Genome location: Pf3D7_14_v3:2,387,106..2,389,942(+)
Genome classification: Core
Product Description: cysteine proteinase falcipain 1
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:0005764 | lysosome |
| Function | GO:0004197 | cysteine-type endopeptidase activity |
| Function | GO:0008234 | cysteine-type peptidase activity |
| Process | GO:0044409 | entry into host |
| 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 | 1.45 | 0.39 |
| Trophozoite | expressed | 0.79 | 0.57 |
| Schizont | expressed | 0.32 | 0.80 |
| Gametocyte | expressed | 0.62 | 0.65 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1458000
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: 0.138 | MFS: -3.008 | #Insertions: 0
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1321700)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1321700)
Modification: Tagged | RMgm-4362
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I6V0
"Best" AlphaFill ligand hit: E64 (n-[n-[1-hydroxycarboxyethyl-carbonyl]leucylamino-butyl]-guanidine, Local RMSD=0.10) with 3BPF (Global RMSD=2.26)
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 |
|---|---|---|---|---|
| P25805 | Trophozoite cysteine proteinase | HOGENOM, OMA, 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... |
| Q8IIL0 | Cysteine proteinase falcipain 3 | Plasmodium falciparum | OrthoDB, OrthoMCL, OrthoMCL BLAST | Ac-Leu-Leu-Arg-HAc-Leu-Leu-Arg-HE-64CHEMBL3120849... |
| 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, OrthoMCL BLAST | Trisubsituted thiazole, 14Ac-Leu-Leu-Arg-HAc-Leu-Leu-Arg-HCHEMBL3120848... |
| Q3ZKN1 | Cathepsin K | Canis familiaris | OrthoMCL | CHEMBL2070937CHEMBL2163587 |
| P25779 | Cruzipain | Trypanosoma cruzi | OrthoMCL | FukugetinCHEMBL39253CHEMBL38981CHEMBL39814... |
| Q9NAW4 | Cysteine protease falcipain-3 [5-492] | Plasmodium falciparum | OrthoMCL, OrthoMCL BLAST | GNF-PF-5434CHEMBL224801CHEMBL221833CHEMBL222870... |
| Q9NAW2 | Falcipain-2 | Plasmodium falciparum | OrthoMCL, OrthoMCL BLAST | Phenylurenyl Chalcone deriv. 23Phenylurenyl Chalcone deriv. 24Phenylurenyl Chalcone deriv. 25Phenylurenyl Chalcone deriv. 26... |
| Q9N6S8 | Falcipain 2 | Plasmodium falciparum | OrthoMCL, OrthoMCL BLAST | thiosemicarbazone derivative, 3bthiosemicarbazone derivative, 3cthiosemicarbazone derivative, 3f4-aminoquinoline semicarbazone derivative, 8a... |
| Q3HTL5 | Falcipain 2B | Plasmodium falciparum | OrthoMCL BLAST | CHEMBL207102MDL-28170 |
Ortholog Group (OrthoMCL): OG6_100116
Most Similar Human Ortholog: A0A7P0TAQ0
TM-align score: 0.90 | RMSD: 1.89
Seq Identity: 0.34 | Length: 261 / 569
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000135047 | cathepsin L |
| ENSG00000136943 | cathepsin V |
| ENSG00000143387 | cathepsin K |
| ENSG00000163131 | cathepsin S |
| ENSG00000174080 | cathepsin F |
Protein Length: 569 | Molecular Weight (kDa): 66.914
UniProt ID(s): A0A346CMG7, A0A346CMG9, A0A346CMH0, P25805, Q8I6V0
PDB ID(s): None
Isoelectric Point: 8.61
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 | IPR025660 | Cysteine peptidase, histidine active site |
| InterPro | IPR025661 | Cysteine peptidase, asparagine active site |
| 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 | 2 | 37 | 15 | 41 |
| disruptive | 22 | 90 | 71 | 145 |
| missense | 22 | 90 | 71 | 122 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 6 | 63 | 35 | 48 |
| disruptive | 34 | 225 | 104 | 184 |
| missense | 30 | 210 | 91 | 117 |
PlasmoDB Total SNPs: 141
Non-coding: 96 | Synonymous: 19 | Nonsynonymous: 26 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 1565129 | Isolation and characterization of a cysteine proteinase gene of Plasmodiumfalciparum. | Rosenthal PJ, Nelson RG | 10.1016/0166-6851(92)90209-3 |
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 12368868 | Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14. | Gardner MJ, Shallom SJ, ..., Fraser CM | 10.1038/nature01094 |
| 12471262 | A role for the protease falcipain 1 in host cell invasion by the human malariaparasite. | Greenbaum DC, Baruch A, ..., Bogyo M | 10.1126/science.1077426 |