Affinage · Toxoplasma gondii

GRA46

dense granule protein GRA46 · UniProt S8FC47

Annotated
2026-09-10
1 papers in source corpus 1 papers cited in narrative 2 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRA46 is a dense granule protein of Toxoplasma gondii that is a direct maturation substrate of the Golgi-associated aspartyl protease ASP5, which cleaves an RRL motif within GRA46; mutation of this motif from RRL to ARL abolishes processing, establishing GRA46 as a bona fide ASP5 substrate (PMID:30377279). Beyond its identification and ASP5-dependent maturation (PMID:30377279), nothing further has been characterized about GRA46 in the available corpus.

Mechanistic history

Synthesis pass · year-by-year structured walk · 2 steps
  1. 2018 Medium

    Establishing that GRA46 is a genuine ASP5 substrate answered whether it undergoes ASP5-dependent processing and defined the molecular determinant of that cleavage.

    Evidence TAILS N-terminal peptide enrichment and quantitative proteomics comparing wild-type and Δasp5 parasites, with RRL→ARL motif mutagenesis validation

    PMID:30377279

    Open questions at the time
    • The functional consequence of ASP5 cleavage for GRA46 activity or trafficking is not defined
    • No molecular activity or interaction partners of GRA46 are identified
    • No structural model of the GRA46 cleavage site or mature protein is available
  2. 2018 Low

    Assigning GRA46 to the parasitophorous vacuole and showing it is not exported clarified where the ASP5-matured protein resides relative to the host-parasite interface.

    Evidence Subcellular localization inferred from N-terminal peptide mapping and proteomics of wild-type vs. Δasp5 parasites at the host-parasite interface

    PMID:30377279

    Open questions at the time
    • Localization was inferred from proteomics without direct imaging or fractionation confirmation specifically for GRA46
    • Whether GRA46 sits in the PV lumen or the PVM is not resolved
    • No functional role at the PV/PVM is established

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
ASP5 (GOLGI-ASSOCIATED ASPARTYL PROTEASE THAT CLEAVES THE GRA46 RRL MOTIF)

Evidence

Reading pass · 2 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2018 GRA46 is a dense granule protein identified as a substrate of the Golgi-associated aspartyl protease ASP5; it contains an RRL motif that is cleaved by ASP5, and mutation of the motif from RRL to ARL abolishes processing, confirming direct maturation by ASP5. TAILS (Terminal Amine Isotopic Labeling of Substrates) N-terminal peptide enrichment and quantitative proteomics comparing wild-type and Δasp5 parasites, with RRL→ARL motif mutagenesis validation mBio Medium 30377279
2018 GRA46, as an ASP5 substrate, resides within the parasitophorous vacuole (PV) or its membrane (PVM) and is not exported into the host cell, distinguishing it from the analogous exported substrates in Plasmodium spp. Subcellular localization inferred from N-terminal peptide mapping and proteomics of wild-type vs. Δasp5 parasites; localization assessed at the host-parasite interface mBio Low 30377279

Source papers

Stage 0 corpus · 1 paper · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 Aspartyl Protease 5 Matures Dense Granule Proteins That Reside at the Host-Parasite Interface in Toxoplasma gondii. mBio 45 30377279