Product Description: cysteine proteinase falcipain 3
SignalP Peptide: N/A
# Transmembrane Domains: 1
EC Numbers: 3.4.22.- (Cysteine endopeptidases.)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005615 | extracellular space |
| Component | GO:0020020 | food vacuole |
| Component | GO:0005764 | lysosome |
| Function | GO:0004197 | cysteine-type endopeptidase activity |
| Process | GO:0042540 | hemoglobin catabolic process |
| 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 | expressed | 1.28 | 0.45 |
| Trophozoite | expressed | 1.18 | 0.42 |
| Schizont | expressed | 0.69 | 0.64 |
| Gametocyte | expressed | 0.97 | 0.50 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1115400
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Mutable in CDS
MIS: 0.978 | MFS: -1.959 | #Insertions: 1
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1321700)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IIL0
"Best" AlphaFill ligand hit: MHA (n-(2-acetamido)iminodiacetic acid, Local RMSD=0.10) with 6QLM (Global RMSD=2.47)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.22.- | Ex: staphylococcal cysteine proteinase | NEME64SpiSDSCysEDTAPCMBEGTAPMSFTLCKTPCKMENT... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P25774 | Cathepsin S | Homo sapiens | HOGENOM | US8524710, 841, 2, 3 -Triazole Nitrile Inhibitor, 11a1, 2, 3 -Triazole Nitrile Inhibitor, 11b1, 2, 3 -Triazole Nitrile Inhibitor, 11c... |
| O60911 | Cathepsin L2 | Homo sapiens | HOGENOM | Azepan-3-one compound 1Azepan-3-one compound 10Dipeptidyl nitrile inhibitor, 1Dipeptidyl nitrile inhibitor, 4... |
| P07711 | Procathepsin L | Homo sapiens | HOGENOM | Aldehyde Inhibitor, 2Aldehyde Inhibitor, 12dL-873724trifluoroethylamine inhibitor, 1... |
| P43236 | Cathepsin K | Oryctolagus cuniculus | HOGENOM | L-873724trifluoroethylamine inhibitor, 1CHEMBL400387trifluoroethylamine inhibitor, 3... |
| O70370 | Cathepsin S | HOGENOM | CHEMBL426819BalicatibCHEMBL184514aryl-morpholino-containing analogue, 12... | |
| P07154 | Procathepsin L | Rattus norvegicus | HOGENOM | CHEMBL116910CHEMBL115734CHEMBL419772CHEMBL113761... |
| O35186 | Cathepsin K | Rattus norvegicus | HOGENOM | Azepan-3-one compound 1Azepan-3-one compound 7Azepan-3-one compound 9Azepan-3-one compound 10... |
| Q8IIL0 | Cysteine proteinase falcipain 3 | Plasmodium falciparum | HOGENOM, OMA, OrthoDB, OrthoMCL BLAST | Ac-Leu-Leu-Arg-HAc-Leu-Leu-Arg-HE-64CHEMBL3120849... |
| P25975 | Procathepsin L | Bos taurus | HOGENOM | dipeptide-derived nitrile, 5dipeptide-derived nitrile, 7dipeptidyl nitrile, 1dipeptide-derived nitrile, 9... |
| P06797 | Procathepsin L | Mus musculus | HOGENOM | CID644294Gallinamide ACHEMBL4594870CHEMBL4598338... |
| P43235 | Cathepsin K | Homo sapiens | HOGENOM | 1, 2, 3 -Triazole Nitrile Inhibitor, 11a1, 2, 3 -Triazole Nitrile Inhibitor, 11b1, 2, 3 -Triazole Nitrile Inhibitor, 11dAldehyde Inhibitor, 2... |
| Q9NAW4 | Cysteine protease falcipain-3 [5-492] | Plasmodium falciparum | OMA, OrthoMCL BLAST | GNF-PF-5434CHEMBL224801CHEMBL221833CHEMBL222870... |
| P25805 | Trophozoite cysteine proteinase | OrthoDB, OrthoMCL BLAST | CHEMBL2237705CHEMBL2237700CHEMBL146137CHEMBL146192... | |
| P07688 | Cathepsin B | Bos taurus | OrthoDB | epoxysuccinyl derivative 2epoxysuccinyl derivative 3epoxysuccinyl derivative 4epoxysuccinyl derivative 5... |
| P10605 | Cathepsin B | Mus musculus | OrthoDB | CID644294 |
| P07858 | Cathepsin B | Homo sapiens | OrthoDB | L-873724trifluoroethylamine inhibitor, 1CHEMBL400387trifluoroethylamine inhibitor, 3... |
| H9B8T9 | Cathepsin B | OrthoDB | N-formyl-3,5-diphenylpyrazoline (1a)N-formyl-5-(-2'-chlorophenyl)-3-phenylpyrazoline (1b)N-formyl-5-(-3'-chlorophenyl)-3-phenylpyrazoline (1c)N-formyl-5-(-4'-chlorophenyl)-3-phenylpyrazoline (1d)... | |
| Q9NBD4 | Cysteine proteinase falcipain 2a | Plasmodium falciparum | OrthoMCL BLAST | Trisubsituted thiazole, 14Ac-Leu-Leu-Arg-HAc-Leu-Leu-Arg-HCHEMBL3120848... |
| Q3HTL5 | Falcipain 2B | Plasmodium falciparum | OrthoMCL BLAST | CHEMBL207102MDL-28170 |
| Q9NAW2 | Falcipain-2 | Plasmodium falciparum | OrthoMCL BLAST | Phenylurenyl Chalcone deriv. 23Phenylurenyl Chalcone deriv. 24Phenylurenyl Chalcone deriv. 25Phenylurenyl Chalcone deriv. 26... |
| Q9N6S8 | Falcipain 2 | Plasmodium falciparum | OrthoMCL BLAST | thiosemicarbazone derivative, 3bthiosemicarbazone derivative, 3cthiosemicarbazone derivative, 3f4-aminoquinoline semicarbazone derivative, 8a... |
Ortholog Group (OrthoMCL): OG6_100116
Most Similar Human Ortholog: A0A7P0TAQ0
TM-align score: 0.90 | RMSD: 2.05
Seq Identity: 0.37 | Length: 261 / 492
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000135047 | cathepsin L |
| ENSG00000136943 | cathepsin V |
| ENSG00000143387 | cathepsin K |
| ENSG00000163131 | cathepsin S |
| ENSG00000174080 | cathepsin F |
Protein Length: 492 | Molecular Weight (kDa): 56.666
UniProt ID(s): A0A5J6BZP7, A0A5J6C0S5, Q8IIL0, Q9NAW4, Q9NB39, Q9NBA7
PDB ID(s): None
Isoelectric Point: 6.91
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000169 | Cysteine peptidase, cysteine active site |
| InterPro | IPR000668 | Peptidase C1A, papain C-terminal |
| InterPro | IPR013201 | Cathepsin propeptide inhibitor domain (I29) |
| InterPro | IPR038765 | Papain-like cysteine peptidase superfamily |
| InterPro | IPR039417 | Papain-like cysteine endopeptidase |
| PFam | PF00112 | Peptidase C1A, papain C-terminal |
| PFam | PF08246 | Cathepsin propeptide inhibitor domain (I29) |
| Superfamily | SSF54001 | Papain-like cysteine peptidase superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 6 | 12 | 13 | 30 |
| disruptive | 7 | 42 | 26 | 55 |
| missense | 7 | 42 | 24 | 52 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 6 | 39 | 24 | 32 |
| disruptive | 14 | 87 | 42 | 104 |
| missense | 10 | 79 | 36 | 70 |
PlasmoDB Total SNPs: 130
Non-coding: 97 | Synonymous: 20 | Nonsynonymous: 12 | Stop Codon: 1
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 9343345 | Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. | Francis SE, Sullivan DJ Jr, Goldberg DE | 10.1146/annurev.micro.51.1.97 |
| 11716777 | Expression and characterization of the Plasmodium falciparum haemoglobinasefalcipain-3. | Sijwali PS, Shenai BR, ..., Rosenthal PJ | 10.1042/0264-6021:3600481 |
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 15664655 | Biosynthesis, localization, and processing of falcipain cysteine proteases ofPlasmodium falciparum. | Dahl EL, Rosenthal PJ | https://pubmed.ncbi.nlm.nih.gov/15664655/ |
| 16776649 | Substrate mapping and inhibitor profiling of falcipain-2, falcipain-3 andberghepain-2: implications for peptidase anti-malarial drug discovery. | Ramjee MK, Flinn NS, ..., Watts JP | 10.1042/BJ20060422 |
| 16890302 | Gene disruptions demonstrate independent roles for the four falcipain cysteineproteases of Plasmodium falciparum. | Sijwali PS, Koo J, Singh N, Rosenthal PJ | 10.1016/j.molbiopara.2006.06.013 |
| 17565983 | Falcipain cysteine proteases require bipartite motifs for trafficking to thePlasmodium falciparum food vacuole. | Subramanian S, Sijwali PS, Rosenthal PJ | 10.1074/jbc.M703316200 |
| 19357776 | Hemoglobin cleavage site-specificity of the Plasmodium falciparum cysteineproteases falcipain-2 and falcipain-3. | Subramanian S, Hardt M, ..., Rosenthal PJ | 10.1371/journal.pone.0005156 |
| 23077573 | The Ionic and hydrophobic interactions are required for the auto activation ofcysteine proteases of Plasmodium falciparum. | Sundararaj S, Singh D, ..., Pandey KC | 10.1371/journal.pone.0047227 |
| 36601587 | Microsecond-long simulation reveals the molecular mechanism for the dualinhibition of falcipain-2 and falcipain-3 by antimalarial lead compounds | Danazumi AU, Balogun EO | 10.3389/fmolb.2022.1070080 |
| 37711130 | Three decades targeting falcipains to develop antiplasmodial agents: what have welearned and what can be done next? | Hernandez Gonzalez JE, Salas-Sarduy E, ..., Pascutti PG | 10.2174/0929867331666230913165219 |
| 35631126 | Inhibitor of Cysteine Protease of Plasmodium malariae Regulates Malapains,Endogenous Cysteine Proteases of the Parasite | Le HG, Kang JM, ..., Na BK | 10.3390/pathogens11050605 |
| 35462917 | Target-Based Virtual Screening of Natural Compounds Identifies a PotentAntimalarial With Selective Falcipain-2 Inhibitory Activity | Uddin A, Gupta S, ..., Abid M | 10.3389/fphar.2022.850176 |