About Gene List

PF3D7_0924300 (TPK)

Genome location: Pf3D7_09_v3:984,509..986,117(-)

Genome classification: Core

Function and Localization

Product Description: thiamine pyrophosphokinase

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 2.7.6.2 (Thiamine diphosphokinase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005829 cytosol
Component GO:0005739 mitochondrion
Function GO:0004788 thiamine diphosphokinase activity
Process GO:0009229 thiamine diphosphate biosynthetic process

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 0.13 0.93
Trophozoite expressed 0.42 0.75
Schizont possibly expressed 0.32 0.80
Gametocyte expressed 0.33 0.81

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0924300

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: 0.141 | MFS: -2.895 | #Insertions: 0

PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_0825200)

  • Relative Growth Rate: 1.01 ± 0.09
  • Confidence: 6.26

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0825200)

Modification: Disrupted | RMgm-2413

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: C0H556

"Best" AlphaFill ligand hit: VIB (3-(4-amino-2-methyl-pyrimidin-5-ylmethyl)-5-(2-hydroxy-ethyl)-4-methyl-thiazol-3-ium, Local RMSD=0.19) with 3LM8 (Global RMSD=7.72)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.7.6.2 thiamine diphosphokinase AMPNEMKCNNaFPCMBALT-711molybdatediphosphateoxythiaminepyrithiamineiodoacetamideButylthiamine...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_101973

Most Similar Human Ortholog: Q9H3S4

TM-align score: 0.91 | RMSD: 1.80

Seq Identity: 0.34 | Length: 236 / 400

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000196511 thiamin pyrophosphokinase 1

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 2 28 7 23
disruptive 2 49 26 71
missense 2 48 26 65

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 6 37 16 27
disruptive 8 103 51 113
missense 6 95 46 84

PlasmoDB Total SNPs: 34

Non-coding: 6 | Synonymous: 16 | Nonsynonymous: 12 | Stop Codon: 0

Protein Information

Protein Length: 400 | Molecular Weight (kDa): 46.709

UniProt ID(s): C0H556, Q14RW4

PDB ID(s): None

Isoelectric Point: 8.87

Protein Domain Annotations:

Source Family ID Description
InterPro IPR006282 Thiamin pyrophosphokinase
InterPro IPR007371 Thiamin pyrophosphokinase, catalytic domain
InterPro IPR007373 Thiamin pyrophosphokinase, thiamin-binding domain
InterPro IPR036371 Thiamin pyrophosphokinase, thiamin-binding domain superfamily
InterPro IPR036759 Thiamin pyrophosphokinase, catalytic domain superfamily
PFam PF04263 Thiamin pyrophosphokinase, catalytic domain
PFam PF04265 Thiamin pyrophosphokinase, thiamin-binding domain
Superfamily SSF63862 Thiamin pyrophosphokinase, thiamin-binding domain superfamily
Superfamily SSF63999 Thiamin pyrophosphokinase, catalytic 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
17132104 The human malaria parasite Plasmodium falciparum expresses an atypicalN-terminally extended pyrophosphokinase with specificity for thiamine. Eschbach ML, Muller IB, ..., Wrenger C 10.1515/BC.2006.197
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