Detailed view for LmjF.28.1280

Basic information

TDR Targets ID: 22485
Leishmania major, phenylalanine-4-hydroxylase,phenylalanine-4-hydroxylase, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.4198 | Length (AA): 453 | MW (Da): 51454 | Paralog Number: 0

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

Druggability Group : DG3

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

PF00351   Biopterin-dependent aromatic amino acid hydroxylase

Gene Ontology

Mouse over links to read term descriptions.
GO:0016714   oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced pteridine as one donor, and incorporation of one atom of oxygen  
GO:0005506   iron ion binding  
GO:0004497   monooxygenase activity  
GO:0055114   oxidation reduction  
GO:0009072   aromatic amino acid family 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
34 432 1phz (A) 27 422 45.00 0 1 1.43 -1.59
124 432 1j8u (A) 118 422 51.00 0 1 1.48 -2.1
24 448 5den (A) 24 439 42.00 0 1 1.48229 -0.8
27 437 1phz (A) 20 427 43.00 0 1 1.51178 -1.12
121 414 5j6d (B) 102 391 53.00 0 1 1.21151 -1.2
123 446 2xsn (A) 193 517 47.00 0 1 1.41373 -1.56

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
Lower 20-40% percentile amastigotes, metacyclic. 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_131392)

Species Accession Gene Product
Caenorhabditis elegans CELE_K08F8.4   Protein PAH-1, isoform A
Dictyostelium discoideum DDB_G0278781   phenylalanine 4-monooxygenase
Drosophila melanogaster Dmel_CG7399   Henna
Homo sapiens ENSG00000171759   phenylalanine hydroxylase
Leishmania braziliensis LbrM.28.1380   phenylalanine-4-hydroxylase, putative;with=GeneDB:LmjF28.1280
Leishmania donovani LdBPK_281390.1   phenylalanine-4-hydroxylase, putative
Leishmania infantum LinJ.28.1390   phenylalanine-4-hydroxylase, putative
Leishmania major LmjF.28.1280   phenylalanine-4-hydroxylase,phenylalanine-4-hydroxylase, putative
Leishmania mexicana LmxM.28.1280   phenylalanine-4-hydroxylase, putative
Mus musculus ENSMUSG00000020051   phenylalanine hydroxylase
Neospora caninum NCLIV_069680   hypothetical protein
Toxoplasma gondii TGME49_287510   aromatic amino acid hydrolase AAH1
Toxoplasma gondii TGME49_212710   phenylalanine-4-hydroxylase
Toxoplasma gondii TGME49_212740   aromatic amino acid hydrolase AAH2

Essentiality

LmjF.28.1280 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
CELE_K08F8.4 Caenorhabditis elegans embryonic lethal wormbase
Show/Hide essentiality data references
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.

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): 0.9

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
Rattus norvegicus Phenylalanine-4-hydroxylase Compounds References
Homo sapiens phenylalanine hydroxylase Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Rattus norvegicus Tryptophan 5-monooxygenase 1 444 aa 42.8% 404 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0137 0.2579 1
0.0129 0.259 1
0.023 0.8069 1
0.022 0.5989 1
0.0139 0.2562 1
0.034 0.4907 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.

If you have references for this gene, please enter them in a user comment (below) or Contact us.

User comments

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Gene identifier LmjF.28.1280 (Leishmania major), phenylalanine-4-hydroxylase,phenylalanine-4-hydroxylase, putative
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