Product Description: porphobilinogen deaminase
SignalP Peptide: MHLLSFLSFIIWFIHCTA
# Transmembrane Domains: 0
EC Numbers: 2.5.1.61 (Hydroxymethylbilane synthase);4.2.1.75 (Uroporphyrinogen-III synthase)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Component | GO:0005737 | cytoplasm |
| Function | GO:0004418 | hydroxymethylbilane synthase activity |
| Function | GO:0004852 | uroporphyrinogen-III synthase activity |
| Process | GO:0006783 | heme biosynthetic process |
| Process | GO:0006779 | porphyrin-containing compound biosynthetic process |
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 | not expressed | 0.01 | 0.99 |
| Trophozoite | not expressed | 0.03 | 0.98 |
| Schizont | possibly expressed | 0.05 | 0.96 |
| Gametocyte | expressed | 0.20 | 0.88 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1209600
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: 0.132 | MFS: -2.946 | #Insertions: 0
PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_0608000)
RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_0608000)
Modification: Disrupted | RMgm-4834
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I5V3
"Best" AlphaFill ligand hit: DPM (3-[5-{[3-(2-carboxyethyl)-4-(carboxymethyl)-5-methyl-1h-pyrrol-2-yl]methyl}-4-(carboxymethyl)-1h-pyrrol-3-yl]propanoic acid, Local RMSD=0.35) with 1GTK (Global RMSD=6.31)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 2.5.1.61 | hydroxymethylbilane synthase | NH4+VO2+NaBH4UO22+IodineanilineglycerolPb(NO3)2hydrazinemethylaminemethoxyaminehydroxylamine... |
| 4.2.1.75 | uroporphyrinogen-III synthase | NH4+PbCl2iodoacetamidehydroxylaminePhenylglyoxalUroporphyrinsiodoacetic acidCoproporphyrinsN-ethylmaleimideButane-2,3-dionediethyl dicarbonatesulphydryl reagents... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| P08397 | Porphobilinogen deaminase | OMA, OrthoDB | US9138423, 2,4-dimethyl-1H-pyrroleUS9138423, 2,5-dimethyl-1H-pyrrole |
Ortholog Group (OrthoMCL): OG6_101048
Most Similar Human Ortholog: F5H0P4
TM-align score: 0.93 | RMSD: 1.49
Seq Identity: 0.33 | Length: 224 / 435
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000256269 | hydroxymethylbilane synthase |
Protein Length: 435 | Molecular Weight (kDa): 50.348
PDB ID(s): None
Isoelectric Point: 10.04
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000860 | Porphobilinogen deaminase |
| InterPro | IPR022417 | Porphobilinogen deaminase, N-terminal |
| InterPro | IPR022418 | Porphobilinogen deaminase, C-terminal |
| InterPro | IPR036803 | Porphobilinogen deaminase, C-terminal domain superfamily |
| PFam | PF01379 | Porphobilinogen deaminase, N-terminal |
| PFam | PF03900 | Porphobilinogen deaminase, C-terminal |
| Superfamily | SSF53850 | Porphobilinogen deaminase, C-terminal domain superfamily |
| Superfamily | SSF54782 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 5 | 25 | 10 | 30 |
| disruptive | 10 | 63 | 32 | 89 |
| missense | 10 | 63 | 32 | 85 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 8 | 48 | 23 | 42 |
| disruptive | 21 | 135 | 55 | 104 |
| missense | 19 | 124 | 55 | 74 |
PlasmoDB Total SNPs: 64
Non-coding: 21 | Synonymous: 27 | Nonsynonymous: 16 | 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 |
| 17962188 | Unique properties of Plasmodium falciparum porphobilinogen deaminase. | Nagaraj VA, Arumugam R, ..., Padmanaban G | 10.1074/jbc.M706861200 |
| 30212465 | Integrative proteomics and bioinformatic prediction enable a high-confidenceapicoplast proteome in malaria parasites. | Boucher MJ, Ghosh S, ..., Yeh E | 10.1371/journal.pbio.2005895 |