Detailed view for TcCLB.508373.10

Basic information

TDR Targets ID: 42323
Trypanosoma cruzi, glutamine dependent carbamoyl-phosphate synthase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.7027 | Length (AA): 1253 | MW (Da): 141895 | Paralog Number: 2

Signal peptide: N | GPI Anchor: N | 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

PF00764   Arginosuccinate synthase
PF02786   Carbamoyl-phosphate synthase L chain, ATP binding domain
PF02787   Carbamoyl-phosphate synthetase large chain, oligomerisation domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0046872   metal ion binding  
GO:0005524   ATP binding  
GO:0004086   carbamoyl-phosphate synthase activity  
GO:0004055   argininosuccinate synthase activity  
GO:0003824   catalytic activity  
GO:0008152   metabolic process  
GO:0006807   nitrogen compound metabolic process  
GO:0006526   arginine biosynthetic process  

Structural information

Modbase 3D models:

There are 8 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
2 868 1a9x (A) 219 1072 38.00 0 1 1.15 -1.16
873 1252 1k92 (A) 1 407 17.00 0 1 0.39 -0.78
1 864 5dot (A) 634 1494 48.00 0 1 1.18575 -0.29
345 483 1lss (A) 3 128 21.00 0 1 0.288634 -0.41
726 850 1wo8 (A) 2 121 15.00 0 0.2 0.203461 -0.87
870 1245 5us8 (A) 0 401 20.00 0 1 0.49478 -0.33
882 943 3bl5 (A) 3 65 15.00 0.48 0.2 0.188181 -0.37
994 1215 4nzp (A) 122 357 28.00 0.00000037 1 0.236375 0.98

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
Mid 40-60% percentile epimastigote, metacyclic. Smircich P
Show/Hide expression data references
  • Smircich P Ribosome profiling reveals translation control as a key mechanism generating differential gene expression in Trypanosoma cruzi.

Orthologs

Ortholog group members (OG5_126835)

Species Accession Gene Product
Arabidopsis thaliana AT1G29900   carbamoyl phosphate synthetase B
Babesia bovis BBOV_III003590   carbamoyl phosphate synthetase
Brugia malayi Bm1_55375   carbamoyl-phosphate synthase, large subunit
Candida albicans CaO19.9896   aspartate transcarbamylase similar to S. cerevisiae URA2 (YJL130C) pyrimidine biosynthesis enzyme
Candida albicans CaO19.2360   aspartate transcarbamylase similar to S. cerevisiae URA2 (YJL130C) pyrimidine biosynthesis enzyme
Candida albicans CaO19.3221   likely carbamoyl-phosphate synthase large subunit similar to S. cerevisiae CPA2 (YJR109C) invovled in arginine biosynthesis
Candida albicans CaO19.10732   likely carbamoyl-phosphate synthase large subunit similar to S. cerevisiae CPA2 (YJR109C) invovled in arginine biosynthesis
Caenorhabditis elegans CELE_D2085.1   Protein PYR-1
Dictyostelium discoideum DDB_G0276335   aspartate carbamoyltransferase
Drosophila melanogaster Dmel_CG18572   rudimentary
Escherichia coli b0033   carbamoyl-phosphate synthase large subunit
Homo sapiens ENSG00000021826   carbamoyl-phosphate synthase 1, mitochondrial
Homo sapiens ENSG00000084774   carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase
Leishmania braziliensis LbrM.16.0600   carbamoyl-phosphate synthase, putative
Leishmania donovani LdBPK_160590.1   carbamoyl-phosphate synthase, putative
Leishmania infantum LinJ.16.0590   carbamoyl-phosphate synthase, putative
Leishmania major LmjF.16.0590   carbamoyl-phosphate synthase, putative
Leishmania mexicana LmxM.16.0590   carbamoyl-phosphate synthase, putative
Mycobacterium leprae ML0536   Probable carbamoyl-phosphate synthase large subunit CarB (Carbamoyl-phosphate synthetase ammonia chain)
Mus musculus ENSMUSG00000013629   carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase
Mus musculus ENSMUSG00000025991   carbamoyl-phosphate synthetase 1
Mycobacterium tuberculosis Rv1384   Probable carbamoyl-phosphate synthase large chain CarB (carbamoyl-phosphate synthetase ammonia chain)
Mycobacterium ulcerans MUL_1784   carbamoyl phosphate synthase large subunit
Neospora caninum NCLIV_052220   hypothetical protein
Oryza sativa 4326346   Os01g0570700
Plasmodium berghei PBANKA_1406700   carbamoyl phosphate synthetase, putative
Plasmodium falciparum PF3D7_1308200   carbamoyl phosphate synthetase
Plasmodium knowlesi PKNH_1408600   carbamoyl phosphate synthetase, putative
Plasmodium vivax PVX_122240   carbamoyl phosphate synthetase, putative
Plasmodium yoelii PY04780   carbamoyl phosphate synthetase II-related
Plasmodium yoelii PY04781   carbamoyl phosphate synthetase II-related
Plasmodium yoelii PY06257   carbamoyl phosphate synthetase II-related
Saccharomyces cerevisiae YJR109C   carbamoyl-phosphate synthase (glutamine-hydrolyzing) CPA2
Saccharomyces cerevisiae YJL130C   bifunctional carbamoylphosphate synthetase/aspartate transcarbamylase
Schistosoma japonicum Sjp_0026210   ko:K01465 dihydroorotase [EC3.5.2.3], putative
Schistosoma japonicum Sjp_0080610   CAD protein [Includes: Glutamine-dependent carbamoyl-phosphate synthase, putative
Schistosoma japonicum Sjp_0026200   ko:K00609 aspartate carbamoyltransferase catalytic chain [EC2.1.3.2C], putative
Schistosoma mansoni Smp_186670   carbamoyl-phosphate synthetase
Schistosoma mansoni Smp_106150   aspartate carbamoyltransferase
Schmidtea mediterranea mk4.003398.06  
Schmidtea mediterranea mk4.035059.00   CAD protein
Schmidtea mediterranea mk4.015554.00  
Schmidtea mediterranea mk4.032484.00  
Schmidtea mediterranea mk4.003398.05   CAD protein
Schmidtea mediterranea mk4.016070.00  
Schmidtea mediterranea mk4.014140.00  
Trypanosoma brucei gambiense Tbg972.5.5270   glutamine hydrolysing (not ammonia-dependent) carbomoyl phosphate synthase, putative
Trypanosoma brucei Tb927.5.3800   glutamine hydrolysing (not ammonia-dependent) carbomoyl phosphate synthase, putative
Trypanosoma congolense TcIL3000_5_4250   glutamine hydrolysing (not ammonia-dependent) carbomoyl phosphate synthase, putative
Trypanosoma cruzi TcCLB.507059.80   glutamine-dependent carbamoyl-phosphate synthetase, putative
Trypanosoma cruzi TcCLB.511647.4   glutamine-dependent carbamoyl-phosphate synthetase, putative
Trypanosoma cruzi TcCLB.508373.10   glutamine dependent carbamoyl-phosphate synthase, putative
Toxoplasma gondii TGME49_215260   carbamoylphosphate synthetase
Theileria parva TP03_0048   glutamine-dependent carbamoyl phosphate synthase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0512   carbamoyl phosphate synthase large subunit

Essentiality

TcCLB.508373.10 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.5.3800 Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb927.5.3800 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb927.5.3800 Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb927.5.3800 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b0033 Escherichia coli non-essential goodall
CELE_D2085.1 Caenorhabditis elegans embryonic arrest wormbase
CELE_D2085.1 Caenorhabditis elegans embryonic lethal wormbase
CELE_D2085.1 Caenorhabditis elegans larval lethal wormbase
CELE_D2085.1 Caenorhabditis elegans slow growth wormbase
PBANKA_1406700 Plasmodium berghei Essential plasmo
TGME49_215260 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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)

We have no manually annotated phenotypes for this target. What does this mean? / Care to help?

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): 0.7

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 carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase 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

  • Reagent:
  • Target Type Source Notes
    TcCLB.508373.10 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Trypanosoma cruzi ( 1 )

Bibliographic References

5 literature references were collected for this gene.

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Gene identifier TcCLB.508373.10 (Trypanosoma cruzi), glutamine dependent carbamoyl-phosphate synthase, putative
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