Product Description: cysteine proteinase falcipain 2b
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: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 | expressed | 0.42 | 0.80 |
| Trophozoite | expressed | 0.47 | 0.75 |
| Schizont | expressed | 0.04 | 0.97 |
| Gametocyte | not expressed | 0.11 | 0.94 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1115300
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: 0.91 | MFS: -2.729 | #Insertions: 1
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1321700)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I6U5
"Best" AlphaFill ligand hit: MHA (n-(2-acetamido)iminodiacetic acid, Local RMSD=0.10) with 6QLM (Global RMSD=2.97)
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, 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... |
| 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... |
| Q9NAW4 | Cysteine protease falcipain-3 [5-492] | Plasmodium falciparum | OrthoMCL BLAST | GNF-PF-5434CHEMBL224801CHEMBL221833CHEMBL222870... |
| 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: 1.92
Seq Identity: 0.34 | Length: 261 / 482
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000135047 | cathepsin L |
| ENSG00000136943 | cathepsin V |
| ENSG00000143387 | cathepsin K |
| ENSG00000163131 | cathepsin S |
| ENSG00000174080 | cathepsin F |
Protein Length: 482 | Molecular Weight (kDa): 55.803
UniProt ID(s): A0A346CMD7, A0A346CMJ4, A0A346CMJ6, A0A346CMJ7, A0A346CMK3, A0A346CML2, A0A346CML3, A0A5J6BZR0, A0A5J6BZS4, Q56CY9, Q8I6U5
PDB ID(s): None
Isoelectric Point: 8.03
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 | 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 | 1 | 5 | 2 | 8 |
| disruptive | 10 | 28 | 18 | 28 |
| missense | 10 | 28 | 17 | 26 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 3 | 6 | 4 | 12 |
| disruptive | 17 | 46 | 14 | 26 |
| missense | 17 | 44 | 12 | 24 |
PlasmoDB Total SNPs: 185
Non-coding: 57 | Synonymous: 63 | Nonsynonymous: 65 | Stop Codon: 0
| 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 |
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 16095562 | Characterization of amino acid variation at strategic positions in parasite andhuman proteases for selective inhibition of falcipains in Plasmodium falciparum | Goh LL, Sim TS | 10.1016/j.bbrc.2005.07.147 |
| 16722625 | Novel peptidomimetic cysteine protease inhibitors as potential antimalarialagents | Micale N, Kozikowski AP, ..., Chishti AH | 10.1021/jm060405f |