Detailed view for Tb927.8.2610

Basic information

TDR Targets ID: 14102
Trypanosoma brucei, 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.5125 | Length (AA): 781 | MW (Da): 88612 | 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

PF01717   Cobalamin-independent synthase, Catalytic domain
PF08267   Cobalamin-independent synthase, N-terminal domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0005575   cellular_component  
GO:0008270   zinc ion binding  
GO:0003871   5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase activity  
GO:0009086   methionine biosynthetic process  
GO:0008652   amino acid biosynthetic process  

Structural information

Modbase 3D models:

There are 4 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
9 774 3ppc (B) 0 767 44.00 0 1 1.55199 -0.91
11 776 4zty (A) 2 767 42.00 0 1 1.60499 -1.14
12 775 1t7l (A) 2 733 43.00 0 1 1.53143 -0.83
13 773 1u1j (A) 3 760 47.00 0 1 1.56259 -0.56

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 60-80% percentile Bloodstream Form. Siegel TN
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile Procyclic. 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_128715)

Species Accession Gene Product
Arabidopsis thaliana AT3G03780   methionine synthase 2
Arabidopsis thaliana AT5G17920   5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase
Arabidopsis thaliana AT5G20980   methionine synthase 3
Candida albicans CaO19.2551   likely cobalamin-independent methionine synthase similar to S. cerevisiae MET6 (YER091C) involved in methionine biosynthesis
Candida albicans CaO19.10083   likely cobalamin-independent methionine synthase similar to S. cerevisiae MET6 (YER091C) involved in methionine biosynthesis
Dictyostelium discoideum DDB_G0279211   cobalamin-independent methionine synthase
Escherichia coli b3829   5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase
Leishmania braziliensis LbrM.31.0010   5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase, putative
Leishmania donovani LdBPK_310010.1   5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase, putative
Leishmania infantum LinJ.31.0010   5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase, putative
Leishmania major LmjF.31.0010   5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase
Leishmania mexicana LmxM.30.0010   5-methyltetrahydropteroyltriglutamate--homocyst ei nemethyltransferase, putative
Mycobacterium leprae ML0961c   PROBABLE5-METHYLTETRAHYDROPTEROYLTRIGLUTAMATE--HOMOCYSTEINE METHYLTRANSFERASE METE (methionine synthase, vitamin-B12 independent
Mycobacterium tuberculosis Rv1133c   Probable 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase MetE (methionine synthase, vitamin-B12 independen
Mycobacterium ulcerans MUL_0138   5-methyltetrahydropteroyltriglutamate/homocysteine S-methyltransferase
Oryza sativa 4352833   Os12g0624000
Oryza sativa 4352832   Os12g0623900
Saccharomyces cerevisiae YER091C   5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase
Schmidtea mediterranea mk4.040620.01  
Schmidtea mediterranea mk4.049372.00  
Trypanosoma brucei gambiense Tbg972.8.2100   5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase
Trypanosoma brucei Tb927.8.2610   5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase, putative
Trypanosoma congolense TcIL3000_8_2420   5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase, putative

Essentiality

Tb927.8.2610 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.2610 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.2610 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.8.2610 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.2610 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b3829 Escherichia coli non-essential goodall
Show/Hide essentiality data references
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.
  • 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 3 days). References: 21363968
cell proliferation (GO:0008283) increased (PATO:0000470) 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: increased cell proliferation (significant 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 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
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.

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Gene identifier Tb927.8.2610 (Trypanosoma brucei), 5-methyltetrahydropteroyltriglutamate-homocysteine S-methyltransferase, putative
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