Genome location: Pf3D7_14_v3:2,056,641..2,059,885(+)
Genome classification: Core
Product Description: NADPH--cytochrome P450 reductase, putative
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 1.6.2.4 (NADPH--hemoprotein reductase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005829 | cytosol |
| Component | GO:0005739 | mitochondrion |
| Function | GO:0010181 | FMN binding |
| Function | GO:0003958 | NADPH-hemoprotein reductase activity |
| Function | GO:0050660 | flavin adenine dinucleotide binding |
| Function | GO:0016491 | oxidoreductase activity |
| Function | GO:0016709 | oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | possibly expressed | N/A | N/A |
| Ring | expressed | 0.33 | 0.83 |
| Trophozoite | expressed | 0.31 | 0.81 |
| Schizont | expressed | 0.18 | 0.88 |
| Gametocyte | expressed | 0.33 | 0.81 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1450300
Resistome Missense Mutations: Q784K
Resistome Compounds with Missense Mutations: AN13762
Resistome # Samples with Disruptive Mutations: 1 (1 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.157 | MFS: -3.25 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1314000)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IKX3
"Best" AlphaFill ligand hit: FMN (flavin mononucleotide, Local RMSD=0.12) with 2BF4 (Global RMSD=5.46)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 1.6.2.4 | NADPH-hemoprotein reductase | NAD+EDTANADP+HgCl2AlCl3TlCl32'-AMP5'-ADPMersalylalizarinsteapsinquercetin... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P29477 | Nitric oxide synthase, inducible | Mus musculus | OrthoDB | Ngamma-nitro-L-argininehDDAH inhibitor, 1e(S)-2-Amino-5-formimidamidopentanoic acid (7)hDDAH inhibitor, 1d... |
| P29474 | Nitric oxide synthase, endothelial | OrthoDB | quinolinone, 23quinolinone, 24quinolinone, 40quinolinone, 41... | |
| P35228 | Nitric oxide synthase, inducible | Homo sapiens | OrthoDB | quinolinone, 7quinolinone, 8quinolinone, 9quinolinone, 10... |
| P70313 | Nitric oxide synthase, endothelial | Mus musculus | OrthoDB | CHEMBL1946352 |
| Q06518 | Nitric oxide synthase, inducible | Rattus norvegicus | OrthoDB | CHEMBL1956107ONO-1714L-NIO, 12CHEMBL2414836... |
| P29475 | Nitric oxide synthase, brain | Homo sapiens | OrthoDB | quinolinone, 12quinolinone, 15quinolinone, 19quinolinone, 20... |
| Q28969 | Nitric oxide synthase, endothelial | Sus scrofa | OrthoDB | CHEMBL318427CHEMBL101399CHEMBL100659CHEMBL327287 |
| Q9Z0J4 | Nitric oxide synthase, brain | Mus musculus | OrthoDB | US9783500, Compound 4US9783500, Compound 11US9783500, Compound 12US9783500, Compound 14... |
| Q62600 | Nitric oxide synthase, endothelial | Rattus norvegicus | OrthoDB | nNOS inhibitor, 2CHEMBL3262022CHEMBL3819046CHEMBL3819644... |
| P29476 | Nitric oxide synthase, brain | Rattus norvegicus | OrthoDB | Ngamma-nitro-L-arginineCHEMBL227937CHEMBL228077N omega-Nitro-L-Arginine-Containing Dipeptide, 3... |
| P22696 | Peptidyl-prolyl cis-trans isomerase ESS1 | Saccharomyces cerevisiae | OrthoMCL | MLS000882828MLS000882836MLS000882796MLS000882822... |
Ortholog Group (OrthoMCL): OG6_100390
Most Similar Human Ortholog: Q9UHB4
TM-align score: 0.83 | RMSD: 3.72
Seq Identity: 0.20 | Length: 570 / 865
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000127445 | peptidylprolyl cis/trans isomerase, NIMA-interacting 1 |
| ENSG00000188566 | NADPH dependent diflavin oxidoreductase 1 |
Protein Length: 865 | Molecular Weight (kDa): 103.074
UniProt ID(s): Q8IKX3
PDB ID(s): None
Isoelectric Point: 8.71
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR008254 | Flavodoxin/nitric oxide synthase |
| InterPro | IPR017938 | Riboflavin synthase-like beta-barrel |
| InterPro | IPR029039 | Flavoprotein-like superfamily |
| InterPro | IPR039261 | Ferredoxin-NADP reductase (FNR), nucleotide-binding domain |
| PFam | PF00258 | Flavodoxin/nitric oxide synthase |
| Superfamily | SSF52218 | Flavoprotein-like superfamily |
| Superfamily | SSF52343 | Ferredoxin-NADP reductase (FNR), nucleotide-binding domain |
| Superfamily | SSF63380 | Riboflavin synthase-like beta-barrel |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 14 | 61 | 30 | 64 |
| disruptive | 33 | 126 | 55 | 156 |
| missense | 17 | 106 | 44 | 122 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 24 | 107 | 55 | 60 |
| disruptive | 81 | 236 | 100 | 238 |
| missense | 47 | 185 | 73 | 156 |
PlasmoDB Total SNPs: 116
Non-coding: 30 | Synonymous: 53 | Nonsynonymous: 33 | 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 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 34494883 | A Prioritized and Validated Resource of Mitochondrial Proteins in PlasmodiumIdentifies Unique Biology. | van Esveld SL, Meerstein-Kessel L, ..., Huynen MA | 10.1128/mSphere.00614-21 |
| 38411047 | Delayed gametocyte clearance in Plasmodium vivax malaria is associated withpolymorphisms in the cytochrome P450 reductase (CPR) | Salazar YEAR, Louzada J, ..., Sousa TNd | 10.1128/aac.01204-23 |