Detailed view for Tb927.10.230

Basic information

TDR Targets ID: 16052
Trypanosoma brucei, proteasome subunit alpha type-5, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 4.6353 | Length (AA): 246 | MW (Da): 27177 | 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

PF00227   Proteasome subunit
PF10584   Proteasome subunit A N-terminal signature

Gene Ontology

Mouse over links to read term descriptions.
GO:0019773   proteasome core complex, alpha-subunit complex  
GO:0005839   proteasome core complex  
GO:0004298   threonine endopeptidase activity  
GO:0004175   endopeptidase activity  
GO:0051603   proteolysis involved in cellular protein catabolic process  
GO:0043161   proteasomal ubiquitin-dependent protein catabolic process  
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
2 246 5dsv (C) 1 242 31.00 0 1 1.34964 -0.25
9 242 5le5 (D) 9 241 55.00 0 1 1.67892 -0.99
9 245 4r17 (D) 1 238 51.00 0 1 1.63741 -1.06

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:

PDB tag
  • 1FNT:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1YA7:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1YAR:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1YAU:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1Z7Q:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

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_127593)

Species Accession Gene Product
Arabidopsis thaliana AT3G14290   20S proteasome alpha subunit E2
Arabidopsis thaliana AT1G53850   proteasome subunit alpha type-5-A
Babesia bovis BBOV_I001480   proteasome alpha 5 subunit, putative
Brugia malayi Bm1_37390   20S proteasome alpha5 subunit
Candida albicans CaO19.8328   similar to S. cerevisiae PUP2 (YGR253C) proteasome subunit
Candida albicans CaO19.709   similar to S. cerevisiae PUP2 (YGR253C) proteasome subunit
Caenorhabditis elegans CELE_F25H2.9   Protein PAS-5
Cryptosporidium hominis Chro.50200   proteasome subunit alpha type 5
Cryptosporidium parvum cgd5_1820   proteasome subunit alpha type 5
Dictyostelium discoideum DDB_G0268538   20S proteasome subunit alpha-5
Drosophila melanogaster Dmel_CG10938   Proteasome alpha5 subunit
Echinococcus granulosus EgrG_001182700   subfamily T1A non peptidase ue
Entamoeba histolytica EHI_023020   proteasome subunit alpha type 5, putative
Entamoeba histolytica EHI_004760   proteasome subunit alpha type 5, putative
Echinococcus multilocularis EmuJ_001182700   subfamily T1A non peptidase ue
Giardia lamblia GL50803_2980   20S proteasome alpha subunit 5
Homo sapiens ENSG00000143106   proteasome (prosome, macropain) subunit, alpha type, 5
Leishmania braziliensis LbrM.33.0890   proteasome alpha 5 subunit, putative
Leishmania donovani LdBPK_212200.1   proteasome subunit alpha type-5, putative
Leishmania infantum LinJ.21.2200   proteasome alpha 5 subunit, putative,20S proteasome subunit alpha 5, (putative)
Leishmania major LmjF.21.1830   proteasome alpha 5 subunit, putative,20S proteasome subunit alpha 5, (putative)
Leishmania mexicana LmxM.21.1830   proteasome alpha 5 subunit, putative,20S proteasome subunit alpha 5, (putative)
Loa Loa (eye worm) LOAG_01073   20S proteasome alpha5 subunit
Mus musculus ENSMUSG00000068749   proteasome (prosome, macropain) subunit, alpha type 5
Neospora caninum NCLIV_065750   Alpha 2 subunit of 20S proteasome (ISS), related
Oryza sativa 4350922   Os11g0615700
Plasmodium berghei PBANKA_0211500   proteasome subunit alpha type-5, putative
Plasmodium falciparum PF3D7_0727400   proteasome subunit alpha type-5, putative
Plasmodium knowlesi PKNH_0212000   proteasome subunit alpha type-5, putative
Plasmodium vivax PVX_081675   proteasome subunit alpha type-5, putative
Plasmodium yoelii PY02094   proteasome subunit alpha type 5
Saccharomyces cerevisiae YGR253C   proteasome core particle subunit alpha 5
Schistosoma mansoni Smp_032580.2   subfamily T1A non-peptidase homologue (T01 family)
Schistosoma mansoni Smp_032580.3   subfamily T1A non-peptidase homologue (T01 family)
Schistosoma mansoni Smp_032580.1   subfamily T1A non-peptidase homologue (T01 family)
Schmidtea mediterranea mk4.001348.01   Proteasome subunit alpha type
Schmidtea mediterranea mk4.006696.00   Proteasome subunit alpha type
Trypanosoma brucei gambiense Tbg972.10.140   proteasome alpha 5 subunit, putative,20S proteasome subunit alpha 5
Trypanosoma brucei Tb927.10.230   proteasome subunit alpha type-5, putative
Trypanosoma congolense TcIL3000_10_90   proteasome subunit alpha type-5, putative
Trypanosoma cruzi TcCLB.511145.43   proteasome subunit alpha type-5, putative
Trypanosoma cruzi TcCLB.504069.53   proteasome subunit alpha type-5, putative
Toxoplasma gondii TGME49_249590   proteasome subunit alpha type 5-2, putative
Theileria parva TP01_1231   proteasome subunit alpha type 5, putative
Trichomonas vaginalis TVAG_293540   Family T1, proteasome alpha subunit, threonine peptidase

Essentiality

Tb927.10.230 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.230 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.10.230 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.10.230 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.230 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_F25H2.9 Caenorhabditis elegans embryonic lethal wormbase
CELE_F25H2.9 Caenorhabditis elegans larval arrest wormbase
CELE_F25H2.9 Caenorhabditis elegans larval lethal wormbase
CELE_F25H2.9 Caenorhabditis elegans slow growth wormbase
CELE_F25H2.9 Caenorhabditis elegans sterile wormbase
YGR253C Saccharomyces cerevisiae inviable yeastgenome
PBANKA_0211500 Plasmodium berghei Essential plasmo
TGME49_249590 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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
  • 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
  • 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) 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) subunit, alpha type, 5 Compounds References
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
0.0132 0.387 0.4034
0.0126 0.3046 0.5387
0.0283 0.3674 0.5402
0.0288 0.3667 0.5402
0.0162 0.2508 0.2531
0.0153 0.3674 0.5387
0.0281 0.3801 0.5498
0.014 0.3674 0.5387
0.0123 0.3674 0.5387
0.0255 0.3687 0.5402
0.0153 0.3674 0.5387
0.0153 0.3687 0.5402
0.0265 0.3687 0.5402
0.0148 0.3663 0.5376
0.0153 0.3674 0.5387
0.0275 0.3687 0.5402
0.0153 0.3674 0.5387
0.0153 0.3687 0.5402
0.0135 0.3867 0.4058

Assayability

Assay information

  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Trypanosoma brucei ( 2 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    Tb927.10.230 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Trypanosoma brucei ( 2 )

Bibliographic References

35 literature references were collected for this gene.

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Gene identifier Tb927.10.230 (Trypanosoma brucei), proteasome subunit alpha type-5, putative
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