About Gene List

PF3D7_1430200 (PMIX)

Genome location: Pf3D7_14_v3:1,187,398..1,191,764(+)

Genome classification: Core

Function and Localization

Product Description: plasmepsin IX

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 3.4.23.- (Aspartic endopeptidases.)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0020008 rhoptry
Function GO:0004190 aspartic-type endopeptidase activity
Process GO:0044409 entry into host
Process GO:0006508 proteolysis
Process GO:0009410 response to xenobiotic stimulus

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 possibly expressed 0.05 0.98
Trophozoite expressed 0.29 0.84
Schizont expressed 1.29 0.42
Gametocyte expressed 1.23 0.54

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1430200

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: 0.238 | MFS: -2.729 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1222500)

  • Relative Growth Rate: 0.36 ± 0.32
  • Confidence: 3.65

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8ILG2

"Best" AlphaFill ligand hit: CPS (chaps, Local RMSD=0.44) with 7VE0 (Global RMSD=5.82)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
3.4.23.- Ex: renin I2YYKCNSDSIAANBSDANEDTAPI-3DMSOPCMBTLCK...

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
Q8ILG2 Plasmepsin IX HOGENOM, OMA, OrthoDB, OrthoMCL, OrthoMCL BLAST CHEMBL5191783CHEMBL5190700CHEMBL5190700CHEMBL5182418...
Q8IAS0 Plasmepsin X OrthoDB, OrthoMCL, OrthoMCL BLAST CHEMBL5172999CHEMBL5208335CHEMBL5191783CHEMBL5204196...

Orthology Information

Ortholog Group (OrthoMCL): OG6_119797

No human ortholog(s)

Protein Information

Protein Length: 627 | Molecular Weight (kDa): 74.183

UniProt ID(s): Q2KNX9, Q8ILG2

PDB ID(s): None

Isoelectric Point: 9.62

Protein Domain Annotations:

Source Family ID Description
InterPro IPR001461 Aspartic peptidase A1 family
InterPro IPR021109 Aspartic peptidase domain superfamily
InterPro IPR033121 Peptidase family A1 domain
InterPro IPR034164 Pepsin-like domain
PFam PF00026 Peptidase family A1 domain
Superfamily SSF50630 Aspartic peptidase domain superfamily

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 3 29 15 26
disruptive 3 40 28 89
missense 3 39 28 85

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 9 53 20 43
disruptive 18 122 69 134
missense 10 103 60 105

PlasmoDB Total SNPs: 392

Non-coding: 345 | Synonymous: 33 | Nonsynonymous: 14 | Stop Codon: 0

Associated Publications

PMID Title Authors DOI/Link
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
29074774 Plasmepsins IX and X are essential and druggable mediators of malaria parasiteegress and invasion. Nasamu AS, Glushakova S, ..., Goldberg DE 10.1126/science.aan1478
32109369 Dual Plasmepsin-Targeting Antimalarial Agents Disrupt Multiple Stages of theMalaria Parasite Life Cycle. Favuzza P, de Lera Ruiz M, ..., Cowman AF 10.1016/j.chom.2020.02.005
35460613 Basis for drug selectivity of plasmepsin IX and X inhibition in Plasmodiumfalciparum and vivax Hodder AN, Christensen J, ..., Cowman AF 10.1016/j.str.2022.03.018
38179191 Design, synthesis and modelling of photoreactive chemical probes forinvestigating target engagement of plasmepsin IX and X in Plasmodium falciparum Lisauskaite M, Nixon GL, ..., O'Neill PM 10.1039/d3cb00109a
29074775 A multistage antimalarial targets the plasmepsins IX and X essential for invasionand egress Pino P, Caldelari R, ..., Soldati-Favre D 10.1126/science.aaf8675
36385924 The Invention of WM382, a Highly Potent PMIX/X Dual Inhibitor toward theTreatment of Malaria de Lera Ruiz M, Favuzza P, ..., McCauley JA 10.1021/acsmedchemlett.2c00355
36432016 Bridging the Gap in Malaria Parasite Resistance, Current Interventions, and theWay Forward from in Silico Perspective: A Review Kumi RO, Oti B, ..., Soliman MES 10.3390/molecules27227915