Genome location: Pf3D7_12_v3:1,044,957..1,050,130(+)
Genome classification: Core
Product Description: ubiquitin-activating enzyme E1
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 6.2.1.45 (E1 ubiquitin-activating enzyme);6.3.2.19 (Transferred entry: 2.3.2.23, 2.3.2.27 and 6.2.1.45)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Component | GO:0005634 | nucleus |
| Function | GO:0004839 | ubiquitin activating enzyme activity |
| Process | GO:0006974 | cellular response to DNA damage stimulus |
| Process | GO:0032446 | protein modification by small protein conjugation |
| Process | GO:0016567 | protein ubiquitination |
| Process | GO:0009410 | response to xenobiotic stimulus |
| Process | GO:0006511 | ubiquitin-dependent protein catabolic process |
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 | 0.71 | 0.67 |
| Trophozoite | expressed | 1.36 | 0.36 |
| Schizont | expressed | 0.71 | 0.63 |
| Gametocyte | expressed | 0.68 | 0.63 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1225800
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: 0.121 | MFS: -2.922 | #Insertions: 0
PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_1440700)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1440700)
Modification: Disrupted | RMgm-3944
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I5F9
"Best" AlphaFill ligand hit: AMP (adenosine monophosphate, Local RMSD=0.19) with 4NNJ (Global RMSD=5.93)
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... |
| 6.3.2.19 | ubiquitin-protein ligase | No BRENDA inhibitors |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| A0AVT1 | Ubiquitin-like modifier-activating enzyme 6 | Homo sapiens | HOGENOM, OrthoDB | US9593121, 1-01US9593121, I-02US9593121, I-03US9593121, I-04... |
| P41226 | Ubiquitin-like modifier-activating enzyme 7 | Homo sapiens | HOGENOM, OrthoDB | CHEMBL2017005 |
| P22314 | Ubiquitin-like modifier-activating enzyme 1 | Homo sapiens | HOGENOM, OMA, OrthoDB | Compound ICompound ICompound IUS9796725, Compound I-001... |
| Q9UBT2 | SUMO-activating enzyme subunit 2 | OrthoDB | US9796725, Compound I-001US9796725, Compound I-098US9796725, Compound I-003US9796725, Compound I-004... | |
| Q8TBC4 | NEDD8-activating enzyme E1 catalytic subunit | OrthoDB | MITOXANTRONEPevonedistatCHEMBL4878088CHEMBL4865086... |
Ortholog Group (OrthoMCL): OG6_100444
Most Similar Human Ortholog: P22314
TM-align score: 0.92 | RMSD: 2.35
Seq Identity: 0.36 | Length: 1013 / 1140
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000033178 | ubiquitin like modifier activating enzyme 6 |
| ENSG00000130985 | ubiquitin like modifier activating enzyme 1 |
| ENSG00000145241 | centromere protein C |
| ENSG00000182179 | ubiquitin like modifier activating enzyme 7 |
Protein Length: 1140 | Molecular Weight (kDa): 131.778
UniProt ID(s): Q8I5F9
PDB ID(s): None
Isoelectric Point: 5.51
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR000011 | Ubiquitin/SUMO-activating enzyme E1 |
| InterPro | IPR000594 | THIF-type NAD/FAD binding fold |
| InterPro | IPR018965 | Ubiquitin-activating enzyme E1, C-terminal |
| InterPro | IPR019572 | Ubiquitin-activating enzyme, catalytic cysteine domain |
| InterPro | IPR032418 | Ubiquitin-activating enzyme E1, FCCH domain |
| InterPro | IPR032420 | Ubiquitin-activating enzyme E1, four-helix bundle |
| InterPro | IPR033127 | Ubiquitin-activating enzyme E1, Cys active site |
| InterPro | IPR035985 | Ubiquitin-activating enzyme |
| PFam | PF00899 | THIF-type NAD/FAD binding fold |
| PFam | PF09358 | Ubiquitin-activating enzyme E1, C-terminal |
| PFam | PF10585 | Ubiquitin-activating enzyme, catalytic cysteine domain |
| PFam | PF16190 | Ubiquitin-activating enzyme E1, FCCH domain |
| PFam | PF16191 | Ubiquitin-activating enzyme E1, four-helix bundle |
| Superfamily | SSF69572 | Ubiquitin-activating enzyme |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 10 | 28 | 26 | 58 |
| disruptive | 6 | 47 | 28 | 132 |
| missense | 6 | 46 | 27 | 118 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 15 | 80 | 39 | 62 |
| disruptive | 15 | 148 | 88 | 222 |
| missense | 11 | 125 | 74 | 159 |
PlasmoDB Total SNPs: 223
Non-coding: 180 | Synonymous: 34 | Nonsynonymous: 9 | 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 |
| 16267556 | A protein interaction network of the malaria parasite Plasmodium falciparum. | LaCount DJ, Vignali M, ..., Hughes RE | 10.1038/nature04104 |
| 22912882 | Characterization of the ubiquitylating components of the human malaria parasite'sprotein degradation pathway. | Chung DW, Ponts N, ..., Le Roch KG | 10.1371/journal.pone.0043477 |