Genome location: Pf3D7_14_v3:1,331,919..1,339,361(-)
Genome classification: Core
Product Description: DNA topoisomerase 2
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 5.6.2.2 (DNA topoisomerase (ATP-hydrolyzing));5.99.1.3 (Transferred entry: 5.6.2.2)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005634 | nucleus |
| Function | GO:0003918 | DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity |
| Process | GO:0006265 | DNA topological change |
| Process | GO:0044774 | mitotic DNA integrity checkpoint signaling |
| Process | GO:0000712 | resolution of meiotic recombination intermediates |
| Process | GO:0000819 | sister chromatid segregation |
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 | expressed | 1.84 | 0.33 |
| Trophozoite | expressed | 0.79 | 0.58 |
| Schizont | expressed | 0.70 | 0.60 |
| Gametocyte | not expressed | 0.80 | 0.61 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1433500
Resistome Missense Mutations: D941Y
Resistome Compounds with Missense Mutations: Desoxyepothilone B
Resistome # Samples with Disruptive Mutations: 1 (1 missense, 1 "interesting" missense)
Zhang Phenotype: Mutable in CDS
MIS: 0.774 | MFS: -2.962 | #Insertions: 1
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1454000)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8ILC8
"Best" AlphaFill ligand hit: AX7 (1h-benzimidazol-2-amine, Local RMSD=0.04) with 5Z4O (Global RMSD=5.28)
BRENDA EC Inhibitors:
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P11388 | DNA topoisomerase 2-alpha | HOGENOM, OrthoDB | BNS-22BNS-65CHEMBL4061346CHEMBL4064887... | |
| P15348 | DNA topoisomerase 2 | Drosophila melanogaster | HOGENOM, OMA, OrthoDB, OrthoMCL, OrthoMCL BLAST | CHEMBL91382CHEMBL3109309 |
| Q02880 | DNA topoisomerase 2-beta | Homo sapiens | OMA, OrthoDB | OFLOXACINNORFLOXACINLEVOFLOXACINCiprofloxacin... |
| P0AES6 | DNA gyrase subunit B | Escherichia coli | OrthoMCL | CHEMBL4097472CHEMBL4076393CHEMBL4064127CHEMBL4104625... |
| P9WG45 | DNA gyrase subunit B | OrthoMCL | CHEMBL4238919CHEMBL4238919CHEMBL4250651CHEMBL4250651... | |
| P20083 | DNA topoisomerase 4 subunit B | Escherichia coli | OrthoMCL | CHEMBL3329317CHEMBL3329318CHEMBL4279313CHEMBL4294536... |
| P05653 | DNA gyrase subunit A/B | Bacillus subtilis | OrthoMCL BLAST | PD125275Ciprofloxacin |
| P0C1U9 | DNA topoisomerase 4 subunit A | Staphylococcus aureus | OrthoMCL BLAST | CHEMBL202753CHEMBL379022CHEMBL425234CHEMBL203851... |
| Q2FYS4 | DNA topoisomerase 4 subunit A/B | OrthoMCL BLAST | US9040542, 23 | |
| Q45066 | DNA topoisomerase 4 subunit A [V210L]/B | Bacillus subtilis | OrthoMCL BLAST | PD125275Ciprofloxacin |
| Q931S2 | DNA topoisomerase 4 subunit A | OrthoMCL BLAST | CHEMBL363725CHEMBL186870CHEMBL184489CHEMBL365638... | |
| P20831 | DNA gyrase subunit A/B | Staphylococcus aureus | OrthoMCL BLAST | NOVOBIOCINBenzimidazole carbamate analogue, 1Benzimidazole urea analogue, 2Benzimidazole urea analogue, 3... |
| P0AFI2 | DNA topoisomerase 4 subunit A | Escherichia coli | OrthoMCL BLAST | NOVOBIOCINBenzimidazole urea analogue, 2Benzimidazole urea analogue, 3Benzimidazole urea analogue, 4... |
| P0AES4 | DNA gyrase subunit A/B | Escherichia coli | OrthoMCL BLAST | NOVOBIOCINBenzimidazole urea analogue, 2Benzimidazole urea analogue, 3Benzimidazole urea analogue, 4... |
| Q47245 | DNA gyrase subunit A | OrthoMCL BLAST | OFLOXACINMoxifl-oxacinCHEMBL4459270CHEMBL4470688... |
Ortholog Group (OrthoMCL): OG6_100284
Most Similar Human Ortholog: J3KTB7
TM-align score: 0.87 | RMSD: 1.26
Seq Identity: 0.56 | Length: 136 / 1472
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000077097 | DNA topoisomerase II beta |
| ENSG00000131747 | DNA topoisomerase II alpha |
Protein Length: 1472 | Molecular Weight (kDa): 169.227
PDB ID(s): None
Isoelectric Point: 8.57
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001154 | DNA topoisomerase II, eukaryotic-type |
| InterPro | IPR001241 | DNA topoisomerase, type IIA |
| InterPro | IPR002205 | DNA topoisomerase, type IIA, subunit A/C-terminal |
| InterPro | IPR003594 | Histidine kinase/HSP90-like ATPase |
| InterPro | IPR006171 | TOPRIM domain |
| InterPro | IPR013506 | DNA topoisomerase, type IIA, subunit B, domain 2 |
| InterPro | IPR013760 | DNA topoisomerase, type IIA-like domain superfamily |
| InterPro | IPR018522 | DNA topoisomerase, type IIA, conserved site |
| InterPro | IPR020568 | Ribosomal protein S5 domain 2-type fold |
| InterPro | IPR031660 | C-terminal associated domain of TOPRIM |
| InterPro | IPR034157 | DNA topoisomerase 2, TOPRIM domain |
| InterPro | IPR036890 | Histidine kinase/HSP90-like ATPase superfamily |
| PFam | PF00204 | DNA topoisomerase, type IIA, subunit B, domain 2 |
| PFam | PF00521 | DNA topoisomerase, type IIA, subunit A/C-terminal |
| PFam | PF01751 | TOPRIM domain |
| PFam | PF02518 | Histidine kinase/HSP90-like ATPase |
| PFam | PF16898 | C-terminal associated domain of TOPRIM |
| Superfamily | SSF54211 | Ribosomal protein S5 domain 2-type fold |
| Superfamily | SSF55874 | Histidine kinase/HSP90-like ATPase superfamily |
| Superfamily | SSF56719 | DNA topoisomerase, type IIA-like domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 19 | 71 | 51 | 104 |
| disruptive | 22 | 62 | 41 | 113 |
| missense | 15 | 60 | 40 | 91 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 33 | 185 | 62 | 96 |
| disruptive | 39 | 188 | 111 | 281 |
| missense | 23 | 145 | 93 | 184 |
PlasmoDB Total SNPs: 308
Non-coding: 246 | Synonymous: 45 | Nonsynonymous: 17 | 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 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 23181666 | Organellar proteomics reveals hundreds of novel nuclear proteins in the malariaparasite Plasmodium falciparum. | Oehring SC, Woodcroft BJ, ..., Voss TS | 10.1186/gb-2012-13-11-r108 |
| 26055707 | Topoisomerase II from Human Malaria Parasites: EXPRESSION, PURIFICATION, ANDSELECTIVE INHIBITION. | Mudeppa DG, Kumar S, ..., Rathod PK | 10.1074/jbc.M115.639039 |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |