Genome location: Pf3D7_12_v3:1,483,501..1,486,097(+)
Genome classification: Core
Product Description: serine hydroxymethyltransferase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 2.1.2.1 (Glycine hydroxymethyltransferase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005739 | mitochondrion |
| Function | GO:0016597 | amino acid binding |
| Function | GO:0050897 | cobalt ion binding |
| Function | GO:0004372 | glycine hydroxymethyltransferase activity |
| Function | GO:0042803 | protein homodimerization activity |
| Function | GO:0030170 | pyridoxal phosphate binding |
| Function | GO:0070905 | serine binding |
| Function | GO:0008270 | zinc ion binding |
| Process | GO:0070178 | D-serine metabolic process |
| Process | GO:0006565 | L-serine catabolic process |
| Process | GO:1904482 | cellular response to tetrahydrofolate |
| Process | GO:0046655 | folic acid metabolic process |
| Process | GO:0019264 | glycine biosynthetic process from serine |
| Process | GO:0006544 | glycine metabolic process |
| Process | GO:0006730 | one-carbon metabolic process |
| Process | GO:0035999 | tetrahydrofolate interconversion |
| Process | GO:0046653 | tetrahydrofolate metabolic 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 | not expressed | 0.06 | 0.97 |
| Trophozoite | expressed | 0.56 | 0.68 |
| Schizont | expressed | 0.31 | 0.80 |
| Gametocyte | expressed | 0.34 | 0.80 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1235600
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: 0.126 | MFS: -2.803 | #Insertions: 0
PlasmoGEM Phenotype: N/A
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1450200)
Modification: Mutated | RMgm-5224
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I566
"Best" AlphaFill ligand hit: PLP (pyridoxal-5'-phosphate, Local RMSD=0.08) with 7E13 (Global RMSD=2.15)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.1.2.1 | glycine hydroxymethyltransferase | KClSDSKCNDTTNaFGR1NAD+EDTAPCMBCTABNH2OHD1694... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q9U638 | Glycine hydroxymethyltransferase | OMA, OrthoMCL, OrthoMCL BLAST | CHEMBL4089096CHEMBL4073903CHEMBL4064002CHEMBL4085568... | |
| P34896 | Serine hydroxymethyltransferase, cytosolic | Homo sapiens | OrthoDB | US10934305, Compound 68US10934305, Compound 11US10934305, Compound 71US10934305, Compound 72... |
| P34897 | Serine hydroxymethyltransferase, mitochondrial [30-504] | OrthoDB | US10934305, Compound 4US10934305, Compound 68US10934305, Compound 1US10934305, Compound 1... |
Ortholog Group (OrthoMCL): OG6_100262
Most Similar Human Ortholog: P34896
TM-align score: 0.99 | RMSD: 0.84
Seq Identity: 0.47 | Length: 442 / 442
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000176974 | serine hydroxymethyltransferase 1 |
| ENSG00000182199 | serine hydroxymethyltransferase 2 |
| ENSG00000284320 | serine hydroxymethyltransferase 1 |
Protein Length: 442 | Molecular Weight (kDa): 49.78
PDB ID(s): 4O6Z
Isoelectric Point: 8.06
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001085 | Serine hydroxymethyltransferase |
| InterPro | IPR015424 | Pyridoxal phosphate-dependent transferase |
| InterPro | IPR039429 | Serine hydroxymethyltransferase-like domain |
| PFam | PF00464 | Serine hydroxymethyltransferase-like domain |
| 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 | 20 | 6 | 27 |
| disruptive | 2 | 13 | 6 | 16 |
| missense | 2 | 10 | 4 | 10 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 11 | 39 | 17 | 18 |
| disruptive | 12 | 23 | 20 | 45 |
| missense | 8 | 14 | 17 | 32 |
PlasmoDB Total SNPs: 93
Non-coding: 85 | Synonymous: 6 | Nonsynonymous: 2 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 11197757 | Characterization of three genes encoding enzymes of the folate biosyntheticpathway in Plasmodium falciparum. | Lee CS, Salcedo E, ..., Hyde JE | 10.1017/s0031182000006946 |
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 19591881 | Characterization of Plasmodium falciparum serine hydroxymethyltransferase-Apotential antimalarial target. | Maenpuen S, Sopitthummakhun K, ..., Leartsakulpanich U | 10.1016/j.molbiopara.2009.06.010 |
| 19591883 | Catalytic and ligand-binding characteristics of Plasmodium falciparum serinehydroxymethyltransferase. | Pang CK, Hunter JH, ..., Rathod PK | 10.1016/j.molbiopara.2009.06.011 |
| 21129192 | Dynamic subcellular localization of isoforms of the folate pathway enzyme serinehydroxymethyltransferase (SHMT) through the erythrocytic cycle of Plasmodiumfalciparum. | Read M, Muller IB, ..., Hyde JE | 10.1186/1475-2875-9-351 |
| 24524072 | Vitamin B6-dependent enzymes in the human malaria parasite Plasmodium falciparum:a druggable target? | Kronenberger T, Lindner J, ..., Wrenger C | 10.1155/2014/108516 |
| 38052329 | Engineering serine hydroxymethyltransferases for efficient synthesis of L-serinein Escherichia coli | Teng Z, Pan X, ..., Rao Z | 10.1016/j.biortech.2023.130153 |
| 37820886 | A first-in-class dimethyl 2-acetamido terephthalate inhibitor targeting Conyzacanadensis SHMT1 with a novel herbicidal mode-of-action | Luo D, Bai Z, ..., Li Z | 10.1016/j.jare.2023.10.003 |
| 37543353 | Mangiferin is a new potential antimalarial and anticancer drug for targetingserine hydroxymethyltransferase | Maenpuen S, Mee-Udorn P, ..., Chitnumsub P | 10.1016/j.abb.2023.109712 |
| 37700610 | Novel tetrahydrofolate-dependent d-serine dehydratase activity of serine hydroxymethyltransferases | Miyamoto T, Fushinobu S, ..., Homma H | 10.1111/febs.16953 |
| 37810721 | In Silico and In Vitro Potential of FDA-Approved Drugs for Antimalarial DrugRepurposing against Plasmodium Serine Hydroxymethyltransferases | Mee-Udorn P, Phiwkaow K, ..., Rungrotmongkol T | 10.1021/acsomega.3c01309 |
| 36896963 | Serine hydroxymethyl transferase is required for optic lobe neuroepitheliadevelopment in Drosophila | Silva EAB, Venda AM, Homem CCF | 10.1242/dev.201152 |
| 38171331 | Serine synthesis via reversed SHMT2 activity drives glycine depletion andacetaminophen hepatotoxicity in MASLD | Ghrayeb A, Finney AC, ..., Gottlieb E | 10.1016/j.cmet.2023.12.013 |
| 37183313 | A gene-nutrient interaction between vitamin B6 and serine hydroxymethyltransferase (SHMT) affects genome integrity in Drosophila | Pilesi E, Angioli C, ..., Verni F | 10.1002/jcp.31033 |
| 37532884 | Revealing protonation states and tracking substrate in serine hydroxymethyltransferase with room-temperature X-ray and neutron crystallography | Drago VN, Campos C, ..., Kovalevsky A | 10.1038/s42004-023-00964-9 |
| 38171330 | Glycine homeostasis requires reverse SHMT flux | McBride MJ, Hunter CJ, ..., Rabinowitz JD | 10.1016/j.cmet.2023.12.001 |