About Gene List

PF3D7_1312600 (BCKDHA)

Genome location: Pf3D7_13_v3:529,137..531,966(+)

Genome classification: Core

Function and Localization

Product Description: 2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial, putative

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 1.2.4.4 (3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring))

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005947 mitochondrial alpha-ketoglutarate dehydrogenase complex
Component GO:0005739 mitochondrion
Function GO:0003826 alpha-ketoacid dehydrogenase activity
Function GO:0003729 mRNA binding
Process GO:0009083 branched-chain amino acid catabolic process

Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):

Stage LR class MCA mean MCA prop. zeros
Sporozoite expressed N/A N/A
Ring not expressed 0.06 0.97
Trophozoite expressed 0.32 0.81
Schizont expressed 0.41 0.74
Gametocyte expressed 0.52 0.70

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1312600

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.204 | MFS: -2.736 | #Insertions: 0

PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1411100)

  • Relative Growth Rate: 0.55 ± 0.08
  • Confidence: 6.44

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1411100)

Modification: Disrupted | RMgm-3794

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IEJ6

"Best" AlphaFill ligand hit: LMR (l-malate, Local RMSD=0.20) with 6YAK (Global RMSD=2.60)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
1.2.4.4 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) ATPNADHpyruvateClofibratemicroRNA 29amicroRNA 29b2-oxoglutarate2-oxobutanoate2-oxopentanoateisobutanoyl-CoAisopentanoyl-CoAcinnamylpyruvate...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_101723

Most Similar Human Ortholog: F5H5P2

TM-align score: 0.91 | RMSD: 2.06

Seq Identity: 0.39 | Length: 413 / 429

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000248098 branched chain keto acid dehydrogenase E1 subunit alpha
ENSG00000255730 novel protein

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 5 14 12 30
disruptive 5 25 17 41
missense 5 24 15 40

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 7 40 16 30
disruptive 7 59 37 77
missense 7 51 33 55

PlasmoDB Total SNPs: 74

Non-coding: 55 | Synonymous: 7 | Nonsynonymous: 12 | Stop Codon: 0

Protein Information

Protein Length: 429 | Molecular Weight (kDa): 49.871

UniProt ID(s): Q8IEJ6

PDB ID(s): None

Isoelectric Point: 7.46

Protein Domain Annotations:

Source Family ID Description
InterPro IPR001017 Dehydrogenase, E1 component
InterPro IPR029061 Thiamin diphosphate-binding fold
InterPro IPR034616 2-oxoisovalerate dehydrogenase subunit alpha
PFam PF00676 Dehydrogenase, E1 component
Superfamily SSF52518 Thiamin diphosphate-binding fold

Associated Publications

PMID Title Authors DOI/Link
27381095 The mRNA-bound proteome of the human malaria parasite Plasmodium falciparum. Bunnik EM, Batugedara G, ..., Le Roch KG 10.1186/s13059-016-1014-0
34494883 A Prioritized and Validated Resource of Mitochondrial Proteins in PlasmodiumIdentifies Unique Biology. van Esveld SL, Meerstein-Kessel L, ..., Huynen MA 10.1128/mSphere.00614-21