Product Description: thioredoxin reductase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 1.8.1.9 (Thioredoxin-disulfide reductase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005739 | mitochondrion |
| Function | GO:0004791 | thioredoxin-disulfide reductase activity |
| Process | GO:0045454 | cell redox homeostasis |
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 | possibly expressed | nd | nd |
| Trophozoite | expressed | nd | nd |
| Schizont | expressed | nd | nd |
| Gametocyte | expressed | nd | nd |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0923800.2
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: 0.999 | MFS: -2.406 | #Insertions: 2
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_0824700)
Modification: Disrupted | RMgm-586
More info: PhenoPlasm Link
AlphaFill Uniprot ID: A0A143ZVU1
"Best" AlphaFill ligand hit: GSH (glutathione, Local RMSD=0.04) with 1GRA (Global RMSD=4.25)
BRENDA EC Inhibitors:
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q16881 | Thioredoxin reductase 1, cytoplasmic | HOGENOM, OrthoDB, OrthoMCL BLAST | US9018255, 3aUS9018255, L-3aUS9018255, D-3aUS9018255, 3b... | |
| P61076 | Thioredoxin reductase | Plasmodium falciparum (isolate 3D7) | HOGENOM, OMA, OrthoDB, OrthoMCL, OrthoMCL BLAST | CHEMBL383084CHEMBL383084CHEMBL383084CHEMBL380953... |
| Q962Y6 | Thioredoxin glutathione reductase | Schistosoma mansoni | HOGENOM, OrthoDB, OrthoMCL BLAST | CHEMBL3322356CHEMBL3322293CHEMBL3322292CHEMBL3322288... |
| Q9Z0J5 | Thioredoxin reductase 2, mitochondrial | Rattus norvegicus | OMA, OrthoDB, OrthoMCL BLAST | PseudohypericinPseudohypericin |
| P00390 | Glutathione reductase, mitochondrial | OrthoDB | KETOTIFENMeloxicam sodiumUS11028067, Example 2US11161815, Example 6... | |
| O15770 | Glutathione reductase | Plasmodium falciparum (isolate 3D7) | OrthoDB | CHEMBL135287CHEMBL135287methylthioninium chloride |
| P41921 | Glutathione reductase | Saccharomyces cerevisiae | OrthoDB | hypericum redPseudohypericin |
| Q86VQ6 | Thioredoxin reductase 3 | OrthoDB, OrthoMCL BLAST | CHEMBL32856CHEMBL3814977CHEMBL89232CHEMBL89366... | |
| A4HSF7 | Trypanothione reductase | OrthoDB | CHEMBL242165CHEMBL4105040CHEMBL4080816CHEMBL4076896... | |
| O89049 | Thioredoxin reductase 1, cytoplasmic | Rattus norvegicus | OrthoMCL BLAST | PseudohypericinPseudohypericinPseudohypericinCHEMBL4071967... |
Ortholog Group (OrthoMCL): OG6_100956
Most Similar Human Ortholog: A0A182DWF2
TM-align score: 0.96 | RMSD: 1.51
Seq Identity: 0.46 | Length: 484 / 617
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000184470 | thioredoxin reductase 2 |
| ENSG00000197763 | thioredoxin reductase 3 |
| ENSG00000198431 | thioredoxin reductase 1 |
Protein Length: 617 | Molecular Weight (kDa): 68.698
UniProt ID(s): P61076
Isoelectric Point: 8.82
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR004099 | Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain |
| InterPro | IPR006338 | Thioredoxin/glutathione reductase selenoprotein |
| InterPro | IPR012999 | Pyridine nucleotide-disulphide oxidoreductase, class I, active site |
| InterPro | IPR016156 | FAD/NAD-linked reductase, dimerisation domain superfamily |
| InterPro | IPR023753 | FAD/NAD(P)-binding domain |
| InterPro | IPR036188 | FAD/NAD(P)-binding domain superfamily |
| PFam | PF02852 | Pyridine nucleotide-disulphide oxidoreductase, dimerisation domain |
| PFam | PF07992 | FAD/NAD(P)-binding domain |
| Superfamily | SSF51905 | FAD/NAD(P)-binding domain superfamily |
| Superfamily | SSF55424 | FAD/NAD-linked reductase, dimerisation domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 27 | 23 | 45 |
| disruptive | 10 | 28 | 20 | 51 |
| missense | 9 | 27 | 18 | 48 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 6 | 72 | 32 | 32 |
| disruptive | 21 | 71 | 42 | 125 |
| missense | 16 | 56 | 36 | 103 |
PlasmoDB Total SNPs: 31
Non-coding: 12 | Synonymous: 10 | Nonsynonymous: 9 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 22889878 | Crystal structure of Plasmodium falciparum thioredoxin reductase, a validateddrug target. | Boumis G, Giardina G, ..., Miele AE | 10.1016/j.bbrc.2012.07.156 |
| 23845423 | Crystal structure of the Plasmodium falciparum thioredoxin reductase-thioredoxincomplex. | Fritz-Wolf K, Jortzik E, ..., Becker K | 10.1016/j.jmb.2013.06.037 |
| 26111176 | Plasmodium falciparum Thioredoxin Reductase (PfTrxR) and Its Role as a Target forNew Antimalarial Discovery. | McCarty SE, Schellenberger A, ..., Calderon AI | 10.3390/molecules200611459 |
| 27043496 | Preliminary LC-MS Based Screening for Inhibitors of Plasmodium falciparumThioredoxin Reductase (PfTrxR) among a Set of Antimalarials from the Malaria Box. | Tiwari NK, Reynolds PJ, Calderon AI | 10.3390/molecules21040424 |
| 29485860 | A Seleno Effect Differentiates the Roles of Redox Active Cysteine Residues inPlasmodium falciparum Thioredoxin Reductase. | O'Keefe JP, Dustin CM, ..., Hondal RJ | 10.1021/acs.biochem.8b00004 |