About Gene List

PF3D7_0510500 (TopoI)

Genome location: Pf3D7_05_v3:445,554..448,872(-)

Genome classification: Core

Function and Localization

Product Description: topoisomerase I

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 5.99.1.2 (Transferred entry: 5.6.2.1)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005730 nucleolus
Component GO:0005634 nucleus
Component GO:0031298 replication fork protection complex
Function GO:0003917 DNA topoisomerase type I (single strand cut, ATP-independent) activity
Process GO:0006260 DNA replication
Process GO:0006265 DNA topological change
Process GO:0006338 chromatin remodeling
Process GO:0007059 chromosome segregation
Process GO:0042493 response to drug
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 expressed 0.46 0.79
Trophozoite expressed 1.27 0.39
Schizont expressed 0.62 0.67
Gametocyte expressed 0.75 0.61

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_0510500

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: 0.12 | MFS: -3.151 | #Insertions: 0

PlasmoGEM Phenotype: N/A

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8I3Z9

"Best" AlphaFill ligand hit: No AlphaFill hits

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
5.99.1.2 DNA topoisomerase No BRENDA inhibitors

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
P11387 DNA topoisomerase 1 OMA, OrthoDB CHEMBL4064887CHEMBL4065223CHEMBL4076393CHEMBL4064127...
Q04750 DNA topoisomerase 1 Mus musculus OMA, OrthoDB CHEMBL289665SN-38CHEMBL453303CHEMBL507686...
P04786 DNA topoisomerase 1 OMA, OrthoDB, OrthoMCL combretastatins A-1combretastatins A-1
Q9WUL0 DNA topoisomerase 1 Rattus norvegicus OrthoDB acs.jmedchem.1c00409_ST.600acs.jmedchem.1c00409_ST.600
E9B7X3 DNA topoisomerase type IB small subunit OrthoMCL BLAST Camptothecin (CPT)Camptothecin (CPT)
Q95Z89 Topoisomerase I subunit B Leishmania major OrthoMCL BLAST CHEMBL2153502Camptothecin (CT)
Q16611 Bcl-2 homologous antagonist/killer OrthoMCL BLAST Apogossypol derivative, 8kCHEMBL5203189CHEMBL5182721CHEMBL605114...
Q2HPH0 Topoisomerase I OrthoMCL BLAST CHEMBL4176420CHEMBL4159820

Orthology Information

Ortholog Group (OrthoMCL): OG6_101409

Most Similar Human Ortholog: E5RFS0

TM-align score: 0.95 | RMSD: 1.35

Seq Identity: 0.38 | Length: 221 / 839

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000184428 DNA topoisomerase I mitochondrial
ENSG00000198900 DNA topoisomerase I

Protein Information

Protein Length: 839 | Molecular Weight (kDa): 98.11

UniProt ID(s): Q26024, Q8I3Z9

PDB ID(s): None

Isoelectric Point: 9.84

Protein Domain Annotations:

Source Family ID Description
InterPro IPR001631 DNA topoisomerase I
InterPro IPR008336 DNA topoisomerase I, DNA binding, eukaryotic-type
InterPro IPR011010 DNA breaking-rejoining enzyme, catalytic core
InterPro IPR013499 DNA topoisomerase I, eukaryotic-type
InterPro IPR013500 DNA topoisomerase I, catalytic core, eukaryotic-type
InterPro IPR018521 DNA topoisomerase I, active site
InterPro IPR025834 Topoisomerase I C-terminal domain
InterPro IPR036202 DNA topoisomerase I, DNA binding, eukaryotic-type, N-terminal domain superfamily
PFam PF01028 DNA topoisomerase I, catalytic core, eukaryotic-type
PFam PF02919 DNA topoisomerase I, DNA binding, eukaryotic-type
PFam PF14370 Topoisomerase I C-terminal domain
Superfamily SSF56349 DNA breaking-rejoining enzyme, catalytic core
Superfamily SSF56741 DNA topoisomerase I, DNA binding, eukaryotic-type, N-terminal domain superfamily

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 1 24 27 35
disruptive 9 44 30 45
missense 9 43 28 39

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 2 73 16 31
disruptive 22 105 46 102
missense 16 80 37 74

PlasmoDB Total SNPs: 53

Non-coding: 22 | Synonymous: 24 | Nonsynonymous: 7 | Stop Codon: 0

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
22446744 Mapping the genome of Plasmodium falciparum on the drug-like chemical spacereveals novel anti-malarial targets and potential drug leads. Jensen K, Plichta D, Panagiotou G, Kouskoumvekaki I 10.1039/c2mb00008c
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
24651068 Theoretical and experimental studies of new modified isoflavonoids as potentialinhibitors of topoisomerase I from Plasmodium falciparum. Cortopassi WA, Penna-Coutinho J, ..., Krettli AU 10.1371/journal.pone.0091191
36983048 StaR Is a Positive Regulator of Topoisomerase I Activity Involved in SupercoilingMaintenance in Streptococcus pneumoniae de Vasconcelos Junior AA, Tirado-Velez JM, ..., de la Campa AG 10.3390/ijms24065973