Genome location: Pf3D7_09_v3:1,089,380..1,092,648(+)
Genome classification: Core
Product Description: glutamine-dependent NAD(+) synthetase, putative
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 6.3.1.5 (NAD(+) synthase);6.3.5.1 (NAD(+) synthase (glutamine-hydrolyzing))
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Function | GO:0003952 | NAD+ synthase (glutamine-hydrolyzing) activity |
| Function | GO:0004359 | glutaminase activity |
| Process | GO:0009435 | NAD 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 | 0.05 | 0.97 |
| Trophozoite | expressed | 0.22 | 0.86 |
| Schizont | expressed | 0.05 | 0.96 |
| Gametocyte | not expressed | 0.05 | 0.97 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0926700
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: 1 | MFS: -2.407 | #Insertions: 4
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_0827500)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0827500)
Modification: Disrupted | RMgm-2424
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I2P2
"Best" AlphaFill ligand hit: AMP (adenosine monophosphate, Local RMSD=0.19) with 1WXE (Global RMSD=2.40)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 6.3.1.5 | NAD+ synthase | RifampinthrombinadenosineampicillinDecoyinineMethicillindoxycyclineclotrimazoleCiprofloxacinPsicofuranineN-[8-(4-benzyloxyphenoxy)-1-octyl]-2-guanidino-2-phenylacetamide1-(4-benzyloxyphenoxy)-8-(2-guanidino-2-phenyl-1-ethyloxy)-octane... |
| 6.3.5.1 | NAD+ synthase (glutamine-hydrolysing) | gossypolazaserinep-chloromercuribenzoate6-diazo-5-oxo-L-norleucinediisopropyl fluorophosphatenicotinic acid-adenine dinucleotideadenosine 5'-[alpha,beta-methylene]triphosphate4-[([8-[5-(benzyloxy)-1H-indol-1-yl]octyl]oxy)carbonyl]-N,N,N-trimethylanilinium3-[([7-[5-(benzyloxy)-2-(methoxycarbonyl)-1H-indol-1-yl]heptyl]oxy)carbonyl]-1-methylpyridinium4-[([7-[5-(benzyloxy)-2-(methoxycarbonyl)-1H-indol-1-yl]heptyl]oxy)carbonyl]-N,N,N-trimethylanilinium4-[2-([9-[5-(benzyloxy)-2-(methoxycarbonyl)-1H-indol-1-yl]nonyl]oxy)-2-oxoethyl]-N,N,N-trimethylanilinium |
Orthology to BindingDB Entries:
Ortholog Group (OrthoMCL): OG6_100679
Most Similar Human Ortholog: E9PND0
TM-align score: 0.94 | RMSD: 0.96
Seq Identity: 0.28 | Length: 88 / 839
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000172890 | NAD synthetase 1 |
Protein Length: 839 | Molecular Weight (kDa): 97.764
UniProt ID(s): Q8I2P2
PDB ID(s): None
Isoelectric Point: 6.81
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR003694 | NAD(+) synthetase |
| InterPro | IPR022310 | NAD/GMP synthase |
| PFam | PF02540 | NAD/GMP synthase |
| Superfamily | SSF52402 | N/A |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 2 | 23 | 36 | 57 |
| disruptive | 16 | 72 | 39 | 121 |
| missense | 16 | 72 | 39 | 115 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 2 | 65 | 44 | 63 |
| disruptive | 27 | 154 | 71 | 167 |
| missense | 26 | 148 | 67 | 131 |
PlasmoDB Total SNPs: 128
Non-coding: 87 | Synonymous: 24 | Nonsynonymous: 17 | 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 |
| 24747974 | Targeting NAD+ metabolism in the human malaria parasite Plasmodium falciparum. | O'Hara JK, Kerwin LJ, ..., Llinas M | 10.1371/journal.pone.0094061 |