Detailed view for Tb927.4.4650

Basic information

TDR Targets ID: 19167
Trypanosoma brucei, diphthine synthase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.9023 | Length (AA): 269 | MW (Da): 29490 | Paralog Number: 0

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

Druggability Group : DG4

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

PF00590   Tetrapyrrole (Corrin/Porphyrin) Methylases

Gene Ontology

Mouse over links to read term descriptions.
GO:0008168   methyltransferase activity  
GO:0004164   diphthine synthase activity  
GO:0017183   peptidyl-diphthamide biosynthetic process from peptidyl-histidine  
GO:0008152   metabolic process  

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
1 267 1vhv (A) 1 240 38.00 0 1 1.32337 0.02
1 266 3i4t (A) 1 266 55.00 0 1 1.59415 -0.43
1 267 2z6r (A) 2 254 39.00 0 1 1.43937 -0.44

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_127443)

Species Accession Gene Product
Arabidopsis thaliana AT4G31790   Probable diphthine synthase
Babesia bovis BBOV_IV002920   diphthine synthase
Brugia malayi Bm1_10785   diphthine synthase
Candida albicans CaO19.6676   one of two genes similar to S. cerevisiae DPH5 (YLR172C) diphthamide methyltransferase (Tetrapyrrole Methylase domain)
Candida albicans CaO19.6682   similar to C terminus of S. cerevisiae DPH5 (YLR172C) diphthamide methyltransferase
Caenorhabditis elegans CELE_B0491.7   Protein B0491.7
Cryptosporidium hominis Chro.60154   tetrapyrrole methylases
Cryptosporidium parvum cgd6_1200   diphthine synthase; diphthamide biosynthesis methyltransferase
Dictyostelium discoideum DDB_G0276115   diphthamide biosynthesis protein 5
Drosophila melanogaster Dmel_CG31289   Diphthamide methyltransferase
Echinococcus granulosus EgrG_000439900   diphthine synthase
Entamoeba histolytica EHI_127240   diphthine synthase, putative
Echinococcus multilocularis EmuJ_000439900   diphthine synthase
Giardia lamblia GL50803_28666   Diphthine synthase
Homo sapiens 51611   diphthamide biosynthesis 5
Leishmania braziliensis LbrM.31.1820   diphthine synthase-like protein
Leishmania donovani LdBPK_311640.1   diphthine synthase-like protein
Leishmania infantum LinJ.31.1640   diphthine synthase-like protein
Leishmania major LmjF.31.1610   diphthine synthase-like protein
Leishmania mexicana LmxM.30.1610   diphthine synthase-like protein
Loa Loa (eye worm) LOAG_02159   hypothetical protein
Mus musculus ENSMUSG00000033554   DPH5 homolog (S. cerevisiae)
Neospora caninum NCLIV_066040   diphthine synthase, putative
Oryza sativa 4332866   Os03g0355800
Plasmodium berghei PBANKA_1207300   diphthine methyl ester synthase, putative
Plasmodium falciparum PF3D7_1009000   diphthine methyl ester synthase, putative
Plasmodium knowlesi PKNH_0808700   diphthine methyl ester synthase, putative
Plasmodium vivax PVX_094665   diphthine synthase, putative
Plasmodium yoelii PY01561   diphthine synthase
Saccharomyces cerevisiae YLR172C   diphthine synthase
Schistosoma japonicum Sjp_0305750   ko:K00586 diphthine synthase [EC2.1.1.98], putative
Schistosoma japonicum Sjp_0098940   Diphthine synthase, putative
Schistosoma mansoni Smp_025570.2   diphthine synthase
Schmidtea mediterranea mk4.001420.03   Diphthine synthase
Trypanosoma brucei gambiense Tbg972.4.4830   diphthine synthase, putative
Trypanosoma brucei Tb927.4.4650   diphthine synthase, putative
Trypanosoma congolense TcIL3000_4_4000   diphthine synthase, putative
Trypanosoma cruzi TcCLB.407477.30   diphthine synthase, putative
Trypanosoma cruzi TcCLB.511389.130   diphthine synthase, putative
Toxoplasma gondii TGME49_249920   diphthine synthase, putative
Theileria parva TP01_0634   diphthine synthase, putative

Essentiality

Tb927.4.4650 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.4.4650 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.4.4650 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.4.4650 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.4.4650 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
TGME49_249920 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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
  • 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.
  • 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.
  • 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
  • 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.
  • 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

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) 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 procyclic forms . 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

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
Leishmania major diphthine synthase-like protein Compounds References
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 Tb927.4.4650 (Trypanosoma brucei), diphthine synthase, putative
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