Product Description: dipeptidyl aminopeptidase 1
SignalP Peptide: MAKRIFSVSFLLVLLNVLHICIKFSVA
# Transmembrane Domains: 1
EC Numbers: 3.4.14.1 (Dipeptidyl-peptidase I)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005615 | extracellular space |
| Component | GO:0020020 | food vacuole |
| Component | GO:0005764 | lysosome |
| Component | GO:0020003 | symbiont-containing vacuole |
| Function | GO:0004197 | cysteine-type endopeptidase activity |
| Process | GO:0051603 | proteolysis involved in cellular protein catabolic process |
| 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 | expressed | 1.45 | 0.38 |
| Trophozoite | expressed | 1.36 | 0.37 |
| Schizont | expressed | 0.40 | 0.79 |
| Gametocyte | expressed | 0.29 | 0.83 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1116700
Resistome Missense Mutations: N62H, L415P, L437S
Resistome Compounds with Missense Mutations: MMV029272
Resistome # Samples with Disruptive Mutations: 6 (6 missense, 6 "interesting" missense)
Zhang Phenotype: Mutable in CDS
MIS: 1 | MFS: -1.432 | #Insertions: 4
PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_1460700)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0931300)
Modification: Disrupted | RMgm-810
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IIJ9
"Best" AlphaFill ligand hit: E64 (n-[n-[1-hydroxycarboxyethyl-carbonyl]leucylamino-butyl]-guanidine, Local RMSD=0.22) with 3BPF (Global RMSD=4.88)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.14.1 | dipeptidyl-peptidase I | NEMPCMBFY01SAK2Leu-NH2Phe-NH2Gly-NH2Arg-NH2Lys-NH2Trp-NH2fluorideantipain... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| O97578 | Dipeptidyl peptidase 1 | OrthoDB | CHEMBL3900409 | |
| Q9R1T3 | Cathepsin Z | Rattus norvegicus | OrthoDB | Cathepsin Inhibitor IIIAc-YFR-AMOK 10b |
| P80067 | Dipeptidyl peptidase 1 | OrthoDB | CHEMBL3900409 | |
| Q9UBR2 | Cathepsin Z | Homo sapiens | OrthoDB | CHEMBL567785CHEMBL567341CHEMBL568171CHEMBL567134... |
| P53634 | Dipeptidyl peptidase 1 | OrthoDB | US8871783, 1US8871783, 2US8871783, 3US8871783, 4... | |
| P97821 | Dipeptidyl peptidase 1 | Mus musculus | OrthoDB | ML4057ML4066ML4046AHN3019... |
Ortholog Group (OrthoMCL): OG6_103622
Most Similar Human Ortholog: A0A7I2V466
TM-align score: 0.78 | RMSD: 3.51
Seq Identity: 0.29 | Length: 393 / 700
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000109861 | cathepsin C |
Protein Length: 700 | Molecular Weight (kDa): 80.412
UniProt ID(s): A0A144A2G5, Q8IIJ9
PDB ID(s): None
Isoelectric Point: 6.11
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000668 | Peptidase C1A, papain C-terminal |
| InterPro | IPR014882 | Cathepsin C exclusion |
| InterPro | IPR025660 | Cysteine peptidase, histidine active site |
| InterPro | IPR025661 | Cysteine peptidase, asparagine active site |
| InterPro | IPR036496 | Cathepsin C, exclusion domain superfamily |
| InterPro | IPR038765 | Papain-like cysteine peptidase superfamily |
| InterPro | IPR039412 | Cathepsin C |
| 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 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 12 | 44 | 17 | 44 |
| disruptive | 15 | 40 | 21 | 61 |
| missense | 15 | 38 | 20 | 56 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 16 | 78 | 23 | 48 |
| disruptive | 23 | 85 | 40 | 126 |
| missense | 21 | 72 | 35 | 92 |
PlasmoDB Total SNPs: 214
Non-coding: 171 | Synonymous: 27 | Nonsynonymous: 16 | 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 |
| 15304495 | A Plasmodium falciparum dipeptidyl aminopeptidase I participates in vacuolarhemoglobin degradation. | Klemba M, Gluzman I, Goldberg DE | 10.1074/jbc.M408123200 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 29326268 | Mapping the malaria parasite druggable genome by using in vitro evolution andchemogenomics. | Cowell AN, Istvan ES, ..., Winzeler EA | 10.1126/science.aan4472 |
| 23836185 | Plasmodium dipeptidyl aminopeptidases as malaria transmission-blocking drugtargets | Tanaka TQ, Deu E, ..., Williamson KC | 10.1128/AAC.02495-12 |
| 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 |
| 20833209 | Biochemical characterization of Plasmodium falciparum dipeptidyl aminopeptidase1 | Wang F, Krai P, ..., Klemba M | 10.1016/j.molbiopara.2010.08.004 |
| 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 |