Detailed view for Tb927.10.290

Basic information

TDR Targets ID: 13218
Trypanosoma brucei, proteasome alpha 2 subunit, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.337 | Length (AA): 231 | MW (Da): 25355 | 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:0006511   ubiquitin-dependent protein catabolic process  

Metabolic Pathways

Proteasome (KEGG)

Structural information

Modbase 3D models:

There are 5 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
34 264 1j2p (A) 4 233 39.00 0 1 1.409 -0.64
36 265 1ryp (B) 3 250 53.00 0 1 1.50792 -0.99
37 265 5le5 (A) 4 232 53.00 0 1 1.59445 -1.07
43 208 1ryp (G) 12 177 42.00 0 1 1.19812 -0.69
116 183 5o01 (A) 7 72 33.00 0.88 0.92 0.745304 -1.14

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
  • 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_127791)

Species Accession Gene Product
Arabidopsis thaliana AT1G16470   20S proteasome subunit PAB1
Arabidopsis thaliana AT1G79210   proteasome subunit alpha type-2-B
Babesia bovis BBOV_III000310   proteasome A-type and B-type family protein
Brugia malayi Bm1_21080   proteasome subunit alpha type 2
Candida albicans CaO19.7335   multicatalytic endopeptidase
Caenorhabditis elegans CELE_D1054.2   Protein PAS-2
Cryptosporidium hominis Chro.70408   proteasome subunit alpha type 2 (20S proteasome alpha subunit B) (20S proteasome subunit alpha-2)
Cryptosporidium parvum cgd7_3660   proteasome subunit alpha2, protease of the acylase family and NTN hydrolase fold
Dictyostelium discoideum DDB_G0292122   20S proteasome subunit alpha-2
Drosophila melanogaster Dmel_CG5266   Proteasome alpha2 subunit
Echinococcus granulosus EgrG_001120300   proteasome subunit alpha type 2
Entamoeba histolytica EHI_052140   proteasome subunit alpha type 2-A, putative
Echinococcus multilocularis EmuJ_001120300   proteasome subunit alpha type 2
Giardia lamblia GL50803_11434   20S proteasome alpha subunit 2
Homo sapiens ENSG00000106588   proteasome (prosome, macropain) subunit, alpha type, 2
Leishmania braziliensis LbrM.21.2010   proteasome alpha 2 subunit, putative
Leishmania donovani LdBPK_212070.1   proteasome alpha 2 subunit, putative
Leishmania infantum LinJ.21.2070   proteasome alpha 2 subunit, putative
Leishmania major LmjF.21.1700   proteasome alpha 2 subunit, putative
Leishmania mexicana LmxM.21.1700   proteasome alpha 2 subunit, putative
Loa Loa (eye worm) LOAG_08245   proteasome subunit alpha type 2
Mus musculus ensembl-mmu:ENSMUSG00000015671   proteasome (prosome, macropain) subunit, alpha type 2
Neospora caninum NCLIV_013780   hypothetical protein
Oryza sativa 4333000   Os03g0387100
Oryza sativa 4330075   Os02g0634900
Plasmodium berghei PBANKA_0107100   proteasome subunit alpha type-2, putative
Plasmodium falciparum PF3D7_0608500   proteasome subunit alpha type-2, putative
Plasmodium knowlesi PKNH_1141700   proteasome subunit alpha type-2, putative
Plasmodium vivax PVX_113585   proteasome subunit alpha type-2, putative
Plasmodium yoelii PY03034   proteasome subunit alpha type 2
Saccharomyces cerevisiae YML092C   proteasome core particle subunit alpha 2
Schistosoma japonicum Sjp_0204140   ko:K02726 20S proteasome subunit alpha 2, putative
Schistosoma mansoni Smp_067890   proteasome subunit alpha 2 (T01 family)
Trypanosoma brucei gambiense Tbg972.10.200   proteasome alpha 2 subunit, putative
Trypanosoma brucei Tb927.10.290   proteasome alpha 2 subunit, putative
Trypanosoma congolense TcIL3000_10_150   proteasome alpha 2 subunit, putative
Trypanosoma cruzi TcCLB.504069.10   proteasome alpha 2 subunit, putative
Trypanosoma cruzi TcCLB.416883.18   proteasome alpha 2 subunit, putative
Toxoplasma gondii TGME49_287210   proteasome subunit alpha2, protease of the acylase family and NTN hydrolase fold, putative
Theileria parva TP03_0809   proteasome subunit alpha type 2, putative
Trichomonas vaginalis TVAG_103780   Family T1, proteasome alpha subunit, threonine peptidase

Essentiality

Tb927.10.290 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.290 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.10.290 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.10.290 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.290 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_D1054.2 Caenorhabditis elegans embryonic lethal wormbase
CELE_D1054.2 Caenorhabditis elegans larval lethal wormbase
YML092C Saccharomyces cerevisiae inviable yeastgenome
TGME49_287210 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • 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
  • 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
  • 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
  • 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.

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, 2 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
0.0146 0.3484 0.5109
0.0146 0.3484 0.5109
0.0275 0.3479 0.5124
0.0146 0.3498 0.5124
0.0271 0.3485 0.5124
0.0243 0.3498 0.5124
0.0126 0.3687 0.3839
0.0141 0.3473 0.5097
0.0268 0.3615 0.5226
0.0118 0.3484 0.5109
0.0253 0.3498 0.5124
0.0134 0.3484 0.5109
0.0129 0.3683 0.3861
0.0146 0.3498 0.5124
0.0121 0.2889 0.5109
0.0146 0.3484 0.5109
0.0146 0.3484 0.5109
0.0262 0.3498 0.5124

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
    Tb927.10.290 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 Tb927.10.290 (Trypanosoma brucei), proteasome alpha 2 subunit, putative
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