Detailed view for LmjF.26.1550

Basic information

TDR Targets ID: 24270
Leishmania major, trifunctional enzyme alpha subunit, mitochondrial precursor-like protein
Source Database / ID:  TriTrypDB  GeneDB

pI: 8.8981 | Length (AA): 726 | MW (Da): 79442 | Paralog Number: 1

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

PF00378   Enoyl-CoA hydratase/isomerase
PF00725   3-hydroxyacyl-CoA dehydrogenase, C-terminal domain
PF02737   3-hydroxyacyl-CoA dehydrogenase, NAD binding domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0050662   coenzyme binding  
GO:0016491   oxidoreductase activity  
GO:0005488   binding  
GO:0003857   3-hydroxyacyl-CoA dehydrogenase activity  
GO:0003824   catalytic activity  
GO:0055114   oxidation reduction  
GO:0008152   metabolic process  
GO:0006631   fatty acid metabolic process  

Structural information

Modbase 3D models:

There are 6 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
7 708 1wdk (A) 28 715 32.00 0 1 1.43 -1.01
305 588 1f0y (A) 13 302 32.00 0 1 0.76 -1.23
1 707 1wdk (A) 22 714 32.00 0 1 1.36333 -0.37
1 723 3zwc (A) 16 719 27.00 0 1 1.24537 0.1
307 588 4r1n (A) 1 281 39.00 0 1 0.93493 -0.79
308 345 2hmt (A) 7 44 32.00 0 0.28 0.432842 -0.6

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 metacyclic. Fernandes MC
Upregulation Percent Ranking Stage Dataset
Upper 60-80% 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_127588)

Species Accession Gene Product
Arabidopsis thaliana AT4G29010   fatty acid beta-oxidation multifunctional protein AIM1
Arabidopsis thaliana AT3G06860   fatty acid beta-oxidation multifunctional protein MFP2
Brugia malayi Bm1_51120   hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase, putative
Caenorhabditis elegans CELE_C29F3.1   Protein ECH-1
Caenorhabditis elegans CELE_T08B2.7   Protein T08B2.7, isoform B
Drosophila melanogaster Dmel_CG4389   Mitochondrial trifunctional protein alpha subunit
Escherichia coli b2341   fused enoyl-CoA hydratase and epimerase and isomerase/3-hydroxyacyl-CoA dehydrogenase
Homo sapiens ENSG00000084754   hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit
Homo sapiens ENSG00000113790   enoyl-CoA, hydratase/3-hydroxyacyl CoA dehydrogenase
Leishmania braziliensis LbrM.33.2880   enoyl-CoA hydratase/Enoyl-CoA isomerase/3- hydroxyacyl-CoA dehydrogenase, putative
Leishmania braziliensis LbrM.26.1570   trifunctional enzyme alpha subunit, mitochondrial precursor-like protein
Leishmania donovani LdBPK_332740.1   enoyl-CoA hydratase/Enoyl-CoA isomerase/3- hydroxyacyl-CoA dehydrogenase, putative
Leishmania donovani LdBPK_261530.1   trifunctional enzyme alpha subunit, mitochondrial precursor-like protein
Leishmania infantum LinJ.26.1530   trifunctional enzyme alpha subunit, mitochondrial precursor-like protein
Leishmania infantum LinJ.33.2740   enoyl-CoA hydratase/Enoyl-CoA isomerase/3- hydroxyacyl-CoA dehydrogenase, putative
Leishmania major LmjF.33.2600   enoyl-CoA hydratase/Enoyl-CoA isomerase/3- hydroxyacyl-CoA dehydrogenase, putative
Leishmania major LmjF.26.1550   trifunctional enzyme alpha subunit, mitochondrial precursor-like protein
Leishmania mexicana LmxM.26.1550   trifunctional enzyme alpha subunit, mitochondrial precursor-like protein
Leishmania mexicana LmxM.32.2600   enoyl-CoA hydratase/Enoyl-CoA isomerase/3- hydroxyacyl-CoA dehydrogenase, putative
Loa Loa (eye worm) LOAG_09850   hadha protein
Mycobacterium leprae ML2161c   PROBABLE FATTY OXIDATION PROTEIN FADB
Mus musculus ENSMUSG00000022853   enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase
Mus musculus ENSMUSG00000025745   hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alpha su
Mycobacterium tuberculosis Rv0860   Probable fatty oxidation protein FadB
Mycobacterium ulcerans MUL_4868   enoyl-CoA hydratase, EchA8_7
Mycobacterium ulcerans MUL_0295   fatty oxidation protein FadB
Oryza sativa 4337848   Os05g0155000
Oryza sativa 4326503   Os01g0348600
Oryza sativa 4328997   Os02g0274100
Onchocerca volvulus OVOC11914   Trifunctional enzyme subunit alpha, mitochondrial homolog
Schmidtea mediterranea mk4.000377.08  
Schmidtea mediterranea mk4.003350.01  
Trypanosoma brucei gambiense Tbg.972.2.2280   enoyl-CoA hydratase/Enoyl-CoA isomerase/3-hydroxyacyl-CoA dehydrogenase, putative
Trypanosoma brucei Tb927.2.4130   enoyl-CoA hydratase/Enoyl-CoA isomerase/3-hydroxyacyl-CoA dehydrogenase, putative
Trypanosoma cruzi TcCLB.509701.10   trifunctional enzyme alpha subunit, mitochondrial precursor-like protein, putative
Trypanosoma cruzi TcCLB.508981.39   trifunctional enzyme alpha subunit, mitochondrial precursor-like protein
Trypanosoma cruzi TcCLB.508441.70   enoyl-CoA hydratase/Enoyl-CoA isomerase/3-hydroxyacyl-CoA dehydrogenase, putative
Trypanosoma cruzi TcCLB.507547.40   enoyl-CoA hydratase/Enoyl-CoA isomerase/3-hydroxyacyl-CoA dehydrogenase, putative

Essentiality

LmjF.26.1550 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
mtu876 Mycobacterium tuberculosis non-essential nmpdr
Tb927.2.4130 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.2.4130 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.2.4130 Trypanosoma brucei significant gain of fitness in procyclic forms alsford
Tb927.2.4130 Trypanosoma brucei significant gain of fitness in differentiation of procyclic to bloodstream forms alsford
b2341 Escherichia coli non-essential goodall
CELE_T08B2.7 Caenorhabditis elegans larval arrest wormbase
Show/Hide essentiality data references
  • 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
  • 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
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs

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
No additional associated druggable targets
Obtained from network model
No druggable targets predicted through repurposing network model

Assayability

Assay information

  • Assay for β-Hydroxyacyl-COA Dehydrogenase (1.1.1.35 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • Assay for Crotonase (4.2.1.17 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.

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.26.1550 (Leishmania major), trifunctional enzyme alpha subunit, mitochondrial precursor-like protein
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