Detailed view for LmjF.15.1300

Basic information

TDR Targets ID: 25328
Leishmania major, ubiquitin hydrolase, putative,cysteine peptidase, Clan CA, family C19, putative

Source Database / ID:  TriTrypDB  GeneDB

pI: 5.5002 | Length (AA): 1412 | MW (Da): 155044 | Paralog Number: 0

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

Pfam domains

PF00443   Ubiquitin carboxyl-terminal hydrolase

Gene Ontology

Mouse over links to read term descriptions.
GO:0036459   GO:thiol-dependent ubiquitinyl hydrolase activity  

GO:0016579   protein deubiquitination  
GO:0004221   ubiquitin thiolesterase activity  
GO:0006511   ubiquitin-dependent protein catabolic process  

Metabolic Pathways

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

Structural information

Modbase 3D models:

There are 9 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
12 490 2f1z (A) 119 551 30.00 0 1 0.57 0.14
109 493 1nb8 (A) 208 554 35.00 0 1 0.62 -0.61
27 486 2f1z (A) 120 547 27.00 0.41 1 0.431579 0.68
112 848 5j7t (A) 211 881 22.00 0 1 0.528755 1.07
115 576 5j7t (A) 214 623 35.00 0 1 0.578395 0.6
115 493 5jtv (A) 214 554 30.00 0 1 0.522114 -0.11
917 1052 2y44 (A) 45 177 27.00 0.26 0.17 0.348517 -0.04
931 1079 4cfi (A) 161 296 36.00 0.31 0.16 0.213724 0.89
1092 1158 5c6d (A) 817 881 26.00 0 0.95 0.30615 -0.03

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 metacyclic. Fernandes MC
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile amastigotes. Fernandes MC
Show/Hide expression data references
  • Fernandes MC Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.

Orthologs

Ortholog group members (OG5_151295)

Species Accession Gene Product
Leishmania braziliensis LbrM.15.1240   ubiquitin hydrolase, putative,cysteine peptidase, Clan CA, family C19, putative
Leishmania donovani LdBPK_151320.1   ubiquitin hydrolase, putative
Leishmania infantum LinJ.15.1320   ubiquitin hydrolase, putative,cysteine peptidase, Clan CA, family C19, putative
Leishmania major LmjF.15.1300 this record   ubiquitin hydrolase, putative,cysteine peptidase, Clan CA, family C19, putative
Leishmania mexicana LmxM.15.1300   ubiquitin hydrolase, putative,cysteine peptidase, Clan CA, family C19, putative
Trypanosoma brucei gambiense Tbg972.9.2940   ubiquitin carboxyl-terminal hydrolase, putative,cysteine peptidase, Clan CA, family C19, putative
Trypanosoma brucei Tb927.9.5520   ubiquitin carboxyl-terminal hydrolase, putative
Trypanosoma congolense TcIL3000_0_04870   ubiquitin carboxyl-terminal hydrolase, putative
Trypanosoma cruzi TcCLB.508277.360   ubiquitin hydrolase, putative

Essentiality

LmjF.15.1300 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb09.160.4020 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb09.160.4020 Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb09.160.4020 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb09.160.4020 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
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
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • 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
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from bioassay (ECO:0000094) Leishmania mexicana 337527   561727   585910  
Annotator: aaronjr@u.washington.edu. Comment: Drug: 4174-73-6. chemical inhibition with known cysteine peptidase inhibitors leads to slow growth of Leishmania sp. in cell assay; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 7179420
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania mexicana 337527   561727   585910  
Annotator: aaronjr@u.washington.edu. Comment: Drug: 4174-73-6. chemical inhibition with known cysteine peptidase inhibitors leads to slow growth of Leishmania sp. in cell assay; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 7179420
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from enzyme assay (ECO:0000005) Leishmania mexicana 337527   561727   585910  
Annotator: aaronjr@u.washington.edu. Comment: Drug: 4174-73-6. chemical inhibition with known cysteine peptidase inhibitors leads to reduced enzyme activity in vitro; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 7179420
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from bioassay (ECO:0000094) Leishmania amazonensis No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: L-Amino acid esters appear to be hydrolyzed by cysteine peptidase and lead to slow growth of Leishmania sp. in cell assay; . References: 1428504 2235078 2345655
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from bioassay (ECO:0000094) Leishmania mexicana No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: chemical inhibition with known cysteine peptidase inhibitors leads to slow growth of Leishmania sp. in cell assay; . References: 2270108
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from enzyme assay (ECO:0000005) Leishmania amazonensis 81384   576750  
Annotator: aaronjr@u.washington.edu. Comment: chemical inhibition with known cysteine peptidase inhibitors leads to reduced enzyme activity in vitro; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 8023752
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from enzyme assay (ECO:0000005) Leishmania major 81384   576750  
Annotator: aaronjr@u.washington.edu. Comment: chemical inhibition with known cysteine peptidase inhibitors leads to reduced enzyme activity in vitro; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 8023752
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) host (GO:0018995) Leishmania donovani No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: 81989-95-9. chemical inhibition with known cysteine peptidase inhibitors leads to slow growth of Leishmania sp. in vivo (balb/c mouse) and cure of parasite burden; also provided protection against further infection (partial vaccine); General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 11238649
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from bioassay (ECO:0000094) Leishmania donovani No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: 81989-95-9. chemical inhibition with known cysteine peptidase inhibitors leads to slow growth of Leishmania sp. in vivo (balb/c mouse) and cure of parasite burden; also provided protection against further infection (partial vaccine); General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 11238649
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) host (GO:0018995) Leishmania tropica No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: 233277-99-1. chemical inhibition with known cysteine peptidase inhibitors leads to slow growth of Leishmania sp. in vivo (balb/c mouse lesions) and reduced lesion size; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 15172223
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) amastigote (BTO:0000062) inferred from bioassay (ECO:0000094) Leishmania tropica No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: 233277-99-1. chemical inhibition with known cysteine peptidase inhibitors leads to slow growth of Leishmania sp. in vivo (balb/c mouse lesions) and reduced lesion size; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 15172223
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania tropica No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: 233277-99-1. chemical inhibition with known cysteine peptidase inhibitors leads to slow growth of Leishmania sp. in cell assay; inhibitors overcome redundancy?; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 15172223
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania donovani 0   6693   81384   236103   327961   376038   543486   543487   575389   575390   575391   576750  
Annotator: aaronjr@u.washington.edu. Comment: Drug: 22386-37-4; Drug: 36677-78-8; Drug: 52090-11-6; Drug: 98319-30-3; Drug: 300670-24-0; Drug: 302939-54-4; Drug: 303216-44-6; Drug: 309742-24-3; Drug: 312280-89-0; Drug: 315703-20-9; Drug: 320369-30-0; Drug: 322409-94-9; Drug: 330220-86-5; Drug: 335206-77-4; Drug: 347910-28-5; Drug: 352560-86-2; Drug: 363180-61-4; Drug: 413580-11-7; Drug: 416878-80-3; Drug: 419547-26-5; Drug: 428852-79-3; Drug: 825612-08-6; Drug: 825612-09-7; Drug: 825612-10-0. in silico virtual screening of falcipains lead to bioactive compounds against Leishmania promastigotes; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 15588096
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from in-silico analysis (ECO:0000043) Leishmania donovani 0   6693   81384   236103   327961   376038   543486   543487   575389   575390   575391   576750  
Annotator: aaronjr@u.washington.edu. Comment: Drug: 22386-37-4; Drug: 36677-78-8; Drug: 52090-11-6; Drug: 98319-30-3; Drug: 300670-24-0; Drug: 302939-54-4; Drug: 303216-44-6; Drug: 309742-24-3; Drug: 312280-89-0; Drug: 315703-20-9; Drug: 320369-30-0; Drug: 322409-94-9; Drug: 330220-86-5; Drug: 335206-77-4; Drug: 347910-28-5; Drug: 352560-86-2; Drug: 363180-61-4; Drug: 413580-11-7; Drug: 416878-80-3; Drug: 419547-26-5; Drug: 428852-79-3; Drug: 825612-08-6; Drug: 825612-09-7; Drug: 825612-10-0. in silico virtual screening of falcipains lead to bioactive compounds against cysteine protease in vitro; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 15588096
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Leishmania donovani 0   6693   81384   236103   327961   376038   543486   543487   575389   575390   575391   576750  
Annotator: aaronjr@u.washington.edu. Comment: Drug: 22386-37-4; Drug: 36677-78-8; Drug: 52090-11-6; Drug: 98319-30-3; Drug: 300670-24-0; Drug: 302939-54-4; Drug: 303216-44-6; Drug: 309742-24-3; Drug: 312280-89-0; Drug: 315703-20-9; Drug: 320369-30-0; Drug: 322409-94-9; Drug: 330220-86-5; Drug: 335206-77-4; Drug: 347910-28-5; Drug: 352560-86-2; Drug: 363180-61-4; Drug: 413580-11-7; Drug: 416878-80-3; Drug: 419547-26-5; Drug: 428852-79-3; Drug: 825612-08-6; Drug: 825612-09-7; Drug: 825612-10-0. in silico virtual screening of falcipains lead to bioactive compounds against cysteine protease in vitro; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 15588096
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania donovani No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: 2935-91-3; Drug: 24117-97-3; Drug: 98647-23-5; Drug: 198124-18-4; Drug: 256238-87-6; Drug: 257287-52-8; Drug: 263157-80-8; Drug: 294854-43-6; Drug: 303124-84-7; Drug: 303147-38-8; Drug: 321579-84-4; Drug: 331247-87-1; Drug: 337923-53-2; Drug: 338791-39-2; Drug: 675828-74-7; Drug: 676226-56-5; Drug: 678967-57-2; Drug: 681213-40-1; Drug: 686272-33-3; Drug: 696586-43-3; Drug: 705250-31-3; Drug: 708987-83-1; Drug: 831234-40-3; Drug: 882161-95-7; Drug: 882161-98-0; Drug: 882161-99-1; Drug: 882162-00-7; Drug: 882162-01-8; Drug: 882162-02-9; Drug: 882162-03-0; Drug: 882162-04-1; Drug: 882162-05-2; Drug: 882162-06-3; Drug: 882162-07-4; Drug: 882162-08-5; Drug: 882162-09-6; Drug: 882162-10-9; Drug: 882162-11-0; Drug: 882162-12-1; Drug: 882162-13-2; Drug: 882162-14-3. in silico virtual screening of falcipains lead to bioactive compounds against Leishmania promastigotes; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 16509575
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from in-silico analysis (ECO:0000043) Leishmania donovani No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: 2935-91-3; Drug: 24117-97-3; Drug: 98647-23-5; Drug: 198124-18-4; Drug: 256238-87-6; Drug: 257287-52-8; Drug: 263157-80-8; Drug: 294854-43-6; Drug: 303124-84-7; Drug: 303147-38-8; Drug: 321579-84-4; Drug: 331247-87-1; Drug: 337923-53-2; Drug: 338791-39-2; Drug: 675828-74-7; Drug: 676226-56-5; Drug: 678967-57-2; Drug: 681213-40-1; Drug: 686272-33-3; Drug: 696586-43-3; Drug: 705250-31-3; Drug: 708987-83-1; Drug: 831234-40-3; Drug: 882161-95-7; Drug: 882161-98-0; Drug: 882161-99-1; Drug: 882162-00-7; Drug: 882162-01-8; Drug: 882162-02-9; Drug: 882162-03-0; Drug: 882162-04-1; Drug: 882162-05-2; Drug: 882162-06-3; Drug: 882162-07-4; Drug: 882162-08-5; Drug: 882162-09-6; Drug: 882162-10-9; Drug: 882162-11-0; Drug: 882162-12-1; Drug: 882162-13-2; Drug: 882162-14-3. in silico virtual screening of falcipains lead to bioactive compounds against cysteine protease in vitro; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 16509575
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Leishmania donovani No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: 2935-91-3; Drug: 24117-97-3; Drug: 98647-23-5; Drug: 198124-18-4; Drug: 256238-87-6; Drug: 257287-52-8; Drug: 263157-80-8; Drug: 294854-43-6; Drug: 303124-84-7; Drug: 303147-38-8; Drug: 321579-84-4; Drug: 331247-87-1; Drug: 337923-53-2; Drug: 338791-39-2; Drug: 675828-74-7; Drug: 676226-56-5; Drug: 678967-57-2; Drug: 681213-40-1; Drug: 686272-33-3; Drug: 696586-43-3; Drug: 705250-31-3; Drug: 708987-83-1; Drug: 831234-40-3; Drug: 882161-95-7; Drug: 882161-98-0; Drug: 882161-99-1; Drug: 882162-00-7; Drug: 882162-01-8; Drug: 882162-02-9; Drug: 882162-03-0; Drug: 882162-04-1; Drug: 882162-05-2; Drug: 882162-06-3; Drug: 882162-07-4; Drug: 882162-08-5; Drug: 882162-09-6; Drug: 882162-10-9; Drug: 882162-11-0; Drug: 882162-12-1; Drug: 882162-13-2; Drug: 882162-14-3. in silico virtual screening of falcipains lead to bioactive compounds against cysteine protease in vitro; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 16509575
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania major No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: 872361-01-8; Drug: 872361-02-9; Drug: 886061-72-9; Drug: 886061-73-0; Drug: 886061-74-1; Drug: 886061-75-2; Drug: 886061-76-3; Drug: 886061-77-4; Drug: 886061-78-5; Drug: 886061-79-6; Drug: 886061-80-9; Drug: 886061-81-0; Drug: 886061-82-1; Drug: 886061-85-4; Drug: 886061-86-5; Drug: 886061-87-6; Drug: 886061-88-7; Drug: 886061-89-8; Drug: 886061-90-1; Drug: 886061-91-2; Drug: 886061-92-3; Drug: 886061-93-4; Drug: 886061-99-0; Drug: 886062-00-6; Drug: 886062-05-1; Drug: 886062-06-2; Drug: 886062-07-3; Drug: 886062-08-4; Drug: 886062-09-5; Drug: 886062-10-8; Drug: 886062-11-9; Drug: 886062-12-0; Drug: 886062-13-1; Drug: 886062-14-2; Drug: 886062-15-3; Drug: 886062-16-4; Drug: 886062-17-5; Drug: 906674-95-1. chemical inhibition with peptidomimetics and Aziridine-2,3-dicarboxylates leads to slow growth of Leishmania sp. in cell assay; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 16801424

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 log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or contact us.

Annotated validation

  • Validation: in vivo inhibition
  • annotated by: aaronjr@u.washington.edu.
  • References: 11238649 15172223

Associated compounds / Druggability

Known modulators for this target

Compound Source Reference
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References

Predicted associations

By orthology with druggable targets
Non orthologous druggable targets
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Leishmania major ubiquitin hydrolase, putative,cysteine peptidase, Clan CA, family C19, putative 457 aa 26.8% 418 aa Compounds References

Obtained from network model

Ranking Plot


Putative Drugs List


Compound Raw Global Species
0.0259 0.288 0.3117
0.0263 0.2944 0.2944
0.0317 0.303 0.3027

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

11 literature references were collected for this gene.

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Gene identifier LmjF.15.1300 (Leishmania major), ubiquitin hydrolase, putative,cysteine peptidase, Clan CA, family C19, putative
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