Detailed view for Tb927.6.4780

Basic information

TDR Targets ID: 11157
Trypanosoma brucei, DNA ligase I, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.5603 | Length (AA): 746 | MW (Da): 82671 | Paralog Number: 0

Signal peptide: Y | GPI Anchor: | Predicted trans-membrane segments: 1

Druggability Group : DG3

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

PF01068   ATP dependent DNA ligase domain
PF04675   DNA ligase N terminus
PF04679   ATP dependent DNA ligase C terminal region

Gene Ontology

Mouse over links to read term descriptions.
GO:0071897   GO:DNA biosynthetic process  

GO:0051103   DNA ligation during DNA repair  
GO:0003910   DNA ligase (ATP) activity  
GO:0003909   DNA ligase activity  
GO:0005524   ATP binding  
GO:0003677   DNA binding  
GO:0006310   DNA recombination  
GO:0006281   DNA repair  
GO:0006260   DNA replication  

Structural information

Modbase 3D models:

There is 1 model calculated for this protein. More info on this model, including the model itself is available at: Modbase

Target Beg Target End Template Template Beg Template End Identity Evalue Model Score MPQS zDope
95 736 1x9n (A) 263 901 47.00 0 1 1.42539 -0.46

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

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile Procyclic, Bloodstream Form. Siegel TN
Show/Hide expression data references
  • Siegel TN Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites.

Orthologs

Ortholog group members (OG5_127375)

Species Accession Gene Product
Arabidopsis thaliana AT1G08130   DNA ligase 1
Arabidopsis thaliana AT1G49250   ATP-dependent DNA ligase
Babesia bovis BBOV_IV001520   DNA ligase I
Brugia malayi Bm1_26765   DNA ligase
Candida albicans CaO19.6155   DNA ligase
Caenorhabditis elegans CELE_C29A12.3   Protein LIG-1, isoform B
Cryptosporidium hominis Chro.30432   hypothetical protein
Cryptosporidium parvum cgd3_3820   DNA LIGASE I
Dictyostelium discoideum DDB_G0274493   DNA ligase I
Drosophila melanogaster Dmel_CG5602   DNA ligase I
Echinococcus granulosus EgrG_000614700   DNA ligase 1
Entamoeba histolytica EHI_111060   DNA ligase, putative
Echinococcus multilocularis EmuJ_000614700   DNA ligase 1
Giardia lamblia GL50803_7649   DNA ligase
Homo sapiens ENSG00000105486   ligase I, DNA, ATP-dependent
Leishmania braziliensis LbrM.30.3480   DNA ligase I, putative
Leishmania donovani LdBPK_303490.1   DNA ligase I, putative
Leishmania infantum LinJ.30.3490   DNA ligase I, putative
Leishmania major LmjF.30.3440   DNA ligase I, putative
Leishmania mexicana LmxM.29.3440   DNA ligase I, putative
Loa Loa (eye worm) LOAG_06875   DNA ligase
Mus musculus ENSMUSG00000056394   ligase I, DNA, ATP-dependent
Mycobacterium tuberculosis Rv3062   Probable ATP-dependent DNA ligase LigB (polydeoxyribonucleotide synthase [ATP]) (polynucleotide ligase [ATP]) (sealase) (DNA rep
Mycobacterium ulcerans MUL_3413   ATP-dependent DNA ligase
Neospora caninum NCLIV_003210   DNA ligase (Polydeoxyribonucleotide synthase [ATP])(Lig(Tk)) (EC 6.5.1.1), related
Oryza sativa 4348965   Os10g0489200
Plasmodium berghei PBANKA_1402600   DNA ligase I, putative
Plasmodium falciparum PF3D7_1304100   DNA ligase I
Plasmodium knowlesi PKNH_1404300   DNA ligase I, putative
Plasmodium vivax PVX_122045   DNA ligase I, putative
Plasmodium yoelii PY01533   DNA ligase 1
Saccharomyces cerevisiae YDL164C   DNA ligase (ATP) CDC9
Schistosoma japonicum Sjp_0300290   ko:K01971 DNA ligase (ATP) [EC6.5.1.1], putative
Schistosoma mansoni Smp_019840.1   DNA ligase I
Schistosoma mansoni Smp_019840.2   DNA ligase I
Schmidtea mediterranea mk4.002204.01   DNA ligase 1
Schmidtea mediterranea mk4.002204.02  
Trypanosoma brucei gambiense Tbg972.6.4610   DNA ligase I, putative
Trypanosoma brucei Tb927.6.4780   DNA ligase I, putative
Trypanosoma cruzi TcCLB.506945.80   DNA ligase I, putative
Trypanosoma cruzi TcCLB.506835.120   DNA ligase I, putative
Toxoplasma gondii TGME49_208580   DNA ligase 1, putative
Theileria parva TP03_0549   DNA ligase I, putative
Trichomonas vaginalis TVAG_162990   DNA ligase IV, putative

Essentiality

Tb927.6.4780 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.6.4780 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.6.4780 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.6.4780 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.6.4780 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_C29A12.3 Caenorhabditis elegans embryonic lethal wormbase
CELE_C29A12.3 Caenorhabditis elegans sterile wormbase
YDL164C Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1402600 Plasmodium berghei Essential plasmo
TGME49_208580 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
cell proliferation (GO:0008283) normal (PATO:0000461) bloodstream stage trypomastigotes (PLO:0027) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: normal cell proliferation (no significant loss or gain of fitness) in bloodstream forms (stage 3 days). References: 21363968
cell proliferation (GO:0008283) decreased (PATO:0000468) bloodstream stage trypomastigotes (PLO:0027) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: decreased cell proliferation (significant loss of fitness) in bloodstream forms (stage 6 days). References: 21363968
cell proliferation (GO:0008283) normal (PATO:0000461) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: normal cell proliferation (no significant loss or gain of fitness) in procyclic forms . References: 21363968
cell proliferation (GO:0008283) decreased (PATO:0000468) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: decreased cell proliferation (significant loss of fitness) in differentiation of procyclic to bloodstream forms . References: 21363968

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

Druggability index (range: 0 to 1): 0.2

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
Homo sapiens ligase I, DNA, ATP-dependent Compounds References
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets
Obtained from network model

Ranking Plot

No enough druggable targets predicted through repurposing network model to make a plot

Putative Drugs List

Compound Raw Global Species
0.0017 1 0.5

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

1 literature reference was collected for this gene.

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Gene identifier Tb927.6.4780 (Trypanosoma brucei), DNA ligase I, putative
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