Detailed view for Tb927.10.3520

Basic information

TDR Targets ID: 20076
Trypanosoma brucei, protease regulatory ATPase subunit 4
Source Database / ID:  TriTrypDB  GeneDB

pI: 7.4757 | Length (AA): 399 | MW (Da): 44856 | Paralog Number: 0

Signal peptide: N | GPI Anchor: | Predicted trans-membrane segments: 0

Druggability Group : DG3

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

PF00004   ATPase family associated with various cellular activities (AAA)

Gene Ontology

Mouse over links to read term descriptions.
GO:0005737   cytoplasm  
GO:0005634   nucleus  
GO:0005524   ATP binding  
GO:0000166   nucleotide binding  
GO:0017111   nucleoside-triphosphatase activity  
GO:0016787   hydrolase activity  
GO:0030163   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
14 390 5kwa (A) 123 509 27.00 0 1 1.09826 0.88
132 390 3h4m (A) 159 418 54.00 0.00011 1 1.36742 -0.99
139 389 5eqt (A) 102 352 55.00 0.033 1 1.30837 -0.8
314 383 3aji (B) 337 406 29.00 0 1 0.684839 -1.49
326 379 2dzn (D) 357 410 30.00 0.43 0.99 0.622738 -0.96

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 Bloodstream Form. Siegel TN
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile Procyclic. 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_127828)

Species Accession Gene Product
Arabidopsis thaliana AT5G43010   26S proteasome AAA-ATPase subunit RPT4a
Babesia bovis BBOV_II003900   26S proteasome AAA-ATPase subunit RPT4a, putative
Brugia malayi Bm1_31980   Probable 26S protease regulatory subunit S10B
Candida albicans CaO19.482   likely ATPase similar to S. cerevisiae RPT4 (YOR259C) ATPase subunit of the 19S regulatory particle of the 26S proteasome
Candida albicans CaO19.8112   likely ATPase similar to S. cerevisiae RPT4 (YOR259C) ATPase subunit of the 19S regulatory particle of the 26S proteasome
Caenorhabditis elegans CELE_F23F1.8   Protein RPT-4, isoform B
Cryptosporidium hominis Chro.80103   26S proteasome regulatory subunit
Cryptosporidium parvum cgd8_840   26S proteasome regulatory subunit S10b like AAA+ ATpase
Dictyostelium discoideum DDB_G0284517   26S protease regulatory subunit S10B
Drosophila melanogaster Dmel_CG7257   Regulatory particle triple-A ATPase 4-related
Drosophila melanogaster Dmel_CG3455   Regulatory particle triple-A ATPase 4
Echinococcus granulosus EgrG_000440700   26s protease regulatory subunit s10b
Entamoeba histolytica EHI_194570   26S protease regulatory subunit, putative
Echinococcus multilocularis EmuJ_000440700   26s protease regulatory subunit s10b
Giardia lamblia GL50803_21331   26S protease regulatory subunit 7
Homo sapiens ENSG00000100519   proteasome (prosome, macropain) 26S subunit, ATPase, 6
Leishmania braziliensis LbrM.03.0450   26S protease regulatory subunit, putative,serine peptidase, Clan SJ, family S16, putative
Leishmania donovani LdBPK_030520.1   26S protease regulatory subunit, putative
Leishmania infantum LinJ.03.0520   26S protease regulatory subunit, putative,serine peptidase, Clan SJ, family S16, putative
Leishmania major LmjF.03.0540   26S protease regulatory subunit, putative,serine peptidase, Clan SJ, family S16, putative
Leishmania mexicana LmxM.03.0540   26S protease regulatory subunit, putative,serine peptidase, Clan SJ, family S16, putative
Loa Loa (eye worm) LOAG_01658   hypothetical protein
Loa Loa (eye worm) LOAG_01659   proteasome 26S subunit
Mus musculus ENSMUSG00000021832   proteasome (prosome, macropain) 26S subunit, ATPase, 6
Neospora caninum NCLIV_045220   hypothetical protein
Oryza sativa 4341487   Os06g0607800
Oryza sativa 4328642   Os02g0199900
Plasmodium berghei PBANKA_1404900   26S protease regulatory subunit 10B, putative
Plasmodium falciparum PF3D7_1306400   26S protease regulatory subunit 10B, putative
Plasmodium knowlesi PKNH_1406600   26S protease regulatory subunit 10B, putative
Plasmodium vivax PVX_122155   26S protease regulatory subunit 10B, putative
Plasmodium yoelii PY02590   26s protease regulatory subunit s10b (p44) (conserved atpase domain protein 44). [thirteen-lined ground squirrel]
Saccharomyces cerevisiae YOR259C   proteasome regulatory particle base subunit RPT4
Schistosoma japonicum Sjp_0072420   ko:K03064 26S proteasome regulatory subunit T4, putative
Schistosoma mansoni Smp_017070   26S protease regulatory subunit S10b
Schmidtea mediterranea mk4.005974.00  
Schmidtea mediterranea mk4.046932.01   Probable 26S protease regulatory subunit 10B
Schmidtea mediterranea mk4.003129.03   Probable 26S protease regulatory subunit 10B
Schmidtea mediterranea mk4.002912.01   Probable 26S protease regulatory subunit 10B
Schmidtea mediterranea mk4.003008.06   Probable 26S protease regulatory subunit 10B
Schmidtea mediterranea mk4.001038.02   Probable 26S protease regulatory subunit 10B
Schmidtea mediterranea mk4.000012.02   Probable 26S protease regulatory subunit 10B
Schmidtea mediterranea mk4.006062.00   Probable 26S protease regulatory subunit 10B
Schmidtea mediterranea mk4.002773.04   Probable 26S protease regulatory subunit 10B
Schmidtea mediterranea mk4.013876.00   Probable 26S protease regulatory subunit 10B
Schmidtea mediterranea mk4.002912.00  
Schmidtea mediterranea mk4.012190.01   Probable 26S protease regulatory subunit 10B
Schmidtea mediterranea mk4.001647.01   Probable 26S protease regulatory subunit 10B
Trypanosoma brucei gambiense Tbg972.10.4380   Tbgamb.27571 protease regulatory ATPase subunit, putative
Trypanosoma brucei Tb927.10.3520   protease regulatory ATPase subunit 4
Trypanosoma congolense TcIL3000_10_2910   serine peptidase, Clan SJ, family S16, putative
Trypanosoma cruzi TcCLB.510311.70   26S protease regulatory subunit, putative
Trypanosoma cruzi TcCLB.510265.20   serine peptidase, Clan SJ, family S16, putative
Toxoplasma gondii TGME49_228210   26S proteasome regulatory subunit
Theileria parva TP04_0152   26S proteasome regulatory subunit, putative
Trichomonas vaginalis TVAG_115420   26S protease regulatory subunit, putative

Essentiality

Tb927.10.3520 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.10.3520 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.3520 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.10.3520 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.10.3520 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
CELE_F23F1.8 Caenorhabditis elegans embryonic arrest wormbase
CELE_F23F1.8 Caenorhabditis elegans embryonic lethal wormbase
CELE_F23F1.8 Caenorhabditis elegans larval lethal wormbase
CELE_F23F1.8 Caenorhabditis elegans slow growth wormbase
CELE_F23F1.8 Caenorhabditis elegans sterile wormbase
YOR259C Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1404900 Plasmodium berghei Essential plasmo
TGME49_228210 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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

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 3 days). References: 21363968
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 procyclic forms . 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 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) 26S subunit, ATPase, 6 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.

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Gene identifier Tb927.10.3520 (Trypanosoma brucei), protease regulatory ATPase subunit 4
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