Product Description: DNA damage-inducible protein 1
SignalP Peptide: N/A
# Transmembrane Domains: 0
EC Numbers: 3.4.23.- (Aspartic endopeptidases.)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0005737 | cytoplasm |
| Function | GO:0004190 | aspartic-type endopeptidase activity |
| Process | GO:0006508 | proteolysis |
| Process | GO:0009410 | response to xenobiotic stimulus |
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 | not expressed | 0.08 | 0.96 |
| Trophozoite | expressed | 0.64 | 0.65 |
| Schizont | expressed | 1.60 | 0.30 |
| Gametocyte | expressed | 0.91 | 0.52 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_1409300
Resistome Missense Mutations: E43K
Resistome Compounds with Missense Mutations: GNF-Pf-3600
Resistome # Samples with Disruptive Mutations: 1 (1 missense, 1 "interesting" missense)
Zhang Phenotype: Non - Mutable in CDS
MIS: 0.13 | MFS: -2.861 | #Insertions: 0
PlasmoGEM Phenotype: Essential (Pb ortholog: PBANKA_1033200)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1033200)
Modification: Mutated | RMgm-5126
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8IM03
"Best" AlphaFill ligand hit: ANP (phosphoaminophosphonic acid-adenylate ester, Local RMSD=10.54) with 7JUZ (Global RMSD=14.73)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.23.- | Ex: renin | I2YYKCNSDSIAANBSDANEDTAPI-3DMSOPCMBTLCK... |
No evidence of orthology to BindingDB entries
Ortholog Group (OrthoMCL): OG6_101685
Most Similar Human Ortholog: Q8WTU0
TM-align score: 0.54 | RMSD: 5.49
Seq Identity: 0.30 | Length: 286 / 382
All Human Orthologs (OrthoMCL):
| Gene ID | Description |
|---|---|
| ENSG00000170967 | DNA damage inducible 1 homolog 1 |
| ENSG00000197312 | DNA damage inducible 1 homolog 2 |
| ENSG00000215695 | regulator of solute carriers 1 |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 1 | 19 | 12 | 15 |
| disruptive | 7 | 15 | 11 | 43 |
| missense | 5 | 15 | 11 | 39 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 2 | 35 | 14 | 25 |
| disruptive | 10 | 50 | 30 | 87 |
| missense | 6 | 42 | 26 | 66 |
PlasmoDB Total SNPs: 131
Non-coding: 100 | Synonymous: 29 | Nonsynonymous: 1 | Stop Codon: 1
Protein Length: 382 | Molecular Weight (kDa): 43.839
UniProt ID(s): Q8IM03
PDB ID(s): None
Isoelectric Point: 4.68
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR019103 | Aspartic peptidase, DDI1-type |
| InterPro | IPR021109 | Aspartic peptidase domain superfamily |
| InterPro | IPR029071 | Ubiquitin-like domain superfamily |
| PFam | PF09668 | Aspartic peptidase, DDI1-type |
| Superfamily | SSF50630 | Aspartic peptidase domain superfamily |
| Superfamily | SSF54236 | Ubiquitin-like domain superfamily |
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368864 | Genome sequence of the human malaria parasite Plasmodium falciparum. | Gardner MJ, Hall N, ..., Barrell B | 10.1038/nature01097 |
| 34832620 | Artemisinin Binds and Inhibits the Activity of Plasmodium falciparum Ddi1, a Retroviral Aspartyl Protease | Onchieku NM, Kumari S, ..., Malhotra P | 10.3390/pathogens10111465 |
| 35677776 | Structural and functional insights into the DNA damage-inducible protein 1 (Ddi1) from protozoa | Asaithambi K, Biswas I, Suguna K | 10.1016/j.crstbi.2022.05.003 |
| 33143019 | Yeast Rpn4 Links the Proteasome and DNA Repair via RAD52 Regulation | Spasskaya DS, Nadolinskaia NI, ..., Karpov DS | 10.3390/ijms21218097 |
| 32808330 | Toxoplasma gondii UBL-UBA shuttle proteins contribute to the degradation ofubiquitinylated proteins and are important for synchronous cell division andvirulence | Zhang H, Liu J, ..., Liu Q | 10.1096/fj.202000759RR |
| 35843171 | HIV protease inhibitor nelfinavir is a potent drug candidate against echinococcosis by targeting Ddi1-like protein | Liu Z, Guo X, ..., Wang S | 10.1016/j.ebiom.2022.104177 |
| 37144685 | Ubx5-Cdc48 assists the protease Wss1 at DNA-protein crosslink sites in yeast | Noireterre A, Serbyn N, Bagdiul I, Stutz F | 10.15252/embj.2023113609 |
| 36657610 | Plasmodium DDI1 is a potential therapeutic target and importantchromatin-associated protein | Tanneru N, Nivya MA, ..., Sijwali PS | 10.1016/j.ijpara.2022.11.007 |
| 34727385 | Toxoplasma gondii UBL-UBA shuttle proteins regulate several important cellularprocesses | Zhang H, Xue Y, ..., Liu Q | 10.1096/fj.202100662RR |
| 38260495 | Multiple DNA repair pathways prevent acetaldehyde-induced mutagenesis in yeast | Porcher L, Vijayraghavan S, ..., Saini N | 10.1101/2024.01.07.574575 |