Detailed view for Tb927.8.7020

Basic information

TDR Targets ID: 16580
Trypanosoma brucei, peptidase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 4.8344 | Length (AA): 1064 | MW (Da): 118861 | 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

PF00675   Insulinase (Peptidase family M16)
PF05193   Peptidase M16 inactive domain
PF16187   Middle or third domain of peptidase_M16

Gene Ontology

Mouse over links to read term descriptions.
GO:0005575   cellular_component  
GO:0046872   metal ion binding  
GO:0008270   zinc ion binding  
GO:0004222   metalloendopeptidase activity  
GO:0003824   catalytic activity  
GO:0006508   proteolysis  

Metabolic Pathways

This gene is not mapped to any metabolic pathway in KEGG.

Structural information

Modbase 3D models:

There are 4 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
5 1019 1q2l (A) 31 960 21.00 0 1 1.14825 0.05
8 1031 3cww (A) 54 1006 25.00 0 1 1.21971 -0.18
25 264 4nnz (A) 14 242 32.00 0.000007 1 0.390864 0.44
358 473 5cwh (A) 35 140 9.00 0 0.01 0.140723 -0.47

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 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_126910)

Species Accession Gene Product
Arabidopsis thaliana AT3G57470   insulinase family protein
Arabidopsis thaliana AT1G06900   Insulinase (peptidase family M16) family protein
Arabidopsis thaliana AT2G41790   zinc-metallopeptidase PXM16
Brugia malayi Bm1_26615   insulin-degrading enzyme
Candida albicans CaO19.5561   likely protease similar to S. cerevisiae STE23 (YLR389C) involved in a-factor maturation
Candida albicans CaO19.13007   likely protease similar to S. cerevisiae STE23 (YLR389C) involved in a-factor maturation
Caenorhabditis elegans CELE_C02G6.1   Protein C02G6.1
Caenorhabditis elegans CELE_C28F5.4   Protein C28F5.4
Caenorhabditis elegans CELE_Y70C5C.1   Protein Y70C5C.1
Caenorhabditis elegans CELE_C02G6.2   Protein C02G6.2
Caenorhabditis elegans CELE_F44E7.4   Protein F44E7.4, isoform C
Cryptosporidium hominis Chro.20103   involved in a-factor processing; Ste23p
Cryptosporidium hominis Chro.20104   ENSANGP00000016000
Cryptosporidium parvum cgd2_920   peptidaseinsulinase-like peptidase
Cryptosporidium parvum cgd2_930   peptidaseinsulinase-like peptidase
Chlamydia trachomatis CT_806   insulinase family protease III
Dictyostelium discoideum DDB_G0287851   hypothetical protein
Drosophila melanogaster Dmel_CG2025   CG2025 gene product from transcript CG2025-RA
Drosophila melanogaster Dmel_CG10588   CG10588 gene product from transcript CG10588-RB
Drosophila melanogaster Dmel_CG5517   Insulin degrading metalloproteinase
Escherichia coli b2821   protease III
Echinococcus granulosus EgrG_000765600   insulin degrading enzyme
Echinococcus granulosus EgrG_000935900   nardilysin
Echinococcus granulosus EgrG_000921800   3'partial|nardilysin
Echinococcus multilocularis EmuJ_000765600   insulin degrading enzyme
Echinococcus multilocularis EmuJ_000935900   nardilysin
Echinococcus multilocularis EmuJ_000921800   nardilysin
Echinococcus multilocularis EmuJ_000935700   nardilysin
Homo sapiens ENSG00000078618   nardilysin (N-arginine dibasic convertase)
Homo sapiens ENSG00000119912   insulin-degrading enzyme
Leishmania braziliensis LbrM.31.3520   phosphoglycan beta 1,3 galactosyltransferase 5
Leishmania braziliensis LbrM.31.3470   phosphoglycan beta 1,3 galactosyltransferase 5
Leishmania donovani LdBPK_313210.1   phosphoglycan beta 1,3 galactosyltransferase 5
Leishmania infantum LinJ.31.3210   phosphoglycan beta 1,3 galactosyltransferase 5
Leishmania major LmjF.31.3090   phosphoglycan beta 1,3 galactosyltransferase 5
Leishmania mexicana LmxM.30.3090   peptidase, putative,metallo-peptidase, Clan ME, Family M16
Loa Loa (eye worm) LOAG_08082   insulin-degrading enzyme
Mus musculus ENSMUSG00000056999   insulin degrading enzyme
Mus musculus ENSMUSG00000053510   nardilysin, N-arginine dibasic convertase, NRD convertase 1
Neospora caninum NCLIV_036700   M16 family peptidase, putative
Neospora caninum NCLIV_019040   Peptidase M16 domain protein, related
Oryza sativa 4343659   Os07g0570300
Oryza sativa 4332762   Os03g0336300
Oryza sativa 4326434   Os01g0779100
Oryza sativa 4326432   Os01g0778800
Oryza sativa 4343660   Os07g0570500
Saccharomyces cerevisiae YLR389C   Ste23p
Schistosoma japonicum Sjp_0009920   ko:K01408 insulysin [EC3.4.24.56], putative
Schistosoma japonicum Sjp_0208470   ko:K01411 nardilysin [EC3.4.24.61], putative
Schistosoma japonicum Sjp_0009910   ko:K01408 insulysin [EC3.4.24.56], putative
Schistosoma mansoni Smp_061510.2   nardilysin (M16 family)
Schistosoma mansoni Smp_146010   insulysin unit 3 (M16 family)
Schistosoma mansoni Smp_128100   insulysin (M16 family)
Schistosoma mansoni Smp_061510.1   nardilysin (M16 family)
Schistosoma mansoni Smp_011100   insulysin unit 3 (M16 family)
Schmidtea mediterranea mk4.016155.00   Insulin-degrading enzyme
Schmidtea mediterranea mk4.000765.07   Nardilysin
Schmidtea mediterranea mk4.000756.05   Nardilysin
Schmidtea mediterranea mk4.002922.03   Nardilysin
Schmidtea mediterranea mk4.000765.06   Insulin-degrading enzyme
Schmidtea mediterranea mk4.024270.00  
Schmidtea mediterranea mk4.000185.08   Nardilysin
Schmidtea mediterranea mk4.030516.01  
Schmidtea mediterranea mk4.018476.00   Insulin-degrading enzyme
Trypanosoma brucei gambiense Tbg972.8.7240   peptidase, putative,metallo-peptidase, Clan ME, Family M16, putative
Trypanosoma brucei Tb927.8.7020   peptidase, putative
Trypanosoma congolense TcIL3000_8_7090   peptidase, putative
Trypanosoma congolense TcIL3000_8_7000   peptidase, putative
Trypanosoma cruzi TcCLB.507389.70   peptidase, putative
Trypanosoma cruzi TcCLB.509911.90   peptidase, putative
Toxoplasma gondii TGME49_244490   insulysin, putative
Toxoplasma gondii TGME49_257010   sporozoite developmental protein
Toxoplasma gondii TGME49_269885   rhoptry metalloprotease toxolysin TLN1
Toxoplasma gondii TGME49_244480   peptidase M16 inactive domain-containing protein

Essentiality

Tb927.8.7020 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.8.7020 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (3 days) alsford
Tb927.8.7020 this record Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.8.7020 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.8.7020 this record Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b2821 Escherichia coli non-essential goodall
TGME49_244480 Toxoplasma gondii Probably non-essential sidik
TGME49_269885 Toxoplasma gondii Probably non-essential sidik
TGME49_244490 Toxoplasma gondii Probably non-essential sidik
TGME49_257010 Toxoplasma gondii Probably non-essential sidik
TGME49_244480 Toxoplasma gondii Essentiality uncertain sidik
TGME49_269885 Toxoplasma gondii Essentiality uncertain sidik
TGME49_244490 Toxoplasma gondii Essentiality uncertain sidik
TGME49_257010 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • 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
  • 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
  • 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.
  • 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
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
cell proliferation (GO:0008283) increased (PATO:0000470) 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: increased cell proliferation (significant gain 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
Mus musculus insulin degrading enzyme Compounds References
Homo sapiens insulin-degrading enzyme 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
0.0262 1 0.5
0.0051 1 0.5
0.0278 1 0.5
0.0029 1 0.5
0.0029 1 0.5
0.0051 1 0.5
0.0263 1 0.5
0.0024 0.4825 0
0.0051 1 0.5
0.0072 1 1
0.0029 1 0.5
0.0238 1 0.5
0.0025 0.5256 1
0.0283 0.2926 1
0.0081 0.2682 0.7741
0.0051 1 0.5
0.0283 0.2926 1
0.0025 0.266 0
0.0083 1 0.5
0.009 1 0.5
0.0051 1 0.5
0.0023 1 1
0.0051 1 0.5
0.0029 0.2912 0.5
0.0029 0.5354 0.5
0.0047 0.2703 0.2703
0.0272 1 0.5
0.0051 1 0.5
0.0049 1 1

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

56 literature references were collected for this gene.

If you have references for this gene, please enter them in a user comment (below) or Contact us.

User comments

No user comments are available for this gene. Log in to add comments, or register.

Enter your comment

User ()
Gene identifier Tb927.8.7020 (Trypanosoma brucei), peptidase, putative
Title for this comment
Comment