Genome location: Pf3D7_12_v3:1,967,712..1,971,234(+)
Genome classification: Core
Product Description: dipeptidyl aminopeptidase 2
SignalP Peptide: MNTFYIFFLFVLTTCFVKG
# Transmembrane Domains: 0
EC Numbers: 3.4.14.1 (Dipeptidyl-peptidase I)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0071944 | cell periphery |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005615 | extracellular space |
| Component | GO:0005764 | lysosome |
| Component | GO:0044310 | osmiophilic body |
| Function | GO:0004197 | cysteine-type endopeptidase activity |
| Function | GO:0008239 | dipeptidyl-peptidase activity |
| Process | GO:0035891 | exit from host cell |
| Process | GO:0006508 | proteolysis |
| 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 | expressed | N/A | N/A |
| Ring | not expressed | 0.02 | 0.99 |
| Trophozoite | possibly expressed | 0.02 | 0.99 |
| Schizont | expressed | 0.20 | 0.87 |
| Gametocyte | expressed | 1.43 | 0.48 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1247800
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: 0.802 | MFS: -2.151 | #Insertions: 0
PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_1460700)
RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PY17X_1463300)
Modification: Disrupted | RMgm-4794
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I0V1
"Best" AlphaFill ligand hit: E64 (n-[n-[1-hydroxycarboxyethyl-carbonyl]leucylamino-butyl]-guanidine, Local RMSD=0.18) with 3H7D (Global RMSD=4.80)
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 |
|---|---|---|---|---|
| P53634 | Dipeptidyl peptidase 1 | OMA, OrthoDB, OrthoMCL BLAST | US8871783, 1US8871783, 2US8871783, 3US8871783, 4... | |
| P97821 | Dipeptidyl peptidase 1 | Mus musculus | OMA, OrthoDB, OrthoMCL BLAST | ML4057ML4066ML4046AHN3019... |
| P80067 | Dipeptidyl peptidase 1 | OMA, OrthoDB, OrthoMCL BLAST | CHEMBL3900409 | |
| O97578 | Dipeptidyl peptidase 1 | OrthoDB, OrthoMCL, OrthoMCL BLAST | CHEMBL3900409 | |
| Q9R1T3 | Cathepsin Z | Rattus norvegicus | OrthoDB | Cathepsin Inhibitor IIIAc-YFR-AMOK 10b |
| Q9UBR2 | Cathepsin Z | Homo sapiens | OrthoDB | CHEMBL567785CHEMBL567341CHEMBL568171CHEMBL567134... |
Ortholog Group (OrthoMCL): OG6_103622
Most Similar Human Ortholog: A0A7I2V466
TM-align score: 0.81 | RMSD: 3.57
Seq Identity: 0.30 | Length: 413 / 590
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000109861 | cathepsin C |
Protein Length: 590 | Molecular Weight (kDa): 69.642
UniProt ID(s): Q8I0V1
PDB ID(s): None
Isoelectric Point: 8.22
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 | 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 | 5 | 27 | 22 | 49 |
| disruptive | 5 | 49 | 26 | 59 |
| missense | 5 | 46 | 24 | 56 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 8 | 65 | 35 | 32 |
| disruptive | 11 | 114 | 51 | 117 |
| missense | 8 | 100 | 49 | 71 |
PlasmoDB Total SNPs: 221
Non-coding: 188 | Synonymous: 27 | Nonsynonymous: 6 | 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 |
| 27432909 | Comparative Proteomics and Functional Analysis Reveal a Role of Plasmodiumfalciparum Osmiophilic Bodies in Malaria Parasite Transmission. | Suarez-Cortes P, Sharma V, ..., Alano P | 10.1074/mcp.M116.060681 |
| 28351685 | Transcript and protein expression analysis of proteases in the blood stages ofPlasmodium falciparum. | Weissbach T, Golzmann A, ..., Julius Ngwa C | 10.1016/j.exppara.2017.03.006 |
| 23836185 | Plasmodium dipeptidyl aminopeptidases as malaria transmission-blocking drugtargets | Tanaka TQ, Deu E, ..., Williamson KC | 10.1128/AAC.02495-12 |