Notum (also called Wingful) was originally discovered in screens in fruit flies for genes interacting with the Wnt protein Wingless. Loss of Notum in flies leads to wing overgrowth, indicating that Wnt proteins (which drive wing growth and patterning) have become unrestrained. Typically, Wnt signals also turn on the expression of Notum, typical for negative feedback regulation where such signals intrinsically limit their own activity. Notum is an extracellular de-acylase, enzymatically removing the lipid from Wnt, thereby rendering it inactive.
Reviewed in Nusse (2015)
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Kakugawa, S., Langton, P.F., Zebisch, M., Howell, S.A., Chang, T.H., Liu, Y., Feizi, T., Bineva, G., O'Reilly, N., Snijders, A.P., Jones, E.Y., and Vincent, J.P. (2015). Notum deacylates Wnt proteins to suppress signalling activity. Nature 519, 187-192.
Zhang, X., Cheong, S.M., Amado, N.G., Reis, A.H., MacDonald, B.T., Zebisch, M., Jones, E.Y., Abreu, J.G., and He, X. (2015). Notum Is Required for Neural and Head Induction via Wnt Deacylation, Oxidation, and Inactivation. Developmental cell.