Carboxylesterase that acts as a key negative regulator of the Wnt signaling pathway by specifically mediating depalmitoleoylation of WNT proteins. Serine palmitoleoylation of WNT proteins is required for efficient binding to frizzled receptors (PubMed:25731175). [Wnt protein]-O-(9Z)-hexadecenoyl-L-serine + H2O = (9Z)-hexadecenoate + [Wnt protein]-L-serine + H(+) Rarely expressed in adult normal tissues. Up-regulated in hepatocellular carcinoma (HCC) with high intracellular beta-catenin. Belongs to the pectinacetylesterase family. Notum subfamily. The molecular function of NOTUM has remained unclear for many years. It was initially thought to hydrolyze glycosaminoglycan (GAG) chains of glypicans, thereby affecting glypicans ability to interact with Wnt ligands. It was later reported to trigger glypican shedding, by mediating cleavage of their GPI-anchor. However, while NOTUM specifically inhibit the Wnt signaling pathway, more pleiotropic effects would be expected from an enzyme affecting glypicans. It was finally shown that it requires glypicans to suppress Wnt signaling, but does not cleave their GPI-anchor. It acts by mediating depalmitoleoylation of WNT proteins, impairing WNT binding to frizzled receptors (PubMed:25731175). Truncated N-terminus. Truncated N-terminus. Truncated N-terminus. The art of biocuration - Issue 177 of March 2016