Genome location: Pf3D7_03_v3:523,023..528,087(-)
Genome classification: Core
Product Description: glycogen synthase kinase-3 beta
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.7.11.1 (Non-specific serine/threonine protein kinase);2.7.11.26 ([Tau protein] kinase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020036 | Maurer's cleft |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0034399 | nuclear periphery |
| Function | GO:0004674 | protein serine/threonine kinase activity |
| Process | GO:0048469 | cell maturation |
| Process | GO:0044409 | entry into host |
| Process | GO:0009410 | response to xenobiotic stimulus |
| Process | GO:0007165 | signal transduction |
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 | 0.11 | 0.94 |
| Trophozoite | expressed | 0.78 | 0.57 |
| Schizont | expressed | 0.74 | 0.58 |
| Gametocyte | expressed | 0.90 | 0.52 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0312400
Resistome Missense Mutations: None
Resistome Compounds with Missense Mutations: None
Resistome # Samples with Disruptive Mutations: 1 (0 missense, 0 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.152 | MFS: -2.791 | #Insertions: 0
PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_0410400)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0410400)
Modification: Disrupted | RMgm-1890
More info: PhenoPlasm Link
AlphaFill Uniprot ID: O77344
"Best" AlphaFill ligand hit: 2AN (8-anilino-1-naphthalene sulfonate, Local RMSD=0.09) with 3PXF (Global RMSD=4.69)
BRENDA EC Inhibitors:
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| O77344 | Glycogen synthase kinase 3 | Plasmodium falciparum (isolate 3D7) | HOGENOM, OMA, OrthoDB, OrthoMCL, OrthoMCL BLAST | HymenialdisineCHEMBL5208060CHEMBL2313853IKK-16... |
| Q9WV60 | Glycogen synthase kinase-3 beta | Mus musculus | HOGENOM, OMA, OrthoDB | TWS-119TWS-119TWS-119TWS-119... |
| P49841 | Glycogen synthase kinase-3 beta | Homo sapiens | HOGENOM, OMA, OrthoDB | CDK Inhibitor, 1pyrazolo[1,5-b]pyridazine deriv. 16pyrazolo[1,5-b]pyridazine deriv. 18pyrazolo[1,5-b]pyridazine deriv. 19... |
| G1T8E2 | Glycogen synthase kinase-3 beta [7-25] | Oryctolagus cuniculus | HOGENOM | Pyrazine-Pyridine deriv. 15Pyrazine-Pyridine deriv. 15Pyrazine-Pyridine Biheteroaryl 39Pyrazine-Pyridine Biheteroaryl 56... |
| A0A0D1CGS9 | Putative glycogen synthase kinase 3 alpha | OMA, OrthoDB, OrthoMCL | PIK-75, 1GSK3 Inhibitor, 2diaryl urea compound 10Hit compound, 8... | |
| B2LUN4 | Glycogen synthase kinase-3 beta/[Tau protein] kinase | OrthoDB | CHEMBL1910191CHEMBL1910192CHEMBL1910195CHEMBL1910196... | |
| P18266 | Glycogen synthase kinase-3 beta | Rattus norvegicus | OrthoDB | Paullone Analog 1Paullone Analog 2Paullone Analog 3Paullone Analog 4... |
| I6YP72 | Glycogen synthase kinase-3 beta | Porcellium fiumanum | OrthoDB | Indirubin derivative, 1Indirubin-3 -monoximeindirubin-3 -acetoximeindirubin deriv. 9b... |
| P49840 | Glycogen synthase kinase-3 alpha | Homo sapiens | OrthoDB | 4-arylmaleimide deriv. 6a4-arylmaleimide deriv. 6b4-arylmaleimide deriv. 6c4-arylmaleimide deriv. 6d... |
Ortholog Group (OrthoMCL): OG6_100482
Most Similar Human Ortholog: A0A7I2V2I5
TM-align score: 0.98 | RMSD: 0.31
Seq Identity: 0.71 | Length: 45 / 440
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000082701 | glycogen synthase kinase 3 beta |
| ENSG00000105723 | glycogen synthase kinase 3 alpha |
Protein Length: 440 | Molecular Weight (kDa): 51.616
UniProt ID(s): O77344
PDB ID(s): None
Isoelectric Point: 5.27
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000719 | Protein kinase domain |
| InterPro | IPR008271 | Serine/threonine-protein kinase, active site |
| InterPro | IPR011009 | Protein kinase-like domain superfamily |
| InterPro | IPR017441 | Protein kinase, ATP binding site |
| InterPro | IPR039192 | Glycogen synthase kinase 3, catalytic domain |
| PFam | PF00069 | Protein kinase domain |
| Superfamily | SSF56112 | Protein kinase-like domain superfamily |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
No passing variants found
PlasmoDB Total SNPs: 432
Non-coding: 408 | Synonymous: 21 | Nonsynonymous: 1 | Stop Codon: 2
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 10448855 | The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum. | Bowman S, Lawson D, ..., Barrell BG | 10.1038/22964 |
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 15023360 | Plasmodium falciparum glycogen synthase kinase-3: molecular model, expression,intracellular localisation and selective inhibitors. | Droucheau E, Primot A, ..., Meijer L | 10.1016/j.bbapap.2003.11.023 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 25861860 | Selective inhibitors of Plasmodium falciparum glycogen synthase-3 (PfGSK-3): Newantimalarial agents? | Masch A, Kunick C | 10.1016/j.bbapap.2015.03.013 |
| 35961464 | Functional inactivation of Plasmodium falciparum glycogen synthase kinase GSK3modulates erythrocyte invasion and blocks gametocyte maturation. | Alder A, Wilcke L, ..., Gilberger TW | 10.1016/j.jbc.2022.102360 |