Genome location: Pf3D7_09_v3:775,058..780,804(+)
Genome classification: Core
Product Description: gamma-glutamylcysteine synthetase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 6.3.2.2 (Glutamate--cysteine ligase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Function | GO:0004357 | glutamate-cysteine ligase activity |
| Process | GO:0006750 | glutathione biosynthetic 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 | possibly expressed | 0.35 | 0.82 |
| Trophozoite | not expressed | 0.61 | 0.66 |
| Schizont | possibly expressed | 0.19 | 0.87 |
| Gametocyte | not expressed | 0.50 | 0.71 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0918900
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: 0.137 | MFS: -2.846 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0819800)
Modification: Disrupted | RMgm-1417
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I2W4
"Best" AlphaFill ligand hit: GSH (glutathione, Local RMSD=0.13) with 3LVW (Global RMSD=6.49)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 6.3.2.2 | glutamate-cysteine ligase | BRENDA SOAP query unsuccessful |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P48506 | Glutamate--cysteine ligase catalytic subunit | Homo sapiens | HOGENOM, OrthoDB | (2S)-2-ammonio-4-[(2-carboxylatobutyl)phosphinato]butanoate2-ammonio-4-[(2-carboxylatobutyl)sulfonyl]butanoateCHEMBL1627263 |
Ortholog Group (OrthoMCL): OG6_102076
Most Similar Human Ortholog: P48506
TM-align score: 0.91 | RMSD: 2.36
Seq Identity: 0.37 | Length: 604 / 1063
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000001084 | glutamate-cysteine ligase catalytic subunit |
Protein Length: 1063 | Molecular Weight (kDa): 124.463
UniProt ID(s): Q8I2W4, Q9TY17, Q9TYH5, Q9UB86
PDB ID(s): None
Isoelectric Point: 5.1
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR004308 | Glutamate-cysteine ligase catalytic subunit |
| InterPro | IPR014746 | Glutamine synthetase/guanido kinase, catalytic domain |
| PFam | PF03074 | Glutamate-cysteine ligase catalytic subunit |
| Superfamily | SSF55931 | Glutamine synthetase/guanido kinase, catalytic domain |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 8 | 61 | 26 | 71 |
| disruptive | 20 | 125 | 75 | 144 |
| missense | 17 | 112 | 70 | 120 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 16 | 109 | 41 | 77 |
| disruptive | 53 | 261 | 119 | 268 |
| missense | 44 | 224 | 90 | 158 |
PlasmoDB Total SNPs: 280
Non-coding: 216 | Synonymous: 44 | Nonsynonymous: 20 | 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 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 36627553 | Optimization of glutathione production in Saccharomyces cerevisiae HBSD-W08 usingPlackett-Burman and central composite rotatable designs | Hu X, Shen X, ..., Shuai Y | 10.1186/s12866-022-02742-4 |