Detailed view for LmjF.20.1200

Basic information

TDR Targets ID: 24322
Leishmania major, calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative

Source Database / ID:  TriTrypDB  GeneDB

pI: 7.0681 | Length (AA): 743 | MW (Da): 82593 | Paralog Number: 0

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

Pfam domains

PF00648   Calpain family cysteine protease
PF09149   Domain of unknown function (DUF1935)

Gene Ontology

Mouse over links to read term descriptions.
GO:0005622   intracellular  
GO:0004198   calcium-dependent cysteine-type endopeptidase activity  
GO:0006508   proteolysis  

Metabolic Pathways

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

Structural information

Modbase 3D models:

There are 7 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
23 134 1r75 (A) 12 117 28.00 0 0.34 0.3 -0.23
140 743 1df0 (A) 3 585 20.00 0 1 0.54 0.98
163 505 2g8j (A) 33 351 26.00 0 1 0.67 -0.67
17 152 2fe0 (A) 6 129 36.00 0 1 0.501442 -0.19
165 743 3bow (A) 23 573 20.00 0 1 0.868673 0.8
173 468 2r9f (A) 41 314 32.00 0 1 0.649885 0.26
173 504 1zcm (A) 41 350 27.00 0 1 0.736837 -0.35

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 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_183552)

Species Accession Gene Product
Leishmania braziliensis LbrM.20.5410   calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative
Leishmania donovani LdBPK_201240.1   calpain-like cysteine peptidase, putative
Leishmania infantum LinJ.20.1240   calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative
Leishmania major LmjF.20.1200 this record   calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative
Leishmania mexicana LmxM.20.1200   calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative

Essentiality

No essentiality data collected for this gene and/or its orthologs.

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
growth (GO:0040007) decreased time (PATO:0000716) single cell organism (CARO:0000064) promastigote (BTO:0001124) inferred from bioassay (ECO:0000094) Leishmania amazonensis 30267  
Annotator: aaronjr@u.washington.edu. Comment: chemical inhibition with calpain inhibitor leads to slow growth of Leishmania sp. in cell assay; General cysteine peptidase inhibition with anti-leishmanial activity; specific target unknown. References: 16842979

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: inhibition during in vitro culture
  • annotated by: aaronjr@u.washington.edu.
  • References: 16842979
  • 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
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 calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative 732 aa 30.1% 734 aa Compounds References
Leishmania major small myristoylated protein-3, putative 115 aa 27.6% 127 aa Compounds References
Leishmania major small myristoylated protein-1 131 aa 34.3% 137 aa Compounds References
Leishmania major cytoskeleton-associated protein CAP5.5, putative,cysteine peptidase, Clan CA, family C2, putative 723 aa 30.1% 708 aa Compounds References
Leishmania major small myristoylated protein-2 136 aa 26.5% 117 aa Compounds References
Leishmania major hypothetical protein, conserved,calpain-like cysteine peptidase, Clan CA, family C2 146 aa 29.9% 117 aa Compounds References
Leishmania major calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative 414 aa 29.5% 417 aa Compounds References
Leishmania major small myristoylated protein 4, putative 152 aa 27.6% 123 aa Compounds References
Leishmania major calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative 687 aa 32.8% 742 aa Compounds References
Leishmania major calpain family cysteine protease-like protein 705 aa 29.0% 735 aa Compounds References

Obtained from network model

Ranking Plot


Putative Drugs List


Compound Raw Global Species
0.0786 0.5638 0.8944
0.0784 0.9459 0.9459
0.0934 0.9463 0.9463
0.0756 0.8735 0.9466

Assayability

Assay information

  • Assay for Cathepsin B (3.4.22.1 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.

Reagent availability

No reagent availability information for this target.

Bibliographic References

30 literature references were collected for this gene.

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Gene identifier LmjF.20.1200 (Leishmania major), calpain-like cysteine peptidase, putative,cysteine peptidase, Clan CA, family C2, putative
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