Detailed view for Tb927.11.4160

Basic information

TDR Targets ID: 10384
Trypanosoma brucei, predicted C2 domain protein
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.4576 | Length (AA): 1235 | MW (Da): 136307 | Paralog Number: 0

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

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

PF00168   C2 domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0008150   biological_process  
GO:0005575   cellular_component  
GO:0003674   molecular_function  
GO:0005544   calcium-dependent phospholipid binding  

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
2 128 4iqh (A) 1 126 24.00 0.66 1 0.504534 -0.75
3 135 2dmh (A) 8 137 24.00 0 1 0.449092 -0.62
3 105 1w15 (A) 303 401 38.00 0.0068 0.69 0.271901 0.31
3 111 3fdw (A) 372 482 24.00 0 0.65 0.320659 -0.24
1038 1118 5et5 (A) 243 321 13.00 0.44 0.07 0.146287 -0.27

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 Procyclic. Siegel TN
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile 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_130428)

Species Accession Gene Product
Brugia malayi Bm1_00685   C2 domain containing protein
Caenorhabditis elegans CELE_F52H2.7   Protein F52H2.7
Dictyostelium discoideum DDB_G0269546   C2 calcium-dependent membrane targeting domain-containing protein
Drosophila melanogaster Dmel_CG6454   CG6454 gene product from transcript CG6454-RC
Echinococcus granulosus EgrG_000799100   C2 calcium dependent membrane targeting
Echinococcus multilocularis EmuJ_000799100   C2 calcium dependent membrane targeting
Homo sapiens ENSG00000111731   C2 calcium-dependent domain containing 5
Leishmania braziliensis LbrM.13.0580   hypothetical protein, conserved
Leishmania donovani LdBPK_130650.1   C2 domain containing protein, putative
Leishmania infantum LinJ.13.0650   hypothetical protein, conserved
Leishmania major LmjF.13.0760   hypothetical protein, conserved
Leishmania mexicana LmxM.13.0760   hypothetical protein, conserved
Loa Loa (eye worm) LOAG_06395   C2 domain-containing protein
Mus musculus ENSMUSG00000030279   C2 calcium-dependent domain containing 5
Onchocerca volvulus OVOC5589  
Plasmodium berghei PBANKA_0305200   conserved Plasmodium protein, unknown function
Plasmodium falciparum PF3D7_0208100   conserved Plasmodium protein, unknown function
Plasmodium knowlesi PKNH_0413000   conserved Plasmodium protein, unknown function
Plasmodium vivax PVX_003855   hypothetical protein, conserved
Plasmodium yoelii PY06292   fulmal1
Plasmodium yoelii PY03495   hypothetical protein
Schistosoma japonicum Sjp_0044000   Conserved hypothetical protein
Schistosoma japonicum Sjp_0131600   similar to Uncharacterized protein KIAA0528 homolog, putative
Schistosoma japonicum Sjp_0314790   similar to Uncharacterized protein KIAA0528 homolog, putative
Schistosoma mansoni Smp_133590   hypothetical protein
Schmidtea mediterranea mk4.020079.02  
Schmidtea mediterranea mk4.028373.00  
Schmidtea mediterranea mk4.018587.00  
Schmidtea mediterranea mk4.008967.01  
Schmidtea mediterranea mk4.025011.01  
Schmidtea mediterranea mk4.018071.01  
Trypanosoma brucei gambiense Tbg972.11.4750   hypothetical protein, conserved,predicted C2 domain protein
Trypanosoma brucei Tb927.11.4160   predicted C2 domain protein
Trypanosoma congolense TcIL3000.11.4200   predicted C2 domain protein
Trypanosoma cruzi TcCLB.506737.40   hypothetical protein, conserved
Trypanosoma cruzi TcCLB.511855.50   hypothetical protein, conserved

Essentiality

Tb927.11.4160 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.02.1630 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb11.02.1630 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb11.02.1630 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.02.1630 this record Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_F52H2.7 Caenorhabditis elegans embryonic lethal wormbase
Show/Hide essentiality data references
  • 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
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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.

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
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) increased (PATO:0000470) procyclic (PLO:0034) 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 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

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0072 0.2639 1
0.0109 0.4866 0.5
0.005 0.2612 0.5
0.0018 0.5 0.5
0.0125 0.3893 0.3893
0.0121 1 1
0.0071 0.2549 1
0.0058 0.5 0.5
0.0057 0.3491 0.5
0.0107 0.5 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.

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

User comments

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Gene identifier Tb927.11.4160 (Trypanosoma brucei), predicted C2 domain protein
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