?cl38917: Tiki_TraB-like Superfamily (this model, PSSM-Id:422953 is obsolete and has been replaced by 453888)
 
diverse proteins related to the Tiki and TraB protease domains The extracellular domain of Tiki family proteins shares homology with bacterial TraB/PrgY proteins which are known for their roles in the inhibition of mating pheromones. Tiki and TraB/PrgY proteins share limited sequence identity, but their predicted secondary structures reveal that several catalytic residues are anchored in a similar manner, consistent with a common evolutionary origin. Tiki domains are related to the erythromycin esterase, gumN plant pathogens, RtxA toxins, and Campylobacter Jejuni heme-binding, ChaN-like proteins. Tiki is a membrane-associated metalloprotease (MEROPS family M96) that inhibits Wnt via the cleavage of its amino terminus, diminishing Wnt's binding to receptors. Wnt is essential in animal development and homeostasis. In Xenopus, Tiki is critical in head development. In human cells, Tiki inhibits Wnt-signaling, which is important in embryogenesis, homeostasis, and regeneration. Deregulation of Wnt contributes to birth defects, cancer and various diseases. TraB/PrgY protein has been identified in gut bacterium Enterococcus faecalis, but its function has not been well characterized. Plasmid-borne TraB has been implicated in the regulation of pheromone sensitivity and specificity. Based on homology to Tiki activity, it has been proposed that TraB acts as a metalloprotease in the inactivation of mating pheromone. Pasteurella multicida toxin has structural and sequence similarity to the Tiki/TraB family of proteases. However, unlike related multidomain toxins in this family, they do not exhibit conservation of the typical active site residues. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",