Detailed view for LmxM.28.2280

Basic information

TDR Targets ID: 450390
Leishmania mexicana, DNA topoisomerase ii

Source Database / ID: 

pI: 7.2916 | Length (AA): 1497 | MW (Da): 168589 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 0

Druggability Group : DG

Targets have been classified into druggability groups (DG) according to their druggability score in network driven prioritizations. DGs range from 1 to 5; the higher the group number, the higher the chance of the target to be druggable

Pfam domains

PF00204   DNA gyrase B
PF00521   DNA gyrase/topoisomerase IV, subunit A
PF02518   Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase
PF16898   C-terminal associated domain of TOPRIM

Gene Ontology

Mouse over links to read term descriptions.
GO:0003918   DNA topoisomerase (ATP-hydrolyzing) activity  
GO:0005524   ATP binding  
GO:0003677   DNA binding  
GO:0006265   DNA topological change  

Metabolic Pathways

This gene is not mapped to any metabolic pathway in KEGG.

Structural information

Modbase 3D models:

There are 5 models calculated for this protein. More info on these models, including the models themselves is available at: Modbase

Target Beg Target End Template Template Beg Template End Identity Evalue Model Score MPQS zDope
4 380 1zxm (B) 29 410 48.00 0 1 0.868337 -0.84
4 1161 4gfh (A) 7 1169 47.00 0 1 1.26005 -0.07
678 1300 1zvu (A) 28 668 19.00 0 1 0.381666 1.24
1008 1257 3rr5 (A) 90 338 29.00 0.21 0.22 -0.0315993 2.18
1349 1449 4ke2 (A) 29 131 35.00 0.2 0.1 0.283868 0.91

Help me make sense of these data.

Target Beg: first modeled residue
Target End: last modeled residue
Template: template structure used for modelling (PDB accession and chain)
Template Beg: first template residue in target-template alignment
Template End: last template residue in target-template alignment
Identity: sequence identity
Evalue: E value for target-template hit
Model Score: GA341 score (>0.7 for reliable model)
MPQS: ModPipe Quality Score (>1.1 for reliable model)
zDope: zDope Score (negative for reliable model)

A more detailed description of these scores is available at the Modbase Model Evaluation Help Pages, and in the papers referenced therein.

PDB Structures:

No structure availble in the PDB for this protein

Expression

No expression data available for this gene

Orthologs

Ortholog group members (OG5_127113)

Species Accession Gene Product
Arabidopsis thaliana AT3G23890   DNA topoisomerase 2
Babesia bovis BBOV_III004820   DNA topoisomerase II, putative
Brugia malayi Bm1_08705   DNA topoisomerase II, alpha isozyme
Brugia malayi Bm1_44575   DNA gyrase/topoisomerase IV, A subunit family protein
Brugia malayi Bm1_46835   Probable DNA topoisomerase II
Candida albicans CaO19.2873   DNA topoisomerase II similar to S. cerevisiae TOP2 (YNL088W)
Candida albicans CaO19.10391   DNA topoisomerase II similar to S. cerevisiae TOP2 (YNL088W)
Caenorhabditis elegans CELE_ZK1127.7   Protein CIN-4
Caenorhabditis elegans CELE_K12D12.1   Protein TOP-2
Cryptosporidium hominis Chro.40097   DNA topoisomerase II
Cryptosporidium parvum cgd4_780   DNA topoisomerase II
Chlamydia trachomatis CT_661   DNA gyrase subunit B
Dictyostelium discoideum DDB_G0270418   DNA topoisomerase II
Dictyostelium discoideum DDB_G0279737   DNA topoisomerase II
Drosophila melanogaster Dmel_CG10223   Topoisomerase 2
Escherichia coli b3030   DNA topoisomerase IV, subunit B
Echinococcus granulosus EgrG_000601600   DNA topoisomerase 2 alpha
Entamoeba histolytica EHI_120640   DNA topoisomerase II, putative
Echinococcus multilocularis EmuJ_000601600   DNA topoisomerase 2 alpha
Giardia lamblia GL50803_16975   DNA topoisomerase II
Homo sapiens ENSG00000077097   topoisomerase (DNA) II beta 180kDa
Homo sapiens ENSG00000131747   topoisomerase (DNA) II alpha 170kDa
Leishmania braziliensis LbrM.28.2480   DNA topoisomerase ii
Leishmania donovani LdBPK_282450.1   DNA topoisomerase ii
Leishmania infantum LinJ.28.2450   DNA topoisomerase ii
Leishmania major LmjF.28.2280   DNA topoisomerase ii
Leishmania mexicana LmxM.28.2280   DNA topoisomerase ii
Loa Loa (eye worm) LOAG_04734   hypothetical protein
Loa Loa (eye worm) LOAG_02122   TOPoisomerase family member
Loa Loa (eye worm) LOAG_05200   hypothetical protein
Loa Loa (eye worm) LOAG_05204   hypothetical protein
Loa Loa (eye worm) LOAG_07391   hypothetical protein
Loa Loa (eye worm) LOAG_05201   hypothetical protein
Loa Loa (eye worm) LOAG_09672   hypothetical protein
Loa Loa (eye worm) LOAG_14142   hypothetical protein
Mus musculus ENSMUSG00000017485   topoisomerase (DNA) II beta
Mus musculus ENSMUSG00000020914   topoisomerase (DNA) II alpha
Neospora caninum NCLIV_055820   hypothetical protein
Oryza sativa 4330426   Os02g0699700
Onchocerca volvulus OVOC8298   Putative DNA topoisomerase 2, mitochondrial
Onchocerca volvulus OVOC1920   DNA topoisomerase 2 homolog
Onchocerca volvulus OVOC9878   DNA topoisomerase 2 homolog
Plasmodium berghei PBANKA_1011400   DNA topoisomerase 2, putative
Plasmodium falciparum PF3D7_1433500   DNA topoisomerase 2
Plasmodium knowlesi PKNH_0420100   DNA topoisomerase 2, putative
Plasmodium vivax PVX_084855   DNA topoisomerase II, putative
Plasmodium yoelii PY03394   DNA topoisomerase II, putative
Saccharomyces cerevisiae YNL088W   DNA topoisomerase 2
Schistosoma japonicum Sjp_0073920   ko:K03164 DNA topoisomerase II, putative
Schistosoma japonicum Sjp_0073910   expressed protein
Schistosoma mansoni Smp_065840   DNA topoisomerase II
Schmidtea mediterranea mk4.001684.00   Putative DNA topoisomerase 2, mitochondrial
Schmidtea mediterranea mk4.005340.03  
Schmidtea mediterranea mk4.021128.00   Putative DNA topoisomerase 2, mitochondrial
Schmidtea mediterranea mk4.008074.00   DNA topoisomerase 2
Schmidtea mediterranea mk4.000055.15  
Schmidtea mediterranea mk4.007149.01   Putative DNA topoisomerase 2, mitochondrial
Schmidtea mediterranea mk4.000055.16   Putative DNA topoisomerase 2, mitochondrial
Schmidtea mediterranea mk4.012109.03   Putative DNA topoisomerase 2, mitochondrial
Schmidtea mediterranea mk4.013554.01  
Schmidtea mediterranea mk4.000055.14  
Schmidtea mediterranea mk4.007149.00  
Schmidtea mediterranea mk4.000055.18   Putative DNA topoisomerase 2, mitochondrial
Schmidtea mediterranea mk4.013554.02   Putative DNA topoisomerase 2, mitochondrial
Schmidtea mediterranea mk4.002666.04   DNA topoisomerase 2
Schmidtea mediterranea mk4.004760.01   Putative DNA topoisomerase 2, mitochondrial
Schmidtea mediterranea mk4.000055.21   Putative DNA topoisomerase 2, mitochondrial
Schmidtea mediterranea mk4.000055.20  
Schmidtea mediterranea mk4.043355.01  
Schmidtea mediterranea mk4.005340.02   Putative DNA topoisomerase 2, mitochondrial
Trypanosoma brucei gambiense Tbg972.11.12970   DNA topoisomerase II, putative
Trypanosoma brucei gambiense Tbg972.11.12960   DNA topoisomerase II, putative
Trypanosoma brucei Tb927.11.11560   DNA topoisomerase II beta, putative
Trypanosoma brucei Tb927.11.11550   DNA topoisomerase II alpha, putative
Trypanosoma congolense TcIL3000.11.12160   DNA topoisomerase II, putative
Trypanosoma congolense TcIL3000.11.12150   DNA topoisomerase II, putative
Trypanosoma cruzi TcCLB.509203.70   DNA topoisomerase II, putative
Trypanosoma cruzi TcCLB.508699.10   DNA topoisomerase II, putative
Toxoplasma gondii TGME49_312230   DNA topoisomerase 2, putative
Theileria parva TP02_0467   DNA topoisomerase II, putative
Trichomonas vaginalis TVAG_038880   DNA topoisomerase II, putative

Essentiality

LmxM.28.2280 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb11.01.3390 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.01.3390 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb11.01.3390 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.01.3390 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b3030 Escherichia coli essential goodall
CELE_K12D12.1 Caenorhabditis elegans embryonic lethal wormbase
CELE_K12D12.1 Caenorhabditis elegans larval arrest wormbase
CELE_ZK1127.7 Caenorhabditis elegans embryonic lethal wormbase
CELE_ZK1127.7 Caenorhabditis elegans larval arrest wormbase
YNL088W Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1011400 Plasmodium berghei Essential plasmo
TGME49_312230 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • goodall The Essential Genome of Escherichia coli K-12 (Transposon directed high-throughput mutagenesis) Goodall, Emily CA, et al. "The essential genome of Escherichia coli K-12." mBio 9.1 (2018): e02096-17.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • sidik A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes. Sidik, Saima M., et al. "A genome-wide CRISPR screen in toxoplasma identifies essential apicomplexan genes." Cell 166.6 (2016): 1423-1435.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • plasmo Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes. Bushell, Ellen, et al. "Functional profiling of a Plasmodium genome reveals an abundance of essential genes." Cell 170.2 (2017): 260-272.
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs

Phenotypes and Validation (curated)

We have no manually annotated phenotypes for this target. What does this mean? / Care to help?

In TDR Targets, information about phenotypes that are caused by drugs, or by genetic manipulation of cells (e.g. gene knockouts or knockdowns) is manually curated from the literature. These descriptions help to describe the potential of the target for drug development. If no information is available for this gene or if the information is incomplete, this may mean that i) the papers containing this information either appeared after the curation effort for this organism was carried out or they were inadvertently missed by curators; or that ii) the curation effort for this organism has not yet started.

In any case, if you have information about papers containing relevant validation data for this target, please contact us.


Annotated validation

No validation data for this target

Associated compounds / Druggability

Known modulators for this target

No chemical compounds associated to this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Drosophila melanogaster Topoisomerase 2 Compounds References
Homo sapiens topoisomerase (DNA) II alpha 170kDa Compounds References
Leishmania major DNA topoisomerase ii Compounds References
Escherichia coli DNA topoisomerase IV, subunit B Compounds References
Homo sapiens topoisomerase (DNA) II beta 180kDa Compounds References
Trypanosoma cruzi DNA topoisomerase II, putative Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Staphylococcus aureus DNA gyrase 644 aa 23.1% 668 aa Compounds References
Staphylococcus aureus Topoisomerase IV 663 aa 26.0% 651 aa Compounds References
Staphylococcus aureus DNA topoisomerase 4 subunit B 663 aa 26.0% 651 aa Compounds References
Staphylococcus aureus subsp. aureus Mu50 DNA gyrase 644 aa 22.9% 668 aa Compounds References
Staphylococcus aureus DNA gyrase subunit B 644 aa 23.1% 668 aa Compounds References
Mycobacterium smegmatis DNA gyrase subunit B 675 aa 23.8% 559 aa Compounds References
Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4) DNA gyrase subunit B 648 aa 23.9% 657 aa Compounds References
Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155) DNA gyrase subunit B 675 aa 23.8% 559 aa Compounds References
Streptococcus pneumoniae ParE 638 aa 23.7% 651 aa Compounds References

Obtained from network model
No druggable targets predicted through repurposing network model

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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Gene identifier LmxM.28.2280 (Leishmania mexicana), DNA topoisomerase ii
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