Product Description: dipeptidyl aminopeptidase 3
SignalP Peptide: MILIFQLFLINILFLNFIKC
# Transmembrane Domains: 0
EC Numbers: 3.4.14.1 (Dipeptidyl-peptidase I);3.4.14.4 (Dipeptidyl-peptidase III)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0045177 | apical part of cell |
| Component | GO:0005615 | extracellular space |
| Component | GO:0044164 | host cell cytosol |
| Component | GO:0005764 | lysosome |
| Component | GO:0020005 | symbiont-containing vacuole membrane |
| Function | GO:0004177 | aminopeptidase activity |
| Function | GO:0004197 | cysteine-type endopeptidase activity |
| Function | GO:0008234 | cysteine-type peptidase activity |
| Process | GO:0044409 | entry into host |
| Process | GO:0030163 | protein catabolic process |
| Process | GO:0051603 | proteolysis involved in cellular protein catabolic process |
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 | 0.11 | 0.94 |
| Trophozoite | not expressed | 0.19 | 0.90 |
| Schizont | expressed | 3.08 | 0.08 |
| Gametocyte | not expressed | 0.06 | 0.97 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0404700
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 2 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.166 | MFS: -2.81 | #Insertions: 0
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1002400)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1002400)
Modification: Disrupted | RMgm-2709
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I1Y2
"Best" AlphaFill ligand hit: E64 (n-[n-[1-hydroxycarboxyethyl-carbonyl]leucylamino-butyl]-guanidine, Local RMSD=0.42) with 3BPF (Global RMSD=17.65)
BRENDA EC Inhibitors:
No evidence of orthology to BindingDB entries
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 8 | 34 | 25 | 61 |
| disruptive | 30 | 87 | 82 | 140 |
| missense | 12 | 65 | 63 | 116 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 12 | 84 | 41 | 59 |
| disruptive | 55 | 243 | 116 | 262 |
| missense | 20 | 176 | 89 | 176 |
PlasmoDB Total SNPs: 248
Non-coding: 106 | Synonymous: 76 | Nonsynonymous: 66 | Stop Codon: 0
Protein Length: 939 | Molecular Weight (kDa): 110.479
UniProt ID(s): Q8I1Y2
PDB ID(s): None
Isoelectric Point: 5.24
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000169 | Cysteine peptidase, cysteine active site |
| InterPro | IPR000668 | Peptidase C1A, papain C-terminal |
| InterPro | IPR014882 | Cathepsin C exclusion |
| InterPro | IPR025660 | Cysteine peptidase, histidine active site |
| InterPro | IPR036496 | Cathepsin C, exclusion domain superfamily |
| InterPro | IPR038765 | Papain-like cysteine peptidase superfamily |
| PFam | PF00112 | Peptidase C1A, papain C-terminal |
| PFam | PF08773 | Cathepsin C exclusion |
| Superfamily | SSF54001 | Papain-like cysteine peptidase superfamily |
| Superfamily | SSF75001 | Cathepsin C, exclusion domain superfamily |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 20037583 | Transcriptional profiling of growth perturbations of the human malaria parasitePlasmodium falciparum. | Hu G, Cabrera A, ..., Bozdech Z | 10.1038/nbt.1597 |
| 29509772 | The cysteine protease dipeptidyl aminopeptidase 3 does not contribute to egressof Plasmodium falciparum from host red blood cells. | Ghosh S, Chisholm SA, ..., de Koning-Ward TF | 10.1371/journal.pone.0193538 |
| 29768491 | Plasmodium falciparum dipeptidyl aminopeptidase 3 activity is important forefficient erythrocyte invasion by the malaria parasite. | Lehmann C, Tan MSY, ..., Deu E | 10.1371/journal.ppat.1007031 |
| 31177613 | Characterization of P. falciparum dipeptidyl aminopeptidase 3 specificityidentifies differences in amino acid preferences between peptide-based substratesand covalent inhibitors | de Vries LE, Sanchez MI, ..., Deu E | 10.1111/febs.14953 |
| 18246061 | Identification of proteases that regulate erythrocyte rupture by the malariaparasite Plasmodium falciparum | Arastu-Kapur S, Ponder EL, ..., Bogyo M | 10.1038/nchembio.70 |
| 31851699 | Identification of Plasmodium dipeptidyl aminopeptidase allosteric inhibitors byhigh throughput screening | Sanchez MI, de Vries LE, ..., Deu E | 10.1371/journal.pone.0226270 |
| 20797610 | Functional studies of Plasmodium falciparum dipeptidyl aminopeptidase I usingsmall molecule inhibitors and active site probes | Deu E, Leyva MJ, ..., Bogyo M | 10.1016/j.chembiol.2010.06.007 |