Detailed view for Tb927.10.6410

Basic information

TDR Targets ID: 15847
Trypanosoma brucei, DNA mismatch repair protein MSH6, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.7959 | Length (AA): 997 | MW (Da): 110320 | Paralog Number: 0

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

Druggability Group : DG1

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

PF00488   MutS domain V
PF01624   MutS domain I
PF05190   MutS family domain IV
PF05192   MutS domain III

Gene Ontology

Mouse over links to read term descriptions.
GO:0030983   mismatched DNA binding  
GO:0005524   ATP binding  
GO:0006298   mismatch repair  

Metabolic Pathways

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

Structural information

Modbase 3D models:

There are 3 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
11 978 2o8b (B) 373 1331 26.00 0 1 1.14241 0.59
585 970 1ewr (B) 1300 1762 31.00 0 1 0.567061 0.82
745 782 2awn (C) 6 50 42.00 0.48 0.28 0.473514 0.07

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_126895)

Species Accession Gene Product
Arabidopsis thaliana AT4G02070   DNA mismatch repair protein MSH6
Arabidopsis thaliana AT3G24495   DNA mismatch repair protein Msh6-2
Babesia bovis BBOV_I004430   DNA repair protein, putative
Brugia malayi Bm1_41770   MutS domain III family protein
Candida albicans CaO19.4945   repair of insertion-deletion mispairs
Candida albicans CaO19.496   similar to S. cerevisiae MutS Homolog involved in Mitochondrial DNA mismatch repair
Candida albicans CaO19.12411   repair of insertion-deletion mispairs
Candida albicans CaO19.8126   similar to S. cerevisiae MutS Homolog involved in Mitochondrial DNA mismatch repair
Caenorhabditis elegans CELE_Y47G6A.11   Protein MSH-6
Cryptosporidium hominis Chro.80049   DNA repair protein
Cryptosporidium parvum cgd8_370   DNA repair protein
Chlamydia trachomatis CT_792   DNA mismatch repair protein MutS
Dictyostelium discoideum DDB_G0275999   DNA mismatch repair protein
Dictyostelium discoideum DDB_G0268614   DNA mismatch repair protein
Drosophila melanogaster Dmel_CG7003   CG7003 gene product from transcript CG7003-RA
Escherichia coli b2733   methyl-directed mismatch repair protein
Echinococcus granulosus EgrG_000822900   dna mismatch repair protein msh6
Entamoeba histolytica EHI_193340   mutS family protein
Echinococcus multilocularis EmuJ_000822900   dna mismatch repair protein msh6
Homo sapiens ENSG00000116062   mutS homolog 6
Leishmania braziliensis LbrM.35.2160   mismatch repair protein MSH8, putative
Leishmania donovani LdBPK_362050.1   DNA mismatch repair protein MSH6, putative
Leishmania infantum LinJ.36.2050   mismatch repair protein MSH8, putative
Leishmania major LmjF.36.1950   mismatch repair protein MSH8, putative
Leishmania mexicana LmxM.36.1950   mismatch repair protein MSH8, putative
Loa Loa (eye worm) LOAG_03556   hypothetical protein
Mus musculus ENSMUSG00000005370   mutS homolog 6 (E. coli)
Neospora caninum NCLIV_042630   DNA mismatch repair protein mutS, related
Oryza sativa 4347016   Os09g0407600
Oryza sativa 4325353   Os01g0180600
Plasmodium berghei PBANKA_1105100   DNA mismatch repair protein MSH6, putative
Plasmodium falciparum PF3D7_0505500   DNA mismatch repair protein MSH6, putative
Plasmodium knowlesi PKNH_1028100   DNA mismatch repair protein MSH6, putative
Plasmodium vivax PVX_097835   DNA mismatch repair protein MSH6, putative
Plasmodium yoelii PY02936   G/T mismatch binding protein-related
Saccharomyces cerevisiae YHR120W   mismatch repair ATPase MSH1
Saccharomyces cerevisiae YDR097C   mismatch repair ATPase MSH6
Schistosoma japonicum Sjp_0104370   ko:K08737 DNA mismatch repair protein MSH6, putative
Schistosoma japonicum Sjp_0058170   ko:K08737 DNA mismatch repair protein MSH6, putative
Schistosoma japonicum Sjp_0058180   DNA mismatch repair protein Msh6, putative
Schistosoma mansoni Smp_042670.1   hypothetical protein
Schistosoma mansoni Smp_042670.2   hypothetical protein
Schmidtea mediterranea mk4.038361.03  
Schmidtea mediterranea mk4.000110.01   Msh6
Schmidtea mediterranea mk4.000110.00  
Trypanosoma brucei gambiense Tbg972.10.7830   mismatch repair protein MSH8, putative,mismatch repair protein
Trypanosoma brucei Tb927.10.6410   DNA mismatch repair protein MSH6, putative
Trypanosoma cruzi TcCLB.510187.430   DNA mismatch repair protein MSH6, putative
Toxoplasma gondii TGME49_290640   DNA mismatch repair protein MSH6-1, putative
Treponema pallidum TP0328   DNA mismatch repair protein MutS
Theileria parva TP01_0185   DNA repair protein, putative
Trichomonas vaginalis TVAG_484110   mismatch repair protein Msh6 (mutS homolog)
Wolbachia endosymbiont of Brugia malayi Wbm0257   DNA mismatch repair protein MutS

Essentiality

Tb927.10.6410 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.6410 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.6410 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.6410 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.6410 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b2733 Escherichia coli non-essential goodall
PBANKA_1105100 Plasmodium berghei Essential plasmo
TGME49_290640 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.

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 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

Known modulators for this target

No chemical compounds associated to this gene

Predicted associations

By orthology with druggable targets
Non orthologous druggable targets
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets
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

1 literature reference was collected for this gene.

If you have references for this gene, please enter them in a user comment (below) or Contact us.

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Gene identifier Tb927.10.6410 (Trypanosoma brucei), DNA mismatch repair protein MSH6, putative
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