Product Description: M1-family alanyl aminopeptidase
SignalP Peptide: N/A
# Transmembrane Domains: 1
EC Numbers: 3.4.11.2 (Membrane alanyl aminopeptidase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0009986 | cell surface |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005829 | cytosol |
| Component | GO:0020020 | food vacuole |
| Component | GO:0020009 | microneme |
| Component | GO:0005634 | nucleus |
| Function | GO:0004177 | aminopeptidase activity |
| 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 | not expressed | N/A | N/A |
| Ring | expressed | 1.23 | 0.46 |
| Trophozoite | expressed | 1.69 | 0.27 |
| Schizont | possibly expressed | 0.47 | 0.72 |
| Gametocyte | not expressed | 0.58 | 0.69 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1311800
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: 0.127 | MFS: -3.225 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1410300)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IEK1
"Best" AlphaFill ligand hit: B3P (2-[3-(2-hydroxy-1,1-dihydroxymethyl-ethylamino)-propylamino]-2-hydroxymethyl-propane-1,3-diol, Local RMSD=0.03) with 6Q4R (Global RMSD=4.35)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.11.2 | membrane alanyl aminopeptidase | NEMKCNLeuProE64EDTAEGTAPMSFSCN-PC18EC27L-Arg... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| O96935 | M1 family aminopeptidase | Plasmodium falciparum (isolate FcB1 / Columbia) | HOGENOM, OMA, OrthoMCL BLAST | MLS000075837MLS000074693MLS000037985MLS000090825... |
| P04825 | Aminopeptidase N | Escherichia coli | OMA, OrthoMCL, OrthoMCL BLAST | CHEMBL198796CHEMBL413567 |
Protein Length: 1085 | Molecular Weight (kDa): 126.062
UniProt ID(s): Q8IEK1
Isoelectric Point: 7.57
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001930 | Peptidase M1, alanine aminopeptidase/leukotriene A4 hydrolase |
| InterPro | IPR012779 | Peptidase M1, alanyl aminopeptidase |
| InterPro | IPR014782 | Peptidase M1, membrane alanine aminopeptidase |
| InterPro | IPR024601 | Peptidase M1, alanyl aminopeptidase, C-terminal |
| InterPro | IPR035414 | Peptidase M1, alanyl aminopeptidase, Ig-like fold |
| InterPro | IPR042097 | Aminopeptidase N-like , N-terminal |
| PFam | PF01433 | Peptidase M1, membrane alanine aminopeptidase |
| PFam | PF11940 | Peptidase M1, alanyl aminopeptidase, Ig-like fold |
| PFam | PF17432 | Peptidase M1, alanyl aminopeptidase, C-terminal |
| PFam | PF17900 | |
| Superfamily | SSF55486 | Aminopeptidase N-like , N-terminal |
| Superfamily | SSF63737 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 11 | 55 | 32 | 78 |
| disruptive | 11 | 59 | 41 | 106 |
| missense | 10 | 53 | 37 | 92 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 24 | 117 | 52 | 62 |
| disruptive | 23 | 150 | 83 | 213 |
| missense | 13 | 124 | 64 | 136 |
PlasmoDB Total SNPs: 110
Non-coding: 69 | Synonymous: 27 | Nonsynonymous: 11 | Stop Codon: 3
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12166515 | Properties, stage-dependent expression and localization of Plasmodium falciparumM1 family zinc-aminopeptidase. | Allary M, Schrevel J, Florent I | 10.1017/s0031182002001828 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 17326615 | Novel selective inhibitors of the zinc plasmodial aminopeptidase PfA-M1 aspotential antimalarial agents. | Flipo M, Beghyn T, ..., Deprez-Poulain RF | 10.1021/jm061169b |
| 19206106 | Characterisation of Plasmodium invasive organelles; an ookinete micronemeproteome. | Lal K, Prieto JH, ..., Sinden RE | 10.1002/pmic.200800404 |
| 20133789 | Structure of the Plasmodium falciparum M17 aminopeptidase and significance forthe design of drugs targeting the neutral exopeptidases. | McGowan S, Oellig CA, ..., Whisstock JC | 10.1073/pnas.0911813107 |
| 20591164 | Plasmodium falciparum PfA-M1 aminopeptidase is trafficked via the parasitophorousvacuole and marginally delivered to the food vacuole. | Azimzadeh O, Sow C, ..., Florent I | 10.1186/1475-2875-9-189 |
| 21659511 | Distribution and biochemical properties of an M1-family aminopeptidase inPlasmodium falciparum indicate a role in vacuolar hemoglobin catabolism. | Ragheb D, Dalal S, ..., Klemba M | 10.1074/jbc.M111.225318 |
| 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 |
| 27128092 | Interrogating the Plasmodium Sporozoite Surface: Identification ofSurface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP byMass Spectrometry-Based Proteomics. | Swearingen KE, Lindner SE, ..., Sinnis P | 10.1371/journal.ppat.1005606 |
| 28934959 | Selective inhibition of PfA-M1, over PfA-M17, by an amino-benzosuberonederivative blocks malaria parasites development in vitro and in vivo. | Bounaadja L, Schmitt M, ..., Florent I | 10.1186/s12936-017-2032-4 |
| 30318749 | Mapping the Pathway and Dynamics of Bestatin Inhibition of the Plasmodiumfalciparum M1 Aminopeptidase PfA-M1. | Yang W, Riley BT, ..., McGowan S | 10.1002/cmdc.201800563 |
| 33536500 | Biochemical and cellular characterisation of the Plasmodium falciparum M1 alanylaminopeptidase (PfM1AAP) and M17 leucyl aminopeptidase (PfM17LAP). | Mathew R, Wunderlich J, ..., Dalton JP | 10.1038/s41598-021-82499-4 |
| 34832608 | Overexpression of Plasmodium falciparum M1 Aminopeptidase Promotes an Increase in Intracellular Proteolysis and Modifies the Asexual Erythrocytic Cycle Development | Hoff CC, Azevedo MF, ..., Gazarini ML | 10.3390/pathogens10111452 |