Product Description: bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, putative
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 1.5.1.5 (Methylenetetrahydrofolate dehydrogenase (NADP(+)));3.5.4.9 (Methenyltetrahydrofolate cyclohydrolase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005829 | cytosol |
| Component | GO:0005739 | mitochondrion |
| Function | GO:0004477 | methenyltetrahydrofolate cyclohydrolase activity |
| Function | GO:0004488 | methylenetetrahydrofolate dehydrogenase (NADP+) activity |
| Process | GO:0006730 | one-carbon metabolic process |
| Process | GO:0035999 | tetrahydrofolate interconversion |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | possibly expressed | N/A | N/A |
| Ring | possibly expressed | 0.08 | 0.95 |
| Trophozoite | possibly expressed | 0.14 | 0.91 |
| Schizont | not expressed | 0.09 | 0.94 |
| Gametocyte | possibly expressed | 0.06 | 0.97 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0630700
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: -0.595 | #Insertions: 3
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: C6KTE2
"Best" AlphaFill ligand hit: No AlphaFill hits
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 1.5.1.5 | methylenetetrahydrofolate dehydrogenase (NADP+) | ATPGTPITPNAD+NADPHBorateguanineLY354899phosphatefolic acidiodoacetateformaldehyde... |
| 3.5.4.9 | methenyltetrahydrofolate cyclohydrolase | NADP+folatesuraminLY354899LY3745712',5'-ADPfolic acidaminopterinmethotrexatedihydrofolatePyridine nucleotidep-chloromercuribenzoate... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P13995 | Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial | OrthoDB | US11504368, Example 1US11504368, Example 2US11504368, Example 3US11504368, Example 4... |
Ortholog Group (OrthoMCL): OG6_100216
Most Similar Human Ortholog: Q5JYA3
TM-align score: 0.78 | RMSD: 2.62
Seq Identity: 0.15 | Length: 114 / 657
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000065911 | methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase |
| ENSG00000100714 | methylenetetrahydrofolate dehydrogenase, cyclohydrolase and formyltetrahydrofolate synthetase 1 |
| ENSG00000120254 | methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1 like |
| ENSG00000163738 | methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2 like |
Protein Length: 657 | Molecular Weight (kDa): 78.441
UniProt ID(s): C6KTE2
PDB ID(s): None
Isoelectric Point: 10.01
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000672 | Tetrahydrofolate dehydrogenase/cyclohydrolase |
| InterPro | IPR020630 | Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain |
| InterPro | IPR020631 | Tetrahydrofolate dehydrogenase/cyclohydrolase, NAD(P)-binding domain |
| InterPro | IPR036291 | NAD(P)-binding domain superfamily |
| PFam | PF00763 | Tetrahydrofolate dehydrogenase/cyclohydrolase, catalytic domain |
| PFam | PF02882 | Tetrahydrofolate dehydrogenase/cyclohydrolase, NAD(P)-binding domain |
| Superfamily | SSF51735 | NAD(P)-binding domain superfamily |
| Superfamily | SSF53223 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 6 | 22 | 15 | 33 |
| disruptive | 23 | 81 | 35 | 85 |
| missense | 23 | 81 | 34 | 80 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 9 | 51 | 16 | 35 |
| disruptive | 37 | 153 | 51 | 137 |
| missense | 34 | 134 | 41 | 111 |
PlasmoDB Total SNPs: 116
Non-coding: 72 | Synonymous: 16 | Nonsynonymous: 28 | 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 |
| 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 |