About Gene List

PF3D7_1342100 (IRP)

Genome location: Pf3D7_13_v3:1,655,461..1,660,193(+)

Genome classification: Core

Function and Localization

Product Description: aconitate hydratase

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 4.2.1.3 (Aconitate hydratase);4.2.1.33 (3-isopropylmalate dehydratase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005829 cytosol
Component GO:0020020 food vacuole
Component GO:0005739 mitochondrion
Function GO:0051539 4 iron, 4 sulfur cluster binding
Function GO:0003994 aconitate hydratase activity
Function GO:0005506 iron ion binding
Process GO:0006101 citrate metabolic process
Process GO:0006447 regulation of translational initiation by iron
Process GO:0006099 tricarboxylic acid cycle

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

Stage LR class MCA mean MCA prop. zeros
Sporozoite not expressed N/A N/A
Ring not expressed 0.12 0.94
Trophozoite not expressed 0.34 0.79
Schizont expressed 0.73 0.58
Gametocyte possibly expressed 0.30 0.82

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1342100

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: Mutable in CDS

MIS: 0.807 | MFS: -2.209 | #Insertions: 1

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1355200)

  • Relative Growth Rate: 0.15 ± 0.25
  • Confidence: 4.18

RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_1355200)

Modification: Disrupted | RMgm-4081

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IDR8

"Best" AlphaFill ligand hit: No AlphaFill hits

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
4.2.1.3 aconitate hydratase ATPADPGDPEDTAPCMBHOClHOSCNmalateoxygencitratenitriteMaleate...
4.2.1.33 3-isopropylmalate dehydratase KFKClKCNK3PO4cysteine(NH4)2SO4glutathionemercaptoethanolisopropylmalateN-ethylmaleimidedimethylmesaconate1,10-phenanthroline...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_101028

Most Similar Human Ortholog: P21399

TM-align score: 0.99 | RMSD: 0.84

Seq Identity: 0.54 | Length: 882 / 909

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000122729 aconitase 1
ENSG00000136381 iron responsive element binding protein 2

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 7 57 29 60
disruptive 12 50 35 104
missense 12 50 34 87

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 9 110 48 71
disruptive 22 128 54 172
missense 21 113 49 121

PlasmoDB Total SNPs: 194

Non-coding: 158 | Synonymous: 22 | Nonsynonymous: 14 | Stop Codon: 0

Protein Information

Protein Length: 909 | Molecular Weight (kDa): 103.379

UniProt ID(s): Q8IDR8, Q9Y007

PDB ID(s): None

Isoelectric Point: 7.7

Protein Domain Annotations:

Source Family ID Description
InterPro IPR000573 Aconitase A/isopropylmalate dehydratase small subunit, swivel domain
InterPro IPR001030 Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
InterPro IPR006249 Aconitase/Iron-responsive element-binding protein 2
InterPro IPR036008 Aconitase, iron-sulfur domain
PFam PF00330 Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
PFam PF00694 Aconitase A/isopropylmalate dehydratase small subunit, swivel domain
Superfamily SSF52016 Aconitase, iron-sulfur domain
Superfamily SSF53732

Associated Publications

PMID Title Authors DOI/Link
15963579 An iron regulatory-like protein expressed in Plasmodium falciparum displaysaconitase activity. Hodges M, Yikilmaz E, ..., Loyevsky M 10.1016/j.molbiopara.2005.05.004
25843709 Genetic investigation of tricarboxylic acid metabolism during the Plasmodiumfalciparum life cycle. Ke H, Lewis IA, ..., Vaidya AB 10.1016/j.celrep.2015.03.011
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