Genome location: Pf3D7_12_v3:1,915,513..1,918,080(+)
Genome classification: Core
Product Description: delta-aminolevulinic acid synthetase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.3.1.37 (5-aminolevulinate synthase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005739 | mitochondrion |
| Function | GO:0003870 | 5-aminolevulinate synthase activity |
| Process | GO:0006783 | heme biosynthetic process |
| Process | GO:0001666 | response to hypoxia |
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 | not expressed | 0.05 | 0.97 |
| Trophozoite | expressed | 0.07 | 0.96 |
| Schizont | not expressed | 0.04 | 0.98 |
| Gametocyte | expressed | 0.35 | 0.79 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1246100
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: 0.177 | MFS: -2.8 | #Insertions: 0
PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_1459200)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1459200)
Modification: Disrupted | RMgm-5262
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I4X1
"Best" AlphaFill ligand hit: SCA (succinyl-coenzyme a, Local RMSD=0.03) with 2BWO (Global RMSD=1.54)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.3.1.37 | 5-aminolevulinate synthase | ATPCoAGTPFeCl3heminlightacetatecyanideaspirinlithiumpyruvatemorphine... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P22557 | 5-aminolevulinate synthase, erythroid-specific, mitochondrial | HOGENOM, OrthoDB | US11479532, Compound SZ10TA40US11479532, Compound SZ12TA42 | |
| O15270 | Serine palmitoyltransferase 2 | Homo sapiens | OrthoDB | CHEMBL1241090CHEMBL4226297CHEMBL4229253CHEMBL4226045... |
| O15269 | Serine palmitoyltransferase 1 | Homo sapiens | OrthoDB | CHEMBL1241090CHEMBL4541898CHEMBL4584997CHEMBL4541898... |
Ortholog Group (OrthoMCL): OG6_100359
Most Similar Human Ortholog: O75600
TM-align score: 0.84 | RMSD: 2.31
Seq Identity: 0.29 | Length: 375 / 630
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000023330 | 5-aminolevulinate synthase 1 |
| ENSG00000100116 | glycine C-acetyltransferase |
| ENSG00000158578 | 5-aminolevulinate synthase 2 |
Protein Length: 630 | Molecular Weight (kDa): 73.547
PDB ID(s): None
Isoelectric Point: 9.63
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001917 | Aminotransferase, class-II, pyridoxal-phosphate binding site |
| InterPro | IPR004839 | Aminotransferase, class I/classII |
| InterPro | IPR010961 | Tetrapyrrole biosynthesis, 5-aminolevulinic acid synthase |
| InterPro | IPR015424 | Pyridoxal phosphate-dependent transferase |
| PFam | PF00155 | Aminotransferase, class I/classII |
| Superfamily | SSF53383 | Pyridoxal phosphate-dependent transferase |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 5 | 25 | 19 | 43 |
| disruptive | 4 | 29 | 30 | 77 |
| missense | 4 | 29 | 28 | 71 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 10 | 56 | 27 | 47 |
| disruptive | 11 | 110 | 57 | 158 |
| missense | 8 | 96 | 52 | 107 |
PlasmoDB Total SNPs: 112
Non-coding: 78 | Synonymous: 27 | Nonsynonymous: 7 | 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 |
| 15144063 | Enzymes for heme biosynthesis are found in both the mitochondrion and plastid ofthe malaria parasite Plasmodium falciparum. | Sato S, Clough B, Coates L, Wilson RJ | 10.1078/1434461000169 |
| 25352601 | The heme biosynthesis pathway is essential for Plasmodium falciparum developmentin mosquito stage but not in blood stages. | Ke H, Sigala PA, ..., Vaidya AB | 10.1074/jbc.M114.615831 |
| 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 |
| 38315033 | mSphere of Influence: Compartmentalized cAMP signals in American trypanosomes | Lander N | 10.1128/msphere.00635-23 |