Detailed view for Tb927.11.16290

Basic information

TDR Targets ID: 15122
Trypanosoma brucei, AUT2/APG4/ATG4 cysteine peptidase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 5.5081 | Length (AA): 348 | MW (Da): 37781 | 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

PF03416   Peptidase family C54

Gene Ontology

Mouse over links to read term descriptions.
GO:0000422   mitochondrion degradation  
GO:0008150   biological_process  
GO:0005737   cytoplasm  
GO:0004197   cysteine-type endopeptidase activity  
GO:0008233   peptidase activity  
GO:0000045   autophagic vacuole formation  

Metabolic Pathways

Regulation of autophagy (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
15 332 2cy7 (A) 15 377 30.00 0 1 1.30699 -0.65
22 320 2p82 (A) 26 359 29.00 0 1 1.2404 -0.73
50 312 2z0d (A) 50 351 34.00 0 1 1.12935 -0.5

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 60-80% 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_127111)

Species Accession Gene Product
Arabidopsis thaliana AT2G44140   cysteine protease ATG4a
Arabidopsis thaliana AT3G59950   peptidase family C54 protein
Brugia malayi Bm1_03885   Peptidase family C54 containing protein
Candida albicans CaO19.9938   potential protease similar to S. cerevisiae ATG4 (YNL223W) microtubule-binding anchor protein involved in attachment of autophag
Candida albicans CaO19.2401   potential protease similar to S. cerevisiae ATG4 (YNL223W) microtubule-binding anchor protein involved in attachment of autophag
Caenorhabditis elegans CELE_Y87G2A.3   Protein ATG-4.1, isoform B
Caenorhabditis elegans CELE_ZK792.8   Protein ATG-4.2
Dictyostelium discoideum DDB_G0273553   autophagy protein 4
Dictyostelium discoideum DDB_G0283753   hypothetical protein
Dictyostelium discoideum DDB_G0273443   autophagy protein 4
Drosophila melanogaster Dmel_CG4428   Autophagy-specific gene 4a
Drosophila melanogaster Dmel_CG6194   Autophagy-specific gene 4b
Echinococcus granulosus EgrG_000458100   cysteine protease atg4b
Echinococcus granulosus EgrG_000098800   Peptidase C54
Entamoeba histolytica EHI_141400   peptidase, C54 family
Echinococcus multilocularis EmuJ_000458100   cysteine protease atg4b
Echinococcus multilocularis EmuJ_000098800   Peptidase C54
Homo sapiens ENSG00000101844   autophagy related 4A, cysteine peptidase
Homo sapiens ENSG00000168397   autophagy related 4B, cysteine peptidase
Homo sapiens ENSG00000125703   autophagy related 4C, cysteine peptidase
Homo sapiens ENSG00000130734   autophagy related 4D, cysteine peptidase
Leishmania braziliensis LbrM.32.4130   AUT2/APG4/ATG4 cysteine peptidase, putative
Leishmania donovani LdBPK_324040.1   AUT2/APG4/ATG4 cysteine peptidase, putative
Leishmania infantum LinJ.32.4040   AUT2/APG4/ATG4 cysteine peptidase, putative
Leishmania major LmjF.32.3890   AUT2/APG4/ATG4 cysteine peptidase, putative
Leishmania mexicana LmxM.31.3890   AUT2/APG4/ATG4 cysteine peptidase, putative,cysteine peptidase, Clan CA, family C54, putative
Loa Loa (eye worm) LOAG_03889   hypothetical protein
Mus musculus ENSMUSG00000028550   autophagy related 4C, cysteine peptidase
Mus musculus ENSMUSG00000079418   autophagy related 4A, cysteine peptidase
Mus musculus ENSMUSG00000002820   autophagy related 4D, cysteine peptidase
Mus musculus 66615   autophagy related 4B, cysteine peptidase
Oryza sativa 4337435   Os04g0682000
Oryza sativa 4333022   Os03g0391000
Saccharomyces cerevisiae YNL223W   Atg4p
Schistosoma japonicum Sjp_0218550   ko:K08342 autophagy-related protein 4, putative
Schistosoma japonicum Sjp_0069880   ko:K08342 autophagy-related protein 4, putative
Schistosoma mansoni Smp_124830.2   family C54 unassigned peptidase (C54 family)
Schistosoma mansoni Smp_039820   autophagin-1 (C54 family)
Schistosoma mansoni Smp_124830.1   family C54 unassigned peptidase (C54 family)
Schmidtea mediterranea mk4.000897.06  
Schmidtea mediterranea mk4.005819.05   Autophagin-1
Schmidtea mediterranea mk4.002341.00   Autophagin-1
Trypanosoma brucei gambiense Tbg972.11.18290   peptidase, putative
Trypanosoma brucei Tb927.11.16290   AUT2/APG4/ATG4 cysteine peptidase, putative
Trypanosoma congolense TcIL3000.11.16200   AUT2/APG4/ATG4 cysteine peptidase, putative
Trypanosoma cruzi TcCLB.511527.50   AUT2/APG4/ATG4 cysteine peptidase, putative
Trichomonas vaginalis TVAG_258880   Clan CA, family C54, ATG4-like cysteine peptidase
Trichomonas vaginalis TVAG_023970   Clan CA, family C54, ATG4-like cysteine peptidase
Trichomonas vaginalis TVAG_456380   Clan CA, family C54, ATG4-like cysteine peptidase
Trichomonas vaginalis TVAG_397150   Clan CA, family C54, ATG4-like cysteine peptidase
Trichomonas vaginalis TVAG_122030   Clan CA, family C54, ATG4-like cysteine peptidase

Essentiality

Tb927.11.16290 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb11.01.7970 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.01.7970 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb11.01.7970 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb11.01.7970 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
Show/Hide essentiality data references
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • 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
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.

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) 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

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 autophagy related 4B, cysteine peptidase Compounds References
Leishmania major AUT2/APG4/ATG4 cysteine peptidase, putative 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
0.0059 0.3157 0.8324
0.0071 0.9186 1
0.0062 0.3 0.412
0.0071 0.3087 0.5989
0.0062 0.3 0.412
0.0071 1 1
0.0042 0.3087 0.5989
0.0059 0.3157 0.8324
0.006 1 1

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 Tb927.11.16290 (Trypanosoma brucei), AUT2/APG4/ATG4 cysteine peptidase, putative
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