Detailed view for Tb927.11.14330

Basic information

TDR Targets ID: 12497
Trypanosoma brucei, HECT-domain (ubiquitin-transferase), putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.5921 | Length (AA): 1609 | MW (Da): 176832 | 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

PF00569   Zinc finger, ZZ type
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:0005488   binding  
GO:0004842   ubiquitin-protein ligase activity  
GO:0006464   protein modification process  

Metabolic Pathways

Ubiquitin mediated proteolysis (KEGG)

Structural information

Modbase 3D models:

There are 10 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
3 92 2ru4 (A) 23 111 16.00 0.042 0.13 0.242901 -0.59
26 442 4uad (A) 83 501 14.00 0.00000000097 1 0.477006 -0.23
192 344 4rzp (A) 45 194 23.00 0.015 1 0.485831 -1.32
290 435 4hxt (A) 55 199 12.00 0.67 0.07 0.224683 -0.62
443 484 2n1a (B) 204 243 30.00 0 0.59 0.272287 0.5
443 484 2n1a (B) 204 241 45.00 0.9 1 0.420887 0.44
1156 1608 5lp8 (A) 3937 4372 22.00 0 1 0.470366 0.26
1214 1602 1zvd (A) 374 741 22.00 0 1 0.473615 -0.17
1312 1602 5tj7 (A) 587 863 32.00 0 1 0.427545 0.22
1511 1601 3pt3 (A) 2709 2792 31.00 0.0014 0.54 0.177522 -0.52

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_128439)

Species Accession Gene Product
Arabidopsis thaliana AT5G02880   E3 ubiquitin-protein ligase UPL4
Arabidopsis thaliana AT4G38600   HECT ubiquitin protein ligase family protein
Babesia bovis BBOV_IV000570   ubiquitin transferase, HECT domain containing protein
Brugia malayi Bm1_16175   thyroid receptor interacting protein 12
Candida albicans CaO19.3237   similar to S. cerevisiae UFD4 (YKL010C) ubiquitin--protein ligase
Candida albicans CaO19.10747   similar to S. cerevisiae UFD4 (YKL010C) ubiquitin--protein ligase
Dictyostelium discoideum DDB_G0287221   armadillo repeat-containing protein
Drosophila melanogaster Dmel_CG42574   circadian trip
Echinococcus granulosus EgrG_000106000   E3 ubiquitin protein ligase TRIP12
Echinococcus multilocularis EmuJ_000106000   E3 ubiquitin protein ligase TRIP12
Homo sapiens ENSG00000153827   thyroid hormone receptor interactor 12
Leishmania braziliensis LbrM.32.1190   hypothetical protein, conserved
Leishmania donovani LdBPK_321150.1   HECT-domain (ubiquitin-transferase), putative
Leishmania infantum LinJ.32.1150   hypothetical protein, conserved
Leishmania major LmjF.32.1090   hypothetical protein, conserved
Leishmania mexicana LmxM.31.1090   hypothetical protein, conserved
Loa Loa (eye worm) LOAG_05367   hypothetical protein
Loa Loa (eye worm) LOAG_14322   hypothetical protein
Loa Loa (eye worm) LOAG_11488   thyroid hormone receptor interactor 12
Mus musculus ENSMUSG00000026219   thyroid hormone receptor interactor 12
Oryza sativa 4339037   Os05g0463900
Oryza sativa 4327983   Os02g0101700
Oryza sativa 4337658   Os05g0122400
Saccharomyces cerevisiae YKL010C   putative ubiquitin-protein ligase UFD4
Schistosoma japonicum Sjp_0131350   expressed protein
Schistosoma japonicum Sjp_0063470   E3 ubiquitin-protein ligase UPL3, putative
Schistosoma mansoni Smp_172420   ubiquitin protein ligase E3a
Schmidtea mediterranea mk4.004160.03  
Schmidtea mediterranea mk4.000217.04  
Schmidtea mediterranea mk4.016586.01  
Schmidtea mediterranea mk4.014585.00  
Schmidtea mediterranea mk4.000514.00  
Trypanosoma brucei gambiense Tbg972.11.16050   hypothetical protein, conserved
Trypanosoma brucei Tb927.11.14330   HECT-domain (ubiquitin-transferase), putative
Trypanosoma congolense TcIL3000.11.14630   Zinc finger, ZZ type, putative
Trypanosoma cruzi TcCLB.511725.160   HECT-domain (ubiquitin-transferase), putative
Theileria parva TP01_0078   hypothetical protein
Trichomonas vaginalis TVAG_056400   hect E3 ubiquitin ligase, putative
Trichomonas vaginalis TVAG_248540   ubiquitin protein ligase E3a, putative
Trichomonas vaginalis TVAG_201990   ubiquitin protein ligase E3a, putative
Trichomonas vaginalis TVAG_269910   ubiquitin protein ligase E3a, putative
Trichomonas vaginalis TVAG_248520   conserved hypothetical protein
Trichomonas vaginalis TVAG_119130   ubiquitin protein ligase E3a, putative
Trichomonas vaginalis TVAG_063800   ubiquitin protein ligase E3a, putative

Essentiality

Tb927.11.14330 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.01.5930 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.01.5930 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb11.01.5930 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.01.5930 this record Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • 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
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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.
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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 3 days). References: 21363968
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
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 Tb927.11.14330 (Trypanosoma brucei), HECT-domain (ubiquitin-transferase), putative
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