Gene Ontology annotation through association of InterPro records with GO terms
Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features
Automatic Gene Ontology annotation based on Rhea mapping
TreeGrafter-generated GO annotations
Combined Automated Annotation using Multiple IEA Methods
ROP18 is a rhoptry kinase controlling the intracellular proliferation of Toxoplasma gondii.
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ROP18 is a rhoptry bulb protein that relocalizes to the parasitophorous vacuole membrane during invasion and is an active kinase.
"We show here that ROP18, a member of the ROP2 family, is located in the rhoptries and re-localises at the parasitophorous vacuole membrane during invasion."
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Overexpression of ROP18 stimulates intravacuolar parasite multiplication in a catalysis-dependent manner.
"In contrast, when counting the number of parasites per vacuole at 16 h after infection, we observed a significant increase in parasite proliferation in the ROP18-Ty–transfected parasites, compared with that of wild-type tachyzoites."
A secreted serine-threonine kinase determines virulence in the eukaryotic pathogen Toxoplasma gondii.
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ROP18 was positionally cloned as a polymorphic secreted serine-threonine kinase controlling acute virulence, and the phenotype requires kinase activity.
"polymorphic serine-threonine kinase that was secreted into the host cell during parasite invasion."
Polymorphic secreted kinases are key virulence factors in toxoplasmosis.
Phosphorylation of immunity-related GTPases by a Toxoplasma gondii-secreted kinase promotes macrophage survival and virulence.
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ROP18 binds and phosphorylates host immunity-related GTPases and blocks Irgb6 recruitment to the vacuole, which is required for parasite destruction.
"Parasites expressing active ROP18 largely resisted IRG recruitment, while efficient Irgb6 loading was observed on vacuoles containing parasites deficient in ROP18 (Figure 3A,B)."
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Autophosphorylation and substrate phosphorylation are lost in the kinase-dead mutant, establishing direct catalysis.
"both auto-phosphorylation of several forms of ROP18 and labeling of Irgb6 were readily detected by the active ROP18 but not the kinase-dead form (Figure 4B)."
Phosphorylation of mouse immunity-related GTPase (IRG) resistance proteins is an evasion strategy for virulent Toxoplasma gondii.
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ROP18 phosphorylates Irga6 on two threonines in switch region I, inactivating the GTPase and impairing its accumulation on the vacuole membrane.
"We show here that the ROP18 kinase from highly virulent strains targets Irga6, phosphorylating two threonines in the switch I loop."
The arginine-rich N-terminal domain of ROP18 is necessary for vacuole targeting and virulence of Toxoplasma gondii.
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ROP18 is tethered to the cytosolic face of the parasitophorous vacuole membrane through an arginine-rich amphipathic region upstream of the kinase domain.
"Following secretion into the host cell, ROP18 traffics to the parasitophorous vacuole membrane (PVM) where it is tethered to the cytosolic face of this host-pathogen interface."
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Vacuole-targeting mutants retain intrinsic kinase activity but cannot phosphorylate Irga6, cannot divert IRGs and are avirulent, showing that location is required for function.
"Vacuole-targeting mutants of ROP18 failed to phosphorylate Irga6 and were unable to divert IRGs from the PVM, despite retaining intrinsic kinase activity."
ATF6β is a host cellular target of the Toxoplasma gondii virulence factor ROP18.
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The N-terminal extension of ROP18 binds host ATF6beta and promotes its proteasome-dependent degradation in a manner requiring kinase activity.
"The kinase activity of ROP18 is essential for proteasome-dependent degradation of ATF6β and for parasite virulence."
The Toxoplasma gondii rhoptry protein ROP18 is an Irga6-specific kinase and regulated by the dense granule protein GRA7.
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GRA7 is a component of the ROP5/ROP18 vacuolar kinase complex, recruited through direct binding to ROP5, and its loss reduces Irga6 phosphorylation.
"In this study, we confirmed the dense granule protein GRA7 as an additional component of the ROP5/ROP18 kinase complex and identified GRA7 association with the PVM by direct binding to ROP5."
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Among IRG proteins, Irga6 is the specific target of ROP18.
"We show that the only specific target of ROP18 among IRG proteins is in fact Irga6."
The rhoptry proteins ROP18 and ROP5 mediate Toxoplasma gondii evasion of the murine, but not the human, interferon-gamma response.
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The type II allele carried by ME49 is expressed and functional, while type III strains carry a promoter insertion that prevents expression.
"ROP18 is highly expressed in types I and II strains but an insertion in the promoter prevents expression in type III strains."
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Neither ROP18 nor ROP5 affects survival in interferon-activated human cells, which lack the expanded IRG family of rodents.
"However, neither ROP18 nor ROP5 markedly affect survival in IFNγ-activated human cells, which lack the multitude of IRGs present in murine cells."
UniProt entry A0A125YQL1 (ROP18, Toxoplasma gondii ME49)