Product Description: rhomboid protease ROM4
SignalP Peptide: N/A
# Transmembrane Domains: 6
EC Numbers: 3.4.21.105 (Rhomboid protease)
Curated GO (PlasmoDB):
| Type | GO Term | Name |
|---|---|---|
| Component | GO:0009986 | cell surface |
| Component | GO:0005886 | plasma membrane |
| Function | GO:0008233 | peptidase activity |
| Process | GO:0006465 | signal peptide processing |
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 | 0.16 | 0.92 |
| Trophozoite | expressed | 0.31 | 0.83 |
| Schizont | expressed | 1.86 | 0.24 |
| Gametocyte | expressed | 0.70 | 0.65 |
More info:
Old (Pf3D7v3) Gene ID: PF3D7_0506900
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: 0.135 | MFS: -3.16 | #Insertions: 0
PlasmoGEM Phenotype: Slow (Pb ortholog: PBANKA_1106500)
RMgmDB ABS Phenotype: Different from wild type (Pb ortholog: PBANKA_1106500)
Modification: Disrupted | RMgm-2951
More info: PhenoPlasm Link
AlphaFill Uniprot ID: Q8I433
"Best" AlphaFill ligand hit: ANP (phosphoaminophosphonic acid-adenylate ester, Local RMSD=8.41) with 2R5T (Global RMSD=19.56)
BRENDA EC Inhibitors:
| EC # | Name | EC Inhibitors |
|---|---|---|
| 3.4.21.105 | rhomboid protease | dodecyl maltosidedichloroisocoumarin3,4-dichloroisocoumarinn-nonyl-beta-D-glucosidediisopropyl fluorophosphonate3,4-dichloro-1H-2-benzopyran-1-one7-amino-4-chloro-3-methoxyisocoumarin3-butyl-4-(pent-4-yn-1-yl)oxetan-2-one1-myristoyl-sn-glycero-3-phosphocholine1,2-dihexanoyl-sn-glycero-3-phosphocholine1,2-dimyristoyl-sn-glycero-3-phosphocholinephenyl 2-oxo-4-phenylazetidine-1-carboxylate... |
Orthology to BindingDB Entries:
| UniProt | Protein Name | Species | Homology Source | BindingDB Ligands |
|---|---|---|---|---|
| Q9WZ53 | Rhomboid domain-containing protein | OrthoMCL BLAST | cid_1609 | |
| P54493 | Rhomboid protease GluP | OrthoMCL BLAST | cid_1609CHEMBL4225584CHEMBL4225103CHEMBL79597... | |
| A0A2R3FW87 | Rhomboid protease GlpG | OrthoMCL BLAST | cid_16094‐Chloro‐7‐nitro‐3‐[(5‐phenylpentyl)oxy]isochromen‐1‐one (21) |
Protein Length: 759 | Molecular Weight (kDa): 86.654
UniProt ID(s): Q8I433
PDB ID(s): None
Isoelectric Point: 9.49
Protein Domain Annotations:
| Source | Family ID | Description |
|---|---|---|
| InterPro | IPR002610 | Peptidase S54, rhomboid |
| InterPro | IPR017092 | Peptidase S54, rhomboid-like, Rom4/Rom5, apicomplexa |
| InterPro | IPR022764 | Peptidase S54, rhomboid domain |
| PFam | PF01694 | Peptidase S54, rhomboid domain |
| Superfamily | SSF144091 | N/A |
MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:
Homozygous genotype calls only
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 6 | 22 | 15 | 51 |
| disruptive | 33 | 36 | 17 | 62 |
| missense | 26 | 25 | 14 | 42 |
Any inclusion in genotype call
| variant type | common | rare | doubleton | singleton |
|---|---|---|---|---|
| synonymous | 12 | 59 | 19 | 55 |
| disruptive | 49 | 76 | 44 | 82 |
| missense | 32 | 47 | 37 | 59 |
PlasmoDB Total SNPs: 159
Non-coding: 81 | Synonymous: 39 | Nonsynonymous: 39 | Stop Codon: 0
| PMID | Title | Authors | DOI/Link |
|---|---|---|---|
| 12368867 | Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13. | Hall N, Pain A, ..., Barrell BG | 10.1038/nature01095 |
| 17000879 | Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyteinvasion by the malaria parasite. | O'Donnell RA, Hackett F, ..., Blackman MJ | 10.1083/jcb.200604136 |
| 17040128 | Two Plasmodium rhomboid proteases preferentially cleave different adhesinsimplicated in all invasive stages of malaria. | Baker RP, Wijetilaka R, Urban S | 10.1371/journal.ppat.0020113 |
| 27128092 | Interrogating the Plasmodium Sporozoite Surface: Identification ofSurface-Exposed Proteins and Demonstration of Glycosylation on CSP and TRAP byMass Spectrometry-Based Proteomics. | Swearingen KE, Lindner SE, ..., Sinnis P | 10.1371/journal.ppat.1005606 |
| 24217438 | Characterization of the interaction between Toxoplasma gondii rhoptry neckprotein 4 and host cellular beta-tubulin | Takemae H, Sugi T, ..., Kato K | 10.1038/srep03199 |
| 25336455 | Functional analysis of rhomboid proteases during Toxoplasma invasion | Shen B, Buguliskis JS, Lee TD, Sibley LD | 10.1128/mBio.01795-14 |
| 32888502 | Designed Parasite-Selective Rhomboid Inhibitors Block Invasion and ClearBlood-Stage Malaria | Gandhi S, Baker RP, ..., Urban S | 10.1016/j.chembiol.2020.08.011 |
| 29317874 | Molecular Cloning, Expression and Characterization of Plasmid Encoding Rhomboid 4(ROM4) of Tachyzoite of Toxoplasma gondii RH Strain | Rahimi MT, Sarvi S, ..., Daryani A | https://pubmed.ncbi.nlm.nih.gov/29317874/ |
| 25846828 | Distinct contribution of Toxoplasma gondii rhomboid proteases 4 and 5 tomicronemal protein protease 1 activity during invasion | Rugarabamu G, Marq JB, ..., Soldati-Favre D | 10.1111/mmi.13021 |
| 23490234 | Loss-of-function analyses defines vital and redundant functions of the Plasmodiumrhomboid protease family | Lin JW, Meireles P, ..., Khan SM | 10.1111/mmi.12187 |
| 27909791 | Immunological evaluation of a DNA cocktail vaccine with co-delivery of calciumphosphate nanoparticles (CaPNs) against the Toxoplasma gondii RH strain in BALB/cmice | Rahimi MT, Sarvi S, ..., Daryani A | 10.1007/s00436-016-5325-6 |
| 20421941 | Rhomboid 4 (ROM4) affects the processing of surface adhesins and facilitates hostcell invasion by Toxoplasma gondii | Buguliskis JS, Brossier F, Shuman J, Sibley LD | 10.1371/journal.ppat.1000858 |
| 28077075 | Protection via a ROM4 DNA vaccine and peptide against Toxoplasma gondii in BALB/cmice | Han Y, Zhou A, ..., He S | 10.1186/s12879-016-2104-z |
| 26111968 | Protective efficacy of two novel DNA vaccines expressing Toxoplasma gondiirhomboid 4 and rhomboid 5 proteins against acute and chronic toxoplasmosis inmice | Zhang NZ, Xu Y, ..., Zhu XQ | 10.1586/14760584.2015.1061938 |