Genome location: Pf3D7_14_v3:2,194,694..2,198,480(-)
Genome classification: Core
Product Description: NAD(P) transhydrogenase, putative
SignalP Peptide: MYRNIFASIILCLLLFLSSNCYG
# Transmembrane Domains: 12
EC Numbers: 1.4.1.1 (Alanine dehydrogenase);1.6.1.1 (NAD(P)(+) transhydrogenase (Si-specific));1.6.1.2 (NAD(P)(+) transhydrogenase (Re/Si-specific));7.1.1.1 (Proton-translocating NAD(P)(+) transhydrogenase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Component | GO:0044312 | crystalloid |
| Component | GO:0016021 | integral component of membrane |
| Component | GO:0005739 | mitochondrion |
| Function | GO:0051287 | NAD binding |
| Function | GO:0008746 | NAD(P)+ transhydrogenase activity |
| Function | GO:0050661 | NADP binding |
| Process | GO:0006740 | NADPH regeneration |
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 | 0.03 | 0.98 |
| Trophozoite | possibly expressed | 0.03 | 0.98 |
| Schizont | expressed | 0.02 | 0.99 |
| Gametocyte | expressed | 0.42 | 0.79 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1453500
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: 0.246 | MFS: -2.681 | #Insertions: 0
PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_1317200)
RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_1317200)
Modification: Mutated | RMgm-4730
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IKU3
"Best" AlphaFill ligand hit: NAP (nadp nicotinamide-adenine-dinucleotide phosphate, Local RMSD=0.01) with 4J16 (Global RMSD=2.63)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 1.4.1.1 | alanine dehydrogenase | GTPKClDTTNAD+NADHEDTANH4+PCMBDTNBNADPHHgCl2MgCl2... |
| 1.6.1.1 | NAD(P)+ transhydrogenase (Si-specific) | ATPADPGTPCTPDTTTTPNAD+EDTADMSONADPHNADP+5'-AMP... |
| 1.6.1.2 | NAD(P)+ transhydrogenase (Re/Si-specific) | ADPCoAD2ONAD+NADHNADPHNADP+5'-AMP3'-AMP2'-AMProtenoneadenosine... |
| 7.1.1.1 | proton-translocating NAD(P)+ transhydrogenase | NADHNADPHNADP+5'-AMP2'-AMPNAD(P)+valinomycinN-ethylmaleimideButane-2,3-dioneDicyclohexylcarbodiimideN,N'-dicyclohexylcarbodiimideN,N'-Dicylclohexylcarbodiimide... |
No evidence of orthology to BindingDB entries
Ortholog Group (OrthoMCL): OG6_101345
Most Similar Human Ortholog: A0A590UJM2
TM-align score: 0.77 | RMSD: 3.04
Seq Identity: 0.34 | Length: 409 / 1176
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000112992 | nicotinamide nucleotide transhydrogenase |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 8 | 76 | 33 | 77 |
| disruptive | 7 | 78 | 40 | 103 |
| missense | 7 | 77 | 39 | 97 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 15 | 132 | 65 | 71 |
| disruptive | 20 | 154 | 69 | 162 |
| missense | 18 | 133 | 64 | 143 |
PlasmoDB Total SNPs: 87
Non-coding: 23 | Synonymous: 47 | Nonsynonymous: 17 | Stop Codon: 0
Protein Length: 1176 | Molecular Weight (kDa): 131.29
UniProt ID(s): Q8IKU3
PDB ID(s): None
Isoelectric Point: 6.75
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR007698 | Alanine dehydrogenase/pyridine nucleotide transhydrogenase, NAD(H)-binding domain |
| InterPro | IPR007886 | Alanine dehydrogenase/pyridine nucleotide transhydrogenase, N-terminal |
| InterPro | IPR008143 | Alanine dehydrogenase/pyridine nucleotide transhydrogenase, conserved site-2 |
| InterPro | IPR024605 | NAD(P) transhydrogenase, alpha subunit, C-terminal |
| InterPro | IPR029035 | DHS-like NAD/FAD-binding domain superfamily |
| InterPro | IPR034300 | NADP transhydrogenase beta-like domain |
| InterPro | IPR036291 | NAD(P)-binding domain superfamily |
| PFam | PF01262 | Alanine dehydrogenase/pyridine nucleotide transhydrogenase, NAD(H)-binding domain |
| PFam | PF02233 | NADP transhydrogenase beta-like domain |
| PFam | PF05222 | Alanine dehydrogenase/pyridine nucleotide transhydrogenase, N-terminal |
| PFam | PF12769 | NAD(P) transhydrogenase, alpha subunit, C-terminal |
| Superfamily | SSF51735 | NAD(P)-binding domain superfamily |
| Superfamily | SSF52283 | DHS-like NAD/FAD-binding domain superfamily |
| Superfamily | SSF52467 |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 31951090 | NAD(P) transhydrogenase has vital non-mitochondrial functions in malaria parasitetransmission. | Saeed S, Tremp AZ, ..., Dessens JT | 10.15252/embr.201947832 |