About Gene List

PF3D7_1213800 (PRS)

Genome location: Pf3D7_12_v3:589,729..593,777(-)

Genome classification: Core

Function and Localization

Product Description: proline--tRNA ligase

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 6.1.1.15 (Proline--tRNA ligase)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0017101 aminoacyl-tRNA synthetase multienzyme complex
Component GO:0005737 cytoplasm
Component GO:0005634 nucleus
Function GO:0043906 Ala-tRNA(Pro) hydrolase activity
Function GO:0004827 proline-tRNA ligase activity
Process GO:0006433 prolyl-tRNA aminoacylation
Process GO:0042493 response to drug
Process GO:0009410 response to xenobiotic stimulus
Process GO:0006418 tRNA aminoacylation for protein translation

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 0.44 0.78
Trophozoite expressed 0.74 0.59
Schizont expressed 0.12 0.92
Gametocyte expressed 0.27 0.84

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1213800

Resistome Missense Mutations: L482F, T512S

Resistome Compounds with Missense Mutations: Halofuginone, NCP26

Resistome # Samples with Disruptive Mutations: 5 (5 missense, 5 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Non - Mutable in CDS

MIS: 0.12 | MFS: -3.106 | #Insertions: 0

PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1429600)

  • Relative Growth Rate: 0.14 ± 0.17
  • Confidence: 4.93

RMgmDB ABS Phenotype: N/A

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8I5R7

"Best" AlphaFill ligand hit: BU1 (1,4-butanediol, Local RMSD=0.03) with 7V9D (Global RMSD=0.87)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
6.1.1.15 proline-tRNA ligase KClNH4ClPyrroleL-prolineglyburideL-cysteinecysteamine3-pyrrolinePyrrolidinefebrifuginehalofuginoneTCMDC-124506...

Orthology to BindingDB Entries:

UniProt Protein Name Species Homology Source BindingDB Ligands
Q8I5R7 Proline--tRNA ligase HOGENOM, OMA, OrthoDB, OrthoMCL, OrthoMCL BLAST CHEMBL322782
P07814 Bifunctional glutamate/proline--tRNA ligase Homo sapiens OrthoDB CHEMBL357355CHEMBL357355

Orthology Information

Ortholog Group (OrthoMCL): OG6_100749

Most Similar Human Ortholog: P07814

TM-align score: 0.74 | RMSD: 3.74

Seq Identity: 0.44 | Length: 601 / 746

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000136628 glutamyl-prolyl-tRNA synthetase 1

Protein Information

Protein Length: 746 | Molecular Weight (kDa): 86.647

UniProt ID(s): A0A144A0G8, Q8I5R7

PDB ID(s): 4NCX, 4OLF, 4Q15, 4TWA, 4WI1, 4YDQ, 5IFU, 6T7K, 7F96, 7F97, 7QB7, 7QC1, 7QC2, 7V9D

Isoelectric Point: 7.4

Protein Domain Annotations:

Source Family ID Description
InterPro IPR002314 Aminoacyl-tRNA synthetase, class II (G/ P/ S/T)
InterPro IPR002316 Proline-tRNA ligase, class IIa
InterPro IPR004154 Anticodon-binding
InterPro IPR004499 Proline-tRNA ligase, class IIa, archaeal-type
InterPro IPR007214 YbaK/aminoacyl-tRNA synthetase-associated domain
InterPro IPR016061 Proline-tRNA ligase, class II, C-terminal
InterPro IPR017449 Prolyl-tRNA synthetase, class II
InterPro IPR033721 Prolyl-tRNA synthetase, catalytic domain
InterPro IPR036754 YbaK/aminoacyl-tRNA synthetase-associated domain superfamily
PFam PF00587 Aminoacyl-tRNA synthetase, class II (G/ P/ S/T)
PFam PF03129 Anticodon-binding
PFam PF04073 YbaK/aminoacyl-tRNA synthetase-associated domain
PFam PF09180 Proline-tRNA ligase, class II, C-terminal
Superfamily SSF52954 YbaK/aminoacyl-tRNA synthetase-associated domain superfamily
Superfamily SSF55681 Prolyl-tRNA synthetase, class II
Superfamily SSF55826
Superfamily SSF64586

Genetic Variation

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

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 9 36 24 47
disruptive 14 47 29 88
missense 8 40 23 68

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 19 75 29 46
disruptive 28 119 82 148
missense 18 77 62 88

PlasmoDB Total SNPs: 152

Non-coding: 123 | Synonymous: 19 | Nonsynonymous: 10 | Stop Codon: 0

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
22355703 Uneven spread of cis- and trans-editing aminoacyl-tRNA synthetase domains withintranslational compartments of P. falciparum. Khan S, Sharma A, ..., Sharma A 10.1038/srep00188
25047712 Structural and functional analysis of the anti-malarial drug target prolyl-tRNAsynthetase. Jain V, Kikuchi H, ..., Yogavel M 10.1007/s10969-014-9186-x
25395010 A genomic and evolutionary approach reveals non-genetic drug resistance inmalaria. Herman JD, Rice DP, ..., Wirth DF 10.1186/PREACCEPT-1067113631444973
30379851 Identification of Plasmodium falciparum nuclear proteins by mass spectrometry andproposed protein annotation. Briquet S, Ourimi A, ..., Vaquero C 10.1371/journal.pone.0205596