In Drosophila, the notum gene is regulated by the Wingless pathway and encodes a secreted hydrolase that modifies heparan sulfate proteoglycans. The mammalian homolog has been shown to be able to cleave glypicans and can release GPI-anchored proteins from the mammalian cell surface. Like the Drosophilia NOTUM, the mammalian protein can act as a negative regulator of the Wnt signaling pathway. NOTUM is expressed at a low level in most mammalian tissues, although it is overexpressed in a subset of human hepatocellular carcinomas. Its transcription is regulated by beta-catenin/TCF and is a target of the Wnt signaling pathway, forming a negative feedback loop that regulates the expression and activity of the Wnt pathway.
