MIC12

TgMIC12 is a Toxoplasma gondii microneme transmembrane protein implicated in the intramembrane proteolytic shedding cascade that accompanies host cell invasion (PMID:15913633). Its transmembrane domain serves as a substrate for the rhomboid intramembrane-cleaving serine protease TgROM2, as demonstrated by cleavage of chimeric reporters bearing the TgMIC12 TM segment (PMID:15913633). Beyond this single substrate relationship, no further mechanistic detail — including the native protein's function, adhesive partners, or invasion phenotype — has been characterized in the available corpus.

1. 2005 Medium

   To establish which micronemal proteins are processed by parasite rhomboid proteases during invasion, this work tested whether the TgMIC12 transmembrane domain is a cleavage substrate, defining TgMIC12 as part of the rhomboid-mediated shedding cascade.

   Evidence In vitro/cell-based cleavage assay using chimeric proteins carrying TgMIC12 TM domains as substrates for TgROM2, in Toxoplasma gondii

   PMID:15913633

   Open questions at the time

   • Cleavage was shown with chimeric constructs, not the native full-length TgMIC12 protein
   • Demonstrated by a single lab with a single method; no reciprocal or in vivo confirmation
   • The biological function of TgMIC12 and the consequence of its cleavage for invasion were not established

• The native function of TgMIC12, its adhesive or receptor-binding partners, its subcellular trafficking, and the functional consequence of TgROM2-mediated cleavage for host cell invasion remain uncharacterized in the available corpus.
• No functional or knockout phenotype for TgMIC12 reported
• No identification of binding partners or ligands
• No structural characterization