Genome location: Pf3D7_13_v3:1,360,971..1,367,998(+)
Genome classification: Core
Product Description: ubiquitin-activating enzyme
SignalP Peptide: N/A
# Transmembrane Domains: 3
EC Numbers: 6.2.1.45 (E1 ubiquitin-activating enzyme)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0020011 | apicoplast |
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005634 | nucleus |
| Function | GO:0016887 | ATP hydrolysis activity |
| Function | GO:0019781 | NEDD8 activating enzyme activity |
| Function | GO:0004842 | ubiquitin-protein transferase activity |
| Process | GO:0032446 | protein modification by small protein conjugation |
| Process | GO:0045116 | protein neddylation |
| Process | GO:0016567 | protein ubiquitination |
| Process | GO:0010564 | regulation of cell cycle process |
| Process | GO:0009410 | response to xenobiotic stimulus |
| Process | GO:0030433 | ubiquitin-dependent ERAD pathway |
Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):
| Stage | LR class | MCA mean | MCA prop. zeros |
|---|---|---|---|
| Sporozoite | expressed | N/A | N/A |
| Ring | expressed | 0.15 | 0.92 |
| Trophozoite | expressed | 0.66 | 0.64 |
| Schizont | expressed | 0.38 | 0.78 |
| Gametocyte | possibly expressed | 0.39 | 0.78 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1333200
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: 0.125 | MFS: -2.915 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1347900)
RMgmDB ABS Phenotype: N/A
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IDZ6
"Best" AlphaFill ligand hit: POP (pyrophosphate 2-, Local RMSD=0.45) with 6DC6 (Global RMSD=4.22)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 6.2.1.45 | E1 ubiquitin-activating enzyme | LMO2PYR-41AtMUB3largazoletrichostatin Aginsenoside Reginsenoside Rg1[ubiquitin carrier protein Ubc4]-L-cysteine5'-[[(L-cysteinylglycylglycyl)sulfamoyl]amino]-5'-deoxyadenosine1-(3-chloro-4-fluorophenyl)-4-[(5-nitro-2-furyl)methylene]-3,5-pyrazolidinedione4[4-(5-nitro-furan-2-ylmethylene)-3,5-dioxo-pyrazolidin-1-yl]-benzoic acid ethyl ester(5R,8S)-11-ethenyl-5-methyl-8-(propan-2-yl)-10-oxa-3,17-dithia-7,14,19,20-tetraazatricyclo[14.2.1.1~2,5~]icosa-1(18),2(20),16(19)-triene-6,9,13-trione... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| A0AVT1 | Ubiquitin-like modifier-activating enzyme 6 | Homo sapiens | OrthoDB | US9593121, 1-01US9593121, I-02US9593121, I-03US9593121, I-04... |
| P41226 | Ubiquitin-like modifier-activating enzyme 7 | Homo sapiens | OrthoDB | CHEMBL2017005 |
| Q9UBT2 | SUMO-activating enzyme subunit 2 | OrthoDB | US9796725, Compound I-001US9796725, Compound I-098US9796725, Compound I-003US9796725, Compound I-004... | |
| P22314 | Ubiquitin-like modifier-activating enzyme 1 | Homo sapiens | OrthoDB | Compound ICompound ICompound IUS9796725, Compound I-001... |
| Q8TBC4 | NEDD8-activating enzyme E1 catalytic subunit | OrthoDB | MITOXANTRONEPevonedistatCHEMBL4878088CHEMBL4865086... |
Protein Length: 1838 | Molecular Weight (kDa): 218.525
UniProt ID(s): Q8IDZ6
PDB ID(s): None
Isoelectric Point: 9.29
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000011 | Ubiquitin/SUMO-activating enzyme E1 |
| InterPro | IPR000594 | THIF-type NAD/FAD binding fold |
| InterPro | IPR019572 | Ubiquitin-activating enzyme, catalytic cysteine domain |
| InterPro | IPR035985 | Ubiquitin-activating enzyme |
| PFam | PF00899 | THIF-type NAD/FAD binding fold |
| PFam | PF10585 | Ubiquitin-activating enzyme, catalytic cysteine domain |
| Superfamily | SSF69572 | Ubiquitin-activating enzyme |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 13 | 100 | 61 | 99 |
| disruptive | 61 | 219 | 135 | 302 |
| missense | 46 | 205 | 126 | 276 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 27 | 186 | 78 | 112 |
| disruptive | 105 | 453 | 202 | 395 |
| missense | 72 | 393 | 180 | 295 |
PlasmoDB Total SNPs: 280
Non-coding: 137 | Synonymous: 81 | Nonsynonymous: 62 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 19502583 | An unusual ERAD-like complex is targeted to the apicoplast of Plasmodiumfalciparum. | Spork S, Hiss JA, ..., Przyborski JM | 10.1128/EC.00083-09 |
| 23785288 | An apicoplast localized ubiquitylation system is required for the import ofnuclear-encoded plastid proteins. | Agrawal S, Chung DW, ..., Le Roch KG | 10.1371/journal.ppat.1003426 |
| 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 |
| 32569299 | Ubiquitin activation is essential for schizont maturation in Plasmodiumfalciparum blood-stage development. | Green JL, Wu Y, ..., Holder AA | 10.1371/journal.ppat.1008640 |