Detailed view for PF3D7_1312600

Basic information

TDR Targets ID: 2063
Plasmodium falciparum, 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial, putative
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 7.4559 | Length (AA): 429 | MW (Da): 49871 | Paralog Number: 0

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

Druggability Group : DG1

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

PF00676   Dehydrogenase E1 component

Gene Ontology

Mouse over links to read term descriptions.
GO:0005947   mitochondrial alpha-ketoglutarate dehydrogenase complex  
GO:0003863   3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity  
GO:0003826   alpha-ketoacid dehydrogenase activity  
GO:0016624   oxidoreductase activity, acting on the aldehyde or oxo group of donors, disulfide as acceptor  
GO:0009083   branched chain family amino acid catabolic process  
GO:0008152   metabolic process  

Structural information

Modbase 3D models:

There are 5 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
10 411 1qs0 (A) 3 408 28.00 0 1 1.32 -0.7
55 415 1umd (A) 9 367 33.00 0 1 1.36 -1.02
12 411 1qs0 (A) 5 408 28.00 0 1 1.3155 -0.35
28 429 2bfd (A) 6 400 39.00 0 1 1.27166 0.01
46 419 1w85 (A) 9 368 34.00 0 1 1.28649 -0.44

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 gametocyte, Oocyst, Sporozoite, Female Gametocyte, Male Gametocyte. PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, sporozoite, early schizont, late schizont. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, merozoite, early trophozoite, late trophozoite, Ring. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 24 hs. Otto TD
Show/Hide expression data references
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.
  • PlasmoDB Data on upregulation of P. falciparum genes in different life cycle stages, combined from several microarray experiments available in PlasmoDB
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.

Orthologs

Ortholog group members (OG5_128261)

Species Accession Gene Product
Arabidopsis thaliana AT5G09300   thiamin diphosphate-binding fold (THDP-binding) domain-containing protein
Arabidopsis thaliana AT1G21400   thiamin diphosphate-binding fold protein
Babesia bovis BBOV_III008200   dehydrogenase E1 component family protein
Brugia malayi Bm1_00280   2-oxoisovalerate dehydrogenase alpha subunit, mitochondrial precursor
Caenorhabditis elegans CELE_Y39E4A.3   Protein Y39E4A.3, isoform A
Dictyostelium discoideum DDB_G0286335   3-methyl-2-oxobutanoate dehydrogenase
Drosophila melanogaster Dmel_CG8199   CG8199 gene product from transcript CG8199-RA
Homo sapiens ENSG00000248098   branched chain keto acid dehydrogenase E1, alpha polypeptide
Leishmania braziliensis LbrM.21.1810   2-oxoisovalerate dehydrogenase alpha subunit, putative
Leishmania donovani LdBPK_211670.1   2-oxoisovalerate dehydrogenase alpha subunit, putative
Leishmania infantum LinJ.21.1670   2-oxoisovalerate dehydrogenase alpha subunit, putative
Leishmania major LmjF.21.1430   2-oxoisovalerate dehydrogenase alpha subunit, putative
Leishmania mexicana LmxM.21.1430   2-oxoisovalerate dehydrogenase alpha subunit, putative
Loa Loa (eye worm) LOAG_02337   2-oxoisovalerate dehydrogenase alpha subunit
Mus musculus ENSMUSG00000060376   branched chain ketoacid dehydrogenase E1, alpha polypeptide
Mycobacterium tuberculosis Rv2497c   Probable branched-chain keto acid dehydrogenase E1 component, alpha subunit BkdA
Mycobacterium ulcerans MUL_3775   pyruvate dehydrogenase E1 component subunit PdhA
Neospora caninum NCLIV_016110   hypothetical protein
Neospora caninum NCLIV_012850   hypothetical protein
Oryza sativa 4351684   Os12g0183100
Onchocerca volvulus OVOC9485   Bckdha protein homolog
Plasmodium berghei PBANKA_1411100   2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial
Plasmodium falciparum PF3D7_1312600   2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial, putative
Plasmodium knowlesi PKNH_1413300   2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial, putative
Plasmodium vivax PVX_122460   2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial, putative
Plasmodium yoelii PY05086   branched-chain alpha-keto acid dehydrogenase E1-alpha subunit
Schmidtea mediterranea mk4.002135.04  
Schmidtea mediterranea mk4.021022.00  
Schmidtea mediterranea mk4.002323.03   Bckdha protein
Schmidtea mediterranea mk4.031844.00  
Schmidtea mediterranea mk4.002135.02   2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial
Schmidtea mediterranea mk4.031108.01  
Schmidtea mediterranea mk4.021158.03  
Schmidtea mediterranea mk4.017274.02   Bckdha protein
Trypanosoma brucei gambiense Tbg972.10.680   2-oxoisovalerate dehydrogenase alpha subunit, putative
Trypanosoma brucei Tb927.10.660   2-oxoisovalerate dehydrogenase alpha subunit, putative
Trypanosoma congolense TcIL3000_10_520   2-oxoisovalerate dehydrogenase alpha subunit, putative
Trypanosoma cruzi TcCLB.506853.50   2-oxoisovalerate dehydrogenase alpha subunit, putative
Trypanosoma cruzi TcCLB.508781.110   2-oxoisovalerate dehydrogenase alpha subunit, putative
Toxoplasma gondii TGME49_292100   2-oxoisovalerate dehydrogenase subunit alpha, putative
Toxoplasma gondii TGME49_239490   dehydrogenase E1 component family protein
Theileria parva TP04_0719   branched-chain alpha keto-acid dehydrogenase, putative

Essentiality

PF3D7_1312600 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
mtu2540 Mycobacterium tuberculosis non-essential nmpdr
Tb927.10.660 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.10.660 Trypanosoma brucei significant gain of fitness in bloodstream forms (6 days) alsford
Tb927.10.660 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.10.660 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
PBANKA_1411100 Plasmodium berghei Slow plasmo
TGME49_239490 Toxoplasma gondii Essentiality uncertain sidik
TGME49_292100 Toxoplasma gondii Essentiality uncertain sidik
TGME49_239490 Toxoplasma gondii Probably non-essential sidik
TGME49_292100 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection

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 α-Ketoglutarate Dehydrogenase (1.2.4.2 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.

Reagent availability

  • Pfal006371AAA;
  • Type Source Notes
    soluble recombinant protein Structural Genomics for Pathogenic Protozoa (SGPP) Pfal006371; Recombinant protein: full-length; Source: P falciparum; branched-chain alpha keto-acid dehydrogenase, putative ;
  • Reagent:
  • Target Type Source Notes
    PF3D7_1312600 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Plasmodium falciparum ( 1 )

Bibliographic References

4 literature references were collected for this gene.

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Gene identifier PF3D7_1312600 (Plasmodium falciparum), 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial, putative
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