Product Description: orotidine 5'-phosphate decarboxylase
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 4.1.1.23 (Orotidine-5'-phosphate decarboxylase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Function | GO:0004590 | orotidine-5'-phosphate decarboxylase activity |
| Function | GO:0005515 | protein binding |
| Process | GO:0006207 | 'de novo' pyrimidine nucleobase biosynthetic 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 | expressed | 0.22 | 0.89 |
| Trophozoite | expressed | 0.28 | 0.83 |
| Schizont | expressed | 0.05 | 0.97 |
| Gametocyte | possibly expressed | 0.25 | 0.85 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1023200
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: 0.614 | MFS: -2.664 | #Insertions: 1
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_0507400)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_0507400)
Modification: Disrupted | RMgm-1969
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IJH3
"Best" AlphaFill ligand hit: XMP (xanthosine-5'-monophosphate, Local RMSD=0.08) with 3BPW (Global RMSD=0.62)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 4.1.1.23 | orotidine-5'-phosphate decarboxylase | BRENDA SOAP query unsuccessful |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q8T6J6 | Orotidine-5'-phosphate decarboxylase | Plasmodium falciparum | OMA, OrthoMCL, OrthoMCL BLAST | JMC521648 Compound 36JMC521648 Compound 376-aza-UMP6-aza-UMP |
| Q8I3Y0 | Orotate phosphoribosyltransferase | OrthoDB, OrthoMCL | OPRT inhibitor, 1 OPRT inhibitor, 2OPRT inhibitor, 3OPRT inhibitor, 4... | |
| P03962 | Orotidine 5'-phosphate decarboxylase | Saccharomyces cerevisiae | OrthoMCL | 6-aza-UMPCHEMBL253328CHEMBL11649536-hydroxy-UMP... |
| O26232 | Orotidine 5'-phosphate decarboxylase | Methanobacterium thermaggregans | OrthoMCL BLAST | JMC521648 Compound 36JMC521648 Compound 37JMC521648 Compound 36JMC521648 Compound 37... |
Ortholog Group (OrthoMCL): OG6_100519
Most Similar Human Ortholog: P11172
TM-align score: 0.64 | RMSD: 2.58
Seq Identity: 0.17 | Length: 230 / 323
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000114491 | uridine monophosphate synthetase |
Protein Length: 323 | Molecular Weight (kDa): 37.824
PDB ID(s): 2F84, 2Q8L, 2Q8Z, 2QAF, 3BAR, 3BPW, 3MWA, 3N2M, 3N34, 3N3M, 3S9Y
Isoelectric Point: 7.56
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR001754 | Orotidine 5'-phosphate decarboxylase domain |
| InterPro | IPR011060 | Ribulose-phosphate binding barrel |
| InterPro | IPR011995 | Orotidine 5'-phosphate decarboxylase, type 2 |
| InterPro | IPR018089 | Orotidine 5'-phosphate decarboxylase, active site |
| PFam | PF00215 | Orotidine 5'-phosphate decarboxylase domain |
| Superfamily | SSF51366 | Ribulose-phosphate binding barrel |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 2 | 14 | 5 | 18 |
| disruptive | 3 | 18 | 11 | 38 |
| missense | 3 | 18 | 11 | 34 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 6 | 23 | 7 | 22 |
| disruptive | 6 | 56 | 42 | 84 |
| missense | 6 | 45 | 41 | 66 |
PlasmoDB Total SNPs: 103
Non-coding: 87 | Synonymous: 13 | Nonsynonymous: 3 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 15683248 | A novel enzyme complex of orotate phosphoribosyltransferase and orotidine5'-monophosphate decarboxylase in human malaria parasite Plasmodium falciparum:physical association, kinetics, and inhibition characterization. | Krungkrai SR, DelFraino BJ, ..., Krungkrai J | 10.1021/bi048439h |
| 18303855 | Structure and inhibition of orotidine 5'-monophosphate decarboxylase fromPlasmodium falciparum. | Langley DB, Shojaei M, ..., Christopherson RI | 10.1021/bi702390k |
| 19800871 | Kinetic benefits and thermal stability of orotate phosphoribosyltransferase andorotidine 5'-monophosphate decarboxylase enzyme complex in human malaria parasitePlasmodium falciparum. | Kanchanaphum P, Krungkrai J | 10.1016/j.bbrc.2009.09.128 |
| 24507637 | A unique insertion of low complexity amino acid sequence underliesprotein-protein interaction in human malaria parasite orotatephosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase. | Imprasittichail W, Roytrakul S, Krungkrai SR, Krungkrail J | 10.1016/S1995-7645(14)60018-3 |
| 30279319 | Re-refinement of Plasmodium falciparum orotidine 5'-monophosphate decarboxylaseprovides a clearer picture of an important malarial drug target. | Novak WRP, West KHJ, Kirkman LMD, Brandt GS | 10.1107/S2053230X18010610 |
| 23980694 | Trypanosoma brucei (UMP synthase null mutants) are avirulent in mice, but recovervirulence upon prolonged culture in vitro while retaining pyrimidine auxotrophy | Ong HB, Sienkiewicz N, ..., Fairlamb AH | 10.1111/mmi.12376 |
| 28389349 | Bifunctional activity of fused Plasmodium falciparum orotatephosphoribosyltransferase and orotidine 5'-monophosphate decarboxylase | Paojinda P, Imprasittichai W, ..., Krungkrai J | 10.1016/j.parint.2017.04.003 |
| 25776745 | Nonreplicating, cyst-defective type II Toxoplasma gondii vaccine strainsstimulate protective immunity against acute and chronic infection | Fox BA, Bzik DJ | 10.1128/IAI.02756-14 |
| 37322556 | A live attenuated RHDeltaompdcDeltauprt mutant of Toxoplasma gondii induces strongprotective immunity against toxoplasmosis in mice and cats | Shen Y, Zheng B, ..., Lu S | 10.1186/s40249-023-01109-9 |