Detailed view for Tb927.9.9670

Basic information

TDR Targets ID: 19496
Trypanosoma brucei, proteasome alpha 1 subunit, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.6254 | Length (AA): 250 | MW (Da): 27544 | 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 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
2 249 5le5 (G) 5 245 41.00 0 1 1.4944 -0.39
3 183 1ryp (F) 3 174 29.00 0.00000000021 1 1.0915 -0.43
4 250 1ryp (A) 10 252 42.00 0 1 1.5355 -0.73

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_127623)

Species Accession Gene Product
Arabidopsis thaliana AT5G35590   proteasome alpha subunit A1
Babesia bovis BBOV_II002330   proteasome subunit alpha type 6 protein, putative
Brugia malayi Bm1_05700   proteasome subunit alpha type 6
Candida albicans CaO19.12833   proteasome subunit
Candida albicans CaO19.5378   proteasome subunit
Caenorhabditis elegans CELE_C15H11.7   Protein PAS-1
Cryptosporidium hominis Chro.30255   proteasome subunit alpha type 6 (20S proteasome alpha subunit A) (20S proteasome subunit alpha-1) (Proteasome iota subunit)
Cryptosporidium hominis Chro.30254   20S proteasome subunit PAA1
Cryptosporidium parvum cgd3_2170   proteasome subunit alpha1
Dictyostelium discoideum DDB_G0278847   20S proteasome subunit alpha-6
Drosophila melanogaster Dmel_CG18495   Proteasome alpha1 subunit
Drosophila melanogaster Dmel_CG30382   CG30382 gene product from transcript CG30382-RB
Echinococcus granulosus EgrG_000877400   proteasome subunit alpha type 6
Entamoeba histolytica EHI_153190   proteasome subunit alpha type 6, putative
Echinococcus multilocularis EmuJ_000877400   proteasome subunit alpha type 6
Giardia lamblia GL50803_16924   20S proteasome alpha subunit 1
Homo sapiens ENSG00000100902   proteasome (prosome, macropain) subunit, alpha type, 6
Leishmania braziliensis LbrM.34.4810   proteasome alpha 1 subunit, putative
Leishmania donovani LdBPK_354910.1   proteasome alpha 1 subunit, putative
Leishmania infantum LinJ.35.4910   proteasome alpha 1 subunit, putative
Leishmania major LmjF.35.4850   proteasome alpha 1 subunit, putative
Leishmania mexicana LmxM.34.4850   proteasome alpha 1 subunit, putative
Loa Loa (eye worm) LOAG_03012   proteasome subunit alpha type 6
Mus musculus ENSMUSG00000021024   proteasome (prosome, macropain) subunit, alpha type 6
Neospora caninum NCLIV_017470   Proteasome subunit alpha type (EC 3.4.25.1), related
Oryza sativa 4331828   Os03g0180400
Plasmodium berghei PBANKA_1223100   proteasome subunit alpha type-6, putative
Plasmodium falciparum PF3D7_0807500   proteasome subunit alpha type-6, putative
Plasmodium knowlesi PKNH_0111300   proteasome subunit alpha type-6, putative
Plasmodium vivax PVX_088170   proteasome subunit alpha type-6, putative
Plasmodium yoelii PY04190   proteasome subunit alpha Type 6-B
Saccharomyces cerevisiae YGL011C   proteasome core particle subunit alpha 1
Schistosoma japonicum Sjp_0204320   ko:K02730 20S proteasome subunit alpha 1, putative
Schistosoma japonicum Sjp_0023990   ko:K04715 ceramide kinase [EC2.7.1.138], putative
Schistosoma mansoni Smp_130110   proteasome subunit alpha 6 (T01 family)
Schmidtea mediterranea mk4.000779.07   Proteasome subunit alpha 6
Trypanosoma brucei gambiense Tbg972.9.5530   proteasome alpha 1 subunit, putative,20S proteasome subunit alpha-6, (putative)
Trypanosoma brucei Tb927.9.9670   proteasome alpha 1 subunit, putative
Trypanosoma congolense TcIL3000_9_3500   proteasome alpha 1 subunit, putative
Trypanosoma cruzi TcCLB.510729.70   proteasome alpha 1 subunit, putative
Trypanosoma cruzi TcCLB.506885.350   proteasome alpha 1 subunit, putative
Toxoplasma gondii TGME49_242290   proteasome subunit alpha1, putative
Theileria parva TP04_0366   proteasome subunit alpha, putative
Trichomonas vaginalis TVAG_267300   Family T1, proteasome alpha subunit, threonine peptidase

Essentiality

Tb927.9.9670 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb09.211.1250 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb09.211.1250 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb09.211.1250 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb09.211.1250 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_C15H11.7 Caenorhabditis elegans embryonic lethal wormbase
CELE_C15H11.7 Caenorhabditis elegans larval arrest wormbase
CELE_C15H11.7 Caenorhabditis elegans slow growth wormbase
YGL011C Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1223100 Plasmodium berghei Essential plasmo
TGME49_242290 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.

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

Druggability index (range: 0 to 1): 0.2

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, 6 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
0.0163 0.2523 0.2546
0.029 0.3694 0.5443
0.0285 0.3702 0.5443
0.0127 0.307 0.5429
0.0133 0.3898 0.4064
0.0124 0.3702 0.5429
0.0257 0.3715 0.5443
0.0141 0.3702 0.5429
0.0154 0.3702 0.5429
0.0283 0.3829 0.5538
0.0149 0.3691 0.5417
0.0267 0.3715 0.5443
0.0154 0.3702 0.5429
0.0154 0.3702 0.5429
0.0154 0.3715 0.5443
0.0154 0.3702 0.5429
0.0154 0.3715 0.5443
0.0136 0.3895 0.4088
0.0276 0.3715 0.5443

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 Tb927.9.9670 (Trypanosoma brucei), proteasome alpha 1 subunit, putative
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