Detailed view for Tb927.2.2440

Basic information

TDR Targets ID: 55064
Trypanosoma brucei, proteasome regulatory non-ATPase subunit 6
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.4025 | Length (AA): 513 | MW (Da): 57324 | 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

PF01399   PCI domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0005838   proteasome regulatory particle  
GO:0004175   endopeptidase activity  
GO:0006511   ubiquitin-dependent protein catabolic process  

Metabolic Pathways

Proteasome (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
3 420 4d10 (B) 30 442 14.00 0.000000000044 1 0.947515 0.47
10 154 4a1s (A) 223 364 12.00 0.0005 0.28 0.497351 -1.07
39 393 3txn (A) 38 390 42.00 0 1 1.28641 -0.91

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_127922)

Species Accession Gene Product
Arabidopsis thaliana AT1G29150   26S proteasome non-ATPase regulatory subunit 9
Babesia bovis BBOV_III008580   PCI domain containing protein
Brugia malayi Bm1_41190   Proteasome regulatory particle, non-atpase-like protein 6
Candida albicans CaO19.1299   similar to S. cerevisiae RPN6 (YDL097C) subunit of the 19S regulatory particle of the 26S proteasome
Candida albicans CaO19.8879   similar to S. cerevisiae RPN6 (YDL097C) subunit of the 19S regulatory particle of the 26S proteasome
Caenorhabditis elegans CELE_F57B9.10   Protein RPN-6.1, isoform B
Cryptosporidium hominis Chro.60414   26S proteasome non-ATPase regulatory subunit
Cryptosporidium parvum cgd6_3590   26S proteasome regulatory subunit Rpn6-like; PINT domain containing protein
Dictyostelium discoideum DDB_G0281315   26S proteasome non-ATPase regulatory subunit 11
Drosophila melanogaster Dmel_CG10149   Regulatory particle non-ATPase 6
Echinococcus granulosus EgrG_000736900   26S proteasome non ATPase regulatory subunit
Entamoeba histolytica EHI_182600   proteasome regulatory subunit, putative
Echinococcus multilocularis EmuJ_000736900   26S proteasome non ATPase regulatory subunit
Giardia lamblia GL50803_16659   Hypothetical protein
Homo sapiens ENSG00000108671   proteasome (prosome, macropain) 26S subunit, non-ATPase, 11
Leishmania braziliensis LbrM.02.0400   proteasome regulatory non-ATPase subunit 6, putative
Leishmania donovani LdBPK_020340.1   proteasome regulatory non-ATPase subunit 6, putative
Leishmania infantum LinJ.02.0340   proteasome regulatory non-ATPase subunit 6, putative
Leishmania major LmjF.02.0370   proteasome regulatory non-ATPase subunit 6, putative
Leishmania mexicana LmxM.02.0370   proteasome regulatory non-ATPase subunit 6, putative
Loa Loa (eye worm) LOAG_04911   proteasome regulatory particle
Mus musculus ENSMUSG00000017428   proteasome (prosome, macropain) 26S subunit, non-ATPase, 11
Neospora caninum NCLIV_045440   proteasome PCI domain-containing protein, putative
Oryza sativa 4333303   Os03g0576400
Oryza sativa 4335951   Os04g0444600
Plasmodium berghei PBANKA_1039600   26S proteasome regulatory subunit RPN6, putative
Plasmodium falciparum PF3D7_1402300   26S proteasome regulatory subunit RPN6
Plasmodium knowlesi PKNH_1355800   26S proteasome regulatory subunit RPN6, putative
Plasmodium vivax PVX_086315   26S proteasome regulatory subunit RPN6, putative
Plasmodium yoelii PY00119   hypothetical protein
Saccharomyces cerevisiae YDL097C   proteasome regulatory particle lid subunit RPN6
Schistosoma japonicum Sjp_0096060   ko:K03036 26S proteasome regulatory subunit N6, putative
Schistosoma mansoni Smp_061650   26S proteasome subunit S9
Schmidtea mediterranea mk4.001308.00   26S proteasome subunit S9, putative
Trypanosoma brucei gambiense Tbg.972.2.990   proteasome regulatory non-ATPase subunit 6
Trypanosoma brucei Tb927.2.2440   proteasome regulatory non-ATPase subunit 6
Trypanosoma cruzi TcCLB.508741.300   proteasome regulatory non-ATPase subunit 6, putative
Toxoplasma gondii TGME49_227960   PCI domain-containing protein
Theileria parva TP04_0762   proteosome subunit, putative
Trichomonas vaginalis TVAG_388670   26S proteasome subunit S9, putative

Essentiality

Tb927.2.2440 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.2.2440 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.2.2440 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.2.2440 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.2.2440 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_F57B9.10 Caenorhabditis elegans adult lethal wormbase
CELE_F57B9.10 Caenorhabditis elegans embryonic lethal wormbase
CELE_F57B9.10 Caenorhabditis elegans larval lethal wormbase
CELE_F57B9.10 Caenorhabditis elegans slow growth wormbase
CELE_F57B9.10 Caenorhabditis elegans sterile wormbase
YDL097C Saccharomyces cerevisiae inviable yeastgenome
TGME49_227960 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • 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.
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • 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
  • 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) normal (PATO:0000461) single cell organism (CARO:0000064) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
cell morphogenesis (GO:0000902) normal (PATO:0000461) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
regulation of cell motility (GO:0051270) normal (PATO:0000461) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
cell cycle (GO:0007049) normal (PATO:0000461) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
mitochondrion organization and biogenesis (GO:0007005) normal (PATO:0000461) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
regulation of cell motility (GO:0051270) normal (PATO:0000461) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
endocytosis (GO:0006897) normal (PATO:0000461) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 16963636
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) 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

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
Homo sapiens proteasome (prosome, macropain) 26S subunit, non-ATPase, 11 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.

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

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Gene identifier Tb927.2.2440 (Trypanosoma brucei), proteasome regulatory non-ATPase subunit 6
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