Genome location: Pf3D7_12_v3:2,094,748..2,096,876(-)
Genome classification: Core
Product Description: thymidylate kinase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.7.4.9 (dTMP kinase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005829 | cytosol |
| Component | GO:0005739 | mitochondrion |
| Component | GO:0005634 | nucleus |
| Function | GO:0004550 | nucleoside diphosphate kinase activity |
| Function | GO:0004798 | thymidylate kinase activity |
| Function | GO:0009041 | uridylate kinase activity |
| Process | GO:0006233 | dTDP biosynthetic process |
| Process | GO:0006235 | dTTP biosynthetic process |
| Process | GO:0006227 | dUDP biosynthetic process |
| Process | GO:0009410 | response to xenobiotic stimulus |
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 | 0.04 | 0.98 |
| Trophozoite | possibly expressed | 0.39 | 0.75 |
| Schizont | possibly expressed | 0.22 | 0.85 |
| Gametocyte | expressed | 0.42 | 0.75 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1251300
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.158 | MFS: -2.775 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I4S1
"Best" AlphaFill ligand hit: ADP (adenosine-5'-diphosphate, Local RMSD=0.16) with 2WWF (Global RMSD=1.62)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.7.4.9 | dTMP kinase | BRENDA SOAP query unsuccessful |
Orthology to BindingDB Entries:
Ortholog Group (OrthoMCL): OG6_100714
Most Similar Human Ortholog: P23919
TM-align score: 0.94 | RMSD: 1.56
Seq Identity: 0.38 | Length: 208 / 210
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000168393 | deoxythymidylate kinase |
Protein Length: 210 | Molecular Weight (kDa): 24.691
UniProt ID(s): Q8I4S1
PDB ID(s): 2WWF, 2WWG, 2WWH, 2WWI, 2YOF, 2YOG, 2YOH
Isoelectric Point: 6.76
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR018094 | Thymidylate kinase |
| InterPro | IPR018095 | Thymidylate kinase, conserved site |
| InterPro | IPR027417 | P-loop containing nucleoside triphosphate hydrolase |
| InterPro | IPR039430 | Thymidylate kinase-like domain |
| PFam | PF02223 | Thymidylate kinase-like domain |
| Superfamily | SSF52540 | P-loop containing nucleoside triphosphate hydrolase |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 3 | 10 | 4 | 18 |
| disruptive | 2 | 9 | 10 | 12 |
| missense | 2 | 9 | 9 | 11 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 27 | 12 | 12 |
| disruptive | 3 | 25 | 17 | 30 |
| missense | 2 | 21 | 13 | 21 |
PlasmoDB Total SNPs: 190
Non-coding: 183 | Synonymous: 6 | Nonsynonymous: 1 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 18477629 | Molecular characterization, heterologous expression and kinetic analysis ofrecombinant Plasmodium falciparum thymidylate kinase. | Kandeel M, Kitade Y | 10.1093/jb/mvn062 |
| 20353400 | Structural basis for the efficient phosphorylation of AZT-MP(3'-azido-3'-deoxythymidine monophosphate) and dGMP by Plasmodium falciparum typeI thymidylate kinase. | Whittingham JL, Carrero-Lerida J, ..., Gonzalez-Pacanowska D | 10.1042/BJ20091880 |
| 29684273 | Interaction of alpha-Thymidine Inhibitors with Thymidylate Kinase from Plasmodiumfalciparum. | Chen MD, Sinha K, Rule GS, Ly DH | 10.1021/acs.biochem.8b00162 |
| 38127294 | Structure-based virtual screening against multiple Plasmodium falciparum kinases reveals antimalarial compounds | Godara P, Reddy KS, ..., Prusty D | 10.1007/s11030-023-10770-z |