Detailed view for Tb927.11.16260

Basic information

TDR Targets ID: 18569
Trypanosoma brucei, SPRY domain/HECT-domain (ubiquitin-transferase), putative

Source Database / ID:  TriTrypDB  GeneDB

pI: 6.7935 | Length (AA): 4128 | MW (Da): 455026 | Paralog Number: 0

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

Druggability Group : DG2

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

PF00622   SPRY domain
PF00632   HECT-domain (ubiquitin-transferase)

Gene Ontology

Mouse over links to read term descriptions.
GO:0005622   intracellular  
GO:0016881   acid-amino acid ligase activity  
GO:0008270   zinc ion binding  
GO:0005515   protein binding  
GO:0004842   ubiquitin-protein ligase activity  
GO:0006464   protein modification process  

Metabolic Pathways

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

Structural information

Modbase 3D models:

There are 14 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
87 256 3zxp (A) 8 184 20.00 0 0.94 0.294282 -0.21
1333 1496 4uos (A) 18 183 9.00 0.06 0.04 0.189929 -0.83
1556 1711 2iwg (B) 2 170 10.00 0.0000000022 0.28 0.0429907 0.26
2292 2472 2yue (A) 2 162 17.00 0 0.8 0.0339469 0.41
2500 2544 2dip (A) 34 73 43.00 0.0029 0.62 0.339901 0.33
3385 3515 2j1o (A) 115 289 35.00 0.2 0.42 0.0927345 1.21
3417 3598 2v24 (A) 40 226 24.00 0 1 0.268189 -0.23
3476 3600 2yyo (A) 37 163 18.00 0 1 0.243381 -0.82
3476 3591 3kb5 (A) 341 460 19.00 0 0.87 0.306201 -0.8
3477 3563 4xw3 (A) 130 209 40.00 0.000058 1 0.499076 -0.68
3742 4122 5tjq (A) 493 864 18.00 0 1 0.162397 0.61
3786 4120 1zvd (A) 401 740 23.00 0 1 0.274253 0.08
3843 4128 5lp8 (B) 4065 4374 19.00 0 1 0.296483 -0.04
4046 4119 3pt3 (A) 2713 2791 27.00 0.0017 0.45 0.310126 -0.94

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
Mid 40-60% 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_151799)

Species Accession Gene Product
Leishmania braziliensis LbrM.32.4170   hypothetical protein, conserved
Leishmania donovani LdBPK_324080.1   SPRY domain/HECT-domain (ubiquitin-transferase), putative
Leishmania infantum LinJ.32.4080   hypothetical protein, conserved
Leishmania major LmjF.32.3930   hypothetical protein, conserved
Leishmania mexicana LmxM.31.3930   hypothetical protein, conserved
Trypanosoma brucei gambiense Tbg972.11.18250   hypothetical protein, conserved
Trypanosoma brucei Tb927.11.16260   SPRY domain/HECT-domain (ubiquitin-transferase), putative
Trypanosoma congolense TcIL3000_0_12400   SPRY domain/HECT-domain (ubiquitin-transferase), putative
Trypanosoma cruzi TcCLB.398751.10   SPRY domain/HECT-domain (ubiquitin-transferase), putative
Trypanosoma cruzi TcCLB.508525.60   SPRY domain/HECT-domain (ubiquitin-transferase), putative
Trypanosoma cruzi TcCLB.511527.9   SPRY domain/HECT-domain (ubiquitin-transferase), putative

Essentiality

Tb927.11.16260 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.01.7940 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb11.01.7940 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb11.01.7940 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.01.7940 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
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
  • 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.
  • 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
  • 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.
  • 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.
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
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

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 Tb927.11.16260 (Trypanosoma brucei), SPRY domain/HECT-domain (ubiquitin-transferase), putative
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