Genome location: Pf3D7_11_v3:1,120,716..1,123,490(+)
Genome classification: Core
Product Description: spermidine synthase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.5.1.16 (Spermidine synthase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005829 | cytosol |
| Component | GO:0005739 | mitochondrion |
| Component | GO:0005634 | nucleus |
| Function | GO:0003723 | RNA binding |
| Function | GO:0004766 | spermidine synthase activity |
| Process | GO:0006596 | polyamine biosynthetic process |
| Process | GO:0008295 | spermidine 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 | expressed | 0.59 | 0.74 |
| Trophozoite | expressed | 1.63 | 0.28 |
| Schizont | expressed | 0.27 | 0.83 |
| Gametocyte | not expressed | 0.38 | 0.79 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1129000
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: 0.166 | MFS: -2.784 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_0919300)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PY17X_0921400)
Modification: Tagged | RMgm-5260
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8II73
"Best" AlphaFill ligand hit: 1PG (2-(2-{2-[2-(2-methoxy-ethoxy)-ethoxy]-ethoxy}-ethoxy)-ethanol, Local RMSD=0.13) with 2PSS (Global RMSD=0.81)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.5.1.16 | spermidine synthase | PCMBDTNBBerenilspermineagmatinearginineCGC-11144CGC-11157CGC-11158CGC-11160CGC-11038CGC-11098... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P19623 | Spermidine synthase | Homo sapiens | OMA, OrthoDB | CHEMBL608868CHEMBL608868CHEMBL330673 |
| Q99MI5 | Spermidine synthase | Rattus norvegicus | OrthoDB | CHEMBL608868CHEMBL330673CHEMBL315995CHEMBL330673 |
| Q9NFS5 | Spermidine synthase | Plasmodium falciparum | OrthoMCL, OrthoMCL BLAST | cis-4-methylcyclohexanamine |
Ortholog Group (OrthoMCL): OG6_100634
Most Similar Human Ortholog: P19623
TM-align score: 0.92 | RMSD: 2.12
Seq Identity: 0.43 | Length: 292 / 321
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000116649 | spermidine synthase |
Protein Length: 321 | Molecular Weight (kDa): 36.596
PDB ID(s): 2HTE, 2I7C, 2PSS, 2PT6, 2PT9, 2PWP, 3B7P, 3RIE, 4BP1, 4BP3, 4CWA, 4CXM, 4UOE, 6HY1, 6I1N
Isoelectric Point: 7.73
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001045 | Spermidine/spermine synthases |
| InterPro | IPR029063 | S-adenosyl-L-methionine-dependent methyltransferase |
| InterPro | IPR030373 | Polyamine biosynthesis domain, conserved site |
| InterPro | IPR035246 | Spermidine synthase, tetramerisation domain |
| PFam | PF01564 | Spermidine synthase, tetramerisation domain |
| PFam | PF17284 | |
| Superfamily | SSF53335 | S-adenosyl-L-methionine-dependent methyltransferase |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 4 | 15 | 11 | 19 |
| disruptive | 9 | 9 | 9 | 29 |
| missense | 9 | 9 | 8 | 24 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 7 | 29 | 22 | 17 |
| disruptive | 11 | 39 | 30 | 81 |
| missense | 9 | 33 | 24 | 62 |
PlasmoDB Total SNPs: 146
Non-coding: 130 | Synonymous: 8 | Nonsynonymous: 8 | 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 |
| 15913804 | The spermidine synthase of the malaria parasite Plasmodium falciparum: molecularand biochemical characterisation of the polyamine synthesis enzyme. | Haider N, Eschbach ML, ..., Luersen K | 10.1016/j.molbiopara.2005.04.004 |
| 17196392 | Structural and mechanistic insights into the action of Plasmodium falciparumspermidine synthase. | Burger PB, Birkholtz LM, ..., Louw AI | 10.1016/j.bmc.2006.12.017 |
| 17822713 | Crystal structure of Plasmodium falciparum spermidine synthase in complex withthe substrate decarboxylated S-adenosylmethionine and the potent inhibitors 4MCHAand AdoDATO. | Dufe VT, Qiu W, ..., Al-Karadaghi S | 10.1016/j.jmb.2007.07.053 |
| 25760598 | Three-dimensional structures of Plasmodium falciparum spermidine synthase withbound inhibitors suggest new strategies for drug design. | Sprenger J, Svensson B, ..., Al-Karadaghi S | 10.1107/S1399004714027011 |
| 30379851 | Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. | Briquet S, Ourimi A, ..., Vaquero C | 10.1371/journal.pone.0205596 |
| 33906926 | Functional Characterization of the m(6)A-Dependent Translational Modulator PfYTH | Sinha A, Baumgarten S, ..., Scherf A | 10.1128/mBio.00661-21 |
| 36983520 | Spermidine Synthase and Saccharopine Reductase Have Co-Expression Patterns Bothin Basidiomycetes with Fusion Form and Ascomycetes with Separate Form | Yang Y, Shi L, ..., Tao Y | 10.3390/jof9030352 |