Detailed view for Tb927.9.5260

Basic information

TDR Targets ID: 10291
Trypanosoma brucei, ERAD-associated E3 ubiquitin-protein ligase HRD1, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.3186 | Length (AA): 488 | MW (Da): 54871 | Paralog Number: 0

Signal peptide: Y | GPI Anchor: | Predicted trans-membrane segments: 6

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

PF13639   Ring finger domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0008150   biological_process  
GO:0005575   cellular_component  
GO:0008270   zinc ion binding  
GO:0005515   protein binding  

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
277 333 5d0m (C) 259 338 32.00 0 1 0.513803 -0.79
289 345 4lad (B) 341 586 44.00 0.000000038 0.94 0.478703 1.13
289 333 2csy (A) 18 59 29.00 0 0.92 0.372213 0.2

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_128080)

Species Accession Gene Product
Arabidopsis thaliana AT1G65040   HRD1-like protein
Arabidopsis thaliana AT3G16090   HRD1-like protein
Babesia bovis BBOV_IV010180   zinc finger, C3HC4 type domain containing protein
Brugia malayi Bm1_28085   hypothetical protein
Candida albicans CaO19.8338   similar to putative zinc finger C3H4 type
Candida albicans CaO19.719   similar to putative zinc finger C3H4 type
Caenorhabditis elegans CELE_F55A11.3   Protein SEL-11
Cryptosporidium hominis Chro.80300   hypothetical protein
Cryptosporidium parvum cgd8_2560   HRD1 like membrane associated RING finger containing protein signal peptide plus 6 transmembrane domains
Dictyostelium discoideum DDB_G0287847   hypothetical protein
Drosophila melanogaster Dmel_CG1937   septin interacting protein 3
Echinococcus granulosus EgrG_001189600   E3 ubiquitin protein ligase synoviolin B
Entamoeba histolytica EHI_166440   zinc finger domain containing protein
Echinococcus multilocularis EmuJ_001189600   E3 ubiquitin protein ligase synoviolin B
Homo sapiens ENSG00000162298   synovial apoptosis inhibitor 1, synoviolin
Leishmania braziliensis LbrM.15.1410   hypothetical protein, conserved
Leishmania donovani LdBPK_151460.1   ERAD-associated E3 ubiquitin-protein ligase HRD1, putative
Leishmania infantum LinJ.15.1460   hypothetical protein, conserved
Leishmania major LmjF.15.1410   hypothetical protein, conserved
Leishmania mexicana LmxM.15.1410   hypothetical protein, conserved
Loa Loa (eye worm) LOAG_09127   hypothetical protein
Mus musculus ensembl-mmu:ENSMUSG00000024807   synovial apoptosis inhibitor 1, synoviolin
Neospora caninum NCLIV_019800   hypothetical protein
Oryza sativa 4340826   Os06g0301000
Onchocerca volvulus OVOC7463  
Plasmodium berghei PBANKA_1020900   ERAD-associated E3 ubiquitin-protein ligase HRD1, putative
Plasmodium falciparum PF3D7_1422500   ERAD-associated E3 ubiquitin-protein ligase HRD1
Plasmodium knowlesi PKNH_1335500   ERAD-associated E3 ubiquitin-protein ligase HRD1, putative
Plasmodium vivax PVX_085355   ERAD-associated E3 ubiquitin-protein ligase HRD1, putative
Plasmodium yoelii PY00025   FLJ00221 protein
Saccharomyces cerevisiae YOL013C   E3 ubiquitin-protein ligase HRD1
Schistosoma japonicum Sjp_0049530   ko:K10601 E3 ubiquitin-protein ligase synoviolin, putative
Schistosoma mansoni Smp_157360   synoviolin
Schmidtea mediterranea mk4.009937.01  
Schmidtea mediterranea mk4.018973.00   E3 ubiquitin-protein ligase hrd-1
Schmidtea mediterranea mk4.016856.00   E3 ubiquitin-protein ligase hrd-1
Trypanosoma brucei gambiense Tbg972.9.2790   hypothetical protein, conserved
Trypanosoma brucei Tb927.9.5260   ERAD-associated E3 ubiquitin-protein ligase HRD1, putative
Trypanosoma congolense TcIL3000_9_1750   ERAD-associated E3 ubiquitin-protein ligase HRD1, putative
Trypanosoma cruzi TcCLB.509945.10   ERAD-associated E3 ubiquitin-protein ligase HRD1, putative
Trypanosoma cruzi TcCLB.508277.190   ERAD-associated E3 ubiquitin-protein ligase HRD1, putative
Toxoplasma gondii TGME49_304460   zinc finger, C3HC4 type (RING finger) domain-containing protein
Theileria parva TP01_0655   hypothetical protein, conserved
Trichomonas vaginalis TVAG_474070   synoviolin, putative
Trichomonas vaginalis TVAG_159290   synoviolin, putative

Essentiality

Tb927.9.5260 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb09.160.3780 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb09.160.3780 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb09.160.3780 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb09.160.3780 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
TGME49_304460 Toxoplasma gondii Probably essential sidik
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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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 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) 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 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): 0.1

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 Tb927.9.5260 (Trypanosoma brucei), ERAD-associated E3 ubiquitin-protein ligase HRD1, putative
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