Genome location: Pf3D7_14_v3:1,403,360..1,407,209(+)
Genome classification: Core
Product Description: methionine aminopeptidase 2
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 3.4.11.18 (Methionyl aminopeptidase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005634 | nucleus |
| Function | GO:0008235 | metalloexopeptidase activity |
| Process | GO:0006464 | cellular protein modification process |
| Process | GO:0006417 | regulation of translation |
| Process | GO:0006412 | translation |
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 | 1.01 | 0.54 |
| Trophozoite | expressed | 0.75 | 0.59 |
| Schizont | expressed | 0.15 | 0.91 |
| Gametocyte | expressed | 0.54 | 0.69 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1434600
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.154 | MFS: -3.203 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1010200)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8ILB8
"Best" AlphaFill ligand hit: No AlphaFill hits
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.11.18 | methionyl aminopeptidase | BRENDA SOAP query unsuccessful |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| O08663 | Methionine aminopeptidase 2 | Mus musculus | HOGENOM, OrthoDB | AGM-1470OvalicinFOS-72FOS-68... |
| P50579 | Methionine aminopeptidase 2 | Homo sapiens | OrthoDB | 1,2,4-Triazole Compound, 61,2,4-Triazole Compound, 121,2,4-Triazole Compound, 131,2,4-Triazole Compound, 14... |
| Q8TA23 | Methionine aminopeptidase 2 | Plasmodium falciparum | OrthoMCL BLAST | TNP-470 |
Ortholog Group (OrthoMCL): OG6_100815
Most Similar Human Ortholog: F8VZX9
TM-align score: 0.86 | RMSD: 1.92
Seq Identity: 0.47 | Length: 149 / 628
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000111142 | methionyl aminopeptidase 2 |
Protein Length: 628 | Molecular Weight (kDa): 71.743
PDB ID(s): None
Isoelectric Point: 8.49
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000994 | Peptidase M24 |
| InterPro | IPR001714 | Peptidase M24, methionine aminopeptidase |
| InterPro | IPR002468 | Peptidase M24A, methionine aminopeptidase, subfamily 2 |
| InterPro | IPR018349 | Peptidase M24A, methionine aminopeptidase, subfamily 2, binding site |
| InterPro | IPR036005 | Creatinase/aminopeptidase-like |
| InterPro | IPR036390 | Winged helix DNA-binding domain superfamily |
| PFam | PF00557 | Peptidase M24 |
| Superfamily | SSF46785 | Winged helix DNA-binding domain superfamily |
| Superfamily | SSF55920 | Creatinase/aminopeptidase-like |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 7 | 35 | 14 | 38 |
| disruptive | 17 | 71 | 32 | 89 |
| missense | 12 | 63 | 29 | 75 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 19 | 72 | 27 | 46 |
| disruptive | 34 | 144 | 86 | 184 |
| missense | 22 | 118 | 73 | 128 |
PlasmoDB Total SNPs: 199
Non-coding: 138 | Synonymous: 46 | Nonsynonymous: 15 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 23181666 | Organellar proteomics reveals hundreds of novel nuclear proteins in the malariaparasite Plasmodium falciparum. | Oehring SC, Woodcroft BJ, ..., Voss TS | 10.1186/gb-2012-13-11-r108 |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |
| 36247237 | Methionine aminopeptidase 2 as a potential target in pancreatic ductal adenocarcinoma | Steinberg E, Esa R, ..., Benny O | https://pubmed.ncbi.nlm.nih.gov/36247237/ |
| 37874291 | Fumagillin inhibits growth of the enteric protozoan parasite Entamoebahistolytica by covalently binding to and selectively inhibiting methionineaminopeptidase 2 | Watanabe N, Saito-Nakano Y, ..., Nozaki T | 10.1128/aac.00560-23 |
| 37940144 | Novel Methionine Aminopeptidase 2 Inhibitor M8891 Synergizes with VEGF Receptor Inhibitors to Inhibit Tumor Growth of Renal Cell Carcinoma Models | Friese-Hamim M, Ortiz Ruiz MJ, ..., Zenke FT | 10.1158/1535-7163.MCT-23-0102 |
| 36674953 | Identification of Potential Druggable Targets and Structure-Based Virtual Screening for Drug-like Molecules against the Shrimp Pathogen Enterocytozoonhepatopenaei | Paria P, Tassanakajon A | 10.3390/ijms24021412 |
| 35637333 | Newly synthesized methionine aminopeptidase 2 inhibitor hinders tumor growth | Esa R, Steinberg E, ..., Benny O | 10.1007/s13346-022-01187-6 |
| 37798538 | Preclinical Pharmacokinetics and Translational Pharmacokinetic/Pharmacodynamic Modeling of M8891, a Potent and Reversible Inhibitor of Methionine Aminopeptidase2 | Lignet F, Friese-Hamim M, ..., Rohdich F | 10.1007/s11095-023-03611-z |
| 37637935 | A First-in-human, Dose-escalation Study of the Methionine Aminopeptidase 2Inhibitor M8891 in Patients with Advanced Solid Tumors | Carducci MA, Wang D, ..., LoRusso P | 10.1158/2767-9764.CRC-23-0048 |