayashi Y, Sahara T, ..., Fujimori KE 10.1186/s13568-018-0670-8
32653007 The influence of transketolase on lipid biosynthesis in the yeast Yarrowialipolytica Dobrowolski A, Mironczuk AM 10.1186/s12934-020-01398-x