Detailed view for LmjF.17.0060

Basic information

TDR Targets ID: 27915
Leishmania major, mitogen-activated protein kinase kinase 3, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 9.7234 | Length (AA): 553 | MW (Da): 61361 | Paralog Number: 0

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

Druggability Group : DG2

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

PF00069   Protein kinase domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0004713   protein tyrosine kinase activity  
GO:0004674   protein serine/threonine kinase activity  
GO:0004672   protein kinase activity  
GO:0005524   ATP binding  
GO:0005515   protein binding  
GO:0006468   protein amino acid phosphorylation  

Metabolic Pathways

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

Structural information

Modbase 3D models:

There are 10 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
27 395 1omw (A) 189 552 23.00 0 1 0.72 0.25
29 285 2bdw (A) 13 271 32.00 0 1 0.94 -1.02
2 285 3ag9 (B) 17 297 29.00 0 1 0.859162 -0.32
3 346 1kob (A) 29 367 27.00 0 1 0.964661 -0.19
21 417 3nyv (A) 43 435 28.00 0 1 0.931502 0.5
117 174 2lav (A) 148 201 44.00 0.031 0.97 0.464382 0.48
128 172 4ix3 (A) 295 340 40.00 0.0078 0.97 0.532874 0.06
381 473 1pgv (A) 228 319 15.00 0 0.91 0.517774 -1.49
406 537 4im6 (A) 799 941 30.00 0.35 0.91 0.540198 -0.5
467 524 4f07 (A) 44 103 33.00 0.96 0.9 0.455382 0.4

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_131734)

Species Accession Gene Product
Arabidopsis thaliana AT1G49580   CDPK-related kinase 8
Arabidopsis thaliana AT3G49370   CDPK-related kinase 6
Arabidopsis thaliana AT3G50530   CDPK-related kinase
Arabidopsis thaliana AT2G46700   CDPK-related kinase 3
Arabidopsis thaliana AT3G19100   CDPK-related kinase 2
Arabidopsis thaliana AT3G56760   CDPK-related kinase 7
Arabidopsis thaliana AT2G41140   CDPK-related kinase 1
Arabidopsis thaliana AT5G24430   CDPK-related kinase 4 (AtCRK4)
Leishmania braziliensis LbrM.17.0070   mitogen-activated protein kinase kinase 3, putative
Leishmania donovani LdBPK_170070.1   mitogen-activated protein kinase kinase 3, putative
Leishmania infantum LinJ.17.0070   mitogen-activated protein kinase kinase 3, putative
Leishmania major LmjF.17.0060   mitogen-activated protein kinase kinase 3, putative
Leishmania mexicana LmxM.17.0060   mitogen-activated protein kinase kinase 3, putative
Neospora caninum NCLIV_008260   CAM kinase (incomplete catalytic triad), putative
Oryza sativa 4343929   Os07g0619800
Oryza sativa 4332914   Os03g0366200
Oryza sativa 4344066   Os07g0641200
Oryza sativa 4342059   Os06g0714200
Oryza sativa 4349091   Os10g0510700
Schmidtea mediterranea mk4.001490.11   Serine/threonine-protein kinase PAK mbt
Schmidtea mediterranea mk4.000369.08  
Schmidtea mediterranea mk4.006962.00  
Trypanosoma brucei gambiense Tbg972.7.7190   protein kinase, putative
Trypanosoma brucei Tb927.7.6220   calcium/calmodulin-dependent protein kinase, putative
Trypanosoma congolense TcIL3000_7_5060   protein kinase, putative
Trypanosoma cruzi TcCLB.508919.70   calcium/calmodulin-dependent protein kinase, putative
Trypanosoma cruzi TcCLB.506513.50   calcium/calmodulin-dependent protein kinase, putative
Toxoplasma gondii TGME49_253940   CAM Kinase family, incomplete catalytic triad

Essentiality

LmjF.17.0060 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.7.6220 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.7.6220 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.7.6220 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.7.6220 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
TGME49_253940 Toxoplasma gondii Probably non-essential sidik
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.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170

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

Known modulators for this target

No chemical compounds associated to this gene

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
Plasmodium falciparum (isolate 3D7) Cell division control protein 2 homolog 288 aa 29.0% 290 aa Compounds References
Patiria pectinifera Cdc2 300 aa 27.7% 292 aa Compounds References
Rattus norvegicus MAP kinase p38 alpha 360 aa 25.6% 297 aa Compounds References
Rattus norvegicus Jak1 protein 210 aa 24.8% 210 aa Compounds References
Zea mays Casein kinase II alpha 332 aa 24.1% 307 aa Compounds References
Rattus norvegicus Mitogen-activated protein kinase 1 358 aa 27.9% 322 aa Compounds References
Schizosaccharomyces pombe 972h- Casein kinase II subunit alpha 332 aa 21.8% 298 aa Compounds References
Rattus norvegicus Cell division protein kinase 5 292 aa 28.4% 292 aa Compounds References
Homo sapiens Cyclin-dependent kinase 1/cyclin B1 297 aa 26.9% 290 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0093 0.8828 0
0.0032 0.5 0.5
0.0056 1 0.5
0.0088 0.4477 1
0.0081 1 0.5
0.0064 0.3377 0
0.0059 1 1
0.0022 0.5 0.5
0.0063 0.7244 0.2543
0.0007 0.5 0.5
0.0016 0.5 0.5
0.0033 1 1
0.0012 0.5 0.5
0.0003 0.5 0.5
0.0012 0.5 0.5
0.0012 0.5 0.5
0.0037 1 0.5
0.0032 0.5 0.5
0.0039 0.5 0.5
0.0059 1 1
0.0069 0.3067 1
0.0042 0.5 0.5
0.0018 0.5 0.5
0.0007 0.5 0.5
0.0004 0.5 0.5
0.0091 1 0.5
0.0081 0.5 0.5
0.0063 1 1
0.0033 0.5 0.5
0.0059 1 1
0.0062 0.6935 0
0.0008 0.5 0.5
0.0029 0.5 0.5
0.0011 1 0.5
0.0092 1 0.5
0.0007 0.5 0.5
0.0023 0.5 0.5
0.0098 0.3242 0.2614
0.0039 0.9485 0.5
0.0036 0.5 0.5
0.0061 0.6883 0.5304
0.0039 0.5 0.5
0.0026 0.5 0.5
0.0066 0.3101 0
0.0027 1 0.5
0.0067 0.5 0.5
0.0016 0.5 0.5

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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Gene identifier LmjF.17.0060 (Leishmania major), mitogen-activated protein kinase kinase 3, putative
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