About Gene List

PF3D7_1456100 (SHMT)

Genome location: Pf3D7_14_v3:2,301,208..2,302,942(-)

Genome classification: Core

Function and Localization

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:0005739 mitochondrion
Function GO:0016597 amino acid binding
Function GO:0050897 cobalt ion binding
Function GO:0004372 glycine hydroxymethyltransferase activity
Function GO:0030170 pyridoxal phosphate binding
Function GO:0070905 serine binding
Function GO:0008270 zinc ion binding
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: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 0.01 0.99
Trophozoite not expressed 0.06 0.96
Schizont not expressed 0.00 1.00
Gametocyte not expressed 0.05 0.97

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1456100

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Mutable in CDS

MIS: 0.916 | MFS: -2.908 | #Insertions: 2

PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1319800)

  • Relative Growth Rate: 0.17 ± 0.07
  • Confidence: 6.67

RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1319800)

Modification: Disrupted | RMgm-3503

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8IKR8

"Best" AlphaFill ligand hit: PLP (pyridoxal-5'-phosphate, Local RMSD=0.07) with 6QVG (Global RMSD=4.26)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
2.1.2.1 glycine hydroxymethyltransferase KClSDSKCNDTTNaFGR1NAD+EDTAPCMBCTABNH2OHD1694...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_533449

No human ortholog(s)

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 0 18 13 40
disruptive 9 53 41 92
missense 9 52 39 83

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 5 41 24 50
disruptive 17 135 83 150
missense 16 119 67 105

PlasmoDB Total SNPs: 91

Non-coding: 63 | Synonymous: 17 | Nonsynonymous: 9 | Stop Codon: 2

Protein Information

Protein Length: 462 | Molecular Weight (kDa): 55.24

UniProt ID(s): Q8IKR8

PDB ID(s): None

Isoelectric Point: 8.34

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

Associated Publications

PMID Title Authors DOI/Link
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
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
33821563 Non-canonical metabolic pathways in the malaria parasite detected byisotope-tracing metabolomics. Cobbold SA, V Tutor M, ..., McConville MJ 10.15252/msb.202010023
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
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