About Gene List

PF3D7_1454400 (APP)

Genome location: Pf3D7_14_v3:2,232,798..2,236,926(+)

Genome classification: Core

Function and Localization

Product Description: aminopeptidase P

SignalP Peptide: MQLNFLLFVFIFLMVFH

# Transmembrane Domains: 1

EC Numbers: 3.4.11.9 (Xaa-Pro aminopeptidase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005829 cytosol
Component GO:0020020 food vacuole
Function GO:0004177 aminopeptidase activity
Function GO:0070006 metalloaminopeptidase activity
Function GO:0042803 protein homodimerization activity
Process GO:0042540 hemoglobin catabolic process
Process GO:0006508 proteolysis

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 expressed 0.85 0.61
Trophozoite expressed 1.45 0.33
Schizont expressed 0.30 0.81
Gametocyte expressed 0.65 0.64

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1454400

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 6 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.142 | MFS: -3.25 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1318100)

  • Relative Growth Rate: 0.21 ± 0.14
  • Confidence: 5.33

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1318100)

Modification: Disrupted | RMgm-813

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: A0A144A2H0

"Best" AlphaFill ligand hit: AR6 (adenosine-5-diphosphoribose, Local RMSD=14.38) with 8DMR (Global RMSD=18.41)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
3.4.11.9 Xaa-Pro aminopeptidase NEMDTTEDTAPCMBEGTAPMSFLeu-ProArg-ProSer-ProCH3HgClbestatinantipain...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_100896

Most Similar Human Ortholog: Q5T6H7

TM-align score: 0.93 | RMSD: 1.88

Seq Identity: 0.33 | Length: 533 / 777

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000108039 X-prolyl aminopeptidase 1
ENSG00000122121 X-prolyl aminopeptidase 2

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 4 41 27 58
disruptive 29 63 40 113
missense 24 59 37 90

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 10 90 33 63
disruptive 39 177 108 219
missense 29 143 84 120

PlasmoDB Total SNPs: 227

Non-coding: 165 | Synonymous: 40 | Nonsynonymous: 22 | Stop Codon: 0

Protein Information

Protein Length: 777 | Molecular Weight (kDa): 90.13

UniProt ID(s): A0A144A2H0

PDB ID(s): 5JQK, 5JR6

Isoelectric Point: 6.79

Protein Domain Annotations:

Source Family ID Description
InterPro IPR000587 Creatinase, N-terminal
InterPro IPR000994 Peptidase M24
InterPro IPR001131 Peptidase M24B, X-Pro dipeptidase/aminopeptidase P, conserved site
InterPro IPR029149 Creatinase/Aminopeptidase P/Spt16, N-terminal
InterPro IPR032416 Peptidase M24, C-terminal domain
InterPro IPR033740 Aminopeptidase P
InterPro IPR036005 Creatinase/aminopeptidase-like
PFam PF00557 Peptidase M24
PFam PF01321 Creatinase, N-terminal
PFam PF16188 Peptidase M24, C-terminal domain
PFam PF16189
Superfamily SSF53092 Creatinase/Aminopeptidase P/Spt16, N-terminal
Superfamily SSF55920 Creatinase/aminopeptidase-like

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
16267556 A protein interaction network of the malaria parasite Plasmodium falciparum. LaCount DJ, Vignali M, ..., Hughes RE 10.1038/nature04104
19574214 Evidence for catalytic roles for Plasmodium falciparum aminopeptidase P in thefood vacuole and cytosol. Ragheb D, Bompiani K, Dalal S, Klemba M 10.1074/jbc.M109.018424
21136929 Food vacuole proteome of the malarial parasite Plasmodium falciparum. Lamarque M, Tastet C, ..., Dubremetz JF 10.1002/prca.200700112
27458998 Transcripts in the Plasmodium Apicoplast Undergo Cleavage at tRNAs and Editing,and Include Antisense Sequences. Nisbet RER, Kurniawan DP, Bowers HD, Howe CJ 10.1016/j.protis.2016.06.003